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Hyperammonemic crisis (HAC) remains a major risk factor for urea cycle disorders (UCD), and practical outpatient predictors are limited. We tested whether short-term changes in plasma glutamine (ΔGln) and ammonia (ΔNH3) predict HAC and whether effects differ by onset type. In a retrospective cohort (2014-2024) of 18 patients with UCD (neonatal-onset [NO] nine; late-onset [LO] nine), HAC was defined as ammonia (NH3) > 150 μg/dL (88.1 μmol/L). For each patient, ΔGln and ΔNH3 were calculated between sequential outpatient samples. Investigation 1 compared the changes observed between 31-60 days and 8-30 days before HAC, with stable period changes. Investigation 2 compared changes at 61-90 and 31-60 days before HAC with stable period changes. Associations were evaluated using generalized linear mixed-effects models with onset-specific effects. In NO, larger ΔGln during Investigation 1 was associated with higher HAC risk (p < 0.001) whereas ΔNH3 was not associated with HAC (p = 0.361). The probability of HAC in NO was estimated to reach 67.1% at ΔGln +500 μmol/L. In LO, neither ΔGln nor ΔNH3 during Investigation 1 showed a significant association with HAC, and the estimated probabilities remained low across the observed ranges. During Investigation 2, no significant associations between biomarkers and HAC were observed in either group. Progressive increases in plasma glutamine levels within the 31-60 and 8-30 days pre-HAC window may serve as early markers of HAC risk in NO-UCD, supporting the utility of longitudinal monitoring. These trends were not associated with LO-UCD, suggesting the need for alternative surveillance strategies tailored to the onset phenotype.

DOI： 10.1002/jmd2.70105

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BACKGROUND: Mitral annular calcification (MAC)-related mitral stenosis is associated with increased mortality, but robust long-term outcomes remain unclear. OBJECTIVES: The aim of this study was to investigate 5-year outcomes, including causes of death and valve-related prognostic factors, in patients with MAC-related mitral stenosis. METHODS: The retrospective, multicenter JAMAC (Japan Multicenter Mitral Annular Calcification) study included adult patients from 11 Japanese centers who underwent echocardiography between 2016 and 2017 and had MAC with a transmitral mean gradient ≥5 mm Hg. Mitral stenosis etiology, mitral valve area (MVA), and anterior MAC in the parasternal long-axis view were evaluated. Posterior MAC was graded as mild (less than one-third), moderate (one-third to two-thirds), or severe (more than two-thirds) of the posterior mitral annular circumference in the parasternal short-axis view. The primary outcome was all-cause mortality; secondary outcomes were cardiac and noncardiac death. To determine valve-related prognostic factors, multivariable analysis was performed including key clinical variables. RESULTS: Among 264 patients (median age 78 years; 73% female), 201 (76%) had calcific mitral stenosis and 63 (24%) had rheumatic mitral stenosis. Median MVA was 1.40 cm2, transmitral mean gradient was 6.1 mm Hg, and 63% had anterior MAC. Posterior MAC was severe in 47% and moderate in 25%. Five-year survival was 57%; cardiac and noncardiac mortality was 16% and 24%, respectively. Calcific mitral stenosis showed higher mortality compared with rheumatic mitral stenosis (cardiac death: 18% vs 11%; noncardiac death: 28% vs 13%). Anterior and severe posterior MAC were associated with increased mortality. MVA <1.5 cm2 predicted mortality in calcific mitral stenosis. On multivariable analysis, MVA remained associated with mortality (adjusted HR: 1.56; 95% CI: 1.03-2.38), independent of age and chronic kidney disease, both strong predictors of death. CONCLUSIONS: The prognosis of MAC-related mitral stenosis was poor, with a 5-year survival of 57%, mainly driven by noncardiac mortality in calcific mitral stenosis. Severity of mitral stenosis was one of the independent predictors in this high-risk population.

DOI： 10.1016/j.jacc.2025.12.004

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PURPOSE: To investigate the effect of high-iodine concentration contrast material for dual-energy CT angiography (DECTA) on arterial visualizations by comparing it with medium-iodine concentration. METHOD: This prospective, single-blind, randomized controlled trial included 100 consecutive participants undergoing DECTA from November 2023 to February 2025. The participants were randomly assigned into two protocols: receiving high-iodine concentration contrast material of 370 mgI/mL (Group A, n = 51) and receiving medium-iodine concentration of 300 mgI/mL (Group B, n = 49). The axial, coronal, and volume-rendered (VR) images were reconstructed at 40 keV in both groups. Two radiologists reviewed three image types and assessed the arterial visualizations using a five-point scale. The primary outcome was the score for the iliolumbar artery on the VR images, whereas secondary outcomes were the scores for all others. The Wilcoxon rank sum test was conducted to compare the outcomes between the two groups. RESULTS: No statistical significance in terms of the score for the iliolumbar artery on the VR images was found between the two groups; however, the median score was higher in Group A than in Group B (3.5 vs. 3.0; P = .05). The scores for secondary outcomes in Group A were equal to or greater than that in Group B, and significant differences were observed, especially in the small arteries, including the bronchial, internal thoracic, intercostal, left gastric, and inferior phrenic arteries (P < .05). CONCLUSION: In small arteries, the protocol with high-iodine concentration contrast material exhibited better arterial visualizations compared with medium-iodine concentration in DECTA at 40 keV.

DOI： 10.1016/j.ejro.2026.100733

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DOI： 10.1213/ANE.0000000000008070

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BACKGROUND: Home health care is an essential alternative to hospital care and its use is expanding. However, early recognition of clinical deterioration in the home setting is difficult, particularly in older adults with complex health conditions. AIM: We investigated whether the National Early Warning Score (NEWS), a tool based on vital signs, could predict short-term mortality following unscheduled home visits in patients receiving home health care. DESIGN & SETTING: This retrospective cohort study focused on unscheduled home visits conducted in four centres in Japan from June 2023 to May 2024. METHOD: This study included 589 unscheduled home visits to 234 patients. Vital signs were recorded by visiting nurses during unscheduled visits, and the NEW scores were calculated later. The primary and secondary outcomes were 2-day and 7-day mortality, respectively. Generalised linear mixed models were used to predict the probability of death. RESULTS: The median patient age was 80 years, and the median NEW score was 3. The 2-day mortality was 29/234 (12.4%), and the 7-day mortality was 44/234 (18.8%). The NEW score was a significant predictor of both 2-day mortality (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.42-2.52, P<0.001) and 7-day mortality (OR 2.14, 95% CI 1.59-2.89, P<0.001). The risk of death increased as the NEW score increased. CONCLUSIONS: The NEW score during unscheduled home visits is associated with significantly increased short-term mortality. By identifying patients at high risk of death, wider implementation of NEWS could support clinical decision-making and improve patient safety.

DOI： 10.3399/BJGPO.2026.0035

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Background

Administration of andexanet alfa has shown to achieve hemostatic efficacy in factor Xa inhibitor (FXai)-associated intracranial hemorrhage (ICrH). Code stroke (CS), implemented through the visual task management application Task Calc. Stroke (TCS) facilitates timely reperfusion therapy for acute ischemic stroke. However, the association between TCS-based CS and in-hospital treatment time of andexanet for FXai-associated ICrH remains unknown.

Methods

In this single-center retrospective study, patients with FXai-associated ICrH who received andexanet were enrolled from May 2022 to May 2025. TCS was activated via prehospital notification when patients presented with at least one of the clinical symptoms including face dropping, arm weakness, or speech difficulty with a time from onset or last known well of &amp;lt;24 h. Multivariable linear regression was performed to investigate the association between TCS-based CS and door-to-andexanet administration time.

Results

Forty-two patients (22 men, median age 80 years) were included. The primary location of hemorrhage was intracerebral ( n  = 26), epidural/subdural ( n  = 8), or subarachnoid ( n  = 8). Among them, 17 (41.5%) were treated with TCS-based CS. The door-to-andexanet administration time was shorter in patients treated with TCS-based CS compared to those without (90 min vs. 132 min, p  &amp;lt; 0.01). Multivariable analysis showed that TCS-based CS was associated with door-to-andexanet administration time (Exp [ β ] 0.58, 95% confidence interval 0.43–0.77) after adjustment with arrival during regular hours and baseline hematoma volume.

Conclusion

TCS-based CS was associated with a shorter door-to-andexanet administration time for FXai-associated ICrH. The outcome benefit from improved treatment times warrants further investigation.

DOI： 10.3389/fneur.2026.1765311

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BACKGROUND: Granulocyte and monocyte adsorption therapy has been explored as an adjunctive treatment for sepsis due to its potential to modulate excessive systemic inflammation. However, clinical evidence characterizing its real-world use for sepsis remains limited. This study aimed to conduct an exploratory comparative assessment of granulocyte and monocyte adsorption apheresis-direct hemoperfusion (G1-DHP) in patients with sepsis. METHODS: We conducted a retrospective comparative study using a prospective multicenter dataset of patients treated with G1-DHP (G-1 trial) and three independent sepsis datasets (Japan Septic Disseminated Intravascular Coagulation [JSEPTIC-DIC], Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma [FORECAST], and Japan Medical Data Center [JMDC]) as controls. Propensity score matching was performed using one-to-one nearest-neighbor matching. The primary outcome was 28-day mortality. Secondary outcomes included ventilator-free period, intensive care unit (ICU)-free period, and improvements in organ dysfunction scores. Ordinal logistic regression and linear regression were used based on outcome characteristics. RESULTS: After matching, the cohorts included 71, 72, and 68 patient pairs for comparisons with JSEPTIC-DIC, FORECAST, and JMDC, respectively. 28-day mortality was significantly lower in the G-1 trial across all matched datasets (G-1 trial vs. JSEPTIC-DIC: 5.6% vs. 23%; G-1 trial vs. FORECAST: 5.6% vs. 28%; G-1 trial vs. JMDC: 5.9% vs. 38%, all P < 0.01). The G-1 trial had a significantly longer ventilator-free period and a trend toward a longer ICU-free period. G1-DHP was also associated with greater observed improvement in Sequential Organ Failure Assessment (SOFA) score by day 7 in comparison to controls. Improvements in liver and coagulation SOFA subscores were particularly notable. CONCLUSIONS: In this multi-dataset analysis, patients treated with G1-DHP showed lower mortality and more favorable clinical outcomes in comparison to external controls. These exploratory findings provide preliminary insights into the potential role of G1-DHP as an immunomodulatory approach in sepsis and warrant further evaluation in prospective studies.

DOI： 10.1186/s40560-026-00872-9

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OBJECTIVES: We aimed to develop and validate a model to predict gait independence at discharge from inpatient rehabilitation in individuals with subacute hemiparetic stroke who have very severe gait disorder. METHODS: Overall, 298 individuals with subacute hemiparetic stroke and completely dependent gait were selected in one hospital as the training cohort. Seventy-seven individuals were selected in another hospital as the validation cohort. The prediction model was developed using multivariable logistic regression analysis, with individual characteristics selected based on a p-value threshold (<0.10) in the training cohort. Sensitivity, specificity, and area under the curve of the receiver operating characteristic curve were calculated in the training cohort, and external validation was conducted using the validation cohort. RESULTS: In total, 102 (34.2%) and 40 (52.0%) individuals in the training and validation cohorts achieved independent gait while hospitalized, respectively. The prediction model factors were age, days from onset to admission, stroke type, affected side, severity of paresis, unaffected side function, and cognitive function. The sensitivity, specificity, and area under the curve in the training cohort were 0.81, 0.80, and 0.88, respectively. Corresponding values in the validation cohort were 0.82, 0.70, and 0.83, respectively. CONCLUSIONS: A model combining age, days from onset to admission, stroke type, affected side, severity of paresis, unaffected side muscle strength, and cognitive function effectively predicted gait independence at discharge in individuals with very severe gait disorder due to subacute hemiparetic stroke.

DOI： 10.20407/fmj.2025-026

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DOI： 10.1007/s12325-025-03464-5

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INTRODUCTION: Dienogest (DNG) is widely used to manage endometriosis-associated pain; however, long-term data comparing low and standard doses are limited. Therefore, this study aimed to evaluate the efficacy and safety of 48-week DNG treatment (1 mg/day vs. 2 mg/day) in patients with endometriosis-related dysmenorrhea (composite score). METHODS: In this randomized, open-label, parallel-group, trial, 88 patients with endometriosis were enrolled, all of whom had at least one ovarian endometriotic cyst confirmed by imaging. Other phenotypes of endometriosis, such as deep infiltrating or peritoneal lesions, were not systematically assessed and may have been present. Patients were randomized to receive either 1-mg/day or 2-mg/day DNG. The primary endpoint was the change in menstrual pain measured using a visual analog scale (VAS). Secondary endpoints included changes in the dysmenorrhea score, ovarian endometrioma volume, serum estradiol levels, bone mineral density (BMD), and menopausal symptoms. RESULTS: Both groups demonstrated a significant reduction in menstrual pain (VAS). The mean VAS scores decreased by 44.63 and 54.19 mm in the 1-mg and 2-mg groups, respectively. However, the between-group difference (- 9.57 mm; 95% confidence interval: - 22.7 to 3.56) was not above the predefined non-inferiority margin of - 15 mm; thus, non-inferiority of the 1-mg dose could not be confirmed. Improvements in dysmenorrhea scores and endometrioma volume were also observed in both groups, although greater effects were noted in the 2-mg group than in the 1-mg group. Serum estradiol suppression was comparable between the groups, whereas BMD loss was less pronounced in the 1-mg group than in the 2-mg group. CONCLUSIONS: This study did not demonstrate statistical non-inferiority of 1-mg/day DNG treatment over 2-mg/day DNG treatment for pain relief. These results suggest that the 2-mg/day dose may offer more robust analgesic effects, particularly during the early treatment phase. However, 1-mg/day DNG still showed meaningful symptom improvement with fewer adverse events than 2-mg/day DNG, supporting its potential use in selected patients requiring long-term therapy. Trial Registration Japan Registry of Clinical Trials, trial registration number: jRCTs041210016.

DOI： 10.1007/s12325-025-03397-z

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BACKGROUND: Various digital biomarkers have been explored to detect cognitive impairment in community-dwelling older individuals, among which electricity consumption (EC) data obtained from smart meters are novel and promising because they pose no burden to the individuals. OBJECTIVE: The study aimed to explore the potential of EC as a digital biomarker to screen older individuals with cognitive impairment living alone. METHODS: We recruited 40 older individuals living alone and recorded their 1-year daily household EC data. We used the Japanese version of the Montreal Cognitive Assessment to categorize participants into 2 groups: those with and without cognitive impairment. As the pattern of daily household EC is different between lower and higher temperature ranges because of the use of heating and cooling equipment, we divided the daily household EC into 3 temperature ranges. Using a linear mixed model, we evaluated the association between daily household EC, daily outside temperature, and the groups. RESULTS: After excluding 12 participants, they were categorized into 2 groups: those with (10/28, 36%) and without cognitive impairment (18/28, 64%). The daily household EC data consisting of 9391 points showed two characteristics: (1) daily household EC was significantly lower in the group with cognitive impairment than in the group without cognitive impairment in the high temperature range (2.158 kWh at 25 °C, P=.02; 3.712 kWh at 30 °C, P<.001). The increase in EC with rising temperature from 25 °C to 30 °C was less in the group with cognitive impairment (2.387 kWh, P<.001) than in the group without cognitive impairment (3.940 kWh, P<.001); and (2) a tendency for lower daily household EC in the group with cognitive impairment was observed in the moderate temperature range (1.795 kWh at 15 °C, P=.06; 1.582 kWh at 20 °C, P=.08). CONCLUSIONS: The group with cognitive impairment may use less cooling equipment in the high temperature range and fewer home appliances in the moderate temperature range. Daily household EC might be useful in screening cognitive impairment in older individuals living alone.

DOI： 10.2196/71265

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BACKGROUND: Glucocorticoids (GCs) are often administered locally to inhibit the synthesis and release of pro-inflammatory cytokines, thereby alleviating local pain. While GCs are known to exacerbate hyperglycemia, we previously reported changes in glucose levels following a single-dose dexamethasone injection in patients who did not have diabetes mellitus (DM). In patients without DM, blood glucose levels increased on the first day but were generally not critical. However, the exact changes in blood glucose levels due to GCs and the risk factors for blood glucose elevation in DM patients remain unclear. OBJECTIVES: To measure changes in glucose levels following a single-dose dexamethasone injection in patients with DM and identify the risk factors for hyperglycemia. STUDY DESIGN: Cohort study. SETTING: Gifu University Hospital, Japan. METHOD: Fifty DM patients undergoing elective pulsed radiofrequency of the lumbar or sacral nerve root or radiofrequency of the lumbar medial branch of the posterior primary ramus were analyzed. Each patient received 0.1 mg/kg of dexamethasone and was subjected to interstitial glucose monitoring using a continuous glucose monitoring system. Hyperglycemia was defined as a blood glucose level >= 200 mg/dL. The area under the curve (AUC) for glucose levels >= 200 mg/dL was calculated. Risk factors for hyperglycemia were analyzed using an ordinal regression model, with AUC as the objective variable and 4 factors (glycosylated hemoglobin [HbA1c], age, body mass index, and pre-procedure glucose levels) as explanatory variables. Nonlinear regression models were used to predict the blood glucose trends. RESULTS: Blood glucose levels increased immediately after the dexamethasone injections. The median (interquartile range) maximum glucose level was 328 (250-386) mg/dL, with a median time to peak of 592 (400-700) min. Among the 4 factors, age and HbA1c level were significant predictors of hyperglycemia (P = 0.035 and 0.023, respectively). Patients treated with insulin were predicted to have significantly higher blood glucose levels than those treated for DM with non-insulin medications or no pharmacological medications (P < 0.001). LIMITATIONS: Firstly, GCs are metabolized by cytochrome p450 3A4, and medications that affect this pathway may alter the clearance of GCs. Some of our patients were taking medications that influenced the cytochrome pathway. Secondly, preoperative insulin management details (dosing, timing, and types) were not fully documented. Thirdly, stress-induced hyperglycemia could not be ruled out. Finally, patients' meal timing and caloric intake were not recorded. CONCLUSION: Patients with DM experienced significant hyperglycemia even after a single dose of dexamethasone. Age and HbA1c levels were risk factors for hyperglycemia. Higher preprocedural HbA1c levels, reflecting poorer daily glucose control, were associated with increased blood glucose levels.

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BACKGROUND: Robot-assisted gait training (RAGT) has proven effective in addressing gait disorders in patients with stroke. However, its efficacy in patients with acute stroke has not yet been demonstrated. This pilot study is designed to evaluate the following: (1) feasibility of conducting a randomized controlled trial on RAGT for enhancing gait postacute stroke and (2) to obtain preliminary estimates regarding the potential efficacy of RAGT for achieving gait independence during the acute phase. METHODS: We will conduct an assessor-blinded, single-center, randomized controlled pilot trial involving 32 patients with acute stroke who are unable to walk. Participants will be randomly assigned to either the RAGT or the conventional gait training (CGT) groups. Each participant will receive 180 min of daily rehabilitation, including 60 min dedicated to gait training. The RAGT group will receive 40 min of RAGT and 20 min of CGT, while the CGT group will engage in 60 min of CGT. Interventions will continue for up to 8 weeks, or until participants achieve gait independence, as indicated by a Functional Ambulation Category score of ≥ 3. Feasibility outcomes will include recruitment, enrollment, protocol adherence, and retention rates. The primary clinical outcome will be the incidence of achieving gait independence during the intervention period. Secondary clinical outcomes will include gait performance measures, assessments of physical function and activity, and intervention dose. Adverse events associated with RAGT and CGT will also be documented to evaluate the safety of both interventions. DISCUSSION: Implementing RAGT during the acute phase of stroke may facilitate earlier attainment of gait independence compared to CGT. We aim to provide valuable insights into the feasibility of the proposed study design and generate preliminary data on the potential effects of RAGT on gait independence in the acute phase of stroke, providing a framework for future larger-scale trials. TRIAL REGISTRATION: This clinical trial was registered with the Japan Clinical Trials Registry (jRCT) on 19 June 2023 (registration number: jRCTs042230040). The study protocol was initially registered as version 1.0 and has since undergone minor amendments-currently on version 4.0. This protocol was written based on the latest version (ver. 4.0) registered with jRCT.

DOI： 10.1186/s40814-025-01694-6

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OBJECTIVES: To identify the optimal material decomposition (MD) images for diagnosis of pancreatic ductal adenocarcinoma (PDAC) and evaluate the added value of the MD image to 50-keV virtual monoenergetic images (VMIs) by comparing with iodine-based images and 50-keV VMIs. METHODS: This retrospective study included patients who underwent pancreatic protocol dual-energy CT (DECT) between February 2019 and May 2023. First, a radiologist evaluated 702 image datasets generated using 27 different materials to identify the top three MD images which provided maximum contrast difference between normal pancreas and PDAC, and subsequently, the best MD image was selected based on z value and image quality by four radiologists. Then, another four radiologists independently interpreted the conventional image dataset (iodine-based images and 50-keV VMIs) and new optimal image dataset (optimal MD images and 50-keV VMIs), and graded the presence or absence of PDAC. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were compared between the two image datasets using generalized estimating equations. RESULTS: Overall, 110 patients (median age, 73 years; 63 men) were included. Among them, 67 patients (61%) had pathologically proven PDAC, and the optimal MD image selected was Silicon/Struvite. The optimal image dataset had higher specificity (88% vs. 81%; P = 0.006), PPV (93% vs. 89%; P < 0.001), and accuracy (94% vs. 92%; P = 0.01) than the conventional image dataset. No difference was found in the sensitivity (P = 0.34) and NPV (P = 0.33) between the two image datasets. CONCLUSION: Silicon/Struvite images provided high contrast difference between normal pancreas and PDAC and higher diagnostic performance for diagnosis of PDAC in combination of 50-keV VMIs compared to iodine-based images and 50-keV VMIs.

DOI： 10.1007/s11604-025-01856-9

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BACKGROUND: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) is a standard third-line therapy for unresectable advanced or recurrent colorectal cancer. The standard dosing schedule (5 days of administration followed by 2 days off) is associated with a high incidence of severe neutropenia. Conversely, a biweekly dosing schedule (5 days of administration followed by 9 days off) reportedly reduces this incidence. However, no direct comparison of these regimens has been made. In this study, we retrospectively compared the efficacy and safety of these two dosing schedules. METHODS: We analyzed data from patients who received FTD/TPI + BEV treatment between June 2016 and January 2024 at three hospitals affiliated with Fujita Health University. The effects of the dosing schedules on hematological toxicity, overall survival (OS), and time to treatment failure (TTF) were assessed. RESULTS: Among the 125 patients, 26 and 99 were classified into the standard and biweekly groups, respectively. Grade ≥ 3 neutropenia occurred in 50.0% of patients in the standard group and 29.3% of those in the biweekly group (P = .062), with multivariable analysis confirming the dosing schedule impact (P = .048). Median TTF was 5.4 and 7.0 months, while median OS was 16.4 and 14.5 months (P = .908, 0.947) in the standard and biweekly groups, respectively. CONCLUSION: The biweekly regimen of FTD/TPI + BEV resulted in a lower tendency for severe neutropenia than that in the standard regimen, while maintaining comparable OS and TTF in patients with unresectable advanced or recurrent colorectal cancer.

DOI： 10.1093/jjco/hyaf108

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Secretory carcinomas (SCs) of the salivary gland have recently been recognized as low-grade, malignant tumors. Before this designation, most SCs were diagnosed as variants of acinic cell carcinomas (AciCCs). SCs harbor the t(12;15)(p13;q25) translocation that generates an oncogenic fusion gene, ETS variant transcription factor 6/Neurotrophic tyrosine receptor kinase(ETV6::NTRK3). However, detecting fusion genes in a clinical setting is time-consuming and costly. In this study, we examined 31 cases previously diagnosed as AciCC and SC using pathological analyses with detection of fusion genes using ETV6 break-apart fluorescence in-situ hybridization and reverse transcription-polymerase chain reaction. After re-analysis, we found that these 31 cases actually comprised 21 SCs and 10 AciCCs. We examined the diagnostic utility of immunohistochemistry by comparing results with the fusion gene, Pan-Trk, which despite having recently been reported as effective for diagnosis of SC, was not universally accurate. However, combining mammaglobin and S-100 could be particularly useful in diagnosing SC. This practical method will contribute to accurate diagnosis of SCs, while saving time in daily clinical practice.

DOI： 10.1007/s12672-025-03072-3

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Background/Objectives: Dietary patterns vary with age and sex. The aim of this study was to clarify the differences in dietary patterns among young and middle-aged Japanese individuals by age group and sex via statistical methods such as alpha diversity and beta diversity analyses. Methods: Using data from a dietary survey of 10 food items during health checkups of 2743 Fujita Health University employees, we examined the effects of age and sex on alpha diversity (Shannon index) and beta diversity (nonmetric multidimensional scaling (NMDS) and RDA). Unlike principal component analysis which assumes linear relationships, redundancy analysis (RDA) incorporates explanatory variables to directly assess how external factors shape multivariate patterns. Results: The Shannon index increased with age and was greater in males across age groups. Type III ANOVA revealed significant main effects of age (p < 0.001) and sex (p < 0.001), and the effect of the interaction between age and sex approached significance (p = 0.08). Visualization of the NMDS data revealed that women aged 20-29 years and women aged 30 years and older and men aged 20-39 years and men aged 50-59 years have different dietary patterns. The RDA model accounted for 2.01% of the variance (adjusted R2 = 1.94%), with age and sex contributing 56.7% and 43.3%, respectively. RDA1 and RDA2 were correlated with age (r = 0.26, -0.14) and sex (r = 0.15, 0.21). The RDA1 values increased with age and were greater in females, whereas the RDA2 values decreased with age and were greater in females. RDA1 (1.41% of the total variance in food group intake, 70.1% of the constrained variance) was positively associated with fruits, milk, and seaweed and negatively associated with meat and eggs. In RDA2 (0.60% of total variance, 29.9% contribution), fruits, potatoes, and vegetables had positive effects, whereas fish had negative effects. Conclusions: Dietary patterns vary by age and sex, with meat, fish, eggs, and fruit as key determinants. Nutritional guidance must account for variations in dietary patterns influenced by age and sex.

DOI： 10.3390/nu17132205

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DOI： 10.1007/s10803-025-06858-0

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BACKGROUND: The treatment of endometriosis includes analgesics, hormone therapy, and surgery. Even after surgical removal of endometriotic lesions, the risk of recurrence remains high once the normal menstrual cycle resumes. Therefore, long-term hormone therapy is essential to prevent recurrence. Among hormonal treatments, low-dose estrogen progestin preparations are not recommended for patients older than 40 years due to the increased risk of thrombotic side effects. In contrast, dienogest does not carry a thrombotic risk, making it a suitable option for older patients. Although dienogest requires long-term administration until menopause in patients with endometriosis, data on its long-term efficacy and potential adverse effects remain limited. In particular, comparative studies assessing the safety and effectiveness of long-term use of dienogest at different doses (1 mg/day vs 2 mg/day) have not been conducted, highlighting the need for further investigation. OBJECTIVE: The purpose of this study is to investigate the efficacy and the incidence of adverse events of dienogest 1 mg/day after 48 weeks in patients with dysmenorrhea due to endometriosis, compared with dienogest 2 mg/day. METHODS: This randomized, open-label, parallel-group, dose-comparison, multicenter trial follows the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 guidelines and is conducted at 6 centers in Japan. Participants are randomly assigned in a 1:1 ratio to receive either dienogest 1 mg/day or 2 mg/day. The drug is administered for 48 weeks, and its therapeutic effects and side effects are evaluated. Hospital visits include the use of questionnaires, vital sign measurements, imaging studies (magnetic resonance imaging and ultrasound), blood tests, and bone density assessments. The primary endpoint is the change in the pain visual analog scale (VAS) score from baseline to 48 weeks. The VAS is a 10 cm horizontal scale where 0 cm represents no pain and 10 cm represents the maximum imaginable pain; participants indicate their pain level on the scale, and the change is analyzed over time. The target sample size is 88, determined with a noninferiority margin based on existing literature. The protocol was approved by the Nagoya City University Hospital Clinical Research Review Board. Findings will be presented at academic conferences and published in peer-reviewed journals. RESULTS: Currently, data collection is ongoing. The first participant was enrolled in August 2021. As of March 22, 2025, a total of 88 participants had been enrolled in this clinical trial. CONCLUSIONS: This is the first trial to compare efficacy and safety between 1 mg/day and 2 mg/day of long-term dienogest use in patients with dysmenorrhea caused by endometriosis. Combining diagnostic imaging with patient questionnaires and blood tests allows the determination of efficacy against endometriosis itself. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs041210016; https://jrct.mhlw.go.jp/en-latest-detail/jRCTs041210016. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/66246.

DOI： 10.2196/66246

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PURPOSE: A clinically applicable nomogram predicting locally advanced prostate cancer (PCa) (defined as pathological T stage ≥ 3) of patients with clinical T stage ≤ 2 was released (MSUG nomogram). We performed external validation, ensuring its applicability to patients undergoing robot-assisted radical prostatectomy (RARP). Therefore, we also compared the external validation for the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. PATIENTS AND METHODS: We collected the data for 8194 patients who underwent RARP at Daimonji Clinical Application Database Group (Dai-CAD) as the validation cohort and performed the external validation using this cohort. The primary endpoint was the accuracy of the MSUG nomogram, and the secondary endpoint was comparison with the MSKCC nomogram. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were calculated to quantify the accuracy of the nomogram at predicting pT ≥ 3. A calibration plot was performed to evaluate the extent of over- and underestimation. RESULTS: Locally advanced PCa was diagnosed in 677 of 2530 patients (26.8%) in the MSUG cohort and 1472 of 5799 patients (25.3%) in the validation cohort. The ROC curve for the validation cohorts fit to the MSUG nomogram and the MSKCC nomogram, with AUC of 0.66 and 0.65, respectively. For calibration plots, it overestimated the risk of locally advanced PCa when probability thresholds are over 70% in the MSUG nomogram, while it may overestimate when probability thresholds are over 30% in the MSKCC nomogram. CONCLUSIONS: We conducted external validation of a clinically applicable nomogram that predicts the probability of locally advanced PCa in patients undergoing RARP using available clinical parameters.

DOI： 10.1245/s10434-025-17385-8

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OBJECTIVE: Eosinophilic gastrointestinal disorders (EGIDs) are pathologically diagnosed by manually counting the eosinophils in biopsy tissue under microscopy. However, the skill of the individual examiner is considered to influence the accuracy of the resulting eosinophil count (EC). This study aimed to examine the effects of different examiners and histopathological staining types on the EC results of pathological tissues from patients with EGIDs. METHODS: Infiltrating eosinophils in lesion tissues from 10 eosinophilic esophagitis and 28 eosinophilic gastroenteritis cases were counted by three pathologists and one cytotechnologist. The intra- and inter-observer variabilities in ECs related to hematoxylin-eosin (HE), May-Grünwald Giemsa (MG), and direct fast scarlet (DFS) staining were investigated. The effects of examiner expertise and staining method on ECs were analyzed using a linear mixed effects model. The difference in color value (ΔE) for each staining method was obtained using the Commission International de l'Eclairage luminance-a-b model (L*a*b*). RESULTS: There was no significant intra-observer variability in eosinophil counting. Regarding inter-observer agreement, the examiner with the most EGIDs experience reported higher ECs than the other examiners for all three staining types (P<0.001). ECs were significantly higher with MG and DFS staining than with HE staining, regardless of the examiner (both P<0.001). Additionally, the ΔE values with DFS were higher than those with MG and HE. CONCLUSIONS: DFS staining offered the most selective visualization of eosinophils. ECs may vary depending on both the skill of the examiner and the staining method.

DOI： 10.20407/fmj.2024-019

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BACKGROUND: This study aimed to determine the index of the sacral vertebrae fusion period in children and adolescents to diagnose the lesion around the sacral spine accurately. METHODS: Patients aged 0-40 years who underwent computed tomography (CT), including the normal sacrum for screening abdominal disorders and pan-scan in trauma between 2019 and 2022 were retrospectively examined. There were 402 eligible sacra (385 patients: 206 women and 179 men). We evaluated bony fusion at six parts of the sacral vertebrae (anterior or posterior of each intervertebral and both side lateral masses). The predicted probability of bony fusion obtained from the logistic regression model is depicted graphically by sex. RESULTS: The association between bony fusion in each vertebral segment and age was evaluated using a logistic regression model with a Huber-White robust sandwich estimator, including the patient as a clustering variable. Bony fusion of the sacral bodies of S1/S2 was slowest, with 80% of patients achieving bony fusion at 28.7 and 24.6 years of age for men and women, respectively. Compared to men, women exhibited earlier fusion of the intervertebral segments of the sacral vertebrae; however, no significant difference between the sexes in terms of eventual bony fusion at the lateral mass was observed, while the initiation of bony fusion occurred earlier in women. CONCLUSION: The predicted probability of bony fusion could aid pediatricians, orthopedists, radiologists, and other physicians in understanding the normal development of the sacral spine and accurately differentiating the lesion around the sacral spine.

DOI： 10.1186/s12891-025-08597-w

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BACKGROUND: Robot-assisted gait training (RAGT) is an effective method for treating gait disorders in individuals with stroke. However, no previous studies have demonstrated the effectiveness of RAGT in individuals with acute stroke. This study aimed to investigate the effects of RAGT initiation within 1 week after onset on degree of gait independence in individuals with hemiparetic stroke. METHODS: This retrospective cohort study used propensity-score matching. Individuals admitted to Fujita Health University Hospital after stroke onset and underwent RAGT between March 2017 and June 2023 were enrolled. Ninety-two individuals were eligible and grouped into the acute (≤ 7 days after the onset) and subacute groups (8-90 days after onset). RAGT was conducted using Welwalk, primarily comprising a knee-ankle-foot orthosis type robot worn on one paralyzed lower extremity, with training sessions lasting approximately 40 min/day, occurring 3-7 days/week. The primary outcome was the gait under supervision within 90 days of onset, which was compared between groups using the log-rank test. RESULTS: After propensity-score matching, 36 individuals were included in the analysis, including 18 each in the acute and subacute groups; the participant demographics were not significantly different between the groups. RAGT was initiated at a median of 6 and 25 days after onset in the acute and subacute groups, respectively. The Kaplan-Meier curves after the log-rank test showed a significantly higher percentage and shorter median days to achieve gait under supervision in the acute group than in the subacute group. The cumulative incidence of gait under supervision events at 90 days after onset was 82.2% and 55.6% in the acute and the subacute groups, respectively. Half of the individuals achieved gait under supervision within 49 days and 75 days in the acute and subacute groups, respectively (p = 0.038). No significant differences were observed in the dose of rehabilitation program and gait training per day from onset to achieving gait under supervision. CONCLUSION: Initiation of RAGT within 1 week after stroke onset in individuals with hemiparesis may reduce the number of days required to achieve gait under supervision and increase the percentage of gait under supervision.

DOI： 10.1186/s12984-025-01581-4

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DOI： 10.1007/s42058-025-00183-2

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BACKGROUND: Although preserved internal jugular veins can become occluded after neck dissection, we have not experienced free jejunal flap necrosis when the veins were used as recipient vessels. Thus, we investigated whether using the internal jugular veins as the recipient vessel for free jejunal flap transfer after neck dissection might contribute to postoperative internal jugular vein patency. METHODS: This retrospective cohort study involved patients who underwent internal jugular vein-preserving neck dissection for hypopharyngeal malignant tumors. We identified and assessed 2 treatment groups: patients with and without preserved internal jugular vein as the recipient vein. To guarantee 80% power for detecting differences between groups using the chi-squared test at a 5% significance level, the enrollment continued until at least 40 patients were included. The primary outcome assessed was internal jugular vein patency on post-contrast computed tomography scans 3 months post-operatively. Preoperative radiation therapy, central venous catheter, left side, and pectoralis major myocutaneous flap reconstruction were included as covariates in the multivariable model. RESULTS: During this period, 123 neck dissections were conducted in 80 eligible patients. Using the internal jugular veins as the recipient vein for free jejunal flap transfer contributed to 19% improvement in patency. Supplemental analysis with additional covariates also showed that patency was significantly improved by 15%. CONCLUSIONS: We strongly recommend that the internal jugular veins of the dissected side should be used as the recipient vein to improve postoperative patency of internal jugular veins.

DOI： 10.1016/j.bjps.2025.01.091

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OBJECTIVE: To determine the impact of mobilization training time during the first postoperative week on the length of hospital stay for postoperative patients admitted to an intensive care unit. DESIGN: A retrospective cohort study. PATIENTS: Consecutive patients who underwent elective surgery and stayed in the intensive care unit of a university hospital for more than 48 h between July 2017 and August 2020 were enrolled. METHODS: The total duration of mobilization training during the first postoperative week and clinical variables, including demographic information, were collected from medical records. Multivariable regression analysis was used to investigate the impact of mobilization training time on the length of hospital stay, adjusting for potentially confounding variables. RESULTS: In total, 773 patients (504 males; median age, 70 years) were enrolled. Multivariable regression analysis showed that an increase in mobilization training time during the first postoperative week was associated with a shorter length of hospital stay (β = -0.067, 95% confidence interval: -0.120, -0.017, p = 0.010), with each 1-h increase in training time associated with a 4.02-day reduction in the length of hospital stay. CONCLUSION: Increased mobilization training during the first postoperative week significantly reduced the length of hospital stay in postoperative patients.

DOI： 10.2340/jrm.v57.41015

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To identify patients with infantile hemangioma (IH) in need of early-stage treatment in this multicenter, prospective, observational study, we investigated the potential of plasma cytokines as a clinically useful marker. Plasma samples were collected at three time points from 41 patients with infantile hemangioma: baseline (days 14-60 after delivery), visit 1 (days 61-150, the proliferative phase), and visit 2 (days 151-395, the involuting phase). With a twofold or more increase in tumor volume during the baseline-visit 1 period regarded as progression, progression was seen in 15 cases (36.6%). In the first step, cytokine arrays were performed using plasma samples in five progressive and five non-progressive cases. Plasma levels of six cytokines at baseline were selected for a prediction marker of change in tumor volume during baseline-visit 1. Validation enzyme-linked immunosorbent assay indicated that the baseline growth differentiation factor 1 (GDF1) concentration tended to correlate with the proliferation ratio of total lesions or target lesion during baseline-visit 1, although without statistical significance. However, the plasma GDF1 concentrations were significantly lower in patients with a fourfold or more increase in total volume (p = 0.013). Furthermore, changes in plasma interleukin (IL)-7Rα levels showed a statistically significant inverse correlation between volume change of the target lesion during baseline-visit 1 (p = 0.0069). Our results suggest that plasma GDF1 measurement after birth is a useful marker for progression of IH. Additionally, the downregulation of IL-7Rα that begins several months after birth may also contribute to tumor growth. (UMIN-CTR: UMIN000038574).

DOI： 10.1111/1346-8138.17639

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BACKGROUND: The Detection of Indicators and Vulnerabilities for Emergency Room Trips (DIVERT) scale, the Community Assessment Risk Screen (CARS), and the Emergency Admission Risk Likelihood Index (EARLI) are scales that assess the risk of emergency department (ED) visits among home health care patients. This study validated these scales and explored factors that could improve their predictive accuracy among Japanese home health care patients. METHODS: This was a single-center retrospective cohort study. The primary outcome of unplanned ED visits was used to assess the validity of the DIVERT scale, CARS, and EARLI. Additionally, we examined whether the addition of patient age and receipt of advance care planning as variables on these assessments could enhance their precision. RESULTS: Altogether, 40 (17.8%) had at least one ED visit during the 6 months study period. In these patients, the DIVERT scale, CARS, and EARLI of the patients with ≥1 ED visit was superior compared with no ED visit (both p < 0.05). The area under the curve (AUC) of the DIVERT scale, CARS, and EARLI were 0.62, 0.59, and 0.60, respectively. Adding patient age and receipt of advance care planning improved the AUC in all three scales. CONCLUSIONS: Our findings suggest that these assessment scales could be applicable to home health care patients in Japan. Furthermore, adding age and receipt of advance care planning as variables was found to enhance the predictive accuracy of the scales.

DOI： 10.1002/jgf2.738

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Studies have associated neutrophil-to-lymphocyte ratio (NLR) with overall survival (OS) and progression-free survival (PFS) in patients with gastric cancer (GC). The present study aimed to examine the relationship between dynamic changes in NLR during treatment and disease progression in patients with unresectable or recurrent GC treated with nivolumab monotherapy as a third-line or later regimen. Patients treated with nivolumab as a third-line or later therapy for unresectable or recurrent GC at Gifu University Hospital (Gifu, Japan) from April 2017 to December 2021 were included. Pretreatment data and those obtained every 2 weeks after the treatment commenced were evaluated. The association between all NLR values and disease progression for each patient was evaluated using a time-dependent Cox proportional hazards model and restricted cubic spline (RCS) curves. The study included 44 patients (23 men and 21 women). The response and disease control rates were 6.8 and 27.3%, respectively. The median PFS and OS of all patients were 1.84 months [95% confidence interval (CI), 1.32-2.14] and 5.93 months (95% CI, 3.75-10.75), respectively. The risk for progressive disease (PD) increased with higher NLR (hazard ratio, 2.25; 95% CI, 1.3-3.87). The RCS curves also indicated that the higher the NLR, the higher the risk for PD, especially if the NLR value was <3.0. NLR during treatment could predict the risk of PD, suggesting that NLR could be integrated with tumor markers, computed tomographic images and other modalities to enable treatment selection without delay.

DOI： 10.3892/ol.2024.14766

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BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used to improve glycemic control and induce weight loss in individuals with type 2 diabetes (T2D), yet treatment responses vary significantly among individuals. Eating behavior has been hypothesized to influence therapeutic efficacy, but supporting evidence remains limited. METHODS: In this multicenter, prospective observational study, we enrolled 92 individuals with T2D initiating GLP-1RA therapy (liraglutide, dulaglutide, oral semaglutide, or injectable semaglutide) at four institutions in Gifu Prefecture, Japan. Participants were assessed at baseline, 3 months, and 12 months for clinical parameters, dietary intake, and eating behaviors using validated tools (Food Frequency Questionnaire and the Japanese version of the Dutch Eating Behavior Questionnaire [DEBQ-J]). Primary and secondary outcomes included changes in HbA1c, body weight, and eating behavior patterns over 12 months. RESULTS: GLP-1RA therapy significantly reduced HbA1c, body weight, and body fat percentage at 12 months. Notably, external eating scores showed a sustained decrease, while emotional and restrained eating scores exhibited transient changes. Higher baseline external eating scores were independently associated with greater weight reduction and showed a trend toward enhanced glycemic improvement. No significant associations were observed between emotional or restrained eating scores and clinical outcomes. CONCLUSION: This study demonstrates that GLP-1RAs improve both metabolic parameters and external eating behavior in T2D individuals. External eating emerged as a potential behavioral marker predictive of treatment response. These findings suggest that integrating eating behavior assessments may help personalize GLP-1RA therapy and optimize outcomes in clinical practice. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials identifier, UMIN000045362.

DOI： 10.3389/fcdhc.2025.1638681

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AIMS/INTRODUCTION: Diabetic retinopathy (DR) often remains asymptomatic until it reaches advanced stages, when delayed treatment can lead to irreversible visual impairment. To promote timely ophthalmology visits, this study investigated the utility of a simple nerve conduction device, DPNCheck®, as a predictor of DR severity. Previous research has established a relationship between diabetic neuropathy (assessed by conventional nerve conduction studies) and DR progression; however, the specialized equipment and expertise required limit its practicality. In contrast, DPNCheck® is a simpler alternative that quantifies neuropathy severity through the severity of the estimated modified Baba classification (eMBC). MATERIALS AND METHODS: Using electronic medical records (EHRs), we identified individuals with diabetes who underwent DPNCheck® and subsequent ophthalmologic assessment for DR. Based on age and sural nerve conduction data, an eMBC was calculated. Meanwhile, DR severity was scored using a modified Davis classification, defining four stages (DR severity scores 0-3). RESULTS: Of 181 individuals extracted from our hospital's EHRs, 146 were eligible for analysis. Ordinal logistic regression showed that eMBC was significantly associated with DR stage, independent of diabetes duration and HbA1c. Receiver operating characteristic (ROC) curve analyses yielded eMBC cut-off values of 1.11, 1.51, and 1.51 to predict DR severity scores of ≥1, ≥2, and ≥3, respectively. Sensitivities ranged from 0.67 to 0.78, and specificities from 0.66 to 0.81. An eMBC of 1.51 or above was strongly associated with preproliferative or proliferative DR, indicating a need for urgent ophthalmology referral. CONCLUSIONS: DPNCheck®, a simple nerve conduction measurement device, may help predict DR severity and facilitate timely ophthalmologic care.

DOI： 10.3389/fcdhc.2025.1590407

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Owing to its mitogenic and angiogenic characteristics, the use of basic fibroblast growth factor (bFGF) to promote wound healing has been investigated. However, its clinical efficacy has fallen short of expectations due to its instability. Heparin has been reported to stabilize bFGF. Therefore, we hypothesized that the combination of these agents would more effectively promote wound healing than bFGF alone; a single-center, two-arm parallel, single-blind, and a prospective randomized controlled pilot study was therefore performed involving 12 patients who underwent split-thickness skin graft harvesting. To ensure a feasible clinical treatment model, commercially available agents were used. The patients were randomly assigned to either the control group treated with bFGF (n = 6) or the intervention group treated with bFGF and heparin (n = 6) in a 1:1 ratio. The wound area and the wound area variation was assessed each week postoperatively, as was the number of days required for epithelialization. As a supplementary analysis, the least-squares means were calculated using a linear mixed-effects model. The results of this study indicate that the combination of bFGF and heparin may more effectively promote wound healing than bFGF alone, consistent with our hypothesis. A multicenter trial based on these data is ongoing.

DOI： 10.1016/j.conctc.2024.101375

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BACKGROUND: Posthepatectomy liver failure (PHLF) remains a severe complication after liver resection. This retrospective study investigated the correlation of three hepatic functional tests and whether 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy and modified albumin-bilirubin (ALBI) score are useful for predicting PHLF. METHODS: This retrospective cohort study included 413 consecutive patients undergoing hepatectomies between January 2017 and December 2020. To evaluate preoperative hepatic functional reserve, modified ALBI grade, indocyanine green clearance (ICG-R15), and 99mTc-GSA scintigraphy (LHL15) were examined before scheduled hepatectomy. Based on a retrospective chart review, multivariable logistic regression analysis adjusted for confounding factors was performed to confirm that mALBI, ICG-R15, and LHL15 are independent risk factors for PHLF. RESULTS: ICG-R15 and LHL15 were moderately correlated (r =  - 0.61) but this correlation weakened when ICG-R15 was about ≥ 20. Weak correlations were observed between LHL15 and ALBI score (r =  - 0.269) and ALBI score and ICG-R15 (r = 0.339). Of 413 patients, 66 (19%) developed PHLF (20 grade A, 44 grade B, 2 grade C). Multivariable logistic regression analyses, major hepatectomy (P < 0.001), mALBI grade (P = 0.01), ICG-R15 (P < 0.001), and Esophagogastric varices (P = 0.007) were significant independent risk factors for PHLF. Subgroup analysis showed that ICG-R15 < 19, major hepatectomy, and mALBI grade and ICG-R15 ≥ 19, major hepatectomy, LHL15, and Esophagogastric varices were significant independent risk factors for PHLF (P = 0.033, 0.017, 0.02, 0.02, and 0.001, respectively). CONCLUSION: LHL15, the assessment of Esophagogastric varices, and mALBI grade are complementary to ICG-R15 for predicting PHLF risk.

DOI： 10.1186/s12893-024-02624-8

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OBJECTIVES: We aimed to determine (1) the prevalence of constipation among inpatients, (2) the prevalence and symptoms of difficult defecation among constipated inpatients, and (3) the factors associated with constipation. METHODS: We performed a retrospective cohort study over a single day at one university hospital. We analyzed the nursing records for inpatients who had been hospitalized for at least 3 days. The survey items included the symptoms associated with defecation difficulty and nutritional intake. The symptoms of difficult defecation were defined as (1) fewer than three spontaneous bowel movements per week; (2) lumpy or hard stools (Bristol stool form scale types 1-2); (3) straining during defecation; and (4) the sensation of incomplete evacuation during defecation, based on the Roma-IV diagnostic criteria. Constipation was defined as the presence of two or more symptoms of defecation difficulty. Univariate and multivariate analyses were performed to determine the constipation status of the patients. RESULTS: The prevalence of constipation in the university hospital was 12.2%, and the department with the highest prevalence of difficulty with defecation was the Psychiatry Department (64.1%). Of the patients with constipation, 36.8% exhibited symptoms of defecation difficulty other than low frequency of defecation. The factor that was significantly associated with constipation after admission was pre-admission constipation (odds ratio=8.92, p<0.01). CONCLUSIONS: Subjective assessment has limitations for the accurate determination of constipation status. In addition, patients with a history of constipation before admission require early interventions to aid defecation following their admission.

DOI： 10.20407/fmj.2024-006

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This study aimed to validate the DFS (direct fast scarlet) staining in the diagnosis of EC (eosinophilic colitis). The study included 50 patients with EC and 60 with control colons. Among the 60 control samples, 39 and 21 were collected from the ascending and descending colons, respectively. We compared the median number of eosinophils and frequency of eosinophil degranulation by HE (hematoxylin and eosin) and DFS staining between the EC and control groups. In the right hemi-colon, eosinophil count by HE was useful in distinguishing between EC and control (41.5 vs. 26.0 cells/HPF, p < 0.001), but the ideal cutoff value is 27.5 cells/HPF (high-power field). However, this method is not useful in the left hemi-colon (12.5 vs. 13.0 cells/HPF, p = 0.990). The presence of degranulation by DFS allows us to distinguish between the groups even in the left hemi-colon (58% vs. 5%, p < 0.001). DFS staining also enabled a more accurate determination of degranulation than HE. According to the current standard to diagnose EC (count by HE staining ≥20 cells/HPF), mucosal sampling from left hemi-colon is problematic since the number of eosinophils could not be increased even in EC. Determination of degranulated eosinophils by DFS may potentiate the diagnostic performance even in such conditions.

DOI： 10.1111/pin.13475

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Students with developmental disabilities are anxious about a change in environment when graduating from high school to college. Existing research, which is scarce, focuses on the mental health status of students with developmental disabilities entering university. This study investigated the frequency of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) among first-year Japanese university students and their mental health risks post-admission. We conducted a cross-sectional survey for university students within a month of admission, using the Autism Spectrum Quotient (AQ) and Adult ADHD Test (A-ADHD) to demonstrate the frequency of ASD and ADHD. The Counseling Center Assessment of Psychological Symptoms (CCAPS)-Japanese (depression, eating concerns, hostility, social anxiety, family distress, alcohol use, generalized anxiety, and academic distress) evaluated their mental health condition.Of 711 students (20.3 ± 2.1 years; 330 male, 381 female), the number of those showing either ASD or ADHD tendencies was 61 (8.58%). Twenty-three (3.23%) showed symptoms of only ASD, 34 (4.78%) of ADHD, and four (0.56%) of ASD and ADHD. No significant differences existed in the frequency of ASD and ADHD between each sex and major. The scores and frequency of high risk (over the cut-off points) students on all CCAPS-Japanese subscales (except alcohol use) were significantly higher among the ASD and ADHD groups than the control group, which showed no ASD or ADHD tendencies. The frequency of ASD and ADHD characteristics among first-year Japanese university students was 8.58%. They have a high risk of mental health problems when they enter university.

DOI： 10.1007/s10803-024-06515-y

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DOI： 10.1007/s00330-024-11051-5

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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BACKGROUND: Stenotrophomonas maltophilia is a carbapenem-resistant Gram-negative pathogen increasingly responsible for difficult-to-treat nosocomial infections. OBJECTIVES: To describe the contemporary clinical characteristics and genome epidemiology of patients colonized or infected by S. maltophilia in a multicentre, prospective cohort. METHODS: All patients with a clinical culture growing S. maltophilia were enrolled at six tertiary hospitals across Japan between April 2019 and March 2022. The clinical characteristics, outcomes, antimicrobial susceptibility and genomic epidemiology of cases with S. maltophilia were investigated. RESULTS: In total, 78 patients were included representing 34 infection and 44 colonization cases. The median age was 72.5 years (IQR, 61-78), and males accounted for 53 cases (68%). The most common comorbidity was localized solid malignancy (39%). Nearly half of the patients (44%) were immunosuppressed, with antineoplastic chemotherapy accounting for 31%. The respiratory tract was the most common site of colonization (86%), whereas bacteraemia accounted for most infection cases (56%). The 30 day all-cause mortality rate was 21%, which was significantly higher in infection cases than colonization cases (35% versus 9%; adjusted HR, 3.81; 95% CI, 1.22-11.96). Susceptibility rates to ceftazidime, levofloxacin, minocycline and sulfamethoxazole/trimethoprim were 14%, 65%, 87% and 100%, respectively. The percentage of infection ranged from 13% in the unclassified group to 86% in genomic group 6A. The percentage of non-susceptibility to ceftazidime ranged from 33% in genomic group C to 100% in genomic groups 6 and 7 and genomic group geniculate. CONCLUSIONS: In this contemporary multicentre cohort, S. maltophilia primarily colonized the respiratory tract, whereas patients with bacteraemia had the highest the mortality from this pathogen. Sulfamethoxazole/trimethoprim remained consistently active, but susceptibility to levofloxacin was relatively low. The proportions of cases representing infection and susceptibility to ceftazidime differed significantly based on genomic groups.

DOI： 10.1093/jac/dkae168

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OBJECTIVE: The risk factors for residual liver recurrence after resection of colorectal cancer liver metastases were analyzed separately for synchronous and metachronous metastases. METHODS: This retrospective study included 236 patients (139 with synchronous and 97 with metachronous lesions) who underwent initial surgery for colorectal cancer liver metastases from April 2010 to December 2021 at the Fujita Health University Hospital. We performed univariate and multivariate analyses of risk factors for recurrence based on clinical background. RESULTS: Univariate analysis of synchronous liver metastases identified three risk factors: positive lymph nodes (p = 0.018, HR = 2.067), ≥3 liver metastases (p < 0.001, HR = 2.382), and use of adjuvant chemotherapy (p = 0.013, HR = 0.560). Multivariate analysis identified the same three factors. For metachronous liver metastases, univariate and multivariate analysis identified ≥3 liver metastases as a risk factor (p = 0.002, HR = 2.988); however, use of adjuvant chemotherapy after hepatic resection was not associated with a lower risk of recurrence for metachronous lesions. Inverse probability of treatment weighting analysis of patients with these lesions with or without adjuvant chemotherapy after primary resection showed that patients with metachronous liver metastases who did not receive this treatment had fewer recurrences when adjuvant therapy was administered after subsequent liver resection, although the difference was not significant. Patients who received adjuvant chemotherapy after hepatic resection had less recurrence but less benefit from this treatment. CONCLUSION: Risk factors for liver recurrence after resection of synchronous liver metastases were positive lymph nodes, ≥3 liver metastases, and no postoperative adjuvant chemotherapy. Adjuvant chemotherapy is recommended after hepatic resection of synchronous liver metastases.

DOI： 10.1016/j.asjsur.2024.07.001

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BACKGROUND: Sarcopenia is known to bring about adverse outcomes in elderly populations and dialysis patients. However, whether it is a risk factor in kidney transplant recipients (KTRs) has not yet been established. In the present study, the association of sarcopenia with mortality was investigated in KTRs. METHODS: We conducted a single-center prospective cohort study and recruited KTRs who were more than 1-year posttransplant from August 2017 to January 2018. The participants were followed for 5 years, and the Kaplan-Meier method and Cox proportional hazards model were used to assess patient survival. RESULTS: A total of 212 KTRs with a median age of 54 years and median transplant vintage of 79 months were enrolled in this study. Among them, 33 (16%) had sarcopenia according to the Asia Working Group for Sarcopenia 2019 at baseline. During the 5-year follow-up period, 20 (9.4%) died, 5 returned to dialysis after graft loss, and 4 were lost to follow-up. The 5-year overall survival rate was 90%. After 1:1 propensity score matching, a matched cohort with 60 KTRs was generated. The overall survival rate was significantly lower in the sarcopenia group compared to the non-sarcopenia group (p = 0.025, log-rank test). Furthermore, mortality risk was significantly higher in the sarcopenia group compared to the non-sarcopenia group (hazard ratio = 7.57, 95% confidence interval = 0.94-62). CONCLUSION: Sarcopenia was a predictor of mortality in KTRs. KTRs with suboptimal muscle status who were at risk for poor survival could have a clinical benefit by interventions for sarcopenia.

DOI： 10.1111/iju.15539

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

The purpose of this study was to investigate the utility of reconstructed CT images perpendicular to the artery for assessing arterial involvement from pancreatic cancer and compare the interobserver variability between it and the current diagnostic imaging method. This retrospective study included patients with pancreatic cancer in the pancreatic body or tail who underwent preoperative pancreatic protocol CT and distal pancreatectomy. Five radiologists used axial and coronal CT images (current method) and perpendicular reconstructed CT images (proposed method) to determine if the degree of solid soft-tissue contact with the splenic artery was ≤180° or &gt;180°. The generalized estimating equations were used to compare the diagnostic performance of solid soft-tissue contact &gt;180° between the current and proposed methods. Fleiss’ ĸ statistics were used to assess interobserver variability. The sensitivity and negative predictive value for diagnosing solid soft-tissue contact &gt;180° were higher (p &lt; 0.001 for each) and the specificity (p = 0.003) and positive predictive value (p = 0.003) were lower in the proposed method than the current method. Interobserver variability was improved in the proposed method compared with the current method (ĸ = 0.87 vs. 0.67). Reconstructed CT images perpendicular to the artery showed higher sensitivity and negative predictive value for diagnosing solid soft-tissue contact &gt;180° than the current method and demonstrated improved interobserver variability.

DOI： 10.3390/cancers16122271

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BACKGROUND: Synthetic patient data (SPD) generation for survival analysis in oncology trials holds significant potential for accelerating clinical development. Various machine learning methods, including classification and regression trees (CART), random forest (RF), Bayesian network (BN), and conditional tabular generative adversarial network (CTGAN), have been used for this purpose, but their performance in reflecting actual patient survival data remains under investigation. OBJECTIVE: The aim of this study was to determine the most suitable SPD generation method for oncology trials, specifically focusing on both progression-free survival (PFS) and overall survival (OS), which are the primary evaluation end points in oncology trials. To achieve this goal, we conducted a comparative simulation of 4 generation methods, including CART, RF, BN, and the CTGAN, and the performance of each method was evaluated. METHODS: Using multiple clinical trial data sets, 1000 data sets were generated by using each method for each clinical trial data set and evaluated as follows: (1) median survival time (MST) of PFS and OS; (2) hazard ratio distance (HRD), which indicates the similarity between the actual survival function and a synthetic survival function; and (3) visual analysis of Kaplan-Meier (KM) plots. Each method's ability to mimic the statistical properties of real patient data was evaluated from these multiple angles. RESULTS: In most simulation cases, CART demonstrated the high percentages of MSTs for synthetic data falling within the 95% CI range of the MST of the actual data. These percentages ranged from 88.8% to 98.0% for PFS and from 60.8% to 96.1% for OS. In the evaluation of HRD, CART revealed that HRD values were concentrated at approximately 0.9. Conversely, for the other methods, no consistent trend was observed for either PFS or OS. CART demonstrated better similarity than RF, in that CART caused overfitting and RF (a kind of ensemble learning approach) prevented it. In SPD generation, the statistical properties close to the actual data should be the focus, not a well-generalized prediction model. Both the BN and CTGAN methods cannot accurately reflect the statistical properties of the actual data because small data sets are not suitable. CONCLUSIONS: As a method for generating SPD for survival data from small data sets, such as clinical trial data, CART demonstrated to be the most effective method compared to RF, BN, and CTGAN. Additionally, it is possible to improve CART-based generation methods by incorporating feature engineering and other methods in future work.

DOI： 10.2196/55118

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INTRODUCTION: Young adults are hesitant to receive the coronavirus disease 2019 (COVID-19) vaccination owing to concerns regarding adverse events despite the effectiveness of vaccines in preventing SARS-CoV-2 infection-associated serious illness, hospitalization, and death. METHODS: A retrospective cohort study was conducted in Gifu University students receiving the mRNA-1273 vaccine and boosters to elucidate the real incidence of adverse events and factors that prevent them. We examined the adverse events and identified potential risk factors through a self-administered questionnaire on the participants' physical condition after COVID-19 vaccination. RESULTS: Focal/systemic adverse events were highly frequent among university students after receiving the COVID-19 vaccine; however, there were no life-threatening cases or hospitalizations over two years. A higher number of vaccinations (p < 0.001), female sex (p < 0.001), and lower body mass index (BMI) (p = 0.002) were associated with an increased incidence of adverse events on the day of COVID-19 vaccination or the day after vaccination. Regular breakfast consumption was significantly associated with a decreased incidence of post-vaccination itching (p = 0.019) and abdominal pain and diarrhea (p = 0.042). Sufficient sleep duration was significantly associated with a decreased incidence of post-vaccination abdominal pain and diarrhea (p = 0.042). CONCLUSIONS: High frequency of adverse events of COVID-19 mRNA-1273 among Japanese university students was reported. A higher number of shots, female sex, and lower BMI were associated with a higher incidence of adverse events. Regular breakfast and sufficient sleep were associated with fewer adverse events. This study may provide a possible solution to the worldwide problem of vaccine hesitancy.

DOI： 10.1016/j.jvacx.2024.100516

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BACKGROUND: Synthetic patient data (SPD) generation for survival analysis in oncology trials holds significant potential for accelerating clinical development. Various machine learning methods, including classification and regression trees (CART), random forest (RF), Bayesian network (BN), and CTGAN, have been employed for this purpose, but their performance in reflecting actual patient survival data remains under investigation. OBJECTIVE: The aim of this study was to determine the most suitable SPD generation method for oncology trials, specifically focusing on both progression free survival (PFS) and overall survival (OS), which are the primary evaluation endpoints in oncology trials. To achieve this goal, we conducted a comparative simulation of 4 generation methods: CART, RF, BN, and the CTGAN, and the performance of each method was evaluated. METHODS: Using multiple clinical trial datasets, 1000 datasets were generated by using each method for each clinical trial dataset and evaluated as follows: 1) median survival time (MST) of PFS and OS, 2) hazard ratio distance (HRD), which indicates the similarity between the actual survival function and a synthetic survival function, and 3) visual analysis of Kaplan‒Meier (KM) plots. Each method's ability to mimic the statistical properties of real patient data was evaluated from these multiple angles. RESULTS: In most simulation cases, CART demonstrated the high percentages of MSTs of synthetic data falling within the range of 95% confidence interval (CI) of the MST of actual data. These percentages ranged from 88.8% to 98.0% for PFS and from 60.8% to 96.1% for OS. In the evaluation of HRD, CART demonstrated that HRD values were concentrated at approximately 0.9. Conversely, for the other methods, no consistent trend was observed for either PFS or OS. The reason why CART demonstrated better similarity than RF was that CART caused overfitting and RF, which is a kind of ensemble learning, prevented it. In SPD generation, the statistical properties close to the actual data should be the focus, not a well-generalized prediction model. Both the BN and CTGAN methods cannot accurately reflect the statistical properties of the actual data because small datasets are not suitable. CONCLUSIONS: As a method for generating SPD for survival data from small datasets, such as clinical trial data, CART demonstrated to be the most effective method compared to RF, BN, and CTGAN. Additionally, it is possible to improve CART-based generation methods by incorporating feature engineering and other methods in future work.

DOI： 10.2196/55118

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PURPOSE: This study aimed to assess the imaging features and postoperative natural course of 18F-fluorodeoxyglucose (FDG) uptake in the cervical muscles after neck dissection. MATERIALS AND METHODS: This study included 83 patients who underwent preoperative and postoperative 18F-FDG-PET/CT and were diagnosed with head and neck malignancy after neck dissection. Postoperative 18F-FDG-PET/CT was performed within 5 years after neck dissection. Preoperative and postoperative FDG uptake of the trapezius, sternocleidomastoid, scalene, pectoralis major, and deltoid muscles was visually assessed. Increased postoperative uptake was visually defined as higher postoperative FDG uptake than the preoperative one in the corresponding muscle. The maximum standardized uptake value (SUVmax) was measured in cases with increased postoperative uptakes. RESULTS: Increased postoperative uptakes were observed in 43 patients (52%). The trapezius (31/83, 37%), sternocleidomastoid (19/83, 23%), and scalene (12/83, 14%) muscles were involved, as opposed to the pectoralis major and deltoid muscles were not. Increased postoperative uptakes were observed on the dissected side in all 43 patients. Significant differences between SUVmax estimated from the mixed-effects model and postoperative months were observed in the trapezius muscle (Coefficient (β) = -0.038; 95% confidence interval (CI): [-0.047, -0.028]; p < 0.001) and sternocleidomastoid muscle (β =  -0.015; 95% CI: [-0.029, -0.001]; p = 0.046). CONCLUSIONS: Increased postoperative uptakes in the cervical muscles were observed on the dissected side in approximately half of the patients after neck dissection. The SUVmax in the trapezius and sternocleidomastoid muscles decreased after surgery over time.

DOI： 10.1007/s11604-024-01568-6

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BACKGROUND: Mirtazapine blocks 5-hydroxytryptamine type (5-HT)2A, 5-HT2C, 5-HT3 and histamine H1 receptors, similarly to olanzapine. This study aimed to investigate the efficacy and safety of mirtazapine plus granisetron and dexamethasone for carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic cancers. METHODS: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four institutions in Japan. Registered patients were moderately to highly emetogenic chemotherapy-naïve, and were scheduled to receive CBDCA at area under the curve (AUC) ≥ 4 mg/mL per minute. Patients received mirtazapine 15 mg/day orally at bedtime for four consecutive days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the delayed period (24-120 h). RESULTS: Between July 2022 and July 2023, 52 patients were enrolled, and 48 patients were evaluated. CR rates in the delayed (24-120 h), overall (0-120 h), and acute periods (0-24 h) were 83.3%, 83.3%, and 100%, respectively. No grade 3 or higher treatment-related adverse events were observed except for one patient who had grade 3 dry mouth as evaluated by Common Terminology Criteria for Adverse Events version 5.0. CONCLUSIONS: Prophylactic antiemetic therapy with mirtazapine plus granisetron and dexamethasone shows promising efficacy and an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic cancers receiving a CBDCA-based regimen at AUC ≥ 4 mg/mL per minute.

DOI： 10.1016/j.lungcan.2024.107801

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BACKGROUND/AIM: Progress has been made in a triplet preoperative chemotherapy regimen for advanced esophageal cancer. We performed a preliminary investigation of the radiomics features of pathological lymph node metastasis after neoadjuvant chemotherapy using dual-energy computed tomography (DECT). PATIENTS AND METHODS: From January to December 2022, 36 lymph nodes from 10 patients with advanced esophageal cancer who underwent contrast-enhanced DECT after neoadjuvant chemotherapy and radical surgery in our department were studied. Radiomics features were extracted from iodine-based material decomposition images at the portal venous phase constructed by DECT using MATLAB analysis software. Receiver operating characteristic (ROC) analysis and cut-off values were determined for the presence or absence of pathological metastasis. RESULTS: ROC for the short axis of the pathologically positive lymph nodes showed an AUC of 0.713. Long run emphasis (LRE) within gray-level run-length matrix (GLRLM) was confirmed with a high AUC of 0.812. Sensitivity and specificity for lymph nodes with a short axis >10 mm were 0.222 and 1, respectively. Sensitivity and specificity for LRE within GLRLM were 0.722 and 0.833, respectively. Sensitivity and specificity for small zone emphasis (SZE) within gray-level size zone matrix (GLSZM) were 0.889 and 0.667, and zone percentage (ZP) values within GLSZM were 0.722 and 0.778, respectively. Discrimination of existing metastases using radiomics showed significantly higher sensitivity compared to lymph node short axis >10 mm (odds ratios of LRE, SZE, and ZP: 9.1, 28, and 9.1, respectively). CONCLUSION: Evaluation of radiomics analysis using DECT may enable a more detailed evaluation of lymph node metastasis after neoadjuvant chemotherapy.

DOI： 10.21873/anticanres.16965

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PURPOSE: To compare the diagnostic performance of 40 keV and 70 keV virtual monoenergetic images (VMIs) generated from dual-energy CT in the detection of pancreatic cancer. METHODS: This retrospective study included patients who underwent pancreatic protocol dual-energy CT from January 2019 to August 2022. Four radiologists (1-11 years of experience), who were blinded to the final diagnosis, independently and randomly interpreted 40 keV and 70 keV VMIs and graded the presence or absence of pancreatic cancer. For each image set (40 keV and 70 keV VMIs), the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. The diagnostic performance of each image set was compared using generalized estimating equations. RESULTS: Overall, 137 patients (median age, 71 years; interquartile range, 63-78 years; 77 men) were included. Among them, 62 patients (45%) had pathologically proven pancreatic cancer. The 40 keV VMIs had higher specificity (75% vs. 67%; P < .001), PPV (76% vs. 71%; P < .001), and accuracy (85% vs. 81%; P = .001) than the 70 keV VMIs. On the contrary, 40 keV VMIs had lower sensitivity (96% vs. 98%; P = .02) and NPV (96% vs. 98%; P = .004) than 70 keV VMIs. However, the diagnostic confidence in patients with (P < .001) and without (P = .001) pancreatic cancer was improved in 40 keV VMIs than in 70 keV VMIs. CONCLUSIONS: The 40 keV VMIs showed better diagnostic performance in diagnosing pancreatic cancer than the 70 keV VMIs, along with higher reader confidence.

DOI： 10.1007/s11547-024-01806-x

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Recently, conversion surgery (CS) has been reported to improve the prognosis in patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) with a favorable response to intense chemotherapy or chemoradiotherapy. However, few pretherapeutic parameters predict the attainability of CS in patients with UR-PDAC. The present study aimed to explore the pretherapeutic predictors for the attainability of CS in patients with UR-PDAC. The present study retrospectively evaluated 130 patients with UR-PDAC treated at Gifu University Hospital (Gifu, Japan) from January 2015 to December 2021. Survival analysis was performed using the Simon and Makuch-modified Kaplan-Meier method. The hazard ratio (HR) was estimated using a time-varying Cox regression model. The association between each predictor and CS was evaluated using the univariate analysis and age-adjusted Fine-Gray sub-distribution hazard model. The bootstrap bias-corrected area under the receiver operating characteristic curve analysis for predicting CS was used to assess the cut-off values for each predictor. The cumulative incidence rate was calculated with CS as the outcome when divided into two groups based on the cut-off value of each pretherapeutic predictor. Among the 130 patients included in the analysis, only 14 (11%) underwent CS. The median survival time was significantly longer in patients who underwent CS compared with patients without CS (56.3 vs. 14.1 months; P<0.001). The age-adjusted Fine-Gray sub-distribution hazard regression showed that the total protein (TP) [HR 2.81, 95% confidence interval (CI) 1.19-6.65; P=0.018], neutrophil-to-lymphocyte ratio (NLR) (HR 0.53, 95% CI 0.31-0.90; P=0.020), and lymphocyte-to-monocyte ratio (LMR) (HR 1.28, 95% CI 1.07-1.53; P=0.006) were significantly associated with CS. Moreover, TP ≥6.8, NLR <2.84 and LMR ≥3.87 were associated with a higher cumulative incidence of CS. In conclusion, pretherapeutic TP, NLR and LMR are clinically feasible biomarkers for predicting the attainability of CS in patients with UR-PDAC.

DOI： 10.3892/ol.2024.14304

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Publishing type：Research paper (scientific journal)   Publisher：Ivyspring International Publisher  

DOI： 10.7150/jca.91675

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INTRODUCTION: Acute kidney injury (AKI), with a fatality rate of 8.6%, is one of the most common types of multiorgan failure in the intensive care unit (ICU). Thus, AKI should be diagnosed early, and early interventions should be implemented. Urinary liver-type fatty acid-binding protein (L-FABP) could aid in the diagnosis of AKI. METHODS: In this prospective, single-center, observational study, we included 100 patients with trauma. Urinary L-FABP levels were measured using a semi-quantitative rapid assay kit 6 and 12 h after injury. Negative, weakly positive, and strongly positive urinary L-FABP levels were examined using two protocols. Using protocol 1, measurements were performed at 6 h after injury negative levels were considered "negative," and weakly positive and strongly positive levels were considered "positive." Using protocol 2, strongly positive levels at 6 h after injury were considered "positive," and negative or weakly positive levels at 6 h after injury were considered "positive" if they were weakly positive or positive at 12 h after injury. RESULTS: Fifteen patients were diagnosed with AKI. Using protocol 1, the odds ratio (OR) was 20.55 (p = 0.001) after adjustment for the injury severity score (ISS), contrast media use, and shock index. When the L-FABP levels at 6 and 12 h were similarly adjusted for those three factors, the OR was 18.24 (p < 0.001). The difference in ORs for protocols 1 and 2 was 1.619 (p = 0.04). DISCUSSION: Associations between urinary L-FABP and AKI can be examined more precisely by performing measurements at 6 and 12 h after injury than only one time at 6 h.

DOI： 10.3389/fmed.2024.1346183

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BACKGROUND: Medical care and long-term care utilization in the last year of life of frail older adults could be a key indicator of their quality of life. This study aimed to identify the medical care expenditure (MCE) trajectories in the last year of life of frail older adults by investigating the association between MCE and long-term care utilization in each trajectory. METHODS: The retrospective cohort study of three municipalities in Japan included 405 decedents (median age at death, 85 years; 189 women [46.7%]) from a cohort of 1,658 frail older adults aged ≥65 years who were newly certified as support level in the long-term care insurance program from April 2012 to March 2013. This study used long-term care and medical insurance claim data from April 2012 to March 2017. The primary outcome was MCE over the 12 months preceding death. Group-based trajectory modeling was conducted to identify the MCE trajectories. A mixed-effect model was employed to examine the association between long-term care utilization and MCE in each trajectory. RESULTS: Participants were stratified into four groups based on MCE trajectories over the 12 months preceding death as follows: rising (n = 159, 39.3%), persistently high (n = 143, 35.3%), minimal (n = 56, 13.8%), and descending (n = 47, 11.6%) groups. Home-based long-term care utilization was associated with increased MCE in the descending trajectory (coefficient, 1.48; 95% confidence interval [CI], 1.35-1.62). Facility-based long-term care utilization was associated with reduced MCE in the rising trajectory (coefficient, 0.59; 95% CI, 0.50-0.69). Both home-based (coefficient, 0.92; 95% CI, 0.85-0.99) and facility-based (coefficient; 0.53; 95% CI, 0.41-0.63) long-term care utilization were associated with reduced MCE in the persistently high trajectory. CONCLUSIONS: These findings may facilitate the integration of medical and long-term care models at the end of life in frail older adults.

DOI： 10.1371/journal.pone.0297198

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DOI： 10.1186/s12893-023-02278-y

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BACKGROUND: The genus Aeromonas is increasingly implicated in human infections, but knowledge of its clinical characteristics and antimicrobial resistance profiles has been limited owing to its complex taxonomy. METHODS: We conducted a multicenter prospective cohort study of patients with Aeromonas infections at hospitals across Japan. Patients were eligible for inclusion if they had an Aeromonas spp. strain in a clinical culture and were considered infected at the culture site. Clinical data were collected, and isolates underwent susceptibility testing and whole-genome sequencing. RESULTS: A total of 144 patients were included. Hepatobiliary infection accounted for a majority of infections (73% [105 of 144]), which mostly occurred in elderly patients with comorbid conditions, including hepatobiliary complications. The all-cause 30-day mortality rate was 10.0% (95% confidence interval, 4.9%-14.8%). By whole-genome sequencing, 141 strains (98%) belonged to 4 Aeromonas species-A caviae, A hydrophila, A veronii, and A dhakensis-with significant intraspecies diversity. A caviae was predominant in all infection sites except skin and soft tissue, for which A hydrophila was the prevailing species. The genes encoding chromosomally mediated class B, C, and D β-lactamases were harbored by 92%-100% of the isolates in a species-specific manner, but they often lacked association with resistance phenotypes. The activity of cefepime was reliable. All isolates of A hydrophila and A dhakensis carried an mcr-3-like colistin resistance gene and showed reduced susceptibility to colistin. CONCLUSIONS: Hepatobiliary tract was the most common infection site of Aeromonas spp., with A caviae being the dominant causative species. The resistance genotype and phenotype were often incongruent for β-lactam agents.

DOI： 10.1093/ofid/ofad587

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OBJECTIVES: About 90% of Japanese kidney transplantations are conducted from living donors, and their safety and the maintenance of their renal function are critical. This study aims to identify factors that affect the compensation of renal function in living kidney donors after donor nephrectomy. METHOD: In a retrospective cohort study, we reviewed data from 120 patients who underwent nephrectomy as living kidney transplant donors in our department from 2012 to 2021. Univariable and multivariable linear regression analyses were performed for donor factors affecting renal function after donor nephrectomy. RESULT: The multivariable linear regression model revealed that the donor's age (p = 0.025), preoperative estimated Glomerular Filtration Rate (eGFR) (p < 0.001), and hemoglobin A1c (HbA1c) (p = 0.043) were independent risk factors for eGFR at six months after nephrectomy. The eGFR deterioration was more strongly associated with age in females than in males, whereas higher HbA1c values were more strongly associated with eGFR deterioration in males. Higher donor age and higher HbA1c each enhance the deterioration of eGFR six months after living donor nephrectomy. The data suggest that old age in especially female donors and preoperative higher HbA1c in male donors have a harmful impact on their renal function compensation.

DOI： 10.1007/s11255-023-03877-7

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Naldemedine is structurally designed to prevent passage across the blood-brain barrier (BBB), resulting in the attenuation of opioid-induced constipation without interfering with the analgesic effects of opioids. However, the influence of brain metastasis (BM), as one indicator of BBB disruption, on the analgesic effects of opioids in patients treated with naldemedine remains unclear. To examine whether the analgesic effects of opioids following naldemedine treatment are lower in patients with BM than in those without BM, we surveyed inpatients with lung and breast cancers treated with naldemedine at Fujita Health University Hospital between April 2017 and March 2022. Changes in the numeric rating scale (NRS) scores, morphine milligram equivalents (MMEs), and the number of rescues were assessed as analgesia-related outcomes during the first 7 days of naldemedine treatment in patients with or without BM, matched by the propensity score. In total, 172 patients were enrolled. After propensity-score matching, 30 patients with BM and 60 patients without BM were included in the analysis. Changes in NRS scores, MMEs, and the number of rescues did not differ between patients with and without BM. In the linear mixed-effects model, the coefficient of interaction between patients with or without BM and the days for each outcome was not statistically significant. BM does not influence the analgesic effect of opioids in patients with lung and breast cancers treated with naldemedine. Naldemedine may be useful for treating BM.

DOI： 10.3390/jcm12226997

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The diagnostic accuracy of exercise stress echocardiography (ESE) for myocardial ischemia requires improvement, given that it currently depends on the physicians' experience and image quality. To address this issue, we aimed to develop artificial intelligence (AI)-based slow-motion echocardiography using inter-image interpolation. The clinical usefulness of this method was evaluated for detecting regional wall-motion abnormalities (RWMAs). In this study, an AI-based echocardiographic image-interpolation pipeline was developed using optical flow calculation and prediction for in-between images. The accuracy for detecting RWMAs and image readability among 25 patients with RWMA and 25 healthy volunteers was compared between four cardiologists using slow-motion and conventional ESE. Slow-motion echocardiography was successfully developed for arbitrary time-steps (e.g., 0.125×, and 0.5×) using 1,334 videos. The RWMA detection accuracy showed a numerical improvement, but it was not statistically significant (87.5% in slow-motion echocardiography vs. 81.0% in conventional ESE; odds ratio: 1.43 [95% CI: 0.78-2.62], p = 0.25). Interreader agreement analysis (Fleiss's Kappa) for detecting RWMAs among the four cardiologists were 0.66 (95%CI: 0.55-0.77) for slow-motion ESE and 0.53 (95%CI: 0.42-0.65) for conventional ESE. Additionally, subjective evaluations of image readability using a four-point scale showed a significant improvement for slow-motion echocardiography (2.11 ± 0.73 vs. 1.70 ± 0.78, p < 0.001).In conclusion, we successfully developed slow-motion echocardiography using in-between echocardiographic image interpolation. Although the accuracy for detecting RWMAs did not show a significant improvement with this method, we observed enhanced image readability and interreader agreement. This AI-based approach holds promise in supporting physicians' evaluations.

DOI： 10.1007/s10554-023-02997-6

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PURPOSE: Robot-assisted surgery has a multi-joint function, which improves manipulation of the deep pelvic region and contributes significantly to perioperative safety. However, the superiority of robot-assisted surgery to laparoscopic surgery remains controversial. This study compared the short-term outcomes of laparoscopic and robot-assisted surgery for rectal tumors. METHODS: This single-center, retrospective study included 273 patients with rectal tumors who underwent surgery with anastomosis between 2017 and 2021. In total, 169 patients underwent laparoscopic surgery (Lap group), and 104 underwent robot-assisted surgery (Robot group). Postoperative complications were compared via propensity score matching based on inverse probability of treatment weighting (IPTW). RESULTS: The postoperative complication rates based on the Clavien-Dindo classification (Lap vs. Robot group) were as follows: grade ≥ II, 29.0% vs. 19.2%; grade ≥ III, 10.7% vs. 5.8%; anastomotic leakage (AL), 6.5% vs. 4.8%; and urinary dysfunction (UD), 12.1% vs. 3.8%. After adjusting for the IPTW method, although AL rates did not differ significantly between groups, postoperative complications of both grade ≥ II (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.50-0.87, p < 0.01) and grade ≥ III (OR 0.29, 95% CI 0.16-0.53, p < 0.01) were significantly less frequent in the Robot group than in the Lap group. Furthermore, urinary dysfunction also tended to be less frequent in the Robot group than in the Lap group (OR 0.62, 95% CI 0.38-1.00; p = 0.05). CONCLUSION: Robot-assisted surgery for rectal tumors provides better short-term outcomes than laparoscopic surgery, supporting its use as a safer approach.

DOI： 10.1007/s00595-023-02758-x

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BACKGROUND: The most common postoperative complication in malignant rectal surgery is anastomotic leakage (AL). AL after anterior or low anterior resection in rectal tumors is a fatal postoperative complication. Recently, the first automated suture circular stapler, which is expected to reduce the incidence of AL, (J&J). MATERIALS AND METHODS: This study included a total of 248 rectal tumor patients who underwent double stapler technique (DST) anastomotic procedures in the department of gastroenterological surgery /pediatric surgery at Gifu University School of Medicine from January 2017 to December 2021. The experience of a single institution utilizing the The Echelon circular™ stapler (ECP stapler:Manual VS Automatic) in rectal surgery cases was evaluated retrospectively from maintained database. RESULT: One hundred thirty-nine patients (58.4%) were performed by manual circular stapling, 99 patients (41.6%) by powerd circular stapling. Diverting stoma was performed in 45 cases (32.4%) by manual circular stapling, 42 patients (42.4%) by powerd circular stapling Postoperative complications were occurred clavien-dindo grade II or higher in 57 cases (23.9%) and grade III or higher in 20 cases (8.4%). Anastomotic leakage occurred in 14 patients (5.9%) within all grades. After IPTW, the variables of patient characteristics was SMD ≤ 0.2 (Table.3), and there was a significant difference in anastomotic leakage (Odds Ratio (OR), 0.57; 95% Confidence Interval(CI), 0.34-0.98; p = 0.041). In addition, there was no significant difference in postoperative complications in grade II or higher (OR, 0.88; 95%CI, 0.65-1.19; p = 0.417) and grade III or higher (OR, 0.46; 95%CI, 0.29-0.74; p = 0.001) were significantly remarkable lower in powered circular stapling group. CONCLUSION: In this IPTW comparison of patients undergoing rectal reconstructions, the ECP trial cohort had lower risks of several surgical complications AL and statistically signifcant lower rates of ileus/bowel obstruction, infection, and bleeding as Clavien-Dindo ≥ grade II and III as compared with for whom manual circular staplers were used.

DOI： 10.1186/s12893-023-02218-w

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Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.

DOI： 10.1038/s41598-023-44094-7

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Objective The objective of this study was to estimate the humoral immune response evaluated by immunoglobulin G (IgG) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD-IgG) following the third mRNA COVID-19 vaccination in patients with kidney disease who received immunosuppressive treatment. Methods The primary outcome was RBD-IgG levels after the third SARS-CoV-2 vaccination. The primary comparison was the RBD-IgG levels between patients with kidney disease who received immunosuppressive treatment (n=124) and those who did not (n=33). Results The RBD-IgG levels were significantly lower in the patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. The RBD-IgG levels were lower in patients treated with glucocorticoid monotherapy than in those who did not receive immunosuppressive treatment. Even in patients who received ≤ 5 mg prednisolone, the RBD-IgG levels were significantly lower. Nine of the 10 patients who received rituximab within one year before the first vaccination did not experience seroconversion after the third vaccination. Meanwhile, all nine patients who received rituximab only after the second vaccination experienced seroconversion, even if B cell recovery was insufficient. Patients treated with mycophenolate mofetil plus glucocorticoid plus belimumab had significantly lower RBD-IgG levels than those treated with mycophenolate mofetil plus glucocorticoid. Conclusions The RBD-IgG levels were lower in patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. Low-dose glucocorticoid monotherapy affected the humoral immune response following the third mRNA COVID-19 vaccination.

DOI： 10.2169/internalmedicine.1949-23

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DOI： 10.1093/annweh/wxad056

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INTRODUCTION: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) every morning, and ARC condition was defined as eGFRCKD-EPI ≥ 130 mL/min/1.73 m2. Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC. RESULTS: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001). CONCLUSIONS: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC.

DOI： 10.1016/j.jiac.2023.09.017

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Language：Japanese   Publisher：(一社)日本神経学会  

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Aneurysmal subarachnoid hemorrhage (aSAH) is a serious condition with high mortality and a high permanent disability rate. In this study, we examined the association of clinical outcome with the Controlling Nutritional Status (CONUT) score during hospitalization in aSAH patients. A single-center, retrospective observational study was conducted at Gifu University Hospital. Patients transported to the emergency room for aSAH and diagnosed with World Federation of Neurosurgical Societies (WFNS) grade III and IV aSAH between April 2004 and March 2021 were enrolled. A logistic regression model was constructed to evaluate the association of the CONUT score with a modified Rankin scale (mRS) ≥ 3 and delayed cerebral ischemia (DCI). 127 patients diagnosed with WFNS grade III and IV aSAH were analyzed. CONUT score was significantly associated with mRS ≥ 3 during hospitalization. The score obtained by subtracting the CONUT score at admission from the maximum CONUT score was significantly associated with mRS ≥ 3 at discharge. Moreover, the score obtained by subtracting the CONUT score at admission from the maximum CONUT score during the first 14 days was significantly associated with DCI within 14 days from admission. These findings indicate that CONUT score during hospitalization may be a useful daily marker for predicting poor outcomes in aSAH patients.

DOI： 10.1038/s41598-023-39938-1

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OBJECTIVES: Intestinal rotavirus (RV) vaccine replication and host immune response are suggested to be affected by several factors, including maternal antibodies, breastfeeding history, and gut microbiome, which are thought to be similar in pairs of twins. The aim of this study was to determine whether viral shedding from the fecal RV vaccine strain Rotarix® (RV1) and IgG and IgA responses to RV show similarity in pairs of twins. METHODS: Quantitative reverse transcription polymerase chain reaction specific to RV vaccine strain RV1 was used to monitor fecal RV1 viral shedding. RV IgG and IgA titers were measured using an in-house enzyme-linked immunosorbent assay. Fecal RV1 viral shedding and immune responses were compared between twins and singletons with mixed effects and fixed effects models. RESULTS: A total of 347 stool and 54 blood samples were collected from four pairs of twins and twelve singletons during the observation period. Although the kinetics of fecal RV1 viral shedding and immune responses differed among vaccinated individuals, they appeared to be similar within twin pairs. RV shedding after the first dose (P=0.049) and RV IgG titers during the entire observation period (P=0.015) had a significantly better fit in the fixed effect model that assumed that twins have the same response versus the model that assumed that twins have a different response. CONCLUSIONS: The similarity of RV vaccine viral replication in intestine and host immune responses in twin pairs was demonstrated using statistical analysis.

DOI： 10.20407/fmj.2022-039

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Depression in later life is associated with dementia. Changes in motivated behavior are an important mechanism contributing to dysfunctional cognitive control in depression. Although continuous intake of quercetin-rich onion suppresses cognitive decline in aged people by improving their emotional condition, the effect of quercetin-rich onion on emotional condition in people living with cognitive impairment remains unclear. In this randomized, double-blind, placebo-controlled study of subjects with cognitive impairment, we found that subjects wrote more adjectives and adverbs per sentence on the Mini-Mental State Examination after intake of quercetin-rich onion powder than before intake, although regional cerebral blood flow on n-isopropyl-4-[123]iodoamphetamine hydrochloride single-photon emission computed tomography was not changed. In the EPM, mice that had received a quercetin-supplemented chow diet made a significantly increased number of exploratory head dips from the open arms of the maze. Moreover, the 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl decay rate, reflecting redox activity, was increased in mice fed a quercetin-added diet. These results indicate that quercetin-rich onion may affect motivated behavior in subjects with cognitive impairment, for whom quercetin intake may preserve redox homeostasis in the brain.

DOI： 10.1016/j.heliyon.2023.e18401

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OBJECTIVE: This retrospective study aimed to investigate factors associated with inhibition of early aneurysm obliteration after flow diverter (FD) treatment. We also created the early obliteration inhibition (EOI) score for pre-operative evaluation. METHODS: We examined 110 cerebral aneurysms in 104 patients who underwent FD treatment. The following parameters were investigated: age, sex, symptoms, aneurysm location and type, maximum aneurysm diameter, parent vessel diameter, neck diameter, and dome-neck ratio. We also noted aneurysm location relative to the curvature of the parent artery and any branches arising from the aneurysm dome. Procedural factors such as FD diameter and length, number of FDs placed, type of FD, and use of adjunctive coiling were also investigated. Aneurysm obliteration was evaluated using digital subtraction angiography 3 months after the procedure. Adequate obliteration was defined as grade C or D on the O'Kelly-Marotta scale. RESULTS: The following factors inhibited early obliteration: 1) extradural location, 2) saccular aneurysm, 3) aneurysm neck located at the outer convexity of the parent artery, and 4) arterial branch arising from the aneurysm dome. Odds ratios were used to create an EOI score. Receiver operating characteristic curve analysis showed that the optimal cut-off EOI score for adequate obliteration was 1.5 (area under the curve, 0.81; 95% confidence interval, 0.73-0.9; sensitivity, 0.9; specificity, 0.57). CONCLUSION: The EOI score, which is based on factors that inhibit early obliteration, may predict early treatment outcomes of FD placement.

DOI： 10.20407/fmj.2022-033

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BACKGROUND: The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) to determine preoperative chemotherapy's efficacy for esophageal cancer patients. PATIENTS AND METHODS: We investigated the predictability of N-NOSE screening for the clinical effects of preoperative chemotherapy for esophageal cancer patients receiving radical surgery. The index reduction score (IRS) was calculated via the chemotaxis of C. elegans at three points: before treatment, before surgery, and after surgery, and its clinical relevance was examined. RESULT: Thirty-nine patients with esophageal cancer were enrolled from August 2020 to December 2021, and 30 patients receiving radical surgery were examined. Complete response or partial response was achieved in 23 cases (76.7%). When the target of the treatment effect was complete response only, the prediction accuracies of the IRS calculated by area under the curve was 0.85 (95% Confidence interval: 0.62-1) in clinically achieving complete response group, and the sensitivity and specificity were 1 and 0.63, respectively. CONCLUSION: Index reduction score using N-NOSE screening may reflect the efficacy of chemotherapy for esophageal cancer patients. A large-scale prospective study at multiple centers is desired in the future.

DOI： 10.3390/cancers15153870

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DOI： 10.1245/s10434-023-13856-y

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OBJECTIVES: To assess whether using adult day services or personal assistance services can delay the onset of frailty among older adults with low care needs during a 5-year follow-up study. DESIGN: This prospective cohort study was conducted using long-term care and health insurance claims data. SETTING AND PARTICIPANTS: This was a population-based study of 3 municipalities in Osaka, Japan. Initially, 655 nonfrail or prefrail individuals were included from a cohort of 790 population-based adults aged ≥65 years, who were newly certified as being on a support level of the long-term care insurance program from September 2012 to March 2013. METHODS: Using long-term care and health insurance claims data from the Southern Osaka Health and Aging Study, conducted between April 2012 and March 2017, monthly usage of adult day and personal assistance services was measured. Data were analyzed from December 2021 to January 2022. RESULTS: Of the 655 individuals (median age at baseline: 79 years), 436 (66.6%) were female, 388 (59.2%) were nonfrail, and 267 (40.8%) were prefrail, according to the Veterans Affairs Frailty Index. During the 5-year follow-up period, 222 individuals (33.9%) experienced the onset of frailty. The time-dependent Cox regression models showed that using adult day services lowered the risk of frailty when compared with not using such services [hazard ratio (HR) 0.60, 95% CI 0.42-0.86; P = .006], although personal assistance services usage was not associated with the onset of frailty (HR 0.70, 95% CI 0.48-1.03, P = .07). CONCLUSIONS AND IMPLICATIONS: Using adult day services lowered the risk of frailty in older adults with low care needs over the 5-year follow-up period. The findings support the value of providing adult day services to prevent frailty for those in need of long-term care.

DOI： 10.1016/j.jamda.2023.05.036

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BACKGROUND: Dual antiplatelet therapy (DAPT) is necessary to prevent thromboembolic complications after stent-assisted coiling (SAC) or flow-diversion (FD) for cerebral aneurysms, but the optimal antiplatelet regimen remains unclear. OBJECTIVE: To determine the optimal DAPT duration in patients with SAC/FD. METHODS: This multicenter cohort study enrolled patients who received SAC/FD for cerebral aneurysms at seven Japanese institutions between January 2010 and December 2020. The primary outcome was the time from procedure to the occurrence of a composite of target vessel-related thromboembolic events, procedure-unrelated major bleeding events, or death. The cumulative event-free survival rates were analyzed using a Kaplan-Meier curve, and the differences in each outcome between the groups dichotomized by the duration of DAPT were analyzed using the log-rank test. RESULTS: Of 632 patients (median observational period, 646 days), primary outcome occurred in 63 patients (10.0%), most frequently within 30 days after the procedure. The cumulative event-free survival rates at 30 days, 1 year, and 2 years after the procedure were 93.3% (91.4 to 95.3%), 91.5% (89.3 to 93.7%), and 89.5% (87.0 to 92.0%), respectively. The cumulative event-free survival rates after switching to monotherapy were similar for the >91 and <90 days DAPT groups in the population limited to patients who were switched from DAPT to monotherapy without major clinical events. CONCLUSIONS: Thromboembolic events rarely occurred beyond 30 days after SAC/FD. The duration of DAPT may be shortened if patients have a periprocedural period without events. Further prospective studies are warranted to determine the optimal duration of antiplatelet therapy. TRIAL REGISTRATION NUMBER: UMIN000044122 :https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050384.

DOI： 10.1136/jnis-2023-020285

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PURPOSE: We created a clinically applicable nomogram to predict locally advanced prostate cancer using preoperative parameters and performed external validation using an external independent validation cohort. PATIENTS AND METHODS: From a retrospective multicenter cohort study of 3622 Japanese patients with prostate cancer who underwent robot-assisted radical prostatectomy at ten institutions, the patients were divided into two groups (MSUG cohort and validation cohort). Locally advanced prostate cancer was defined as pathological T stage ≥ 3a. A multivariable logistic regression model was used to identify factors strongly associated with locally advanced prostate cancer. Bootstrap area under the curve was calculated to assess the internal validity of the prediction model. A nomogram was created as a practical application of the prediction model, and a web application was released to predict the probability of locally advanced prostate cancer. RESULTS: A total of 2530 and 427 patients in the MSUG and validation cohorts, respectively, met the criteria for this study. On multivariable analysis, initial prostate-specific antigen, prostate volume, number of cancer-positive and cancer-negative biopsy cores, biopsy grade group, and clinical T stage were independent predictors of locally advanced prostate cancer. The nomogram predicting locally advanced prostate cancer was demonstrated (area under the curve 0.72). Using a nomogram cutoff of 0.26, 464 of 1162 patients (39.9%) could be correctly diagnosed with pT3, and 2311 of 2524 patients (91.6%) could avoid underdiagnosis. CONCLUSIONS: We developed a clinically applicable nomogram with external validation to predict the probability of locally advanced prostate cancer in patients undergoing robot-assisted radical prostatectomy.

DOI： 10.1245/s10434-023-13747-2

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PURPOSE: Optimal size selection is important for successful Woven EndoBridge (WEB) treatment. Conventional recommendations for WEB sizing based on aneurysm width and height sometimes require device exchange. We aimed to design a novel volume-based parameter, the ideal WEB-aneurysm volume (iWAVe) ratio, for optimal WEB sizing. METHODS: Consecutive patients who underwent WEB treatment for wide-neck bifurcation aneurysms between January 2021 and May 2022 were retrospectively reviewed. Aneurysm volume was automatically calculated using software. We measured the aneurysm volume based on the expected position of the device within the aneurysm. The WAVe ratio was defined as the ratio of the aneurysm volume to WEB volume. We dichotomized aneurysms treated with a successful sizing or unsuccessful sizing for WEB (successful group and unsuccessful group, respectively). RESULTS: Thirty-five patients were eligible for study enrollment. Ten patients (28.6%) needed to exchange the WEB on the first attempt and required another WEB on the second attempt resulting in deployment success. Hence, 35 aneurysms were in the successful group and 10 were in the unsuccessful group. The median WAVe ratio was 1.0 (range 0.76-1.31) in the successful group and 1.27 (0.58-1.89) in the unsuccessful group. Using logistic regression, iWAVe ratio was from 0.90-1.16 to secure a >80% probability of success by the 95% lower confidence limit. The sensitivity and specificity of the iWAVe ratio for optimal size selection on the first attempt were 0.60 and 1.00, respectively. CONCLUSION: Decision-making based on aneurysm width and the iWAVe ratio could promote optimal WEB sizing.

DOI： 10.1016/j.jocn.2023.06.003

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OBJECTIVES: To investigate the diagnostic performance and interobserver variability in the determination of arterial invasion in pancreatic ductal adenocarcinoma (PDAC) and determine the best CT imaging criterion. METHODS: We retrospectively evaluated 128 patients with PDAC (73 men and 55 women) who underwent preoperative contrast-enhanced CT. Five board-certified radiologists (expert) and four fellows (non-expert]) independently assessed the arterial invasion (celiac, superior mesenteric, splenic, and common hepatic arteries) using a 6-point score: 1, no tumor contact; 2, hazy attenuation ≤ 180°; 3, hazy attenuation > 180°; 4, solid soft tissue contact ≤ 180°; 5, solid soft tissue contact > 180°; and 6, contour irregularity. ROC analysis was performed to evaluate the diagnostic performance and determine the best diagnostic criterion for arterial invasion, with pathological or surgical findings as references. Interobserver variability was assessed using Fleiss's ĸ statistics. RESULTS: Among the 128 patients, 35.2% (n = 45/128) received neoadjuvant treatment (NTx). Solid soft tissue contact ≤ 180° was the best diagnostic criterion for arterial invasion as defined by the Youden Index both in patients who did and did not receive NTx (sensitivity, 100% vs. 100%; specificity, 90% vs. 93%; and AUC, 0.96 vs. 0.98, respectively). Interobserver variability among the non-expert was not inferior to that among the expert (ĸ = 0.61 vs 0.61; p = .39 and ĸ = 0.59 vs 0.51; p < .001 in patients treated with and without NTx, respectively). CONCLUSIONS: Solid soft tissue contact ≤ 180° was the best diagnostic criterion for the determination of arterial invasion in PDAC. Considerable interobserver variability was seen among the radiologists. KEY POINTS: • Solid soft tissue contact ≤ 180° was the best diagnostic criterion for the determination of arterial invasion in pancreatic ductal adenocarcinoma. • Interobserver agreement among non-expert radiologists was almost comparable to that among expert radiologists.

DOI： 10.1007/s00330-023-09521-3

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OBJECTIVE: Although a qualitative diagnosis of plaque causing carotid stenosis has been attempted with carotid computed tomography angiography (CaCTA), no clear findings have been reported. We examined the correlation between the plaque CT values and plaque images obtained by magnetic resonance imaging to derive a qualitative diagnosis of the plaque using CaCTA. METHODS: Preoperative CaCTA images acquired from patients stented for carotid stenosis were retrospectively analyzed with respect to magnetization-prepared rapid acquisition with gradient echo and time-of-flight magnetic resonance angiography data. Carotid plaques in the stenosed region were quantified in terms of CT density and the plaque/muscle ratio (magnetization-prepared rapid acquisition with gradient echo), and correlations between these 2 features were determined. Plaques were classified as stable or unstable based on the plaque/muscle ratio, with the smallest plaque/muscle ratio observed among plaques positive for intraplaque hemorrhage set as the cutoff value (1.76). RESULTS: A total of 165 patients (179 plaques) were included. Perioperative complications included minor stroke (n = 3), major stroke (n = 1, fatal), and hyperperfusion (n = 2). The correlation between CT density and the plaque/muscle ratio was nonlinear (P = 0.0139) and negative (P < 0.0001). The cutoff point (1.76) corresponded to a CT density of 83 HU, supporting this value as a standard reference for plaque stability. CONCLUSIONS: Computed tomography density exhibits a nonlinear (P = 0.0139) and highly negative correlation (P < 0.0001) with the plaque/muscle ratio. Our results demonstrate that plaque characteristics can be meaningfully diagnosed based on CaCTA image data.

DOI： 10.1097/RCT.0000000000001416

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

BACKGROUND

<p lang="en">Reperfusion therapy for acute ischemic stroke efficacy is highly time dependent; therefore, stroke centers are required to further reduce the delays from hospital arrival to treatment efficiently. We developed a visual task management application, Task Calculation Stroke (Task Calc. Stroke: TCS), to facilitate hospital acute ischemic stroke treatment by supporting parallel staff task completion. We evaluated TCS for the reduction of reperfusion therapy delays and improvement of clinical outcomes.

</p> METHODS

<p lang="en">In this multicenter cohort study, patients were directly admitted to 4 comprehensive stroke centers in Japan and given intravenous tissue plasminogen activator and/or mechanical thrombectomy from June 2018 to December 2020. The research team visited each facility and instructed the staff on TCS use for acute ischemic stroke (training stage), after which the staff used TCS independently (TCS stage). We then compared door‐to‐needle time for intravenous tissue plasminogen activator, door‐to‐puncture time for mechanical thrombectomy, and clinical outcomes at discharge according to the modified Rankin Scale among patients treated before training (original stage), during the training stage, or the TCS stage.

</p> RESULTS

<p lang="en"> During the study period, 316 patients with acute ischemic stroke received reperfusion therapy; of these, 246 received intravenous tissue plasminogen activator and 162 mechanical thrombectomy (including 92 receiving both the treatments). The mean door‐to‐needle time was significantly reduced from 58.0 minutes in the original stage to 54.6 minutes in the training stage ( P =0.049) and 47.8 minutes in the TCS stage ( P &lt;0.001). The door‐to‐puncture time did not change during the training stage; however, in the TCS stage, it significantly reduced from 93.8 minutes in the original stage to 88.5 minutes ( P =0.004). The distribution of modified Rankin Scale scores at discharge significantly shifted favorably at the TCS stage ( P =0.003).

</p> CONCLUSION

<p lang="en">In this study, TCS application could reduce workflow time for reperfusion therapy and might have led to improved clinical outcomes.

</p>

DOI： 10.1161/svin.122.000551

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BACKGROUND: Early use of hemostasis strategies, transcatheter arterial embolization (TAE) is critical in cases of pelvic injury because of the risk of hemorrhagic shock and other fatal injuries. We investigated the influence of delays in TAE administration on mortality. METHODS: Patients admitted to the Advanced Critical Care Center at Gifu University with pelvic injury between January 2008 and December 2019, and who underwent acute TAE, were retrospectively enrolled. The time from when the doctor decided to administer TAE to the start of TAE (needling time) was defined as "decision-TAE time." RESULTS: We included 158 patients, of whom 23 patients died. The median decision-TAE time was 59.5 min. Kaplan-Meier curves for overall survival were compared between patients with decision-TAE time above and below the median cutoff value; survival was significantly better for patients with values below the median cutoff value (p = 0.020). Multivariable Cox proportional hazards regression analysis revealed that the longer the decision-TAE time, the higher the risk of mortality (p = 0.031). TAE duration modified the association between decision-TAE time and overall survival (p = 0.109), as shorter TAE duration (procedure time) was associated with the best survival rate (p for interaction = 0.109). CONCLUSION: Decision-TAE time may play a key role in establishing resuscitation procedures in patients with pelvic fracture, and efforts to shorten this time should be pursued.

DOI： 10.3389/fmed.2023.1329167

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INTRODUCTION: Non-technical skills are essential for surgical patient safety and are implemented in clinical practice. However, training for non-technical skills has not been thoroughly investigated. This study aimed to evaluate the learning curve for non-technical skill-based education in herniorrhaphy. METHODS: Quality improvement initiatives, including non-technical skill-based intervention, were performed in the department of surgery. The intervention included declaring the patient safety policy, briefing and debriefing, and criterion for the switching of places of the trainee and instructor as defined by the department. Patients who underwent herniorrhaphy from April 2014 to September 2017 were included. RESULTS: A total of 14 trainees and nine instructors in the pre-intervention period and 14 trainees and seven instructors in the intervention period were included in this study. The median experience of each trainee was 28 and 15 cases in the pre-intervention and intervention groups, respectively. A total of 749 patients were included: 473 in the pre-intervention period and 328 in the intervention period. Demographics and hernia types were mostly similar between groups, and morbidity was not statistically different between the two groups (3.4 vs. 1.2%, p = 0.054). The nonlinear regression model showed an early decline and deep plateau phase of the learning curve in the intervention group. A significant difference was observed in the plateau operation time (61 min in the pre-intervention group and 52 min in the intervention group). CONCLUSION: This study demonstrated the effectiveness of non-technical skill-based intervention for surgical training. An early decline and deep plateau of the learning curve can be achieved with well-implemented quality improvement initiatives. Nonetheless, further studies are needed to establish a training program for non-technical skill-based learning.

DOI： 10.1371/journal.pone.0291698

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Language：Japanese   Publishing type：Research paper (scientific journal)  

BACKGROUND: A few previous studies have compared the patch test (PT) results obtained using different types of PT units. OBJECTIVES: This study aimed to compare PT results between the Patch Tester 'Torii' and Finn Chamber. METHODS: Thirty-four patients with intractable scalp dermatitis were enrolled in this study. PT were performed with three kinds of amphoteric surfactants, cocamidopropyl betaine (CAPB), high-concentration CAPB (h-CAPB), and lauramidopropyl betaine (LAPB), using both the Patch Tester 'Torii' and Finn Chamber, and the changes in the subjects' symptoms after they stopped using these surfactants were examined. RESULTS: Regarding the PT results for CAPB, h-CAPB, and LAPB, the results obtained with the Finn Chamber included a significantly lower frequency of irritant reactions (CAPB; p=0.003, h-CAPB; p=0.046, LAPB; p=0.002) than those obtained with the Patch Tester 'Torii'. However, there were no significant differences in the frequencies of positive reactions between the Patch Tester 'Torii' and Finn Chamber in each surfactant. The same tendency was seen in PT with LAPB (p=0.041) in 17 selected patients, who showed positive or doubtful reactions in PT performed with the surfactant-containing products they had used and whose symptoms 'markedly improved' or 'improved' after they stopped using these products. Among these surfactants, CAPB exhibited the highest positivity rate; however, the differences were not significant. CONCLUSION: In patients with intractable scalp dermatitis, PT of the abovementioned surfactants performed using the Finn Chamber were superior to those conducted using the Patch Tester 'Torii' because they resulted in fewer irritant reactions.

DOI： 10.15036/arerugi.72.1038

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Language：English  

[This corrects the article DOI: 10.3389/fmed.2022.1089219.].

DOI： 10.3389/fmed.2023.1281829

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BACKGROUND: Snow sports are a popular recreational activity; however, the incidence of injury of snow sports can be high for skiers and snowboarders. Our hospital receives severe trauma cases from snow resorts and hospitals throughout the region. This study aimed to determine whether the risk of snow sports-related major trauma that requires emergency surgery under general anesthesia varies by the equipment and injury mechanism. METHODS: This retrospective cohort study included patients with snow sports trauma referred to Gifu University Hospital, Japan between November 2010 and March 2020. We analyzed the need for emergency operation under general anesthesia within 24 h using Fisher's exact test. We identified 106 patients: (1) 90 in the snowboarders' group and 16 in the skiers' group or (2) 46 in the fall after jumping group (jumping group), 27 in the collide with other people and obstacle group (collision group), and 33 in the fall during gliding group (gliding group). RESULTS: Snowboarders were nearly twice as likely as skiers to require emergency surgery under general anesthesia (44% vs. 25%; p = 0.236]. No significant associations were found between emergency surgery under general anesthesia and injury mechanism, but half of the patients in the jumping group required emergency surgery. CONCLUSIONS: Snowboard as equipment and falls after jumping as a mechanism of injury tended to be associated with emergency surgery under general anesthesia, with no significant differences. In order to provide adequate resources for snow sports trauma, the cause of the patient's injury is strongly related to the urgency of the condition, and transport to a trauma center should be actively considered. Further studies are warranted with respect to the effects of personal protective equipment and skill level.

DOI： 10.1016/j.injury.2022.12.028

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DOI： 10.1016/j.prnil.2022.06.003

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OBJECTIVES: This study aimed to determine the impact of the approval of prothrombin complex concentrates on the treatment of vitamin K antagonist-related intracerebral hemorrhage. MATERIALS AND METHODS: We retrospectively studied all patients with vitamin K antagonist-related intracerebral hemorrhage treated with prothrombin complex concentrate at our institutes between January 2010 and June 2021. Before approval, prothrombin complex concentrate was administered as either 500 or 1000 IU at the physician's discretion (previous dose group). After approval, we adopted the manufacturer's recommended regimen (recommended dose group). The primary outcome was post-administration international normalized ratio. Secondary outcomes were the amount of prothrombin complex concentrate administered and proportion of post-administration international normalized ratio <1.5, hematoma expansion, thrombotic events within 30 days, modified Rankin scale 0-3 at discharge, and in-hospital mortality. RESULTS: Thirty-two and 19 patients in the previous and recommended dose groups, respectively, were included. The post-administration international normalized ratio significantly differed between groups. The prothrombin complex concentrate dose and proportion of patients achieving post-administration international normalized ratio <1.5 were significantly higher in the recommended dose group than in the previous dose group (1500 IU vs. 500 IU, p<0.001 and 100% vs. 68%, p = 0.008). The proportions of hematoma expansion, thromboembolic events, modified Rankin scale 0-3, and mortality did not differ between groups. CONCLUSION: After prothrombin complex concentrate approval, prothrombin time-international normalized ratio correction was more effective with a significant increase in the prothrombin complex concentrates dose for vitamin K antagonist-associated intracerebral hemorrhage; however, there was no apparent difference in clinical outcomes.

DOI： 10.1016/j.jstrokecerebrovasdis.2022.106861

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Language：Japanese   Publisher：(NPO)日本脳神経血管内治療学会  

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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INTRODUCTION: Favipiravir, an antiviral agent with activity against SARS-CoV-2, was made available to hospitals in Japan for off-label use among COVID-19 patients between 2020 and 2021. METHODS: A nationwide observational cohort study was conducted on patients who received favipiravir as part of clinical care between February 2020 and December 2021. Information was collected on demographics, comorbidities, severity of illness, use of favipiravir and other medications targeting COVID-19, adverse events, clinical status at 7 and 14 days and clinical outcome one month after admission to the hospital. RESULTS: A total of 17,508 hospitalized patients who received favipiravir were registered from 884 hospitals. In terms of demographics, 55.9% were age ≥60 years, and 62.3% were male. At least one of the four surveyed comorbidities was present in 45.5% of the patients. The rates of clinical improvement at 7 and 14 days were 72.4％ and 87.5%, 61.4% and 76.6%, and 45.4% and 59.5% for mild, moderate, and severe diseases, respectively. The case fatality rates within a month from hospitalization were 3.3%, 12.6%, and 29.1% for mild, moderate, and severe diseases, respectively. Significant correlations were observed between death and advanced age, male sex, moderate or severe disease, diabetes, cardiovascular diseases, and immunosuppression. Commonly reported adverse events included uric acid level increase or hyperuricemia (16.8%), liver function abnormalities (6.9%), and rash (1.0%). CONCLUSIONS: Favipiravir was well tolerated among COVID-19 patients. The study provides insights into the use of this agent at hospitals across Japan in the early phase of the pandemic.

DOI： 10.1016/j.jiac.2022.10.008

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BACKGROUND: To create a nomogram for predicting prostate cancer (PCa) with lymph node involvement (LNI) in the robot-assisted radical prostatectomy (RARP) era. METHODS: A retrospective multicenter cohort study was conducted on 3195 patients with PCa who underwent RARP at nine institutions in Japan between September 2012 and August 2021. A multivariable logistic regression model was used to identify factors strongly associated with LNI. The Bootstrap-area under the curve (AUC) was calculated to assess the internal validity of the prediction model. RESULTS: A total of 1855 patients were enrolled in this study. Overall, 93 patients (5.0%) had LNI. On multivariable analyses, initial prostate-specific antigen, number of cancer-positive and-negative biopsy cores, biopsy Gleason grade, and clinical T stage were independent predictors of PCa with LNI. The nomogram predicting PCa with LNI has been demonstrated (AUC 84%). Using a nomogram cut-off of 6%, 492 of 1855 patients (26.5%) would avoid unnecessary pelvic lymph node dissection, and PCa with LNI would be missed in two patients (0.1%). The sensitivity, specificity, and negative predictive values associated with a cutoff of 6% were 74%, 80%, and 99.6%, respectively. CONCLUSIONS: We developed a clinically applicable nomogram for predicting the probability of patients with PCa with LNI.

DOI： 10.3390/diagnostics12102545

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BACKGROUND: During one-lung ventilation (OLV), deterioration of pulmonary oxygenation reduces arterial oxygen saturation and cerebral oxygen saturation (rSO2). However, oxidative stress during OLV causes lung injury, so the fraction of inspiratory oxygen (FiO2) should be kept as low as possible. We investigated the changes in rSO2 under propofol or desflurane anesthesia while percutaneous oxygen saturation (SpO2) was kept as low as possible during OLV. METHODS: Thirty-six patients scheduled for thoracic surgery under OLV in the lateral decubitus position were randomly assigned to propofol (n = 19) or desflurane (n = 17) anesthesia. FiO2 was set to 0.4 at the start of surgery under two-lung ventilation (measurement point: T3) and then adjusted to maintain an SpO2 of 92% to 94% after the initiation of OLV. The primary outcome was the difference in the absolute value of the decrease in rSO2 from T3 to 30 minutes after the initiation of OLV (T5), which was analyzed by an analysis of covariance adjusted for the rSO2 value at T3. RESULTS: The mean rSO2 values were 61.5% ± 5.1% at T3 and 57.1% ± 5.3% at T5 in the propofol group and 62.2% ± 6.0% at T3 and 58.6% ± 5.3% at T5 in the desflurane group. The difference in the absolute value of decrease between groups (propofol group - desflurane group) was 0.95 (95% confidence interval, [-0.32, 2.2]; P = .152). CONCLUSIONS: Both propofol and desflurane anesthesia maintain comparable cerebral oxygenation and can be used safely, even when the SpO2 is kept as low as possible during OLV.

DOI： 10.1097/MD.0000000000030030

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Language：Japanese   Publisher：(株)医学書院  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00270&link_issn=&doc_id=20221026050015&doc_link_id=10.11477%2Fmf.1681202034&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1681202034&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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Healthcare-associated COVID-19 among vulnerable patients leads to disproportionate morbidity and mortality. Early pharmacologic intervention may reduce negative sequelae and improve survival in such settings. This study aimed to describe outcome of patients with healthcare-associated COVID-19 who received early short-course remdesivir therapy. We reviewed the characteristics and outcome of hospitalized patients who developed COVID-19 during an outbreak that involved two wards at a non-acute care hospital in Japan and received short-course remdesivir. Forty-nine patients were diagnosed with COVID-19, 34 on a comprehensive inpatient rehabilitation ward and 15 on a combined palliative care and internal medicine ward. Forty-seven were symptomatic and 46 of them received remdesivir. The median age was 75, and the median Charlson comorbidity index was 6 among those who received it. Forty-one patients had received one or two doses of mRNA vaccines, while none had received a third dose. Most patients received 3 days of remdesivir. Of the patients followed up to 14 and 28 days from onset, 41/44 (95.3%) and 35/41(85.4%) were alive, respectively. Six deaths occurred by 28 days in the palliative care/internal medicine ward and two of them were possibly related to COVID-19. Among those who survived, the performance status was unchanged between the time of onset and at 28 days.

DOI： 10.1016/j.jiac.2022.08.025

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OBJECTIVES: Delta C-peptide derived by the glucagon stimulation test is a reliable value for the evaluation of the pancreatic endocrine function after pancreas transplantation. We examined the associations between delta C-peptide as pancreatic graft endocrine function and donor background factors. METHODS: Sixty-five cases of pancreatic transplantation from brain-dead donors, which were performed in our facility, were enrolled in this study. Enrolled recipients underwent a glucagon stimulation test within 1 to 3 months after transplantation to evaluate the pancreatic graft endocrine function with delta C-peptide to compare donor background factors. RESULTS: The following factors were associated with significant deterioration of the delta C-peptide: age of 50 years or greater, death from cerebrovascular accident, hemoglobin A1c level of 5.6% or greater, creatinine level of 1.0 mg/dL or greater, C-reactive protein level of 25 mg/dL or greater, and sodium level of 150 mmol/L or greater. In addition, increased numbers of these donor factors indicated significantly greater deterioration of the posttransplant pancreatic endocrine function (P < 0.001). CONCLUSIONS: To secure insulin independence after pancreas transplantation, which means maintaining a delta C-peptide level of 1.0 ng/mL or greater on a glucagon stimulation test, the utilization of donors, who possesses more than equal to 3 of the donor factors identified in this study, should be carefully considered.

DOI： 10.1097/MPA.0000000000002093

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Mobile food records are currently used to determine the nutrition of healthy subjects. To determine the accuracy of such records, we evaluated the nutritional composition of a test meal (noodles and fruit juice) and a hospital meal (Japanese set meal) using two types of mobile food records. Eighteen healthy subjects (2 males and 16 females) were enrolled. Using these diets and validated nutrient-composition information, we evaluated the accuracy of the dietary assessments made by two dietary-record applications, Asken® and Calomeal®, over 5 days. For the test meal, the values provided by the two applications were close to the actual values. In contrast, for the hospital meal, the values provided by the two applications were approximately 1.5 times higher than the actual values. A linear-mixed-model analysis showed that the total energy, carbohydrate, and salt contents were significantly overestimated in the hospital meal. Protein also tended to be overestimated, while the fat content was not significantly overestimated. Furthermore, the total energy and fat contents increased significantly over time. No association with age was observed. A comparison of the coefficients of variation (CVs) for each nutrient in the hospital meal indicated that the fat levels were significantly higher than those in the test meal. In conclusion, the accuracy of mobile food records depends on the type of meal. Our data will provide lessons for the use of meal-recording applications in special cases, such as hospital food.

DOI： 10.3390/nu14183754

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Language：English   Publisher：(公社)日本医学放射線学会  

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BACKGROUND: The modified Glasgow prognostic score (mGPS) includes C-reactive protein and serum albumin levels and is a useful prognostic tool for malignant tumors. The immune system affects cancer progression and recurrence and treatment response. We hypothesized that increasing the lymphocyte count improves mGPS, and we created a new prognostic marker termed immune-mGPS (imGPS). METHODS: This study included 461 patients with head and neck squamous cell carcinoma (HNSCC). The imGPS was calculated as the conventional mGPS with one additional point for a low lymphocyte count (<1250/μL). RESULTS: Addition of the lymphocyte count to mGPS significantly increased the area under the time-dependent receiver operating characteristic curve for overall and progression-free survivals. The added predictive abilities of this tool were supported by improvement in both net reclassification and integrated discrimination. CONCLUSION: imGPS is a more accurate predictor of clinical outcome in patients with HNSCC than mGPS.

DOI： 10.1002/hed.27170

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Blood purification is performed to control cytokines in critically ill patients. The relationship between the clearance (CL) and the membrane area during adsorption is not clear. We hypothesized that the CL increases with the hydrophobic area when hydrophobic binding contributes to cytokine adsorption. We investigated the relationship between the hemofilter membrane area and the CL of the high mobility group box 1 protein (HMGB-1) and interleukin-6 (IL-6). We performed experimental hemofiltration in vitro using polymethyl methacrylate membranes CH-1.8W (1.8 m2) and CH-1.0N (1.0 m2), as well as polysulfone membrane NV-18X (1.8 m2). After adding 100 mg of HMGB1 or 10 μg of IL-6 into the test solution, experimental hemofiltration was conducted for 360 min in a closed-loop circulation system, and the same amount of HMGB1 and IL-6 was added after 180 min. With CH-1.8W and CH-1.0N, both HMGB-1 and IL-6 showed a rapid concentration decrease of more than 70% at 180 min and 360 min after the re-addition. At 15 min, the CL of HMGB-1 was CH-1.8W: 28.4 and CH-1.0N: 19.8, and that of IL-6 was CH-1.8W: 41.1 and CH-1.0N: 25.4. CH-1.8W and CH-1.0N removed HMGB1 and IL-6 by adsorption and CH-1.8W was superior in CL, which increased with a greater membrane area.

DOI： 10.3390/membranes12080811

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PURPOSE: To identify the risk factors for a recurrence of a bleb-related infection (BRI). STUDY DESIGN: Retrospective cohort study. METHODS: The medical records of all patients diagnosed with BRI at Gifu University Hospital between January 1989 and December 2020 were reviewed. The time when conjunctival hyperemia could not be detected and when the anterior chamber was quiet were defined as the resolution time of the BRI. The primary endpoint was a recurrence of a BRI. Kaplan-Meier estimation and the Cox proportional hazards model were used to determine the risk of a recurrence from the initial onset data of each eye. Bacteriological studies were performed to determine the pathogen causing the BRI. RESULTS: There were 108 eyes of 103 patients followed for at least 3 months after the initial BRI. A recurrent bleb infection developed in 21 (19.4%) eyes of 21 patients (13 men, 8 women). Log-rank test at the 10-year follow-up examination revealed that hypotony at the onset of the BRI (P=0.004), the prophylactic use of topical antibiotics at the onset of the BRI (P=0.046), and bleb leakage after the resolution of the BRI (P=0.021) were significantly associated with a BRI recurrence. Cox proportional hazards model showed that ocular hypotony at the onset of the BRI (unadjusted, P=0.007; adjusted for bleb leakage, P=0.015) and bleb leakage after the resolution of the BRI (unadjusted, P=0.027; adjusted for hypotony, P=0.024) were significantly associated with a BRI recurrence. Other factors were not significantly associated with the recurrence of a BRI. CONCLUSION: We recommend close observations when a bleb leakage is detected after the BRI has resolved.

DOI： 10.1007/s10384-022-00937-w

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BACKGROUND & AIMS: Skeletal muscle mass decreases in patients with chronic kidney disease, especially those on dialysis with end-stage kidney disease. On the other hand, the recovery of renal function due to successful kidney transplantation (KT) improves skeletal muscle mass loss. However, low protein intake may influence the changes in skeletal muscle mass after KT. The aim of the present study is to examine the association of the changes in skeletal muscle mass with protein intake in kidney transplant recipients (KTRs). METHODS: A cohort study was conducted in KTRs and living-kidney donors (LKDs). Skeletal muscle mass index (SMI) was measured using bioelectrical impedance analysis before KT and at 1 month and 12 months after KT. Protein intake was calculated with 24-h urine urea nitrogen from the Maroni formula at 12 months after KT. To evaluate the association between protein intake and the changes in SMI during the first year after KT, we performed a multivariable regression analysis adjusted for covariates including age, sex, cumulative glucocorticoids, cumulative hospitalization, diabetes mellitus, and SMI before KT. RESULTS: In KTRs (n = 64), the median SMI was 7.26 kg/m2 before KT, which decreased to 7.01 kg/m2 at 1 month after KT and increased to 7.55 kg/m2 at 12 months after KT. In LKDs (n = 17), the median SMI was 6.24 kg/m2 before KT which increased to 6.40 kg/m2 at 1 month after KT and further increased to 6.95 kg/m2 at 12 months after KT. The changes in SMI during the 1-year period after KT exhibited a positive correlation with protein intake (p = 0.015) after adjustment. The predicted value of protein intake in KTRs, whose values of SMI before KT and at 12 months after KT were the same, was 0.72 g/kg ideal body weight (IBW)/day using the multivariable non-linear regression model. CONCLUSIONS: In KTRs, insufficient protein intake adversely affected the recovery from skeletal muscle mass loss after KT. Therefore, a protein intake of at least more than 0.72 g/kg IBW/day, the predicted value obtained in the present study, might be recommended for KTRs suffering from skeletal muscle mass loss.

DOI： 10.1016/j.clnu.2022.07.028

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BACKGROUND: Despite the popularity and superiority of resorbable alloplastic materials in orbital fracture reconstruction, it is unclear whether the reconstructed wall is maintained after implant resorption. Although unsintered hydroxyapatite/poly-L-lactide (u-HA/PLLA) is one such material, it is different from conventional materials for the replacement of natural bones. Therefore, this study investigated the intermediate-term safety and efficacy of u-HA/PLLA implants compared to those of implants made with other alloplastic materials. METHODS: We retrospectively analyzed 240 eligible patients who underwent orbital fracture reconstruction with one alloplastic material between January 2006 and October 2018. Materials used for treatment were as follows: u-HA/PLLA sheet in 101 patients; u-HA/PLLA mesh in 38 patients; poly-L-lactic acid (PLA)/poly-glycolic acid (PGA) mesh in 47 patients; silicone sheet in 35 patients; and titanium mesh in 19 patients. Intermediate-term follow-up was performed for a median duration of 48.2 months. A chart review was performed. Postoperative complications and factors affecting them were studied. Reconstructed area deformities were assessed using computed tomography. RESULTS: Postoperative complications occurred significantly more frequently in patients reconstructed with the silicone sheet than in those reconstructed with the u-HA/PLLA sheet. Deformities were found for the silicone sheet (28.6%) and PLA/PGA mesh (31.9%). These deformity rates were significantly higher than those for the u-HA/PLLA sheet. CONCLUSIONS: Compared to other alloplastic materials, u-HA/PLLA has low rates of postoperative complications and reconstructed area deformities. Because of its complete absorption, clinicians should consider using u-HA/PLLA as an alloplastic material for orbital wall reconstruction.

DOI： 10.1097/PRS.0000000000009554

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Background: An association has been reported between rotator cuff tear and inflammation. We hypothesized that blood flow in the anterior humeral circumflex artery would reflect synovial inflammation in the shoulder. This study aimed to clarify the association of blood flow in the anterior humeral circumflex artery with synovial inflammation and shoulder pain in patients with rotator cuff tears. Methods: In this prospective, cross-sectional study, tissue samples from the synovium in the rotator interval were obtained from 33 patients undergoing arthroscopic rotator cuff repair. Reverse transcription-polymerase chain reaction and real-time polymerase chain reaction were performed to determine the messenger RNA expression of inflammatory mediators, growth factors, and matrix metalloproteinases. Additional tissue samples were fixed for histologic evaluation. Before surgery, we measured the peak systolic velocity in the anterior humeral circumflex artery using pulse Doppler ultrasonography. Results: The peak systolic velocity in the anterior humeral circumflex artery was positively correlated with the messenger RNA expression of interleukin 1β, interleukin 8, and matrix metalloproteinase 3 genes (r = 0.49, P = .004; r = 0.55, P = .001; and r = 0.39, P = .026, respectively), as well as histologic synovitis scores (r = 0.48, P = .005). Additionally, it was significantly higher in patients with resting pain than in those without resting pain (P = .048). Conclusion: The peak systolic velocity in the anterior humeral circumflex artery is associated with the severity of synovial inflammation. Our results suggest that assessing the peak systolic velocity in the anterior humeral circumflex artery is useful for evaluating the severity of synovial inflammation.

DOI： 10.1016/j.jseint.2022.04.006

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PURPOSE: To compare the diagnostic performance for detecting vascular involvement and determining resectability differences regarding pancreatic ductal adenocarcinoma (PDAC) between contrast-enhanced CT and MRI. METHODS: This retrospective study evaluated 82 patients (73 years, 46 men) with PDAC who underwent both preoperative contrast-enhanced CT and MRI from January 2008 to March 2021. Two radiologists independently categorized vascular involvements for celiac, superior mesenteric, splenic, and common hepatic arteries, and portal, superior mesenteric, and splenic veins into no tumor contact, solid soft-tissue contact ≤ 180°, or solid soft-tissue contact > 180°. The radiologists also classified resectability into resectable, borderline resectable, or locally advanced. Receiver-operating-characteristic (ROC) analysis was conducted to evaluate the diagnostic performances for detecting vascular involvements which were confirmed by pathological or intraoperative findings. The proportion of resectability classifications was compared between CT and MRI by the Fisher's exact test. RESULTS: No statistical difference was found in the diagnostic performances for detecting vascular involvement in CT (area under the ROC curve [AUC], 0.50-0.89) and MRI (AUC, 0.51-0.75) (P = 0.06-> 0.99). Resectability on CT were 79% and 68%, 20% and 26%, and 1% and 6% for resectable, borderline resectable, and locally advanced tumors for reviewers 1 and 2; those on MRI were 87% and 81%, 12% and 13%, and 1% and 6%, respectively. The proportion of resectability classifications was not different between CT and MRI (P = 0.48 and = 0.15 for reviewers 1 and 2, respectively). CONCLUSION: The diagnostic performance for detecting vascular involvement and determining resectability of PDAC on contrast-enhanced MRI were comparable with pancreatic protocol CT.

DOI： 10.1007/s00261-022-03581-7

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Language：Japanese   Publisher：(一社)日本外傷学会  

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DOI： 10.1099/mgen.0.000797

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Language：Japanese   Publisher：(一社)医療の質・安全学会  

当院では、2017年4月1日から2018年3月31日の間に放射線診断専門医によって報告書が作成された30298件の画像検査について依頼医による確認状況を調査した。その結果、87件の確認不足症例があり、このうち28件の偶発所見の見落とし症例を認めた。本研究では、画像所見での偶発所見の見落とし症例における報告書様式の特徴について検討した。28件の見落とし症例と偶発所見が適切に対応された28症例(対照群)を対象とした。見落とし群と対照群との間に患者背景に差は認められず、所見欄で指摘された病変の数と所見欄の文字数にも有意差はなかった。対照群では見落とし群と比較して、所見要約に偶発所見の記載がある様式1の割合が高い傾向にあり、偶発所見に対する具体的な指示のある報告書の割合が高かった。医師26名に対するアンケート調査では、15人(58%)が所見欄から確認すると答えた一方、11人(42%)が所見要約欄から確認するとしていた。確認不足対策を講じる以前の報告書を振り返ることで様式に応じた「見落とし要因」を推測することができ、改めて視認性に配慮した報告書の作成が見落とし防止に有用であることが確認された。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J04895&link_issn=&doc_id=20220523280004&doc_link_id=10.11397%2Fjsqsh.17.144&url=https%3A%2F%2Fdoi.org%2F10.11397%2Fjsqsh.17.144&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

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BACKGROUND: Autophagy is a cellular process that degrades a cell's own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM). OBJECTIVES: The authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart. METHODS: Using left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy. RESULTS: The clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period. CONCLUSIONS: The authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart.

DOI： 10.1016/j.jacc.2021.11.059

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BACKGROUND: To evaluate the utility of histogram analysis (HA) of apparent diffusion coefficient (ADC) values to predict the overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) and to correlate with pathologically evaluated massive intratumoral necrosis (MITN). MATERIALS AND METHODS: Thirty-nine patients were included in this retrospective study with surgically resected PDAC who underwent preoperative magnetic resonance imaging. Twelve patients received neoadjuvant chemotherapy. HA on the ADC maps were performed to obtain the tumor HA parameters. Using Cox proportional regression analysis adjusted for age, time-dependent receiver-operating-characteristic (ROC) curve analysis, and Kaplan-Meier estimation, we evaluated the association between HA parameters and OS. The association between prognostic factors and pathologically confirmed MITN was assessed by logistic regression analysis. RESULTS: The median OS was 19.9 months. The kurtosis (P < 0.001), entropy (P = 0.013), and energy (P = 0.04) were significantly associated with OS. The kurtosis had the highest area under the ROC curve (AUC) for predicting 3-year survival (AUC 0.824) among these three parameters. Between the kurtosis and MITN, the logistic regression model revealed a positive correlation (P = 0.045). Lower survival rates occurred in patients with high kurtosis (cutoff value > 2.45) than those with low kurtosis (≤ 2.45) (P < 0.001: 1-year survival rate, 75.2% versus 100%: 3-year survival rate, 14.7% versus 100%). CONCLUSIONS: HA derived kurtosis obtained from tumor ADC maps might be a potential imaging biomarker for predicting the presence of MITN and OS in patients with PDAC.

DOI： 10.1186/s12880-022-00751-3

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OBJECTIVE: To assess the magnetic resonance imaging (MRI) findings of endometrial cancers and to reveal the differences between endometrioid carcinoma (EC), serous carcinoma (SC), and clear cell carcinoma (CCC). METHODS: In this study, 274 consecutive patients with histopathologically confirmed endometrial cancer (231 ECs, 25 SCs, and 18 CCCs) who underwent MRI before hysterectomy were enrolled. MRI images were retrospectively reviewed and compared between the three pathologies. RESULTS: The maximum diameters (55.6 ± 34.7 vs. 39.3 ± 21.6 vs. 39.4 ± 26.8 mm) (p < 0.05) and apparent diffusion coefficient (ADC) values (1.11 ± 0.21 vs. 0.84 ± 0.17 vs. 0.86 ± 0.16 × 10-3 mm2/s) (p < 0.01) were significantly greater in CCCs than in ECs and SCs, respectively. Infiltrative growth pattern (33% vs. 6%) (p < 0.01) was more frequent in CCCs than in ECs. Peritoneal dissemination (16% vs. 0%) (p < 0.01) and heterogeneous signal on diffusion-weighted (61% vs. 32%) (p < 0.05) images were more frequent in SCs than in ECs, respectively. Abnormal ascites (12% vs. 11% vs. 0%) and heterogeneous signal on T1-weighted (28% vs. 50% vs. 9%), T2-weighted (64% vs. 72% vs. 36%), and fat-suppressed gadolinium-enhanced T1-weighted (80% vs. 90% vs. 46%) images were more frequent in SCs and CCCs than in ECs, respectively (p < 0.05). CONCLUSIONS: SCs frequently exhibited a heterogeneous signal with peritoneal dissemination and abnormal ascites. Alternatively, CCCs tended to have a larger tumor size and higher ADC values with an infiltrative growth pattern, heterogeneous signal, and abnormal ascites. KEY POINTS: • SCs tend to have a heterogeneous signal intensity with peritoneal dissemination and abnormal ascites compared to ECs. • CCCs tend to have a heterogeneous signal intensity with an infiltrative growth pattern and abnormal ascites compared to ECs. • CCCs have a larger tumor size and higher ADC values compared to ECs and SCs.

DOI： 10.1007/s00330-021-08512-6

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BACKGROUND: Recovery of renal function after transplantation leads to improved uremic conditions, increased physical activity, and liberation from severe dietary restrictions. Consequently, the muscle mass of kidney transplant recipients increases for several years after their transplant. However, the change in muscle mass and its associated factors among these patients remain largely unknown. Herein, we carried out a prospective cohort study with 1-year follow-up to investigate how muscle mass changes and to identify its risk factors among kidney transplant recipients. PATIENTS AND METHODS: We performed a single-center, 1-year, prospective, observational cohort study from August 2017 to February 2019 at Osaka City University Hospital in Japan. The skeletal muscle mass index (SMI) was measured by bioelectrical impedance analysis. The risk factors related to the change in muscle mass were analyzed using multivariate linear regression models of age, sex, body mass index (BMI), dialysis vintage, transplant vintage, diabetes mellitus, hemoglobin, C-reactive protein, estimated glomerular filtration rate, and SMI at baseline. RESULTS: A total of 180 kidney transplant recipients were enrolled in the present study. The median age was 55 years, and the median transplant vintage was 78 months. The median rate of change in SMI was +2.07%, and SMI increased in 118 (66%) patients during the 1-year follow-up. By multivariate analysis, the change in SMI at 1-year follow-up was independently associated with age (P = 0.017) and BMI (P = .023). CONCLUSIONS: SMI increased in most of the kidney transplant recipients, and age and BMI might be the risk factors for this change in muscle mass among these patients.

DOI： 10.1016/j.transproceed.2021.08.064

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research USA Inc.  

Background/Aim: Prognostic nutritional index (PNI) and neutrophil-to-lymphocyte ratio (NLR) indicate nutritional status and host immunity. We used immunohistochemistry and apparent diffusion coefficient (ADC) values calculated using diffusion-weighted imaging (DWI) to investigate relationships of these factors with pathological and radiological characteristics in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT). Patients and Methods: We evaluated expression levels of VEGFA, CD8, CD33, and ADC values in tumors pre/post nCRT; and analyzed the relationships between those factors and PNI, NLR in 32 patients. Results: Pretreatment PNI negatively correlated with change in tumor stromal CD8+ T cells and positively correlated with ADC values. Pretreatment NLR and PNI change correlated with recurrence-free survival (RFS). Conclusion: Patients with higher pretreatment PNI had greater changes in ADC values and stromal CD8+ T-cell counts, and those with greater PNI reduction from nCRT had a worse prognosis. Proper nutritional management during nCRT benefits patients and may lead to better prognosis in rectal cancer.

DOI： 10.21873/cdp.10074

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Tissue injury and hemorrhage induced by trauma lead to degradation of the endothelial glycocalyx, causing syndecan-1 (SDC-1) to be shed into the blood. In this study, we investigated whether serum SDC-1 is useful for evaluating trauma severity in patients. A single-center, retrospective, observational study was conducted at Gifu University Hospital. Patients transported to the emergency room for trauma and subsequently admitted to the intensive care unit from January 2019 to December 2021 were enrolled. A linear regression model was constructed to evaluate the association of serum SDC-1 with injury severity score (ISS) and probability of survival (Ps). A total of 76 trauma patients (54 men and 22 women) were analyzed. ISS was significantly associated with serum SDC-1 level in trauma patients. Among the six body regions defined in the AIS used to calculate the ISS score, "chest" and "abdominal or pelvic contents" were significantly associated with serum SDC-1 level, and "extremities or pelvic girdle" also tended to show an association with serum SDC-1 level. Moreover, increasing serum SDC-1 level was significantly correlated with decreasing Ps. Serum SDC-1 may be a useful biomarker for monitoring the severity of trauma in patients. Further large-scale studies are warranted to verify these results.

DOI： 10.3389/fmed.2022.985955

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OBJECTIVE: This study aimed to compare outcomes among patients who sustained major trauma from injury with and without receiving antiplatelet therapy (APT) or anticoagulant therapy (ACT) to test the hypothesis that APT does not increase the risk of mortality. However, ACT increases the mortality risk in the acute phase of trauma. METHODS: Patients registered in the Japanese Observational body for Coagulation and Thrombolysis in Early Trauma 2 between April 2017 and March 2018 who had sustained a severe injury in any anatomic region of the body, as determined using an injury severity score (ISS) ≥ 16 were included in this retrospective cohort study. We analyzed the mortality within 24 h from the arrival using a multivariable linear regression analysis adjusted for several confounding variables. RESULTS: We identified 1,186 eligible participants who met the inclusion criteria for this study: 105 in the APT (cases), 1,081 in the non-antiplatelet therapy (nAPT) group (controls), 65 in the ACT (cases), and 1,121 in the non-anticoagulant therapy (nACT) group (controls). The mortality within 24 h in the ACT group was significantly higher than in the nACT group (odds ratio 4.5; 95%CI: 1.2-16.79; p = 0.025); however, there was no significant difference between the two groups with or without the antiplatelet drug (odds ratio 0.32; 95%CI: 0.04-2.79; p = 0.3) administration. Other outcomes, like the 28-day mortality, mortality at discharge, and surgery for hemostasis, were not significantly different between regular users and non-users of either antiplatelet or anticoagulant drugs. CONCLUSION: Regular antiplatelet medications did not increase mortality within 24 h, 28 days, or at discharge in patients with major trauma, suggesting that standard treatment, including surgery, is sufficient.

DOI： 10.3389/fmed.2022.1089219

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DOI： 10.1097/01.tp.0000804632.54965.b3

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BACKGROUND/AIM: We report the end results of a study evaluating the safety and efficacy of preoperative chemoradiotherapy with S-1 plus oxaliplatin. PATIENTS AND METHODS: Eligible patients had histopathologically confirmed locally advanced rectal carcinoma (LARC; cT3-T4, any N). They received oral S-1 (80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33) and oxaliplatin by infusion (50 mg/m2/day on days 1, 8, 22, and 29) along with radiotherapy (1.8 Gy/day, total dose: 45 Gy/25 fractions). A chemotherapy gap was included in the third week of radiotherapy. The study endpoint was pathological response rate (Grade 2, 3). Secondary endpoints included rates of pathologic complete response (pCR), R0 resection, disease-free survival (DFS), overall survival (OS), local and distant recurrence, and safety and relative dose intensity. RESULTS: The study enrolled 23 patients at three Centres in Gifu, Japan. All patients received chemoradiotherapy, and 22 underwent surgery. Rates of pathological response, R0 resection, and pathological down-staging were 56.5% (13/23), 95.7% (22/23), and 63.6% (14/22), respectively. There were no grade 4 adverse events, but grade 3 events occurred in 21.7% of patients. The cumulative 3-year local recurrence rate was 8.7%. Distant metastasis occurred in 10 (43.5%) patients, 2 (8.7%) from local recurrence and 2 from secondary pancreatic cancer and lung cancer. There were 8 patients with lung metastasis, 2 with liver metastasis, one with ovarian metastasis, and one with bone metastasis. Three-year rates of DFS and OS were 51.1% (median follow-up 34.3 months) and 91.1% (45.2 months), respectively. CONCLUSION: The study showed high pathological response rate without severe toxicity and good follow-up results. Unexpectedly, however, this regimen could not control local recurrence and distant metastasis. Nevertheless, adding oxaliplatin to preoperative chemoradiotherapy with S-1 in patients with LARC appears feasible and may safely result in better local control than standard treatment. The study suggests adding treatment with induction chemotherapy in consideration of CEA level and N factor.

DOI： 10.21873/anticanres.15445

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BACKGROUND & AIMS: Recently, prognostic factors for cancer cachexia patients have been reported. We hypothesized that phase angle (PhA), which is measured by bioelectrical impedance analysis (BIA), might be a promising marker for assessing the nutritional status and prognosis of cancer patients. This study aimed to evaluate the predictive utility of PhA, which is mediated by several BIA factors and other anthropometric parameters, such as calf circumference, for the prognosis of cancer cachexia patients. METHODS: Consecutive patients (114, both outpatients and inpatients) with an unselected stage of cancer cachexia were recruited between July 2018 and December 2019 in Fujita Health University Hospital for this retrospective cohort study. Their mean age was 74.0 years (standard deviation, 8.5); among the total, 70 were men and 44 women. A time-dependent Cox proportional-hazards regression analysis (adjusted for age and sex) was performed to assess the following: 1) the association between potential mediators and mortality; 2) the association between five PhAs and statistically significant mediators from 1); and 3) the association between the five PhAs and mortality. Finally, Kaplan-Meier survival curves were constructed and compared between the two groups based on the patients' median baseline ratio of extracellular water (ECW) to total body water (TBW) using a log-rank test. RESULTS: The ECW/TBW ratio (hazard ratio [HR] per 1-interquartile range [IQR] increase: 2.87; 95% confidence interval [CI]: 1.46, 5.46; p < 0.001) and skeletal muscle mass index (HR per 1-IQR increase: 0.67; 95% CI: 0.51, 0.89; p = 0.001) were associated with mortality. All five PhAs were associated with the ECW/TBW ratio (p < 0.001). Before adjustment for the ECW/TBW ratio, all five PhAs were associated with mortality (p < 0.001); only the association of the PhAs of the left arm and the trunk retained the statistical significance after adjusting for confounders (p < 0.05). The median survival times in the low (370 days; 95% CI: 168, not calculated) and high ECW/TBW groups (101 days; 95% CI: 61, 219) differed significantly (p < 0.001). CONCLUSIONS: The association between PhA and mortality in cancer cachexia patients was largely mediated by the ECW/TBW ratio. We believe that adjusting PhA for the ECW/TBW ratio may improve the prognostication of cancer patients with cachexia, ultimately improving their palliative care.

DOI： 10.1016/j.clnesp.2021.10.009

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Language：Japanese   Publisher：(一社)日本救急医学会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

DOI： 10.1016/j.isci.2021.103140

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The incidence of delayed injection site reaction after the first dose of mRNA-1273 vaccine was 12.5% among females and 1.5% among males in a cohort of primarily elderly Japanese. After the second dose, 48.4% of those who could be contacted reported recurrence. The reaction may be relatively common among Asian females.

DOI： 10.1093/ofid/ofab497

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PURPOSE: To analyze the causes of debonding of computer-aided design/computer-aided manufacturing (CAD/CAM) indirect resin composite premolar crowns with a focus on the morphological factors of the crown and abutment teeth. METHODS: The clinical courses of 109 CAD/CAM indirect resin composite crowns were observed, and the patients' background characteristics, crown locations, luting methods, types of abutments, distal-most/non-distal-most molars, and types of resin blocks were confirmed. To investigate the influence of the morphology of the crown and abutment teeth, the 1) vertical dimension of the abutment teeth, 2) taper, and 3) thickness of the crown occlusal surface during events were measured from the three-dimensional digital data. The Kaplan-Meier method and multivariable Cox proportional hazard model were used for the statistical analyses. The nonlinearity of the effect of each comparison factor was included in the model. RESULTS: Complications included 21 debonding cases, two crown fractures, five root fractures, and two core debondings. The cumulative no-debonding and no-crown-fracture rate over 1423 days (3 years and 11 months) was 77.4%. The multivariable Cox regression analysis revealed that the abutment teeth type of tooth (first or second premolar) (P = 0.02) and luting materials (P < 0.01) significantly influenced the debonding frequency. All morphological factors (1-3) significantly influenced the debonding. The hazard ratios and nonlinear graph indicated that the crown thickness was less effective than the vertical dimension and taper. CONCLUSIONS: The combination analysis of clinical outcomes and 3D digital data revealed that preparation of the abutment is important for avoiding crown debonding.

DOI： 10.2186/jpr.JPR_D_20_00287

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To evaluate the effect of cryoprecipitate (CRYO) transfusion in women referred for postpartum hemorrhage (PPH). This retrospective cohort study included patients with primary PPH referred to Gifu University Hospital between April 2013 and March 2020. We analyzed the effect of CRYO transfusion on fluid balance 24 h after the initial examination using a multivariable linear regression model adjusted for several confounding variables. To evaluate whether outcomes were modified by active bleeding, an interaction term of CRYO*active bleeding was incorporated into the multivariable model. We identified 157 women: 38 in the CRYO group (cases) and 119 in the control group. Fluid balance in the aforementioned period tended to decrease in the CRYO group compared with that in the control group (coefficient - 398.91; 95% CI - 1298.08 to + 500.26; p = 0.382). Active bleeding on contrast-enhanced computed tomography affected the relationship between CRYO transfusion and fluid balance (p = 0.016). Other outcomes, except for the overall transfusion requirement, were not significantly different; however, the interaction effect of active bleeding was significant (p = 0.016). CRYO transfusion may decrease the fluid balance in the first 24 h in PPH patients, especially in those without active bleeding.

DOI： 10.1038/s41598-021-97954-5

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BACKGROUND: The nasal to temporal amplitudes ratio (N/T) of multifocal electroretinography (mfERG) scans measured within 5° of the macula can be used to detect glaucomatous change. The photopic negative response (PhNR) of mfERG elicited by a circular stimulus centered on the fovea was significantly reduced in eyes with glaucoma. The PhNR to B-wave ratio (PhNR/B) is the optimal measure of the PhNR. However, clinical superiority for evaluating glaucoma patients has not been determined between N/T and PhNR/B yet. METHODS: For morphological assessments, ganglion cell complex (GCC) in six regions and the average were measured by optical coherence tomography (OCT). For functional assessment, Humphrey visual fields (VF) with mean sensitivities (MT) and mfERG scans with parameters of N/T and the multifocal photopic negative response to B-wave ratio (mfPhNR/B) were measured. Sixty-nine eyes of 44 glaucoma patients were included and correlations between mfERG parameters and OCT or VF parameters were evaluated. RESULTS: The mean age of patients was 59.4 years. The mean deviation for all eyes obtained with the VF 30-2 and VF 10-2 was - 7.00 and - 6.31 dB, respectively. Significant correlations between GCC thickness or VF parameter and the N/T were found, especially in the inferior and inforotemporal retinal areas corresponding to superior and superonasal VF sectors (GCC vs N/T; coefficient = - 7.916 and - 7.857, and MT vs N/T; coefficient = - 4.302 and - 4.437, in the inferior and inforotemporal retinal areas, respectively, all p values < 0.05). However, similar associations were not obtained between mfPhNR/B and OCT or VF parameters. The mfPhNR/B only in the inferotemporal sector was significantly correlated with the average thickness of GCC (coefficient = 4.823, P = 0.012). CONCLUSIONS: The N/T was correlated with GCC and VF in more numbers of measurement areas than the mfPhNR/B in the current study, however, a future study modifying the stimuli and amplitudes to obtain the spatial correspondence to OCT and VF measurement will be required to evaluate the value of mfERG.

DOI： 10.1186/s12886-021-02061-8

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BACKGROUND: Cancer chemotherapy usually improves clinical outcomes in patients with advanced pancreatic cancer (APC), but can also cause moderate-to-severe adverse events (AEs). We investigated the relationship between moderate-to-severe AEs and quality of life (QOL) in patients with APC who received outpatient chemotherapy. METHODS: We recruited APC patients who received outpatient chemotherapy in Gifu University Hospital between September 2017 and December 2018. Adverse events related to chemotherapy were assessed by a pharmacist collaborating with a physician using common terminology criteria for AEs (CTCAE) ver 4.0, and QOL of patients was self-assessed by patients using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L Japanese edition 2). Associations between the EQ-5D-5L utility value and serious AEs were assessed using proportional odds logistic regression. RESULTS: A total of 59 patients who received 475 chemotherapy cycles were included. The proportional odds logistic regression indicated that grade ≥ 2 anorexia, pain and peripheral neuropathy were significantly correlated with a decreased EQ-5D-5L utility value. Pharmaceutical intervention for these AEs significantly improved the patients' EQ-5D-5L utility value. CONCLUSIONS: Anorexia, pain and peripheral neuropathy were significantly associated with a decrease in QOL. It is assumed that appropriate pharmaceutical intervention with particular emphasis on these AEs can improve the QOL of pancreatic cancer patients receiving outpatient chemotherapy.

DOI： 10.1186/s40780-021-00210-1

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Background The bolus-tracking technique from single-energy CT has been applied to dual-energy CT (DECT) without optimization or validation. Further optimization is imperative because of a paucity of literature and differences in the attenuation profile of virtual monoenergetic images (VMIs). Purpose To determine the optimal trigger threshold with bolus-tracking technique for DECT angiography (DECTA) in a phantom study and assess the feasibility of an optimized threshold for bolus-tracking technique in DECTA at 40 keV with a 50% reduced iodine dose in human participants. Materials and Methods A phantom study with rapid kilovoltage-switching DECT was performed to determine the optimal threshold for each kiloelectron-volt VMI. In a prospective study, consecutive participants who underwent whole-body CT angiography (CTA) from August 2018 to July 2019 were randomized into three groups: single-energy CTA (SECTA) with standard iodine dose (600 mg of iodine per kilogram), DECTA with 50% reduced iodine dose (300 mg of iodine per kilogram) by using a conventional threshold, and DECTA with 300 mg of iodine per kilogram by using an optimized threshold. A trigger threshold of 100 HU at 120 kVp was used as a reference for comparison. Injected iodine doses and aortic CT numbers were compared among the three groups using Kruskal-Wallis test. Results Ninety-six participants (mean age ± standard deviation, 72 years ± 9; 80 men) were evaluated (32 participants in each group). The optimized threshold for VMIs at 40 keV was 30 HU. The median iodine dose was lower in the optimized DECTA group (13 g) compared with conventional DECTA (19 g) and SECTA (26 g) groups (P < .017 for each comparison). The median aortic CT numbers were higher in the order corresponding to conventional DECTA (655-769 HU), optimized DECTA (543-610 HU), and SECTA (343-359 HU) groups (P < .001). Conclusion The optimized trigger threshold of 30 HU for bolus-tracking technique during dual-energy CT angiography at 40 keV achieved lower iodine load while maintaining aortic enhancement. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Malayeri in this issue.

DOI： 10.1148/radiol.2021210102

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Language：Japanese   Publisher：(一社)日本熱傷学会  

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Information regarding the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic carriers is scarce. In order to determine the duration of infectivity and its correlation with reverse transcription-PCR (RT-PCR) results and time since initial positive PCR test in this population, we evaluated SARS-CoV-2 cell infectivity in nasopharyngeal samples longitudinally obtained from asymptomatic carriers who disembarked from a cruise ship during a COVID-19 outbreak. Of 166 nasopharyngeal samples collected from 39 asymptomatic carriers every 48 h until two consecutive negative PCR test results were obtained, SARS-CoV-2 was successfully isolated from 9 PCR-positive samples which were obtained from 7 persons (18%; 7/39). Viable viruses were isolated predominantly within 7 days after the initial positive PCR test, except for one person who shed viable virus until day 15. The median crossing point (Cp) value of RT-PCR of culture-positive samples was 24.6 (interquartile range [IQR], 20.4 to 25.8; range, 17.9 to 30.3), and Cp values were significantly associated with isolation of viable virus (odds ratio, 0.496; 95% confidence interval [CI], 0.329 to 0.747; P value, 0.001), which was consistent with existing data for symptomatic patients. Genome sequence analysis of SARS-CoV-2 samples consecutively obtained from a person who shed viable virus for 15 days identified the emergence of two novel single nucleotide variants (C8626T transition and C18452T transition) in the sample collected on day 15, with the latter corresponding to an amino acid substitution in nonstructural protein 14. The impact of these mutations on prolonged viable-virus shedding is unclear. These findings underscore the potential role of asymptomatic carriers in transmission.IMPORTANCE A growing number of studies suggest the potential role of asymptomatic SARS-CoV-2 carriers as a major driver of the COVID-19 pandemic; however, virological assessment of asymptomatic infection has largely been limited to reverse transcription-PCR (RT-PCR), which can be persistently positive without necessarily indicating the presence of viable virus (e.g., replication-competent virus). Here, we evaluated the infectivity of asymptomatic SARS-CoV-2 carriers by detecting SARS-CoV-2-induced cytopathic effects on Vero cells using longitudinally obtained nasopharyngeal samples from asymptomatic carriers. We show that asymptomatic carriers can shed viable virus until 7 days after the initial positive PCR test, with one outlier shedding until day 15. The crossing point (Cp) value of RT-PCR was the leading predictive factor for virus viability. These findings provide additional insights into the role of asymptomatic carriers as a source of transmission and highlight the importance of universal source control measures, along with isolation policy for asymptomatic carriers.

DOI： 10.1128/mSphere.00019-21

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PURPOSE: To evaluate image quality, image noise, and conspicuity of pancreatic ductal adenocarcinoma (PDAC) in pancreatic low-dose computed tomography (LDCT) reconstructed using deep learning image reconstruction (DLIR) and compare with those of images reconstructed using hybrid iterative reconstruction (IR). METHODS: Our institutional review board approved this prospective study. Written informed consent was obtained from all patients. Twenty-eight consecutive patients with PDAC undergoing chemotherapy (14 men and 14 women; mean age, 68.4 years) underwent pancreatic LDCT for therapy evaluation. The LDCT images were reconstructed using 40% adaptive statistical iterative reconstruction-Veo (hybrid-IR) and DLIR at medium and high levels (DLIR-M and DLIR-H). The image noise, diagnostic acceptability, and conspicuity of PDAC were qualitatively assessed using a 5-point scale. CT numbers of the abdominal aorta, portal vein, pancreas, PDAC, background noise, signal-to-noise ratio (SNR) of the anatomical structures, and tumor-to-pancreas contrast-to-noise ratio (CNR) were calculated. Qualitative and quantitative parameters were compared between the hybrid-IR, DLIR-M, and DLIR-H images. RESULTS: CT dose-index volumes and dose-length product in pancreatic LDCT were 2.3 ± 1.0 mGy and 74.9 ± 37.0 mGy•cm, respectively. The image noise, diagnostic acceptability, and conspicuity of PDAC were significantly better in DLIR-H than those in hybrid-IR and DLIR-M (all P < 0.001). The background noise was significantly lower in the DLIR-H images (P < 0.001) and resulted in improved SNRs (P < 0.001) and CNR (P < 0.001) compared with those in the hybrid-IR and DLIR-M images. CONCLUSION: DLIR significantly reduced image noise and improved image quality in pancreatic LDCT images compared with hybrid-IR.

DOI： 10.1007/s00261-021-03111-x

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OBJECTIVES: To determine the optimal scan delay corresponding to individual hemodynamic status for pancreatic parenchymal phase in dynamic contrast-enhanced CT of the abdomen. METHODS: One hundred and fourteen patients were included in this retrospective study (69 males and 45 females; mean age, 67.9 ± 12.1 years; range, 39-87 years). These patients underwent abdominal dynamic contrast-enhanced CT between November 2019 and May 2020. We calculated and recorded the time from contrast material injection to the bolus-tracking trigger of 100 Hounsfield unit (HU) at the abdominal aorta (s) (TimeTRIG) and scan delay from the bolus-tracking trigger to the initiation of pancreatic parenchymal phase scanning (s) (TimeSD). The scan delay ratio (SDR) was defined by dividing the TimeSD by TimeTRIG. Non-linear regression analysis was conducted to assess the association between CT number of the pancreas and SDR and to reveal the optimal SDR, which was ≥120 HU in pancreatic parenchyma. RESULTS: The non-linear regression analysis showed a significant association between CT number of the pancreas and the SDR (p < 0.001). The mean TimeTRIG and TimeSD were 16.1 s and 16.8 s, respectively. The SDR to peak enhancement of the pancreas (123.5 HU) was 1.00. An SDR between 0.89 and 1.18 shows an appropriate enhancement of the pancreas (≥120 HU). CONCLUSION: The CT number of the pancreas peaked at an SDR of 1.00, which means TimeSD should be approximately the same as TimeTRIG to obtain appropriate pancreatic parenchymal phase images in dynamic contrast-enhanced CT with bolus-tracking method. ADVANCES IN KNOWLEDGE: The hemodynamic state is different in each patient; therefore, scan delay from the bolus-tracking trigger should also vary based on the time from contrast material injection to the bolus-tracking trigger. This is necessary to obtain appropriate late hepatic arterial or pancreatic parenchymal phase images in dynamic contrast-enhanced CT of the abdomen.

DOI： 10.1259/bjr.20210315

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BACKGROUND: The gut microbiota are reported to be altered in critical illness. The pattern and impact of dysbiosis on prognosis has not been thoroughly investigated in the ICU setting. AIMS: We aimed to evaluate changes in the gut microbiota of ICU patients via 16S rRNA gene deep sequencing, assess the association of the changes with antibiotics use or disease severity, and explore the association of gut microbiota changes with ICU patient prognosis. METHODS: Seventy-one mechanically ventilated patients were included. Fecal samples were collected serially on days 1-2, 3-4, 5-7, 8-14, and thereafter when suitable. Microorganisms of the fecal samples were profiled by 16S rRNA gene deep sequencing. RESULTS: Proportions of the five major phyla in the feces were diverse in each patient at admission. Those of Bacteroidetes and Firmicutes especially converged and stabilized within the first week from admission with a reduction in α-diversity (p < 0.001). Significant differences occurred in the proportional change of Actinobacteria between the carbapenem and non-carbapenem groups (p = 0.030) and that of Actinobacteria according to initial SOFA score and changes in the SOFA score (p < 0.001). An imbalance in the ratio of Bacteroidetes to Firmicutes within seven days from admission was associated with higher mortality when the ratio was > 8 or < 1/8 (odds ratio: 5.54, 95% CI: 1.39-22.18, p = 0.015). CONCLUSIONS: Broad-spectrum antibiotics and disease severity may be associated with gut dysbiosis in the ICU. A progression of dysbiosis occurring in the gut of ICU patients might be associated with mortality.

DOI： 10.1007/s10620-021-07000-7

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Syndecan-1 (SDC-1) is found in the endothelial glycocalyx and shed into the blood during systemic inflammatory conditions. We investigated organ dysfunction associated with changing serum SDC-1 levels for early detection of organ dysfunction in critically ill patients. To evaluate the effect of SDC-1 on laboratory parameters measured the day after SDC-1 measurement with consideration for repeated measures, linear mixed effects models were constructed with each parameter as an outcome variable. A total of 94 patients were enrolled, and 831 samples were obtained. Analysis using mixed effects models for repeated measures with adjustment for age and sex showed that serum SDC-1 levels measured the day before significantly affected several outcomes, including aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE), blood urea nitrogen (BUN), antithrombin III, fibrin degradation products, and D-dimer. Moreover, serum SDC-1 levels of the prior day significantly modified the effect between time and several outcomes, including AST, ALT, CRE, and BUN. Additionally, increasing serum SDC-1 level was a significant risk factor for mortality. Serum SDC-1 may be a useful biomarker for daily monitoring to detect early signs of kidney, liver and coagulation system dysfunction, and may be an important risk factor for mortality in critically ill patients.

DOI： 10.1038/s41598-021-88303-7

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Blood purification has been widely performed for critically ill patients, even in cases without renal failure. Effective anticoagulation of the extracorporeal circuit is necessary to prevent circuit clotting. We hypothesized that administration of recombinant human-soluble thrombomodulin (rhsTM) to septic patients undergoing blood purification may prevent circuit clotting, because this agent regulates coagulation. We performed a retrospective, single-center, propensity-matched cohort study in the intensive care unit of Nishichita General Hospital. We included septic patients admitted to the intensive care unit from May 2015 to August 2020 who underwent blood purification. Patients who received rhsTM during intensive care unit admission to the end of the first blood purification (rhsTM group) were matched 1:1 with other patients (control group). The primary outcome was the occurrence of circuit clotting during the first blood purification. A total of 138 patients were included in the study [43 patients (31%) in the rhsTM group and 95 patients (69%) in the control group]. After propensity score matching, 42 pairs of patients were selected, and patients in the rhsTM group had a lower incidence of circuit clotting (21 vs. 55%, P = 0.003). One case of major bleeding occurred in the rhsTM group, but there was no difference in the incidence of major bleeding between groups (2 vs. 0%, P = 1.0). In conclusion, this propensity-matched cohort study indicated that the administration of rhsTM to septic patients undergoing blood purification may prevent extracorporeal circuit clotting.

DOI： 10.1007/s10047-021-01268-2

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ABSTRACT: Nivolumab has shown good prognosis in renal cell carcinoma (RCC) patients previously treated with targeted therapy. We aimed to study irAE (immune-related adverse event) due to nivolumab and numbers of previous treatment lines in RCC patients. Between October 2016 and November 2019, 114 patients were treated with nivolumab as second- and later-line therapy. Among them, 110 patients with complete data were evaluated in this retrospective observational study. The primary endpoint was the relation between irAE and numbers of previous targeted therapies. Secondary endpoints were the relation of irAE with the duration of nivolumab treatment and with best overall response. For the primary analysis, proportional odds logistic regression was used to assess the effect of the number of prior therapies on the grade of any irAE as the ordinal variable. For the secondary analysis, binomial logistic regression models adjusted for the covariates were prepared to confirm the association between the incidence of irAE and the number of courses, number of nivolumab treatments and best overall response. Overall, 69, 66, 33, 13, 9 and 9 patients were treated with sunitinib, axitinib, pazopanib, sorafenib, temsirolimus and everolimus, respectively, prior to nivolumab. In total, 60 adverse events (Grade 1, 21; Grade 2, 21; Grade 3, 14; Grade 4, 2; not evaluated, 2) were identified in the patients treated with nivolumab. Ordered logistic regression analysis showed that the adjusted odds ratios of numbers of prior treatment for grade of irAE were 1.12 (numbers of prior treatment: 2 to 1) and 1.31 (3 to 1). Odds ratios of the numbers of nivolumab treatments and best overall response for the incidence of irAE were not significant. No statistically significant relations were found between grade of irAE and numbers of treatments prior to nivolumab. Patients treated with nivolumab should be closely monitored for irAE regardless number of previous therapies.

DOI： 10.1097/MD.0000000000025402

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Vascular anomalies comprise a heterogeneous group of disorders caused by abnormal proliferation or development of vascular and/or lymphatic vessels. Vascular anomalies present with various symptoms and complications, but no standardized methods evaluate their severity, and to measure treatment outcomes is difficult. To assess the responsiveness of measurement scores for evaluating vascular anomaly skin lesions, we conducted a validation study to compare these measurement scores with patients' objective data. In this study, data were collected from treated and untreated patients. Skin lesions were photographed at baseline and after a follow-up period of 3-6 months. The volume of skin lesions, the degree of red or purple coloration, and color tone were measured objectively. Two external dermatologists evaluated patients' photographs and determined scores, which represented criteria for improvements in skin lesions (size and color) and 6-point Physician Global Assessment scores. The correlation between these scores and patients' objective data (lesion volume and color) was assessed to validate the scores. Twenty-three cases of vascular anomaly (seven vascular tumors, five lymphatic malformations, three venous malformations, and eight lymphatic-venous malformations) were examined. Scores for improvements in vascular anomaly skin lesions (size and color) correlated with a change in lesion volume, the degree of red or purple coloration, color tone score, and 6-point Physician Global Assessment score. Our findings suggest that these measurement scores are responsive to changes in vascular anomaly skin lesions after observation.

DOI： 10.1111/1346-8138.15839

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BACKGROUND: There is controversy over late and long-lasting reactions to gold sodium thiosulfate (GST). OBJECTIVES: To study the GST patch-test reaction by observing the application site after 1 month, and to clarify the relevance of GST sensitization by piercings and dental metals. PATIENTS: A retrospective analysis was performed on 746 patients (143 male; 603 female) who were patch tested using GST of the TRUE Test. We conducted a questionnaire on the presence of piercings or dental metals in these patients. RESULTS: The GST positive rate was 27.9% at day (D)3 and/or D7 and 40.3% up to the 1-month reading. The positive rate was significantly higher in female patients and increased with age. Sixty-two percent of cases with a positive reaction at D7 continued to show a positive reaction after 1 month. Eleven percent of cases with a negative reaction at D3 and D7 showed a late reaction. Both piercings and dental metals were related to gold sensitization. CONCLUSIONS: The GST of the TRUE Test had a high positive and low false-negative rate. The 1-month reading after the patch test was important for identifying late reactions. Piercing history and dental metal were associated with gold sensitization.

DOI： 10.1111/cod.13827

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Language：Japanese   Publisher：(公社)日本放射線技術学会  

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BACKGROUND/AIM: We evaluated the efficacy of primary prophylaxis with pegfilgrastim (PEG) for febrile neutropenia (FN) in small cell lung cancer (SCLC) patients receiving amrubicin (AMR). PATIENTS AND METHODS: A retrospective cohort study was conducted in patients with SCLC receiving AMR as second-line therapy. RESULTS: A total of 33 patients were treated with AMR (no PEG group), while 13 patients were treated with AMR plus prophylactic administration of PEG (PEG group). The severity of neutropenia was significantly reduced in the PEG group compared to the no PEG group (p=0.02). The incidence of FN in the no PEG and PEG groups was 27.3% and 7.7%, respectively. The time to development of FN tended to be longer in the PEG group compared to the no PEG group (p=0.132). CONCLUSION: Primary prophylaxis with PEG may be beneficial in reducing the risk of FN in patients with SCLC receiving AMR.

DOI： 10.21873/anticanres.14923

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Language：Japanese   Publisher：(公社)日本放射線技術学会  

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BACKGROUND: Thromboembolic complications (TECs) are frequent during the endovascular treatment of unruptured aneurysms. To prevent TECs, dual antiplatelet therapy using aspirin and clopidogrel is recommended for the perioperative period. In patients with a poor response, clopidogrel is a risk factor for TECs. To prevent TECs, our study assessed the stratified use of prasugrel. METHODS: Patients who underwent endovascular therapy for unruptured cerebral aneurysms from April 2017 to August 2019 were enrolled in this clinical study and given premedication with aspirin and clopidogrel for 2 weeks prior to the procedure. P2Y12 reaction units (PRU) were measured using the VerifyNow assay on the day before the procedure (tailored group). In subgroups with PRU <240, the clopidogrel dose was maintained (CPG subgroup). In subgroups with PRU ≥240, clopidogrel was changed to prasugrel (PSG subgroup). We compared the occurrence of TECs with retrospective consecutive cases from January 2015 to March 2017 without PRU assessments (non-tailored group). The frequency of TECs within 30 days was assessed as the primary endpoint. RESULTS: The tailored and non-tailored groups comprised 167 and 50 patients, respectively. TECs occurred in 11 (6.6%) and 8 (16%) patients in the tailored and non-tailored groups (P=0.048), respectively. The HR for TECs was significantly reduced in the tailored group (HR 0.3, 95% CI 0.11 to 0.81); P=0.017) compared with the non-tailored group. CONCLUSION: The results suggest that tailored dual antiplatelet therapy medication with PRU significantly reduces the frequency of TECs without increasing hemorrhagic complications.

DOI： 10.1136/neurintsurg-2020-016994

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Objectives We investigated the 5-year disease-related mortality risk, including that associated with neoplasms, mental/behavioral/neurodevelopmental disorders, and diseases of the circulatory system and respiratory system,in ambulatory frail Japanese older adults.Methods We retrospectively analyzed long-term care and health insurance claims data in this cohort study performed between April 2012 and March 2017. The primary outcome was mortality, and the secondary outcome was care-need level decline. Risk factors were determined based on the International Statistical Classification of Disease and Related Health Problems, 10th Revision codes, hospitalization, and institutionalization. The study included 1,239 ambulatory frail older adults newly certified as needing Support-Level care at baseline (April 2012-March 2013) across three Japanese municipalities.Results Of the 1,239 participants, 454 (36.6%) died. Neoplasms (hazard ratio [HR] 2.69, 95% confidence interval [CI] 1.97-3.68) or respiratory system diseases (HR 1.62, 95%CI 1.26-2.08) were independently associated with mortality. Mental/behavioral/neurodevelopmental disorders (HR 1.39, 95%CI 1.17-1.66) or diseases of the respiratory system(HR 86, 95%CI 75-99) were independently associated with care-need level decline.Conclusions This study suggests that neoplasms or respiratory system diseases were associated with a high mortality risk and that mental/behavioral/neurodevelopmental disorders were associated with care-need level decline among ambulatory frail older adults. Optimal disease management and effective long-term care are important to delay the onset of these events in older adults certified as needing Support-Level care.

DOI： 10.11236/jph.20-002

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INTRODUCTION: Endoscopic submucosal dissection (ESD) is an effective treatment for gastric neoplasms in elderly patients; however, it involves several adverse events, including pneumonia. This study aimed to investigate whether skeletal muscle depletion (SMD) was associated with the development of pneumonia in elderly patients who underwent gastric ESD. METHODS: This retrospective observational cohort study included 157 patients (≥80 years) who had undergone gastric ESD. The skeletal muscle cross-sectional area was measured by computed tomography (CT), and the value of the third lumbar vertebra skeletal muscle index (L3 SMI) was evaluated. The SMD was defined as an L3 SMI value ≤38.0 cm2/m2 for women and ≤42.0 cm2/m2 for men. Pneumonia was also diagnosed using CT to identify all included patients. RESULTS: Among 157 patients, 66 (42.0%) showed SMD. In the SMD group, the incidence of pneumonia was 21.2%, whereas it was 7.7% in the non-SMD group (p=0.018). The longest hospitalization duration was 19 days. Antibiotics were administered in 61.9% of the patients. Procedure time was not significantly different between the groups (72 ± 54 minutes vs. 62 ± 44 minutes, p=0.201). On multivariate analysis, SMD was an independent risk factor for the development of pneumonia (odds ratio=3.16, 95% confidence interval, 1.18-8.50, p=0.023). CONCLUSIONS: SMD was not a rare entity in patients aged ≥80 years with gastric neoplasms. SMD was a significant risk factor for pneumonia related to gastric ESD in elderly patients.

DOI： 10.1159/000514275

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WHAT IS KNOWN AND OBJECTIVE: Ifosfamide, an alkylating agent, is widely used in the treatment of malignant diseases. However, these treatments are often limited due to the incidence of neuropsychiatric symptoms such as delirium, seizures, hallucinations and agitation. In this study, we examined risk factors for neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy. METHODS: The study cases were patients with cancer receiving ifosfamide-based chemotherapy between April 2007 and March 2018. Risk analysis for ifosfamide-related neuropsychiatric symptoms was determined by time-dependent Cox proportional hazard regression analysis. RESULTS AND DISCUSSION: Of 183 eligible patients, 32 patients (17.5%) experienced ifosfamide-related neuropsychiatric symptoms. Time-dependent Cox proportional hazard model showed that the albumin-bilirubin (ALBI) score was significantly correlated with the incidence of ifosfamide-related neuropsychiatric symptoms (hazard ratio [HR] =1.45, 95% confidence interval [CI] = 1.05-2.01, p = 0.025). Additionally, there were correlations between the predicted risk of neuropsychiatric symptoms and ifosfamide-dose per cycle (HR =0.51, 95% CI = 0.27-0.94, p = 0.030) and creatinine clearance (Ccr) (HR = 0.53, 95% CI = 0.28-1.00, p = 0.050). In contrast, neither serum albumin nor total bilirubin was a significant risk factor for neuropsychiatric symptoms. WHAT IS NEW AND CONCLUSION: These findings indicate that ALBI score may be a useful biomarker for predicting neuropsychiatric symptoms in patients receiving ifosfamide-based chemotherapy.

DOI： 10.1111/jcpt.13355

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<title>Abstract</title>
<sec>
<title>Background</title>
Gliomas typically escape surgical resection and recur due to their “diffuse invasion” phenotype, enabling them to infiltrate diffusely into the normal brain parenchyma. Over the past 80 years, studies have revealed 2 key features of the “diffuse invasion” phenotype, designated the Scherer’s secondary structure, and include perineuronal satellitosis (PS) and perivascular satellitosis (PVS). However, the mechanisms are still unknown.


</sec>
<sec>
<title>Methods</title>
We established a mouse glioma cell line (IG27) by manipulating the histone H3K27M mutation, frequently harboring in diffuse intrinsic pontine gliomas, that reproduced the diffuse invasion phenotype, PS and PVS, following intracranial transplantation in the mouse brain. Further, to broadly apply the results in this mouse model to human gliomas, we analyzed data from 66 glioma patients.


</sec>
<sec>
<title>Results</title>
Increased H3K27 acetylation in IG27 cells activated glucose transporter 1 (Glut1) expression and induced aerobic glycolysis and TCA cycle activation, leading to lactate, acetyl-CoA, and oncometabolite production irrespective of oxygen and glucose levels. Gain- and loss-of-function in vivo experiments demonstrated that Glut1 controls the PS of glioma cells, that is, attachment to and contact with neurons. GLUT1 is also associated with early progression in glioma patients.


</sec>
<sec>
<title>Conclusions</title>
Targeting the transporter Glut1 suppresses the unique phenotype, “diffuse invasion” in the diffuse glioma mouse model. This work leads to promising therapeutic and potential useful imaging targets for anti-invasion in human gliomas widely.


</sec>

DOI： 10.1093/noajnl/vdaa150

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BACKGROUND: Glucocorticoids (GCs) are expected to inhibit the synthesis and release of proinflammatory cytokines, which induces local pain. Serious side effects or complications are considered rare with single-dose GC use. However, the amount of systemic absorption and the side effects induced by local GC injections are not well understood. OBJECTIVES: We measured the changes in glucose levels after single-does dexamethasone injection with nerve blockade using a continuous glucose monitoring system (CGMS) in non-diabetes mellitus (DM) patients and investigated the risk factors for hyperglycemia. STUDY DESIGN: This is a cohort study. SETTING: This study was conducted at Gifu University Hospital in Japan. METHODS: Forty-six non-DM patients who underwent elective lumbar or sacral nerve root pulsed radiofrequency or lumbar medial branch of the posterior primary rami conventional radiofrequency with dexamethasone (0.1 mg/kg) were analyzed. The patients underwent monitoring of their interstitial glucose using a CGMS. Hyperglycemia was defined as a blood glucose level >= 200 mg/dL. The area under the curve (AUC) where the blood glucose level was over 200 mg/dL was calculated and analyzed. The risk factors of hyperglycemia were determined using an applied ordinal regression model analysis with the AUC as the objective variable and 4 factors (age, body mass index, glucose level just before GC injection, and glycosylated hemoglobin) as explanatory variables. The blood glucose levels were predicted by a nonlinear regression model. RESULTS: The AUC and maximum glucose level were higher on the first day than after the second day. None of the 4 factors were predictors of hyperglycemia. The glucose level before the procedure was associated with the predicted blood glucose level on the first day (P = 0.042). However, the 95% upper confidence limit of the maximum predicted blood glucose level was less than the safety margin. The predicted blood glucose levels returned to the usual level after the second day. LIMITATIONS: First, GCs are metabolized by cytochrome p450 3A4, and it is possible that the inhibition of this pathway decreases the clearance of GCs. Some of our patients were taking medications that influence this cytochrome pathway. Second, we cannot eliminate the possibility of stress-induced hyperglycemia. Finally, we were unable to record the exact meal timing and calories the patients had consumed. CONCLUSIONS: The blood glucose levels were higher than usual on the first day following a local dexamethasone injection, but the levels were not critical in most cases. Because we cannot predict which patients will develop hyperglycemia, we must determine whether or not GCs can be safely administered and inform patients about potential complications.

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OBJECTIVE: Periprocedural thromboembolic events are a serious complication associated with coil embolization of unruptured intracranial aneurysms. However, no established clinical rule for predicting thromboembolic events exists. This study aimed to clarify the significance of adding preoperative clopidogrel response value to clinical factors when predicting the occurrence of thromboembolic events during/after coil embolization and to develop a nomogram for thromboembolic event prediction. METHODS: In this prospective, single-center, cohort study, we included 345 patients undergoing elective coil embolization for unruptured intracranial aneurysm. Thromboembolic event was defined as the occurrence of intra-procedural thrombus formation and postprocedural symptomatic cerebral infarction within 7 days. We evaluated preoperative clopidogrel response and patients' clinical information. We developed a patient-clinical-information model for thromboembolic event using multivariate analysis and compared its efficiency with that of patient-clinical-information plus preoperative clopidogrel response model. The predictive performances of the two models were assessed using area under the receiver-operating characteristic curve (AUC-ROC) with bootstrap method and compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: Twenty-eight patients experienced thromboembolic events. The clinical model included age, aneurysm location, aneurysm dome and neck size, and treatment technique. AUC-ROC for the clinical model improved from 0.707 to 0.779 after adding the clopidogrel response value. Significant intergroup differences were noted in NRI (0.617, 95% CI: 0.247-0.987, p < .001) and IDI (0.068, 95% CI: 0.021-0.116, p = .005). CONCLUSIONS: Evaluation of preoperative clopidogrel response in addition to clinical variables improves the prediction accuracy of thromboembolic event occurrence during/after coil embolization of unruptured intracranial aneurysm.

DOI： 10.1371/journal.pone.0249766

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Syndecan-1 is found in the endothelial glycocalyx and is released into the bloodstream during stressed conditions, including severe diseases such as acute kidney injury, chronic kidney disease, and cardiovascular disease. This study investigated the prognostic value of serum syndecan-1 concentration in patients with heart failure upon admission. Serum syndecan-1 concentration was analyzed in 152 patients who were hospitalized for worsening heart failure from September 2017 to June 2018. The primary outcome of the study was readmission-free survival, defined as the time from the first admission to readmission for worsened heart failure or death from any cause, which was assessed at 30 months after discharge from the hospital. The secondary outcome of the study was survival time. Blood samples and echocardiogram data were analyzed. Univariate and multivariable time-dependent Cox regression analyses adjusted for age, creatinine levels, and use of antibiotics were conducted. The serum syndecan-1 concentration was significantly associated with readmission-free survival. Subsequently, the syndecan-1 concentration may have gradually decreased with treatment. The administration of human atrial natriuretic peptide and antibiotics may have modified the relationship between readmission-free survival and serum syndecan-1 concentration (p = 0.01 and 0.008, respectively). Serum syndecan-1 concentrations, which may indicate injury to the endothelial glycocalyx, predict readmission-free survival in patients with heart failure.

DOI： 10.1371/journal.pone.0260350

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Glycocalyx is present on the surface of healthy endothelium, and the concentration of serum syndecan-1 can serve as an injury marker. This study aimed to assess endothelial injury using serum syndecan-1 as a marker of endothelial glycocalyx injury in patients who underwent hemodialysis. In this single-center, retrospective, observational study, 145 patients who underwent hemodialysis at the Gifu University Hospital between March 2017 and December 2019 were enrolled. The median dialysis period and time were 63 months and 3.7 h, respectively. The serum syndecan-1 concentration significantly increased from 124.6 ± 107.8 ng/ml before hemodialysis to 229.0 ± 138.1 ng/ml after hemodialysis (P < 0.001). Treatment with anticoagulant nafamostat mesylate inhibited hemodialysis-induced increase in the levels of serum syndecan-1 in comparison to unfractionated heparin. Dialysis time and the change in the syndecan-1 concentration were positively correlated. Conversely, the amount of body fluid removed and the changes in the syndecan-1 concentration were not significantly correlated. The reduction in the amount of body fluid removed and dialysis time inhibited the change in the syndecan-1 levels before and after hemodialysis. In conclusion, quantitative assessment of the endothelial glycocalyx injury during hemodialysis can be performed by measuring the serum syndecan-1 concentration, which may aid in the selection of appropriate anticoagulants, reduction of hemodialysis time, and the amount of body fluid removed.

DOI： 10.3389/fmed.2021.791309

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INTRODUCTION: Degenerative aortic valve stenosis (AS) is a chronic progressive disease that resembles atherosclerosis development. Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is reportedly associated with accelerated atherosclerosis. This study aimed to examine the development of AS in patients with myeloperoxidase-AAV (MPO-AAV) with renal involvement at more than 1 year after the onset of vasculitis. METHODS: We performed a retrospective review of clinical records of MPO-AAV patients with renal involvement without AS at the onset of vasculitis who were treated in three hospitals and three dialysis clinics. RESULTS: The study included 97 MPO-AAV patients with renal involvement and 230 control patients with chronic kidney disease (CKD). Among them, 64 patients had AS. The prevalence rates of AS were 28.9% and 15.7% in MPO-AAV and control patients, respectively (p = 0.006). The multivariable logistic regression analysis showed that MPO-AAV, dialysis dependence, and hypertension were independently associated factors for AS. In MPO-AAV patients, systolic blood pressure was positively significantly associated with AS, whereas glucocorticoid dose of induction therapy was negatively significantly associated. The use of cyclophosphamide tended to be negatively associated with AS. The survival rate was significantly lower for patients with AS than for those without AS. CONCLUSIONS: The AS prevalence rate was significantly higher in MPO-AAV patients at more than 1 year after the onset of vasculitis than in control CKD patients. Therefore, regular monitoring of echocardiography during MPO-AAV treatment is suggested.

DOI： 10.1371/journal.pone.0245869

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DOI： 10.1016/j.joca.2020.08.003

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BACKGROUND: Double-lumen endobronchial tubes (DLTs) are used for one-lung ventilation (OLV) during thoracic surgery. Overinflation into the bronchial cuff causes damage to the tracheobronchial mucosa, whereas underinflation leads to an incomplete collapse of the nonventilated lung or incomplete ventilation of the ventilated lung. However, how to determine the appropriate bronchial cuff volume and pressure during OLV is unclear. The objective of this study is to compare the required bronchial cuff volume for lung separation obtained by 2 different cuff inflation methods under closed- and open-chest conditions. METHODS: A total of 64 patients scheduled to undergo elective thoracic surgery requiring OLV were recruited. Left DLTs were used for both right- and left-sided surgery. The patients were randomly assigned to 1 of 2 inflation-type groups to estimate the bronchial cuff volume. In the capnogram waveform-guided bronchial cuff inflation group (capno group, n = 27), the bronchial cuff was inflated until a capnometer sampling gas containing CO2 from the nonventilated lung displayed a flat line. The corresponding bronchial cuff volume and pressure were then recorded. In the pressure-guided bronchial cuff inflation group (pressure group, n = 29), the bronchial cuff was inflated by a cuff inflator to a pressure of 20 cm H2O. Lung separation was confirmed when a flat line of a capnometer was observed after gas sampling from the nonventilated lung. RESULTS: Under closed-chest conditions, the bronchial cuff sealing volume for the capno group was significantly lower than that for the pressure group (mean [standard deviation {SD}], 1.00 [0.65] mL vs 1.44 [0.59] mL, mean difference, - 0.44; 97.5% confidence interval [CI], -0.78 to - 0.11; P = .010). Under open-chest conditions, the bronchial cuff sealing volume for the capno group was also significantly lower than that for the pressure group (mean [SD], 0.65 [0.66] mL vs 1.22 [0.45] mL, mean difference, -0.58; 97.5% CI, -0.88 to -0.27; P < .001). CONCLUSIONS: The lowest cuff volume providing an air-tight bronchial seal was obtained by the capnogram waveform-guided bronchial cuff inflation method. Since the cuff volume required to achieve an air-tight seal decreases after opening the chest, readjustment of the bronchial cuff volume to prevent bronchial cuff damage to the tracheobronchial mucosa after opening the chest may be advisable.

DOI： 10.1213/ANE.0000000000005179

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BACKGROUND: The impact of pancreas transplantation, including kidney transplantation on patients' life prognoses, is unclear in Japan. An analysis of the data of the Japan Pancreas Transplant Registry was performed to compare the patient survival between on the waiting list and after pancreas transplantation, and investigate the factors that affect the patient survival after pancreatic transplantation. METHODS: The life prognoses of 361 patients who underwent pancreas transplantation from 2000 to December 2018 were examined. RESULTS: The survival rates at 1, 5, and 10 years on the waiting list were 98.4%, 90.3%, and 78.1%, respectively, while those after transplantation were significantly improved (p = 0.029) at 100%, 97.5%, and 88.9%, respectively. Furthermore, the survival rates of patients waiting for simultaneous pancreas and kidney transplantation (SPK) at 1, 5, and 10 years were 98.2%, 89.4%, and 75.4%, respectively, while those after SPK were also significantly improved (p = 0.026) at 100%, 94.6%, and 88.8%. The multivariable analysis revealed that the duration of diabetes before surgery was the only independent risk factor (hazard ratio = 1.095, p = 0.012) that affected the patient survival after SPK. CONCLUSION: Pancreas transplantation was found to improve the life prognosis of patients with type 1 diabetes, especially those with end-stage renal failure waiting for SPK.

DOI： 10.3390/jcm9072134

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Cancer treatment with a fluoropyrimidine (FP) is often accompanied by severe toxicity that may be dependent on the activity of catalytic enzymes encoded by the DPYD, DPYS, and UPB1 genes. Genotype-guided dose individualization of FP therapy has been proposed in western countries, but our knowledge of the relevant genetic variants in East Asian populations is presently limited. To investigate the association between these genetic variations and FP-related high toxicity in a Japanese population, we obtained blood samples from 301 patients who received this chemotherapy and sequenced the coding exons and flanking intron regions of their DPYD, DPYS, and UPB1 genes. In total, 24 single nucleotide variants (15 in DPYD, 7 in DPYS and 2 in UPB1) were identified including 3 novel variants in DPYD and 1 novel variant in DPYS. We did not find a significant association between FP-related high toxicity and each of these individual variants, although a certain trend toward significance was observed for p.Arg181Trp and p.Gln334Arg in DPYS (P = .0813 and .087). When we focused on 7 DPYD rare variants (p.Ser199Asn, p.IIe245Phe, p.Thr305Lys, p.Glu386Ter, p.Ser556Arg, p.Ala571Asp, p.Trp621Cys) which have an allele frequency of less than 0.01% in the Japanese population and are predicted to be loss-of-function mutations by in silico analysis, the group of patients who were heterozygous carriers of at least one these rare variants showed a strong association with FP-related high toxicity (P = .003). Although the availability of screening of these rare loss-of-function variants is still unknown, our data provide useful information that may help to alleviate FP-related toxicity in Japanese patients with cancer.

DOI： 10.1111/cas.14553

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DOI： 10.1056/NEJMc2013020

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OBJECTIVE: To investigate long-term changes in lower urinary tract symptoms in patients with prostate cancer (PCa) who underwent low-dose-rate brachytherapy with iodine-125 (LDR-BT). PATIENTS AND METHODS: In this retrospective study, 313 patients with localized PCa underwent LDR-BT at Gifu University hospital between August 2004 and December 2013. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and quality of life due to urinary symptoms (IPSS-QOL) were measured before LDR-BT; at 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after LDR-BT; and annually thereafter. Study endpoints were chronological changes in IPSS, OABSS, and IPSS-QOL compared to pretreatment values. A multivariable nonlinear regression model with robust sandwich estimator evaluated association between outcomes and time with adjustment for covariates. RESULTS: All scores worsened immediately after LDR-BT compared to preoperative scores. However, symptoms improved with time and returned to baseline in 18-36 months. After a 5-year follow-up after LDR-BT, OABSS significantly worsened in almost all patients compared to baseline although there were gradual improvements in less than 5 years after LDR-BT. CONCLUSIONS: Our results may be of clinical importance in selecting treatment modalities for patients with localized PCa and long-term survival after definitive therapy.

DOI： 10.1016/j.urology.2020.04.106

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PURPOSE: We assessed the association of tumor size with patient survival following diagnosis of solitary hepatocellular carcinoma without vascular invasion. METHODS: The overall population comprised 638 patients who initially underwent hepatic resection with curative intent for a solitary hepatocellular carcinoma without macroscopic vascular invasion (487 had no microscopic vascular invasion). We set 5 cm as the tumor cutoff size for a solitary tumor based on the Milan criteria, and we used a multivariate Cox proportional hazards model and propensity score matching to evaluate the impact of tumor size on survival. RESULTS: Tumor size was significantly associated with a proportional increase in cancer-specific survival in the overall population (P = 0.001) and the subgroup with no microscopic vascular invasion (P = 0.029); however, multivariate analysis revealed no significant risk associated with recurrence-free survival (P = 0.055 and 0.59, respectively). After propensity score matching, the cancer-specific survival of patients with tumors > 5 cm was significantly worse than for those with tumors ≤ 5 cm in the overall population (P = 0.0077); the corresponding 2-year cumulative recurrence rates were 45.8% and 23.5%, respectively (P = 0.0027). Finally, the proportions of extrahepatic to total recurrences were 8% for those with tumors ≤ 5 cm and 29.1% for those with tumors > 5 cm in the unmatched overall population (P < 0.001). CONCLUSION: Tumor size was associated with recurrence within 2 years of surgery and with poor cancer-specific survival in patients with solitary hepatocellular carcinoma, even in the absence of microscopic vascular invasion.

DOI： 10.1007/s11605-019-04273-2

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Background We developed a novel high-sensitive assay for plasma xanthine oxidoreductase (XOR) activity that is not affected by the original serum uric acid level. However, the association of plasma XOR activity with that level has not been fully examined. Methods This cross-sectional study included 191 subjects (91 males, 100 females) registered in the MedCity21 health examination registry. Plasma XOR activity was determined using our assay for plasma XOR activity with [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Serum levels of uric acid and adiponectin, and visceral fat area (VFA) obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index. Results The median values for uric acid and plasma XOR activity were 333 μmol/L and 26.1 pmol/h/mL, respectively. Multivariable linear regression analysis showed a significant and positive association of serum uric acid level (coefficient: 26.503; 95% confidence interval: 2.06, 50.945; p = 0.035) with plasma XOR activity independent of VFA and HOMA-IR, and also age, gender, alcohol drinking habit, systolic blood pressure, estimated glomerular filtration rate (eGFR), glycated hemoglobin A1c, triglyceride, and adiponectin levels. The "gender*XOR activity" interaction was not significant (p = 0.91), providing no evidence that gender modifies the relationship between plasma XOR activity and serum uric acid level. Conclusions Plasma XOR activity was found to be positively associated with serum uric acid level independent of other known confounding factors affecting that level, including gender difference, eGFR, adiponectin level, VFA, and HOMA-IR.

DOI： 10.1515/cclm-2019-0199

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BACKGROUND: Outpatient cancer chemotherapy may lead to improved quality of life (QOL) by allowing treatment to continue without impairing the social lives of patients compared with hospitalization. However, the occurrence of serious adverse events may cause a decline in QOL. We investigated the relationship between outpatient chemotherapy-induced adverse events and QOL. METHODS: A single-center retrospective descriptive study was conducted in patients who received outpatient chemotherapy at Gifu University Hospital (Gifu, Japan) between September 2017 and December 2018. The utility values of QOL, type and severity of adverse events, type of cancer, chemotherapy regimen, and other patient demographics were analyzed. Adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L). Associations between the EQ-5D-5L utility value and serious adverse events were assessed using adjusted (age and sex) odds ratios obtained with a proportional odds logistic regression model. RESULTS: Data from 1008 patients who received 4695 chemotherapy cycles were analyzed. According to proportional odds logistic regression, the adverse events that significantly correlated with a decreased EQ-5D-5L utility value were malaise, edema of the limbs, peripheral neuropathy, pruritus, and dry skin. Based on the proportional odds logistic analysis, neither cancer type nor anticancer drugs were significantly correlated with the EQ-5D-5L utility value in patients who received chemotherapy. Pharmaceutical care for peripheral neuropathy significantly improved patients' EQ-5D-5L utility value from 0.747 to 0.776 (P < 0.01). CONCLUSIONS: Adverse events (i.e., peripheral neuropathy, malaise, and edema of the limbs) are significantly correlated with a decrease in QOL, regardless of the type of cancer or anticancer drugs used. Pharmaceutical care provided by pharmacists in collaboration with physicians may improve QOL.

DOI： 10.1007/s00520-020-05443-8

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BACKGROUND/AIM: The effect of renal dysfunction on the toxicity and efficacy of oxaliplatin remains unclear. We investigated the association between creatinine clearance (Ccr), a marker of renal function, and the toxicity and efficacy of oxaliplatin in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC who received oxaliplatin-based chemotherapy as first-line treatment were included in this study. Primary outcome was peripheral neuropathy (Grade ≥2), while secondary outcomes included neutropenia (Grade ≥3), thrombocytopenia (Grade ≥2) and overall survival (OS). RESULTS: A total of 145 patients with mCRC were eligible. Incidence rates of peripheral neuropathy (Grade ≥2), neutropenia (Grade ≥3) and thrombocytopenia (Grade ≥2) were 30.3%, 37.2% and 16.6%, respectively, and median OS was 29.1 months. Cox proportional hazards analysis indicated that there was no significant relationship between Ccr and any adverse event, or between Ccr and OS. CONCLUSION: Dose reduction of oxaliplatin based on Ccr is not recommended in patients with mCRC.

DOI： 10.21873/anticanres.14207

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OBJECTIVE: TAS-102 is effective for treating patients with metastatic colorectal cancer (mCRC). This study determined whether combining bevacizumab (Bmab) with TAS-102 improves clinical outcomes in refractory mCRC. PATIENTS AND METHODS: We retrospectively analyzed data from Japanese patients with refractory mCRC who received TAS-102 (35 mg/m2 , twice a day) with (T-B group) or without Bmab (TAS-102 monotherapy; T group) between July 2014 and December 2018. The primary endpoint was median overall survival (OS), and secondary endpoints were median time to treatment failure, overall response rate, and the incidence of adverse events. Clinical outcomes were compared using propensity score matched analysis. RESULTS: Data from 57 patients were analyzed (T-B group: 21 patients, T group: 36 patients). Median OS was significantly longer in the T-B group than the T group (14.4 months vs. 4.5 months, p < .001). Cox proportional hazard analysis showed that combination therapy with Bmab was significantly correlated with OS. Propensity score matched analysis confirmed that the median OS was significantly longer in the T-B group than the T group (14.4 months vs. 6.1 months, p = .006) and that there was a significant correlation between Bmab and OS. The incidence of hypertension (grade ≥2) as an adverse event was significantly higher in the T-B group than the T group (23.8% vs. 0.0%, p = .005), whereas other adverse events were comparable between the two groups. CONCLUSION: Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC refractory to standard therapies. IMPLICATIONS FOR PRACTICE: Combining bevacizumab (Bmab) with TAS-102 significantly improved overall survival and several prognostic indicators in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, with manageable toxicities. Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC.

DOI： 10.1634/theoncologist.2019-0541

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Malnutrition is an important risk factor for the development of sarcopenia. Recently, phase angle (PhA) obtained from the bioelectrical impedance analysis is increasingly becoming known as a nutritional status marker and may be considered a good indicator to identify elderly patients at risk of sarcopenia. In this study, we investigated the prevalence of sarcopenia and the relationship between sarcopenia and PhA or body mass index (BMI) as nutritional factors, and evaluated the discrimination performance of these nutritional factors for sarcopenia in 210 kidney transplant recipients. The median age was 55 years and 11.1% had sarcopenia. This prevalence of sarcopenia was lower than previous reports in kidney transplant recipients, maybe because of the differences in sarcopenia definitions and population demographics such as age, sex, race, and comorbidities. Both PhA and BMI were negatively correlated with sarcopenia after adjusting for age, sex, dialysis vintage, time after transplant, presence of diabetes mellitus, hemoglobin, estimated glomerular filtration rate, and the other nutritional factor. The discrimination performance for PhA and BMI had enough power to detect sarcopenia. These results suggest that PhA and BMI can be used in clinical practice to predict sarcopenia in kidney transplant patients.

DOI： 10.1038/s41598-019-57195-z

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BACKGROUND/AIM: To clarify whether renal dysfunction affects the incidence of adverse events associated with oxaliplatin, the present study was designed to investigate the relationship between creatinine clearance (Ccr) and the incidence of oxaliplatin-related adverse events. PATIENTS AND METHODS: A total of 287 CRC patients who received the first cycle of oxaliplatin-based chemotherapy were eligible. Adverse events, including nausea, vomiting, neutropenia and thrombocytopenia, were graded, and the relationship between Ccr and the incidence of adverse events was examined using multivariable logistic regression analysis. RESULTS: A multivariable analysis indicated that the incidence of grade ≥2 nausea increased, while the incidence of other adverse events tended to be higher, as the Ccr decreased. Particularly, renal dysfunction (Ccr <60 ml/min) was a significant risk factor for grade ≥2 nausea (p=0.042). CONCLUSION: Care should be taken to avoid adverse events associated with oxaliplatin in patients with renal dysfunction.

DOI： 10.21873/anticanres.13953

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BACKGROUND: Although surviving sepsis campaign guidelines recommend the use of inotropes in the presence of myocardial dysfunction, the effects of inotropes, including epinephrine, dobutamine, and milrinone, on in-hospital mortality in patients with septic shock remains unclear. MATERIALS AND METHODS: We conducted an international,2-center, retrospective cohort study. The Cox proportional hazards regression model with time-varying covariates was used to investigate whether epinephrine, milrinone, or dobutamine reduces in-hospital mortality in patients with septic shock. Sensitivity analysis was performed using propensity score matching. The primary outcome was in-hospital mortality. The secondary outcome included atrial fibrillation (Afib) with a rapid ventricular response (RVR) in the intensive care unit (ICU) and ICU-free days. RESULTS: A total of 417 patients with septic shock were included, 72 (17.3%) of whom received inotropes. The use of epinephrine and dobutamine was associated with significantly higher in-hospital mortality (epinephrine, hazard ratio [HR]: 4.79, 95% confidence interval [CI]: 2.12-10.82, P = .001; dobutamine, HR: 2.53, 95% CI: 1.30-4.95, P = .046). The effects of epinephrine and dobutamine were time- and dose-dependent. The use of milrinone was not associated with increased mortality (HR: 1.07, 95% CI: 0.42-2.68, P = .345). The use of epinephrine, dobutamine, and milrinone was associated with significantly increased odds of Afib with RVR (epinephrine, odds ratio [OR]: 3.88, 95% CI: 1.11-13.61, P = .034; dobutamine, OR: 3.95, 95% CI: 1.14-13.76; and milrinone, OR: 3.77, 95% CI: 1.05-13.59). On the other hand, the use of epinephrine, dobutamine, and milrinone was not associated with less ICU-free days (epinephrine, adjusted OR: 0.30, 95% CI: 0.09-1.01, P = .053; dobutamine, adjusted OR: 0.91, 95% CI: 0.29-2.84; and milrinone, adjusted OR: 0.60, 95% CI: 0.19-1.87). CONCLUSION: The present study showed that the use of epinephrine and dobutamine was associated with significantly increased in-hospital mortality in patients with septic shock. These effects were both time- and dose-dependent. On the other hand, the use of milrinone was not associated with increased in-hospital mortality.

DOI： 10.1177/0885066619892218

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BACKGROUND: Severely burned patients often suffer white blood cell and platelet drop following the injury. Though coagulopathy after burn injury have been reported, the association between leukopenia or thrombopenia and mortality is still unrevealed. To determine whether early drastic drops in white blood cells (WBCs) and platelets following injury can be prognostic markers in patients with major burns. METHODS: This is a retrospective cohort study setting in a single Burn Center in Japan. Data comprising patients' characteristics and blood cell counts (red blood cells [RBCs], WBCs including neutrophils, monocytes, and lymphocytes, and platelets) over the first 30 days after burn injury were serially collected from patients suffering major burn injury (≥20% TBSA) from January 1, 2006 to December 31, 2015. To determine blood cell counts affecting 60-day mortality, we used multivariable Cox proportional hazard analysis to assess associations between each blood cell count and mortality, adjusting for age and %TBSA as covariates, and evaluated predicted value of the hazard ratio (HR) of death. RESULTS: We enrolled 280 patients. Following burn injury, all blood cell counts were high at admission, then decreased. RBCs diminished progressively and plateaued 2 weeks after injury. WBCs decreased suddenly 2 days after injury, then increased and stabilized. Platelets decreased more rapidly than WBCs to their nadir at 3 days, then continually increased. After covariate adjustment, low RBCs from day 1 (HR: 0.566, 95% C.I. 0.423, 0.759) to day 5 (HR: 0.524, 95% C.I. 0.175, 0.576) were predictors of mortality. Neutrophil count was not a risk factor, but day 3 lymphocyte count (HR: 0.131, 95% C.I. 0.026, 0.646) and day 10 monocyte count (HR: 0.044, 95% C.I. 0.005, 0.396) were risk factors. Low platelet counts from day 3 (HR: 0.545, 95% C.I. 0.300, 0.981) to day 30 following injury were always a predictor of mortality. CONCLUSIONS: Early thrombopenia and lymphopenia were independent risk factors for 60-day mortality, and prolonged thrombopenia and monocytopenia were independent risk factors for mortality. These findings might shed light on mechanisms of immune response following severe burns.

DOI： 10.1016/j.burns.2019.07.014

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OBJECTIVE: TAS-102 is effective for treating patients with metastatic colorectal cancer (mCRC). This study determined whether combining bevacizumab (Bmab) with TAS-102 improves clinical outcomes in refractory mCRC. PATIENTS AND METHODS: We retrospectively analyzed data from Japanese patients with refractory mCRC who received TAS-102 (35 mg/m2, twice a day) with (T-B group) or without Bmab (TAS-102 monotherapy; T group) between July 2014 and December 2018. The primary endpoint was median overall survival (OS), and secondary endpoints were median time to treatment failure, overall response rate, and the incidence of adverse events. Clinical outcomes were compared using propensity score matched analysis. RESULTS: Data from 57 patients were analyzed (T-B group: 21 patients, T group: 36 patients). Median OS was significantly longer in the T-B group than the T group (14.4 months vs. 4.5 months, p < .001). Cox proportional hazard analysis showed that combination therapy with Bmab was significantly correlated with OS. Propensity score matched analysis confirmed that the median OS was significantly longer in the T-B group than the T group (14.4 months vs. 6.1 months, p = .006) and that there was a significant correlation between Bmab and OS. The incidence of hypertension (grade ≥2) as an adverse event was significantly higher in the T-B group than the T group (23.8% vs. 0.0%, p = .005), whereas other adverse events were comparable between the two groups. CONCLUSION: Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC refractory to standard therapies. IMPLICATIONS FOR PRACTICE: Combining bevacizumab (Bmab) with TAS-102 significantly improved overall survival and several prognostic indicators in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, with manageable toxicities. Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC.

DOI： 10.1634/theoncologist.2019-0541

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Language：Japanese   Publisher：(一社)日本神経学会  

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DOI： 10.1016/j.resuscitation.2019.09.001

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BACKGROUND/AIM: Sunitinib is used for the treatment of metastatic renal cell carcinoma (mRCC). Asian patients, including Japanese, tend not to tolerate long-term sunitinib therapy of 50 mg p.o. once daily for 4 weeks, followed by 2 week off treatment due to severe adverse events at this dosage level. The aim of this retrospective study was to investigate the optimal dose of sunitinib for long-term continuation in Asian patients with mRCC. PATIENTS AND METHODS: The study cases were 50 patients with mRCC who were treated with sunitinib between June 2008 and December 2017. Risk analysis for "unacceptable" adverse events (depending on the physician, ranging from grade 2 to ≥ grade 3) leading to discontinuation of sunitinib was determined by time-dependent Cox proportional hazard regression analysis. RESULTS: A total of 54 unacceptable adverse events leading to discontinuation occurred. Multivariable analysis indicated that a sunitinib dose of ≤ 37.5 mg/day significantly reduced the risk of discontinuation due to adverse events in comparison with 50 mg/day [hazard ratio (HR) 0.08, 95% confidence interval (CI) 0.03-0.21, p < 0.001). The progression-free survival (PFS) with a sunitinib dose ≤ 37.5 mg/day was longer than that associated with a dose of 50 mg/day, albeit not to a statistically significant degree (120 days for ≤ 37.5 mg/day vs 41 days for 50 mg/day, HR 0.39, 95% CI 0.10-1.44, p = 0.157). CONCLUSION: Our findings suggest that the optimal dose of sunitinib for Asian, including Japanese, patients with mRCC is ≤ 37.5 mg/day.

DOI： 10.1007/s00280-019-03935-x

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DOI： 10.1016/j.resuscitation.2019.06.288

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Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018 to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by the collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.

DOI： 10.3390/jcm8091320

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Drugs can cause acute respiratory distress syndrome (ARDS). However, there is no established clinical prediction rule for drug-associated ARDS (DARDS). We aimed to develop and validate a scoring system for DARDS prediction. We analysed data collected from a prospective, single-centre, cohort study that included ARDS patients. The ARDS diagnosis was based on the American-European Consensus Conference or Berlin definition. Drug-associated acute lung injury (DALI) was defined as previous exposure to drugs which cause ALI and presence of traditional risk factors for ALI. High-resolution computed tomography (HRCT; indicating extent of lung damage with fibroproliferation), Acute Physiology and Chronic Health Evaluation (APACHE) II, and disseminated intravascular coagulation (DIC; indicating multiorgan failure) scores and PaO2/FiO2 were evaluated for their ability to predict DARDS. Twenty-nine of 229 patients had DARDS. The HRCT, APACHE II, and DIC scores and PaO2/FiO2 were assessed. The model-based predicted probability of DARDS fitted well with the observed data, and discrimination ability, assessed through bootstrap with an area under the receiver-operating curve, improved from 0.816 to 0.875 by adding the HRCT score. A simple clinical scoring system consisting of the APACHE II score, PaO2/FiO2, and DIC and HRCT scores can predict DARDS. This model may facilitate more appropriate clinical decision-making.

DOI： 10.1038/s41598-019-45063-9

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Irinotecan is effective for the treatment of metastatic colorectal cancer (mCRC) and advanced pancreatic cancer (aPC). However, these treatments are often limited due to the incidence of severe neutropenia. We identified risk factors for severe neutropenia in patients with mCRC or aPC, receiving irinotecan-based chemotherapy regimens. The study selected 104 patients (mCRC: 53 and aPC: 51) who received irinotecan-based chemotherapy between January 2014 and May 2018 and who were included in the present study. The initial dose of irinotecan was 150 mg/m2 in all patients, and patients with a lower initial dose of irinotecan were excluded. Severe neutropenia (grade ≥ 3) occurred in 56 patients (53.8%). Multivariable Cox proportional hazards analysis indicated that modified FOLFIRINOX (mFOLFIRINOX) and serum total bilirubin (T-Bil) were significant risk factors for severe neutropenia. Moreover, with receiver-operating characteristic (ROC) curve analysis, the cutoff for T-Bil was found to be 0.7 mg/dL. Among patients treated with mFOLFIRINOX therapy, the incidence of severe neutropenia was significantly higher in patients with high level of T-Bil (> 0.7 mg/dL) than in those without it (93.8% vs 55.0%, P = 0.006). A chemotherapy regimen (modified FOLFIRINOX therapy) and T-Bil > 0.7 mg/dL were significant risk factors for severe neutropenia in patients receiving 150 mg/m2 irinotecan.

DOI： 10.1007/s12032-019-1288-7

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BACKGROUND: Cerebral oximetry (rSO2) may be useful in assessing the probability of return of spontaneous circulation (ROSC). However, the potential of assessing the trend in the rSO2 value has not been discussed when determining the probability of ROSC. METHODS: This was a retrospective study of out-of-hospital cardiac arrest (OHCA) patients with continuous rSO2 values recorded during cardiopulmonary arrest. We used logistic regression analysis at each time point to investigate the best subsets of rSO2-related variables for ROSC, which included rSO2 (baseline), the baseline value of rSO2; amount of maximum rise, the maximum difference of rSO2 from rSO2 (baseline) over t minutes; ΔrSO2 (t):(amount of maximum rise)/rSO2 (baseline) over t minutes after hospital arrival. RESULTS: Among the 90 included patients, 35 achieved ROSC. Area under the curve (AUC) analysis revealed that ΔrSO2 over a 16-min measurement period was significantly higher than ΔrSO2 measured over 4-, 8-, 12-, and 20-min periods. During this 16-min period, the subset showing the best AUC value was interaction of the amount of maximum rise and rSO2 (baseline) rather than the amount of maximum rise or ΔrSO2 alone (AUC = 0.91). CONCLUSIONS: The combination of rSO2 (baseline) with the amount of maximum rise in rSO2 value over time might be a new index for the prediction of ROSC that could be useful in guiding cardiopulmonary resuscitation. Further studies are needed to validate these findings.

DOI： 10.1016/j.resuscitation.2019.04.015

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DOI： 10.1016/j.alit.2018.12.006

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INTRODUCTION: Glycated hemoglobin (A1c) and glycated albumin (GA) are often used as indicators of glycemic control. In this study, we determined whether prednisolone (PSL) administration lowers plasma GA. METHODS: We investigated the factors affecting GA using multivariate analysis in 48 subjects with connective tissue diseases (CTDs). RESULTS: Multiple regression analysis of GA showed that the dose of PSL [β = - 1.36; 95% confidence interval (CI) - 2.59 to - 0.14; p = 0.03], age (β = 0.06; 95% CI 0.03-0.09; p < 0.001), body mass index (BMI) (β = - 0.14; 95% CI - 0.28 to - 0.01; p = 0.042), and A1c (β = 1.4; 95% CI 0.38-2.42; p = 0.008) significantly correlated with GA (adjusted R2 = 0.518). Moreover, GA levels adjusted for age, sex, BMI, plasma albumin (Alb) and creatinine (Cre), and A1c in the subjects taking ≥ 5 mg PSL was significantly lower than those in those taking < 5 mg PSL. Finally, the dose of PSL (as a continuous variable) was negatively correlated with GA adjusted for age, sex, BMI, Alb, Cre, and A1c. CONCLUSION: High dose (≥ 5 mg) PSL reduces GA concentration more than glycemia.

DOI： 10.1007/s13300-018-0552-8

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Background: Higher levels of uric acid production have been reported in individuals with visceral fat obesity, and obesity is known to enhance xanthine oxidoreductase (XOR) activity, although the precise mechanism remains unclear. We investigated the associations of visceral fat area (VFA), serum adiponectin level, and insulin resistance with plasma XOR activity using our novel highly sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Methods: This cross-sectional study included 193 subjects (92 males and 101 females) registered in the MedCity21 health examination registry. Plasma XOR activity, serum adiponectin level, and VFA obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index. Results: The mean values for VFA, log HOMA-IR, and log plasma XOR activity were 76.8 ± 45.8 cm2, 0.14 ± 0.30, and 1.50 ± 0.44 pmol/h/mL, respectively. Multiple regression analysis showed that HOMA-IR was significantly (p=0.020) associated with plasma XOR activity independent of other factors, including VFA and adiponectin level, as well as age, sex, alcohol drinking habit, smoking habit, alanine transaminase, HbA1c, and eGFR. The "sex∗HOMA - IR" interaction was not significant (p=0.020) associated with plasma XOR activity independent of other factors, including VFA and adiponectin level, as well as age, sex, alcohol drinking habit, smoking habit, alanine transaminase, HbA1c, and eGFR. The ". Conclusions: Our results indicate that insulin resistance is associated with plasma XOR activity and that relationship is independent of visceral adiposity and adiponectin level, suggesting that the development of insulin resistance resulting from increased visceral adiposity and/or reduced serum adiponectin contributes to increased uric acid production by stimulating XOR activity.

DOI： 10.1155/2019/1762161

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Background: To maximize the effect of intravenous (IV) thrombolysis and/or endovascular therapy (EVT) for acute ischemic stroke (AIS), stroke centers need to establish a parallel workflow on the basis of a code stroke (CS) protocol. At Kokura Memorial Hospital (KMH), we implemented a CS system in January 2014; however, the process of information sharing within the team has occasionally been burdensome. Objective: To solve this problem using information communication technology (ICT), we developed a novel application for smart devices, named "Task Calc. Stroke" (TCS), and aimed to investigate the impact of TCS on AIS care. Methods: TCS can visualize the real-time progress of crucial tasks for AIS on a dashboard by changing color indicators. From August 2015 to March 2017, we installed TCS at KMH and recommended its use during normal business hours (NBH). We compared the door-to-computed tomography time, the door-to-complete blood count (door-to-CBC) time, the door-to-needle for IV thrombolysis time, and the door-to-puncture for EVT time among three treatment groups, one using TCS ("TCS-based CS"), one not using TCS ("phone-based CS"), and one not based on CS ("non-CS"). A questionnaire survey regarding communication problems was conducted among the CS teams at 3 months after the implementation of TCS. Results: During the study period, 74 patients with AIS were transported to KMH within 4.5 h from onset during NBH, and 53 were treated using a CS approach (phone-based CS: 26, TSC-based CS: 27). The door-to-CBC time was significantly reduced in the TCS-based CS group compared to the phone-based CS group, from 31 to 19 min (p = 0.043). Other processing times were also reduced, albeit not significantly. The rate of IV thrombosis was higher in the TCS-based CS group (78% vs. 46%, p = 0.037). The questionnaire was correctly filled in by 34/38 (89%) respondents, and 82% of the respondents felt a reduction in communication burden by using the TCS application. Conclusions: TCS is a novel approach that uses ICT to support information sharing in a parallel CS workflow in AIS care. It shortens the processing times of critical tasks and lessens the communication burden among team members.

DOI： 10.3389/fneur.2019.01118

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While modified FOLFIRINOX therapy is effective for treating advanced pancreatic cancer, it frequently causes severe neutropenia. The present study investigated the effect of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients who received modified FOLFIRINOX. The study subjects were 51 patients (30 males and 21 females) with advanced pancreatic cancer who received modified FOLFIRINOX (2h bolus injection of oxaliplatin at 85 mg/m², 2 h bolus injection of L-leucovorin at 200 mg/m², 90min bolus injection of irinotecan at 150 mg/m², followed by continuous infusion of 5-fluorouracil for 46 h at 2400 mg/m² without bolus 5-fluorouracil) during the period from January 2014 to May 2018. No patients had prior history of chemotherapy. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were secondary endpoints. Severe neutropenia (grade ≥3) occurred in 39 patients (76.4%), and Cox proportional hazard analysis identified high total bilirubin level as a significant risk factor. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (21.3 months versus 8.9 months, p = 0.020). Moreover, there was a significant correlation between OS and the grade of neutropenia (r = 0.306, p = 0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRINOX therapy.

DOI： 10.3390/cancers10110454

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DOI： 10.1038/s41598-018-33883-0

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OBJECTIVES: The authors stopped using tranexamic acid (TXA) in April 2013. The present study aimed to examine the impact of a "no-TXA-use" policy by comparing the adverse effects of TXA and clinical outcomes before and after the policy change in patients undergoing cardiovascular surgery. DESIGN: A single center retrospective cohort study. SETTING: A single cardiovascular center. PARTICIPANTS: Patients undergoing cardiovascular surgery between January 2008 and July 2015 (n = 3,535). INTERVENTIONS: Patients' outcomes before and after the policy change were compared to evaluate the effects of the change. MEASUREMENTS AND MAIN RESULTS: The seizure rate decreased significantly after the policy change (6.9% v 2.7%, p < 0.001). However, transfusion volumes and blood loss volumes increased significantly after the policy change (1,840 mL v 2,030 mL, p = 0.001; 1,250 mL v 1,372 mL, p < 0.001, respectively). Thirty-day mortality was not statistically different (1.6% v 1.4%, p = 0.82), nor were any of the other outcomes. Propensity-matched analysis and segmented regression analysis showed similar results. CONCLUSIONS: The mortality rate remained the same even though the seizure rate decreased after the policy change. Blood loss volume and transfusion volume both increased after the policy change. TXA use provides an advantageous benefit by reducing the need for blood transfusion.

DOI： 10.1053/j.jvca.2017.10.018

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BACKGROUND: Intraoperative oxygen management is poorly understood. It was hypothesized that potentially preventable hyperoxemia and substantial oxygen exposure would be common during general anesthesia. METHODS: A multicenter, cross-sectional study was conducted to describe current ventilator management, particularly oxygen management, during general anesthesia in Japan. All adult patients (16 yr old or older) who received general anesthesia over 5 consecutive days in 2015 at 43 participating hospitals were identified. Ventilator settings and vital signs were collected 1 h after the induction of general anesthesia. We determined the prevalence of potentially preventable hyperoxemia (oxygen saturation measured by pulse oximetry of more than 98%, despite fractional inspired oxygen tension of more than 0.21) and the risk factors for potentially substantial oxygen exposure (fractional inspired oxygen tension of more than 0.5, despite oxygen saturation measured by pulse oximetry of more than 92%). RESULTS: A total of 1,786 patients were found eligible, and 1,498 completed the study. Fractional inspired oxygen tension was between 0.31 and 0.6 in 1,385 patients (92%), whereas it was less than or equal to 0.3 in very few patients (1%). Most patients (83%) were exposed to potentially preventable hyperoxemia, and 32% had potentially substantial oxygen exposure. In multivariable analysis, old age, emergency surgery, and one-lung ventilation were independently associated with increased potentially substantial oxygen exposure, whereas use of volume control ventilation and high positive end-expiratory pressure levels were associated with decreased potentially substantial oxygen exposure. One-lung ventilation was particularly a strong risk factor for potentially substantial oxygen exposure (adjusted odds ratio, 13.35; 95% CI, 7.24 to 24.60). CONCLUSIONS: Potentially preventable hyperoxemia and substantial oxygen exposure are common during general anesthesia, especially during one-lung ventilation. Future research should explore the safety and feasibility of a more conservative approach for intraoperative oxygen therapy.

DOI： 10.1097/ALN.0000000000002181

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AIMS/INTRODUCTION: To clarify the association between perioperative variables and postoperative bleeding in pars plana vitrectomy for vitreous hemorrhage in diabetic retinopathy. MATERIALS AND METHODS: The present retrospective study enrolled 72 eyes of 64 patients who were admitted to Osaka University Hospital between April 2010 and March 2014, and underwent vitrectomy for vitreous hemorrhage as a result of diabetic retinopathy. RESULTS: Postoperative bleeding developed in 12 eyes. Using binomial logistic regression analysis, we found that the duration of operation was the only significant variable associated with postoperative bleeding within 12 weeks after vitrectomy. Furthermore, Poisson regression analysis identified fasting blood glucose just before vitrectomy, no treatment with antiplatelet drugs and treatment with antihypertensive drugs, as well as duration of operation, to be significantly associated with the frequency of bleeding within 52 weeks after vitrectomy. CONCLUSIONS: Long duration of operation can be used to predict bleeding within both 12 and 52 weeks after vitrectomy. In addition, fasting blood glucose just before vitrectomy, no treatment with antiplatelet drugs and treatment with antihypertensive drugs might be risk factors for postoperative bleeding up to 1 year after vitrectomy.

DOI： 10.1111/jdi.12791

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

DOI： 10.1111/den.12946

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Nature Publishing Group  

DOI： 10.1038/s41430-017-0053-2

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DOI： 10.1371/journal.pone.0208638

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DOI： 10.1371/journal.pone.0182563

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Language：Japanese   Publisher：高尿酸血症・メタボリックシンドロームリサーチフォーラム  

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Language：Japanese   Publisher：泌尿器科紀要刊行会  

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Language：Japanese   Publisher：(株)医学書院  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00270&link_issn=&doc_id=20200714030006&doc_link_id=10.11477%2Fmf.1681201765&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1681201765&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(一社)日本臨床薬理学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本痛風・尿酸核酸学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J07281&link_issn=&doc_id=20190828010034&doc_link_id=10.14867%2Fgnamtsunyo.43.1_72&url=https%3A%2F%2Fdoi.org%2F10.14867%2Fgnamtsunyo.43.1_72&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：泌尿器科紀要刊行会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：日本尿路結石症学会  

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Language：Japanese   Publisher：(一社)日本痛風・尿酸核酸学会  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：日本尿路結石症学会  

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1097/01.ccm.0000529565.64391.72

Web of Science

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Presentation type：Poster presentation  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Poster presentation  

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Language：English   Presentation type：Poster presentation  

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Presentation type：Poster presentation  

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Presentation type：Oral presentation (general)  

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