記述言語：英語  

DOI： 10.1016/j.resinv.2025.01.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Molecular profiling of non-small cell lung cancer (NSCLC) is crucial for personalized treatment, but obtaining adequate tumor tissue can be challenging. This study evaluated the utility of droplet digital polymerase chain reaction (ddPCR) analysis of bronchial washings (BWs) and serum for detecting driver oncogene mutations in NSCLC patients, comparing its performance to standard tissue genotyping methods. METHODS: In this prospective, multicenter study conducted at two university hospitals in Yokohama, Japan, 73 treatment-naïve NSCLC patients underwent bronchoscopy with BW collection and blood sampling between October 2022 and April 2024. ddPCR was performed on BW and serum samples to detect epidermal growth factor receptor (EGFR; L858R, exon 19 deletions, G719X), KRAS (G12/13), and BRAF (V600E) mutations. Results were compared with standard tissue genotyping methods, including AmoyDx and Oncomine Dx Target Test (DxTT) assays. Turnaround time (TAT) for results was also assessed. The study protocol was approved by the institutional review boards, and all participants provided informed consent. RESULTS: ddPCR analysis of BW samples showed high concordance with tissue genotyping, detecting EGFR mutations in 31.5% of cases (identical to tissue). For common EGFR mutations (L858R and exon 19 deletions), BW genotyping demonstrated 100% sensitivity and 98.0% specificity compared to tissue. TAT was significantly shorter for BW ddPCR compared to tissue genotyping (4.4±1.8 vs. 20.4±7.7 days, P<0.001). Serum ddPCR showed lower sensitivity (7.8% vs. 33.3% for EGFR mutations) compared to tissue genotyping, with detection associated with the presence of bone metastases. KRAS and BRAF mutations were detected at similar rates in BW and tissue samples, but at lower rates in serum. CONCLUSIONS: ddPCR analysis of BWs demonstrates high accuracy and rapid TAT for detecting common driver mutations in NSCLC. This approach represents a promising alternative to tissue biopsy for molecular profiling, potentially expediting treatment decisions. While serum ddPCR showed limited utility, it may complement tissue genotyping in specific clinical scenarios.

DOI： 10.21037/tlcr-24-772

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Objectives: Late gadolinium enhancement (LGE)-MRI has proven utility in prognosticating outcomes in patients with non-ischemic cardiomyopathy (NICM). However, evidence regarding its ability to predict responsiveness to optimal medical therapy remains insufficient. This study conducted a meta-analysis to evaluate the predictive utility of LGE-MRI for left ventricular reverse remodeling (LVRR) in response to pharmacological therapy. Methods: Data from 1092 NICM patients across 13 studies were included in the analysis. To assess the predictive ability of LGE-MRI for LVRR following optimal medical therapy, a pooled odds ratio was calculated using an inverse variance random-effects meta-analysis. Subgroup analyses were performed by stratifying patients based on the presence or absence of left ventricular dilation and by LVEF (<30% vs. ≥30%). Results: The pooled odds ratio of the absence of LGE for predicting LVRR in NICM was 3.72 (95% CI: 2.83-4.90, I2 = 0, P for heterogeneity = 0.54). A comparison of pooled odds ratios between dilated cardiomyopathy (DCM) and NICM showed no significant difference (p = 0.16). A subgroup analysis in NICM based on the left ventricular ejection fraction (LVEF) demonstrated no significant difference in odds ratios between patients with LVEF <30% (OR: 2.96, 95% CI: 1.80-4.87) and those with LVEF ≥30% (OR: 3.97, 95% CI: 2.97-5.31), (p = 0.13). Conclusions: This meta-analysis suggested that LGE-MRI serves as a reliable predictor of LVRR in patients with NICM, regardless of left ventricular dilation or baseline LVEF classification.

DOI： 10.3390/jcm14030895

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To characterise patients with trisomy 8 presenting with autoinflammatory features, comparing them to patients with Behçet's disease (BD). METHODS: We comprehensively reviewed studies on trisomy 8-associated autoinflammatory symptoms from four online databases and analysed clinical data from both published cases and our institution. We then compared the clinical features of these patients with those of 657 BD patients from the Yokohama City University Registry. RESULTS: Of 1,542 screened articles, 88 involving 181 patients were eligible, along with six additional patients from our institution, resulting in a total of 187 patients included. Fever was the most common symptom in patients with trisomy 8 (85.8%), followed by oral ulcers (80.8%), gastrointestinal lesions (76.1%), genital ulcers (54.7%), and skin lesions (53.7%). Compared to BD patients, trisomy 8 patients exhibited higher rates of fever and gastrointestinal involvement (p<0.001), but lower rates of oral and genital ulcers, uveitis, and skin involvement (p<0.001), with no significant difference in joint symptoms. Trisomy 8 patients were older and had lower haemoglobin levels, increased mean corpuscular volume, decreased platelet counts, and higher C-reactive protein levels than BD patients. Additionally, the mortality rate was significantly higher in trisomy 8-positive patients (odds ratio, 11.74; 95% confidence interval, 5.94-22.82). CONCLUSIONS: Trisomy 8-associated autoinflammatory disease patients were older and had poorer prognoses, more gastrointestinal involvement, and less frequent oral and genital ulcers and skin involvement, making BD diagnosis less likely. Bone marrow examination should be considered for late-onset BD-like disease patients, particularly with recurrent fever.

DOI： 10.55563/clinexprheumatol/8j7rbr

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Along with lung volume reduction surgery (LVRS), bronchoscopic lung volume reduction is a treatment option for end-stage emphysema. However, comparisons among interventions remain insufficient. METHODS: We searched on PubMed, CENTRAL, Embase, and Web of Science. We included randomized controlled trials with outcomes measuring mid-term mortality within 6 months, changes in forced expiratory volume in one second (FEV1), St. George's Respiratory Questionnaire (SGRQ), six-minute walk distance (6MWD) from baseline, adverse event related to procedures, and long-term mortality within 5 years. Bayesian network meta-analysis was performed. The certainty was assessed by CINeMA. RESULTS: Twenty-five randomized controlled trials involving 4,283 patients were included, identifying seven types of procedures and standard of care. Mid-term mortality increased in LVRS and endobronchial valve (EBV) (LVRS, risk ratio [RR] 3.26, 95% CrI 1.98-6.21, low certainty; EBV, RR 2.06 95% CrI 1.07-4.36, moderate certainty). LVRS showed the largest improvements: change in FEV1 (187.2 mL, 95% CrI 166.4-209.6), 6MWD (42.2 m, 95% CrI 33.2-50.5), and SGRQ (- 13.29 points, 95% CrI - 27.25-0.75). Among bronchoscopic procedures, high efficacy was noted in EBV and endobronchial coil (EBC) for FEV1 changes (EBV, 111.8 mL, 95% CrI 92.2-136.2; EBC, 74.1 mL, 95% CrI 47.6-101.7). Pneumothorax increased in these two procedures (EBV, RR 12.75, 95% CrI 5.52-35.48; EBC, RR 4.95, 95% CrI 1.12-40.90). CONCLUSION: LVRS offers high efficacies but is accompanied by increased mid-term mortality. EBV and EBC also showed effectiveness; however, they increased pneumothorax, and EBV slightly increased mortality. For accurate assessment, long-term survival data of BLVR are needed.

DOI： 10.1007/s00408-024-00777-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Community-acquired pneumonia (CAP) is associated with high mortality rates and often results in prolonged hospital stays. The potential of machine learning to enhance prediction accuracy in this context is significant, yet clinicians often lack the programming skills required for effective data mining. This study aimed to assess the effectiveness of a low-code approach for assisting clinicians with data mining for mortality and length of stay (LOS) prediction in patients with CAP. A retrospective study was conducted using a low-code platform and the PyCaret library in Google Colab on data from patients with community-acquired pneumonia (CAP) admitted between January 2013 and December 2021 to two medical facilities. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) for mortality prediction and the R2 score for LOS prediction, with benchmarks set at AUC > 0.9 and R2 > 0.5. The Shapley Additive Explanations (SHAP) method was used for interpreting individual predictions. A total of 669 CAP patients were enrolled in the analysis.Fifteen models were evaluated for mortality prediction, and nineteen models were evaluated for LOS prediction utilizing the PyCaret library. The Light Gradient Boosting Machine model yielded the highest AUC (0.963) for mortality prediction. In predicting LOS, the Extratrees Regressor model achieved the highest R2 score of 0.585. Factors such as the severity of pneumonia and the Charlson Comorbidity Index (CCI) were significant factors influencing mortality. For the LOS, the CCI score, activities of daily living, and social support were significant predictors. The low-code approach enables medical professionals with limited technical expertise to effectively employ data science in their clinical decision-making process. This approach proved to be a valuable tool in the analysis of CAP patient data.

DOI： 10.1038/s41598-024-82615-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Community-acquired pneumonia (CAP) is a leading cause of death worldwide. Reducing inappropriate and excessive use of extended-spectrum antibiotics is essential for treating CAP effectively. Evaluating the risk of drug-resistant pathogens (DRPs) is crucial for determining initial antibiotic therapy in clinical settings. METHODS: This systematic review and meta-analysis assessed the risk factors for DRPs in patients with CAP. CAP-DRPs were defined as pathogens resistant to commonly used antibiotics for CAP, including nonpseudomonal β-lactams such as ceftriaxone or sulbactam-ampicillin, macrolides and respiratory fluoroquinolones. The studies included were divided into two cohorts, namely an all-patient cohort, comprising both culture-positive and culture-negative patients, and a culture-positive pneumonia cohort, comprising patients with identified causative pathogens. The primary objective of this study was to evaluate the risk factors for CAP-DRPs in the all-patient cohort. RESULTS: 24 articles were included with 11 categorised into the all-patient cohort. The meta-analysis identified 11 significant risk factors for CAP-DRPs, namely prior DRP infection/colonisation, tracheostomy, severe respiratory failure requiring early induction of mechanical ventilation, prior use of antibiotics, chronic lung disease, COPD, wound care, neurological disorders, prior hospitalisation, nursing home residence and low activities of daily living. CONCLUSION: To our knowledge, this is the first systematic review focused on CAP-DRP. Unlike previous reviews, the all-patient and culture-positive pneumonia cohorts were analysed separately. Findings from the all-patient cohort are particularly relevant for guiding initial antimicrobial selection in clinical practice. Furthermore, the abovementioned factors should be considered when developing prediction models for CAP-DRPs.

DOI： 10.1183/16000617.0183-2024

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Pre-existing myocardial fibrosis before aortic valve replacement (AVR) is a major cause of postoperative heart failure (HF). Evaluation of fibrosis by computed tomography extracellular volume (CT-ECV) may allow risk stratification for patients with severe aortic stenosis (AS) scheduled for transaortic AVR (TAVR) or surgical AVR (SAVR). We performed a meta-analysis to determine the prognostic value of CT-ECV for the prediction of adverse events in patients with severe AS scheduled for AVR. METHODS AND RESULTS: Electronic database searches of PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE were performed. A comprehensive literature review was conducted to examine the association between CT-ECV and prognosis in patients with severe AS who underwent AVR. The diagnostic performance of CT-ECV for predicting composite adverse events (all-cause death and hospitalization for HF) was assessed using a pooled odds ratio (OR). Data from 902 patients with severe AS were extracted from six studies, including 881 TAVR and 21 SAVR cases. The pooled OR of abnormal CT-ECV for predicting adverse events was 4.53 [95% confidence interval (CI): 3.13-6.57 (I 2 = 10%, P for heterogeneity = 0.50)]. We performed an OR meta-analysis on five studies with only TAVR cases (n = 807). The pooled OR of abnormal CT-ECV for predicting adverse events in TAVR patients was 4.85 [95% CI: 3.26-7.21 (I² = 0%, P < 0.001)]. CONCLUSION: Considering the high prognostic ability and versatility of CT-ECV, it may be used to predict postoperative adverse events in patients with severe AS who underwent AVR.

DOI： 10.1093/ehjopen/oeaf007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Stereotactic body radiation therapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC), which provides excellent local control (LC) and prolongs overall survival (OS). However, in current guidelines, transcatheter arterial chemoembolization (TACE) has been proposed as a key treatment option for patients with early- and intermediate-stage HCC, whereas SBRT is not. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials and retrospective studies using the propensity score (PS) to compare the outcomes of SBRT and TACE for HCC in a balanced manner. We systematically searched the PubMed, Cochrane, EMBASE, and Web of Science databases to identify randomized controlled trials and studies comparing SBRT and TACE using PS analysis. The hazard ratios (HRs) for OS and LC were pooled. The heterogeneity between the data collected from these studies was also assessed. SBRT led to a comparable OS (HR: 0.83; 95 % confidence interval (CI): 0.52-1.34; p = 0.44) to TACE, and significantly improved LC (HR: 0.25; 95 % CI: 0.09-0.67; p = 0.006). Considerable heterogeneity was observed in the HR of OS and LC. Although there was no significant difference in the rate of grade 3 or higher toxicities between TACE and SBRT, or between studies, liver toxicity was identified as a common adverse event associated with both SBRT and TACE. Compared to TACE, SBRT showed a comparable OS and improved LC without serious toxicity. Therefore, SBRT should be considered an effective treatment option for various stages of HCC, depending on the tumor factors and pretreatment liver function.

DOI： 10.1016/j.radonc.2024.110614

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neoadjuvant immune checkpoint blockade (ICB) combined with chemotherapy has improved survival outcomes in locally-advanced non-small cell lung cancer (NSCLC). However, its impact on surgery has not been fully elucidated. We performed a systematic review and meta-analysis to compare surgical outcomes between neoadjuvant chemoimmunotherapy and chemotherapy alone in resectable NSCLC. PubMed and Embase were searched to select randomized controlled trials (RCTs) evaluating neoadjuvant ICB therapy for resectable NSCLC. The risk difference (RD) and odds ratio (OR) of outcomes such as surgical and R0 resection rates, overall complication rates, treatment-related adverse events (TRAEs), and AEs leading to cancellation of surgery were pooled using the random-effect model meta-analysis. We also evaluated the correlations between overall survival (OS) and surgical and safety outcomes. Eight RCTs with 3,387 patients were analyzed. Neoadjuvant chemoimmunotherapy was associated with improved surgical resection (RD 4.52 %, 95 % confidence interval [CI] 0.95 %-8.09 %, p = 0.01) and R0 resection (RD 4.04 %, 95 % CI 1.69 %-6.40 %, p = 0.0008) without increasing overall complications (RD -0.13 %, 95 % CI -5.14 %-4.88 %, p = 0.96), but an increase in surgery cancellation due to AEs (RD 1.15 %, 95 % CI 0.25 %- 2.05 %; p = 0.01) and grade 3-4 TRAEs (RD 3.42 %, 95 % CI 0.33 %-6.52 %, p = 0.03). OS did not show a direct significant correlation with surgical outcomes or TRAEs. Neoadjuvant chemoimmunotherapy improves resection rates but increases high-grade TRAEs and AEs leading to surgery cancellation. Nevertheless, incorporating ICB into neoadjuvant approach appears reasonable by improving surgical outcomes, potentially leading to improved survival in patients with locally-advanced NSCLC.

DOI： 10.1016/j.ctrv.2024.102833

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Dynamic stress computed tomography (CT) perfusion is a non-invasive method for quantifying myocardial ischaemia by assessing myocardial blood flow (MBF). In this meta-analysis, we evaluated the diagnostic accuracy of dynamic CT perfusion for the detection of significant coronary artery disease (CAD) across various CT scanners, obese patients, and its prognostic value. METHODS AND RESULTS: We systematically searched PubMed, Embase, Web of Science, and Cochrane library for published studies evaluating the accuracy of CT myocardial perfusion in diagnosing functional significant ischaemia by invasive fractional flow reserve. The diagnostic performance of dynamic CT perfusion in detecting ischaemia was evaluated using a summary receiver operating characteristic (sROC) curve. A total of 23 studies underwent meta-analysis. In myocardial region without ischaemia, MBF was measured at 1.39 mL/min/g [95% confidence interval (CI) 1.25-1.54], while in region with ischaemia, it was 0.92 mL/min/g (95% CI 0.83-1.01) (P < 0.001). On the patient-based analysis, the area under the sROC curve of CT-MBF was 0.92, with a sensitivity of 0.82 and specificity of 0.86. Differences in CT type (dual source vs. single source), and body mass index did not significantly affect the diagnostic performance. The pooled hazard ratio of dynamic CT perfusion for predicting adverse events was 4.98 (95% CI 2.08-11.93, P ≤ 0.001, I2 = 61%, P for heterogeneity = 0.07). CONCLUSION: Dynamic CT perfusion has high diagnostic performance in the quantitative assessment of ischaemia and detection of functional myocardial ischaemia as defined by invasive FFR and may be useful in risk stratification of CAD patients.

DOI： 10.1093/ehjci/jeae118

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The activity of osimertinib is not fully characterized in non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. Therefore, we conducted a systematic review and meta-analysis to assess the safety and efficacy of osimertinib in patients with NSCLC harboring uncommon somatic EGFR mutations. METHODS: PubMed, Embase, and the Cochrane Library were searched for eligible studies reporting the efficacy and safety of osimertinib in NSCLC with uncommon EGFR mutations defined as any mutations other than exon 19 deletion, L858R and T790M mutations, and exon 20 insertion, except when in compound. Then, we performed a meta-analysis to pool survival outcomes and antitumoral activity, including intracranial (ic) response and adverse events. RESULTS: Fifteen studies comprising 594 patients were included. The most frequently observed uncommon solitary mutations were G719X in 25% (81/327) of patients and L861Q in 21% (69/327). The most common compound mutations were G719X with T790M in 12% (23/192) of patients and G719X with S768I in 11% (22/192). Pooled analysis showed an objective response rate (ORR) of 51.30% (95% CI, 45.80 to 56.81), a disease control rate (DCR) of 90.11% (95% CI, 86.27 to 92.96), a median progression-free survival of 9.71 months (95% CI, 7.96 to 11.86), and a median overall survival of 16.79 months (95% CI, 9.93 to 28.39). icORR was 45.96% (95% CI, 30.18 to 62.17), and icDCR was 95.76% (95% CI, 69.84 to 100). Osimertinib was well tolerated with a frequency of grade 3 or more adverse events of 21.77% (95% CI, 6.24 to 43.33). CONCLUSION: Osimertinib demonstrated robust response in NSCLC harboring uncommon EGFR mutations, without unanticipated safety concerns.

DOI： 10.1200/PO.24.00331

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (AEs), which pose challenges to the continuation of treatment. Although ICIs are widely used in patients with cancer, studies reporting immune-mediated pancreatitis remain scarce. OBJECTIVES: We performed a systematic review and meta-analysis to address current knowledge gaps and provide clinical guidance for ICI-associated pancreatitis and lipase elevation. PATIENTS AND METHODS: We searched PubMed/Medline, Embase, and Web of Science for phase 3 randomized controlled trials (RCTs) evaluating ICIs. The incidence of any-grade and grade 3-5 pancreatitis/lipase elevation was calculated. Then, we performed a random-effect model meta-analysis to pool the odds ratios (ORs) of these outcomes using RCTs evaluating the addition of an ICI to systemic therapy to assess the effect of ICIs on pancreatic AEs. A systematic review of the treatment of ICI-related pancreatitis was also conducted. RESULTS: The incidence analysis included 81 articles (79 RCTs) comprising 36,871 patients. The incidence of treatment-related pancreatitis was 0.68% (any-grade) and 0.32% (grade 3-5). Meta-analysis revealed that the addition of ICI therapy significantly increased any-grade (OR 2.12, 95% confidence interval [CI] 1.45-3.11, p < 0.001) and grade 3-5 pancreatitis (OR 1.76, 95% CI 1.01-3.08, p < 0.05) with low heterogeneity among ICI subtype subgroups (any-grade: I2 = 0%, p = 0.99; grade 3-5: I2 = 0%, p = 0.63). In analysis of treatment outcome among 146 patients from 53 articles, glucocorticoids were used in 80.6% (n = 108/134) and ICIs were discontinued in 76.5% (n = 101/132; permanent discontinuation: 62.5% [n = 35/56]). CONCLUSIONS: The overall rate of pancreatitis appears low, but the addition of ICI therapy significantly increased the incidence of pancreatitis. These findings provide insight into the incidence and treatment of pancreatitis associated with ICIs.

DOI： 10.1007/s11523-024-01098-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Long-term macrolide therapy for non-cystic fibrosis bronchiectasis (NCFB) can play a significant role. However, such data are insufficient regarding the efficacy against severe exacerbation and adverse effects, including the emergence of macrolide-resistant pathogens and prolonged macrolide use beyond 1 year. METHODS: Randomized controlled trials (RCTs) and prospective observational studies comparing the efficacy and safety of macrolides and placebo in adult patients with NCFB were screened on April 10, 2024. The primary outcome was severe exacerbation frequency. RESULTS: Ten RCTs ≤1 year study durations were included. Most studies mainly included patients with a history of >2 exacerbations. Macrolides had a tendency to reduce the frequency of severe exacerbations compared with placebo (odds ratio = 0.54, 95% confidence interval (CI) = 0.25-1.18). Macrolides significantly reduced the frequency of exacerbations (rate ratio = 0.58, 95% CI = 0.48-0.69), prolonged the time to first exacerbation (rate ratio = 0.41, 95% CI = 0.30-0.55), improved the changes in SGRQ scores [mean difference (MD) = -3.99, 95% CI = -4.63-3.44] and percent predicted forced expiratory volume in 1 s (MD = -2.30, 95% CI = 0.26-4.33), and reduced sputum volume (gram) (MD = -7.44, 95% CI = -9.15-5.74). Additionally, macrolides did not increase drug-related adverse events leading to discontinuation. Qualitative SR of pathogens indicated macrolides might increase the number of macrolide-resistant oropharyngeal and sputum pathogens and the emergence of Pseudomonas aeruginosa. CONCLUSIONS: Our results support macrolide therapy for patients with NCFB. Studies with an observation period of >1 year or those focusing on patients with/without a minimal exacerbation history are required to determine the long-term effects on patients with NCFB.

DOI： 10.1016/j.resinv.2024.09.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Refractory or unexplained chronic cough disrupts quality of life and burdens health care systems around the world. The P2X3 receptor antagonist gefapixant is approved in many countries for its antitussive effects, but taste disturbances are a common adverse effect. Four newer, more selective P2X3 receptor antagonists have been developed to address this problem. RESEARCH QUESTION: How does the benefit-risk profile vary across the five available P2X3 receptor antagonists? STUDY DESIGN AND METHODS: A systematic review and network meta-analysis was conducted to evaluate the efficacy of P2X3 receptor antagonists, including gefapixant, sivopixant, eliapixant, camlipixant, and filapixant. Primary outcomes were a reduction rate in 24-hour cough frequency and incidence of taste disturbance. Dose-response curves and median effective dose (ED50) were calculated. Effect size at ED50 was ranked according to the surface under the cumulative ranking curve. The confidence was evaluated by Confidence In Network Meta-Analysis. RESULTS: Sixteen randomized controlled trials involving 4,904 participants were analyzed. The gefapixant regimen demonstrated an ED50 of 90.7 mg/d for cough frequency reduction. Gefapixant showed the highest antitussive effectiveness at ED50 (reduction rate in 24-hour cough frequency: median, 28.1%; 95% credible interval [CrI], 21.0%-35.6%; ranked 1 of 5; moderate certainty) but the highest prevalence of taste disturbance (absolute risk difference per 100 patients: median, 38; 95% CrI, 27-51; ranked 5 of 5; high certainty) and the highest prevalence of discontinuation. Camlipixant had a well-balanced profile (reduction rate in 24-hour cough frequency: median, 14.7%; 95% CrI, 5.4%-26.0%; ranked 3 of 5; low certainty; and taste disturbance; absolute risk difference per 100 patients; median, 2; 95% CrI, 1-6; ranked 2 of 5; low certainty). Placebo had a mean of 33.1% reduction in 24-hour cough frequency. INTERPRETATION: When used at safe doses, gefapixant had a favorable risk-benefit profile compared with the other four agents. Camlipixant showed initial promise, which may be further investigated by phase III trials currently underway. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Center (UMIN-CTR); No. UMIN000050622; URL: https://center6.umin.ac.jp.

DOI： 10.1016/j.chest.2024.05.015

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記述言語：英語  

DOI： 10.1002/ehf2.14919

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence-based approaches are urgently needed to optimize treatment. METHODS: A systematic review and network meta-analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model. RESULTS: Seven placebo-controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83-8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73-6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84-2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42-2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07-0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30-2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42-1.88). However, network meta-analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety. CONCLUSION: Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.

DOI： 10.1002/cam4.70166

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The usefulness of monitoring treatment effect of tafamidis using magnetic resonance imaging (MRI) extracellular volume fraction (ECV) has been reported. OBJECTIVE: we conducted a meta-analysis to evaluate the usefulness of this method. METHODS: Data from 246 ATTR-CMs from six studies were extracted and included in the analysis. An inverse variance meta-analysis using a random effects model was performed to evaluate the change in MRI-ECV before and after tafamidis treatment. The analysis was also performed by classifying the patients into ATTR-CM types (wild-type or hereditary). RESULTS: ECV change before and after tafamidis treatment was 0.33% (95% CI: -1.83-2.49, I2 = 0%, p = 0.76 for heterogeneity) in the treatment group and 4.23% (95% CI: 0.44-8.02, I2 = 0%, p = 0.18 for heterogeneity) in the non-treatment group. The change in ECV before and after treatment was not significant in the treated group (p = 0.76), but there was a significant increase in the non-treated group (p = 0.03). There was no difference in the change in ECV between wild-type (95% CI: -2.65-3.40) and hereditary-type (95% CI: -9.28-4.28) (p = 0.45). CONCLUSIONS: The results of this meta-analysis suggest that MRI-ECV measurement is a useful imaging method for noninvasively evaluating the efficacy of tafamidis treatment for ATTR-CM.

DOI： 10.3390/tomography10080097

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. METHODS: Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median age of onset 69.3 years (interquartile range 62.1-77.6)]. Peptide nucleic acid-clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR or targeted amplicon deep sequencing was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and -negative patients and assessed the diagnostic value of our system using receiver operating characteristics (ROC) curve analysis. RESULTS: Forty patients (44.9%) with reported pathogenic UBA1 variants were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering age >50 years, cutaneous lesions, lung involvement, chondritis and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). CONCLUSION: Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants.

DOI： 10.1093/rheumatology/kead425

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記述言語：英語  

DOI： 10.1093/rheumatology/kead626

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記述言語：英語  

DOI： 10.1093/rheumatology/kead608

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The prognostic implications of late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) in the context of cardiac sarcoidosis (CS) have attracted considerable attention. Nevertheless, a subset of studies has undistinguished confirmed and suspected CS cases, thereby engendering interpretative ambiguities. In this meta-analysis, we evaluated the differences in cardiac MRI findings and their prognostic utility between confirmed and suspected CS. A literature search was conducted using PubMed, Web of Science, and Cochrane libraries to compare the findings of cardiac MRI and its prognostic value in CS and suspected CS. A meta-analysis was performed to compare the prevalence of LGE MRI, odds ratios, and hazard ratios for predicting cardiac events in both groups. A total of 21 studies encompassing 24 different populations were included in the meta-analysis (CS: 393 cases, suspected CS: 2151 cases). CS had a higher frequency of LGE of the left ventricle (87.2% vs. 36.4%, p < 0.0001) and right ventricle (62.1% vs. 23.8%, p = 0.04) than suspected CS. In patients with suspected CS, the presence of left ventricular LGE was associated with higher all-cause mortality [odds ratio: 5.70 (95%CI: 2.51-12.93), p < 0.0001, I2 = 8%, p for heterogeneity = 0.37] and ventricular arrhythmia [odds ratio: 15.51 (95%CI: 5.65-42.55), p < 0.0001, I2 = 0, p for heterogeneity = 0.94]. In contrast, in CS, not the presence but extent of left ventricular LGE was a significant predictor of outcome (hazard ratio = 1.83 per 10% increase of %LGE (95%CI: 1.43-2.34, p < 0.001, I2 = 15, p for heterogeneity = 0.31). The presence of left ventricular LGE was a strong prognostic factor in suspected sarcoidosis. However, the extremely high prevalence of left ventricular LGE in confirmed CS suggests that the quantitative assessment of LGE is useful for prognostic estimation.

DOI： 10.1007/s10554-024-03191-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Benralizumab, a monoclonal antibody targeting IL-5 receptors, reduces exacerbations and oral corticosteroid requirements for severe, uncontrolled eosinophilic asthma. In Japan, geographic disparities in asthma outcomes suggest differential prescribing and access. This study aimed to quantify regional prescribing variations for benralizumab nationwide. Using Japan's National Database (NDB) of insurance claims (2009-2019), benralizumab standardized claim ratios (SCRs) were calculated for 47 prefectures. Correlations between SCRs and other biologics' SCRs, economic variables like average income, and physician densities were evaluated through univariate analysis and multivariate regressions. Income-related barriers to optimal prescribing were examined. Wide variation emerged in benralizumab SCRs, from 40.1 to 184.2 across prefectures. SCRs strongly correlated with omalizumab (r = 0.61, p < 0.00001) and mepolizumab (r = 0.43, p = 0.0024). Average monthly income also positively correlated with benralizumab SCRs (r = 0.45, p = 0.0016), whereas lifestyle factors were insignificant. Respiratory specialist density modestly correlated with SCRs (r = 0.29, p = 0.047). In multivariate regressions, average income remained the most robust predictor (B = 0.74, p = 0.022). Benralizumab SCRs strongly associate with income metrics more than healthcare infrastructure/population factors. Many regions show low SCRs, constituting apparent prescribing gaps. Access barriers for advanced asthma therapies remain inequitable among Japan's income strata. Addressing affordability alongside specialist allocation can achieve better prescribing quality and asthma outcomes.

DOI： 10.1038/s41598-024-65407-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The clinical spectrum of COVID-19 includes a wide range of manifestations, from mild symptoms to severe pneumonia. HLA system plays a pivotal role in immune responses to infectious diseases. The purpose of our study was to investigate the association between HLA and COVID-19 severity in a Japanese population. The study included 209 Japanese COVID-19 patients aged ≥20 years. Saliva samples were collected and used to determine the HLA genotype by HLA imputation through genome-wide association analyses. The association between HLA genotype and COVID-19 severity was then evaluated. The allele frequency was compared between patients with respiratory failure (severe group: 91 cases) and those without respiratory failure (non-severe group: 118 cases), categorising the data into three time periods: pre-Omicron epidemic period, Omicron epidemic period, and total period of this study (from January 2021 to May 2023). In comparing the severe and non-severe groups, the frequencies of the HLA-DQA1*01:03 (35.1% vs. 10.5%, odds ratio [OR] = 4.57, corrected p [pc] = 0.041) and -DQB1*06:01 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) alleles were significantly higher in the severe group during the pre-Omicron epidemic period. During the Omicron epidemic period, HLA-DQB1*06 (32.4% vs. 7.9%, OR = 5.54, pc = 0.030) was significantly higher in the severe group. During total period of this study, HLA-DQA1*01:03 (30.2% vs. 14.4%, OR = 2.57, corrected pc = 0.0013) and -DQB1*06:01 (44.5% vs. 26.7%, OR = 2.20, pc = 0.013) alleles were significantly higher in the severe group. HLA-DQB1*06:01 and -DQA1*01:03 were in strong linkage disequilibrium with each other (r2 = 0.91) during total period of this study, indicating that these two alleles form a haplotype. The frequency of the HLA-DQA1*01:03-DQB1*06:01 in the severe group was significantly higher than in the non-severe group during pre-Omicron epidemic period (32.4% vs. 7.9%, OR = 5.59, pc = 0.00072), and total period of this study (28.6% vs. 13.1%, OR = 2.63, pc = 0.0013). During Omicron epidemic period, the haplotype did not demonstrate statistical significance, although the odds ratio indicated a value greater 1. Frequencies of the HLA-DQA1*01:03 and -DQB1*06:01 alleles were significantly higher in severe COVID-19 patients, suggesting that these alleles are risk factors for severe COVID-19 pneumonia in the Japanese population.

DOI： 10.1111/tan.15609

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: For simultaneous prediction of phenotypic drug susceptibility test (pDST) for multiple antituberculosis drugs, the whole genome sequencing (WGS) data can be analyzed using either a catalog-based approach, wherein 1 causative mutation suggests resistance, (eg, World Health Organization catalog) or noncatalog-based approach using complicated algorithm (eg, TB-profiler, machine learning). The aim was to estimate the predictive ability of WGS-based tests with pDST as the reference, and to compare the 2 approaches. METHODS: Following a systematic literature search, the diagnostic test accuracies for 14 drugs were pooled using a random-effect bivariate model. RESULTS: Of 779 articles, 44 with 16 821 specimens for meta-analysis and 13 not for meta-analysis were included. The areas under summary receiver operating characteristic curve suggested test accuracy was excellent (0.97-1.00) for 2 drugs (isoniazid 0.975, rifampicin 0.975), very good (0.93-0.97) for 8 drugs (pyrazinamide 0.946, streptomycin 0.952, amikacin 0.968, kanamycin 0.963, capreomycin 0.965, para-aminosalicylic acid 0.959, levofloxacin 0.960, ofloxacin 0.958), and good (0.75-0.93) for 4 drugs (ethambutol 0.926, moxifloxacin 0.896, ethionamide 0.878, prothionamide 0.908). The noncatalog-based and catalog-based approaches had similar ability for all drugs. CONCLUSIONS: WGS accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results reliably predict pDST positive. The 2 approaches had similar ability. CLINICAL TRIALS REGISTRATION: UMIN-ID UMIN000049276.

DOI： 10.1093/infdis/jiad480

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: For advanced non-small cell lung cancer (NSCLC), combination therapies including a PD-1 inhibitor plus chemotherapy or a PD-1 inhibitor, CTLA-4 inhibitor, and chemotherapy are standard first-line options. However, data directly comparing these regimens are lacking. This study compared the efficacy of pembrolizumab plus chemotherapy (CP) against nivolumab plus ipilimumab and chemotherapy (CNI) in a real-world setting. METHODS: In this multicenter retrospective study, we compared the efficacy and safety of CP and CNI as first-line therapies in 182 patients with stage IIIB-IV NSCLC. Primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the response rate (RR) and safety profiles. Kaplan-Meier survival curves and Cox proportional hazards models were utilized for data analysis, adjusting for confounding factors such as age, gender, and PD-L1 expression. RESULTS: In this study, 160 patients received CP, while 22 received CNI. The CP group was associated with significantly better PFS than the CNI group (median 11.7 vs. 6.6 months, HR 0.56, p = 0.03). This PFS advantage persisted after propensity score matching to adjust for imbalances. No significant OS differences were observed. Grade 3-4 adverse events occurred comparably, but immune-related adverse events were numerically more frequent in the CNI group. CONCLUSIONS: In real-world practice, CP demonstrated superior PFS compared with CNI. These findings can inform treatment selection in advanced NSCLC.

DOI： 10.1111/1759-7714.15304

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Computed tomography (CT)-derived extracellular volume fraction (ECV) is a noninvasive method to quantify myocardial fibrosis. Although studies suggest CT is a suitable measure of ECV, clinical use remains limited. OBJECTIVES: A meta-analysis was performed to determine the clinical value of CT-derived ECV in cardiovascular diseases. METHODS: Electronic database searches of PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE were performed. The most pivotal analysis entailed the comparison of ECV ascertained through CT-ECV among the control, aortic stenosis, and cardiac amyloidosis cohorts. The diagnostic test accuracy for detecting cardiac amyloidosis was assessed using summary receiver-operating characteristics curve. RESULTS: Pooled CT-derived ECV values were 28.5% (95% CI: 27.3%-29.7%) in the control, 31.9% (95% CI: 30.2%-33.8%) in the aortic stenosis, and 48.9% (95% CI: 44.5%-53.3%) in the cardiac amyloidosis group. ECV was significantly elevated in aortic stenosis (P = 0.002) (vs controls) but further elevated in cardiac amyloidosis (P < 0.001) (vs aortic stenosis). CT-derived ECV had a high diagnostic accuracy for cardiac amyloidosis, with sensitivity of 92.8% (95% CI: 86.7%-96.2%), specificity of 84.8% (95% CI: 68.6%-93.4%), and area under the summary receiver-operating characteristic curve of 0.94 (95% CI: 0.88-1.00). CONCLUSIONS: This study is the first comprehensive systematic review and meta-analysis of CT-derived ECV evaluation in cardiac disease. The high diagnostic accuracy of CT-ECV suggests the usefulness of CT-ECV in the diagnosis of cardiac amyloidosis in preoperative CT planning for transcatheter aortic valve replacement.

DOI： 10.1016/j.jcmg.2023.10.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Several studies have evaluated immune checkpoint inhibitors (ICIs) for metastatic uveal melanoma; however, the efficacy of ICIs in the previous studies varied greatly. In this systematic review, we searched for prospective or retrospective studies on single or dual-ICIs for metastatic uveal melanoma treatment. A random-effect model meta-analysis with generic inverse-variance was conducted, and 36 articles representing 41 cohorts of 1414 patients with metastatic uveal melanoma were included. The pooled outcomes were as follows: objective response rate (ORR) was 5.6% (95% confidence interval [95%CI] 3.7-7.5%; I2, 36%), disease control rate (DCR) was 32.5% (95% CI 27.2-37.7%; I2, 73%), median progression-free survival was 2.8 months (95% CI 2.7-2.9 months; I2, 26%), and median overall survival (OS) was 11.2 months (95% CI 9.6-13.2 months; I2, 74%). Compared to single-agent ICI, dual ICI led to better ORR (single-agent: 3.4% [95% CI 1.8-5.1]; dual-agent: 12.4% [95% CI 8.0-16.9]; P < 0.001), DCR (single-agent: 29.3%, [95% CI 23.4-35.2]; dual-agent: 44.3% [95% CI 31.7-56.8]; P = 0.03), and OS (single-agent: 9.8 months [95% CI 8.0-12.2]; dual-agent: 16.3 months [95% CI 13.5-19.7]; P < 0.001). Our analysis provided treatment outcomes as described above. Dual-ICIs appear better than single-agent ICIs for the treatment of metastatic uveal melanoma.

DOI： 10.1038/s41598-024-55675-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The objective of this meta-analysis was to assess the clinical utility of anomalous discoveries on cardiac magnetic resonance, particularly the right ventricular extracellular volume (RV-ECV), among individuals who underwent surgical repair for Tetralogy of Fallot (rTOF). METHODS: We conducted a systematic search of electronic databases including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE. Our analysis involved a comparison of ECV levels between rTOF patients and controls, as well as an evaluation of the predictive value of ECV for future adverse events. RESULTS: We identified 16 eligible studies that encompassed 856 rTOF patients and 283 controls. Our meta-analysis showed a significant increase in LV-ECV among rTOF patients compared to control subjects (MD = 2.63, 95%CI: 1.35 to 3.90, p < 0.0001, I2 = 86%, p for heterogeneity < 0.00001). Moreover, RV-ECV was found to be substantially higher in patients compared to LV-ECV. Our meta-analysis also revealed a significant association between RV-ECV and adverse events (HR = 1.15, 95% CI: 1.04 to 1.27, p = 0.005, I2 = 0%, p for heterogeneity = 0.62), while LV-ECV did not show any significant association with adverse events (HR = 1.12, 95% CI: 0.92 to 1.36, p = 0.16, I2 = 0%, p for heterogeneity = 0.46). CONCLUSION: The results of this meta-analysis on RV-ECV confirmed the presence of RV fibrosis as one of the prognostic factors in rTOF patients.

DOI： 10.1007/s00380-023-02332-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. METHODS: Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. RESULTS: We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). CONCLUSIONS: Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

DOI： 10.21037/tlcr-23-855

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記述言語：英語  

DOI： 10.1016/S1470-2045(24)00009-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine the efficacy and safety of macrolide therapy for adult asthma. METHODS: We searched randomized controlled trials from MEDLINE via the PubMed, CENTRAL, and Ichushi Web databases. The primary outcome was asthma exacerbation. The secondary outcomes were serious adverse events (including mortality), asthma-related quality of life (symptom scales, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire), rescue medication (puffs/day), respiratory function (morning peak expiratory flow, evening peak flow, and forced expiratory volume in 1 s), bronchial hyperresponsiveness, and minimum oral corticosteroid dose. Of the 805 studies, we selected seven studies for the meta-analysis, which was conducted using a random-effects model. SYSTEMATIC REVIEW REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000050824). RESULTS: No significant difference between macrolide and placebo for asthma exacerbations was observed (risk ratio 0.71, 95 % confidence interval [CI] 0.46-1.09; p = 0.12). Macrolide therapy for adult asthma showed a significant improvement in rescue medication with short-acting beta-agonists (mean difference -0.41, 95 % CI -0.78 to -0.04; p = 0.03). Macrolide therapy did not show more serious adverse events (odd ratio 0.61, 95 % CI 0.34-1.10; p = 0.10) than those with placebo. The other secondary outcomes were not significantly different between the macrolide and placebo groups. CONCLUSIONS: Macrolide therapy for adult asthma may be more effective than placebo and could be a treatment option.

DOI： 10.1016/j.resinv.2023.12.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The relationship between FMF and pregnancy outcomes remains unclear. This systematic review and meta-analysis aimed to clarify this association. METHODS: Electronic databases-PubMed, Web of Science, Cochrane, and EMBASE-were searched on 20 December 2022, using specific search terms. Case-control, cohort, and randomized clinical trial studies comparing patients with FMF and healthy controls were considered eligible. We excluded systematic reviews, meta-analyses, case series with fewer than five cases, republished articles without new findings on pregnancy outcomes, studies targeting paternal FMF, and those not published in English. The results were summarized in the form of odds ratios (ORs) and 95% CIs, using a random-effects model. This study was registered in the University hospital Medical Information Network Clinical Trials Registry (Japan) as UMIN000049827. RESULTS: The initial electronic search identified 611 records, of which 9 were included in this meta-analysis (177 735 pregnancies, 1242 with FMF, and 176 493 healthy controls). FMF was significantly associated with increased odds of preterm deliveries (OR, 1.67; 95% CI, 1.05-2.67; I2 = 22%) and insignificantly associated with increased odds of fetal growth restriction (OR, 1.45; 95% CI, 0.90-2.34; I2 = 0%) and hypertensive disorders during pregnancy (OR, 1.28; 95% CI, 0.87-1.87; I2 = 0%). CONCLUSION: FMF was significantly associated with preterm delivery and insignificantly associated with fetal growth restriction and hypertensive disorders. All of the included studies were observational studies. Treatment characteristics were not fully collected from the articles, and further analysis of treatments for FMF in pregnancy is still warranted.

DOI： 10.1093/rheumatology/kead417

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記述言語：英語  

DOI： 10.1016/j.jtho.2023.11.004

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記述言語：英語  

DOI： 10.1056/NEJMc2313778

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The ILD-GAP scoring system is known to be useful in predicting prognosis in patients with interstitial lung disease (ILD). An elevated monocyte count was associated with increased risks of IPF poor prognosis. We examined whether the ILD-GAP scoring system combined with the monocyte ratio (ILD-GAPM) is superior to the conventional ILD-GAP model in predicting ILD prognosis. METHODS: In patients with ILD treated between April 2013 and April 2017, we were retrospectively assessed the relationships between baseline clinical parameters, including age, sex, Charlson Comorbidity Index score (CCIS), ILD diagnosis, blood biomarkers, pulmonary function test results, and disease outcomes. In ILD patients were included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD). We also assessed the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPM models. RESULTS: A total of 179 patients (mean age, 73 years) were assessed. All of them were taken pulmonary function test, including percentage predicted diffusion capacity for carbon monoxide. ILD patients included 56 IPF cases, 112 iNSIP and CVD-IP cases, 6 CHP cases and 5 UC-ILD cases. ILD-GAPM provided a greater area under the receiver-operating characteristic curve (0.747) than ILD-GAP (0.710) for predicting 3-year ILD-related events. Furthermore, the log-rank test showed that the Kaplan-Meier curves in ILD-GAPM were significantly different by stage (P = 0.015), but not by stage in ILD-GAP (P = 0.074). CONCLUSIONS: The ILD-GAPM model may be a more accurate predictor of prognosis for ILD patients than the ILD-GAP model.

DOI： 10.1186/s12890-023-02833-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Tuberculosis (TB) remains a leading cause of death globally. Identifying the factors associated with mortality during hospitalization for TB is crucial for improving patient outcomes. This study aimed to investigate the potential risk factors, including T-SPOT.TB test results and routine laboratory markers of inflammation, associated with death during hospitalization due to TB. METHODS: A retrospective analysis was conducted on 244 hospitalized TB patients. Demographic data, clinical characteristics, T-SPOT.TB results, and laboratory parameters were collected. Univariate and multivariate analyses were performed to identify independent risk factors for in-hospital mortality. RESULTS: Among the patients, 206 survived and 38 died during hospitalization. Multivariate analysis revealed that age (HR: 1.08, 95% CI: 1.02-1.15, p = 0.001), a negative T-SPOT.TB test result (HR: 4.01, 95% CI: 1.78-9.01, p < 0.001), elevated C-reactive protein (CRP) levels (HR: 1.04, 95% CI: 1.01-1.08, p = 0.007), and increased neutrophil-to-lymphocyte ratio (NLR) (HR: 1.04, 95% CI: 1.00-1.07, p = 0.025) were independent risk factors for mortality. CONCLUSIONS: This study identified age, a negative T-SPOT.TB result, elevated CRP levels, and a high NLR as significant independent risk factors for death in hospitalized TB patients. These findings underscore the importance of these parameters in the risk stratification and management of hospitalized TB patients. Further research is warranted to elucidate the mechanisms behind these associations and to validate these results in different populations.

DOI： 10.1016/j.jiac.2023.09.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Incorporating immune checkpoint blockade into perioperative cancer therapy has improved clinical outcomes. However, the safety of immune checkpoint blockade needs better evaluation, given the chances of more prolonged disease-free survival. We aimed to assess how adding immune checkpoint blockade to perioperative therapy affects treatment-related adverse events. METHODS: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library from database inception until Aug 8, 2023, for randomised controlled trials that assessed the addition of immune checkpoint blockade to neoadjuvant or adjuvant therapy for cancer, reported treatment-related deaths, and had a design in which the experimental group assessed immune checkpoint blockade in combination with the therapy used in the control group. Meta-analysis was done to pool odds ratios (ORs) of treatment-related deaths, any grade and grade 3-4 treatment-related adverse events, serious adverse events, and adverse events leading to treatment discontinuation. The protocol is registered with PROSPERO, CRD42022343741. FINDINGS: 28 randomised controlled trials with 16 976 patients were included. The addition of immune checkpoint blockade was not significantly associated with increased treatment-related deaths (OR 1·76, 95% CI 0·95-3·25; p=0·073), consistent across immune checkpoint blockade subtype (I2=0%). 40 fatal toxicities were identified across 9864 patients treated with immune checkpoint blockade, with pneumonitis being the most common (six [15·0%]); 13 fatal toxicities occurred among 7112 patients who were not treated with immune checkpoint blockade. The addition of immune checkpoint blockade increased the incidence of grade 3-4 treatment-related adverse events (OR 2·73, 95% CI 1·98-3·76; p<0·0001), adverse events leading to treatment discontinuation (3·67, 2·45-5·51; p<0·0001), and treatment-related adverse events of any grade (2·60 [1·88-3·61], p<0·0001). The immune checkpoint blockade versus placebo design primarily used as adjuvant therapy was associated with increased incidence of treatment-related deaths (4·02, 1·04-15·63; p=0·044) and grade 3-4 adverse events (5·31, 3·08-9·15; p<0·0001), whereas the addition of immune checkpoint blockade in the neoadjuvant setting was not associated with increased incidence of treatment-related death (1·11, 95% CI 0·38-3·29; p=0·84) or grade 3-4 adverse events (1·17, 0·90-1·51; p=0·23). INTERPRETATION: The addition of immune checkpoint blockade to perioperative therapy was associated with an increase in grade 3-4 treatment-related adverse events and adverse events leading to treatment discontinuation. These findings provide safety insights for further clinical trials assessing neoadjuvant or adjuvant immune checkpoint blockade therapy. Clinicians should closely monitor patients for treatment-related adverse events to prevent treatment discontinuations and morbidity from these therapies in earlier-stage settings. FUNDING: None.

DOI： 10.1016/S1470-2045(23)00524-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes in cancer treatment but are also associated with adverse events and financial burdens. Identifying accurate biomarkers is crucial for determining which patients are likely to benefit from ICIs. Current markers, such as PD-L1 expression and tumor mutation burden, exhibit limited predictive accuracy. This study utilizes a Clinical Data Warehouse (CDW) to explore the prognostic significance of novel blood-based factors, such as the neutrophil-to-lymphocyte ratio and red cell distribution width (RDW), to enhance the prediction of ICI therapy benefit. METHODS: This retrospective study utilized an exploratory cohort from the CDW that included a variety of cancers to explore factors associated with pembrolizumab treatment duration, validated in a non-small cell lung cancer (NSCLC) patient cohort from electronic medical records (EMR) and CDW. The CDW contained anonymized data on demographics, diagnoses, medications, and tests for cancer patients treated with ICIs between 2017-2022. Logistic regression identified factors predicting ≤2 or ≥5 pembrolizumab doses as proxies for progression-free survival (PFS), and Receiver Operating Characteristic analysis was used to examine their predictive ability. These factors were validated by correlating doses with PFS in the EMR cohort and re-testing their significance in the CDW cohort with other ICIs. This dual approach utilized the CDW for discovery and EMR/CDW cohorts for validating prognostic biomarkers before ICI treatment. RESULTS: A total of 609 cases (428 in the exploratory cohort and 181 in the validation cohort) from CDW and 44 cases from EMR were selected for study. CDW analysis revealed that elevated red cell distribution width (RDW) correlated with receiving ≤2 pembrolizumab doses (p = 0.0008), with an AUC of 0.60 for predicting treatment duration. RDW's correlation with PFS (r = 0.80, p<0.0001) and its weak association with RDW (r = -0.30, p = 0.049) were confirmed in the EMR cohort. RDW also remained significant in predicting short treatment duration across various ICIs (p = 0.0081). This dual methodology verified pretreatment RDW elevation as a prognostic biomarker for shortened ICI therapy. CONCLUSION: This study suggests the utility of CDWs in identifying prognostic biomarkers for ICI therapy in cancer treatment. Elevated RDW before treatment initiation emerged as a potential biomarker of shorter therapy duration.

DOI： 10.1371/journal.pone.0299760

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Biologics are the important drugs for severe asthma, but clinical trials included few elderly patients. Data on the safety and efficacy of benralizumab in elderly asthma patients are limited. METHODS: This clinical study was a multicentre, retrospective, observational study at two hospitals. Patients aged ≥18 years diagnosed with severe asthma treated with benralizumab were included. Elderly patients were defined as those aged 70 years or older. Efficacy and safety were then analyzed in elderly and non-elderly patients. The primary endpoints were the annual number of asthma exacerbations for efficacy and the discontinuation rate due to adverse events for safety. RESULTS: Between August 2016 and October 2022, 61 patients were enrolled; 10 patients were excluded, and 51 (22 elderly, 29 non-elderly) patients were analyzed. In elderly patients, the annual number of asthma exacerbations before treatment with benralizumab (pre-benralizumab) was 3.78, and the number during treatment with benralizumab was 1.26, a decrease of 2.52 (95% confidence interval [CI], 1.3 to 3.74, p < 0.001). In non-elderly patients, the annual number of asthma exacerbation in the pre-benralizumab period was 3.24, and during treatment with benralizumab it was 0.68, a decrease of 2.56 (95% CI, 1.3 to 3.82, p < 0.001). There was no significant difference in discontinuation due to treatment-related adverse events (elderly vs non-elderly, 2 (9%) vs 0 (0%), p = 0.18). CONCLUSION: Benralizumab reduced the annual number of asthma exacerbations and was well tolerated in elderly patients.

DOI： 10.1080/20018525.2024.2384173

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Riehl's melanosis is a pigmented dermatitis that manifests as brown-gray facial pigmentation with pigment incontinence and infiltration of cells in the upper dermis. The associated inflammation is induced by a variety of products such as drugs and cosmetics. Henna, commonly referred to as a hypoallergenic cosmetic, has been reported to cause Riehl's melanosis in some cases. Although skin depigmenting agents have been occasionally used, satisfactory results have not been obtained and no established therapeutic strategies exist to treat Riehl's melanosis. Meanwhile, picosecond lasers effectively treat other hyperpigmentation disorders. In this study, we report safe and effective treatment of henna induced-atypical Riehl's melanosis using a 755-nm picosecond Alexandrite laser. Immunohistochemical analyses revealed a potential role of CD8-positive lymphocytes in henna-induced inflammation and hyperpigmentation of the basal layer, and a role of melanophages in the pigmented dermis of Riehl's melanosis.

DOI： 10.3389/fmed.2024.1401938

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To unravel the mechanisms underlying cell death in the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome using peripheral blood samples and to assess the clinical value of this knowledge. METHODS: Nine patients undergoing treatment for VEXAS syndrome at Yokohama City University Hospital were included in this study. Monocytes and neutrophils were isolated from peripheral blood and then monocytes were differentiated into polarized macrophages. Viable cell counts, cell death assays and measurements of various indicators such as high mobility group box 1 (HMGB1) concentration, extracellular adenosine triphosphate (ATP) concentration, annexin V level and caspase 1, 3 and 7 activities were performed. RESULTS: Elevated cell death of monocytes and neutrophils was observed in VEXAS syndrome patients, as indicated by cultured cell counts and cell death assays. Annexin V assays and measurements of caspase 1, 3 and 7 activities suggested increased apoptosis and pyroptosis in these cells. Serum HMGB1 levels were significantly elevated in VEXAS syndrome patients and decreased after prednisolone (PSL) dose escalation. Monocytes and neutrophils from the VEXAS group exhibited heightened extracellular ATP secretion, which was significantly reduced by soluble PSL co-culture. CONCLUSION: This study confirms increased cell death of monocytes and neutrophils and damage-associated molecular patterns in VEXAS syndrome, and these findings may be valuable for drug screening, therapeutic strategies and as biomarkers.

DOI： 10.1093/rap/rkae065

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Perioperative use of immune checkpoint blockade (ICB) improves survival in patients with early-stage cancer. Treatment-related adverse events (AEs), frequently involve the endocrine system which may increase perioperative complications and affect quality of life. OBJECTIVE: We conducted a meta-analysis to elucidate the impact of adding ICB to conventional neoadjuvant/adjuvant therapy on the incidence of endocrine AEs. DESIGN: A systematic review and meta-analysis of randomize-controlled trials (RCTs). DATA SOURCES AND METHODS: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed for RCTs comparing groups with and without the addition of ICB to conventional perioperative therapy in patients with cancer. Outcomes included all-grade and grade 3-5 thyroiditis, hyperthyroidism, hypothyroidism, adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, and hyperglycemia. The odds ratios (ORs) of all-grade and grade 3-5 endocrine were pooled using the random-effect model meta-analysis. RESULTS: Twenty-four RCTs comprising 12,199 patients were identified for meta-analysis. The addition of ICB was associated with higher incidence of thyroiditis [all grade: OR = 3.53 (95% confidence interval (CI): 1.88-6.64)], hyperthyroidism [all-grade: 7.18 (4.30-12.01); grade 3-5: 3.93 (1.21-12.82)], hypothyroidism [all-grade: 5.39 (3.68-7.90); grade 3-5: 3.63 (1.18-11.11)], adrenal insufficiency [all-grade: 3.82 (1.88-7.79); grade 3-5: 5.91 (2.36-14.82)], hypophysitis [all-grade: 10.29 (4.97-21.3); grade 3-5: 5.80 (1.99-16.92)], and type 1 diabetes mellitus [all-grade: 2.24 (1.06-4.74); grade 3-5: 3.49 (1.21-10.08)]. The cumulative incidence of each grade 3-5 endocrine AE was low (<1.3%). No grade 5 AEs leading to death were observed. CONCLUSION: The addition of neoadjuvant/adjuvant ICB to conventional therapy was associated with an increased incidence of several endocrine AEs. Clinicians should be aware of the risk of endocrinopathy from the perioperative ICB use to facilitate risk-benefit discussion with patients with early-stage cancer. TRIAL REGISTRATION: The protocol of this research was registered in PROSPERO (CRD42022332624).

DOI： 10.1177/17588359241257874

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The impact of the COVID-19 pandemic was very broad and substantial, affecting a variety of fields worldwide. In Japan, the infection began spreading in March 2020. At that time, the government alerted people to cancel overseas travel, and encouraged wearing of masks, handwashing, sanitizing and keeping social distance. We sought to determine how COVID-19 infections affected other infectious diseases by investigating the trends in seven gastrointestinal infections that are listed among the 77 important infectious diseases designated by the National Institute of Infectious Diseases. We compared seven gastrointestinal infectious diseases, namely cholera, bacterial dysentery, enterohemorrhagic Escherichia coli, typhoid fever, paratyphoid fever, amoebic dysentery, and giardiasis, in terms of numbers of new cases before the COVID-19 pandemic (2012-2019) and during the pandemic (2020-2022). During the COVID-19 pandemic period (2020-2022), the incidence of the seven infections decreased significantly (p < 0.05) compared with before the pandemic (2012-2019). The sharp and significant decline in incidence of these seven infections in Japan during the COVID-19 pandemic period (2020-2022) appears to be due to restrictions on overseas travel and strict anti-infection measures, such as self-quarantine and encouragement of handwashing and sanitizing. The number of new cases of gastrointestinal infections in Japan is expected to increase in 2024 as these measures lapse. It is important for physicians to continue to monitor trends in gastrointestinal infections and educate people about proper infection prevention.

DOI： 10.3390/diseases12010004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Serum heme oxygenase (HO)-1 level has been reported as a clinically reliable diagnostic biomarker for acute exacerbation of interstitial lung disease (ILD); however, its utility for predicting mortality among these patients is unclear. Serum HO-1 levels of patients newly diagnosed with acute exacerbation of ILD were measured at the time of initiating steroid pulse therapy. The relationship between serum HO-1 and various other serum biomarkers, change in HRCT findings, and disease prognosis at 12 weeks after diagnosis of acute exacerbation was evaluated in 51 patients, of whom 17 (33%) had idiopathic pulmonary fibrosis (IPF). Serum HO-1 was higher in patients with acute exacerbation of IPF than in patients with acute exacerbation of other ILDs. Serum HO-1 levels were higher in patients who died within these 12 weeks than in survivors. Among age, sex, comorbidities, IPF diagnosis, HRCT findings, and blood biomarkers, serum HO-1 was a primary predictor of 12-week mortality. In 41 patients who underwent repeat HRCT, serum HO-1 was higher in patients with honeycomb progression than in those without. Serum HO-1 measurement could be useful for evaluating disease mortality and morbidity of patients with acute exacerbation of ILDs.

DOI： 10.1038/s41598-023-49342-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited. METHODS: We retrospectively assessed the real-world efficacy and safety of atezolizumab in addition to carboplatin and etoposide (EP + A), versus carboplatin and etoposide (EP) alone in previously untreated ED-SCLC patients. RESULTS: From a total of 99 patients, 46 were assigned to the EP + A group, and 53 to the EP group. No significant difference was observed in progression-free survival between the groups. However, the overall survival (OS) was significantly longer in the EP + A group (20.8 vs 12.1 months; HR: 0.52; p = 0.0127). Patients older than 70 years, male, with performance status 0-1, without liver metastasis, and low levels of C-reactive protein and neutrophil-lymphocyte ratio, experienced longer OS in the EP + A group compared to the EP group. CONCLUSION: The addition of atezolizumab to the platinum doublet regimen significantly extended OS in ED-SCLC patients, particularly among certain subgroups, suggesting its potential value in personalized treatment strategies. Further investigation is warranted to validate these findings.

DOI： 10.1007/s00432-023-05457-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Patients with adult-onset Still's disease (AOSD) are at risk of developing macrophage activation syndrome (MAS), a life-threatening condition. Some cases of MAS have been reported following the use of biological agents, highlighting the need to identify contributing factors. This study aims to examine the characteristics of MAS in patients with AOSD treated with anakinra (ANA) or tocilizumab (TCZ). METHODS: A systematic search was conducted across four online databases to identify studies reporting the incidence rates of MAS in patients with AOSD treated with ANA or TCZ. Meta-analysis was performed using a random-effects model and the generic inverse variance method to estimate the pooled incidence rates. The difference in incidence rates of MAS between TCZ and ANA was assessed. Additionally, we analyzed laboratory data and clinical features of AOSD cases at our institution, stratifying them into two groups: those who developed MAS after TCZ administration and those who did not. RESULTS: Of the 455 screened articles, we included five ANA and six TCZ studies. The pooled incidence rates of MAS were 1.50% (95% confidence interval [CI], 0-3.36) for ANA (345 patients) and 14.01% (95% CI 4.51-23.51) for TCZ (94 patients). MAS incidence was significantly higher in the TCZ group (P = 0.01). Among the 17 patients from our institution, the six patients who developed MAS had significantly higher white blood cell and neutrophil counts, as well as elevated levels of lactate dehydrogenase, C-reactive protein, and ferritin before TCZ induction (P < 0.05). CONCLUSIONS: In patients with AOSD, the manifestation of MAS is influenced by multiple causative factors. Consequently, the administration of TCZ should be approached with caution, particularly in patients exhibiting elevated inflammatory markers. TRIAL REGISTRATION: This study was registered with the Clinical Trial Registry of the University Hospital Medical Information Network (Japan) as UMIN000049243.

DOI： 10.1007/s40744-023-00600-x

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記述言語：英語  

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various cancers, including non-small cell lung cancer, small cell lung cancer, melanoma, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, urothelial cancer, and renal cell carcinoma [...].

DOI： 10.3390/cancers15225487

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記述言語：英語  

We have read the article authored by Rizzo et al [...].

DOI： 10.3390/cancers15225346

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition with fewer treatments available as the severity increases. Previous systematic reviews have demonstrated the benefits of long-term macrolide use. However, the therapeutic differences between different macrolides and the optimal duration of use remain unclear. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of long-term macrolide use in reducing COPD exacerbations, compare the therapeutic differences among macrolides, and determine the appropriate treatment duration. Four databases (PubMed, Cochrane Library, Web of Science, and ICHU-SHI) were searched until 20 March 2023, and a random-effects model was used to calculate the pooled effect. Results: The meta-analysis included nine randomized controlled trials involving 1965 patients. The analysis revealed an odds ratio (OR) of 0.34 (95% confidence interval [CI] 0.19, 0.59, p < 0.001) for the reduction in exacerbation frequency. Notably, only azithromycin or erythromycin showed suppression of COPD exacerbations. The ORs for reducing exacerbation frequency per year and preventing hospitalizations were -0.50 (95% CI: -0.81, -0.19; p = 0.001) and 0.60 (95% CI: 0.3, 0.97; p = 0.04), respectively. Statistical analyses showed no significant differences between three- and six-month macrolide prescriptions. However, studies involving a twelve-month prescription showed an OR of 0.27 (95% CI: 0.11, 0.68; p = 0.005; I2 = 81%). Although a significant improvement in St George's Respiratory Questionnaire (SGRQ) total scores was observed with a mean difference of -4.42 (95% CI: -9.0, 0.16; p = 0.06; I2 = 94%), the minimal clinically important difference was not reached. While no adverse effects were observed between the two groups, several studies have reported an increase in bacterial resistance. Conclusions: Long-term use of azithromycin or erythromycin suppresses COPD exacerbations, and previous studies have supported the advantages of a 12-month macrolide prescription over a placebo.

DOI： 10.3390/diseases11040152

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

IMPORTANCE: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. OBJECTIVE: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. EVIDENCE REVIEW: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. FINDINGS: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. CONCLUSIONS AND RELEVANCE: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

DOI： 10.1001/jamaoncol.2023.2960

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although microvascular dysfunction (MVD) is considered an essential pathophysiology in patients with heart failure with preserved ejection fraction (HFpEF), the frequency and prognostic impact of MVD are not fully understood. This meta-analysis evaluated the frequency of MVD in patients with HFpEF and its utility in risk stratification. MATERIALS AND METHODS: On May 26, 2022, a literature search was performed on PubMed, Web of Science, the Cochrane library, and Embase using the search terms such as "Heart failure with preserved ejection fraction," "HFpEF," "microvascular dysfunction," and "MVD." The prevalence of MVD in patients with HFpEF was calculated using the general inverse variance method. A comprehensive literature review was conducted to examine the association between MVD and prognosis in patients with HFpEF. RESULTS: Data pertaining to a total of 941 patients diagnosed with HFpEF were extracted from the collective pool of 9 studies. The results of the meta-analysis revealed that the frequency of MVD among patients with HFpEF was found to be 55.5% (95% CI: 34.8%-76.2%), with a substantial degree of heterogeneity (I2  = 98%, p for heterogeneity <.001). Among the five studies that provided data on the association between MVD and prognosis, a significant statistical association was observed in four of them. CONCLUSIONS: This meta-analysis revealed that approximately 50% of patients diagnosed with HFpEF exhibited MVD. Moreover, the presence of MVD demonstrated significant prognostic implications in multiple studies conducted on patients with HFpEF. These findings strongly suggest that MVD plays a crucial role in the underlying pathophysiology of patients with HFpEF.

DOI： 10.1111/micc.12822

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Epidemiological information is essential in providing appropriate empiric antimicrobial therapy for pneumonia. This study aimed to clarify the epidemiology of community-acquired pneumonia (CAP) by conducting a systematic review of published studies in Japan. DESIGN: Systematic review. DATA SOURCE: PubMed and Ichushi web database (January 1970 to October 2022). ELIGIBILITY CRITERIA: Clinical studies describing pathogenic micro-organisms in CAP written in English or Japanese, excluding studies on pneumonia other than adult CAP, investigations limited to specific pathogens and case reports. DATA EXTRACTION AND SYNTHESIS: Patient setting (inpatient vs outpatient), number of patients, concordance with the CAP guidelines, diagnostic criteria and methods for diagnosing pneumonia pathogens as well as the numbers of each isolate. A meta-analysis of various situations was performed to measure the frequency of each aetiological agent. RESULTS: Fifty-six studies were included and 17 095 cases of CAP were identified. Pathogens were undetectable in 44.1% (95% CI 39.7% to 48.5%). Streptococcus pneumoniae was the most common cause of CAP requiring hospitalisation or outpatient care (20.0% (95% CI 17.2% to 22.8%)), followed by Haemophilus influenzae (10.8% (95% CI 7.3% to 14.3%)) and Mycoplasma pneumoniae (7.5% (95% CI 4.6% to 10.4%)). However, when limited to CAP requiring hospitalisation, Staphylococcus aureus was the third most common at 4.9% (95% CI 3.9% to 5.8%). Pseudomonas aeruginosa was more frequent in hospitalised cases, while atypical pathogens were less common. Methicillin-resistant S. aureus accounted for 40.7% (95% CI 29.0% to 52.4%) of S. aureus cases. In studies that used PCR testing for pan-respiratory viral pathogens, human enterovirus/human rhinovirus (9.4% (95% CI 0% to 20.5%)) and several other respiratory pathogenic viruses were detected. The epidemiology varied depending on the methodology and situation. CONCLUSION: The epidemiology of CAP varies depending on the situation, such as in the hospital versus outpatient setting. Viruses are more frequently detected by exhaustive genetic searches, resulting in a significant variation in epidemiology.

DOI： 10.1136/bmjresp-2023-001800

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記述言語：英語  

DOI： 10.1097/XCS.0000000000000698

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Acute exacerbation (AE) of interstitial pneumonia (IP) shows poor prognosis, due to the typical histological pattern of diffuse alveolar damage superimposed upon lung fibrosis. The previous reports comparing clinical features between AE of idiopathic interstitial pneumonias (IIPs) and those of IPs with known etiology are limited. We retrospectively compared clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers at diagnosis of AE, treatment, and 3-month mortality between patients with AE of IIPs and collagen vascular disease-associated interstitial pneumonia (CVD-IP). We assessed 85 patients, comprising 66 patients with AE of IIPs (78%) and 19 patients with AE of CVD-IP (22%). The least absolute shrinkage and selection operator regression selected CCIS (hazard ratio, 1.281; 95% confidence interval, 1.055-1.556; P = 0.012) and log serum lactate dehydrogenase (LDH) (hazard ratio, 6.267; 95% confidence interval, 2.172-18.085; P < 0.001) as significant predictors of 3-month mortality among these patients. Also, the adjusted survival curves using sex, CCIS, and serum LDH showed no significant differences between these two groups. In conclusion, among AE patients, CCIS and serum LDH level may be more important prognostic factors for 3-month mortality rather than two classification of IP subtypes: IIPs and CVD-IP.

DOI： 10.18999/nagjms.85.3.602

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記述言語：英語  

DOI： 10.1016/S2215-0366(23)00159-1

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記述言語：英語  

DOI： 10.1111/1346-8138.16750

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The purpose of this meta-analysis was to comprehensively investigate the diagnostic ability of 1.5 T and 3.0 T whole heart coronary angiography (WHCA) to detect significant coronary artery disease (CAD) on X-ray coronary angiography. METHODS: A literature search of electronic databases, including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE, was performed to retrieve and integrate articles showing significant CAD detectability of 1.5 and 3.0 T WHCA. RESULTS: Data from 1899 patients from 34 studies were included in the meta-analysis. 1.5 T WHCA had a summary area under ROC of 0.88 in the patient-based analysis, 0.90 in the vessel-based analysis, and 0.92 in the segment-based analysis. These values for 3.0 T WHCA were 0.94, 0.95, 0.96, respectively. Contrast-enhanced 3.0 T WHCA had significantly higher specificity than non-contrast-enhanced 1.5 T WHCA on a patient-based analysis (0.87, 95% CI 0.80-0.92 vs. 0.74, 95% CI 0.64-0.82, P = 0.02). There were no differences in diagnostic performance on a patient-based analysis by use of vasodilators, beta-blockers or between Asian and Western countries. CONCLUSIONS: The diagnostic performance of WHCA was deemed satisfactory, with contrast-enhanced 3.0 T WHCA exhibiting higher specificity compared to non-contrast-enhanced 1.5 T WHCA in a patient-based analysis. There were no significant differences in diagnostic performance on a patient-based analysis in terms of vasodilator or beta-blocker use, nor between Asian and Western countries. However, further large-scale multicentre studies are crucial for the widespread global adoption of WHCA.

DOI： 10.1186/s12968-023-00949-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high. METHODS: We evaluated four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM. Genomic sequencing independently identified three heterozygous variants in a specific region of the gene that encodes signal transducer and activator of transcription 4 (STAT4). Primary skin fibroblast and cell-line assays were used to define the functional nature of the genetic defect. We also assayed gene expression using single-cell RNA sequencing of peripheral-blood mononuclear cells to identify inflammatory pathways that may be affected in DPM and that may respond to therapy. RESULTS: Genome sequencing revealed three novel heterozygous missense gain-of-function variants in STAT4. In vitro, primary skin fibroblasts showed enhanced interleukin-6 secretion, with impaired wound healing, contraction of the collagen matrix, and matrix secretion. Inhibition of Janus kinase (JAK)-STAT signaling with ruxolitinib led to improvement in the hyperinflammatory fibroblast phenotype in vitro and resolution of inflammatory markers and clinical symptoms in treated patients, without adverse effects. Single-cell RNA sequencing revealed expression patterns consistent with an immunodysregulatory phenotype that were appropriately modified through JAK inhibition. CONCLUSIONS: Gain-of-function variants in STAT4 caused DPM in the families that we studied. The JAK inhibitor ruxolitinib attenuated the dermatologic and inflammatory phenotype in vitro and in the affected family members. (Funded by the American Academy of Allergy, Asthma, and Immunology Foundation and others.).

DOI： 10.1056/NEJMoa2202318

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICSs) are inhaled medications used to manage chronic obstructive pulmonary disease (COPD). When two classes of medications are required, a LAMA plus an ICS (LABA+ICS) were previously recommended within a single inhaler as the first-line treatment for managing stable COPD in people in high-risk categories. However, updated international guidance recommends a LAMA plus a LABA (LAMA+LABA). This systematic review is an update of a Cochrane Review first published in 2017. OBJECTIVES: To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD. SEARCH METHODS: We performed an electronic search of the Cochrane Airways Group Specialised Register, ClinicalTrials.gov, and the World Health Organization Clinical Trials Search Portal, followed by handsearches. Two review authors screened the selected articles. The most recent search was run on 10 September 2022. SELECTION CRITERIA: We included parallel or cross-over randomised controlled trials of at least one month's duration, comparing LAMA+LABA and LABA+ICS for stable COPD. We included studies conducted in an outpatient setting and irrespective of blinding. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs), with 95% confidence intervals (CIs) using Review Manager 5. Primary outcomes were: participants with one or more exacerbations of COPD; serious adverse events; quality of life, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score change from baseline; and trough forced expiratory volume in one second (FEV1). We used the GRADE framework to rate our certainty of the evidence in each meta-analysis as high, moderate, low or very low.  MAIN RESULTS: This review updates the first version of the review, published in 2017, and increases the number of included studies from 11 to 19 (22,354 participants). The median number of participants per study was 700. In each study, between 54% and 91% (median 70%) of participants were males. Study participants had an average age of 64 years and percentage predicted FEV1 of 51.5% (medians of study means). Included studies had a generally low risk of selection, performance, detection, attrition, and reporting biases. All but two studies were sponsored by pharmaceutical companies, which had varying levels of involvement in study design, conduct, and data analysis. Primary outcomes The odds of having an exacerbation were similar for LAMA+LABA compared with LABA+ICS (OR 0.91, 95% CI 0.78 to 1.06; I2 = 61%; 13 studies, 20,960 participants; moderate-certainty evidence). The odds of having a serious adverse event were also similar (OR 1.02, 95% CI 0.91 to 1.15; I2 = 20%; 18 studies, 23,183 participants; high-certainty evidence). Participants receiving LAMA+LABA had a similar improvement in quality of life, as measured by the SGRQ, to those receiving LABA+ICS (MD -0.57, 95% CI -1.36 to 0.21; I2 = 78%; 9 studies, 14,437 participants; moderate-certainty evidence) but showed a greater improvement in trough FEV1 (MD 0.07, 95% CI 0.05 to 0.08; I2 = 73%; 12 studies, 14,681 participants; moderate-certainty evidence).  Secondary outcomes LAMA+LABA decreased the odds of pneumonia compared with LABA+ICS from 5% to 3% (OR 0.61, 95% CI 0.52 to 0.72; I2 = 0%; 14 studies, 21,829 participants; high-certainty evidence) but increased the odds of all-cause death from 1% to 1.4% (OR 1.35, 95% CI 1.05 to 1.75; I2 = 0%; 15 studies, 21,510 participants; moderate-certainty evidence). The odds of achieving a minimal clinically important difference of four or more points on the SGRQ were similar between LAMA+LABA and LABA+ICS (OR 1.06, 95% CI 0.90 to 1.25; I2 = 77%; 4 studies, 13,614 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Combination LAMA+LABA therapy probably holds similar benefits to LABA+ICS for exacerbations and quality of life, as measured by the St George's Respiratory Questionnaire, for people with moderate to severe COPD, but offers a larger improvement in FEV1 and a slightly lower risk of pneumonia. There is little to no difference between LAMA+LABA and LAMA+ICS in the odds of having a serious adverse event. Whilst all-cause death may be lower with LABA+ICS, there was a very small number of events in the analysis, translating to a low absolute risk. Findings are based on moderate- to high-certainty evidence from heterogeneous trials with an observation period of less than one year. This review should be updated again in a few years.

DOI： 10.1002/14651858.CD012066.pub3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Local control (LC) is an important outcome of local cancer therapy, besides overall survival (OS). We conducted a comprehensive literature search to investigate whether a high LC rate contributes to good OS in radiotherapy for early-stage non-small cell lung cancer (ES-NSCLC). MATERIALS AND METHODS: Studies in patients receiving radiotherapy for peripheral ES-NSCLC, mainly staged as T1-2N0M0 were included for a systematic review. Relevant information was collected including, dose fractionation, T stage, median age, 3-year LC, cancer-specific survival (CSS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and OS. Correlations between outcomes and clinical variables were evaluated. RESULTS: After screening, 101 data points from 87 studies including 13,435 patients were selected for the quantitative synthesis. Univariate meta-regression analysis revealed that the coefficients between the 3-year LC and 3-year DFS, DMFS, CSS, and OS were 0.753 (95% confidence interval (CI): 0.307-1.199; p < 0.001), 0.360 (95% CI: 0.128-0.593; p = 0.002), 0.766 (95% CI: 0.489-1.044; p < 0.001), and 0.574 (95% CI: 0.275-0.822; p < 0.001), respectively. Multivariate analysis revealed that the 3-year LC (coefficient, 0.561; 95% CI: 0.254-0.830; p < 0.001) and T1 proportion (coefficient, 0.207; 95% CI: 0.030-0.385; p = 0.012) were significantly associated with the 3-year OS and CSS (coefficient for 3-year LC, 0.720; 95% CI: 0.468-0.972; p < 0.001 and T1 proportion, 0.002; 95% CI: 0.000-0.003; p = 0.012). Toxicities ≥ grade 3 were low (3.4%). CONCLUSIONS: Three-year LC was correlated with three-year OS in patients receiving radiotherapy for ES-NSCLC. A 5% increase in 3-year LC is expected to improve the 3-year CSS and OS rates by 3.8% and 2.8%, respectively.

DOI： 10.1016/j.radonc.2023.109664

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/CM9.0000000000002652

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: With the increased use of immune checkpoint inhibitors (ICIs) in cancer patients, arthralgia has been the most commonly reported musculoskeletal immune-related adverse event (irAE). We aimed to characterize arthralgia and its association with overall survival (OS). MATERIAL AND METHODS: Randomized controlled trials (RCTs) reporting on data for ICI-induced arthralgia from four online databases were comprehensively investigated. Odds ratios (ORs) with 95% CIs were calculated for arthralgia using a random-effects model meta-analysis. Individual patient data were reconstructed from RCTs assessing OS in patients with or without ICI-induced arthralgia. We also retrospectively collected data on the clinical features and outcomes of ICI-induced arthralgia in the Yokohama City University (YCU) registry. RESULTS: We analysed 14 377 patients from 24 RCTs. The OR of ICI-induced arthralgia was 1.37 (95% CI 1.20, 1.56). Of the 369 patients in the YCU registry, 50 (13.6%) developed ICI-induced arthralgia. Among them, 30 had other grade ≥2 irAEs, which was noticeably more frequent than in those without arthralgia (OR 1.92, 95% CI 1.04, 3.52). By irAE types, a significant difference was found for relative adrenal insufficiency (OR 3.88, 95% CI 1.80, 8.39). In the YCU registry, patients with (vs without) ICI-induced arthralgia had better OS (log-rank, P < 0.001). OS results were validated from RCT patients with matched cancer types, drugs, and time to arthralgia onset (hazard ratio 0.34, 95% CI 0.17, 0.65, P < 0.001). CONCLUSIONS: If arthralgia develops after ICIs, another irAE, such as relative adrenal insufficiency, may have developed. The incidence of arthralgia was associated with better OS, and the condition of patients with irAEs must be carefully evaluated to determine optimal management.

DOI： 10.1093/rheumatology/keac519

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記述言語：英語  

DOI： 10.1016/j.jinf.2023.02.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been a breakthrough in cancer therapy. ICI therapy is generally better tolerated than cytotoxic chemotherapy; however, hematological adverse events (AEs) have not been fully analyzed. Hence, we performed a meta-analysis to evaluate the incidence and risk of ICI-related hematological AEs. METHODS: A systematic literature search was performed using PubMed, EMBASE, Cochrane Library, and the Web of Science Core Collection. Phase III randomized controlled trials (RCTs) involving ICI combination regimens were selected. The experimental group received ICIs with systemic treatment, and the control group received only the same systemic treatment. Odds ratios (ORs) for anemia, neutropenia, and thrombocytopenia were calculated using a random-model meta-analysis. RESULTS: We identified 29 RCTs with 20,033 patients. The estimated incidence rates for anemia of all grades and grades III-V were 36.5% (95% confidence interval (CI) 30.23 - 42.75) and 4.1% (95% CI 3.85 - 4.42), respectively. The incidence of neutropenia (all grades 29.7%, grades III-V 5.3%) and thrombocytopenia (all grades 18.0%, grades III-V 1.6%) was also calculated. CONCLUSION: Treatment with ICIs seemed unlikely to increase the incidence of anemia, neutropenia, and thrombocytopenia in all grades. However, programmed cell death-1 receptor ligand inhibitors significantly increased the risk of grades III-V thrombocytopenia (OR 1.53; 95% CI 1.11 - 2.11). Further research is needed to examine the potential risk factors.

DOI： 10.14740/jh1090

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The clinical features of asthma with connective tissue diseases (CTDs) are not well-known. This study therefore aimed to investigate the clinical characteristics of asthma with CTDs. METHODS: We retrospectively examined the records of adults (≥18 years old) with asthma followed up between January 2010 and December 2019. We then compared the clinical features of asthma with and without CTDs. RESULTS: Among 568 subjects with asthma, 42 subjects (7.4%) had CTDs. The most frequent concomitant CTD was rheumatoid arthritis (n = 23, 54.8%), followed by systemic lupus erythematosus (n = 6, 14.3%). The proportion of women (with vs. without CTDs, 85.7% vs. 56.5%, p < 0.001) and Global Initiative for Asthma step were higher (Step 4 or 5, with vs. without CTDs, 81.0% vs. 62.0%, p = 0.01) in asthma with CTDs, whereas frequency of allergic rhinitis was higher in asthma without CTDs (with vs. without CTDs, 7.1% vs. 26.1%, p = 0.005). Eosinophil ratio (with vs. without CTDs, 2.1% vs. 3.5%, p = 0.009) and total immunoglobulin E level (with vs. without CTDs, 43 IU/mL vs. 237 IU/mL, p = 0.002) were lower in asthma with CTDs. In terms of lung function, percentage predicted forced vital capacity (with vs. without CTDs, 86.7% vs. 99.7%, p = 0.008) and percentage predicted forced expiratory volume in 1 s (%FEV1) (with vs. without CTDs, 77.2% vs. 88.4%, p = 0.02) were all lower in asthma with CTDs. With multivariable analysis, CTDs (odds ratio [OR] 2.8, 95%CI 1.3-6.0; p = 0.008), chronic obstructive pulmonary disease (OR 3.8, 95%CI 2.1-6.7; p < 0.001) and asthma onset at <20 years old (OR 1.8, 95%CI 1.1-3.2; p = 0.03) were associated with low FEV1 (defined as %FEV1 < 80%) in asthma. CONCLUSIONS: Asthma with CTDs was related to lower lung function and low-T2 inflammation asthma.

DOI： 10.1111/crj.13595

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are extensively used in the treatment of non-small cell lung cancer (NSCLC); hence, equal access to them is important. Therefore, this study aimed to identify regional differences in the prescription of EGFR-TKIs and the factors contributing to these differences. In this ecological study, we collected data using the National Database Open Data and the National Cancer Registry. The standardized claim ratio (SCR) was used as an indicator of the number of EGFR-TKI prescriptions. Additionally, we examined the association between SCR and various factors to identify the factors associated with this difference. The average SCR for the top three provinces was 153.4, while the average for the bottom three provinces was 61.6. Multivariate analysis used for evaluating the association of SCR with variables revealed that the number of designated cancer hospitals and radiation therapies were independent factors associated with the SCR of EGFR-TKIs. There were significant regional differences in the prescriptions of EGFR-TKIs in Japan based on the number of coordinated designated cancer hospitals and the number of patients receiving radiotherapy alone. These findings emphasize the need to implement policies to increase the number of hospitals to reduce regional differences.

DOI： 10.1038/s41598-023-31856-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: We aimed to evaluate the efficacy and safety of haematopoietic stem cell transplantation (HSCT) in patients with systemic sclerosis. METHODS: A systematic literature review and meta-analysis were carried out. We compared survival outcomes using the Kaplan-Meier method with patient-level data between HSCT and intravenous pulse cyclophosphamide. Additionally, the incidence rate of treatment-related deaths with HSCT was pooled using a random-effect model. RESULTS: Of the 2091 articles screened, 22 were included: 3 randomized controlled trials and 19 observational studies. HSCT studies showed significant improvement in the skin thickness score and lung function. Despite treatment-related deaths being higher in HSCT than in intravenous pulse cyclophosphamide, the Kaplan-Meier analysis showed a high survival rate of 2 years post-transplant (log-rank, P = 0.004). The pooled frequency of transplant-related death from 700 systemic sclerosis patients was 6.30% (95% confidence interval 4.21-8.38). However, the estimated frequency of treatment-related deaths has been reducing over the last decade. CONCLUSIONS: HSCT is an effective treatment for systemic sclerosis, but the optimal indications must be carefully determined by balancing the risks.

DOI： 10.1093/mr/roac026

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: We aimed to evaluate the diagnostic accuracy of the measurement of serum type IV collagen 7S (T4C7S) concentration for the staging of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A systematic search or published works was carried out using the PubMed, Cochrane Library, and Web of Science Core Collection databases for studies of the accuracy of serum T4C7S concentration for the staging of fibrosis using Fibrosis stage (F)0-4 in patients with NAFLD diagnosed by liver biopsy. RESULTS: Nine articles describing 1475 participants with NAFLD were included. For fibrosis ≥F1, with n = 849, summary estimates of sensitivity of 0.79, specificity of 0.69, and area under the curve (AUC) of 0.80 were obtained using a median T7C4S cut-off value of 4.6 ng/ml. For fibrosis ≥F2, with n = 1,090, summary estimates of sensitivity of 0.78, specificity of 0.78, and AUC of 0.84 were obtained using a median cut-off value of 4.9 ng/ml. For fibrosis ≥F3, with n = 1311 participants and a median cut-off value of 5.4 ng/ml, a pooled sensitivity of 0.82, specificity of 0.81, and AUC of 0.83 were obtained. For fibrosis ≥F4, with n = 753 and a median cut-off value of 6.6 ng/ml, a pooled sensitivity of 0.85, specificity of 0.81, and AUC of 0.85 were obtained. CONCLUSIONS: Serum T4C7S concentration was found to be an accurate method of staging liver fibrosis in patients with NAFLD.

DOI： 10.1111/hepr.13857

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Phase-contrast cine cardiovascular magnetic resonance (CMR) of the coronary sinus has emerged as a non-invasive method for measuring coronary sinus blood flow and coronary flow reserve (CFR). However, its clinical utility has not yet been established. Here we performed a meta-analysis to clarify the clinical value of CMR-derived CFR in various cardiovascular diseases. METHODS: An electronic database search was performed of PubMed, Web of Science Core Collection, Cochrane Advanced Search, and EMBASE. We compared the CMR-derived CFR of various cardiovascular diseases (stable coronary artery disease [CAD], hypertrophic cardiomyopathy [HCM], dilated cardiomyopathy [DCM]) and control subjects. We assessed the prognostic value of CMR-derived CFR for predicting major adverse cardiac events (MACE) in patients with stable CAD. RESULTS: A total of 47 eligible studies were identified. The pooled CFR from our meta-analysis was 3.48 (95% confidence interval [CI], 2.98-3.98) in control subjects, 2.50 (95% CI, 2.38-2.61) in stable CAD, 2.01 (95% CI, 1.70-2.32) in cardiomyopathies (HCM and DCM). The meta-analysis showed that CFR was significantly reduced in stable CAD (mean difference [MD] = -1.48; 95% CI, -1.78 to -1.17; p < 0.001; I2 = 0%; p for heterogeneity = 0.33), HCM (MD = -1.20; 95% CI, -1.63 to -0.77; p < 0.001; I2 = 0%; p for heterogeneity = 0.49), and DCM (MD = -1.53; 95% CI, -1.93 to -1.13; p < 0.001; I2 = 0%; p for heterogeneity = 0.45). CMR-derived CFR was an independent predictor of MACE for patients with stable CAD (hazard ratio = 0.52 per unit increase; 95% CI, 0.37-0.73; p < 0.001; I2 = 84%, p for heterogeneity < 0.001). CONCLUSIONS: CMR-derived CFR was significantly decreased in cardiovascular diseases, and a decreased CFR was associated with a higher occurrence of MACE in patients with stable CAD. These results suggest that CMR-derived CFR has potential for the pathological evaluation of stable CAD, cardiomyopathy, and risk stratification in CAD.

DOI： 10.1186/s12968-023-00912-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21037/qims-22-522

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記述言語：英語  

DOI： 10.1002/ehf2.14236

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The glutamatergic system is thought to play an important role in the pathophysiology of bipolar disorder (BD). While there has been an increase in proton magnetic resonance spectroscopy studies examining this neurotransmission system, the results are inconsistent. Possible reasons for the inconsistency, including clinical features such as mood state and childhood versus adulthood age, were not addressed in previous meta-analyses. METHODS: This systematic review and meta-analysis of proton magnetic resonance spectroscopy studies of BD included 40 studies, with 1135 patients with BD and 964 healthy control (HC) subjects. RESULTS: Glutamate plus glutamine and glutamine levels in the anterior cingulate cortex of patients with BD were significantly elevated compared with those of HC subjects (standardized mean difference = 0.42, 0.48, respectively). Subgroup analyses showed that adult BD patients had significantly higher levels of glutamate plus glutamine than adult HC subjects, but this was not the case in pediatric patients. For mood states, anterior cingulate cortex glutamate plus glutamine levels were higher in patients with bipolar depression than those in HC subjects. CONCLUSIONS: Our results imply that glutamatergic dysfunction in the anterior cingulate cortex may be implicated in the pathophysiology of BD, which is most evident in adult BD patients and patients with bipolar depression.

DOI： 10.1016/j.bpsc.2022.09.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Obesity paradoxes have been reported in many diseases to date. As the wording "paradox" indicates, our intuition rejects the hypothesis that obese people have a better life expectancy or fewer cardiovascular events. One of the most plausible explanations for the obesity paradox is collider bias, but controversy about this is ongoing. If the findings of the original research are affected by collider bias, meta-analyses of that research will also be affected by the same bias. It is to be hoped that the use of appropriate analytical techniques will enable the true nature of the obesity bias to become clear.

DOI： 10.1093/nutrit/nuac077

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記述言語：英語  

DOI： 10.1111/resp.14392

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jmv.28231

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5603/CJ.a2023.0004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Among patients with idiopathic pulmonary fibrosis (IPF), few studies have investigated the clinical impact of anti-fibrotic treatment (AFT) with and without comorbidities. The aim of the study was to determine whether Charlson Comorbidity Index score (CCIS) can predict the efficacy of AFT in patients with IPF. METHODS: We retrospectively assessed data extracted from the medical records of IPF patients who received anti-fibrotic agents between 2009 and 2019. The collected data included age, sex, CCIS, pulmonary function test, high-resolution computed tomography (HRCT) pattern, gender/age/physiology (GAP) score, and 3-year IPF-related events defined as the first acute exacerbation or death within 3 years after starting AFT. RESULTS: We assessed 130 patients (median age, 74 years) who received nintedanib (n = 70) or pirfenidone (n = 60). Median duration of AFT was 425 days. Patients were categorized into high (≥ 3 points) and low (≤ 2 points) CCIS groups. There was no significant difference between the groups in terms of age, sex, duration of AFT, GAP score, or incidence of usual interstitial pneumonia pattern on HRCT except percentage predicted diffusion capacity of lung for carbon monoxide. Also, significant difference was not seen between the groups for 3-year IPF-related events (P = 0.75). Especially, in the low CCIS group but not the high CCIS group, the longer duration of AFT had better disease outcome. CONCLUSION: In the present study, we could not show any relation between CCIS and IPF disease outcomes in patients undergoing AFT, though the longer duration of AFT might be beneficial for IPF outcomes among patients with low CCIS.

DOI： 10.1371/journal.pone.0291489

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs). OBJECTIVE: We aimed to assess the frequency of AEs associated with DT. DESIGN: This study type is a systematic review and meta-analysis. DATA SOURCES AND METHODS: Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751). RESULTS: Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9-87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2-34.4); serious AEs, 34.9% (95% CI: 28.1-41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3-17.4); treatment-related deaths, 0.98% (95% CI: 0.5-1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8-36.3); diarrhea, 21.7% (95% CI: 17.8-25.6); pruritus 17.9% (95% CI: 14.4-21.3); decreased appetite, 17.7% (95% CI: 13.7-22.0); nausea, 15.6% (95% CI: 12.1-19.6). There were no significant differences in these pooled frequencies between subgroups. CONCLUSIONS: The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy.

DOI： 10.1177/17588359231198453

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD) is not adequately studied. METHODS: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of a short-acting muscarinic antagonist (SAMA) therapy combined with a long-acting beta-2 agonist (LABA) in patients with stable COPD. Pulmonary function, dyspnea, health-related quality of life, exercise tolerance, physical activity, exacerbations of COPD, and adverse events during regular use were set as outcomes of interest. RESULTS: We included five controlled trials including two sets of publicly available online data without article publications for the meta-analysis. Additional use of SAMA plus LABA showed a significant improvement in the peak response in FEV1 (mean difference (MD) 98.70 mL, p < .00001), transitional dyspnea index score (MD .85, p = .02), and St George's Respiratory Questionnaire score (MD -2.00, p = .008) compared to LABA treatment. There was no significant difference in the risk of exacerbation of COPD (p = .20) and only a slight trend of increased severe adverse events (OR: 2.16, p = .08) and cardiovascular events (OR: 2.38, p = .06). CONCLUSION: Additional treatment with SAMA combined with LABA could be a feasible choice due to its efficacy and safety.

DOI： 10.1177/14799731231166008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The ILD-GAP scoring system has been widely used to predict the prognosis of patients with interstitial lung disease (ILD). The ability of the ILD-GAP scoring system combined with the Charlson Comorbidity Index score (CCIS) (ILD-GAPC) to predict ILD prognosis was investigated. METHODS: In ILD patients, including idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD), treated between April 2013 and April 2017, the relationships between baseline clinical parameters, including age, sex, CCIS, ILD diagnosis, pulmonary function test results, and disease outcomes, were retrospectively assessed, and the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPC models, respectively. RESULTS: A total of 185 patients (mean age, 71.9 years), all of whom underwent pulmonary function testing, including percentage predicted diffusion capacity for carbon monoxide, were assessed. ILD diagnosis consisted of IPF in 57 cases, iNSIP and CVD-IP in 117 cases, CHP in 6 cases, and UC-ILD in 5 cases. The ILD-GAPC provided a greater area under the receiver operating characteristic curve (0.758) for predicting 3-year ILD-related events than the ILD-GAP (0.721). In addition, log-rank tests showed that the Kaplan-Meier curves differed significantly among low, middle, and high ILD-GAPC scores (P < 0.001), unlike ILD-GAP scores (P = 0.083). CONCLUSIONS: The ILD-GAPC model could provide more accurate information for predicting prognosis in patients with ILD than the ILD-GAP model.

DOI： 10.1155/2023/5088207

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: To assess the usefulness of tumor response and progression-free survival (PFS) as surrogates for overall survival (OS) in non-small cell lung cancer (NSCLC) trials with immune checkpoint inhibitors (ICI), which have not been confirmed. Methods: Patient- and trial-level analyses were performed. The Response Evaluation Criteria in Solid Tumors was preferred for image assessment. For trial-level analysis, surrogacy was assessed using the weighted rank correlation coefficient (r) following "reciprocal duplication." This method duplicates all plots as if the experimental and the reference arms were switched. Monte Carlo simulations were performed for evaluating this method. Results: A total of 3312 cases were included in the patient-level analysis. Patients without response (first line (1L): hazard ratio (HR) 1.95, 95% confidence interval (CI) 1.71-2.23; second or later line (2L-): HR 4.22, 95% CI 3.22-5.53), without disease control (1L: HR 4.34, 95% CI 3.82-4.94; 2L-: HR 3.36, 95% CI 2.96-3.81), or with progression during the first year (1L: HR 3.42, 95% CI 2.60-4.50; 2L-: HR 3.33, 95% CI 2.64-4.20), had a higher risk of death. Systematic searches identified 38 RCTs including 17,515 patients for the study-level analysis. Odds ratio in the objective response rate (N = 38 × 2, r = -0.87) and HR in PFS (N = 38 × 2, r = 0.85) showed an excellent association with HR in overall survival, while this effect was not observed in the disease control rate (N = 26 × 2, r = -0.03). Conclusions: Objective response rate and PFS are reasonable surrogates for OS in NSCLC trials with ICI.

DOI： 10.3390/cancers15010185

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hepatotoxicity is a major immune-related adverse event that may become life-threatening. The impact of adding immune checkpoint blockade (ICB) to systemic therapy on the incidence of hepatotoxicity remains unknown. We performed a systematic review and meta-analysis to compare the incidence of hepatotoxicity among patients with cancer who received therapy with and without addition of ICB. PubMed, Embase, Web of Science, and Cochrane Library were searched to select phase 3 randomized controlled trials (RCTs) evaluating the effect of adding ICB to systemic therapy, placebo, or supportive care. The odds ratio (OR) of any grade and grade 3-5 hepatitis, elevations in aspartate aminotransferase (AST), and alanine aminotransferase (ALT) was pooled for meta-analysis. 43 RCTs with 28,905 participants were analyzed. Addition of ICB increased the incidence of hepatitis (any grade: OR, 2.13, 95% confidence interval [CI] 1.52-2.97, grade 3-5: OR, 2.66, 95% CI 1.72-4.11), elevated AST (any grade: OR, 2.16, 95% CI 1.73-2.70, grade 3-5: OR, 2.72, 95% CI 1.86-3.99), and elevated ALT (any grade: OR, 2.01, 95% CI 1.59-2.54, grade 3-5: OR, 2.40, 95% CI 1.62-3.55). Subgroup analysis based on the ICB mechanism revealed no significant heterogeneity among each mechanism for hepatitis (any Grade: I2 = 11.1%, p for heterogeneity = 0.32, grade 3-5: I2 = 0%, p = 0.48). Adding ICB to systemic therapy increases the incidence of hepatotoxicity regardless of the mechanism of ICB. Hepatotoxicity is common and vigilant monitoring of liver function is required during ICB therapy for patients with cancer.

DOI： 10.1007/s00262-022-03203-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The manifestations of sarcoidosis differ by ethnicity and region. However, the few studies that have focused on elderly sarcoidosis are only from Western countries. Therefore, we investigated elderly sarcoidosis in Japan. METHODS: We retrospectively reviewed the records of adult patients (≥18 years old) who were diagnosed with sarcoidosis from 1 April 2006 to 31 March 2020. The diagnosis was pathologically confirmed in all patients. We compared the clinical features of elderly (diagnosed at ≥65 years old) and non-elderly (diagnosed at <65 years old) patients. RESULTS: Thirty-five (33%) of 106 patients were elderly. The elderly group had significantly more comorbidities than the non-elderly group (median [range], 1 [0-4] vs. 0 [0-5]). The biopsy site at diagnosis included significantly more extrathoracic sites in the elderly than non-elderly group (57.1% vs. 33.8%). The elderly group had significantly more muscle lesions than the non-elderly group at the time of diagnosis (11.4% vs. 1.4%) and at any time during follow-up (17.1% vs. 1.4%). CONCLUSION: In Japan, elderly patients with sarcoidosis might have more muscle involvement and comorbidities than younger patients. Because comorbidities might affect the prognosis of elderly sarcoidosis, further study is needed to clarify the effect of comorbidities on elderly sarcoidosis.

DOI： 10.1177/03000605221142705

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記述言語：英語  

DOI： 10.1016/j.ejim.2022.08.028

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immune checkpoint inhibitors (ICIs) are becoming widely used for novel cancer treatments. Immune-related adverse events, including cardiac toxicity, are frequently observed following immune checkpoint inhibitor (ICI) use. However, little is known regarding the association between ICIs initiation and hypertension in cancer patients. METHODS: A systematic literature search was performed using PubMed, EMBASE, Cochrane Library, and Web of Science Core Collection. The risk of hypertension associated with ICI initiation in randomized controlled trials (RCTs) was evaluated. Hypertension was categorized according to the Common Terminology Criteria for Adverse Events. The odds ratios of grades I to V and grades III to V hypertension were calculated using a random-effects meta-analysis. RESULTS: Thirty-two RCTs (n=19 810 cancer patients) were included. At a median follow-up of 36 months, the median overall survival was 15 months in the ICI group. ICI initiation was not significantly associated with hypertension (grades I-V: odds ratio, 1.12 [95% CI, 0.96-1.30]; grades III-V: odds ratio, 0.95 [95% CI, 0.78-1.16]). Additionally, no significant differences in hypertension risk were evident in ICI combination therapies with various drugs, including anti-VEGF (vascular endothelial growth factor) agents. In a subgroup analysis based on clinical setting (placebo RCT versus nonplacebo RCT), there were discrepancies between the results obtained with different methodologies, with patients in the nonplacebo RCTs having higher grades I-V hypertension (I2=88.6%, P for heterogeneity=0.003). CONCLUSIONS: ICI initiation was not associated with short-term risk of hypertension in cancer patients, and the association was similar regardless of concomitant treatment with other anticancer drugs.

DOI： 10.1161/HYPERTENSIONAHA.122.19865

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To reveal optimal antibiotic prophylactic regimen for postoperative endophthalmitis (POE), we conducted systematic review and network meta-analysis. A total of 51 eligible original articles, including two randomized controlled trials, were identified. In total, 4502 POE cases occurred in 6,809,732 eyes (0.066%). Intracameral injection of vancomycin had the best preventive effect (odds ratio [OR] 0.03, 99.6% confidence interval [CI] 0.00-0.53, corrected P-value = 0.006, P-score = 0.945) followed by intracameral injection of cefazoline (OR 0.09, 99.6% CI 0.02-0.42, corrected P-value < 0.001, P-score = 0.821), cefuroxime (OR 0.18, 99.6% CI 0.09-0.35, corrected P-value < 0.001, P-score = 0.660), and moxifloxacin (OR 0.36, 99.6% CI 0.16-0.79, corrected P-value = 0.003, P-score = 0.455). While one randomized controlled trial supported each of intracameral cefuroxime and moxifloxacin, no randomized controlled trial evaluated vancomycin and cefazoline. Sensitivity analysis focusing on the administration route revealed that only intracameral injection (OR 0.19, 99.4% CI 0.12-0.30, corrected P-value < 0.001, P-score = 0.726) significantly decreased the risk of postoperative endophthalmitis. In conclusion, intracameral injection of either vancomycin, cefazoline, cefuroxime, or moxifloxacin prevented POE.

DOI： 10.1038/s41598-022-21423-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: This study aimed to determine the clinical efficacy of apremilast for oral ulcers (OUs), extra-oral manifestations, and overall disease activity in patients with Behçet's disease (BD). METHODS: A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom-free for individual manifestations and mean difference (MD) of Behçet's Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis. RESULTS: Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: OUs, 45.76 (95% CI, 13.23-158.31); genital ulcers, 4.56 (95% CI, 2.47-8.44); erythema nodosum, 3.59 (95% CI, 1.11-11.61); pseudofolliculitis, 2.81 (95% CI, 1.29-6.15); and arthritis, 3.55 (95% CI, 1.71-7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=-1.38; -1.78 to -0.99). However, the proportion of oral-ulcer-free patients increased at 24 weeks (OR = 14.88; 4.81 to 46.07). CONCLUSIONS: The currently accumulated data indicate an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.

DOI： 10.1093/mr/roab098

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study aimed to determine the effectiveness of liquid biopsy in detecting epidermal growth factor receptor (EGFR) mutations at diagnosis, disease progression, and intermediate stages. METHODS: This prospective, multicenter, observational study included 30 patients with non-small cell lung cancer treated with afatinib, harboring a major EGFR mutation confirmed by tumor tissue biopsy. We collected blood samples for liquid biopsy at diagnosis, intermediate stage, and progressive disease. Tissue and liquid biopsies were examined using Cobas ® EGFR Mutation Test v2. RESULTS: Liquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. The presence of metastasis in the extrathoracic, brain, and adrenal glands correlated positively with the detection of EGFR mutations. Patients with positive EGFR mutations at diagnosis had significantly shorter overall and progression-free survival than patients with negative EGFR mutations. Four of the 18 patients (22.2%) who reached progressive disease had positive EGFR T790M mutations. Three of 10 patients (30.0%) with progressive disease were positive and negative for T790M using tumor re-biopsy and liquid biopsy, respectively. The results of EGFR mutation by tissue re-biopsy were the same as those of liquid biopsy in the three patients who were positive for significant EGFR mutations but negative for the T790M mutation using liquid biopsy at progressing disease. Only two patients were positive for major EGFR mutations at intermediate levels. CONCLUSIONS: Liquid biopsy can be a prognostic factor in EGFR-tyrosine kinase inhibitor treatments at diagnosis. Tumor re-biopsy can be omitted in patients with positive EGFR mutations by liquid biopsy at PD.

DOI： 10.1186/s12885-022-10135-z

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記述言語：英語  

DOI： 10.1002/ehf2.14095

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: This study was designed to evaluate the effect of rehabilitation in preventing decreased functional status (FS) after community-acquired pneumonia (CAP) in elderly patients. DESIGN: This was a retrospective observational study. SETTING: Multicentre study was conducted in two medical facilities from January 2016 to December 2018. PARTICIPANTS: Hospitalised patients with CAP aged over 64 years were enrolled. FS was assessed by the Barthel Index (BI) (range, 0-100, in 5-point increments) at admission and before discharge and graded into three categories: independent, BI 80-100; semidependent, BI 30-75; and dependent, BI 0-25. Multivariable analysis of factors contributing to decreased FS was conducted with two groups: with a decrease of at least one category (decreased group) or without a decrease of category (maintained group). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the effect of rehabilitation in preventing decreased FS. The secondary outcomes were factors associated with decreased FS. RESULTS: The maintained and decreased groups included 400 and 138 patients, respectively. A high frequency of rehabilitation therapy was observed in the decreased group (189 (47.3%) vs 104 (75.4%); p<0.001). Multivariable analysis showed that the factors affecting FS were aspiration pneumonia, Pneumonia Severity Index (PSI) category V, length of stay and age (OR 2.66, 95% CI 1.58 to 4.49; OR 1.92, 95% CI 1.29 to 3.44; OR 1.05, 95% CI 1.04 to 1.07; and OR 1.05, 95% CI 1.02 to 1.09, respectively). After adjusting for factors contributing to decreased FS, rehabilitation showed a limited effect in preventing decreased FS in 166 matched pairs by McNemar's test (p=0.327). CONCLUSIONS: Aspiration and PSI played important roles in reducing FS. The effect of rehabilitation remains unclear in CAP. TRIAL REGISTRATION NUMBER: UMIN000046362.

DOI： 10.1136/bmjopen-2021-051307

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this systematic review and meta-analysis, we sought to evaluate the prevalence of cardiac involvement in patients with COVID-19 using cardiac magnetic resonance imaging. A literature review was performed to investigate the left ventricular (LV) and right ventricular (RV) ejection fraction (EF), the prevalence of LV late gadolinium enhancement (LGE), pericardial enhancement, abnormality on T1 mapping, and T2 mapping/T2-weighted imaging (T2WI), and myocarditis (defined by modified Lake Louis criteria). Pooled mean differences (MD) between COVID-19 patients and controls for LVEF and RVEF were estimated using random-effects models. We included data from 10.462 patients with COVID-19, comprising 1.010 non-athletes and 9.452 athletes from 29 eligible studies. The meta-analysis showed a significant difference between COVID-19 patients and controls in terms of LVEF [MD = - 2.84, 95% confidence interval (CI) - 5.11 to - 0.56, p < 0.001] and RVEF (MD = - 2.69%, 95% CI - 4.41 to - 1.27, p < 0.001). However, in athletes, no significant difference was identified in LVEF (MD = - 0.74%, 95% CI - 2.41 to - 0.93, p = 0.39) or RVEF (MD = - 1.88%, 95% CI - 5.21 to 1.46, p = 0.27). In non-athletes, the prevalence of LV LGE abnormalities, pericardial enhancement, T1 mapping, T2 mapping/T2WI, myocarditis were 27.5% (95%CI 17.4-37.6%), 11.9% (95%CI 4.1-19.6%), 39.5% (95%CI 16.2-62.8%), 38.1% (95%CI 19.0-57.1%) and 17.6% (95%CI 6.3-28.9%), respectively. In athletes, these values were 10.8% (95%CI 2.3-19.4%), 35.4% (95%CI - 3.2 to 73.9%), 5.7% (95%CI - 2.9 to 14.2%), 1.9% (95%CI 1.1-2.7%), 0.9% (0.3-1.6%), respectively. Both LVEF and RVEF were significantly impaired in COVID-19 patients compared to controls, but not in athletes. In addition, the prevalence of myocardial involvement is not negligible in patients with COVID-19.

DOI： 10.1007/s00380-022-02055-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Variations in dose prescription methods in stereotactic body radiotherapy (SBRT) for early stage non-small-cell lung cancer (ES-NSCLC) make it difficult to properly compare the outcomes of published studies. We conducted a comprehensive search of the published literature to summarize the outcomes by discerning the relationship between local control (LC) and dose prescription sites. We systematically searched PubMed to identify observational studies reporting LC after SBRT for peripheral ES-NSCLC. The correlations between LC and four types of biologically effective doses (BED) were evaluated, which were calculated from nominal, central, and peripheral prescription points and, from those, the average BED. To evaluate information on SBRT for peripheral ES-NSCLC, 188 studies were analyzed. The number of relevant articles increased over time. The use of an inhomogeneity correction was mentioned in less than half of the articles, even among the most recent. To evaluate the relationship between the four BEDs and LC, 33 studies were analyzed. Univariate meta-regression revealed that only the central BED significantly correlated with the 3-year LC of SBRT for ES-NSCLC (p = 0.03). As a limitation, tumor volume, which might affect the results of this study, could not be considered due to a lack of data. In conclusion, the central dose prescription is appropriate for evaluating the correlation between the dose and LC of SBRT for ES-NSCLC. The standardization of SBRT dose prescriptions is desirable.

DOI： 10.3390/cancers14153815

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記述言語：英語  

DOI： 10.1111/1346-8138.16385

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記述言語：英語  

Tawbi et al. (2021) have recently reported that nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses (N1I3) provided durable survival for patients with active melanoma brain metastases without symptoms as first-line regimen. While we believe in the usefulness of the regimen proposed by Tawbi et al. (2021) we sought to investigate whether the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses (N3I1) regimen might lead to better safety profile. To compare the risk of adverse events caused by these two regimes, we have recently conducted a meta-analysis using the data of patients with both melanoma and the other malignancies. N1I3 regimen, compared to N3I1 regimen, more frequently induced any adverse events (N1I3, 96%; N3I1, 85%; P = 0.003), grade III or higher adverse events (N1I3, 64%; N3I1, 36%; P < 0.001; Fig. 1), and serious adverse events (N1I3, 61%; N3I1, 48%; P = 0.004). In terms of organ specific side effects, the N1I3 regimen also caused significantly more hepatic dysfunction, diarrhea, colitis, and pyrexia. We hope that there will be further discussion on the best dosage of the combination therapy.

DOI： 10.1016/j.tranon.2022.101449

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The present study aimed to evaluate whether serum heme oxygenase (HO)-1 could be a reliable blood biomarker for diagnosing acute exacerbations (AEs) of both idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia (SIP). Serum HO-1 levels of newly diagnosed patients with IP were measured, and the relationships between serum HO-1 and other serum biomarkers and high-resolution CT scores, were evaluated. Blood samples were collected from 90 patients with IIP, including 32 having an AE, and 32 with SIP, including 9 having an AE. The patients having an AE had significantly higher HO-1 levels than those not having an AE (35.2 ng/mL vs. 16.4 ng/mL; p < 0.001). On receiver operating characteristics (ROC) curve analysis for serum HO-1 ability to detect an AE, the area under the ROC curve (AUC) was 0.87 in patients with IIPs and 0.86 in those with SIPs. Also, in patients with both IIPs and SIPs, the combination of the serum HO-1 level and the GGO score showed favorable AUCs (IIPs: 0.92, SIPs: 0.83), though HO-1-not-including model (combination of LDH and GGO) also showed acceptable AUCs. Serum HO-1 could be a clinically useful biomarker for the accurate diagnosis of patients with AEs.

DOI： 10.1038/s41598-022-17290-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Antinuclear antibodies (ANAs) predicting the safety and efficacy of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate considering previous studies showed quite different results based on different ANA cut-off values. Thus, we investigated the associations between different ANA titers and the safety and efficacy of ICIs. Moreover, we also briefly discussed the effects of anti-thyroglobulin (ATG) and anti-thyroid peroxidase (ATPO) on the safety of ICIs. METHODS: A total of 159 Chinese patients confirmed to have locally-advanced or metastatic NSCLC given ICIs or chemoimmunotherapy in Peking Union Medical College Hospital from January 2015 to December 2020 were analyzed retrospectively and were followed up until December 2020 or death or loss to follow-up. Patients' characteristics were retrieved from medical records. ANAs were detected by the indirect immunofluorescence assay, ATG and ATPO by the electrochemiluminescence immunoassay. The severity of immune-related adverse events (irAEs) was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) and the efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). RESULTS: The incidence of irAEs, median progression-free survival (mPFS) of the ANA negative and positive groups were 26.0% vs. 31.4% (P=0.457), 17.7 vs. 10 months (P=0.603) for the cut-off value of 1:80; 26.2% vs. 33.9% (P=0.305), 11.9 vs. 10.6 months (P=0.957) for 1:160; and 25.9% vs. 45.8% (P=0.047), and 11.9 vs. 7.7 months (P=0.471) for 1:320, separately. Besides, ANA titer ≥1:320 was associated with irAEs [odds ratio (OR) =4.9, 95% confidence interval (CI): 1.45-16.52, P=0.01] and the incidence of adverse skin reactions differed greatly between the negative and positive groups (9.7% vs. 32%, P=0.003). Moreover, a total of 52 out of 159 patients were tested for ATG and ATPO. 46 patients were negative and 6 were positive, with the incidence of abnormal thyroid function being 4.3% vs. 50% (P=0.005), respectively. CONCLUSIONS: Preexisting ANAs may not correlate with the clinical benefit of immunotherapy in patients with NSCLC but may be associated with adverse skin reactions. Besides, ATG or ATPO has the potential to predict thyroid dysfunction.

DOI： 10.21037/tlcr-22-464

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記述言語：英語  

DOI： 10.1093/cid/ciab922

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記述言語：英語  

DOI： 10.1016/j.amjcard.2022.02.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The diagnostic accuracy of the interferon-gamma release assay (IGRA) in immunosuppressed patients remains unclear. METHODS: A systematic review and meta-analysis were performed for diagnostic test accuracy of IGRA in tuberculosis (TB) infection among people living with HIV (PLWHIV). Summary estimates of sensitivity and specificity were calculated using both univariate and bivariate models. RESULTS: The meta-analysis included 45 of the 1,242 first-screened articles. The total number of PLWHIV was 6,525; 3,467 had TB disease, including 806 cases of LTBI and 2,661 cases of active TB. The overall diagnostic odds ratio (DOR) of IGRA in the diagnosis of TB disease was 10.0 (95% confidence interval (CI) 5.59, 25.07), with an area under the curve (AUC) of 0.729. The DOR was better for QFT (14.2 (95%CI 4.359, 46.463)) than T-SPOT (10.0 (95%CI 3.866 26.033)). The sensitivity and specificity of QFT and T-SPOT were 0.663 (95%CI 0.471, 0.813), 0.867 (95%CI 0.683 0.942), and 0.604 (95%CI 0.481, 0.715), 0.862 (95%CI 0.654, 0.954), respectively, in the bivariate model. The sensitivity of IGRA in the diagnosis of LTBI was 0.64 (95%CI 0.61, 0.66). CONCLUSION: IGRA was useful in the diagnostic of TB disease in PLWHIV, and QFT showed a better tendency of DOR than T-SPOT. IGRA showed a limited effect to rule out LTBI in PLWHIV.

DOI： 10.1007/s15010-022-01789-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Platinum-doublet chemotherapy has been conventionally used for patients with advanced gastroenteropancreatic (GEP) neuroendocrine carcinoma (NEC) but evidence of chemotherapy is based on studies with small sample sizes and remains scarce. Thus, we conducted a systematic review and meta-analysis to elucidate the efficacy of platinum-doublet chemotherapy for advanced GEP-NEC. METHODS: We performed a database search in PubMed/MEDLINE and EMBASE. Eligible studies were prospective and retrospective studies documenting the efficacy of platinum plus etoposide (EP) and platinum plus irinotecan (IP) for advanced GEP-NEC. Overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were pooled and weighted using generic inverse variance in a random-effects meta-analysis model. RESULTS: Nineteen studies including 1157 patients were identified. The ORR of the platinum-doublet regimen, EP, and IP was 49.1% (95% confidence interval [CI], 41.8-56.5), 44.4% (95% CI: 35.9-53.0), and 59.4% (95% CI: 48.0-70.8). The pooled median OS of the platinum-doublet regimen, EP, and IP was 12.9 months (95% CI:10.9-15.3), 12.9 months (95% CI: 10.8-15.4), and 12.9 months (95% CI: 6.0-27.8), and the pooled median PFS of the platinum-doublet regimen, EP, and IP was 5.4 months (95% CI: 4.5-6.4), 5.4 months (95% CI 4.5-6.5), and 4.0 months (95% CI: 1.4-11.7), respectively. CONCLUSION: Considerable response rate and survival time of the platinum-doublet regimen for advanced GEP-NEC were observed. IP and EP regimens can be reasonably applicable and these results provide a reference for oncologists in deciding the suitable regimen for patients with advanced GEP-NEC.

DOI： 10.1007/s12672-022-00499-w

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記述言語：英語  

DOI： 10.1016/j.ejca.2022.01.027

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet's disease. METHODS: The Japanese government provided us with a dataset of confirmed or suspected Behçet's disease cases derived from ongoing national registration. ADL were categorized and analysed into four categories in patients who satisfied the International Criteria for Behçet's Disease. RESULTS: Data from 2960 patients (men 38.9%, women 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising limited but not assisted [n = 1058 (35.7%)], partially assisted [n = 116 (3.9%)] and fully assisted [n = 19 (0.6%)]. Logistic regression analysis showed that chronic ocular lesions [odds ratio (OR) 1.85 (95% CI 1.46, 2.35), P < 0.001], paralysis [OR 2.51 (95% CI 1.58, 3.97), P < 0.001], psychosis [OR 3.16 (95% CI 2.02, 4.95), P < 0.001] and arthritis [OR 1.69 (95% CI 1.44, 1.99), P < 0.001] led to the risk of impaired ADL. Chronic ocular lesions [OR 3.61 (95% CI 2.27, 5.72), P < 0.001], paralysis [OR 3.43 (95% CI 1.87, 6.30), P < 0.001] and psychosis [OR 3.60 (95% CI 2.00, 6.50), P < 0.001] were related to the requirement of physical assistance (partially or fully assisted), although arthritis [OR 1.39 (95% CI 0.93, 2.06), P = 0.108] was not a significant factor in this model. CONCLUSION: Ocular lesions, neurological manifestations and arthritis affected ADL. Patients with ocular lesions or neurological manifestations more frequently required physical assistance.

DOI： 10.1093/rheumatology/keab499

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記述言語：英語  

This cohort study examines trends in suicide rates in Japan from 2009 to 2021, including the COVID-19 pandemic.

DOI： 10.1001/jamanetworkopen.2022.4739

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記述言語：英語  

DOI： 10.1016/j.ijrobp.2021.09.050

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記述言語：英語  

See related article

DOI： 10.1111/resp.14186

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pembrolizumab alone or in combination with chemotherapy is a standard treatment for patients with non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression. However, no study has compared the efficacies of these two regimens. Therefore, we aimed to compare the efficacy of pembrolizumab alone and in combination with chemotherapy in NSCLC patients with high PD-L1 expression. METHODS: We conducted a multicenter retrospective trial involving patients with diagnosed unresectable or recurrent NSCLCs who had received pembrolizumab with or without chemotherapy in the first-line setting. Patients were divided into monotherapy and combination therapy groups. The progression-free survival (PFS), overall survival (OS), and response rate (RR) were analyzed and compared between the groups. Clinical characteristics of patients were analyzed to assess their possible relationship with treatment outcomes. RESULTS: We enrolled 96 patients from five hospitals. Of these, 47 and 49 patients received monotherapy and combination therapy, respectively. The median PFS was 343 and 328 days in the monotherapy and combination therapy groups, respectively (hazard ratio 1.003, p = 0.99). No statistically significant differences were observed in the OS and RR between the two groups. However, in patients with metastases to the liver, lung, adrenal glands, bone, or lymph nodes, the PFS was longer in the monotherapy group than in the combination therapy group. CONCLUSION: Although the PFS, OS, and RR were not significantly different between patients treated with pembrolizumab alone and or with pembrolizumab in combination with chemotherapy, patients with NSCLC having metastases to specific sites may benefit more from monotherapy.

DOI： 10.1111/1759-7714.14252

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. It is advisable to select the appropriate treatment based on characteristics of the cancer such as pathology, mutations, and programmed death-ligand 1 (PD-L1) levels. In this study, by remarking squamous NSCLC with low PD-L1 expression without mutations, we investigated the efficacy and safety of regimens that included molecularly targeted drugs such as immune checkpoint inhibitors (ICIs) through a network meta-analysis. METHODS: Databases were searched systematically to identify appropriate articles, in which randomized trials with incurable squamous NSCLC were described. Suitable studies were manually checked by two reviewers. A random model network meta-analysis was conducted, in which the primary outcome was the overall survival rate. RESULTS: We identified 48 studies, which included 16 391 patients. When a platinum + third-generation cytotoxic agent regimen (platinum regimen) was a reference, the platinum regimen + pembrolizumab (Pemb) yielded the best results in regard to the overall survival rate when compared with chemotherapy (hazard ratio [HR] = 0.57, 95% confidence interval [CI] = 0.36-0.90, p = 0.016) followed by the platinum regimen + nivolumab (Niv) + ipilimumab (Ipi) (HR = 0.61, 95% CI = 0.44-0.84, p = 0.003). However, the efficacy of ICI monotherapy was not statistically different from that of the platinum regimen. CONCLUSIONS: The combination therapies, which were the platinum regimen + Pemb and the platinum regimen + Niv + Ipi, rather than ICI monotherapy were effective first-line agents for treating squamous NSCLC with low PD-L1 levels.

DOI： 10.1111/1759-7714.14229

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Inconsistent diagnostic test accuracies of immunohistological staining for squamous cell carcinoma (SQC) of the lung have been frequently reported. There have been few meta-analyses of the diagnostic accuracies of the immunohistochemical markers. METHODS: A systematic review and meta-analysis were performed following standard guidelines for systematic reviews of diagnostic test accuracy. Immunohistochemical markers (p40, p63, CK5/6, and DSC3) were evaluated as index tests for SQC. The diagnostic odds ratio (DOR) was obtained by the DerSimonian-Laird variate model. Summary estimates of sensitivity and specificity were calculated using a bivariate model. The protocol registration ID is UMIN000041664. RESULTS: The meta-analysis included 85 of the 1353 first-screened articles. The total number of patients was 17,893, which consisted 6151 SQC cases and 11,742 non-squamous non-small-cell lung cancer cases. The DOR was better for p40 (377, 95% confidence interval (CI) = 213-644, I 2 = 0%) than for CK5/6 (120, 95% CI = 78-184, I 2 = 2.5%), p63 (70, 95% CI = 55-88, I 2 = 9.1%), and DSC3 (94, 95% CI = 35-250, I 2 = 3.7%). Summary estimates of sensitivity and specificity were followings: p40 sensitivity 0.92 (95% CI = 0.89-0.95), specificity 0.94 (95% CI = 0.93-0.96); p63 sensitivity 0.92 (95% CI = 0.90-0.94), specificity 0.83 (95% CI = 0.80-0.86); CK5/6 sensitivity 0.90 (95% CI = 0.87-0.93), specificity 0.91 (95% CI = 0.89-0.93); DSC3 sensitivity 0.81 (95% CI = 0.73-0.88), and specificity 0.95 (95% CI = 0.85-0.98). CONCLUSION: P40 had the best DOR to diagnose SQC in non-small-cell lung carcinoma. Despite its lower sensitivity, DSC3 had the best specificity among the four markers and might be useful to rule-in the diagnosis of SQC.

DOI： 10.1177/17588359211065152

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: No meta-analysis has assessed the pooled frequencies of adverse events (AEs) induced by concomitant nivolumab plus ipilimumab regimen for anticancer-medications-naïve malignancies. Furthermore, no meta-analysis has compared detailed safety profiles between four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1) and four doses of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3). Objectives of this study was estimating AE frequencies, and comparison of AE frequencies between N3I1 and N1I3 regimens. METHODS: Four major electronic databases were searched; both interventional and observational studies were included. All primary cancer types were permitted. Patients should not have been previously treated with any anti-cancer medications. The frequency of AEs was pooled using a random-model meta-analysis using the generic inverse variance method. Protocol registration: UMIN000044090. RESULTS: Forty articles representing 48 populations with 4,677 patients were included in the study. The pooled frequencies for key indicators were as follows: any AE, 81.3% (95% confidence interval (CI) 77.5-85.1); grade 3 or higher AE, 40.6% (95% CI: 35.7-45.5); serious AE, 32.7% (95% CI: 22.4-43.1); AE leading to discontinuation, 28.3% (95% CI: 23.7-32.8); and treatment-related death, 0.7% (95% CI: 0.4-1.1). AEs with the highest incidence were fatigue (27.9%, 95% CI: 22.6-33.3), followed by diarrhea (26.0%, 95% CI: 21.5-30.5), pruritus (24.6%, 95% CI: 20.3-28.8), rash (24.0% 95% CI: 19.3-28.7), and elevated aspartate aminotransferase (21.2%, 95% CI: 14.9-27.5). Subgroup analyses demonstrated that N3I1, compared to N1I3, less frequently induced any AE (N1I3 95.7%, N3I1 84.5%, p = 0.003), grade 3 or higher AE (N1I3 64.3%, N3I1 35.7%, p < 0.001), and serious AE (N1I3 61.4%, N3I1 47.8%, p = 0.004). CONCLUSIONS: Approximately 40% of patients had grade 3 or higher AE. The N3I1 regimen was substantiated to trigger fewer any AEs, high grade AEs, and serious AE than the N1I3 regimen.

DOI： 10.1177/17588359211058393

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUNDS: Recent studies have reported increased risks of adverse events from systemic corticosteroids even with only low-dose or short-term use. Some patients with asthma experience complications requiring systemic corticosteroids. However, few studies have examined issues associated with administration of systemic corticosteroids for reasons other than asthma among subjects with asthma. OBJECTIVES: We investigated patterns of systemic corticosteroid exposure for reasons other than asthma in subjects with asthma. METHOD: We retrospectively reviewed the records of adult subjects with asthma followed up for >1 year at Yokohama City University Hospital from January 1, 2010, to December 31, 2019. We investigated patterns and reasons for systemic corticosteroid use during follow-up. In addition, factors related to systemic corticosteroid use for reasons likely other than asthma were investigated. RESULTS: Among the 568 subjects with asthma analyzed, 326 (57.4%) had received systemic corticosteroids for some reason. Among those 326 patients, 120 (36.8%) had received systemic corticosteroids for reasons likely other than asthma. Multivariable analysis revealed rheumatoid arthritis, eosinophilic granulomatosis with polyangiitis, other collagen vascular diseases, chronic rhinosinusitis, and malignancy as positively associated with systemic corticosteroid exposure for reasons likely other than asthma in subjects with asthma. CONCLUSIONS: About 40% of systemic corticosteroid use in subjects with asthma was for reasons likely other than asthma. Clinicians should be aware of their asthma patients' exposures to systemic corticosteroids for nonasthma reasons, to avoid missing adverse events or underestimating the severity of asthma, and to reduce systemic corticosteroid use.

DOI： 10.1159/000518461

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記述言語：英語  

DOI： 10.1016/j.hjc.2022.07.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 70-year-old man diagnosed with idiopathic pulmonary fibrosis (IPF) one year earlier developed progressive exertional dyspnea 3 weeks after onset of coronavirus disease 2019 (COVID-19). High-resolution computed tomography showed new extensive ground-glass opacities with rapidly progressive honeycombing. Although he was diagnosed with acute exacerbation (AE) of IPF triggered by COVID-19 and received methylprednisolone pulse therapy twice within one month, there was no improvement of oxygenation and lung involvement. Three months after COVID-19 onset, it was decided to provide best supportive care. An AE of IPF as a sequela of COVID-19, which is recognized as macrophage activation syndrome, is fatal, and in this case, the measurement of serum heme oxygenase-1, which is a macrophage activation biomarker involved in pulmonary cellular protection against oxidative stress, was useful for tracking disease activity.

DOI： 10.1016/j.rmcr.2022.101615

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lung lesions of Hodgkin's lymphoma (HL) are rare and difficult to diagnose by nonsurgical biopsy. We herein present the case of a 72-year-old Japanese male who presented with accumulation of lung infiltrates and masses bilaterally on the lungs for 3 years. Although transbronchial lung biopsy (TBB) and computed tomography-guided biopsy were conducted several times, his diagnosis remained inconclusive. On further deterioration of lung lesions, the patient was transferred to our hospital. Positron emission tomography revealed increased accumulation in the bilateral lungs and right supraclavicular lymph nodes. Surgical biopsy of the lymph node was performed. He was finally diagnosed with HL and underwent chemotherapy with doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin. After chemotherapy, the lung lesion showed significant regression. A literature review indicated that the diagnostic success rate of TBB was low (18.5%) in cases of lung lesions in HL.

DOI： 10.1111/1759-7714.14190

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare subset of lung carcinoma with poor overall survival. METHODS: A systematic review following a meta-analysis of studies was performed to identify the effect of different selections of chemotherapy in LCNEC. Articles providing overall survival data for adjuvant chemotherapy or palliative chemotherapy for LCNEC were eligible. The odds ratio (OR) of mortality at one or two years after chemotherapy was evaluated. RESULTS: A total of 16 reports were finally included in the quantitative synthesis, involving a total of 5916 LCNEC patients. Adjuvant chemotherapy was administered to 1303 patients, and palliative chemotherapy was administered to 313 patients using either a small cell lung cancer (SCLC) or a non-small cell lung cancer (NSCLC) regimen. The OR for adjuvant chemotherapy was 0.73 (95% confidence interval (CI): 0.59 to 0.89, p = 0.002). The SCLC regimen showed an OR of 0.52 (95% CI: 0.11 to 2.38, p = 0.40) after one year, and 0.32 (95% CI: 0.11 to 0.89, p = 0.03) after two years, compared with the NSCLC regimen. CONCLUSIONS: Adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma improved the outcome after surgery. The SCLC regimen showed better survival than the NSCLC regimen as palliative chemotherapy.

DOI： 10.3390/cancers13235948

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.21037/jtd-20-1955

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Malignancy-related ascites (MRA) is one of the symptoms causing discomfort in advanced cancer patients. Cell-free and concentrated ascites reinfusion therapy (CART) is one of the palliative treatments widely conducted in Japan only. METHODS: A systematic review following a meta-analysis of CART was performed. The efficiency and adverse events were evaluated. RESULTS: A total of 2567 patients and 6013 procedures of CART were identified in this study. The mean volume of MRA collected was 4.29 (95% confidence interval (CI) 3.47-5.11) L, and the volume reinfused after concentrating was 0.49 (95% CI 0.39-0.60) L. A total of 86.1 (95% CI 77.1-95.2) g protein and 42.9 (95% CI 36.0-50.0) g albumin was reinfused. The mean time to the next paracentesis was 20.7 (95% CI 15.6-25.8) days. The body weight was reduced by 3.38 (95% CI 1.90-4.86; p < 0.01) kg, and abdominal circumference was reduced by 7.86 (95% CI 6.58-9.14; p < 0.001) cm. Serum albumin increased an average of 0.14 (95% CI -0.01-0.28; p = 0.07) mg/dL the day after CART. Abdominal distension, dyspnea, and fatigue were alleviated by 6.0 (95% CI 5.59-6.51), 2.66 (95% CI 2.05-3.28), and 2.64 (95% CI 1.86-3.42) points using a numerical rating scale system ranging from 0 to 10. Overall, 17% (95% CI 0.03-0.31%) of patients had improved performance status after CART. Significant body temperature elevation was observed, at an average of 0.4 °C (95% CI 0.18-0.62 °C). CONCLUSIONS: CART might be a safe and effective palliative therapy in MRA and further clinical trials are necessary.

DOI： 10.3390/cancers13194873

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We investigated whether delivery of a high biologically effective dose (BED) to primary tumors affects systemic outcomes of cancer-specific death (CSD) and overall survival (OS) rates after stereotactic body radiation therapy (SBRT) in patients with early-stage non-small cell lung cancer (ES-NSCLC). METHODS AND MATERIALS: Among consecutive ES-NSCLC patients treated with SBRT between 2005 and 2019, we retrospectively identified patients who received a prescription of 50 to 60 Gy in 5 fractions with maximum doses of 62.5 to 100 Gy. Patients were categorized by maximum BED within the planning target volume with a threshold dose of 200 Gy. Outcomes were analyzed in all and matched patients. RESULTS: Overall, 433 patients were eligible, and 262 and 171 patients were categorized into HighBED and LowBED groups, respectively. After propensity score matching, pairs of 154 patients were selected. Median follow-up times for the HighBED and LowBED groups were 52.3 months (range, 0.8-107.2 months) and 121.6 months (range, 3.0-162.8 months), respectively. The local recurrence rate in the HighBED group was significantly lower than that in the LowBED group (5-year rate, 1.3% and 7.2%; hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.03-0.65; P = .011). Rates of any recurrence and CSD in the HighBED group were significantly lower (5-year any recurrence: 18.1% and 32.1%; HR, 0.52; 95% CI, 0.33-0.83; P = .0058; 5-year CSD: 9.5% and 21.8%; HR, 0.38; 95% CI, 0.20-0.70; P = .002), and OS in the HighBED group was significantly better compared with the LowBED group (5-year rate: 61.7% and 51.8%; HR, 0.71; 95% CI, 0.50-1.00; P = .047). CONCLUSION: In patients with peripheral ES-NSCLC, SBRT with a high maximum dose may improve not only local control, but also any recurrence, CSD, and OS rates without increased toxicity. Further trials designed to evaluate whether higher intensity SBRT increases local control rates and contributes to improved CSD and OS outcomes are anticipated.

DOI： 10.1016/j.ijrobp.2021.04.014

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. There is a rank order of the efficacy and safety of treatment options, including immune checkpoint inhibitors (ICIs), bevacizumab (Bev), and cytotoxic drugs. When patients have low programmed death-ligand 1 (PD-L1) expression, there are multiple options for treatment. In this study, we focused on ICI regimens in patients with non-squamous NSCLC with low PD-L1 expression and no driver alterations and assessed the efficacy of the regimens using network meta-analysis. METHODS: Randomized trials for incurable chemo-naïve non-squamous NSCLC were collected through electronic searches. The data were independently extracted and cross-checked by two investigators. The primary outcome of this analysis was overall survival (OS). A frequentist weighted least-squares approach random-model network meta-analysis was applied. RESULTS: Sixty-eight eligible studies and 22,619 patients were identified. Using a platinum + third-generation cytotoxic agent regimen (platinum regimen) as a reference, the platinum regimen + pembrolizumab (Pemb) [hazard ratio (HR) =0.55, 95% confidence interval (CI): 0.34-0.89, P=0.015] showed the best OS, followed by the platinum regimen + nivolumab (Niv) + ipilimumab (Ipi) (HR =0.61, 95% CI: 0.44-0.84, P=0.003) with no heterogeneity (I2=0%, P=0.348). CONCLUSIONS: The addition of Pemb or Niv/Ipi to platinum-based chemotherapy seems to be a good therapeutic option for non-squamous NSCLC with a PD-L1 tumor proportion score (TPS) of 1-49%.

DOI： 10.21037/tlcr-21-419

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Stereotactic body radiotherapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC) and has shown excellent local control (LC), as has radiofrequency ablation (RFA). As no randomized controlled trial has compared SBRT and RFA for HCC, data from a propensity score matched study (PSMS) are valuable. However, the results varied greatly and depended on composing factors of Barcelona Clinic Liver Cancer staging (BCLC-factors) adjusted. Therefore, we undertook a systematic review and meta-analyses of the studies focusing on BCLC-factors matching. METHODS: We systematically searched PubMed, the Cochrane database, EMBASE, and Web of Science to identify studies comparing RFA and SBRT using propensity scores. The hazard ratios (HRs) of overall survival (OS) and LC from BCLC-factor-matched and -unmatched PSMS were pooled. Heterogeneity between the data from these studies was assessed. RESULTS: Three BCLC-factor-matched studies were identified. Stereotactic body radiotherapy led to comparable OS (HR, 0.89; 95% CI, 0.74-1.08; p = 0.24; I2  = 0%; p for heterogeneity, 0.56) and significantly better LC (HR, 0.39; 95% CI, 0.30-0.51; p < 0.001; I2  = 0%; p for heterogeneity, 0.67). We also identified three additional BCLC-factor-unmatched studies (HR of OS, 1.41; 95% CI, 1.21-1.65; p < 0.0001; I2  = 0%; p for heterogeneity, 0.63). However, considerable heterogeneity was observed for HR of OS between BCLC-factor-matched and -unmatched studies (I2  = 92.6%; p for heterogeneity, 0.0002). CONCLUSIONS: When BCLC-factors were properly adjusted, the results of the meta-analysis revealed equivalent OS and better LC for SBRT compared with RFA. Stereotactic body radiotherapy could be an alternative treatment option for HCC.

DOI： 10.1111/hepr.13647

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Risk factors associated with mortality in invasive pneumococcal disease remain unclear. The present work is a meta-analysis of studies that enrolled only patients with invasive pneumococcal disease and reported on mortality. Potentially eligible reports were identified from PubMed, CHAHL, and Web of Science, comprising 26 reports in total. Overall mortality for invasive pneumococcal disease was reported as 20.8% (95% confidence interval (CI) 17.5-24%). Factors associated with mortality were age (odds ratio (OR) 3.04, 95% CI 2.5-3.68), nursing home (OR 1.62, 95% CI 1.13-2.32), nosocomial infection (OR 2.10, 95% CI 1.52-2.89), septic shock (OR 13.35, 95% CI 4.54-39.31), underlying chronic diseases (OR 2.34, 95% CI 1.78-3.09), solid organ tumor (OR 5.34, 95% CI 2.07-13.74), immunosuppressed status (OR 1.67, 95% CI 1.31-2.14), and alcohol abuse (OR 3.14, 95% CI 2.13-4.64). Mortality rates with invasive pneumococcal disease remained high, and these findings may help clinicians provide appropriate initial treatment for this disease.

DOI： 10.1038/s41598-021-91234-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become one of the standard treatment options for solid tumours; however, treatment-related adverse events, including pneumonitis, sometimes disrupt the ongoing treatment. To evaluate the impact of ICI addition on the risk of pneumonitis, a meta-analysis was conducted. METHODS: Phase III randomised controlled trials comparing ICIs and conventional therapy with conventional therapy alone were selected by searching databases, including PubMed, Embase, Web of Science and Cochrane Library. The odds ratio (OR) of any grade and grade III-V pneumonitis was calculated. Meta-analysis was performed to compare the incidence of pneumonitis between the treatment arm with additional ICIs and the arm with conventional therapy. RESULTS: A total of 25 randomised controlled trials (RCTs) representing 16,343 patients for grade I-V and 23 RCTs with 15,006 patients for grade III-V pneumonitis were analysed. Adding ICIs was associated with a significant increase in pneumonitis (grade I-V: OR, 2.67, 95% confidence interval [CI]: 2.12-3.37, grade III-V: OR, 1.83, 95% CI: 1.26-2.65). In subgroup analyses based on the mechanism of action of ICIs, cancer types (lung and non-lung cancer) and each ICI, no significant difference in heterogeneity was observed. CONCLUSIONS: Adding ICIs to the conventional treatment for solid tumours significantly increased both grade I-V and grade III-V pneumonitis regardless of the mechanisms of ICIs and cancer type. These results would be helpful for oncologists to choose the appropriate treatment options using ICIs, particularly for patients with known risk factors of pneumonitis or interstitial lung disease.

DOI： 10.1016/j.ejca.2021.03.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Immune checkpoint inhibitors are a standard treatment for advanced lung cancer, although it remains important to identify biomarkers that can accurately predict treatment response. Immune checkpoint inhibitors enhance the antitumor T-cell response, and interferon-γ plays an important role in this process. Therefore, this study evaluated whether the number of interferon-γ-releasing peripheral T cells after phytohemagglutinin stimulation in the interferon-γ release assay might act as a biomarker for the response of non-small cell lung cancer to immune checkpoint inhibitor treatment. METHODS: Data were retrospectively collected regarding 74 patients with non-small cell lung cancer who had received immune checkpoint inhibitors. Pretreatment screening tests had been performed using the T-SPOT.TB assay, which quantifies the number of interferon-γ-releasing T cells (as immunospots) in response to phytohemagglutinin and tuberculosis-specific antigen stimulation. Clinical factors and the number of spots in the T-SPOT fields were evaluated for associations with patient outcomes. The median number of spots was used to categorize patients as having high or low values, and the two groups were compared. RESULTS: Relative to patients with a low ratio, patients with a high ratio of phytohemagglutinin/tuberculosis-specific antigen spots (i.e. more responsive T cells) had significantly better progression-free survival after immune checkpoint inhibitor treatment. When we only considered patients with negative T-SPOT results, a high number of phytohemagglutinin-stimulated spots corresponded to significantly longer progression-free survival. CONCLUSION: The T-SPOT.TB assay can be used to quantify the number of immunospots in response to antigen stimulation, which may predict the response to immune checkpoint inhibitors in patients with non-small cell lung cancer.

DOI： 10.1111/1759-7714.13978

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although objective response rate and disease control rate are commonly used as primary endpoints of lung cancer trials, it remains unclear whether objective response rate and disease control rate correctly reflect the overall survival in a non-small cell lung cancer phase II trial evaluating a non-first-line chemotherapy. Objective response rate might be easily affected by chance because the small number of patients in each trial achieved complete or partial response in the phase II non-first-line setting. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (UMIN000040412). Four databases were searched for eligible trials. A Spearman's rank correlation with hazard ratio of overall survival was calculated each for odds ratio of objective response rate, difference of objective response rate (%), odds ratio of disease control rate, and difference of disease control rate (%). Of 74 eligible trials, 73 reported objective response rate and 68 reported disease control rates. Nine (12%) trials included patients with driver mutation status. Thirteen (18%) and two (3%) RCTs specifically included adenocarcinoma/non-squamous and squamous subtype of non-small cell lung cancer, respectively. The Eastern Cooperative Oncology Group performance status 0-2 (N=41, 55%) and the performance status 0-1 (N=25, 34%) were frequently used performance status criteria. The median number of patients in the two arms was 116 (interquartile range, 82-159). The correlation between trial-level odds ratio of objective response rate and hazard ratio of overall survival was weak (r=-0.29, 95% CI: -0.49 to -0.05, P=0.014). An exploratory subgroup analysis suggested that fewer responders were associated with poorer correlation. Odds ratio of disease control survival (r=-0.53, 95% CI: -0.68 to -0.32, P<0.001) had moderate rank correlations with hazard ratio of overall survival. Instead of objective response rate, disease control rate should be used as the primary endpoint in a randomized phase II trial evaluating non-first-line chemotherapy for non-small cell lung cancer.

DOI： 10.21037/tlcr-20-1120

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Guidelines and systematic reviews frequently warn of inhaled corticosteroid (ICS)-induced glaucoma. However, most of the published studies deny it. METHODS: We performed a systematic review of randomized, cohort, nested-case control, cross-sectional studies by using Meta-analyses of Observational Studies in Epidemiology statement. Four major databases, PubMed, EMBASE, Cochrane Search Manager, and the Web of Science Core Collection as well as meta-analysis were used. Studies comparing incidence, prevalence and intraocular pressure (IOP) between patients who were treated with and without ICSs were included. A random-model meta-analysis was performed using the inverse variance method. RESULTS: Out of 623 studies screened, 18 with 31,665 subjects were finally included. No significant difference between the 2 groups was observed for crude glaucoma incidence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.86-1.04; P = 0.26; I² = 0%; P for heterogeneity = 0.57) as a primary endpoint, adjusted glaucoma incidence (OR, 0.90; 95% CI, 0.65-1.24; P = 0.64), crude prevalence (OR, 1.82; 95% CI, 0.23-14.19; P = 0.57), adjusted prevalence (OR, 1.22; 95% CI, 0.50-2.96; P = 0.66), IOP change during ICS treatment (mean difference [MD] +0.01 mmHg; 95% CI, -0.19-0.20; P = 0.95), and single measurement IOP (MD +0.37 mmHg; 95% CI, -0.24-0.97; P = 0.23). Time-to-event analysis for glaucoma development as one of the secondary endpoints (adjusted hazard ratio, 0.52; 95% CI, 0.28-0.96) suggested a reverse association between ICS and glaucoma. CONCLUSIONS: The ophthalmological side effects of ICSs, such as glaucoma and intraocular hypertension, should not be exaggerated. TRIAL REGISTRATION: University Hospital Medical Information Network Center Clinical Trial Registry Identifier: UMIN000040351.

DOI： 10.4168/aair.2021.13.3.435

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Existing guidelines form no consensus for alopecia areata (AA) treatment due to the absence of a universal standard treatment and arbitrary selection of reference arms in randomized control trials (RCTs). The aim is to identify the best treatment and to rank treatments using systematic review and network meta-analysis. Data were extracted by the two investigators independently. Odds ratio (OR) of treatment success rate was pooled using the frequentist weighted least squares approach to random-model network meta-analysis. RCTs providing data of treatment success rate from PubMed, EMBASE, Web of Science, and manual search were included. About 54 RCTs consisting of 49 treatments and 3149 patients were included. Pentoxifylline plus topical corticosteroids had the highest treatment success rate compared with "no treatment," followed by pentoxifylline alone, topical calcipotriol plus narrowband ultraviolet radiation B phototherapy, topical calcipotriol, intralesional corticosteroids, systemic corticosteroids, minoxidil plus topical corticosteroids, topical bimatoprost, psoralen ultraviolet radiation A phototherapy, and tofacitinib. Even with the network meta-analysis, the best treatment because of independent loops and wide confidence intervals could not be identified. Treatment options above may be reasonable strategies, but further comparison is required.

DOI： 10.1111/dth.14916

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記述言語：英語  

DOI： 10.1016/j.ejca.2021.01.031

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Differences in the resistance mechanisms of epidermal growth factor receptor tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor mutations are unknown. This meta-analysis aimed to clarify the differences in resistance mechanisms after treatment with various epidermal growth factor receptor tyrosine kinase inhibitors. METHODS: We systematically searched PubMed, Cochrane, and Web of Science on July 29, 2020, for relevant studies on acquired resistance mechanisms against epidermal growth factor receptor tyrosine kinase inhibitors. The primary outcome measure was differences in the resistance mechanism between individual or generations of epidermal growth factor receptor tyrosine kinase inhibitors. RESULTS: In total, 33 trials involving 2418 individuals were included and analyzed. T790M was significantly less frequent after afatinib treatment (40.2%, 95% confidence interval [CI]: 31.7%-48.7%) than after gefitinib and erlotinib treatments (52.5%, 95% CI: 48.7%-56.3%, p = 0.005). There were no significant differences between Asian and non-Asian patients in the incidence of T790M after gefitinib, erlotinib, and afatinib treatments. Regarding epidermal growth factor receptor pathway-independent resistant mechanisms, the incidences of small cell lung cancer transformation (osimertinib: 7.9%, 95% CI: 3.6%-12.2%, others: 2.3%, 95% CI: 0.8%-3.8%) and Kirsten rat sarcoma (KRAS) viral oncogene homolog mutation (osimertinib: 4.6%, 95% CI: 1.5%-7.7%, others: 0.2%, 95% CI: 0.0%-1.7%) were significantly higher following osimertinib treatment than with others. CONCLUSIONS: Significant differences in the incidence of resistance mechanisms among epidermal growth factor receptor tyrosine kinase inhibitors exist, which should be taken into consideration when choosing the treatment strategy.

DOI： 10.1111/1759-7714.13878

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Our systematic review and meta-analysis aimed to evaluate the effect of postoperative radiotherapy (PORT) on completely resected Masaoka/Masaoka-Koga (M/MK) stage II/III thymomas. METHODS: We systematically searched four online databases and included studies that compared surgery alone versus surgery plus a PORT for completely resected M/MK stage II/III thymoma. The multivariate-adjusted hazard ratios (HRs) of overall survival (OS) and disease-free survival were evaluated as the primary and secondary end points, respectively. We performed a subgroup analysis for OS with respect to M/MK stage II, III, and inseparable II/III cases. A generic inverse variance meta-analysis using a random model was conducted. RESULTS: Five studies including 4746 patients (among them, 2408 patients received PORT) met our selection criteria. A meta-analysis of these five studies revealed that PORT was associated with a significantly better OS (HR = 0.68, 95% confidence interval [CI]: 0.57-0.83, p < 0.001, I2 = 0%, p for heterogeneity = 0.97). Subgroup analyses for M/MK stage II disease (HR = 0.63, 95% CI: 0.44-0.91, p = 0.01, I2 = 0%, p for heterogeneity = 0.80) and M/MK stage III disease (HR = 0.72, 95% CI: 0.55-0.95, p = 0.02, I2 = 0%, p for heterogeneity = 0.84) revealed similar results. PORT was not associated with an improved disease-free survival (HR = 0.96, 95% CI: 0.70-1.33, p = 0.83, I2 = 0%, p for heterogeneity = 0.72). CONCLUSIONS: Currently available evidence from observational studies suggests PORT for patients with completely resected M/MK stage II/III thymoma. A randomized trial is warranted.

DOI： 10.1016/j.jtho.2020.12.023

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Despite numerous studies on ABO blood group and risk of tuberculosis, no consensus has been reached. METHODS: We conducted a systematic review following the Meta-Analysis of Observational Studies in Epidemiology group statement. English language articles providing odds ratio data regarding tuberculosis risk among ABO groups were eligible. Least-squares approach random-model network and random-model pairwise meta-analyses were conducted. The protocol-specified primary outcome was tuberculosis risk among ABO groups in the form of odds ratios calculated via a network meta-analysis. RESULTS: We identified 28 studies with 30 populations comprising 15,664 patients with tuberculosis and 254,610 controls. Subjects with AB blood type had a higher risk of becoming infected with tuberculosis than those with blood type O (odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.14-1.38), A (OR = 1.25, 95% CI: 1.14-1.38), and B (OR = 1.22, 95% CI: 1.11-1.34). Pairwise comparison revealed that AB blood type was a risk factor for tuberculosis with OR = 1.23 (95% CI: 1.02-1.48) compared to other blood types. Region-based subgroup analyses suggested that the AB blood group was a substantial risk in Africa (OR = 1.78, 95% CI: 1.39-2.28) and India (OR = 1.48, 95% CI: 1.14-1.92). CONCLUSIONS: AB blood group is a risk factor for tuberculosis of a substantial magnitude in Africa and India.

DOI： 10.1016/j.ijid.2021.01.057

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記述言語：英語  

DOI： 10.1016/S1470-2045(21)00008-5

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記述言語：英語  

DOI： 10.1056/NEJMc2032432

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although the US government approved hydroxychloroquine (HCQ) and chloroquine (CQ) for hospitalized coronavirus disease 19 (COVID-19) patients, some studies denied efficacy of HCQ and CQ. We aimed to evaluate HCQ/CQ treatment for COVID-19. METHODS: Five databases were searched on April 15, 2020, without publication date restriction. We followed both Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology statement reporting recommendations. A random-model meta-analysis was conducted to pool odds ratio (OR) and hazard ratio (HR). The quality of evidence for each outcome and the final recommendation was assessed using the GRADE guidelines of the American College of Chest Physicians. RESULTS: We identified four randomized controlled trials (RCTs) and four observational studies with 2,063 COVID-19 cases. All-cause mortality was not affected by the administration of HCQ/CQ [OR: 1.05, 95% confidence interval (CI): 0.53-2.09, P=0.89]. No improvement of viral clearance was found neither by time-to-event analysis (HR: 1.19, 95% CI: 0.74-1.94, P=0.47) nor frequency on day 7 (OR: 1.47, 95% CI: 0.33-6.63, P=0.62). HCQ/CQ treatment increased the risk of the any adverse event with OR of 3.56 (95% CI: 1.62-7.83, P=0.002). CONCLUSIONS: HCQ/CQ failed to decrease the all-cause mortality (very low quality evidence) and did not improve viral clearance (low or very low quality evidence) but increased the risk of any adverse event (moderate quality evidence). Routine administration of HCQ/CQ for COVID-19 patients is not recommended (weak recommendation, Grade 2C).

DOI： 10.21037/jtd-20-2022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Community-acquired pneumonia is one of the most common diseases in elderly persons and usually results in a prolonged hospital stay. Discharge planning plays an important role in reducing the length of hospitalization. This study was designed to determine whether early screening for risk factors for delayed discharge could improve the quality of discharge planning. METHODS: This retrospective, observational study was conducted in two medical facilities from January 2016 to December 2018. Hospital A used a screening tool on admission (screening group): screening for risk factors for delayed discharge and initiating discharge planning immediately for those for whom it was applicable, and discharge planning in the stable phase for those for whom it was not applicable; and Hospital B initiated discharge planning without screening (usual group). Propensity score-matched pneumonia patients in the two groups were then compared. The primary outcome was length of hospital stay. RESULTS: A total of 648 patients were enrolled in this study. After adjusting for age, sex, aspiration, comorbidity, pneumonia severity index, and key person, 118 pairs underwent analysis. Length of stay was significantly different (20 days vs 13 days, p<0.001) between the groups. There were no differences in duration of antibiotic treatment, in-hospital mortality, and 30-day readmission (9 days vs 9 days, p=0.744; 10 (8.5%) vs 10 (8.5%), p=1.000; 10 (8.5%) vs 9 (7.6%), p=0.811, respectively). CONCLUSION: Early screening for delayed discharge improved the quality of discharge planning by reducing the length of stay in pneumonia patients.

DOI： 10.2147/CIA.S296390

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Immune checkpoint inhibitor (ICI)-related myositis is a rare, potentially fatal condition that warrants further studies. Its incidence, clinical features, and prognosis remain poorly understood. To address these gaps, we conducted a systematic review and meta-analysis to evaluate the risk of myositis associated with ICI for solid tumors by analyzing phase III randomized controlled trials of anti-programmed death-1/ligand-1 (PD-1/PD-L1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4). To complement this analysis with clinical data, we evaluated published ICI case reports along with cases from our institutional registry. This registry comprised 422 patients treated with ICIs alone or in combination from September 2014 to June 2021. The analysis revealed an incidence of ICI-related myositis in 6,838 patients in 18 randomized controlled trials of 0.38% (odds ratio 1.96; 95% confidence interval 1.02-3.75) for patients receiving ICIs compared with controls. Detailed analysis of 88 cases from the literature search and our registry showed that myositis induced by PD-1 inhibitors was more frequent than that induced by anti-CTLA-4 agents, revealing a clinically diverse trend including myasthenia gravis and myocarditis. Importantly, having ptosis at the time of onset was significantly associated with the development of concomitant myocarditis (odds ratio 3.81; 95% CI 1.48-9.83), which is associated with poor prognosis. Regarding treatment, most patients received glucocorticoids, and some received immunosuppressants. Our study revealed the incidence of ICI-mediated myositis and the clinical features of myocarditis, highlighting the need for recognition and early intervention.

DOI： 10.3389/fimmu.2021.803410

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Serum Krebs von den Lungen-6 (KL-6) measurement is widely used to assess disease activity or prognosis in patients with interstitial lung diseases (ILDs). However, the clinical differences between high and low serum KL-6 levels at the time of acute exacerbation (AE) of ILD are not well known. METHODS: Clinical parameters including age, sex, Charlson Comorbidity Index score (CCIS), blood biomarkers, high-resolution CT findings, and disease mortality were retrospectively compared between high and low KL-6 (cutoff value: 1000 U/mL) patients at the time of diagnosis of AE of ILDs. RESULTS: Thirty-eight high serum KL-6 and 57 low serum KL-6 patients were included. There was no significant difference in 6-month mortality between them (P = 0.685), whereas serum lactate dehydrogenase was a significant predictor of 6-month mortality in the high serum KL-6 patients (odds ratio (OR): 1.006; 95% confidence interval (CI): 1.003-1.009; P < 0.001), and CCIS (OR: 1.502; 95% CI: 1.242-1.838; P < 0.001) and sex (OR: 5.751; 95% CI: 1.121-105.163; P = 0.033) were significant predictors in low serum KL-6 patients. In addition, the incidences of congestive heart failure, symptomatic chronic pulmonary disease, cerebrovascular disease, and second metastatic solid tumours were significantly higher in nonsurvivors with low serum KL-6 than in other groups (P < 0.05). CONCLUSIONS: The clinical features in patients with AEs of ILDs may differ depending on the serum KL-6 level, and clinicopathological examination according to this subtyping guided by the serum KL-6 level is essential.

DOI： 10.1155/2021/9099802

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The purpose of this retrospective study was to clarify whether the presence of honeycombing on computed tomography (CT) can affect the prognosis of patients with acute exacerbations (AEs) of interstitial lung diseases (ILDs). METHODS: Clinical parameters including age, sex, Charlson Comorbidity Index Score (CCIS), blood biomarkers, and 3-month mortality were retrospectively compared between the CT honeycombing present and absent groups at the diagnosis of AEs of ILDs. RESULTS: Ninety-five patients who were on corticosteroid pulse therapy were assessed. Though log-rank tests showed that Kaplan-Meier survival curves of the high and low ground-glass opacity (GGO) score groups differed significantly in 3-month mortality in patients with AEs of idiopathic ILDs (P = 0.007) and overall patients (P = 0.045), there was no significant difference between the CT honeycombing present and absent groups in patients with AEs of idiopathic ILDs (P = 0.472) and AEs of secondary ILDs (P = 0.905), as well as of overall patients (P = 0.600). In addition, whereas CCIS (OR, 1.436; 95% CI, 1.156-1.842; P < 0.001) was a significant predictor of 3-month mortality in the CT honeycombing absent group, serum LDH (OR, 1.005; 95% CI, 1.002-1.007; P = 0.001) was a significant predictor in the CT honeycombing present group. CONCLUSIONS: The clinical features of patients with or without honeycombing may differ due to the difference in prognostic factors, but these groups were found to have similar prognoses 3 months after AE onset, and clinicopathological examinations according to these groups are essential.

DOI： 10.1155/2021/7456315

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pneumonia is a common disease among the aging population in Japan. Hence, it is important to elucidate the risks related to pneumonia mortality. Since Streptococcus pneumoniae is the most commonly observed pathogen, pneumococcal vaccination is recommended to older adults. Therefore, this study aimed to clarify the clinical features of pneumonia, including the status of pneumococcal vaccination, in hospitalized older adult patients in Japan. METHODS: This single-centered retrospective study was conducted by reviewing the medical records of all patients with acute pneumonia at Fujisawa City Hospital in Japan from April 2018 to March 2019. Patients were divided into two groups based on their history of pneumococcal vaccination. The primary endpoint was in-hospital mortality, while the secondary endpoint was risk factors associated with mortality. RESULTS: We included 93 patients with pneumonia in this retrospective study. Although the mortality rate was higher in the vaccinated group (15.8%) than in the unvaccinated group (9.1%), vaccination status was not identified as a significant risk factor for mortality after multivariable logistic regression (odds ratio: 2.71; 95% confidence interval: 0.667-11.02; p=0.16). In addition, the A-DROP score was identified as an independent risk factor (odds ratio: 2.64; 95% confidence interval: 1.22-5.72; p=0.008). CONCLUSIONS: Our study suggested that the A-DROP score is a risk factor of mortality for pneumonia in older adults. In addition, pneumococcal vaccination history was related to increased mortality; however, the influence of the vaccination remains unclear because of the small sample size.

DOI： 10.1155/2021/5644824

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記述言語：英語  

DOI： 10.1016/S1470-2045(20)30613-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 77-year-old man who had a persistent productive cough for one month was admitted to our hospital. Chest computed tomography (CT) revealed subpleural nodular opacities, irregular pleural thickening with bilateral basal predominance, and a small right pleural effusion. Aspirated fluid was exudative and had the appearance of chylothorax without malignant cells. Surgical lung biopsy specimen showed focal proliferation of neoplastic epithelial cells with lepidic-predominant pattern and abundant mucus in the alveolar spaces, consistent with invasive mucinous adenocarcinoma (IMA). The results of PD-L1 expression and the EGFR, ALK, ROS1, and BRAF mutation status analyzed by next generation sequencer were all negative. IMA should be considered in the differential diagnosis of subpleural micronodular opacities accompanied by pleural effusion (chylothorax) on chest CT. KEY POINTS: Significant findings of the study This case showed subpleural micronodular opacities and chylothorax as unusual chest computed tomography (CT) patterns for invasive mucinous adenocarcinoma (IMA). What this study adds Invasive mucinous adenocarcinoma (IMA) should be considered in the differential diagnosis of subpleural micronodular opacities accompanied by pleural effusion on chest CT.

DOI： 10.1111/1759-7714.13665

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Advanced non-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. However, outcomes have gradually improved after the introduction of novel immunotherapies, including immune checkpoint inhibitors (ICIs). Although programmed death-ligand 1 (PD-L1) expression in tumor tissues is a known biomarker for guiding ICI treatment of NSCLC, challenges such as difficulty of liquid biopsy and heterogeneous results during treatment persist. This study evaluated the potential of miR200b as a surrogate biomarker for PD-L1 expression. METHODS: We used the human lung cancer cell lines H226, H460, H520, A549, and H1975. miR200b expression in blood and bronchoscopy specimens of NSCLC patients was evaluated using reverse-transcription-quantitative PCR. Using flow cytometry, PD-L1 expression in vitro, as well as in tumor tissues, was evaluated after transfection with a mimic miR200b or siRNA. RESULTS: miR200b expression negatively correlated with PD-L1 expression in all cell lines. The induction or knockdown of miR200b also altered PD-L1 expression in vitro. The patient group with a PD-L1 tumor proportion score ≥ 50% had significantly lower miR200b expression in the bronchoscopy specimens (P = 0.025) and serum-derived exosomes (P = 0.022) than that with PD-L1 tumor proportion score < 50%. CONCLUSIONS: miR200b can regulate PD-L1 expression in lung cancer cells, and miR200b expression in clinical specimens negatively correlated with PD-L1 expression. Thus, miR200b may be a useful surrogate biomarker for PD-L1 expression in lung cancer patients. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: High PD-L1 expression was linked to low miR200b expression, whereas low PD-L1 expression was linked to high miR200b expression in human lung cancer patients. Thus, miR200b overexpression or silencing can control PD-L1 expression in cancer cells. What this study adds We demonstrated the potential of miR200b as a surrogate biomarker for PD-L1 expression in lung cancer patients.

DOI： 10.1111/1759-7714.13653

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

DOI： 10.1038/s42003-020-01185-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: As most patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) develop progressive disease after treatment with osimertinib, it is important to develop more effective treatment options. Afatinib has been shown to be more effective in in vitro studies than osimertinib when used in cancer cell lines containing some specific EGFR mutations. Therefore, afatinib may be an effective solution, especially when used in combination with an anti-VEGF agent such as bevacizumab. METHODS: A phase II multicenter, open-label, single-arm trial has been initiated to evaluate the efficacy and safety of afatinib and bevacizumab combination as salvage therapy for EGFR-mutated lung cancer in patients previously treated with osimertinib. The primary endpoint will be the objective response rate (ORR) and secondary endpoints are progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). DISCUSSION: A previous study indicated that afatinib inhibits lung cancer cells with specific EGFR mutations more effectively than other EGFR-TKIs such as osimertinib. Therefore, we expect that combination therapy using afatinib and bevacizumab will be effective in patients previously treated with osimertinib (registration no. jRCTs031190077).

DOI： 10.1111/1759-7714.13503

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Whether hazard ratio (HR) of progression-free survival (HRpfs), odds ratio (OR) of response rate (ORrr), OR of disease control rate (ORdcr), and OR of 1-year overall survival (ORos1y) used for extensive-disease small-cell lung cancer (ED-SCLC) correlate with HR of overall survival (HRos) at a randomized-trial level, especially for a trial that evaluates molecular-targeted therapy (MTT) or immune-checkpoint inhibitor (ICI), is unclear. METHODS: We included an individually randomized controlled trial (RCT) comparing two regimens as the first-line treatment for chemo-naive ED-SCLC, which have been reported in English-language since 2000. A weighted Spearman's rank correlation coefficient (r) was evaluated. RESULTS: We finally found 42 eligible articles consisted of 11,478 cases. Estimated r with HRos were as followings: HRpfs (29 trial, 8,573 cases, r=0.87), ORrr (39 trials, 11,030 cases, r=0.47), ORdcr (29 trials, 7,799 cases, r=0.48), and ORos1y (40 trials, 11,250 cases, r=0.69). Phase III subgroup (16 trials, 7,079 cases) yielded an excellent r between HRpfs and HRos of 0.96. ORdcr presented the best correlation with HRos for phase II trial subgroup (r=-0.64); however, this result was mainly calculated from MTT trials. HRpfs may overestimate the efficacy of MMT in a phase II trial. ORrr and ORdcr might undervalue the efficacy of ICI even in a phase III trial. CONCLUSIONS: HRpfs can be a good surrogate of HRos, especially in a phase III trial. Depending on a single outcome in a randomized phase II trial may result in unneeded phase III trial or inappropriate abandonment of the regimen.

DOI： 10.21037/tlcr-20-377

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This article describes a dataset for a meta-analysis that aimed to investigate the effects of treatment on the neurometabolite status in patients with schizophrenia (DOI of original article: https://doi.org/10.1016/j.schres.2020.03.069[1]). The data search was performed with MEDLINE, Embase, and PsycINFO. The neurometabolites investigated include glutamate, glutamine, glutamate + glutamine, gamma-aminobutyric acid, N-acetylaspartate, and myo-inositol, and the regions of interest (ROIs) include the frontal cortex, temporal cortex, parieto-occipital cortex, thalamus, basal ganglia, and hippocampus. The meta-analysis was conducted with a random-effects model, and the use of the standardized mean difference method between pre- and post-treatment of subjects for neurometabolites in each ROI of three patient groups or more. The dataset covers raw data of 39 patient groups (773 patients with schizophrenia at follow-up) with neurometabolite levels measured by magnetic resonance spectroscopy both before and after treatment. Furthermore, it contains details of clinical characteristics and treatment types for each group. Therefore, the data would be useful for a reinvestigation of treatment effects on the neurometabolite status from diverse points of view, as well as for the development of future treatment strategies for psychiatric diseases.

DOI： 10.1016/j.dib.2020.105862

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記述言語：英語  

See related Reply

DOI： 10.1111/resp.13885

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although there is growing evidence of alterations in the neurometabolite status associated with the pathophysiology of schizophrenia, how treatments influence these metabolite levels in patients with schizophrenia remains poorly studied. METHODS: We conducted a literature search using Embase, Medline, and PsycINFO to identify proton magnetic resonance spectroscopy studies that compared neurometabolite levels before and after treatment in patients with schizophrenia. Six neurometabolites (glutamate, glutamine, glutamate + glutamine, gamma-aminobutyric acid, N-acetylaspartate, myo-inositol) and six regions of interest (frontal cortex, temporal cortex, parieto-occipital cortex, thalamus, basal ganglia, hippocampus) were investigated. RESULTS: Thirty-two studies (n = 773 at follow-up) were included in our meta-analysis. Our results demonstrated that the frontal glutamate + glutamine level was significantly decreased (14 groups; n = 292 at follow-up; effect size = -0.35, P = 0.0003; I2 = 22%) and the thalamic N-acetylaspartate level was significantly increased (7 groups; n = 184 at follow-up; effect size = 0.47, P < 0.00001; I2 = 0%) after treatment in schizophrenia patients. No significant associations were found between neurometabolite changes and age, gender, duration of illness, duration of treatment, or baseline symptom severity. CONCLUSIONS: The current results suggest that glutamatergic neurometabolite levels in the frontal cortex and neuronal integrity in the thalamus in schizophrenia might be modified following treatment.

DOI： 10.1016/j.schres.2020.03.069

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記述言語：英語  

DOI： 10.1164/rccm.202003-0494LE

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

An exciting debate has emerged whether bacille Calmette-Guérin (BCG) vaccination is effective for the coronavirus disease 2019 (COVID-19) pandemic. Some advocated that BCG-vaccinated people are less suffered from the virus because BCG vaccination is recommendedin COVID-19 high burden countries. However, the others objected because this seemingly attractive relationship is explainable with confounding factors. In a multiple regression with 171 countries adjusting socioeconomical and climatic covariates, countries with current universal pediatric BCG policy were associated with 30-fold (95% confidence interval, 17-52) decrease of COVID-19 mortality per population compared to countries without the policy.

DOI： 10.7774/cevr.2020.9.2.179

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Our goal was to organize the data from randomized controlled trials that evaluated first-line chemotherapy for chemo-naïve extensive disease small-cell lung cancer (ED-SCLC). METHODS: The protocol following PRISMA methodology was submitted as PROSPERO 154049. We included individually randomized trials comparing two or more chemotherapy regimens as the first-line treatment for chemo-naïve ED-SCLC regardless of the age, sex, performance status, co-morbidities, and organ functions written in the English language since 2000. Molecular targeted agents and immune checkpoint inhibitors were considered chemotherapy along with cytotoxic medications. We pooled the logarithm of hazard ratio (HR) and its standard error using the frequentist weighted least squares approach random-model network meta-analysis. RESULTS: A total of 46 eligible trials that involved 11,987 patients were included. The primary endpoint, HR of overall survival (OS, HRos) of the selected comparisons was as follows: carboplatin+amrubicin (HRos 0.56, 95% confidence interval (CI) 0.33-0.96), carboplatin+etoposide+atezolizumab (HRos 0.70, 95% CI 0.53-0.92), and carboplatin+irinotecan (HRos 0.73, 95% CI 0.58-0.91) were compared with carboplatin+etoposide. The carboplatin+etoposide+atezolizumab regimen was compared with carboplatin+irinotecan (HRos 0.97, 95% CI 0.68-1.37) and cisplatin+irinotecan regimen (HRos 0.87, 95% CI 0.58-1.31). "Selective carboplatin or cisplatin (CBDCA/CDDP)"+etoposide+durvalumab was compared with CBDCA/CDDP+etoposide (HRos 0.73, 95% CI 0.59-0.91). Platinum+etoposide+durvalumab was compared with platinum+irinotecan (HRos 0.88, 95% CI 0.67-1.15). Cumulative meta-analysis suggested that platinum+irinotecan was associated with better OS than platinum+etoposide as of 2010 through 40 out of 46 trials in our review that used platinum+etoposide as a reference regimen. CONCLUSION: Patients treated with carboplatin+amrubicin, carboplatin+etoposide+atezolizumab, CBDCA/CDDP+etoposide+durvalumab, and platinum+irinotecan showed better HRos than those treated with platinum+etoposide, one of the standard regimens.

DOI： 10.1177/1758835920965841

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Among senior community-acquired pneumonia (CAP) survivors, functional status after hospitalization is often decreased. This study investigated the change of functional status affecting delayed discharge. PATIENTS AND METHODS: This retrospective observational study was conducted in two medical facilities from January 2016 to December 2018. Hospitalized CAP patients >64 years old were divided into two groups: an early group discharged ≤1 week after ending antibiotic treatment and a delayed group discharged >1 week after ending antibiotic treatment. The primary outcome was decline in functional status. RESULTS: The early group comprised 170 patients and the delayed group comprised 155 patients (median age: 78 vs 82 years; p = 0.007). Distribution of the causative microorganisms and initial prescription of antibiotics showed no significant differences in the two groups (p=0.38; p=0.83, respectively) More patients showed decline in functional status in the delayed group than the early group (16 (9.4%) vs 49 (31.6%), p<0.001), even if rehabilitation was more frequently conducted (77 (45.3%) vs 118 (76.1%); p<0.001). Higher medical expenses were observed in the delayed group ($8631 vs $3817, respectively; p<0.001). Multivariable regression analysis of factors contributing delayed discharge revealed that decreased functional status, pneumonia severity index (PSI) categories, rehabilitation enrolled, aspiration and age were independently associated with delayed discharge (odds ratio 4.31, 95% confidence interval (CI) 2.32-7.98; 2.34, 95% CI 1.43-3.82; 15.96, 95% CI 4.56-55.82 (PSI V vs II); 2.48, 95% CI 1.11-5.98; and 1.03, 95% CI 1.01-1.06; respectively). CONCLUSION: Functional status decline was independently associated with extended hospitalization.

DOI： 10.2147/CIA.S267349

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.

DOI： 10.1371/journal.pone.0233464

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

IMPORTANCE: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. OBJECTIVE: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. EVIDENCE REVIEW: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. FINDINGS: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). CONCLUSIONS AND RELEVANCE: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

DOI： 10.1001/jamaoncol.2019.2996

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記述言語：英語  

DOI： 10.1016/j.alit.2019.03.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Alterations in glutamatergic neurotransmission are implicated in the pathophysiology of depression, and the glutamatergic system represents a treatment target for depression. To summarize the nature of glutamatergic alterations in patients with depression, we conducted a meta-analysis of proton magnetic resonance (1H-MRS) spectroscopy studies examining levels of glutamate. We used the search terms: depress* AND (MRS OR "magnetic resonance spectroscopy"). The search was performed with MEDLINE, Embase, and PsycINFO. The inclusion criteria were 1H-MRS studies comparing levels of glutamate + glutamine (Glx), glutamate, or glutamine between patients with depression and healthy controls. Standardized mean differences (SMD) were calculated to assess group differences in the levels of glutamatergic neurometabolites. Forty-nine studies met the eligibility criteria, which included 1180 patients and 1066 healthy controls. There were significant decreases in Glx within the medial frontal cortex (SMD = -0.38; 95% CI, -0.69 to -0.07) in patients with depression compared with controls. Subanalyses revealed that there was a significant decrease in Glx in the medial frontal cortex in medicated patients with depression (SMD = -0.50; 95% CI, -0.80 to -0.20), but not in unmedicated patients (SMD = -0.27; 95% CI, -0.76 to 0.21) compared with controls. Overall, decreased levels of glutamatergic metabolites in the medial frontal cortex are linked with the pathophysiology of depression. These findings are in line with the hypothesis that depression may be associated with abnormal glutamatergic neurotransmission.

DOI： 10.1038/s41380-018-0252-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Community-acquired pneumonia (CAP) due to Legionella has a high mortality rate in patients who do not receive adequate antibiotic therapy. In a previous study, we developed a simple Legionella Score to distinguish patients with Legionella and non-Legionella pneumonia based on clinical information at diagnosis. In the present study, we validated this Legionella Score for the presumptive diagnosis of Legionella CAP. METHODS: This validation cohort included 109 patients with Legionella CAP and 683 patients with non-Legionella CAP. The Legionella Score includes six parameters by assigning one point for each of the following items: being male, absence of cough, dyspnea, C-reactive protein (CRP) ≥ 18 mg/dL, lactate dehydrogenase (LDH) ≥ 260 U/L, and sodium < 134 mmol/L. RESULTS: When the Legionella CAP and non-Legionella CAP were compared by univariate analysis, most of the evaluated symptoms and laboratory test results differed substantially. The six parameters that were used for the Legionella Score also indicated clear differences between the Legionella and non-Legionella CAP. All Legionella patients had a score of 2 points or higher. The median Legionella Scores were 4 in the Legionella CAP cases and 2 in the non-Legionella CAP cases. A receiver operating characteristics curve showed that the area under the curve was 0.93. The proposed best cutoff, total score ≥3, had sensitivity of 93% and specificity of 75%. CONCLUSION: Our Legionella Score was shown to have good diagnostic ability with a positive likelihood of 3.7 and a negative likelihood of 0.10.

DOI： 10.1016/j.jiac.2019.03.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recent reports have indicated that the objective response rate (ORR) and progression-free survival (PFS) cannot serve as surrogates for predicting overall survival (OS) in immune checkpoint inhibitor (ICI) trials. We performed a trial-based correlative analysis to evaluate conventional endpoints as surrogates for predicting OS in ICI-treated non-small cell lung cancer (NSCLC) patients. METHODS: A systematic electronic literature search for randomized clinical trials using ICI monotherapies for NSCLC revealed 7 trials. The correlative analysis to clarify the correlations among clinical outcomes used a weighted Spearman rank correlation coefficient (wS), weighted Pearson correlation coefficient (wP), and weighted linear regression model (wL) in all patients and patients with high PD-L1 expression. RESULTS: The correlative analysis of the total population revealed that the odds ratio of the ORR (OR-ORR) and the hazard ratio of OS (HR-OS) were strongly correlated with the hazard ratio of PFS (HR-PFS) (R for wP and wS, R2 for wL; -0.869, -0.968, 0.756 between OR-ORR and HR-PFS; 0.923, 0.959, 0.851 between HR-PFS and HR-OS). The strongest correlation was observed between one-year overall survival (1y-OS) and the HR-OS (R for wP and wS, R2 for wL; 0.985, 1.000, R2: 0.968). In those with high PD-L1 expression, the ORR and PFS were strongly associated with OS (R2: 0.842 between ORR and OS; 0.771 between PFS and OS). CONCLUSIONS: The OR-ORR and HR-PFS could serve as surrogate endpoints for predicting the HR-OS in randomized trials using ICIs for NSCLC, while the ORR and PFS could be useful endpoints for predicting OS in trials with patient selection based on high PD-L1 expression.

DOI： 10.1016/j.lungcan.2018.12.023

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: We investigated a Turkish family with multiple patients presenting with familial Mediterranean fever (FMF) and Behçet's disease (BD)-like manifestations. The index case and the two daughters with Behçet-like disease, were previously found to have a TNFAIP3 frameshift mutation. The high number of affected cases in this expanded family could be consistent with a dominantly inherited inflammatory disease, although some individuals had clinical features more consistent with recessively inherited FMF. We sequenced DNA from members of this family to determine whether the TNFAIP3 frameshift mutation and/or MEFV variants could explain this autoinflammatory disease pedigree. METHODS: Patients were clinically diagnosed to have FMF or BD. Sanger sequence targeting TNFAIP3 exon 5 and MEFV exon 10 was carried out. RESULTS: The symptomatic mother of the index case and her affected maternal uncle had compound heterozygous FMF-associated MEFV mutations, p.Met680Ile and p.Arg761His. Two affected daughters of the maternal uncle also had compound heterozygous FMF-associated mutations, p.Met680Ile and p.Val726Ala. The index case and her two affected daughters had a TNFAIP3 frameshift mutation (c.799delG; p.Pro268Leufs*19), which is consistent with their HA20 diagnosis, and also carried a heterozygous MEFV p.Arg761His mutation. CONCLUSIONS: Autoinflammatory disease manifestations in a Turkish family with multiple affected cases could be explained by co-inheritance of pathogenic MEFV variants and a heterozygous HA20-associated mutation. FMF-associated p.Arg761His allele carried with the loss of function TNFAIP3 mutation by all three HA20 patients may contribute to their autoinflammatory phenotype and could also be responsible for their favourable response to colchicine.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

IMPORTANCE: The increasing burden due to cancer and other noncommunicable diseases poses a threat to human development, which has resulted in global political commitments reflected in the Sustainable Development Goals as well as the World Health Organization (WHO) Global Action Plan on Non-Communicable Diseases. To determine if these commitments have resulted in improved cancer control, quantitative assessments of the cancer burden are required. OBJECTIVE: To assess the burden for 29 cancer groups over time to provide a framework for policy discussion, resource allocation, and research focus. EVIDENCE REVIEW: Cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) were evaluated for 195 countries and territories by age and sex using the Global Burden of Disease study estimation methods. Levels and trends were analyzed over time, as well as by the Sociodemographic Index (SDI). Changes in incident cases were categorized by changes due to epidemiological vs demographic transition. FINDINGS: In 2016, there were 17.2 million cancer cases worldwide and 8.9 million deaths. Cancer cases increased by 28% between 2006 and 2016. The smallest increase was seen in high SDI countries. Globally, population aging contributed 17%; population growth, 12%; and changes in age-specific rates, -1% to this change. The most common incident cancer globally for men was prostate cancer (1.4 million cases). The leading cause of cancer deaths and DALYs was tracheal, bronchus, and lung cancer (1.2 million deaths and 25.4 million DALYs). For women, the most common incident cancer and the leading cause of cancer deaths and DALYs was breast cancer (1.7 million incident cases, 535 000 deaths, and 14.9 million DALYs). In 2016, cancer caused 213.2 million DALYs globally for both sexes combined. Between 2006 and 2016, the average annual age-standardized incidence rates for all cancers combined increased in 130 of 195 countries or territories, and the average annual age-standardized death rates decreased within that timeframe in 143 of 195 countries or territories. CONCLUSIONS AND RELEVANCE: Large disparities exist between countries in cancer incidence, deaths, and associated disability. Scaling up cancer prevention and ensuring universal access to cancer care are required for health equity and to fulfill the global commitments for noncommunicable disease and cancer control.

DOI： 10.1001/jamaoncol.2018.2706

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hyaluronic acid (HA) is present in the connective tissues of the skin and decreases with age. HA fillers are popular as facial rejuvenation treatments. They are generally considered safe; however, complications, such as cutaneous necrosis and blindness due to vascular embolism, sometimes occur. Because vascular embolisms are likely associated with the deep placement of HA fillers, a strategy that involves injection into superficial regions (the conventional method) is commonly used to reduce risks. However, deep injections to achieve revolumization are becoming common, even in high-risk areas for intravascular infusion. We aimed to study the usefulness of the ultrasonography-guided cannula method for preventing intravascular infusion of HA fillers. An HA filler was injected into the region just under the dermis on the left side of the face of a 38-year-old man using the conventional method, and another HA filler was injected into the periosteum on the right side using the ultrasonography-guided cannula method. The skin blood flow on both sides was compared using laser speckle flowgraphy (LSFG). The ultrasonography-guided method was successful in detecting the cannula and the blood vessel, and the HA filler was safely injected into a deep region. Using LSFG, a difference in skin blood flow between the 2 methods was detected. The ultrasonography-guided cannula method was effective in aiding the safe injection of an HA filler in a deep high-risk area and maintained skin blood flow. LSFG may be adopted to evaluate skin blood flow after HA filler injections.

DOI： 10.1097/GOX.0000000000001776

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記述言語：英語  

DOI： 10.1684/ejd.2017.3106

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. METHODS: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. MAIN OUTCOMES: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. FINDINGS: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. CONCLUSIONS: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.

DOI： 10.1016/j.jamda.2017.09.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

IMPORTANCE: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. EVIDENCE REVIEW: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. FINDINGS: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. CONCLUSION AND RELEVANCE: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

DOI： 10.1001/jamaoncol.2016.5688

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.resinv.2015.09.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Topotecan is the most reliable chemotherapy regimen for relapsed small-cell lung carcinoma (SCLC). The efficacy and adverse effects of topotecan as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for 6-month over-all survival (OS) rate, 1-year OS rate, objective responses, and/or adverse effects of single agent topotecan as a second line chemotherapy for SCLC, written in English language as a full article. Any topotecan regimen were allowed. Binary data were meta-analyzed with the random-model generic inverse variance method. We included 14 articles consisted of 1347 patients. Pooled values were estimated as follows. <Refractory relapse> Six-month OS rate: 37% (95% CI: 28-46%). One-year OS rate: 9% (95% CI: 5-13%). Response rate: 5% (95% CI: 1-8%). <Sensitive relapse> Six-month OS rate: 57% (95% CI: 50-64%). One-year OS rate: 27% (95% CI: 22-32%). Response rate: 17% (95% CI: 11-23%). <Adverse effect> Grade III/IV neutropenia 69% (95% CI: 58-80%). Grade III/IV thrombopenia 41% (95% CI: 34-48%). Grade III/IV anemia 24% (95% CI: 17-30%). Non-hematorogical events were rare. Chemotherapy-related death 2% (95% CI: 1-3%). In conclusion, Topotecan provided a possibly promising outcome for sensitive-relapse SCLC and poor outcome for refractory relapse SCLC. Adverse events were mainly hematological.

DOI： 10.1038/srep15437

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. Four investigators independently searched for eligible articles through PubMed, Embase, and Cochrane databases. Random model was used. The heterogeneity among original studies and subgroups was evaluated with the I(2) statistics. Of 54 articles that met the preliminary criteria, we found 10 eligible RCTs comprising 1780 cases. Our analyses revealed following pooled values by corticosteroids. OR for all-cause death: 0.80 (95% confidence interval (95% CI) 0.53-1.21) from all studies; 0.41 (95% CI 0.19-0.90) from severe-case subgroup; 0.21 (95% CI 0.0-0.74) from intensive care unit (ICU) subgroup. Length of ICU stay: -1.30 days (95% CI (-3.04)-0.44). Length of hospital stay: -0.98 days (95% CI (-1.26)-(-0.71)). Length to clinical stability: -1.16 days (95% CI (-1.73)-(-0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies.

DOI： 10.1038/srep14061

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A case-control study often compares the prevalence of a specific disease among persons with normal alleles and persons with variant alleles, which generates an odds ratio (OR). The most common type of allele variation, single-nucleotide polymorphism, consists of a major allele (M) and a minor allele (m). Thus, the genotype can be a major allele homozygote (MM), a heterozygote (Mm) or a minor allele homozygote (mm). Odds are given for each genotype, and a pair of odds generates an OR. Summarizing data using two-by-two contingency is the simplest method of estimating an OR. Thus, dominant, multiplicative, recessive, and over-dominant models are often used. Traditionally, researchers used to calculate ORs using many models and then select the best model from among these calculated ORs. This may cause problems due to multiple comparisons. Therefore, we should choose the best model before calculating the OR for each model. In this article, we will discuss how to choose the best model among many subject-level models when evaluating the impact of the MM/Mm/mm genotype on the disease prevalence.

DOI： 10.1016/j.mgene.2015.04.003

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記述言語：英語  

DOI： 10.1016/j.resinv.2015.01.006

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In the 1950s, high doses (40-70 mg/kg/day) of pyrazinamide were reported to cause drug-induced liver injury (DILI). It remains unclear whether adding pyrazinamide (Z) at the currently accepted low dose (20-25 mg/kg/day) to a regimen of isoniazid (H), rifampicin (R), and ethambutol (E) increases the risk of DILI. METHOD: We reviewed adult patients admitted for smear-positive tuberculosis who were treated with a daily HRE or HRZE regimen. A Cox model was used to analyze the impact of pyrazinamide on the occurrence of DILI. RESULTS: We reviewed 195 patients (123 men [63%], 72 women [37%], average age 65 ± 19 years, 65 HRE patients [33%], 130 HRZE patients [67%]). The incidence of DILI in the first two months was 15% (29/195). The HRZE regimen was not associated with DILI (hazard ratio 0.55, P = 0.263). CONCLUSION: Addition of low-dose (20-25 mg/kg/day) pyrazinamide to the HRE regimen does not appeared to be associated with increased DILI incidence during the first two months of treatment.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVE: Genetic susceptibility for development of chronic obstructive pulmonary disease (COPD) is under intensive investigation. Among the three alleles of vitamin D binding protein, or group-specific (GC) components, some have suggested that having GC-1F and GC-2 alleles was associated with a risk of COPD. Although previous studies have shown considerable variance, no meta-analysis has been conducted. METHODS: Through four databases, two independent investigators searched for case-control studies providing sufficient data to calculate odds ratios by the vitamin D binding protein allele variant and genotype variant for a case of COPD. Studies whose control did not satisfy the Hardy-Weinberg equilibrium (Chi-square P ≥ 0.05) were excluded. We used a fixed-model to estimate the pooled odds ratio at both allele and genotype level. RESULTS: Of 141 candidate studies, six were included. We analysed 1712 subjects, consisting of 466 Asians, 1246 Caucasians, 531 COPD cases and 1181 non-COPD controls. The prevalence of each allele among the 1181 controls was as follows: GC-1F 14.0%, GC-1S 53.8% and GC-2 31.9%. When compared to GC-1S, the GC-1F allele and GC-2 allele were associated with COPD risk with pooled odds ratios of 1.44 (95% CI 1.14-1.83, P = 0.002) and 0.83 (95% CI 0.69-0.996, P = 0.045), respectively. When compared to the 1S-1S genotype, the 1F-1F genotype was a risk factor of COPD with pooled odds ratio of 2.64 (95% CI 1.29-5.39, P = 0.008). CONCLUSION: The GC-1F allele of the vitamin D binding protein was a risk for COPD in recessive mode.

DOI： 10.1111/resp.12448

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Once-daily dual-bronchodilator therapy with combined indacaterol and glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149, was first approved in 2013 in Japan and Europe. As of November 2014, more than 40 countries had approved this medication except for the USA. This is the first dual bronchodilator in one device. Now, the Breezhaler is the only device that can provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting beta agonist (indacaterol), and a combination of the two medications (QVA149). The choice among the three medications allows a patient to use the same inhalation device even when the regimen is changed from single-bronchodilator therapy to dual-bronchodilator therapy. In addition, the quick bronchodilation effect and once-daily administration can improve patient adherence to medical treatment for chronic obstructive pulmonary disease (COPD). To our knowledge, as of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14 randomized controlled trials. The 14 trials generally showed good safety profiles, and there were better or not-inferior bronchodilator effects of QVA149 when compared with placebo, or other inhaled medication. According to the Japanese Respiratory Society guidelines, QVA149 is a combination of the two first-line bronchodilators. Our meta-analysis indicated that QVA149 is superior to the salmeterol-fluticasone combination to treat COPD in respect of the frequency of adverse effects, exacerbation, pneumonia, and improvement of trough forced expiratory volume in 1 second (FEV1). Thus, we believe that QVA149 can be a key medication for COPD treatments.

DOI： 10.2147/COPD.S56067

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Oral corticosteroids were used to control stable chronic obstructive pulmonary disease (COPD) decades ago. However, recent guidelines do not recommend long-term oral corticosteroids (LTOC) use for stable COPD patients, partly because it causes side-effects such as respiratory muscle deterioration and immunosuppression. Nonetheless, the impact of LTOC on life prognosis for stable COPD patients has not been clarified. METHODS: We used the data of patients randomized to non-surgery treatment in the National Emphysema Treatment Trial. Severe and very severe stable COPD patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in the United States and randomized during 1998-2002. Patients were followed-up for at least five years. Hazard ratios for death by LTOC were estimated by three models using Cox proportional hazard analysis and propensity score matching. RESULTS: The pre-matching cohort comprised 444 patients (prescription of LTOC: 23.0%. Age: 66.6 ± 5.4 year old. Female: 35.6%. Percent predicted forced expiratory volume in one second: 27.0 ± 7.1%. Mortality during follow-up: 67.1%). Hazard ratio using a multiple-variable Cox model in the pre-matching cohort was 1.54 (P = 0.001). Propensity score matching was conducted with 26 parameters (C-statics: 0.73). The propensity-matched cohort comprised of 65 LTOC(+) cases and 195 LTOC(-) cases (prescription of LTOC: 25.0%. Age: 66.5 ± 5.3 year old. Female: 35.4%. Percent predicted forced expiratory volume in one second: 26.1 ± 6.8%. Mortality during follow-up: 71.3%). No parameters differed between cohorts. The hazard ratio using a single-variable Cox model in the propensity-score-matched cohort was 1.50 (P = 0.013). The hazard ratio using a multiple-variable Cox model in the propensity-score-matched cohort was 1.73 (P = 0.001). CONCLUSIONS: LTOC may increase the mortality of stable severe and very severe COPD patients.

DOI： 10.1186/1465-9921-15-37

PubMed

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記述言語：英語  

DOI： 10.4187/respcare.02890

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The global incidence of tuberculosis peaked around the year 2003 and is currently declining gradually. However, the worldwide incidence of new tuberculosis cases is still estimated to be 8.8 million/year, with 1.5 million deaths occurring per year. Considering that previous studies have determined the risk factors for death due to tuberculosis, we aimed at reviewing the literature to collectively evaluate these risk factors. According our literature review of 12 articles published in English language and 7 articles published in Japanese, the risk factors for death due to tuberculosis are age, human immunodeficiency virus (HIV) co-infection, multi-drug resistant tuberculosis (MDR-TB), malnutrition, low activities of daily living, co-morbidities, unemployment, and drug injection. We developed a scoring system to calculate the Tuberculosis Prognostic Score using 4 risk factors, namely, age, serum albumin level, oxygen requirement, and activities of daily living, after assessing several cohorts in Japan, in which HIV co-infection and MDR-TB are rare and their associations with mortality due to tuberculosis patients are unclear. This scoring system was successfully able to estimate life prognosis of inpatients with newly diagnosed, smear-positive, lung tuberculosis without MDR-TB and/or HIV virus co-infection.

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In Japan, tuberculosis (TB) patients aged over 80 years are usually treated with a regimen not including pyrazinamide (PZA) because of the risk of drug-induced hepatitis. PURPOSES: The purpose of this study was to investigate the occurrence of drug-induced hepatitis in TB patients over 80 years of age, who are treated with a regimen including PZA, and compare the findings with those of younger patients. [Methods] Thirty-six patients with pulmonary tuberculosis, who were admitted to Yokohama City University Hospital between June 2011 and March 2012 were included. They were treated with isoniazid, rifampicin, ethambutol, and PZA and had their liver function assessed once a week for 2 months. RESULTS: Hepatitis occurred in 4 of 28 (14.3%) patients aged under 80 years and in 1 of 8 (12.5%) patients aged over 80 years. CONCLUSION: There was no difference in the frequency of drug-induced hepatitis between patients aged under and over 80 years. We conclude that elderly patients aged over 80 years should be treated with a short course regimen that includes PZA.

PubMed

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総ページ数：23,235p   記述言語：日本語  

CiNii Books

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総ページ数：ix, 120p   記述言語：日本語  

CiNii Books

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総ページ数：xxxii, 279p   記述言語：日本語  

CiNii Books

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総ページ数：xx, 218p   記述言語：日本語  

CiNii Books

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その他リンク： https://webview.isho.jp/book/detail/abs/10.18916/9784771905672

総ページ数：xix, 175p   記述言語：日本語  

CiNii Books

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記述言語：英語   出版者・発行元：(一社)日本リウマチ学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

Web of Science

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記述言語：英語   出版者・発行元：Elsevier B.V.  

DOI： 10.1016/j.resinv.2015.09.006

Scopus

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：John Wiley and Sons Ltd  

DOI： 10.1002/14651858.CD012066

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

Web of Science

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記述言語：英語  

DOI： 10.1038/srep15437

Web of Science

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記述言語：英語   出版者・発行元：Elsevier B.V.  

DOI： 10.1016/j.mgene.2015.04.003

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等  

DOI： 10.1038/srep14061

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）   出版者・発行元：Elsevier B.V.  

DOI： 10.1016/j.resinv.2015.01.006

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：Dove Medical Press Ltd.  

Once-daily dual-bronchodilator therapy with combined indacaterol and glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149, was first approved in 2013 in Japan and Europe. As of November 2014, more than 40 countries had approved this medication except for the USA. This is the first dual bronchodilator in one device. Now, the Breezhaler is the only device that can provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting beta agonist (indacaterol), and a combination of the two medications (QVA149). The choice among the three medications allows a patient to use the same inhalation device even when the regimen is changed from single-bronchodilator therapy to dual-bronchodilator therapy. In addition, the quick bronchodilation effect and once-daily administration can improve patient adherence to medical treatment for chronic obstructive pulmonary disease (COPD). To our knowledge, as of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14 randomized controlled trials. The 14 trials generally showed good safety profiles, and there were better or not-inferior bronchodilator effects of QVA149 when compared with placebo, or other inhaled medication. According to the Japanese Respiratory Society guidelines, QVA149 is a combination of the two first-line bronchodilators. Our meta-analysis indicated that QVA149 is superior to the salmeterol–fluticasone combination to treat COPD in respect of the frequency of adverse effects, exacerbation, pneumonia, and improvement of trough forced expiratory volume in 1 second (FEV&lt
inf&gt
1&lt
/inf&gt
). Thus, we believe that QVA149 can be a key medication for COPD treatments.

DOI： 10.2147/COPD.S56067

Scopus

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等  

DOI： 10.1111/resp.12448

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記述言語：日本語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：Japanese Society for Tuberculosis  

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記述言語：英語   掲載種別：書評論文，書評，文献紹介等   出版者・発行元：DOVE MEDICAL PRESS LTD  

Once-daily dual-bronchodilator therapy with combined indacaterol and glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149, was first approved in 2013 in Japan and Europe. As of November 2014, more than 40 countries had approved this medication except for the USA. This is the first dual bronchodilator in one device. Now, the Breezhaler is the only device that can provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting beta agonist (indacaterol), and a combination of the two medications (QVA149). The choice among the three medications allows a patient to use the same inhalation device even when the regimen is changed from single-bronchodilator therapy to dual-bronchodilator therapy. In addition, the quick bronchodilation effect and once-daily administration can improve patient adherence to medical treatment for chronic obstructive pulmonary disease (COPD). To our knowledge, as of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14 randomized controlled trials. The 14 trials generally showed good safety profiles, and there were better or not-inferior bronchodilator effects of QVA149 when compared with placebo, or other inhaled medication. According to the Japanese Respiratory Society guidelines, QVA149 is a combination of the two first-line bronchodilators. Our meta-analysis indicated that QVA149 is superior to the salmeterol-fluticasone combination to treat COPD in respect of the frequency of adverse effects, exacerbation, pneumonia, and improvement of trough forced expiratory volume in 1 second (FEV1). Thus, we believe that QVA149 can be a key medication for COPD treatments.

DOI： 10.2147/COPD.S56067

Web of Science

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記述言語：英語   掲載種別：速報，短報，研究ノート等（学術雑誌）  

DOI： 10.4187/respcare.02890

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