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Objectives: The aim of this study was to investigate the relationship between quality of life (QOL) and residual urine volume in patients undergoing bacille Calmette-Guérin (BCG) therapy. Methods: Patients requiring BCG therapy, including those with carcinoma in situ, were enrolled prospectively. The urine volume collected through urethral catheterization was measured as post-voiding residual volume (PVR) during BCG therapy. Patients were divided into two groups: small PVR (SPVR), with PVR less than 30 ml, and large PVR (LPVR), with PVR greater than or equal to 30 ml. QOL status was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 system before and after BCG therapy. Moreover, some patients were assessed by International Prostate Symptom Score (IPSS) at the same time as assessment with the EORTC QLQ-C30 system. The primary end point was the evaluation of QOL during BCG therapy. Results: Among the 69 patients with non–muscle-invasive bladder cancer included in this study, 43 were in the SPVR group and 26 were in the LPVR group. The proportions of women and analgesic use in the SPVR group were higher than that in the LPVR group; however, medication use for dysuria in the SPVR group was less than that in the LPVR group. In the QOL analyses, cognitive function and emotional function in the functional scale and fatigue, nausea/vomiting, and dyspnoea in the symptomatic scale were worse in the SPVR group than in the LPVR group. In the multivariate analysis, fatigue was worse in the SPVR group than in the LPVR group. Conclusions: During BCG therapy, patients in the SPVR group had worse QOL, especially fatigue, than those in the LPVR group. Level of evidence: Not applicable for this multicentre audit. [ABSTRACT FROM AUTHOR]

The large majority of variants identified by GWAS are non-coding, motivating detailed characterization of the function of non-coding variants. Experimental methods to assess variants' effect on gene expressions in native chromatin context via direct perturbation are low-throughput. Existing high-throughput computational predictors thus have lacked large gold standard sets of regulatory variants for training and validation. Here, we leverage a set of 14,807 putative causal eQTLs in humans obtained through statistical fine-mapping, and we use 6121 features to directly train a predictor of whether a variant modifies nearby gene expression. We call the resulting prediction the expression modifier score (EMS). We validate EMS by comparing its ability to prioritize functional variants with other major scores. We then use EMS as a prior for statistical fine-mapping of eQTLs to identify an additional 20,913 putatively causal eQTLs, and we incorporate EMS into co-localization analysis to identify 310 additional candidate genes across UK Biobank phenotypes. Finding causal variants and genes from GWAS loci results remains a challenge. Here, the authors train a model to predict if a variant affects nearby gene expression, and apply the method to identify new possible causal eQTLs and mechanisms of GWAS loci. [ABSTRACT FROM AUTHOR]

Objectives: To compare overall survival between patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy and those not treated by cytoreductive nephrectomy. Methods: We retrospectively evaluated 278 patients with metastatic renal cell carcinoma treated with first‐line tyrosine kinase inhibitors between January 2008 and November 2019. Patients were divided into two groups: a cytoreductive nephrectomy group (immediate or deferred cytoreductive nephrectomy) and a group who received systemic tyrosine kinase inhibitor therapies alone without cytoreductive nephrectomy (control group). Overall survival comparisons were made in all patients in the control versus the cytoreductive nephrectomy group, the control versus the immediate cytoreductive nephrectomy group, the control versus the deferred cytoreductive nephrectomy group, and the deferred cytoreductive nephrectomy versus the immediate cytoreductive nephrectomy group. Analyses were weighted using the propensity score‐based inverse probability of treatment weighting method to adjust for group imbalances. Results: The median (range) age of the patients was 65 (59–73) years. Of the 278 patients, 132 and 146 were in the control group and the cytoreductive nephrectomy (immediate, n = 107 and deferred, n = 39) group, respectively. A significant difference was noted between the control and cytoreductive nephrectomy groups in age, clinical stage, International Metastatic Renal Cell Carcinoma Database Consortium risk factors, and the number of metastatic sites. Inverse probability of treatment weighting‐adjusted Cox regression analysis showed a significant difference in overall survival between the control and the cytoreductive nephrectomy groups and between the control and the immediate or deferred cytoreductive nephrectomy groups. However, there was no significant difference in overall survival between the immediate and the deferred cytoreductive nephrectomy groups. Conclusions: Our findings suggest that metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy are more likely to have longer overall survival than those who receive tyrosine kinase inhibitor therapy only. [ABSTRACT FROM AUTHOR]

Indoxyl sulfate (IS) is related to the development of cardiovascular disease and total mortality in dialysis patients. High‐performance liquid chromatography (HPLC) is the conventional measurement approach. However, the HPLC method is difficult to perform in real time. Recently, the IS Assay Kit "NIPRO", which enables the measuring of total IS by the enzyme method, was developed. This new reagent allows the easy and quick measurement of many samples using the automatic biochemical analyzer. Moreover, it was reported that it demonstrated satisfactory analytical performance. If this enzyme method is useful for measuring IS in hemodialysis, we can expect that the mechanism in which the IS effects adversely on a body as uremic toxins will be clarified. However, the enzyme method is more easily influenced by other coexisting substances. In this study, we have assessed on how the uremic toxins and anticoagulation effect on this new reagent and evaluate whether it can be put into practice effectively for hemodialysis patients. For the enzyme method, accuracy, simultaneous repeatability, linearity, limit of detection, influence of coexisting materials, and correlation with the HPLC method were examined. Accuracy and simultaneous repeatability were satisfactory, and linearity was good. The limit of detection was acceptable, and there was no influence of coexisting materials. With regard to the correlation, the regression equation was y = 0.947X + 7.987 and the correlation coefficient (r) was 0.972. This new reagent showed sufficient fundamental performance and had a good correlation with the conventional HPLC method for assessing the plasma of dialysis patients. [ABSTRACT FROM AUTHOR]

Background: Prognostic outcomes and safety following treatment with pembrolizumab in patients with advanced urothelial carcinoma (UC) have not been fully elucidated in clinical practice. The aim of this study was to evaluate the oncological efficacy and safety of pembrolizumab after failure of platinum-based chemotherapy in Japanese patients with advanced UC in a routine clinical setting. Methods: This retrospective study included 41 consecutive Japanese patients with advanced UC treated with pembrolizumab as second-line or greater therapy at Iwate Medical University Hospital from January 2018 to April 2019. Results: The mean follow-up period was 6.2 months. The objective response rate, median progression-free survival, and median overall survival were 15%, 2.5 months, and 11.9 months, respectively. Univariate analysis identified poor performance status (> 1), liver metastasis, two or more metastatic organs, low hemoglobin levels, two or more prior regimens, high baseline C-reactive protein levels, higher relative C-reactive protein level change after 6 weeks, and higher relative neutrophil-to-lymphocyte ratio change after 6 weeks as significant predictors of overall survival. Among these factors, poor performance status (> 1), two or more metastatic organs, and higher relative neutrophil-to-lymphocyte ratio change after 6 weeks were identified as independent predictors of overall survival in multivariate analysis. Conclusions: The introduction of pembrolizumab can result in favorable cancer control outcomes in Japanese patients with advanced UC, and the prognosis of these patients can be stratified according to three potential parameters, including poor performance status, high number of metastatic organs, and higher relative neutrophil-to-lymphocyte ratio change. [ABSTRACT FROM AUTHOR]