Chemotherapy, immunotherapy, or combination first-line treatment for metastatic urothelial carcinoma of the bladder: A large real-world experience.

INTRODUCTION: First-line systemic therapy for metastatic urothelial carcinoma of the bladder (mUC) consists of platinum-based chemotherapy in most patients and PD1/L1 inhibitors in selected patients. Multiple combination chemoimmunotherapy trials failed to show a clear benefit over chemotherapy alone. We used real-world data to evaluate clinical and sociodemographic factors associated with receipt of first-line chemotherapy, immunotherapy, or combination chemoimmunotherapy treatment for metastatic bladder cancer and examined differences in overall survival (OS). MATERIALS AND METHODS: We used the National Cancer Database to identify patients with stage IV mUC diagnosed between 2014 and 2018, who were treated with first-line immunotherapy, chemotherapy, or combination treatment. We performed multivariable logistic regression modeling to determine factors associated with treatment receipt Adjusted Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between treatment and OS. RESULTS: In our cohort of 4,169 patients, multivariable analysis identified increasing age (RRR: 1.07, 95%CI, 1.06-1.08) and comorbidity burden (, as independent predictors of receiving immunotherapy. Treatment at an academic facility was associated with increased likelihood of combination treatment (RRR: 1.29, 95%CI, 1.01-1.65). After IPTW, we found that combination therapy (hazard ratio [HR]: 0.72; 95%CI, 0.62-0.83) was associated with improved survival compared to chemotherapy. CONCLUSIONS: Patients with older age and more comorbidities were more likely to receive immunotherapy than chemotherapy for first-line treatment of metastatic urothelial carcinoma of the bladder. Utilization of chemoimmunotherapy was observed to be higher in academic centers and was associated with improved survival compared to chemotherapy.

Comparative real-world survival outcomes of muscle-invasive bladder cancer treated with bladder-only vs. whole-pelvis concurrent chemoradiation.

INTRODUCTION: Elective pelvic nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT ) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiation (WP-CCR) compared to bladder-only (BO )-CCR has not been demonstrated. Using real-world data from the National Cancer Database (NCDB ), we sought to compare the overall survival (OS ) between BO-CCR and WP-CCR for MIBC. METHODS: Using the 2020 NCDB Participant User File, we identified cases of MIBC diagnosed between 2017 and 2019. We selected patients with clinical T2-T4aN0M0 disease receiving CCR as first-line treatment. CCR was defined as transurethral resection of bladder tumor followed by ≥40 Gy radiation to the bladder with concurrent single- or multiple-agent chemotherapy. Based on elective nodal irradiation status, patients were stratified as having received BO-CCR vs. WP-CCR. OS analysis was performed using summary three-month conditional landmark, inverse probability treatment weighting (IPTW)-adjusted Kaplan-Meier estimates, and Cox regression. RESULTS: A total of 604 patients receiving CCR for MIBC were identified: 367 (60.8%) BO-CCR and 237 (39.2%) WP-CCR. Before IPTW, the groups were imbalanced in terms of baseline characteristics. The median followup of the weighted population was 42.3 months (interquartile range 18.1-49.1 months). In IPTW-adjusted Cox proportional hazards regression analysis, WP-CCR was associated with a significant OS benefit compared to BO-CCR (adjusted hazard ratio 0.72, 95% confidence interval 0.54-0.96, p=0.026). CONCLUSIONS: In the setting of CCR for N0 MIBC, this retrospective NCDB analysis revealed that WP-CCR was associated with a benefit in OS compared to BO-CCR.

Postoperative Discharge Destination Impacts 30-Day Outcomes: A National Surgical Quality Improvement Program Multi-Specialty Surgical Cohort Analysis.

Surgical patients can be discharged to a variety of facilities which vary widely in intensity of care. Postoperative readmissions have been found to be more strongly associated with post-discharge events than pre-discharge complications, indicating the importance of discharge destination. We sought to evaluate the association between discharge destination and 30-day outcomes. A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were dichotomized based on discharge destination: home versus non-home. The main outcome of interest was 30-day unplanned readmission. The secondary outcomes included post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. In this cohort study of over 1.5 million patients undergoing common surgical procedures across eight surgical specialties, we found non-home discharge to be associated with adverse 30-day post-operative outcomes, namely, unplanned readmissions, post-discharge pulmonary, infectious, thromboembolic, and bleeding complications, as well as death. Non-home discharge is associated with worse 30-day outcomes among patients undergoing common surgical procedures. Patients and caregivers should be counseled regarding discharge destination, as non-home discharge is associated with adverse post-operative outcomes.

Glomerular hyperfiltration is an independent predictor of postoperative outcomes: A NSQIP multi-specialty surgical cohort analysis.

AIM: While high estimated glomerular filtration rate (eGFR) has been associated with increased overall mortality, its effect on postoperative outcomes is relatively understudied. We sought to investigate the association between high eGFR and 30-day postoperative outcomes using a multi-specialty surgical cohort. METHODS: Using the National Surgical Quality Improvement Program database, we selected adult for whom eGFR could be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. Based on sex-specific distributions of eGFR stratified by age quintiles, we classified patients into low (<5th percentile), normal (5-95th percentile) and high eGFR (>95th percentile). The primary outcome was a composite of any 30-day major adverse outcomes, including: death, reoperation, cardiac arrest, myocardial infarction and stroke. Secondary outcomes included 30-day infectious complications, venous thromboembolism (VTE), bleeding requiring transfusion, prolonged length of stay and unplanned readmission. After matching for demographic differences, comorbidity burden and operative characteristics, logistic regression models were used to evaluate the association between extremes of eGFR and the outcomes of interest. RESULTS: Of 1 668 447 patients, 84 115 (5.07%) had a high eGFR. High eGFR was not associated with major adverse outcomes (odds ratio [OR] 1.00 [95% confidence interval (CI): 0.97, 1.03]); however, it was associated with reoperation (OR 1.04 [95% CI: 1.00,1.08]), infectious complications (OR 1.14 [95% CI: 1.11, 1.16]), VTE (OR 1.15 [95% CI: 1.09, 1.22]) and prolonged length of stay (OR 1.19 [95% CI: 1.16, 1.21]). CONCLUSION: Our findings support an association between high eGFR and adverse 30-day postoperative outcomes.

Functional Outcomes of a Musculoskeletal Integrated Practice Providing Comprehensive Whole Person Care for Hip Osteoarthritis.

BACKGROUND: Outcomes of hip osteoarthritis (OA) management within integrated practice units (IPUs) are lacking. This study reports 6-month and 1-year patient-reported outcomes (PROs) of IPU care, the proportion of patients achieving minimal clinically important difference (MCID) and substantial clinical benefit (SCB) at 1 year, and baseline factors associated with the likelihood of achieving MCID and SCB. METHODS: We retrospectively evaluated 1009 new patients presenting to an IPU with hip OA between October 2017 and June 2020. Patients experienced multidisciplinary team-based management. Individuals with baseline and 6-month PROs or baseline and 1-year PROs (Hip Disability and Osteoarthritis Outcome Score Joint Replacement, HOOS JR) were included. We used anchor-based MCID and SCB thresholds and multivariable binary logistic regression models to identify baseline factors associated with achieving 1-year MCID and SCB. RESULTS: HOOS JR increased from baseline to 6 months (Δ = 19.1 ± 2.1, P = .065) and baseline to 1 year (Δ = 35.8 ± 2.9, P < .001). At 1 year, 72.7% (IPU only) and 88% (IPU-based total hip arthroplasty [THA]) achieved MCID (P < .001), and 62.3% (IPU only) and 88% (IPU-based THA) achieved SCB (P < .001). In multivariable regression, lower baseline HOOS JR scores (r = 0.96, P = .04), undergoing THA (r = 0.213, P < .001), and fewer symptoms of generalized anxiety (r = 0.932, P = .018) were independently associated with achieving MCID at 1 year. The same factors were independently associated with achieving SCB at 1 year. Lower baseline anxiety (Generalized Anxiety Disorder Questionnaire-7 item) and greater hip-related preoperative limitations result in greater likelihood of achieving MCID and SCB. CONCLUSION: Significant improvements in patient outcomes can be achieved by IPUs providing comprehensive care for hip OA including the management of psychological distress. Future prospective studies should compare the outcomes of IPUs with traditional care in managing diverse patient phenotypes.

RiboFlow, RiboR and RiboPy: an ecosystem for analyzing ribosome profiling data at read length resolution.

SUMMARY: Ribosome occupancy measurements enable protein abundance estimation and infer mechanisms of translation. Recent studies have revealed that sequence read lengths in ribosome profiling data are highly variable and carry critical information. Consequently, data analyses require the computation and storage of multiple metrics for a wide range of ribosome footprint lengths. We developed a software ecosystem including a new efficient binary file format named 'ribo'. Ribo files store all essential data grouped by ribosome footprint lengths. Users can assemble ribo files using our RiboFlow pipeline that processes raw ribosomal profiling sequencing data. RiboFlow is highly portable and customizable across a large number of computational environments with built-in capabilities for parallelization. We also developed interfaces for writing and reading ribo files in the R (RiboR) and Python (RiboPy) environments. Using RiboR and RiboPy, users can efficiently access ribosome profiling quality control metrics, generate essential plots and carry out analyses. Altogether, these components create a software ecosystem for researchers to study translation through ribosome profiling. AVAILABILITY AND IMPLEMENTATION: For a quickstart, please see https://ribosomeprofiling.github.io. Source code, installation instructions and links to documentation are available on GitHub: https://github.com/ribosomeprofiling. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In gastroesophageal reflux disease, differential gene expression in the duodenum points towards enhanced chylomicron production and secretion.

BACKGROUND: Duodenal signaling affects esophageal motility and perception, both pathophysiological factors in gastroesophageal reflux disease (GERD). Duodenal gene expression abnormalities, contributing to altered esophageal sensorimotor function, have not been reported to date. AIM: To identify differentially expressed genes in GERD patients' duodenum. METHODS: Twenty GERD patients (total 24-h acid exposure 6-12%, SAP ≥95%) and ten healthy controls (HC) were included. Two weeks prior to duodenal biopsy collection, ten patients discontinued proton pump inhibitor (PPI) treatment and ten took maximum dose PPI. RNA was profiled on an Affymetrix Human Genome U133 Plus 2.0 array (Affymetrix, Santa Clara, CA, USA). Genes exhibiting a fold change ≥ 1.4 (t test p value <1E-4) were considered differentially expressed. A subset of 21 differentially expressed genes was selected for confirmatory TaqMan low-density array RT-PCR. Mucosal apolipoprotein A-IV (apoA-IV) and cholecystokinin (CCK) concentrations were determined by ELISA and RIA, respectively. RESULTS: In GERD patients off PPI, 23 up- and 23 down-regulated genes relative to HC were found. In GERD patients on PPI, 33 and five genes were higher, respectively, lower expressed. The majority of up-regulated genes were associated with lipid absorption, particularly triglyceride resynthesis and intracellular vesicular transport, rate-limiting processes for chylomicron production and secretion. Differential expression of 11 genes was confirmed by RT-PCR. Mucosal apoA-IV and CCK concentrations (signaling proteins released upon chylomicron secretion) were similar in GERD patients and HC. CONCLUSIONS: The identified mRNA expression differences suggest that in GERD patients' duodenum, the chylomicron production and secretion potential is elevated, and may underlie a mechanism by which postprandial duodenal signaling contributes to GERD symptom generation.