Plasma CAF22 and NfL reflect neuromuscular decline during cisplatin-based chemotherapy and radical cystectomy in muscle-invasive bladder cancer.

Plasma levels of Neurofilament light chain correlate with handgrip strength and sarcopenia in patients with chronic obstructive pulmonary disease

Muscle-invasive bladder cancerposes a significant clinical challenge that necessitates effective therapeutic interventions. Radical cystectomy is a primary treatment option, but a comprehensive understanding of its outcomes is crucial for informed clinical decision-making.This systematic review and meta-analysis aimed to investigate and summarize the outcomes associated with radical cystectomy as a primary treatment for muscle-invasive bladder cancer with a focus on survival rates, complications, and quality of life.A systematic search across databases-PubMed, Google Scholar, and others-covered studies from 2017 onwards. Included were studies reporting survival rates, complications, and quality of life post-radical cystectomy in muscle-invasive bladder cancer patients, including randomized controlled trials, cohort, and observational studies. Multidimensional analysis revealed promising findings regarding the efficacy of radical cystectomy in muscle-invasive bladder cancer. Survival outcomes, including overall survival and disease-specific mortality, have demonstrated significant improvements, particularly in recent randomized controlled trials and cohort studies. Complications associated with the surgical procedure, such as positive surgical margins and lymph node yields, were generally acceptable. Quality of life outcomes post-radical cystectomy exhibited positive trends, although variations were noted in the emotional and social domains. This review underscores radical cystectomy's role in enhancing overall survival and reducing disease-specific mortality in muscle-invasive bladder cancer. Despite reported complications, recent studies support its acceptable risk profile. Detailed examination of various factors contributes to a comprehensive understanding of the procedure. These findings emphasize the importance of individualized treatment approaches in the management of muscle-invasive bladder cancer, considering both oncological efficacy and perioperative outcomes.Radical cystectomy remains fundamental in urological oncology, with ongoing advancements refining its significance.

Bladder preservation therapy for muscle-invasive bladder cancer is reported to yield outcomes comparable to those of radical cystectomy, although it receives a relatively low recommendation grade in Japanese guidelines. This study aims to compare the outcomes of trimodal therapy versus radical cystectomy in the treatment of muscle-invasive bladder cancer. This study is a single-center retrospective analysis that included patients treated with either trimodal therapy or radical cystectomy for muscle-invasive bladder cancer (cT2-4N0-2M0) at our institution between January 1998 and December 2022. Trimodal therapy is administered in cases where radical cystectomy is either unfeasible or declined by the patient, and both treatments are performed with the intent of curative outcomes. Propensity score matching was used to compare cancer-specific survival and overall survival rates. A total of 93 patients who underwent trimodal therapy and 84 who underwent radical cystectomy for muscle-invasive bladder cancer were analyzed. Using propensity score matching, 66 patients from each treatment group were selected for a comparative analysis of oncological outcomes. The 5-year distant metastasis-free, cancer-specific and overall survival rates were 64.3 and 51.8% (P=0.096), 83.3 and 69.2% (P=0.104) and 77.8 and 64.2% (P=0.274) for trimodal therapy and radical cystectomy, respectively. Subgroup analyses revealed that trimodal therapy for primary tumors significantly improved cancer-specific survival rates compared with radical cystectomy. The two treatment types had similar adverse events related to hematologic toxicity during perioperative chemotherapy. Trimodal therapy exhibited oncological outcomes comparable to those of radical cystectomy in the treatment of muscle-invasive bladder cancer, indicating that trimodal therapy provides favorable outcomes, particularly in cases of primary muscle-invasive bladder cancer.

Background. Radical cystectomy is the standard treatment for muscle-invasive bladder cancer. Muscle invasion can occur in 48 % of patients. Epidemiologically, the peak incidence of bladder cancer is observed in men at the seventh decade of life. At the time of diagnosis, many of these patients have serious comorbidity. The trauma of radical cystectomy in combination with comorbidity creates an insurmountable barrier to radical treatment in a large part of patients. Refusal to use intestinal segments for urine diversion dramatically reduces the invasiveness of the intervention. However, the implementation of bilateral ureterocutaneostomy is associated with a greater frequency of pyelonephritis due to the use of external stents and scarring of the ureterocutaneostomy. A transureteroureterostomy with a unilateral ureterocutaneostomy can be a definite alternative.Objective: to evaluate the effectiveness of cross ureteroureterostomy for urine derivation after radical cystectomy in patients with muscle-invasive bladder cancer and a high risk of perioperative complications.Materials and methods. The article analyzes 28 cystectomies for muscle-invasive bladder cancer in patients with severe concomitant pathology who underwent transureteroureterostomy with unilateral ureterocutaneostomy for urine derivation. Results. It was shown that this intervention does not have high morbidity, does not increase the incidence of early postoperative complications, and relieves patients from bilateral urostoma. Among late complications, inflammatory ones predominate due to obstruction of the external stent. The authors highlight the tactics and technical aspects of managing such patients with obstructive pyelonephritis and the experience of drainage-free management.Conclusion. Transureteroureterostomy with unilateral ureterocutaneostomy after cystectomy for muscle-invasive bladder cancer can be considered as the operation of choice in patients with a burdened comorbidity.

Asthma-chronic obstructive pulmonary disease overlap is associated with a higher degree of neuromuscular junction degradation than either disease alone.

Comparative Effectiveness of Bladder-Preserving Tri-Modality Therapy versus Radical Cystectomy for Muscle-Invasive Bladder Cancer

Oncological outcomes of patients with node positive disease following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer: A multicenter observational study of the EAU Young Academic Urologists (YAU) urothelial carcinoma working group.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

418 Background: Radical cystectomy (RC) has historically been considered the standard of care for muscle invasive bladder cancer (MIBC). An alternative is tri-modality therapy (TMT), a bladder-sparing approach that often achieves preservation of the native bladder. There are limited randomized data comparing these guideline-recommended approaches but, in appropriately selected patients, both are thought to have similar survival outcomes with different morbidity profiles. Therefore this study compared the effectiveness of TMT and RC using decision-analytic modeling with the primary endpoint of quality-adjusted life years (QALYs). Methods: We developed a Markov model simulating the lifetime outcomes for 67-year-old patients after definitive treatment for American Joint Committee on Cancer clinical Stage T2-T4aN0M0 MIBC using two strategies: TMT or RC +/- neoadjuvant chemotherapy (NAC). Probabilities and utilities were extracted from the literature to determine the incremental effectiveness in QALYs. Sensitivity analyses were performed. Results: TMT was the most effective strategy with an incremental gain of 1.13 QALYs over RC (8.37 versus 7.24 QALYs, respectively; Table). One-way sensitivity analyses demonstrated the model was most sensitive to the quality of life (QoL) parameters (i.e. the utilities) for RC and TMT; TMT was more effective than RC irrespective of the RC utility (the 95% confidence interval of the RC parameter demonstrated an incremental gain with TMT of 0.01 to 4.77 QALYs). The model was relatively less sensitive to the probability of death for either strategy. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC for 75% of model iterations. Conclusions: Treatment of MIBC with organ-sparing TMT in appropriately-selected patients may result in a gain of over 1 QALY relative to RC. Further prospective investigation into the QoL implications of these treatment modalities is warranted. [Table: see text]

Older men with type 2 diabetes mellitus (T2DM) face a heightened risk of sarcopenia. This study aimed to compare the longitudinal effects of semaglutide, a glucagon-like peptide-1 receptor agonist and sitagliptin as the control group on sarcopenia indicators and biomarkers of neuromuscular junction and neuronal health in patients with T2DM over 1 year. A cohort of 141 older men with T2DM (semaglutide, n =68; sitagliptin group, n =73) underwent assessments at baseline, 6months and 1 year. Measured parameters included handgrip strength (HGS), gait speed, appendicular skeletal muscle mass index (ASMI), short physical performance battery (SPPB) and plasma concentrations of C-terminal agrin fragment 22 (CAF22), neurofilament light chain (NfL) and brain-derived neurotrophic factor (BDNF). Over the study period, the semaglutide group exhibited significant reductions in HGS, gait speed, ASMI and SPPB scores (all P < .05). Concurrently, this group exhibited more pronounced elevation of plasma CAF22 and NfL levels compared to the sitagliptin group (all P < .05). Among the patients taking semaglutide, higher CAF22 and NfL levels generally correlated with poorer HGS, ASMI and SPPB scores. In contrast, lower BDNF levels were associated with reduced ASMI and SPPB at specific time points (all P < .05). Multiple regression analysis confirmed significant negative associations between CAF22 and NfL, and a positive association between BDNF and sarcopenia parameters, specifically among patients taking semaglutide. Semaglutide treatment in older men with T2DM may be associated with a decline in muscle strength and physical performance, potentially associated with neuromuscular junction degradation and neuronal damage. These findings underscore the importance of closely monitoring musculoskeletal health in patients receiving semaglutide.

Impairments in geriatric assessment and their associations with different grip strength cutoffs and components of the Short Physical Performance Battery among older adults with cancer.

Heart failure (HF) impairs skeletal muscle mass and function, which contributes to reduced physical performance. We investigated the prognostic impact of gait speed (GS), handgrip strength (HG) and appendicular skeletal muscle index (ASMI) on cardiovascular outcomes in a prospective HF cohort. This single-centre prospective cohort study included adults with stable chronic HF with a previous diagnosis of overtly reduced left ventricular ejection fraction (LVEF) <40% and LVEF<50% at enrolment. GS was measured by the 4m GS test, maximal HG was measured with a hydraulic dynamometer, and ASMI was measured by dual-energy X-ray absorptiometry. The primary combined outcome was cardiovascular death or worsening HF. Fine and Gray regression models were calculated, treating non-cardiovascular death as the competing event. Two hundred five patients (78% male) were analysed. The median age was 66 (quartiles: 58-74) years, 31% had diabetes mellitus, and the median LVEF was 37 (30-43) %. Median GS was 1.0 (0.8-1.0) m/s, median HG was 32 (24-40) kg, and median ASMI was 8.0 (7.2-8.9) kg/m2. During a median follow-up of 4.7 (4.0-5.3) years, the primary outcome was observed in 52 patients. In models adjusted for key clinical covariates, lower GS predicted a higher risk of cardiovascular death or worsening HF [subdistribution hazard ratio (SHR) per 0.1m/s increase=0.81, 95% confidence interval (CI) 0.68-0.95], whereas HG (SHR per 5kg increase=0.97, 95% CI 0.84-1.10) and ASMI (SHR per 1kg/m2 increase=1.17, 95% CI 0.94-1.44) did not. In the analysis of effect modification, these associations were consistent across key clinical subgroups. Higher GS was independently associated with a lower risk of cardiovascular death or worsening HF, whereas HG and ASMI were not. We prospectively confirm GS as a physical performance measure with clear prognostic significance for patients with HF.

Metformin improves skeletal muscle and physical capacity by stabilizing neuromuscular junction in older adults

Comparative Effectiveness of Bladder-preserving Tri-modality Therapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer.

Delays from the diagnosis of muscle-invasive bladder cancer (MIBC) to radical cystectomy (RC) longer than 12weeks result in higher mortality and shorter progression-free survival. This study sought to identify factors associated with RC delays and to determine whether delays in care in the current treatment paradigm, which includes neoadjuvant chemotherapy (NAC), affect survival. Subjects with American Joint Committee on Cancer stage II urothelial carcinoma of the bladder who underwent RC from 2004 to 2012 were identified from the linked Surveillance, Epidemiology, and End Results national cancer registry and the Medicare claims database and were stratified into RC groups with or without NAC. Cox multivariable proportional hazard models and multivariable logistic regression models assessed the significance of delays in RC for survival and identified independent characteristics associated with RC delays, respectively. This study identified 1509 patients with MIBC who underwent RC during the study period. In comparison with timely surgery, delays in RC increased overall mortality, regardless of the use of NAC (hazard ratio [HR] without NAC, 1.34; 95% confidence interval [CI], 1.03-1.76; HR after NAC, 1.63; 95% CI, 1.06-2.52). Patients proceeding to RC without NAC had higher odds of delayed care if they lived in a high-poverty neighborhood (odds ratio [OR], 1.37; 95% CI, 1.01-2.08) or nonmetropolitan area (OR, 1.61; 95% CI, 1.01-2.55), were men (OR, 2.22; 95% CI, 1.25-4.00), or required a provider transfer for bladder cancer care (OR, 1.82; 95% CI, 1.10-3.03). Delays in care from the time of either the initial diagnosis or the completion of NAC to RC are associated with worse overall survival among patients with MIBC. Timely surgery is fundamental in the treatment of MIBC, and this necessitates attention to disparities in access to complex surgical care and care coordination.