Immune-inflammatory-nutritional status predicts oncologic outcomes after radical cystectomy for urothelial carcinoma of bladder.

OBJECTIVE: To perform the first investigation of the role of immune-inflammatory-nutritional status (INS) on oncological outcomes in patients undergoing open radical cystectomy (ORC) for urothelial carcinoma (UC). MATERIALS AND METHODS: The records of consecutive patients who underwent ORC for non-metastatic bladder cancer between 2009 and 2020 were retrospectively analyzed. Neoadjuvant chemotherapy, non-urothelial tumor biology, and absence of oncological follow-up were exclusion criteria. Systemic immune-inflammatory index (SII) and Prognostic Nutritional Index (PNI) values were calculated and optimal cut-off values for these were used to designate four subgroups: "high SII-high PNI", "low SII-high PNI", "low SII-low PNI", and "high SII-low PNI". The Low SII-high PNI INS group had best overall survival (OS) rate while the remainder were included in non-favorable INS group. Survival curves were constructed, and a multivariate Cox regression model was used for OS and recurrence-free survival (RFS). RESULTS: After exclusions, the final cohort size was 173 patients. The mean age was 64.31 ± 8.35 and median follow-up was 21 (IQR: 9-58) months. Optimal cut-off values for SII and PNI were 1216 and 47, respectively. The favorable INS group (low SII-high PNI, n = 89) had the best OS rate (62.9%). Multivariate Cox regression analysis indicated that non-favorable INS (n = 84) was a worse independent prognostic factor for OS (HR: 1.509, 95%CI: 1.104-3.145, p = 0.001) and RFS (HR: 1.285; 95%CI: 1.009-1.636, p = 0.042). CONCLUSION: Preoperative assessment of INS may be a useful prognostic panel for OS and RFS in patients who had ORC for UC.

External validation of the current scoring systems and derivation of a novel scoring system to predict stone free rates after retrograde intrarenal surgery in patients with cumulative stone diameter of 2-4 cm.

OBJECTIVE: Our primary aim is to perform the external validation of the current scoring systems in predicting stone-free status (SFS) after retrograde intrarenal surgery (RIRS) for renal stones 2-4 cm and develop a novel scoring system by re-examining possible predictive factors related to SFS. METHODS: Patients who underwent RIRS due to renal stones with a cumulative stone diameter of 2-4 cm between January 2017 and March 2021 were retrospectively screened. Residual stones ≤2 mm were defined as clinically insignificant, and these cases were considered to have SFS. Possible predictive factors related to SFS were examined using the multivariate logistic regression analysis. A nomogram and a scoring system were developed using independent predictive variables. The prediction ability of the previous and the new scoring system were evaluated with the ROC analysis. RESULTS: The existing scoring systems were found to be insufficient in predicting SFS (AUC < 0.660 for all). The independent predictors of SFS were identified as stone surface area (OR: 0.991, p < 0.001), stone density (OR: 0.998, p < 0.001), number of stones (OR: 0.365, p = 0.033), and stone localization (p = 0.037). Using these predictive markers, a new scoring system with a score ranging between 4 and 15 was developed. The AUC value for this scoring system was 0.802 (0.734-0.870). CONCLUSION: The RUSS, S-ReSC and R.I.R.S. scoring systems and Ito's nomogram failed to predict SFS in stones >2 cm. The SFS predictive ability of our new scoring system was higher in >2 cm stones compared to the other scoring systems.

Medicinal chemistry of drugs used in diabetic cardiomyopathy.

Diabetes mellitus is a common disease and contributes to a high degree of morbidity and mortality. Cardiovascular complications, including diabetic cardiomyopathy are major causes of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy is a condition that affects the myocardium, primarily. It is not necessarily associated with ischemic heart disease, high blood pressure, valvular or congenital anomalies. The pathology of diabetic cardiomyopathy includes interstitial fibrosis, apoptosis of cardiomyocytes, abnormal energy utilization, small vessel disease and cardiac neuropathy. These pathologies are induced by hyperglycemia and oxidative stress. Biochemical as well as electrolyte changes, especially reduced calcium availability also occurs in the myocardium of diabetic patients. The abnormal structure and biochemistry of the myocardium result in functional problems such as diastolic and systolic dysfunctions, which may cause symptoms of dyspnea and inability to tolerate exercise. No single specific therapeutic agent can treat diabetic cardiomyopathy because once the disease is overt, the management may require a variety of approaches such as risk factors and lifestyle modification, glucose control (insulin, alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones and dipeptidyl peptidase 4 (DPP-4) inhibitors); hormones (IGF-1); ACE inhibitors (captopril, enalapril); angiotensin II receptor antagonists (losartan, olmesartan); beta adrenoreceptor antagonists (acebutolol, carvedilol); peptides (adrenomedullin); endothelin-1 receptor antagonists (bosentan, tezosentan); calcium channel blockers (amlodipine, verapamil); antioxidants (methalothionein, alpha tocopherol, alpha lipoic acid) and antihyperlipidemic drugs (simvastatin, fenofibrate, ezetimibe) to effectively treat patients with diabetic cardiomyopathy.