Memorial Sisli Hospital

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Aim: Sepsis-associated acute kidney injury (SA-AKI) remains a major cause of mortality, driven by inflammation and oxidative stress. Pioglitazone, a PPAR-γ agonist, has demonstrated anti-inflammatory and antioxidant effects beyond glycemic control. This study evaluated its renoprotective efficacy in a rat model of sepsis induced by cecal ligation and puncture (CLP). Methods: Thirty-six female Wistar rats were divided into Control, CLP + Saline, and CLP + Pioglitazone (10 mg/kg/day) groups. Survival was analyzed for 5 days. Renal function (BUN, creatinine, NGAL), oxidative stress (MDA), antioxidant signaling (NRF2), and inflammatory mediators (TNF-α, IL-6, HMGB1, TLR-4, NF-κB) were quantified by ELISA. Tubular epithelial necrosis, luminal debris, dilatation, hemorrhage, and inflammation were semi-quantitatively scored. Results: CLP caused marked renal dysfunction with elevated BUN, creatinine, and NGAL (p all <0.001 vs. Control). Pioglitazone significantly reduced these markers (p < 0.001 vs. CLP + Saline) and improved survival. Plasma MDA levels increased and renal Nrf2 levels decreased following CLP induction (both p < 0.001 vs. Control), whereas pioglitazone treatment significantly reduced MDA levels and increased NRF2 expression (p = 0.002 and p < 0.001 vs. CLP + Saline, respectively). Inflammatory mediators were markedly increased in sepsis (TNF-α, IL-6, HMGB1, TLR-4, and NF-κB; all p < 0.001 vs. Control) and significantly downregulated by pioglitazone (p < 0.01, p < 0.001, p < 0.001, p < 0.01, p < 0.01 vs. CLP + Saline, respectively). Histopathological injury was pronounced in septic rats (all p < 0.01 vs. Control) but was markedly ameliorated by pioglitazone p < 0.05, indicating substantial structural recovery. Conclusions: Pioglitazone markedly ameliorates CLP-induced SA-AKI by suppressing TLR-4/NF-κB/TNF-α signaling and oxidative stress, improving renal structure, function, and survival. These findings support its potential repurposing as a therapeutic adjunct in sepsis management.

Introduction & Objective: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with limited treatment options for steroid-resistant cases. Ruxolitinib, a JAK1/2 inhibitor, has shown promise in treating steroid-resistant acute (aGVHD), chronic (cGVHD), and overlap GVHD (oGVHD), but real-world data remain limited. This study evaluated the real-world efficacy and safety of ruxolitinib in allo-HSCT patients with steroid-resistant GVHD. Materials & Methods: This retrospective, multicenter study included adult patients treated with ruxolitinib for Grade II or higher aGVHD or moderate-to-severe cGVHD at nine centers in Turkey (2017-2024). Clinical characteristics, treatment responses, and adverse events were recorded. Primary outcomes were overall response rate (ORR) and overall survival (OS). Results: Among 80 patients (mean age: 39.3 ± 13.3 years; 60 males), 39 had aGVHD, 68 cGVHD, and 15 oGVHD. The ORR was 72 of 80 patients (90.0%) (complete response: 37 of 80 [46.3%], partial response: 35 of 80 [43.8%]). The 1-year and 2-year OS rates were 91.3% and 82.5%. Severe cGVHD (p < 0.001) and lack of response to ruxolitinib (p = 0.018) were associated with reduced OS. Adverse events included infections in 40 of 80 patients (50.0%), cytopenias in 23 of 80 (28.7%), and cytomegalovirus reactivation in 20 of 80 (25.0%). Conclusion: In this retrospective multicenter cohort, ruxolitinib was associated with high response rates in steroid-refractory GVHD, while disease severity remained a key determinant of survival, and findings should be interpreted as exploratory.

This study aimed to evaluate the 48-month visual and anatomical outcomes, as well as the number of clinic visits and intravitreal injections, in patients treated with three consecutive loading doses of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) under real-world conditions in Türkiye. In this retrospective, multicenter study conducted by the BOSPHORUS-DME Study Group, the medical records of 2,424 eyes of 1,696 patients who experienced vision loss due to DME and were treated with intravitreal anti-VEGF injections between January 2019 and January 2023 were reviewed. The study was carried out across eight tertiary referral hospitals located on the European side of İstanbul and in the province of Kocaeli. Seven cohort groups were created based on follow-up at baseline and months 3, 6, 12, 18, 24, 36, and 48. Best-corrected visual acuity (BCVA), central macular thickness (CMT), the number of clinic visits and injections, and the rates of anti-VEGF or dexamethasone switching were analyzed. The study included a total of 2,424 eyes of 1,696 patients (mean age: 60.6±10.0 years; 46.4% female). The mean baseline BCVA and CMT were 0.34±0.24 (decimal) and 400±134 μm, respectively. At month 48, these values improved to 0.49±0.29 (p<0.0001) and 324±115 μm (p<0.0001). The mean cumulative number of injections at years 1, 2, 3, and 4 were 6.5, 9.6, 12.2, and 15.7, respectively. A switch in anti-VEGF therapy occurred between month 3 and 6 in 43.5% of eyes, mostly due to mandatory transition to on-label agents. This is the largest and longest real-world study on DME treatment conducted in Türkiye. It demonstrates that visual and anatomical gains can be sustained over a 48-month period. While the overall trend aligns with previous real-world studies, the higher injection frequency in our cohort appears to have contributed to more favorable outcomes. These findings underscore the importance of early intensive therapy and sustained treatment adherence in the real-world management of DME.

Background/Objectives: Non-invasive fibrosis scores are widely used for risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD); however, their performance in obese individuals remains controversial. The Fibrosis-4 (FIB-4) index is commonly recommended as a first-line tool, yet it may underestimate fibrosis risk in severe obesity. The BAST score, which incorporates metabolic and anthropometric parameters, has been proposed as an alternative. This study aimed to characterize both the degree and direction of discordance between FIB-4 and BAST in obese patients with MASLD. Methods: This predefined secondary analysis included 2950 adults with obesity (BMI ≥ 30 kg/m2) and MASLD from the multicenter OBREDI-TR cohort. Fibrosis risk categories were assigned using standard cut-offs for FIB-4 and BAST, and agreement was assessed using weighted Cohen's kappa. Associations among discordance patterns, obesity class, and the visceral adiposity index (VAI) were evaluated using chi-square tests and general linear models. Results: Overall agreement between FIB-4 and BAST was very poor (κ = 0.041, p < 0.001). Discordance was observed in 22.3% of patients and increased markedly with obesity severity. In class III obesity, discordance was predominantly driven by low-risk classification according to FIB-4 despite high-risk classification according to BAST. Patients with this discordant pattern exhibited significantly higher VAI values than concordant cases (p < 0.001), independently of the study center. Conclusions: In obese patients with MASLD, particularly those with morbid obesity, FIB-4 frequently classifies patients as low risk, while BAST identifies elevated fibrosis risk. This systematic discordance suggests that FIB-4 may underestimate fibrosis burden in the context of severe obesity and visceral adiposity, supporting the need for a phenotype-oriented, multimodal approach to fibrosis risk assessment.

Introduction: Vitamin B12 deficiency may influence cardiac autonomic function and ventricular repolarization. The frontal QRS-T angle is a novel and useful electrocardiographic parameter that reflects the relationship between ventricular depolarisation and repolarisation. The aim of this study was to evaluate the association between serum vitamin B12 levels and the frontal QRS-T angle in asymptomatic individuals. Method: The current retrospective study comprised 92 adults who underwent a standard 12-lead ECG and serum vitamin B12 testing on the same day. Participants were divided into two groups according to their vitamin B12 levels (Group 1 was defined as abnormal having a level of less than 300 pg/mL, while Group 2 was defined as normal having a level of 300 pg/mL or more). The patient's clinical characteristics, laboratory findings and ECG parameters were recorded. The frontal QRS-T angle was calculated automatically using the QRS and T axes provided by the ECG device. Results: The average age of participants was 46.1 (±12.2) years, and 51.9% of participants were female (p &lt; 0.001). Individuals with low vitamin B12 concentrations exhibited a wider frontal QRS-T angle. It was determined that vitamin B12 level is an independent predictive factor for the frontal QRS-T angle. Conclusion: The frontal QRS-T angle may serve as a useful parameter for evaluating electrical changes and susceptibility to ventricular arrhythmias in individuals with vitamin B12 deficiency.

The objective was to compare the outcomes of dorsal and ventral onlay urethroplasties using buccal mucosal grafts for the treatment of urethral strictures in women, focusing on patency, complications, de novo incontinence, and impact on sexual function. A retrospective analysis was conducted on 65 patients who underwent dorsal (n = 38) and ventral (n = 27) onlay female urethroplasty using a buccal mucosal graft between July 2017 and January 2024 across three centers. Patency was determined by the successful passage of a 16-French cystoscope or by a maximum flow rate exceeding 15ml/s. Median age, etiology, and stenosis characteristics of the two groups were comparable. At the final follow-up, the patency rates for dorsal and ventral onlay female urethroplasty were 92.1% and 92.6% respectively (p = 1.0). There was no significant difference in postoperative maximum flow rates, postvoid residual urine, Female Sexual Function Index scores, Patient Global Impressions of Change scores, and de novo incontinence rates between the groups. The median blood loss was significantly lower in the ventral onlay group than in the dorsal onlay group (10 vs 20ml, p = 0.001). Dorsal and ventral onlay urethroplasties with buccal mucosal graft are safe and effective techniques for managing female urethral stricture, with similar patency, complications, de novo incontinence rates, and improvements in sexual function. Ventral onlay female urethroplasty has been associated with reduced intraoperative bleeding. To the best of our knowledge, this study represents the largest individual comparative cohort in the literature that directly evaluates dorsal and ventral onlay female urethroplasty.

Objective: This study retrospectively evaluated the effects of treatment methods (bupropion and varenicline) used in the smoking cessation process on depression and anxiety among individuals who applied to the Hendek State Hospital Smoking Cessation Polyclinic. Materials and Methods: The Fagerström Nicotine Dependence Test (FNDT) and a questionnaire form developed specifically for this study by a pulmonologist working in the outpatient clinic were prepared. In addition, the scores obtained from the Hamilton Depression (HAM-D) rating and Hamilton Anxiety (HAM-A) rating scales were also analyzed. Results: In Spearman correlation analysis, a positive, high-level, statistically significant relationship was found between the HAM-D rating scale scores received by individuals in the first interview and the HAM-A rating scale scores (n=20, r=0.704, p=0.001). A positive, high-level, and statistically significant relationship was found between the scale scores they received in the second interview (n=20, r=0.784, p=0.001). The decrease in anxiety levels was not found to be statistically significant. Statistically significant reductions in depression levels were observed in participants (bupropion group: p=0.016; varenicline group: p=0.028). However, the decrease in anxiety levels was not statistically significant (bupropion group: p=0.069; varenicline group: p=0.150). Conclusions: The findings showed a statistically significant decrease in depression levels in individuals who received both bupropion and varenicline treatment. The research results emphasize that attention should be paid not only to the physical dependence level of individuals but also to their psychological state in the smoking cessation process.