Biruni University

Lower abdominal surgeries in children are associated with significant postoperative pain. While caudal block (CB) is widely used, ultrasound-guided truncal blocks such as retrolaminar block (RLB) may provide more targeted and prolonged analgesia. In this double-blind, randomized controlled trial conducted at two tertiary hospitals (March 1-September 1, 2025), children aged 1-7 years (ASA I-II) scheduled for unilateral orchidopexy were randomized to RLB or CB. CB received 0.125% bupivacaine 1 mL/kg (max 20 mL); RLB received 0.25% bupivacaine 0.1 mL/kg, both under standardized general anesthesia with intraoperative IV paracetamol (10 mg/kg). FLACC scores were recorded at 30 min and 1, 2, 4, 6, 12, and 24 h. Rescue analgesia was IV paracetamol for FLACC 2-4 and IV tramadol for FLACC >4. Primary outcome was analgesic efficacy (FLACC at 12th hour). Secondary outcomes were time to first analgesic and total consumption within 24 h. Sixty-two patients were analyzed (N.=31 per group); baseline demographics did not differ. RLB yielded lower FLACC scores at 6 h (P=0.002), 12 h (P=0.007), and 24 h (P=0.018), with no difference at 30 min or 1 h (P>0.05). Time to first analgesic was longer with RLB (P<0.001), and total 24-h consumption was lower (P=0.001). Fewer patients required rescue analgesia with RLB (3/31) than CB (14/31). No major block-related complications occurred. In pediatric orchidopexy, RLB provided superior and more durable analgesia than CB, reduced 24-h analgesic requirements, and delayed first rescue dosing without major complications, supporting its role within opioid-sparing pediatric ERAS pathways.

Polyphenols are a diverse family of plant secondary metabolites with well-documented antioxidant and anti-inflammatory activities. Bromelain is a pineapple-derived cysteine protease with documented anti-inflammatory activity. This study aimed to comprehensively evaluate the immunomodulatory, anti-inflammatory, and proliferative effects of a plant-derived polyphenol-bromelain (PB) combination (SammyVit, Turkiye) on the murine macrophage cell line J774. Cells were cultured in RPMI-1640 medium and treated with PB at 1%, 2.5%, 5%, 10%, and 20%. Inflammatory responses were assessed by measuring interleukin-6 (IL-6) and interleukin-10 (IL-10) levels; oxidative balance was evaluated using total antioxidant capacity (TAC). Cell-cycle dynamics were analyzed by flow cytometry. PB significantly reduced IL-6, increased IL-10 and TAC, and elevated the proportion of cells in the S and G2/M phases, supporting enhanced proliferative activity. Collectively, the results indicate coordinated anti-inflammatory, antioxidant, and pro-proliferative actions consistent with suppression of redox-sensitive pathways and reinforcement of a repair-compatible macrophage phenotype. The data support further mechanistic dissection and motivate translational testing in primary human macrophages and relevant in vivo models.

Inherited kidney diseases represent a genetically and clinically heterogeneous group of disorders affecting both pediatric and adult populations. Advances in next-generation sequencing (NGS) have improved diagnostic precision; however, genotype-phenotype correlations and diagnostic yield vary substantially across disease entities. We retrospectively evaluated 165 patients referred for genetic testing due to suspected inherited kidney disease. Patients were classified into three clinical groups: polycystic kidney disease, Alport syndrome, and other syndromic patients with inherited kidney diseases. Genetic analysis was performed using NGS with Human Phenotype Ontology-based gene filtering and included evaluation of both single-nucleotide variants and copy number variations. Overall diagnostic yield differed markedly between groups. A molecular diagnosis was achieved in 71.4% of Alport patients, 41.0% of PKD patients, and 70.2% of patients in the Other syndromic group. In the Alport group, variants were identified exclusively in COL4A3, COL4A4, and COL4A5, with pathogenicity and gene involvement correlating with disease severity and the presence of extrarenal manifestations. The PKD group showed predominant involvement of PKD1, followed by PKHD1 and PKD2, while a substantial proportion of patients remained genetically negative, reflecting technical and biological complexity. The Other group exhibited pronounced genetic heterogeneity, with variants distributed across multiple genes involved in tubular, glomerular, metabolic, and ciliopathy-related pathways. Computational assessments demonstrated that several variants of uncertain significance (VUS) were located in functionally critical domains and were predicted to disrupt protein stability, intermolecular interactions, or conserved structural motifs, thereby supporting the biological plausibility of their potential pathogenic impact. Phenotype-driven NGS enables effective molecular diagnosis across diverse inherited kidney diseases while revealing disease-specific differences in diagnostic yield and genotype-phenotype correlations. Systematic inclusion of variants of uncertain significance and careful integration of genetic and clinical data are essential for accurate interpretation and long-term patient management. Collectively, this study enhances understanding of inherited kidney diseases and underscores the value of integrating comprehensive genomic and computational approaches into routine nephrogenetic practice.

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.