Recep Dokuyucu

Background/Objectives: Sentinel lymph-node biopsy (SLNB) may be omitted in selected patients with clinically node-negative, early-stage breast cancer; however, the extent to which nodal information still influences contemporary adjuvant-treatment planning remains uncertain. This study aimed to determine whether disclosure of SLNB pathology changed multidisciplinary systemic-treatment and/or radiotherapy recommendations among patients fulfilling study-defined criteria derived from the 2025 American Society of Clinical Oncology omission pathway. Methods: In this single-center, retrospective, record-based paired decision-impact study, routine clinical records of consecutive postmenopausal women aged ≥ 50 years who underwent breast-conserving surgery and SLNB between 1 January 2015 and 30 June 2026 were reviewed after closure of the prespecified clinical-record window. Each anonymized case was assessed by a six-member virtual tumor board in two stages: first with SLNB pathology concealed and subsequently, after a six-week washout period, with nodal findings disclosed. The primary outcome was a definitive change in chemotherapy, CDK4/6-inhibitor, and/or radiotherapy recommendation. Paired transitions, interobserver agreement, decision confidence, and pre-SLNB factors associated with management-changing information were evaluated. Results: Among 412 eligible patients, occult sentinel-node deposits were identified in 46 (11.2%; 95% confidence interval [CI], 8.5–14.6%), including isolated tumor cells in seven, micrometastases in 13, and macrometastases in 26. Nodal disclosure produced at least one definitive management change in 28 patients (6.8%; 95% CI, 4.7–9.6%), corresponding to 14.7 SLNB procedures per management-changing recommendation. Twenty-six changes represented treatment escalation. Radiotherapy recommendations changed in 22 patients, CDK4/6-inhibitor recommendations in 13, and chemotherapy recommendations in seven, with overlap between domains. The expanded decision-impact endpoint was reached in 43 patients (10.4%; 95% CI, 7.8–13.8%). Management changed in 0.5% of patients with pN0 disease, none with isolated tumor cells, 46.2% with micrometastases, and 76.9% with macrometastases (p < 0.001). Increasing clinical tumor size was associated with management-changing information (adjusted odds ratio per 5 mm increase, 1.58; 95% CI, 1.07–2.37; p = 0.023). Conclusions: SLNB pathology left definitive adjuvant-treatment recommendations unchanged in more than 90% of selected patients but altered management in approximately one in 15, predominantly through radiotherapy-field selection and CDK4/6-inhibitor consideration. These findings support selective, multidisciplinary implementation of SLNB omission while emphasizing that decision changes do not necessarily represent proven oncological benefit.

Background/Objectives: We evaluated the Renal–Inflammatory–Nutritional–Metabolic Index (RIN-IM), a previously published 0–10-point composite biomarker score, for acute kidney injury (AKI) and renal replacement therapy (RRT) initiation in an independent intensive care unit (ICU) cohort. Methods: This retrospective study included 480 adults admitted to two ICUs between October 2023 and August 2026. RIN-IM was calculated within 24 h of admission from creatinine, albumin, systemic immune-inflammation index (platelet count × neutrophil count/lymphocyte count), pan-immune-inflammation value (neutrophil count × platelet count × monocyte count/lymphocyte count), and triglyceride–glucose index (triglyceride and admission glucose concentrations). Patients were classified by RIN-IM Score as low-risk (0–3 points), intermediate-risk (4–6 points), or high-risk (7–10 points). Among patients without AKI or acute RRT initiation at or before the 24-h landmark, subsequent incident AKI was the primary outcome and RRT initiation was the secondary renal outcome. Twenty-eight-day all-cause mortality was evaluated descriptively. Logistic regression and receiver operating characteristic analyses were performed. Results: AKI occurred in 189 patients (39.4%), RRT was initiated in 72 (15.0%), and 157 (32.7%) died within 28 days. In the low-, intermediate-, and high-risk groups, AKI frequencies were 16.0%, 40.0%, and 62.0%; RRT initiation frequencies were 3.3%, 12.2%, and 30.0%; and 28-day mortality was 18.0%, 32.2%, and 48.0%, respectively (all p < 0.001). Adjusted odds ratios per score point was 1.31 (95% confidence interval, 1.16–1.48) for AKI and 1.47 (1.25–1.73) for RRT initiation. Areas under the curve were 0.862 and 0.903, respectively, exceeding those of Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment. Conclusions: Higher RIN-IM scores were associated with AKI, RRT initiation, and higher observed 28-day mortality. The score may support early renal risk stratification, pending prospective assessment of calibration and clinical utility.

Background/Objectives: Early identification of microbiologically confirmed sepsis and antimicrobial-resistant infection remains challenging in critically ill patients. The renal–inflammatory–nutritional–metabolic (RIN-IM) score integrates serum creatinine, the systemic immune-inflammation index, pan-immune inflammation value, serum albumin, and triglyceride–glucose index. This study investigated the association of the RIN-IM score with culture-positive sepsis and antimicrobial resistance phenotypes in critically ill adults. Methods: This single-center retrospective cohort study included 318 adults with sepsis admitted to the intensive care unit between 1 January 2023 and 31 March 2026. The RIN-IM score was calculated from laboratory measurements obtained within 24 h and categorized as low (0–3), intermediate (4–6), or high risk (7–10). The primary outcome was culture-positive sepsis. Secondary analyses, restricted to patients with culture-positive sepsis, examined associations between RIN-IM and multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant phenotypes. Results: Culture-positive sepsis was identified in 154 patients (48.4%). The median RIN-IM score was higher in culture-positive than in culture-negative patients (6 [interquartile range, 4–8] vs. 4 [2–5]; p < 0.001). Culture positivity increased from 29.1% in the low-risk group to 50.4% in the intermediate-risk group and 74.6% in the high-risk group. Each one-point increase in RIN-IM was independently associated with culture-positive sepsis (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.21–1.51), while high- versus low-risk classification was associated with an aOR of 4.65 (95% CI, 2.25–9.62). Among culture-positive patients, 67 (43.5%) had MDR, and 20 (13.0%) had XDR infections. Each one-point score increase was independently associated with MDR infection (aOR, 1.29; 95% CI, 1.12–1.48). The exploratory XDR analysis was based on 20 events and used Firth’s bias-reduced logistic regression; a one-point score increase was associated with XDR infection (aOR, 1.29; 95% CI, 1.09–1.52), but the categorical estimates were imprecise. The score demonstrated moderate discrimination for culture-positive sepsis (AUC, 0.752; 95% CI, 0.699–0.805) and MDR infection (AUC, 0.724; 95% CI, 0.643–0.805); discrimination for XDR infection was exploratory (AUC, 0.742; 95% CI, 0.635–0.849). Twenty-eight-day mortality increased from 13.6% to 27.7% and 47.9% across the three risk categories (p < 0.001). Conclusions: Higher admission RIN-IM scores were associated with culture-positive sepsis. Among patients with culture-positive sepsis, higher scores were also associated with MDR infection; this subgroup analysis was conditioned on microbiological confirmation and should not be interpreted as prediction of resistant infection in the overall sepsis population. The association with XDR infection was exploratory, based on only 20 events, and requires confirmation in larger independent cohorts. Because RIN-IM assessment and microbiological sampling were not fully time-synchronized, these findings should not be interpreted as real-time microbiological prediction or evidence of clinical utility. RIN-IM should not replace culture-based diagnosis, susceptibility testing, individual risk-factor assessment, local antibiograms, or clinical judgment. The observed associations do not establish a direct biological relationship between RIN-IM and microbial burden or antimicrobial resistance.

Background/Objectives: Sleep disturbances are frequently reported in children with primary headache disorders, but differences in sleep-related symptom profiles between pediatric migraine and episodic tension-type headache (TTH) remain unclear. This study aimed to compare Pediatric Sleep Questionnaire (PSQ) total and domain scores among children and adolescents with migraine, episodic TTH, and healthy controls and to examine whether these patterns differed according to sex and age. Methods: This analytical cross-sectional study included 197 participants aged 6–18 years recruited in Mersin, Türkiye, between 1 March 2022 and 31 December 2023. Primary headache disorders were diagnosed according to the International Classification of Headache Disorders, third edition. The headache group comprised 76 patients with migraine and 27 with episodic TTH, while 94 healthy students constituted the control group. Parents completed the validated Turkish extended PSQ. A PSQ total score ≥ 6 was considered indicative of clinically relevant sleep-related symptoms. Headache characteristics and intensity, measured using a 0–10 numerical rating scale, were also recorded. Results: A PSQ total score ≥ 6 was observed in 60/103 participants with headache (58.3%) and 26/94 healthy controls (27.7%; p < 0.001). Compared with controls, participants with headache had higher median PSQ total scores (6 [interquartile range, 4–8] vs. 4 [2–6]; p < 0.001), Breathing Problems scores (2 [1–3] vs. 1.5 [1–3]; p = 0.022), Awakening and Developmental Symptoms scores (2 [1–2] vs. 1 [0–2]; p < 0.001), and Behavioral Problems scores (1 [0–3] vs. 0 [0–1]; p < 0.001). Snoring Problems scores did not differ (p = 0.659). Both migraine and episodic TTH groups had higher PSQ total and Behavioral Problems scores than healthy controls, without significant differences between the two headache diagnoses. Compared with episodic TTH, migraine was associated with a longer headache history (p = 0.011), more frequent attacks (p = 0.021), and greater headache intensity (p = 0.013). Conclusions: Children and adolescents with migraine or episodic TTH exhibit a substantially greater burden of clinically relevant sleep-related symptoms than healthy controls. This burden is primarily reflected in overall, awakening/developmental, and behavioral symptoms rather than snoring. Sleep screening should therefore be incorporated into the clinical assessment of both pediatric migraine and episodic TTH.

Background/Objectives: This study aimed to develop and internally validate the RIN-IM model, which integrates routinely measured biomarkers reflecting renal dysfunction, systemic immune-inflammatory activation, albumin-related alterations during acute illness, and metabolic stress, for prediction of 28-day mortality in critically ill adults. Methods: This retrospective cohort study included 1000 adults admitted to the intensive care unit (ICU) between January 2020 and June 2025. The first available demographic, clinical, and laboratory measurements obtained within 24 h of ICU admission were analyzed. The five prespecified RIN-IM predictors—serum creatinine, serum albumin, SII, PIV, and the TyG index—were initially evaluated as continuous variables; SII and PIV were natural-log-transformed, and potential nonlinear associations were examined using restricted cubic splines. Ridge-penalized logistic regression was used to address coefficient instability arising from correlation between SII and PIV. After evaluation of the primary continuous model, a simplified point-based score was derived by assigning 0–2 points to clinically ordered categories for each component, producing a total score of 0–10. Scores were categorized as low- (0–3), intermediate- (4–6), or high-risk (7–10). The primary outcome was 28-day all-cause mortality. Model performance was assessed using discrimination, calibration, Brier score, formal paired AUC comparisons, incremental-value testing, and decision-curve analysis. The complete development procedure was internally validated using 1000 bootstrap resamples. Results: Overall, 300 of 1000 patients (30.0%) died within 28 days. Mortality increased across the RIN-IM risk categories, from 7.6% (32/420) in the low-risk group to 27.2% (98/360) in the intermediate-risk group and 77.3% (170/220) in the high-risk group (p < 0.001). After adjustment for the clinical reference variables, each one-point increase in the simplified RIN-IM Score was associated with higher odds of 28-day mortality (adjusted OR, 1.68; 95% CI, 1.54–1.84; p < 0.001). The primary continuous model had an apparent AUC of 0.907 (95% CI, 0.885–0.929) and an optimism-corrected AUC of 0.898. The corresponding values for the simplified score were 0.890 (95% CI, 0.861–0.919) and 0.878, respectively. The apparent difference between the continuous and simplified models was 0.017 (95% CI, 0.007–0.028; p = 0.001). The simplified RIN-IM Score had higher discrimination than APACHE II (ΔAUC, 0.070; 95% CI, 0.038–0.102; p < 0.001) and SOFA (ΔAUC, 0.090; 95% CI, 0.057–0.123; p < 0.001). Adding RIN-IM to the clinical reference model increased the apparent AUC from 0.821 to 0.923 (ΔAUC, 0.102; 95% CI, 0.078–0.126; p < 0.001) and improved the Brier score from 0.160 to 0.112. Conclusions: In this single-center cohort, the RIN-IM model showed good discrimination and calibration for predicting 28-day mortality. The simplified score retained most of the predictive information of the continuous model and may complement established clinical severity scores using routinely available early laboratory measurements. External validation and clinical-impact studies are required before routine implementation.

Impaired wound healing and persistent infection are major challenges in diabetic wounds. This study aimed to investigate the therapeutic effects of topical

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, hyperandrogenism, oxidative stress, and disrupted folliculogenesis. The present study aimed to investigate whether combined alpha-lipoic acid (ALA) and vitamin D therapy exerts synergistic effects on metabolic, oxidative, endocrine, and histomorphological parameters in a letrozole-induced rat model of PCOS. Sixty female Wistar Albino rats were randomly divided into six groups: Control, PCOS, PCOS+Metformin (500 mg/kg/day), PCOS+Vitamin D (1000 IU/kg/day), PCOS + ALA (100 mg/kg/day), and PCOS + ALA+Vitamin D. PCOS was induced with letrozole (1 mg/kg/day) for 21 days, followed by 30 days of treatment. Fasting blood glucose (FBG), insulin, and HOMA-IR were assessed to evaluate metabolic status. Ovarian oxidative stress markers (MDA, SOD, CAT, GSH), serum hormonal parameters (testosterone, LH, FSH, LH/FSH ratio), and detailed histomorphometric analyses were performed. Statistical analyses included one-way and two-way ANOVA. Letrozole administration induced persistent diestrus, hyperandrogenemia, increased ovarian weight, elevated HOMA-IR (6.61 ± 1.18 vs. 2.24 ± 0.42, p < 0.001), and marked oxidative stress (MDA: 5.84 ± 0.72 vs. 2.31 ± 0.34 nmol/mg, p < 0.001). ALA and vitamin D monotherapies significantly improved metabolic, oxidative, and endocrine parameters compared with untreated PCOS rats (p < 0.05). The combination therapy group demonstrated the most pronounced improvements, with HOMA-IR (2.43 ± 0.47), MDA (2.52 ± 0.39 nmol/mg), testosterone (1.29 ± 0.27 ng/mL), and LH/FSH ratio (1.03 ± 0.19) values approaching control levels (all p < 0.01 vs. PCOS). Histologically, combined treatment markedly reduced cystic follicles and restored granulosa and theca thickness. Two-way ANOVA revealed significant interaction effects for HOMA-IR, MDA, testosterone, and LH/FSH ratio (p < 0.05). Combined ALA and vitamin D therapy produced enhanced improvements in insulin resistance, oxidative stress, endocrine imbalance, and ovarian morphology in experimental PCOS. Simultaneous targeting of mitochondrial redox dysfunction and endocrine–metabolic signaling pathways may represent a promising multidimensional therapeutic approach in PCOS.

This study aimed to investigate the relaxant effects of doxazosin (an α₁-adrenergic receptor blocker) and vardenafil (a phosphodiesterase type 5 inhibitor) on rabbit ureteral smooth muscle using an in vitro organ-bath model, and to determine whether sequential administration enhances relaxation, particularly in different ureteral segments. Ureteral segments (middle and distal) were obtained from 15 adult male New Zealand White rabbits and mounted in organ baths containing oxygenated Krebs-Henseleit solution at 37 °C. Each ureteral segment (middle and distal) obtained from the animals was treated as an independent experimental unit. Thus, a total of 15 middle and 15 distal ureteral segments were analyzed (n = 15 per group). Contractions were induced by 60 mmol/L KCl, and relaxation responses to doxazosin and vardenafil-applied separately or sequentially-were recorded isometrically. The degree of relaxation was expressed as a percentage of the initial KCl-induced contraction. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test. Both doxazosin and vardenafil produced significant relaxation in KCl-precontracted tissues (p < 0.001). In the middle ureter, relaxation responses were 47.3 ± 3.6% for doxazosin and 33.7 ± 3.5% for vardenafil. In the distal ureter, relaxation increased to 54.6 ± 2.2% and 40.8 ± 2.2%, respectively. Sequential administration of doxazosin followed by vardenafil yielded the greatest relaxation (84.1 ± 3.9% in middle, 88.4 ± 3.1% in distal segments; p < 0.001), whereas the reverse order produced a lower but still significant response (57.4 ± 4.8% and 80.5 ± 4.4%, respectively). Overall, distal segments exhibited greater pharmacologic sensitivity than middle ones. Doxazosin and vardenafil both exert potent relaxant effects on ureteral smooth muscle, with enhanced efficacy when administered sequentially-especially in distal segments. These findings provide mechanistic insight into the synergistic interaction between α₁-adrenergic blockade and PDE5 inhibition and support the rationale for combination therapy in facilitating distal ureteral stone passage.

Background/Objectives: This study aimed to investigate the internalizing characteristics, including anxiety and depressive symptoms, in adolescents presenting with non-cardiac chest pain (NCCP), and to explore the effects of sociodemographic variables and prior psychosocial experiences on psychological distress. Methods: This cross-sectional study was conducted in Turkey and included 128 adolescents aged 10–18 years (57.0% female, 43.0% male) who presented to pediatric cardiology or general pediatric outpatient clinics. The Children’s Depression Inventory (CDI), State–Trait Anxiety Inventory for Children (STAI-C), Screen for Child Anxiety Related Emotional Disorders (SCARED), Brief Symptom Inventory (BSI), and the Social Support Appraisals Scale for Children (SSAS-C). Sociodemographic variables and prior psychosocial symptom history were also recorded. Results: Adolescents with non-cardiac chest pain exhibited elevated anxiety and psychological distress compared to controls. Female participants demonstrated higher levels of stress, anxiety, and overall psychological symptom burden than males. Higher maternal age was associated with lower perceived stress, while a prior history of psychosocial symptoms was linked to increased anxiety and global psychological distress. Participants with a history of psychosocial symptoms had higher anxiety (p = 0.027) and BSI (p = 0.004) scores. Significant positive correlations were found between anxiety, depression, obsessive–compulsive symptoms, and the BSI total score (r values ranging from 0.718 to 0.892). Conclusions: Adolescents with NCCP exhibit significant internalizing symptoms, particularly anxiety and depression. Female gender and prior psychosocial stressors were associated with elevated symptom scores. Maternal age may have a buffering effect on adolescent stress levels. These findings underscore the importance of integrating psychological screening into the evaluation of chest pain in adolescents to enable early identification and intervention.

Objectives: This study aimed to evaluate the effects of thymoquinone (TMQ) on metabolic, hormonal, and ovarian dysfunctions in a letrozole-induced polycystic ovary syndrome (PCOS) rat model and compare its efficacy with metformin, which is widely recognized as the first-line pharmacological treatment for PCOS. Methods: Thirty-two female Wistar Albino rats were randomly assigned into four groups: control (I), PCOS (II), PCOS + metformin (III), and PCOS + Thymoquinone (IV). PCOS was induced using 1 mg/kg/day letrozole for 21 days, followed by treatment with either metformin (500 mg/kg/day) or thymoquinone (50 mg/kg/day) for 30 days. Metabolic (glucose, insulin, HOMA-IR, lipid profile), hormonal (estrone, estradiol, testosterone, androstenedione), and histopathological parameters were assessed. Results: PCOS induction resulted in significant metabolic, hormonal, and ovarian dysfunctions. Final body weight was significantly higher in PCOS (309.0 ± 7.5 g) vs. control (275.3 ± 8.2 g, p < 0.001), but reduced by metformin (294.0 ± 7.4 g, p < 0.01) and thymoquinone (305.7 ± 7.5 g, p < 0.01). Glucose levels were significantly elevated in PCOS (341.8 ± 16.8 mg/dL) vs. control (260.0 ± 15.8 mg/dL, p < 0.01), while metformin (290.2 ± 19.7 mg/dL, p < 0.05) and thymoquinone (320.3 ± 13.7 mg/dL, p < 0.05) reduced glucose levels. Insulin and HOMA-IR were significantly increased in PCOS (p < 0.001), but reduced by both treatments (p < 0.01). Lipid profile improvements were observed, with significant reductions in TG and LDL-C and increases in HDL-C in both treatment groups (p < 0.05–0.01). PCOS induced hyperandrogenism, with increased testosterone and androstenedione (p < 0.05), and a decreased E2/E1 ratio (p < 0.001), which were significantly improved by metformin and thymoquinone (p < 0.01). Ovarian histopathology showed increased cystic and atretic follicles and reduced corpus luteum in PCOS (p < 0.05–0.01), which were significantly improved by both treatments. Conclusions: TMQ exerts metabolic, hormonal, and ovarian protective effects comparable to metformin, supporting its potential as a natural therapeutic alternative for PCOS management. Given that metformin is already established as a first-line pharmacological therapy, our findings suggest that TMQ may provide a promising complementary or alternative approach. Further clinical studies are warranted to evaluate its safety and efficacy in human PCOS patients.