Search Results (12,780)

Background/Objectives: People with HIV (PWH) remain at high risk for cardiovascular and metabolic complications despite effective antiretroviral therapy (ART). Diet quality is an important modifiable factor that may influence these complications. Diets high in ultra-processed foods (UPF) have been linked to adverse metabolic and inflammatory profiles in the general population, but their impact on PWH remains poorly understood. The NOVA 4 classification categorizes foods by degree of processing, from unprocessed/minimally processed (NOVA 1) to UPF (NOVA 4). Methods: We conducted a cross-sectional study of adults with virologically suppressed HIV on stable ART. Assessments included dietary intake consisting of 24 h recalls analyzed with Nutrition Data System for Research software (NDSR) and classified into NOVA categories by a registered dietitian and the following characteristics: body composition (total and regional fat by DEXA and CT scan abdomen), cardiometabolic variables (glucose, HbA1C, HOMA-IR, lipids, blood pressure), and biomarkers of inflammation, immune activation, and gut integrity quantified by ELISA. Patients were stratified into NOVA 4 groups based on the median and quartile proportions of total energy intake from NOVA 4 foods. Associations between dietary NOVA and outcomes were analyzed using generalized additive models (GAMs) adjusted for age, sex, race, and CD4 count. Results: Among 222 PWH (mean age 45.4 ± 14.2 years; 31% female; 66% non-white; BMI 30.61 ± 7.91 kg/m²), median NOVA 4 intake was 45.6% of total energy intake. Participants with higher vs. lower NOVA 4 intake showed differences in diet quality, but in GAMs, higher NOVA 4 intake was not associated with higher levels of inflammatory, cardiometabolic, gut integrity, and body composition variables. Conclusions: In PWH, UPF consumption was high but not associated with markers of cardiometabolic health, systemic inflammation, or gut integrity. This may reflect the multifactorial nature of the heightened inflammation in PWH, potentially obscuring the effect of diet. Full article

Objective: Village Health Volunteers (VHVs) are vital to Thailand’s primary healthcare, yet many face high risks for non-communicable diseases (NCDs). This preliminary study aimed to implement health empowerment theory-based personalized health promotion for individuals in the NCD-risk group. Methods: The preliminary mixed-methods study implemented a 6-month empowerment-based health promotion program for 21 VHV leaders (mean age 62.43 ± 7.28 years) at risk for NCDs. The intervention integrated laboratory data, behavioral and qualitative focus-group insights, and quantitative anthropometric data obtained via bioelectrical impedance analysis (BIA). Results: Participants’ exercise adequacy significantly improved after the intervention, increasing from 8.3% to 61.9% (p = 0.03). BIA revealed a physiological shift toward improved energy homeostasis, including decreased body weight, reduced visceral fat area, and increased muscle hydration. While biochemical markers did not reach statistical significance, clinically favorable downward trends were observed in median HbA1c (8.0% to 7.3%) and LDL cholesterol (141.8 to 119.0 mg/dL), alongside stable renal and liver function. Qualitative thematic analysis identified four primary domains of impact: sustainability and systemic advocacy, personal transformation, broad competence acquisition, and enhanced social capital. Participants reported a marked increase in self-efficacy, transitioning from inactive beneficiaries to active health advocates. This change was largely driven by mastery experiences, such as visible improvements in body composition and functional health literacy. Conclusions: The empowerment program significantly improved physical activity and body composition while fostering the social capital and health literacy necessary for community leadership, suggesting that personal health mastery is a critical precursor to effective systemic advocacy and long-term sustainability in community-led health programs. Full article

Background: Obstructive sleep apnea (OSA) is a common but underrecognized sleep-related breathing disorder characterized by intermittent hypoxemia and autonomic dysfunction. OSA prevalence and clinical relevance in Type 1 Diabetes Mellitus (T1DM), particularly in relation to diabetes-related vascular complications, remain insufficiently explored. Objective: The aim of this study was to evaluate the prevalence of high-risk OSA in adults with T1DM and controls, and to investigate the association between high-risk OSA and microvascular complications among individuals with T1DM. Methods: In this cross-sectional case–control study, 102 adults with T1DM and 126 controls were included. OSA risk was assessed using the modified Berlin Questionnaire (mBQ). Analyses of vascular complications were restricted to participants with T1DM. Multivariable logistic regression models adjusted for age and sex were used to assess associations, with additional adjustments for body mass index, hypertension, current smoking, alcohol use and glycated hemoglobin A1c. Results: High-risk OSA was identified in 18.6% of individuals with T1DM and 11.9% of controls, with no significant difference between groups. Among participants with T1DM, the prevalence of microvascular complications (retinopathy and/or neuropathy) was substantially higher in those with high-risk OSA compared with those at low risk (68.4% vs. 18.07%, p <0.001). In univariate logistic regression analysis, high-risk OSA was significantly associated with microvascular complications (odds ratio [OR] 4.85; 95% confidence interval [CI] 1.65–14.24; p = 0.004). This association remained significant in the fully adjusted model (OR 5.55; 95% CI 1.36–22.65; p = 0.017). Conclusions: High-risk OSA is not more prevalent in adults with T1DM compared with controls; however, among individuals with T1DM, high-risk OSA is strongly and independently associated with microvascular complications. Given the potential contribution of diabetic microvascular and autonomic neuropathy to upper airway dysfunction, the relationship between OSA and vascular complications in T1DM may be bidirectional, warranting further longitudinal investigation. Full article

Background: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality, even at early stages. Postmenopausal women represent a particularly vulnerable population due to estrogen deficiency, which promotes adverse cardiovascular remodeling. However, data specifically characterizing the cardiac phenotype of hypertensive postmenopausal women with mild-to-moderate CKD remain limited. Methods: We conducted a prospective observational cohort study including 413 hypertensive postmenopausal women consecutively referred to a tertiary center between 2019 and 2022. Participants were stratified into a CKD group with stage 3 CKD (estimated glomerular filtration rate of 30–59 mL/min/1.73 m²; n = 213) and a control group without CKD (n = 200). All subjects underwent comprehensive clinical evaluation, laboratory testing, and standardized transthoracic echocardiography. The prevalence of left ventricular hypertrophy (LVH), left ventricular diastolic dysfunction (LVDD), and chronic coronary syndromes (CCS) was assessed. Multivariable logistic regression analyses were performed to evaluate independent associations between CKD and cardiovascular abnormalities. Results: Compared with controls, women with CKD showed a significantly higher prevalence of LVH (46.7% vs. 21.5%), LVDD (55.8% vs. 36.0%), and CCS (15.5% vs. 7.5%) (all p < 0.01). The coexistence of LVH and LVDD identified a high-risk cardiac phenotype that was markedly more frequent in the CKD group (41.3% vs. 12.5%). After adjustment for age, body mass index, blood pressure, duration of hypertension, smoking status, and antihypertensive therapy, stage 3 CKD remained independently associated with LVH, LVDD, and CCS. Conclusions: In hypertensive postmenopausal women, mild-to-moderate CKD is associated with a substantial burden of cardiac structural and functional abnormalities exceeding that attributable to hypertension alone, supporting early cardiovascular screening and an integrated cardiorenal approach. Full article

Background: Obstructive sleep apnea (OSA) is a significant cardiovascular risk factor, frequently co-existing with systemic hypertension. While the association between OSA and blood pressure elevation is well documented, its specific prevalence and impact among patients with resistant hypertension remain a critical area of clinical investigation. Objective: The primary aim of this study was to evaluate the prevalence and severity of obstructive sleep apnea (OSA) specifically within a cohort of patients with resistant hypertension (RHT). Additionally, we sought to identify the clinical and anthropometric factors that distinguish RHT patients with OSA from non-resistant hypertensive and normotensive controls, thereby clarifying the increased hypoxic burden and polysomnographic differences unique to this high-risk population. Methods: A total of 300 patients presenting with OSA symptoms were included. Participants were classified into three groups: Group 0 (n = 100), normotensive individuals; Group 1 (n = 100), non-resistant hypertension; and Group 2 (n = 100), confirmed resistant hypertension. Standard overnight polysomnography (PSG) was performed on all participants. Demographic data, comorbidities, anthropometric measurements, and PSG parameters were recorded and compared across groups. Results: Of the subjects, 50.3% were female (sex), and the mean age was $49.5 \pm 12.3$ years. Patients with RHT (Group 2) were significantly older and had a higher prevalence of diabetes mellitus. OSA prevalence was 94% in Group 2 (37% severe), 89% in Group 1 (22% severe), and 74% in Group 0 (only 2% severe). In PSG analysis, AHI and ODI values were significantly higher in hypertensive groups (Groups 1 and 2) compared to normotensive individuals (Group 0), while minimum and mean oxygen saturations were significantly lower. Conclusions: OSA is both more prevalent and more severe in patients with resistant hypertension. Furthermore, hypertensive OSA patients are characterized by an increased hypoxic load compared to normotensives. Systematic investigation and detailed polysomnographic evaluation of OSA are of paramount importance in hypertensive individuals, particularly those with resistant hypertension. Full article

Background: Ventricular septal rupture (VSR) following acute myocardial infarction (AMI) creates an abrupt left-to-right shunt that can progress to cardiogenic shock (CS). Once CS develops, mortality increases dramatically and delayed repair becomes less feasible. Intra-aortic balloon pumps (IABPs) are widely used to facilitate delayed repair; however, whether initiating IABP before CS onset improves survival remains unclear. Methods: We retrospectively analyzed 124 patients with AMI-related VSR (2009–2024), categorized by IABP timing relative to CS onset (defined as first catecholamine administration) into pre-CS, post-CS, and no-IABP groups. The primary outcome was all-cause mortality within 90 days after AMI onset. Kaplan–Meier curves and Cox proportional hazards models were applied, with subgroup analyses by CS status. Results: The 90-day survival rate was 68.2% in the pre-CS IABP group, 14.3% in the post-CS group, and 35.1% in the no-IABP group. Pre-CS IABP was associated with significantly lower mortality compared with no-IABP (adjusted HR = 0.401, 95% CI 0.174–0.925, p = 0.032) and post-CS IABP (adjusted HR = 0.369, 95% CI 0.149–0.910, p = 0.030). In the CS subgroup, IABP use did not improve survival (19.4% vs. 17.6%, p = 0.365). Among non-CS patients, IABP use was independently associated with lower mortality (85.7% vs. 50.0%, p = 0.027; adjusted HR = 0.178, 95% CI 0.040–0.801, p = 0.025). Conclusions: Given the retrospective design and limited sample size, these findings are hypothesis-generating. Early IABP use was associated with improved short-term survival, an effect not observed once CS had developed. These findings support early risk stratification to identify high-risk patients who may benefit from timely hemodynamic support. Full article

Gestational weight gain (GWG) and birth weight (BW) have a multifactorial etiology, which makes identifying the most influential determinants difficult. The association between variants of the FTO and LEPR genes has been explored as contributing factors to obesity in various age groups; however, their role in GWG and BW in adolescent mothers and their offspring is uncertain. To determine whether the presence of polymorphisms rs9939609 (FTO) and rs1137101 (LEPR) is associated with gestational weight gain and newborn weight in a cohort of adolescent mothers. Methods: A prospective cohort study of 305 mother-child dyads was conducted between 2020 and 2024. Genotyping of the single nucleotide variants (SNVs) rs9939609 of the FTO gene and rs1137101 of the LEPR gene was performed using real-time PCR and high-resolution melting analysis (qPCR-HRM), using maternal peripheral blood and umbilical cord blood samples. GWG, BW, energy intake, and other perinatal data were recorded and classified. Genetic data from 305 mother–offspring dyads were analyzed. The median maternal age was 16 years, and 71.4% had a normal pre-pregnancy body mass index (BMI). The most frequent genotypes were TT for FTO rs9939609 and AG for LEPR rs1137101. In both groups, the genotypic distribution significantly deviated from Hardy–Weinberg equilibrium (p < 0.0001). The AA genotype of FTO was associated with a higher probability of excessive gestational weight gain (GWG) after adjustment for pre-pregnancy BMI and dietary and sociodemographic factors. High protein and lipid intake increased the risk of excessive GWG, whereas adequate intake of carbohydrates and legumes showed a protective effect. An initial significant association was identified between the LEPR rs1137101 variant (AA allele) and low birth weight (LBW); however, this association was lost after adjustment for confounding factors. The FTO rs9939609 variant was significantly associated with GWG. On the other hand, the LEPR rs1137101 variant in the offspring showed an association with BW categorized by percentiles (in crude analysis), while the FTO variant showed no relationship with birth weight. Full article

Background/Objectives: Metabolic syndrome (MS) is associated with an increased cardiovascular risk. The aim of this study was to reveal the effects of Chaenomeles japonica fruit juice (CJFJ) on energy balance and biochemical and histological parameters in rats with diet-induced MS. Methods: Fifty Wistar rats were allocated into five groups. For ten weeks, the Control group received a standard laboratory diet and tap water, while the other groups were given a high-fat high-fructose (HFHF) diet. The Control and MS groups were treated with distilled water, while the other three groups were treated with CJFJ at increasing doses. Results: Rats on an HFHF diet consumed less food and more liquids and had a higher caloric intake than the Control group. Among the CJFJ-treated animals, an increased food consumption, as well as an increased total caloric intake, and no difference in body weight gain were observed in comparison with the MS group. CJFJ did not affect glucose tolerance or the triglyceride and total cholesterol levels. CJFJ prevented an HFHF-induced decrease in superoxide dismutase and caused a decrease in thiobarbituric acid-reactive substances in serum. The medium CJFJ dose prevented an HFHF-induced increase in adipose tissue indices. Liver and adipose tissue histology revealed a protective effect of CJFJ. Conclusions: CJFJ may exert beneficial effects on visceral adiposity, oxidative status, and histopathological changes in the liver and adipose tissue in rats with diet-induced MS. Full article

Background and Objectives: Metaplastic breast carcinoma (MBC) is a rare, aggressive malignancy that is often resistant to conventional chemotherapy and characterized by a triple-negative phenotype. While immune checkpoint inhibition shows promise, the prognostic significance and distribution of programmed death-ligand 1 (PD-L1) expression within the heterogeneous architecture of MBC remain poorly understood. This study aimed to evaluate PD-L1 expression and the density of tumor-infiltrating lymphocytes (TILs) to clarify their roles in patient stratification and overall survival (OS). Materials and Methods: We retrospectively analyzed 48 MBC cases diagnosed between 2010 and 2025. PD-L1 expression was quantified using the Combined Positive Score (CPS) with the 22C3 antibody clone across diverse histological components. The density of stromal TIL density was assessed following internationally standardized guidelines. Clinical outcomes and clinicopathological parameters, including metastasis, lymphovascular invasion (LVI), and histological subtype, were correlated with biomarker status using Kaplan–Meier survival analysis and Cox proportional hazards regression models. Results: PD-L1 positivity (CPS ≥1) was identified in 72.9% of cases, one of the highest rates documented in literature. Notably, an inverse relationship was observed with PD-L1-negative tumors, which exhibited significantly higher rates of distant metastasis (46.2% vs. 17.1%; p = 0.039). Multivariate analysis confirmed that low density of TILs (HR = 9.66; p = 0.016), metastasis (HR = 4.40; p = 0.023), and the presence of LVI (HR = 3.84; p = 0.047) were strong independent predictors of mortality. While PD-L1 status alone did not directly dictate overall survival, mean overall survival was markedly reduced in the low TILs cohort (32.2 months) compared to the high TILs group (114.2 months). Conclusions: The high prevalence of PD-L1 expression supports routine screening for immunotherapy eligibility in MBC. Our findings suggest that PD-L1-negative cases represent a high-risk biological subset driven by alternative immune evasion mechanisms. Integrating TIL density with conventional pathological parameters provides a more robust prognostic framework, enabling personalized therapeutic strategies for this challenging malignancy. Full article

Background/Objectives: Loss of nuclear BAP1 (BRCA1-associated protein 1) expression is a well-established adverse prognostic marker in uveal melanoma (UM). However, data from Central and Southeastern European populations are limited. This descriptive study aimed to evaluate BAP1 immunohistochemical expression in a Croatian enucleation-based UM cohort, characterize its associations with clinicopathological parameters, and contextualize the findings within the published literature. Methods: Formalin-fixed, paraffin-embedded tumor tissue from 58 consecutive patients with primary choroidal and ciliary body melanoma treated with enucleation at University Hospital Centre Zagreb (2006–2016) was analyzed immunohistochemically for BAP1 nuclear expression. Associations with clinicopathological parameters were assessed using chi-square and Fisher’s exact tests. Survival analysis was performed using Kaplan–Meier estimation, log-rank tests, and Cox proportional hazards regression with a median follow-up of 11.2 years. Results: Loss of nuclear BAP1 expression was observed in 53/58 (91.4%) specimens, resulting in a severely imbalanced distribution (53 versus 5 patients) precluding meaningful comparative survival analysis. Five-year and 10-year overall survival rates were 72.4% and 51.7%, respectively, with a median overall survival of 14.5 years. BAP1 loss was associated with longer disease-free survival (log-rank p = 0.020); however, this finding likely reflects a statistical artifact attributable to the extremely small BAP1-retained group (n = 5) harboring concurrent adverse features and should not be interpreted biologically. The study was underpowered to draw prognostic inferences regarding BAP1 status. Exploratory survival analyses are presented for transparency but should not be interpreted inferentially. Conclusions: The exceptionally high prevalence of BAP1 loss reflects the selection bias inherent in enucleation-based cohorts, which are enriched for large, molecularly high-risk tumors. This study provides the first comprehensive BAP1 immunohistochemical data from Croatia, contributing to the growing evidence that enucleation cohorts represent a distinct, biologically high-risk subgroup in which BAP1 immunohistochemistry offers limited discriminatory value. The extended follow-up of 11.2 years confirms the prolonged natural history of UM. Future multi-center studies incorporating molecular validation and diverse treatment modalities are needed to establish the prognostic utility of BAP1 across the full spectrum of UM disease. Full article

This study investigated injury severity in 18,528 police-reported vehicle-to-pedestrian crashes involving elderly pedestrians in legally classified local areas of South Korea during 2012–2021. Injury severity was coded into four ordered categories: fatal, serious, minor, and reported injury. To stabilize scenario extraction from a categorical crash database, an integrated screening workflow was applied, including near-zero-variance filtering, redundancy control among overlapping roadway encodings, representative-variable selection within redundant groups, and chi-square association checks. Classification and regression tree (CART) modeling was then used to identify rule-based combinations of environmental, roadway, driver, pedestrian, and vehicle factors associated with elevated severity, while tree complexity was controlled through cost-complexity pruning and 10-fold cross-validation. A scenario-based sensitivity analysis was further conducted to evaluate counterfactual shifts in severity distributions under targeted control of key conditions within representative high-risk scenarios. The results showed that severe outcomes were concentrated in stacked-risk combinations rather than in single factors alone. A dominant pathway involved nighttime conditions combined with maneuver-related driving contexts and speeding-related violations. High-fatality scenarios persisted even when speed-related predictors were excluded, underscoring the roles of nighttime exposure, visibility limitations, conflict-prone roadway settings, heavy-vehicle involvement, and pedestrian exposure behaviors. The proposed framework translates administrative crash records into concise, operationally interpretable scenarios and intervention-relevant evidence for local-area safety. Full article

Objective: The present study aimed to compare muscle thickness and physical performance in different functional tests predicting falls between older adults with low and high fall risk. Methods: Seventy-one community-dwelling older women (74.5 ± 8.5 years old) volunteered for this study. The Berg Balance Scale (BBS) was used to stratify the sample as low and high risk for fall (BBS cutoff = ≥ 50 points). The performance in the Timed Up and Go Test (TUGT), 5-repetition sit-to-stand test (5xSST), 3 m walk test (3mWT), and 3 m backward walk test (3mBWT) was assessed. The elbow flexor and knee extensor muscle thickness were obtained by ultrasound (USD). A linear mixed model analysis was used to determine between-group differences in functional mobility and muscle thickness, and Bayesian analysis was applied to check the probability to replicate the same results (i.e., the magnitude of the evidence). Results: The low-fall-risk group exhibited significantly better performance only in 3mWT (mean difference = 0.84 s [95% CI: 0.40 to 1.29 s]; p = 0.001) and 3mBWT (mean difference = 1.54 s [95% CI: 0.21 to 2.85 s]; p = 0.024). The Bayes Factor (BF) for performance on the 3mWT and 3mBWT shows that the low-fall-risk group has a probability of 98.7% (BF10 = 77.3) and 99.7% (BF10 = 368), respectively, of performing better than the high-fall-risk group. Conclusions: Based on inferential and Bayesian analysis, the performance in 3mWT and that in 3mBWT were classified as very strong to excellent instruments, respectively, for differentiating older women with high fall risk. Full article

Background: The prognostic assessment of patients with spinal metastases is primarily based on clinical and radiological parameters. Biological tumor characteristics such as the proliferation marker Ki-67 have prognostic relevance in various metastatic settings. This study aimed to evaluate the prognostic impact of the Ki-67 proliferation index on survival outcomes in patients undergoing surgery for spinal metastases. Methods: We included 166 patients who underwent surgical treatment for spinal metastases at our university clinic between 2015 and 2024. Clinical, functional, tumor-related, and perioperative variables were collected. Receiver operating characteristic (ROC) analysis was performed to evaluate the discriminatory ability of Ki-67, and comparisons were made between patient groups according to Ki-67 expression (≤20% vs. >20%). Results: Based on ROC analysis, Ki-67 demonstrated a moderate but significant predictive ability for 1-year mortality (area under the curve [AUC]: 0.69, p = 0.001). Patients with a Ki-67 index of >20% showed a significantly shorter overall survival than those with a lower Ki-67 index of ≤20% (median overall survival: 5.0 vs. 14.5 months, p < 0.001). One-year mortality was significantly higher in the high Ki-67 group (78.9% vs. 41.8%, p = 0.001). High Ki-67 expression was associated with more aggressive tumor characteristics but was not associated with increased perioperative morbidity. Conclusions: The Ki-67 proliferation index is a significant prognostic biomarker in surgically treated patients with spinal metastases. A Ki-67 index threshold of 20% identifies patients at increased risk of early mortality and significantly reduced overall survival. Full article

Background and Objectives: The vedolizumab clinical decision support tool (VDZ-CDST) was developed to predict treatment outcomes in inflammatory bowel disease (IBD). While validated in clinical trial and consortium settings, its real-world performance remains less clear. The aim of our study was to evaluate the predictive value of pre-treatment CDST stratification for clinical and endoscopic outcomes and treatment persistence in real-world VDZ-treated IBD patients. Materials and Methods: We conducted a retrospective analysis of consecutive IBD patients initiating vedolizumab therapy, stratified by CDST risk groups. Clinical remission (CR) and corticosteroid-free remission (CSFR) at weeks 14 and 52 were assessed using PRO-2 in both Crohn’s disease (CD) and ulcerative colitis (UC). Endoscopic outcomes and treatment persistence were also evaluated. Results: 129 IBD patients, 57 with CD and 72 with UC, treated with vedolizumab were retrospectively stratified according to VDZ-CDST. In CD at week 52 the differences in CSFR between CDST groups were statistically significant (p = 0.04). A statistically significant association (p < 0.001) was also observed between CDST groups and endoscopic activity (EA) at follow-up endoscopy. In the low-probability group 69.2% showed persistent EA, whereas in the high-probability group 68.8% achieved endoscopic remission (ER). We also found significant differences (p = 0.004 and p < 0.001, respectively) in treatment persistence between CDST groups in CD. VDZ discontinuation rates were 76.9%, 28.6%, and 6.3% in the low-, intermediate-, and high-response groups, respectively. In UC, no predictive association was observed for either clinical or endoscopic outcomes nor treatment persistence; however, we observed relatively high remission rates despite CDST-based stratification. Conclusions: Although the VDZ-CDST failed to predict CR measured by PRO-2 in real-world IBD patients, it demonstrated meaningful associations with long-term CSFR, endoscopic outcomes and treatment persistence in Crohn’s disease. These findings support its role as a supportive tool in therapeutic decision-making, particularly when objective outcomes such as mucosal healing are prioritized. Prospective multicentre studies incorporating biomarkers and pharmacokinetic data are needed to refine VDZ-CDST for broader clinical application. Full article

Background/Objectives: Central Nervous System (CNS) relapse represents a severe and often fatal complication of Diffuse Large B-Cell Lymphoma (DLBCL). This study aimed to evaluate clinical, biological, and treatment-related factors associated with progression-free survival (PFS) until CNS relapse in patients with DLBCL. Methods: A retrospective cohort study was conducted using clinical data from adult DLBCL patients evaluated and treated at the Regional Institute of Oncology, Iași, Romania, between 2015 and 2023. Associations between clinical, biological, and treatment-related variables and CNS relapse were evaluated using univariate and multivariable Cox proportional hazards models, Fine–Gray competing-risk analyses, and propensity score-based methods to address confounding by indication for CNS prophylaxis. Results: Twenty-six CNS relapse events (6.3%) and 72 deaths without prior CNS relapse occurred over a median follow-up of 12 months. In the prespecified reduced multivariable Cox model, non-R-CHOP regimens (HR 4.57, 95% CI 1.67–12.52; p = 0.003) and high CNS-IPI scores (HR 4.70, 95% CI 1.14–19.46; p = 0.033) were independently associated with CNS relapse. The 20-month cumulative incidence of CNS relapse was 7.0% in the R-CHOP-like group versus 35.2% in the non-R-CHOP group (Gray’s test p < 0.001). Fine–Gray modeling confirmed the association for non-R-CHOP regimens (SHR 3.38, 95% CI 1.21–9.45; p = 0.02). Cell-of-origin subtype, double-expressor phenotype, and Ki-67 were not significantly associated with CNS relapse. Conclusions: High CNS-IPI and treatment with non-R-CHOP regimens independently predicted earlier CNS relapse. Future multicenter studies with molecular profiling are needed to refine CNS risk stratification. Full article