Search Results (3,571)

Background/Objectives: Diagnosing ASD becomes more difficult with age, especially in girls. This study explores developmental factors and diagnostic tools that affect ASD diagnoses after age six. The study also integrates the neurodiversity paradigm to evaluate how diagnostic tools like the ADOS-2 and Social Attribution Test (SAT) capture the heterogeneous presentation of ASD across genders. Methods: This retrospective study analyzed data from 91 children (73 boys, 18 girls) assessed for ASD between ages 6–18. Multivariate Generalized Linear Models (GLMs) were employed to identify independent predictors of diagnosis, controlling for age, gender, and language difficulties. Results: Notable gender differences emerged: boys showed more atypical development and restricted interests, while girls showed higher sensory sensitivity. Multivariate analysis confirmed that Social Affect (SA), age of initial concern, and the absence of structural language difficulties significantly impacted diagnosis likelihood. Conclusions: This study emphasizes the need for gender-sensitive criteria and implicit measures like the SAT to identify “masking” phenotypes. It emphasizes current tool limitations, the risk of diagnostic overshadowing, and the importance of longitudinal studies with comprehensive assessments to better capture ASD diversity, especially in social and language skills. Full article

Background/Objectives: This study aimed to evaluate the prognostic value of ¹⁸F-FDG PET/CT-based secondary lymphoid organ metabolic ratios—spleen/liver (SLR), bone marrow/liver (BLR), and ileocecal region/liver (ILR)—and hematological inflammation markers (neutrophil/lymphocyte ratio [NLR] and systemic immune-inflammation index [SII]) obtained before nivolumab treatment in relation to survival in patients with advanced non-small cell lung cancer (NSCLC). Methods: This retrospective single-center study included 79 advanced NSCLC patients who were treated with nivolumab monotherapy at Marmara University Faculty of Medicine Hospital between 2022 and 2024. Pretreatment SLR, BLR, and ILR ratios were calculated from ¹⁸F-FDG PET/CT examinations; NLR and SII values were obtained from hematological data. Survival outcomes were analyzed using the Kaplan–Meier method, and prognostic factors were assessed using Cox proportional hazards regression analysis. In a subset of patients, an exploratory longitudinal analysis was performed using early follow-up PET/CT to assess follow-up-to-baseline changes in immune-organ metabolic ratios in relation to overall survival. Results: High NLR and SII levels were significantly associated with shorter progression-free survival and overall survival. In contrast, no significant associations were observed between PET/CT-derived metabolic ratios (SLR, BLR, and ILR) and survival. Multivariate analysis identified the presence of liver metastases and a high NLR as independent adverse prognostic factors for overall survival. Conclusions: In this homogeneous real-world cohort treated exclusively with single-agent nivolumab, PET/CT-derived secondary lymphoid organ metabolic ratios showed limited prognostic value at baseline and during early on-treatment assessment. In contrast, hematological inflammation markers, especially high NLR levels, are strong prognostic indicators of survival and may complement established clinical factors in risk stratification. Full article

Genome-wide association studies (GWAS) are essential for identifying genomic regions associated with agronomic traits, but Linear Mixed Model (LMM)-based GWAS face challenges in capturing complex gene interactions. This study explores the potential of machine learning (ML) methodologies to enhance marker identification and association modeling in plant breeding. Unlike LMM-based GWAS, ML approaches do not require prior assumptions about marker–phenotype relationships, enabling the detection of epistatic effects and non-linear interactions. The research sought to assess and contrast approaches utilizing ML (Decision Tree—DT; Bagging—BA; Random Forest—RF; Boosting—BO; and Multivariate Adaptive Regression Splines—MARS) and LMM-based GWAS. A simulated F₂ population comprising 1000 individuals was analyzed using 4010 SNP markers and ten traits modeled with epistatic interactions. The simulation included quantitative trait loci (QTL) counts varying between 8 and 240, with heritability levels set at 0.5 and 0.8. These characteristics simulate traits of candidate crops that represent a diverse range of agronomic species, including major cereal crops (e.g., maize and wheat) as well as leguminous crops (e.g., soybean), such as yield, with moderate heritability and a high number of QTLs, and plant height, with high heritability and an average number of QTLs, among others. To validate the simulation findings, the methodologies were further applied to a real Coffea arabica population (n = 195) to identify genomic regions associated with yield, a complex polygenic trait. Results demonstrated a fundamental trade-off between sensitivity and precision. Specifically, for the most complex trait evaluated (240 QTLs under epistatic control), Ensemble methods (Bagging and Random Forest) maintained a Detection Power (DP) exceeding 90%, significantly outperforming state-of-the-art GWAS methods (FarmCPU), which dropped to approximately 30%, and traditional Linear Mixed Models, which failed to detect signals (0%). However, this sensitivity resulted in lower precision for ensembles. In contrast, MARS (Degree 1) and BLINK achieved exceptional Specificity (>99%) and Precision (>90%), effectively minimizing false positives. The real data analysis corroborated these trends: while standard GWAS models failed to detect significant associations, the ML framework successfully prioritized consensus genomic regions harboring functional candidates, such as SWEET sugar transporters and NAC transcription factors. In conclusion, ML Ensembles are recommended for broad exploratory screening to recover missing heritability, while MARS and BLINK are the most effective methods for precise candidate gene validation. Full article

Objective: To identify key predictors of clinical outcomes in burn survivors and clarify the role of mixed-depth burns and confounding by indication in observational rehabilitation research. Design: Retrospective cohort study using data from a burn rehabilitation registry (January 2024 to July 2025). Setting: Burn rehabilitation center. Participants: 120 adult patients (age ≥ 18 years) with burns affecting ≥1% total body surface area (TBSA) and complete baseline data. Interventions: Not applicable. Main Outcome Measures: Primary outcome was functional improvement (ΔFIM). Secondary outcomes included pain reduction (ΔPain), scar severity (Vancouver Scar Scale; VSS), Activities of Daily Living (ADL) improvement, and Range of Motion (ROM) recovery. Multivariable linear and logistic regression models were used to identify predictors. Results: Patients achieved significant improvements in function (mean ΔFIM = 11.3 ± 8.9 points) and pain (mean ΔPain = 1.28 ± 0.81). Having a mixed-depth burn was the strongest predictor of worse scar outcomes (β = 2.52, 95% CI: 0.93 to 4.12, p = 0.002) and failure to achieve full ROM (OR = 0.089, 95% CI: 0.008 to 0.930, p = 0.043). An apparent association between inpatient ward care and better scar outcomes (β = −1.30, p = 0.020) was determined to be an artifact of confounding by indication, as the outpatient group had a higher proportion of high-risk mixed-depth burns (6.2% vs. 3.5%). Longer therapy duration was the only significant predictor of achieving ADL goals (OR = 1.014, 95% CI: 1.002 to 1.026, p = 0.025). Conclusions: Injury characteristics, particularly the presence of a mixed-depth burn, emerged as the dominant predictors of long-term scar and functional outcomes. This study identifies mixed-depth burns as a potentially high-risk clinical phenotype requiring targeted therapeutic strategies and demonstrates the critical importance of accounting for confounding by indication when evaluating rehabilitation outcomes in observational burn research. Full article

Background/Objectives: Insulin resistance (IR) is a relevant metabolic concern in patients with rheumatic diseases; however, data regarding its clinical influence on the systemic sclerosis (SSc) phenotype is lacking. This study aimed to evaluate the characteristics of patients exhibiting IR in a monocentric SSc cohort. Methods: We conducted a cross-sectional study on 178 SSc patients, stratified according to the presence of IR, defined as a HOMA-IR value >1.85 for men and >2.07 for women, based on thresholds previously validated in the Estudio Epidemiológico de la Insuficiencia Renal en España (EPIRCE) cross-sectional study. The rationale for applying the current cut-offs is based on its discriminative potential when using sex- and age-specific thresholds in a nondiabetic population. This approach is particularly applicable to SSc, where the prevalence of diabetes is very low and the median ages of the two cohorts are comparable. Data collected included demographic-, clinical-, laboratory-, pulmonary function-, capillaroscopic-, and treatment-related parameters. A multivariable logistic regression model was used to identify independent predictors of IR. Results: Patients with IR (n = 76) had a significantly higher prevalence of diffuse cutaneous subset (26.3% vs. 11.8%, p = 0.012) and interstitial lung disease (39.5% vs. 17.6%, p = 0.001), along with the positivity for anti-Scl70 antibodies and the current presence of musculoskeletal symptoms (p = 0.021) and digital ulcers (p = 0.037). As expected, body mass index (BMI) was significantly higher in the IR population (24.6 ± 5.2 vs. 22.9 ± 4.1, p = 0.012), along with fasting glucose, insulin, HOMA-IR, and HbA1c levels. IR patients exhibited higher percentages of dyslipidemia and liver steatosis. Medications such as hydroxychloroquine, statins, and Iloprost were more frequently used in the IR group; as for corticosteroids usage (21.1% vs. 5.9%, p = 0.002), however, cumulative glucocorticoid dosage did not differ between the groups. In multivariable analysis, BMI (OR 1.09; p = 0.038) and interstitial lung disease (ILD) (OR 3.03; p = 0.034) were independent predictors of IR. Conclusions: In SSc, IR is associated with ILD, digital ulcers, musculoskeletal involvement, and anti-Scl70 autoantibodies. Full article

Background: Neurogenic bowel dysfunction (NBD) is a major chronic sequela of spinal cord injury (SCI) with substantial implications for rehabilitation and long-term management. However, population-level evidence describing how gastrointestinal (GI) diagnostic codes are used following SCI, particularly within administrative healthcare systems, remains limited. Methods: We conducted a nationwide retrospective cohort study using administrative claims data from the Korean National Health Insurance Service (NHIS). A total of 584,266 adults with trauma-related SCI encounters between 2009 and 2019 were identified. GI diagnostic codes—paralytic ileus (K56), irritable bowel syndrome (K58), and functional bowel disorders (K59)—were evaluated as administrative proxies for bowel dysfunction. Demographic characteristics, disability status, regional factors, and health behaviors were analyzed using multivariable logistic regression. Results: GI diagnostic codes were frequently recorded after SCI, most commonly irritable bowel syndrome (approximately 30%) and functional bowel disorders (approximately 37%), whereas paralytic ileus was uncommon. Greater disability severity, female sex, older age, and rural residence were consistently associated with higher odds of GI diagnostic coding. Physical activity showed robust inverse associations across all models. Inverse associations observed with smoking and alcohol consumption were interpreted as reflecting residual confounding or health-related selection, rather than biological protective effects. Conclusions: Patterns of GI diagnostic coding after SCI likely reflect the clinical burden and management needs of neurogenic bowel dysfunction within healthcare systems, rather than the development of new gastrointestinal diseases. These findings underscore the importance of individualized bowel management, incorporation of structured physical activity into rehabilitation programs, and equitable access to SCI rehabilitation services, particularly for individuals with greater disability or those living in rural areas. Full article

Background: Antibiotic overuse in Neonatal Intensive Care Units (NICUs) is a major contributor to antimicrobial resistance and adverse neonatal outcomes. This study aims to evaluate baseline antibiotic utilization (AU), identify factors influencing variability, and assess the impact of neonatal characteristics and sepsis incidence. Methods: A multicenter retrospective analysis examined AU in seven NICUs from 2019 to 2023, involving 25,532 neonatal admissions during national antibiotic stewardship program implementation. Data encompassed neonatal clinical parameters, sepsis incidence, and AU metrics, including days of therapy (DOT) per 1000 patient-days. Statistical analyses included correlation assessments and multivariate regression to identify determinants of antibiotic use. Results: Overall, 43.8% of neonates received antimicrobials, with individual NICUs ranging from 24% to 73% (p < 0.001). Antimicrobial-exposed neonates had a mean gestational age of 35.1 weeks [SD ± 4.4] and a mean birth weight of 2360 g [SD ± 970]. Antimicrobial-exposed neonates were generally more premature [35.5 (±4.4) weeks vs. 37.5 (±2.5) weeks (p < 0.001)] and had lower mean birth weight [2360 g (±971) vs. 2817 g (±686) (p < 0.001)] compared to those not exposed to antimicrobials. Total antimicrobial days varied markedly (12,998 to 37,683 days), with DOT per 1000 patient-days ranging from 322 to 1031. Antimicrobial use for culture-negative sepsis varied widely among centers, from 23% to 71%. Antimicrobial-exposed neonates had higher all-cause mortality compared to those who did not [(7.5% vs. 3.2%), (p < 0.001)]. Multivariate analysis revealed individual NICU practice patterns remained significant predictors after adjusting for neonatal characteristics. Conclusions: Neonatal antimicrobial use varied significantly among NICUs, driven primarily by institutional practices rather than neonatal demographics. These findings provide nationally representative baseline data to inform neonatal antimicrobial stewardship interventions and offer transferable lessons for other countries seeking to optimize antibiotic use in NICUs amid rising global antimicrobial resistance. Full article

Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence of EGFR mutations was 11% (145 out of 1267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4–24.9) and 14.2 months (95% CI: 7.4–20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, the EGFR common mutation subtype (HR = 3.71 95%CI: 1.23–11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18–21. Conclusions: The results underscore the prognostic role of distinct EGFR genotypes and the urgency of determining the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mutations and the resulting need for further research to investigate alternative treatment options. Full article

Background/Objectives: Type 1 gastric neuroendocrine tumors (gNET) arise in the setting of autoimmune chronic atrophic gastritis and secondary hypergastrinemia. Vitamin D deficiency (VDD) has been associated with bone impairment and adverse outcomes in patients with neuroendocrine tumor (NET); however, data specifically addressing gNET remain limited. This study aimed to evaluate vitamin D status, supplementation requirements, and bone involvement in patients with type 1 gNET compared with those with entero-pancreatic NET (EP-NET). Methods: This retrospective study included patients with type 1 gNET followed at a tertiary referral center between 2010 and 2025 and an age- and sex-matched EP-NET cohort. VDD prevalence, time and dose required for normalization, supplementation formulations, bone status, and dietary habits were analyzed. Results: Twenty-six patients were included (thirteen gNET and thirteen EP-NET). VDD was significantly more prevalent in the gNET group compared with the EP-NET group (92.3% vs. 46.2%, p = 0.03, OR: 14). gNET required significantly higher daily cholecalciferol doses (3198.9 ± 1629 vs. 1580 ± 1121 IU/day, p = 0.008) and more frequently required multiple supplementation formulations (38.5% vs. 0%, p = 0.04). Multivariable linear regression analysis restricted to VDD patients confirmed that gNET was independently associated with higher daily cholecalciferol dose requirements (p = 0.037). Bone impairment, defined as osteoporosis or osteopenia, was significantly more common in the gNET group (61.5% vs. 15.4%, p = 0.04, OR: 8.8). Dietary adherence did not differ between groups. Conclusions: Type 1 gNET show a higher burden of VDD, increased vitamin D supplementation requirements, and a higher prevalence of bone impairment compared with EP-NET, irrespective of dietary habits. These findings suggest disease-specific mechanisms and support the need for tailored management in these patients. Full article

Introduction: Population aging in Europe is ongoing and linked to poorer outcomes after out-of-hospital cardiac arrest (OHCA), yet age alone should not guide treatment. We aimed to describe age-related survival, identify independent predictors, and develop a predictive model using EMS data. Methods: We analyzed 147,962 adult OHCA cases from the Hungarian National EMS registry. Variables included initial rhythm, witness status, location, and sex. The primary outcome was survival to hospital admission. Multivariable logistic regression assessed independent predictors and age × treatment interactions; performance was evaluated with AUC, Brier score, and cross-validation. Results: Overall survival was 8.8%; elderly patients had lower survival (7.3%) than non-elderly (11.7%, p < 0.001). VF/VT (adjusted OR 5.34), medical personnel witness (OR 4.52), and AED shock (OR 3.52) were the strongest predictors. Age attenuated the survival benefit of VF/VT (interaction OR 0.914) and the protective effect of female sex (interaction OR 0.882; both p < 0.001). Model performance was good (AUC 0.784; Brier 0.0705). Conclusions: Age independently predicts survival after OHCA, but substantial treatment benefits persist in the elderly. Age–treatment interactions support geriatric-tailored resuscitation strategies and potential integration of this high-performing model into clinical decision support systems. Full article

Background/Objectives: The GCS is widely used to assess a patient’s level of consciousness after trauma. Although not a diagnostic tool for traumatic brain injury (TBI), prehospital clinicians frequently rely on GCS findings—along with pupil exam, mechanism of injury, and clinical presentation, to estimate the likelihood that TBI may be present before imaging is available. However, the GCS has known limitations and fails to identify a significant proportion of TBI patients. This study aimed to evaluate the association between GCS scores and the presence of TBI, and whether additional clinical variables improve its discriminatory value. Methods: This retrospective cohort study analyzed data from trauma patients registered in the TraumaRegister DGU^® between 2015 and 2017. TBI was defined as a head injury with an Abbreviated Injury Scale (AISHead) score of ≥2. Inclusion criteria consisted of trauma team activations with a maximum AIS ≥ 3 and/or the need for intensive care. Prognostic values were assessed using multivariable logistic regression analysis. Results: 40,216 patients were included of which 17,205 (42.8%) were diagnosed with TBI and 23,011 (57.2%) were non-TBI patients. In the TBI group, 36.4% (n = 6216) presented with an initial GCS of 15 prehospitally. 17.8% (n = 3059) of TBI patients had anisocoric or bilaterally dilated pupils, 22.1% (n = 3799) had sluggish or fixed light reactivity and 17% (n = 2934) had no motoric response in Eppendorf-Cologne Scale (ECS) motor component. GCS score by itself showed better TBI prediction value than pupil size or reactivity or motor component alone. Nevertheless, substantial misclassification was observed when using GCS alone: 25.7% of patients with a normal GCS (15) had TBI (AIS Head ≥ 2), while 19.1% of patients with GCS 3 had no TBI. In the non-TBI group, 2.7% (n = 622) had a GCS of 3, 2.9% (n = 685) had anisocoric or bilaterally dilated pupils, 4.2% (n = 960) had sluggish or fixed light reactivity and 3.3% (n = 751) had no motoric response. Even at the lowest GCS score of 3, 19.1% of patients did not have TBI, while a normal GCS of 15 still included 25.7% of patients with TBI. Conclusions: The expanded model combining GCS with pupillary assessment and the ECS motor component demonstrated superior performance in prehospital TBI detection compared with the GCS alone. Implementing an extended GCS incorporating pupillary and ECS assessment may facilitate earlier recognition of TBI and support timely triage decisions; however, potential effects on patient outcomes require confirmation in prospective studies. Full article

Aims: The aim of this study was to evaluate clinical outcomes and identify predictors of mortality in preterm infants with respiratory distress syndrome (RDS) treated in a tertiary Pediatric Intensive Care Unit (PICU). Methods: This retrospective study included 86 preterm infants diagnosed with RDS and treated between January 2015 and December 2024. Clinical data were extracted from medical records and included demographic and anthropometric parameters, perinatal history, associated neonatal diagnoses, ventilation type and duration, surfactant administration, use of inotropes and antibiotics, cranial ultrasound findings, and PICU length of stay. Results: Mortality was 18.6%, with the highest rates observed in extremely preterm infants (<28 weeks) and those with extremely low birth weight (<1000 g). Several clinical variables were significantly associated with survival: gestational age, birth weight, birth length, and Apgar scores at 1 and 10 min (all p ≤ 0.005). In multivariable logistic regression, each additional week of gestation (OR 0.72, 95% CI 0.59–0.87), higher birth weight (OR 0.998, 95% CI 0.997–0.999), and higher Apgar scores (OR 0.69 at 1 min; OR 0.60 at 10 min) were significantly associated with survival. Ventilation was required in 97.7% of infants, and outcomes differed significantly by ventilation modality (p = 0.021), with the lowest mortality observed in those treated with combined invasive and non-invasive ventilation. Resuscitation (p < 0.001) and inotropic support (p < 0.001) were strongly associated with death. Length of PICU stay and duration of ventilation were significantly shorter in non-survivors (p < 0.05). Surfactant therapy was used in 79.1% of infants but was not significantly associated with survival. Conclusions: Gestational age, birth weight, and early postnatal condition were the strongest predictors of survival in preterm infants with RDS. Non-invasive and combined ventilation were associated with better outcomes, whereas the need for resuscitation and inotropes indicated markedly higher mortality. These results highlight the importance of early stabilization and optimized respiratory support in improving outcomes. Full article

Background and Objectives: Acute mesenteric ischemia (AMI) lacks reliable prognostic biomarkers, and the prognostic performance of the C-reactive protein–albumin–lymphocyte (CALLY) index in this population has not been previously evaluated. This study aimed to assess the predictive value of the CALLY index for 30-day mortality in patients presenting to the emergency department (ED) with AMI. Materials and Methods: This retrospective cohort study included patients aged ≥18 years who presented to the ED with AMI over a 4-year period. Demographic and clinical data were collected. The CALLY index, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and CRP-to-lactate ratio were calculated. The primary outcome was 30-day mortality. Univariate and multivariate logistic regression analyses were performed to identify predictors of mortality. A receiver operating characteristic (ROC) curve analysis was used to assess predictive performance. A p-value < 0.05 was considered statistically significant. Results: A total of 111 patients were included (mean age, 69.2 ± 11.8 years; 52.3% male). The most common comorbidities were hypertension and coronary artery disease (45% each). The 30-day mortality rate was 55.9%. In a univariate analysis, lower CALLY index values were associated with higher mortality (p = 0.011). However, the CALLY index did not remain independently associated with mortality in multivariate logistic regression analysis (p = 0.773). The ROC analysis indicated that the CALLY index had a modest but statistically significant ability to predict 30-day mortality (AUC = 0.64, 95% CI: 0.54–0.74, p = 0.011). At a cut-off value of 0.0015, the CALLY index showed a sensitivity of 55% and a specificity of 77%. Conclusions: The CALLY index had modest predictive value for 30-day mortality in patients with AMI. Full article

Background: HER2-low breast cancer (HER2 immunohistochemical [IHC] score 1+, or IHC 2+ without HER2 gene amplification) is distinct from HER2-positive and HER2-0 breast cancer (IHC 0), with a differing prognosis and specific therapeutic options. The DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody–drug conjugate trastuzumab deruxtecan over standard chemotherapy in patients with metastatic breast cancer (MBC) defined as HER2-low. More recently, the DESTINY-Breast06 trial confirmed this benefit in hormone receptor-positive and HER2-ultralow (less than 1+, but with ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining) cases, prompting re-evaluation of HER2 diagnostic thresholds and treatment strategies. Methods: Eligible patients were women with HER2-low or HER2-0 MBC evaluated at MD Anderson between January 2006 and January 2019. HER2-low was defined as either (1) IHC 1+ or (2) IHC 2+ and negative on fluorescence in situ hybridization. Multivariate logistic regression was used to evaluate distinct clinicopathologic features of patients with HER2-low status. Overall survival (OS) was estimated by the Kaplan–Meier method. Multivariate Cox proportional hazards regression was applied to assess the effects of covariates of interest on OS across different HER2 groups. Results: We included 3834 women: 2637 (69%) with recurrent and 1197 (31%) with de novo MBC; HER2-low disease was present in 1575 (60%) and 712 (59%), respectively. In de novo cases, higher nuclear grade was associated with HER2-low status (grade 2 vs. 1, OR = 2.02, p = 0.007; grade 3 vs. 1, OR = 1.87, p = 0.015), while recurrent cases were associated with ER-positivity (OR = 1.96, p < 0.001) and prior adjuvant radiotherapy (OR = 0.79, p = 0.007). Median OS was 3.2 years (95% CI 3.0–3.5). In de novo disease, Black race (HR = 1.48), metaplastic (HR = 3.15) or other non-ductal/lobular histologies (HR = 2.36), and grade 3 (HR = 1.67) predicted worse OS, whereas Hispanic ethnicity (HR = 0.74) and Other races (HR = 0.57), higher ER (HR = 0.48–0.41) and PR (HR = 0.72–0.53), and HER2-low status (HR = 0.77) conferred improved outcomes. In recurrent disease, Black race predicted worse OS (HR = 1.21, 95% CI 1.05–1.39), while Other race (HR = 0.78, 95% CI 0.62–0.97), higher ER (HR = 0.69–0.44) and PR (HR = 0.73–0.73), and HER2-low (HR = 0.89) were protective. HER2 discordance between primary and metastatic sites occurred in 38.8% of recurrent and 13.1% of de novo cases. Conclusions: HER2-low status was significantly associated with longer OS compared to HER2-0 status in both recurrent and de novo MBC cases. These real-world data help establish the prevalence of HER2-low status and its distinct outcomes. The discrepancy in HER2-low status between the primary tumor and metastatic sites highlights the potential for changes in HER2 expression over time, exploring the interaction between HER2-low breast cancer and the tumor microenvironment and emphasizing the importance of monitoring and reassessing HER2 status at various stages to guide treatment decisions effectively and the need for more quantitative and reproducible HER assays. Full article

Background: Visceral adiposity has emerged as a clinically relevant determinant of early cardiometabolic dysfunction in pediatric type 1 diabetes mellitus (T1DM), yet its assessment remains underutilized in routine practice. This study evaluated ultrasonographically measured epicardial adipose tissue thickness (EATT) and perirenal adipose tissue thickness (PrATT) as markers of metabolic risk, insulin sensitivity, and subclinical atherosclerosis in children and adolescents with T1DM. Methods: This cross-sectional study included 150 participants with T1DM and 152 age- and sex-matched healthy controls. Anthropometric data, biochemical parameters, hepatic steatosis grade, and insulin sensitivity indices (eGDR) were collected. EATT and PrATT were measured via standardized echocardiographic and abdominal ultrasonographic protocols. Carotid intima–media thickness (cIMT) was assessed as an indicator of subclinical atherosclerosis. Correlation and multivariable logistic regression analyses were performed to identify independent predictors of T1DM status and cardiometabolic risk. Results: Children with T1DM exhibited significantly higher PrATT and EATT values compared with controls (both p < 0.05). All eGDR indices were markedly lower in the T1DM group, reflecting reduced insulin sensitivity. PrATT and EATT showed strong or moderate correlations with hsCRP, hepatic steatosis, atherogenic index of plasma, and multiple anthropometric markers. Both visceral fat depots were positively associated with cIMT. Logistic regression identified PrATT, EATT, hsCRP, cIMT, and eGDR-BMI as independent predictors of case status. Subgroup analyses demonstrated more pronounced visceral adiposity and metabolic impairment among participants with BMI ≥85th percentile. Conclusions: Ultrasonographically measured PrATT and EATT provide valuable insight into early cardiometabolic risk in youth with T1DM, independent of BMI. Their associations with insulin resistance, inflammation, and subclinical atherosclerosis highlight their potential utility as accessible markers for early risk stratification in pediatric diabetes. Routine incorporation of visceral fat assessment may support earlier identification of high-risk individuals and more targeted preventive strategies. Full article