Search Results (2,027)

Background: Accurate assessment of extubation readiness in mechanically ventilated children remains difficult because successful sustained breathing depends on the interaction of respiratory, metabolic, inflammatory, neurological, and cardiovascular factors. This study developed and internally validated machine-learning models for predicting 48 h extubation success using routinely available pre-extubation data. Methods: Of 1097 total PICU admissions, 341 mechanically ventilated children treated between 2021 and 2026 constituted the final analytic cohort. The primary outcome was survival without reintubation during the first 48 h after planned extubation. Demographic, clinical, laboratory, blood gas, illness severity, and ventilator variables were evaluated. Logistic Regression, Random Forest, Gradient Boosting, and Support Vector Machine models were assessed using stratified 5-fold cross-validation. Unsupervised k-means clustering was performed to identify physiological phenotypes. Results: Extubation was successful in 298 children (87.4%) and failed in 43 (12.6%). Failure was associated with higher oxygenation index, lactate, procalcitonin, C-reactive protein, PaCO₂, pSOFA, PEEP, and rapid shallow breathing index, together with lower arterial pH, bicarbonate, ionized calcium, hemoglobin, albumin, sodium, and Glasgow Coma Scale scores. Random Forest yielded the numerically highest discrimination, with an AUC of 0.983 (95% CI, 0.971–0.993), a sensitivity of 0.980, a specificity of 0.814, an accuracy of 0.959, and a Brier score of 0.032. Arterial pH, the oxygenation index, bicarbonate, ionized calcium, procalcitonin, lactate, and PaCO₂ showed the highest Random Forest Gini importance scores. Clustering identified a low-severity phenotype (n = 302; 97% success; 0% mortality) and a high-severity phenotype (n = 39; 10% success; 100% mortality). Conclusions: Multidimensional machine-learning models predicted 48 h pediatric extubation success with strong internal discrimination. Prospective multicenter external validation is required before clinical implementation. Full article

Background/Objectives: Intravascular large B-cell lymphoma (IVLBCL) is a rare and diagnostically challenging disease, often presenting as fever of unknown origin (FUO). This study aimed to develop and validate diagnostic predictive models and scoring systems to distinguish IVLBCL from other causes of FUO in hospitalized patients. Methods: A retrospective analysis was conducted in patients with IVLBCL or other causes of FUO who were treated between February 2015 and October 2023. Two multivariable logistic regression models and corresponding integer-based scoring systems were developed in a training cohort comprising 42 patients with IVLBCL and 45 FUO controls. Internal validation was performed using leave-one-out cross-validation and bootstrap resampling, followed by temporal validation in an independent cohort of 18 patients with IVLBCL and 21 FUO controls. Model 1 was additionally evaluated for sensitivity in an external case-only cohort comprising 40 patients with IVLBCL from eight hospitals. Results: Model 1 incorporated peripheral edema, hypoxemia, neurological symptoms, hemophagocytic lymphohistiocytosis, and interstitial lung abnormalities on computed tomography and achieved an area under the receiver operating characteristic curve (AUC) of 0.916 in the training cohort. Model 2 combined the interleukin-10/interleukin-6 (IL-10/IL-6) ratio with peripheral edema, hypoxemia, and neurological symptoms and demonstrated significantly improved discrimination (AUC = 0.982, p = 0.021 vs. Model 1). In the temporal validation cohort, the AUCs of Models 1 and 2 were 0.975 and 0.997, respectively. The corresponding integer-based scoring systems achieved AUCs of 0.903 and 0.952 in the training cohort and 0.926 and 0.992 in the temporal validation cohort. In the external case-only cohort, both Model 1 and its integer-based score identified 32 of 40 patients, yielding a sensitivity of 80.0%. Random skin biopsy provided the histological diagnosis in 58% of cases, with a positivity rate of 79.5%. Conclusions: Two diagnostic models and their simplified scoring systems were developed and internally and temporally validated to aid the diagnosis of IVLBCL in hospitalized patients with FUO. These models may assist in the diagnostic workup of hospitalized FUO patients, especially when IL-10/IL-6 testing is unavailable. Their performance in outpatient or community settings remains uncertain, and prospective multicenter validation with appropriate FUO controls is warranted. Full article

Background and Objectives: Autoimmune liver diseases (AILD), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), frequently lead to end-stage liver disease requiring transplantation. The factors associated with post-transplant mortality in recipients with autoimmune liver diseases (AILDs) remain incompletely characterized. We aimed to evaluate the clinical, laboratory, disease-related, and comorbidity factors associated with post-transplant mortality in this population. Materials and Methods: This retrospective cohort study included 94 AILD recipients (26 AIH, 28 PBC, 40 PSC) transplanted between 2004 and 2025. We analyzed clinical, laboratory, transplant-related variables, and comorbidities (Charlson Comorbidity Index [CCI]). We assessed survival using Kaplan–Meier and Cox regression analyses. Early mortality was defined as death within 90 days after transplantation. Results: Overall mortality was 17.0% (16/94). Mortality rates were 28.6%, 15.4%, and 10.0% in PBC, AIH, and PSC, respectively, without a statistically significant between-group difference (p = 0.313). Among 93 recipients with ascertainable follow-up, 8 deaths occurred within 90 days (8.6%). In the exploratory Cox regression analysis, preoperative creatinine showed the strongest association with mortality (HR = 8.67 per 1 mg/dL increase, p < 0.001). Transplant age (HR = 1.06 per year, p = 0.010) and disease duration (HR = 1.09 per year, p = 0.004) were also associated with mortality. These associations remained statistically significant in the exploratory multivariable model. MELD, MELD-Na, and MELD 3.0 were not significantly associated with post-transplant mortality in this cohort. Because of the limited number of deaths, the multivariable findings should be regarded as hypothesis-generating. Documented and treated acute rejection was recorded in 32.2% of recipients. In an exploratory analysis, higher BMI was associated with increased odds of this outcome; however, histopathological confirmation was not systematically available. Conclusions: In this single-center AILD cohort, preoperative serum creatinine, disease duration, age at transplantation, and comorbidity burden showed associations with post-transplant mortality, whereas the evaluated liver severity scores were not significantly associated with mortality. These exploratory findings require confirmation in larger multicenter cohorts before they can be incorporated into post-transplant risk-stratification models. Full article

Background/Objectives: Secondary hyperparathyroidism (SHPT) is a prevalent complication of end-stage kidney disease. Although etelcalcetide has demonstrated short-term superiority over cinacalcet in randomized trials, real-world comparative data beyond 12 months remain scarce. This study compared the long-term effectiveness of etelcalcetide versus cinacalcet in hemodialysis patients over 24 months using propensity score matching. Methods: This multicenter retrospective study screened 457 hemodialysis patients across five centers in Türkiye. Propensity score matching on age, sex, hemodialysis vintage, and baseline intact parathyroid hormone (iPTH) yielded balanced cohorts of 21 versus 21 for 12-month and 14 versus 14 for 24-month analyses. The primary outcome was percentage change in iPTH from baseline (%ΔPTH). Secondary outcomes included responder rates, KDIGO target achievement, response trajectory classification, and depth-of-response analysis. Results: At 12 months, etelcalcetide achieved significantly greater iPTH reduction (%ΔPTH: −50.5 ± 25.6% vs. −29.7 ± 40.6%; p = 0.047), with effect sizes increasing from medium to medium–large at 24 months (Cohen’s d: −0.612 to −0.779). Sustained response (≥30% iPTH reduction at both timepoints) was significantly higher with etelcalcetide (78.6% vs. 28.6%; p = 0.021), as was deep response (≥75% reduction) at 24 months (57.1% vs. 14.3%; p = 0.046). At 24 months, etelcalcetide demonstrated significantly lower serum calcium (p = 0.015), calcium–phosphate product (p = 0.023), and superior phosphate target attainment (85.7% vs. 28.6%; p = 0.004). Inter-patient response variability was nearly three-fold lower with etelcalcetide (CV: 42% vs. 151%). Conclusions: Etelcalcetide provided significantly greater, more sustained, and more consistent iPTH suppression than cinacalcet over 24 months, with additional benefits in mineral metabolism control. These findings support etelcalcetide as a potent therapeutic option for SHPT in hemodialysis patients and warrant confirmation in larger prospective trials. Full article

Spontaneous pediatric intracerebral hemorrhage (sICH) is a rare but devastating neurological emergency associated with high mortality and long-term disability. Existing prognostic scores rely on a reduced number of variables and have shown limited validation, highlighting the need for comprehensive tools. This study describes the protocol for the development and internal validation of the CLIMPOUT (Clinical, Laboratory, and Imaging Predictive Outcome) score, a multimodal model designed to improve early prognostic assessment in pediatric sICH. This single-center retrospective cohort study will include consecutive patients (1 month–18 years) admitted to a tertiary pediatric intensive care unit (PICU) with spontaneous sICH between 2018 and 2025. Predictor variables will be restricted to baseline information available at PICU admission, including demographics, clinical status, laboratory markers, and quantitative neuroimaging features. Hematoma and intraventricular hemorrhage volumes will be measured using standardized three-dimensional segmentation. The primary outcome will be poor neurological status at 12 months, defined by the Pediatric Stroke Outcome Measure (PSOM). We will develop a multivariable logistic regression model following contemporary recommendations, including prespecified predictor selection, multiple imputation for missing data, and internal validation by 1000 bootstrap resamples. The CLIMPOUT score is expected to identify independent predictors of poor neurological outcome and provide a standardized, multimodal risk stratification model with improved prognostic performance compared with currently available pediatric scores. This protocol establishes a rigorous framework for developing a clinically applicable prediction model that may support early individualized decision-making, optimize neurocritical care management, and provide the foundation for future multicenter validation. Full article

Background/Objectives: Trauma remains a leading global cause of mortality and morbidity, particularly in low- and middle-income countries. Multitrauma patients often require intensive care and exhibit high mortality rates. Prognostic scoring systems such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Revised Trauma Score (RTS) are widely used to predict outcomes; however, their performance in middle-income settings like Turkey has not been well established. This study aimed to evaluate the prognostic accuracy of APACHE II and RTS in predicting intensive care unit (ICU) mortality among multitrauma patients. Methods: This retrospective observational study was conducted in the General ICU of Diyarbakır Gazi Yaşargil Training and Research Hospital between January 2022 and December 2024. Adult patients (≥18 years) with multitrauma involving at least two anatomical regions were included. Demographic data, clinical scores (APACHE II, RTS, Sequential Organ Failure Assessment [SOFA], Injury Severity Score [ISS], Trauma and Injury Severity Score [TRISS]), laboratory parameters, complications, and outcomes were recorded. Univariate and multivariate logistic regression analyses identified independent predictors of ICU mortality. Receiver operating characteristic (ROC) analysis assessed the discriminatory ability of prognostic scores. Results: A total of 145 patients were analyzed, with an ICU mortality rate of 13.1%. Non-survivors had significantly higher APACHE II (27 ± 4 vs. 13 ± 6, p < 0.001) and SOFA scores (7 [4–13] vs. 2 [1–6], p < 0.001) and lower RTS (4.2 ± 1.7 vs. 7.2 ± 1.1, p < 0.001). Acute kidney injury, sepsis, septic shock, and mechanical ventilation were more frequent among non-survivors (p < 0.01 for all). In multivariate analysis, APACHE II (odds ratio [OR]= 1.54, 95% confidence interval [CI] 1.16–2.04, p = 0.003) and RTS (OR = 0.36, 95% CI 0.16–0.81, p = 0.013) were independent predictors of ICU mortality. ROC analysis showed excellent prognostic performance for APACHE II (area under the curve [AUC] = 0.959) and RTS (AUC = 0.888). Conclusions: In this retrospective single-center cohort, APACHE II and RTS were independently associated with ICU mortality and demonstrated good discriminatory performance for early risk stratification in critically ill multitrauma patients. The lower mortality observed in our cohort should be interpreted cautiously, as it may also reflect differences in case-mix, injury severity, ICU admission practices, and referral patterns. These findings require external validation in larger multicenter cohorts before broader generalization. Future studies should also validate the identified cut-off values and further investigate the prognostic role of biomarkers such as procalcitonin. Full article

Background: Endothelial dysfunction is a key component of sepsis pathophysiology. The Endothelial Activation and Stress Index (EASIX) is a practical biomarker derived from routine laboratory parameters and indirectly reflects endothelial injury. This study aimed to evaluate the prognostic association of EASIX with in-hospital mortality and organ-support requirements among patients with pneumosepsis admitted to the intensive care unit (ICU). Methods: This retrospective cohort study included 1787 adult patients with pneumosepsis admitted to a tertiary ICU from January 2018 to December 2025. EASIX was calculated from laboratory parameters obtained at ICU admission, and log2-EASIX was used in all analyses. The primary outcome was in-hospital mortality. Secondary outcomes included the need for invasive mechanical ventilation (IMV), vasopressor therapy within the first 24 h, second-line vasopressor therapy, and continuous renal replacement therapy (CRRT) within the first 7 days after ICU admission. Associations with the primary and secondary outcomes were evaluated using univariable and multivariable logistic regression, and discriminative performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: The in-hospital mortality rate was 56.2%. Log2-EASIX was independently associated with in-hospital mortality (OR: 1.191, 95% CI: 1.119–1.268; p < 0.001). ROC analysis showed moderate discrimination for predicting in-hospital mortality (AUC: 0.673, 95% CI: 0.648–0.698), with a ROC-derived exploratory cut-off of 1.47. Patients with log2-EASIX ≥ 1.47 had approximately a two-fold higher risk of in-hospital mortality (OR: 2.039, 95% CI: 1.610–2.584; p < 0.001). In multivariable analyses of the secondary outcomes, log2-EASIX remained independently associated with second-line vasopressor requirement (adjusted OR: 1.104, 95% CI: 1.040–1.171; p = 0.001) and CRRT requirement within 7 days (adjusted OR: 1.317, 95% CI: 1.236–1.404; p < 0.001). However, its associations with IMV and initial vasopressor requirements were not statistically significant after adjustment. Adding log2-EASIX to the Acute Physiology and Chronic Health Evaluation (APACHE) II resulted in a statistically significant but small improvement in discrimination compared with APACHE II alone (AUC: 0.761 vs. 0.740; ΔAUC = 0.021; 95% CI: 0.010–0.032; p < 0.001). Conclusions: EASIX was independently associated with in-hospital mortality and second-line vasopressor requirement, and it remained associated with CRRT requirement after multivariable adjustment. However, serum creatinine alone showed superior discrimination for CRRT, suggesting that the association between EASIX and CRRT may be driven, at least in part, by its creatinine component and should therefore be interpreted cautiously. In contrast, the associations of EASIX with early IMV and initial vasopressor requirements were not significant after multivariable adjustment. Although its discriminative performance for mortality was moderate when used alone, EASIX may provide complementary prognostic information when added to established disease severity assessment. These findings warrant validation in prospective, multicenter studies. Full article

Background: Heritable thoracic aortic disease (HTAD) accounts for approximately 20–25% of thoracic aortic aneurysm and dissection (TAAD) cases and is a major cause of premature death in young adults. Methods: This is a narrative, non-systematic review. We performed a selective synthesis of clinical practice guidelines (ACC/AHA 2022, EACTS/STS 2024), the revised Ghent nosology, large multicenter cohort studies (Montalcino Aortic Consortium), randomized pharmacotherapy trials, and molecular mechanism data published between 2010 and 2025; quantitative figures are reported as published in individual primary sources and were not pooled or re-analyzed. Results: The advent of next-generation sequencing (NGS) has driven a paradigm shift in HTAD management, from risk assessment based purely on phenotype (aortic diameter) to risk stratification based on genotype (molecular mutation). The 2022 ACC/AHA guideline identifies eleven genes with confirmed high-penetrance risk for HTAD; these, together with the established Loeys–Dietz gene TGFB3 (recognized through gene–disease validity assessment rather than the ACC/AHA list), can be grouped into three pathogenic mechanisms: extracellular matrix dysregulation, TGF-β signaling dysregulation, and vascular smooth muscle contractile dysfunction. Gene–disease association should be distinguished from guideline-defined classification and regarded as evolving, since additional candidate genes such as LTBP3 are already emerging in gene-negative families. Multigene panel testing identifies a pathogenic or likely pathogenic variant in roughly 8% of patients referred for suspected HTAD, a yield that rises substantially when applied to syndromic or strongly familial presentations. Prophylactic surgical thresholds are individualized by gene and are generally lower (around 4.0 cm) for high-risk TGFBR1/TGFBR2 and PRKG1 variants and higher (around 5.0 cm) for FBN1 and TGFB3, in contrast with the uniform 5.5 cm threshold historically applied to all patients. Randomized trials over the past decade—including the AIMS irbesartan trial, the Marfan Treatment Trialists’ individual patient data meta-analysis, and the celiprolol and irbesartan trials in vascular Ehlers–Danlos syndrome—now provide direct evidence that angiotensin receptor blockade slows the rate of aortic root dilation in Marfan syndrome, with more limited evidence in vascular Ehlers–Danlos syndrome and uncertain effects on dissection or mortality, while valve-sparing aortic root replacement provides durable long-term outcomes in reported single-center experience. These thresholds and pharmacotherapy recommendations rest predominantly on observational cohort, registry, and randomized trial data of varying maturity and should be interpreted as graded, evolving recommendations rather than fixed cut-points. Conclusions: This review synthesizes the molecular pathogenesis, diagnostic nosology, gene-specific epidemiologic and prognostic data, genetic testing yield, pharmacotherapy evidence, surgical outcomes, and updated prophylactic intervention algorithms per the ACC/AHA (2022) and EACTS/STS (2024) guidelines, providing a practical reference framework for individualizing surveillance and surgical decision-making in patients with HTAD. Full article

Background/Objectives: Drug-induced sleep endoscopy (DISE) enables dynamic, real-time visualization of the level, severity, and configuration of upper airway collapse during pharmacologically induced sleep, providing anatomical information that polysomnography cannot. It is increasingly used to guide individualized surgical planning in obstructive sleep apnea (OSA), particularly in children with persistent OSA after adenotonsillectomy or at elevated risk of surgical failure. However, the absence of a universally accepted pediatric-specific classification system and standardized protocol continues to limit comparability across studies and the development of evidence-based treatment algorithms. This review evaluates the role of DISE in pediatric OSA, focusing on airway assessment, classification systems, anesthesia protocols, and its impact on surgical decision-making. Methods: A PubMed literature review (2013–2025) identified 42 pediatric-specific studies, including cohort studies, systematic reviews, and meta-analyses. Data were extracted regarding indications, classification scales, anesthetic techniques, safety, and surgical outcomes. Results: DISE provides dynamic visualization of multilevel obstructions often missed during awake examinations. While adult-derived systems such as VOTE are used, pediatric-specific tools (e.g., Chan–Parikh, NAVOTEL, PedDISE-8, IPSES) offer more age-appropriate assessments. Anesthetic choice is a key factor; dexmedetomidine, alone or with ketamine, best approximates non-rapid eye movement (NREM) sleep while maintaining airway tone and stability. DISE findings altered surgical plans in 30–60% of patients, facilitating targeted procedures such as supraglottoplasty, lingual tonsillectomy, and epiglottopexy. Conclusions: DISE is a valuable diagnostic and decision-support tool for complex pediatric OSA. Clinical utility depends on standardized assessment and anesthesia. Further multicenter studies are required to validate classification systems and determine long-term impacts on quality of life. Full article

Background/Objectives: Magnetic resonance imaging (MRI) of the proximal humeral epiphysis offers a radiation-free alternative for forensic age estimation in living individuals. This study aimed to characterize the relationship between chronological age and epiphyseal maturation using a six-stage ossification classification adapted from the Schmeling–Kellinghaus framework, incorporating one original morphological criterion to distinguish the pre-terminal from the terminal stage of maturation, to establish stage-specific minimum age thresholds, and to evaluate observer reproducibility in a Turkish cohort. Methods: In this retrospective, single-center study, 395 shoulder MRI examinations (222 males, 173 females; age range, 12.17–30.67 years) obtained at Bakırköy Dr. Sadi Konuk Training and Research Hospital were evaluated. The proximal humeral epiphysis was staged on T1-weighted turbo spin echo sequences in the coronal oblique plane using a six-stage classification adapted from Schmeling et al. Two radiologists independently assessed all images; intra- and interobserver reliability were determined using Cohen’s kappa. Results: Spearman’s rank correlation showed a strong positive association between chronological age and ossification stage (rho = 0.825, p < 0.001; males, rho = 0.837; females, rho = 0.808). No significant sex differences in age were found at any stage (p > 0.05). The minimum age at Stage 6, the most mature stage observed, was 21.58 years in males and 21.25 years in females. Intra- and interobserver agreement were κ = 0.827 (95% CI, 0.78–0.87) and κ = 0.811 (95% CI, 0.76–0.86), respectively, corresponding to a high level of agreement. Conclusions: These findings support MRI staging of the proximal humeral epiphysis as a reliable, radiation-free adjunct for forensic age estimation, with stage-specific minimum ages providing population-specific reference values for application under the minimum age principle. Given the retrospective, single-center, single-scanner design, these results should be regarded as hypothesis-generating data pending prospective, multicenter validation. Full article

Background: Patients with end-stage kidney disease (ESKD) and diabetes undergoing maintenance hemodialysis (HD) may be at increased risk of metabolic disturbances and intradialytic complications during Ramadan fasting. However, evidence regarding the safety of fasting in this population remains limited. This study evaluated the association between Ramadan fasting and intradialytic hypoglycemia and other clinical outcomes. Methods: This multicenter prospective cohort study included 153 patients with ESKD and diabetes undergoing maintenance HD at four centers in Thailand during the pre-Ramadan and Ramadan periods in 2024. Participants were categorized as non-fasting, partial fasting, or full fasting. All underwent HD using glucose-containing dialysate (100 mg/dL) and received standardized pre-Ramadan medication adjustments, including insulin dose reduction and oral glucose-lowering medication modification. The primary outcome was intradialytic hypoglycemia, defined as a blood glucose level <70 mg/dL. Secondary outcomes included HD-related complications, blood pressure, interdialytic weight gain (IDWG), dialysis adequacy, and laboratory parameters. Results: Among 153 participants, 73 were non-fasting, 44 were partial fasting, and 36 were full fasting. No intradialytic hypoglycemia occurred in the full- or non-fasting groups, whereas one episode (0.2%) occurred in the partial-fasting group. HD-related complications, blood pressure, IDWG, and dialysis adequacy (Kt/V) were comparable across groups. Serum potassium and parathyroid hormone levels increased during Ramadan in the full- and non-fasting groups without reported clinical events. Overall, participants remained clinically stable under the standardized protocol. Conclusions: In this cohort, Ramadan fasting was not associated with an observed increase in major intradialytic hypoglycemic events and hemodialysis-related complications, indicating that the practice is clinically feasible and well-tolerated under strictly supervised protocols. Therefore, fasting may be considered for carefully selected patients with ESKD and diabetes receiving maintenance hemodialysis, provided it is accompanied by individualized medication adjustments, meticulous monitoring, and shared decision-making. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Over the past decade, immune checkpoint inhibitors have become a core component of first-line treatment for advanced-stage NSCLC lacking driver mutations. Programmed death-ligand 1 (PD-L1) expression is currently used as the standard biomarker, yet its predictive value remains limited, and in most immunotherapy trials, treatment efficacy has been observed independently of PD-L1 expression status. Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator, promotes immune escape by suppressing antigen presentation and impairing CD8+ T-cell function, thereby generating an immune-cold tumor microenvironment, positioning it as a promising candidate biomarker. Methods: We retrospectively analyzed 102 NSCLC patients treated with immunotherapy at a single center between 2018 and 2024. EZH2 expression was assessed by immunohistochemistry. A cohort-derived 25% threshold was used for the primary exploratory analysis, and the analyses were repeated using a 50% threshold as a sensitivity analysis. Patients were classified as EZH2-high (45.1%) and EZH2-low (54.9%) at the 25% threshold. Results: At the 25% threshold, objective response rate (ORR) was 53.6% in the EZH2-low group and 45.7% in the EZH2-high group (Fisher’s exact p = 0.551), while disease control rate (DCR) was 64.3% and 60.9%, respectively (p = 0.837). Median overall survival (OS) was 37 versus 27 months (log-rank p = 0.323), and median progression-free survival (PFS) was 15 versus 12 months (p = 0.387). No significant correlation was found between EZH2 and PD-L1 expression (r = 0.167, p = 0.138). In treatment-line-adjusted Cox models, EZH2 expression was not associated with OS (hazard ratio (HR) 0.953, 95% confidence interval (CI) 0.533–1.704; p = 0.870) or PFS (HR 0.996, 95% CI 0.573–1.733; p = 0.989), whereas squamous histology was an independent predictor of survival. Results remained non-significant at the 50% threshold. Early progression was uncommon and did not differ significantly by EZH2 status overall or within PD-L1 strata. Conclusions: In this real-world cohort, EZH2 expression was not independently associated with response, early progression, OS, or PFS, and showed no correlation with PD-L1. These exploratory findings do not support the clinical use of EZH2 as a biomarker at this stage; prospective, multicenter studies using predefined thresholds and standardized immunohistochemical methods are needed to clarify its potential role as a marker complementary to PD-L1. Full article

Background/Objectives: Accurate preoperative detection of locally advanced breast cancer is essential for neoadjuvant therapy planning. We developed and validated gradient-boosting models using structured BI-RADS mammographic features to simultaneously predict locally advanced breast cancer (LABC), DCIS component, and multifocality in a multi-center cohort. Methods: This retrospective study enrolled 2295 patients from three university-affiliated hospitals; features were coded according to BI-RADS. CatBoost and logistic regression models were built using stratified 60/20/20 splits, with performance assessed via bootstrap resampling, nested cross-validation, and sensitivity analyses. AUROC, AUPRC, Brier score, and calibration metrics assessed discrimination and clinical utility; a leakage audit and SHAP analysis supported interpretation. Results: CatBoost achieved an AUROC of 0.906 (95% CI: 0.876–0.932) for LABC. Because several top predictors overlap with the anatomical criteria defining this outcome, we repeated the analysis excluding them; the reduced model retained a mean AUROC of 0.739, indicating genuine predictive signal beyond the staging overlap. Net benefit was positive across all relevant thresholds, with calibration error of 0.053. DCIS prediction was highly accurate (AUROC 0.979; nested AUROC 0.9707), with no evidence of leakage. Multifocality prediction was more modest (AUROC 0.810), reflecting known limits of two-dimensional mammography. Sensitivity analyses confirmed stable performance across splits, training sizes, and class-weighting schemes. Conclusions: Structured mammographic features combined with gradient-boosting support clinically meaningful, though partly overlapping, risk stratification for LABC; once accounted for, the model still retains independent value. The DCIS model performed very well; multifocality prediction remains more limited, and external validation is needed before clinical use. Full article

Background: Eustachian tube dysfunction (ETD) is associated with several common otologic conditions but lacks standardized diagnostic thresholds in Taiwan. This study aimed to evaluate the diagnostic performance of the GSI TympStar Pro pressure-swallow test and to identify a ROC-derived maximal peak pressure difference (MPD) cutoff for distinguishing clinically diagnosed obstructive Eustachian tube dysfunction (oETD) from healthy controls. Methods: A total of 152 subjects were enrolled, including 100 healthy controls and 52 patients with clinically diagnosed oETD, confirmed by otolaryngologist assessment and supported by ETDQ-7 symptom scoring. Tympanometry and tympanometry-based Eustachian tube function testing using the GSI TympStar Pro ETF–Intact pressure-swallow module, a modified three-tympanogram pressure-swallow protocol, were performed. Group comparisons were conducted using Mann–Whitney U and Chi-square tests. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Results: The median MPD was 11 daPa (IQR 6–17) in the control group, compared to 0 daPa (IQR 0–2) in the ETD group (p < 0.001). ROC analysis demonstrated that a cutoff value of ≤4 daPa yielded a sensitivity of 100.0% and specificity of 91.0% in the per-person analysis, and a sensitivity of 97.5% and specificity of 95.5% in the per-ear analysis. In the Type A-only per-ear analysis, MPD retained discriminatory performance, with an AUC of 0.978 (95% CI, 0.961–0.994). Conclusions: When interpreted in conjunction with ETDQ-7 symptom assessment and routine clinical evaluation, pressure-swallow testing may provide complementary objective information for the functional assessment of patients with suspected obstructive Eustachian tube dysfunction, particularly when resting tympanometry is unremarkable. In this single-center Taiwanese cohort, lower MPD values may serve as an adjunctive indicator of impaired Eustachian tube pressure equalization, and the ROC-derived cutoff of ≤4 daPa showed discriminatory value for differentiating symptomatic obstructive ETD from healthy controls. This cutoff should be interpreted as an exploratory, protocol-specific threshold and requires prospective validation in larger multicenter populations before broader clinical application. Full article

Background/Objectives: Nutritional, inflammatory, and lifestyle-related characteristics may contribute to substantial biological heterogeneity among children with documented previous SARS-CoV-2 infection. This study aimed to characterize an integrated nutritional-inflammatory profile and explore its relationships with biological and clinical features in a hospitalized pediatric cohort. Methods: This retrospective cohort study included 260 children with documented previous SARS-CoV-2 infection. Clinical, anthropometric, and laboratory data were complemented by questionnaire-derived dietary and lifestyle information (n = 213). Analyses combined conventional statistics with correlation and multivariate techniques, including PCA and K-means clustering (n = 231) and exploratory Ridge regression (n = 188). Results: Suboptimal serum 25(OH)D concentrations (<30 ng/mL) were present in 55.8% of participants (95% CI [49.7%, 61.7%]), while 43.5% were overweight or obese (95% CI [37.6%, 49.5%]). BMI correlated with hemoglobin (ρ = 0.23) and CRP (ρ = 0.12), while 25(OH)D correlated with potassium (ρ = 0.22). Increasing daily device use was associated with progressively lower 25(OH)D concentrations (H = 24, p < 0.001, ε² = 0.11), with median values decreasing from 33 ng/mL at <1 h/day to 24 ng/mL at >4 h/day. PCA identified three complementary biological dimensions explaining 55.0% of the total variance, while K-means clustering identified three reproducible exploratory nutritional–inflammatory phenotypes differentiated by age, BMI, hematological and inflammatory characteristics, and selected lifestyle factors. Conclusions: The findings show multidimensional nutritional–inflammatory heterogeneity in children with documented previous SARS-CoV-2 infection. The identified patterns and exploratory phenotypes provide an integrated framework for biological characterization and warrant validation in prospective multicenter cohorts. Full article