Search Results (1,506)

Background and Objectives: Residual coronary anatomical complexity following culprit-lesion-only percutaneous coronary intervention (PCI) remains a major determinant of clinical outcomes in patients with multivessel coronary artery disease (CAD). Platelet distribution width (PDW), a marker of platelet heterogeneity and activation, has been associated with adverse cardiovascular outcomes; however, its relationship with post-procedural residual disease burden remains unclear. This study aimed to evaluate the association between PDW and residual SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score and to determine its incremental predictive value beyond established clinical variables. Materials and Methods: In this retrospective, single-center study, 140 patients with multivessel CAD undergoing culprit-lesion-only PCI followed by planned staged revascularization were included. Clinical presentation was categorized as chronic coronary syndrome (CCS), non-ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI). Residual SYNTAX score was calculated after the index procedure, and patients were stratified into low (≤22) and high (≥23) groups. Associations between PDW and residual SYNTAX score were assessed using correlation and regression analyses. Model discrimination and incremental predictive value were evaluated using ROC analysis, hierarchical logistic regression, and reclassification metrics. Nonlinear relationships were explored using restricted cubic spline analysis, and clinical utility was assessed by decision curve analysis. Results: PDW was significantly correlated with residual SYNTAX score (Spearman ρ = 0.503, p < 0.001) and increased progressively across SYNTAX severity strata and clinical presentation groups. In multivariable analysis, PDW remained independently associated with high residual SYNTAX score (OR 1.38, 95% CI 1.07–1.82, p = 0.016). The addition of PDW to a hierarchical clinical model significantly improved model performance (ΔR² = 0.049, p = 0.012). Although the improvement in area under the curve (AUC) was modest, reclassification analyses demonstrated significant net reclassification and discrimination improvements. Spline analysis revealed a nonlinear relationship, with a marked increase in risk beyond PDW levels of approximately 13 fL. Decision curve analysis confirmed the clinical utility of PDW across a range of threshold probabilities. Conclusions: PDW is independently associated with post-procedural coronary anatomical complexity and provides incremental predictive value beyond established clinical variables. However, PDW should be interpreted as a biomarker reflecting platelet heterogeneity within a thromboinflammatory context, without the ability to distinguish between acute and chronic components. Full article

Advanced glycation end products (AGEs) accumulate under chronic inflammation and metabolic stress and may contribute to long-term tissue damage. Skin autofluorescence (SAF) enables non-invasive assessment of tissue AGE accumulation, but data in inflammatory rheumatic diseases remain limited. The present study evaluated AGE-SAF levels in patients with seropositive rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and investigated their associations with disease activity, inflammatory markers, metabolic parameters, and comorbidities. Patients with RA and AS, along with healthy controls, were included. AGE-SAF was measured non-invasively. Disease activity was assessed using the Disease Activity Score in 28 joints (DAS28) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Between-group comparisons were performed both crudely and after multivariable adjustment for age, sex, and body mass index (BMI). Logistic regression and receiver operating characteristic (ROC) analyses were used to describe the exploratory discriminative performance of AGE-SAF, and propensity score analyses were conducted as sensitivity analyses to address baseline imbalance. In crude comparisons, AGE-SAF levels were higher in RA than in AS and controls, and higher in AS than in controls (p < 0.001). After adjustment for age, sex, and BMI, AGE-SAF remained significantly elevated in both RA (β = 0.440, 95% CI 0.298–0.583, p < 0.001) and AS (β = 0.304, 95% CI 0.183–0.425, p < 0.001) compared with controls; however, the difference between RA and AS was no longer statistically significant (β = 0.136, 95% CI −0.051 to 0.323, p = 0.154). Exploratory ROC analyses showed good discrimination for RA versus controls (AUC = 0.851) and moderate discrimination for AS versus controls (AUC = 0.695), whereas discrimination between RA and AS was limited (AUC = 0.670). In overlap-weighted sensitivity analysis, the RA-AS difference remained non-significant (β = 0.161, p = 0.293). AGE-SAF is elevated in inflammatory rheumatic diseases compared with healthy controls, and this elevation persists after adjustment for age, sex, and BMI. Although crude AGE-SAF values were higher in RA than in AS, this difference attenuated after confounder adjustment, indicating that a substantial part of the between-disease difference is attributable to demographic and treatment-related imbalance. AGE-SAF may therefore reflect cumulative disease-related and vascular–metabolic burden across both diseases rather than a disease-specific phenomenon. Full article

Background and Objectives: The objective of this study was to investigate the relationship between clinical periodontal status and COVID-19 severity, including intensive care unit (ICU) admission and in-hospital mortality, in a cohort of hospitalized patients. Materials and Methods: This single-center, cross-sectional study included 44 patients with polymerase chain reaction-confirmed COVID-19 hospitalized at Buca Seyfi Demirsoy Training and Research Hospital, Izmir, Turkey, between August and December 2021. Of these, 32 (72.7%) were admitted to the ICU and 12 (27.3%) to the inpatient service. All participants underwent a full-mouth clinical periodontal examination to assess probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), and plaque index (PI). Clinical data, demographics, comorbidities, and validated disease severity scores (GCS, APACHE II and SOFA) were extracted from electronic medical records, and a univariate logistic regression analysis was performed to identify factors associated with in-hospital mortality. Results: Patients admitted to the ICU (n = 32) were significantly older, had a higher prevalence of comorbidities, and showed higher CAL (p = 0.049) and PI (p < 0.001) values than those treated in the inpatient service. Deceased patients (n = 15) had a significantly higher PI than survivors (p = 0.024). In the univariate logistic regression analysis, APACHE II was the only variable significantly associated with in-hospital mortality (OR = 0.867, p = 0.003), however none of the periodontal parameters, including CAL and PI, showed a statistically significant association with mortality. Conclusions: Poorer periodontal findings, particularly higher CAL and PI values, were more frequently observed in patients requiring ICU care. However, periodontal parameters were not significantly associated with in-hospital mortality in univariate analysis. Given the cross-sectional design, small sample size, and lack of multivariable adjustment, these findings should be interpreted as unadjusted associations rather than evidence of an independent or causal relationship. Full article

Undergraduate students often engage in nighttime activities and electronic device usage that may adversely affect sleep quality and academic performance; therefore, factors associated with sleep quality are important. The objective of this study was to investigate the prevalence and associated factors of poor sleep quality in undergraduate students. Four hundred and five undergraduate students participated in a cross-sectional study and had no history of psychological disorders or use of medications affecting sleep. Data was collected using the Pittsburgh Sleep Quality Index (PSQI), musculoskeletal discomfort questionnaire, electronic device usage questionnaire and Depression Anxiety Stress Scales (DASS-21). Multivariate logistic regression was employed to analyze the factors associated with poor sleep quality. Among the undergraduate students in this study, 65.93% reported having poor sleep quality. The factors associated with poor sleep quality were stress (OR, 1.03; 95% CI, 1.01–1.06) and musculoskeletal discomfort (OR, 1.92; 95% CI, 1.23–2.99) after controlling for other variables. Undergraduate students frequently experience poor sleep quality, with stress and musculoskeletal discomfort being major contributors. These findings highlight the importance of mental health support and stress management programs in improving sleep quality and overall well-being, as well as in preventing long-term detrimental consequences for undergraduate students’ mental health, physical health and academic performance. Full article

Background: Non-thyroidal illness syndrome is frequent in critically ill patients, but the prognostic value of dynamic changes in thyroid function tests remains unclear. This study evaluated whether serial measurements of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) provide additional predictive value for 30-day mortality beyond conventional severity scores in ICU patients. Methods: This single-center retrospective observational study included 74 adult patients treated for ≥72 h in a general ICU who had TSH and FT3 measured within 24 h of admission and repeated at 48–72 h. Patients aged 18 years or above admitted to the intensive care unit were included in the study. Demographic characteristics, comorbidities, APACHE II, SOFA, modified NUTRIC (mNUTRIC) scores, and routine laboratory data (including albumin, CRP, and lactate) were recorded. The primary outcome was 30-day mortality. Between-group comparisons were performed using t-tests, Mann–Whitney U, and Chi-square tests. Variables significant in univariate analyses were entered into binary logistic regression models, and predictive performance was assessed using receiver operating characteristic (ROC) curves and the Youden index. Results: The mean age was 68.7 ± 14.7 years, and 41.9% (n = 31) of the patients died within 30 days. Non-survivors had higher APACHE II, SOFA, and mNUTRIC scores and lower albumin, lymphocyte count, and second FT3 levels compared with survivors (all p ≤ 0.003). Baseline FT3 and TSH were not associated with mortality, whereas both the subsequent FT3 measurements and the ΔT3 (variance in former to latter FT3) were remarkably predictive. The latter FT3 < 1.63 pg/mL produced an AUC of 0.835 (sensitivity: 77%, specificity: 74%), and a ΔT3 log ratio threshold of −0.09 (≈20% early FT3 decline) produced an AUC of 0.835 (sensitivity: 71%, specificity: 81%). The APACHE II + ΔT3 (numeric) model showed the best discrimination (AUC: 0.921; sensitivity: 87.1%, specificity: 81.4%), outperforming APACHE II alone (AUC: 0.861). Conclusions: In critically ill adult patients, dynamic T3 kinetics—particularly premature decline in FT3 within the first 72 h—provide incremental prognostic value for 30-day mortality beyond APACHE II. Serial FT3 monitoring may help identify high-risk patients whose endocrine adaptation to critical illness is failing. Full article

Background: Neoadjuvant chemotherapy (NACT) response in breast cancer is primarily influenced by tumor biology; however, the independent role of host-related factors such as body mass index (BMI) remains unclear. This study evaluated clinicopathological predictors of a high Miller–Payne response after neoadjuvant chemotherapy in patients with stage II–III non-metastatic breast cancer, with particular focus on the role of body mass index. Methods: In this retrospective cohort study, 647 patients with stage II–III non-metastatic breast cancer treated with standard NACT between January 2010 and December 2020 at a single tertiary center were included. High pathological response was defined as Miller–Payne Grades 4–5. Clinical and tumor-related variables were analyzed, including age, menopausal status, body mass index, clinical stage, tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and Ki-67 proliferation index. Univariate and multivariable logistic regression analyses were performed to determine independent predictors of high pathological response. Results: A total of 647 patients were included (mean age: 49.18 ± 10.94 years; mean BMI: 28.45 ± 5.45 kg/m²), of whom 47.45% were postmenopausal. High Miller–Payne response (Grades 4–5) was observed in 40.96% of patients. High response was significantly associated with clinical stage (p = 0.034), tumor grade (p < 0.001), HER2 status (p < 0.001), ER status (p < 0.001), PR status (p < 0.001), and Ki-67 levels (p < 0.001). Median Ki-67 was higher in the high-response group (35.00% [IQR: 20.00–62.75] vs. 25.00% [IQR: 15.00–45.75], p < 0.001). No significant associations were observed for age (p = 0.299), BMI (p = 0.874), or menopausal status (p = 0.289). In multivariable analysis, HER2 positivity (adjusted OR = 3.71, 95% CI: 2.23–6.20, p < 0.001) and Ki-67 (adjusted OR = 1.01 per 1% increase, 95% CI: 1.00–1.02, p = 0.009) were independently associated with high response, whereas ER positivity (adjusted OR = 0.50, 95% CI: 0.25–0.98, p = 0.043) and postmenopausal status (adjusted OR = 0.37, 95% CI: 0.17–0.81, p = 0.013) were inversely associated. BMI was not independently associated with response (p = 0.964). Conclusions: Response to neoadjuvant chemotherapy appears to be mainly determined by tumor biology, particularly receptor status and proliferative activity, rather than anthropometric measures such as body mass index. Full article

Objective: Given the increasing use of outpatient parenteral antimicrobial therapy (OPAT) and the clinical challenges posed by Pseudomonas aeruginosa infections, this study aimed to evaluate the effectiveness and safety of OPAT for the treatment of P. aeruginosa infections in a real-world cohort. Methods: We conducted a prospective observational study with retrospective analysis including adult patients with P. aeruginosa infections treated within a multidisciplinary OPAT program shared by two tertiary hospitals between November 2012 and December 2024. Clinical characteristics, infection type, antimicrobial therapy, resistance patterns, source control, and clinical outcomes were recorded. Primary outcomes were treatment failure during OPAT and within 30 days after OPAT completion. Secondary outcomes included adverse events and vascular access complications. Bivariate and multivariable logistic regression analyses were performed to identify factors associated with treatment failure. Results: A total of 290 patients were included. The most frequent infections were bronchiectasis exacerbations (39.7%) and complicated urinary tract infections (15.2%). Most patients received monotherapy (72.8%), mainly ceftazidime, while 27.2% received combination therapy with a beta-lactam plus an aminoglycoside. Treatment failure occurred in 7.6% of patients during OPAT and in 15.5% within 30 days after OPAT completion, with an overall clinical success rate of 77%. Male sex and chronic obstructive pulmonary disease (COPD) were independently associated with failure during OPAT. At 30 days, higher Charlson comorbidity index, COPD exacerbation, and endovascular infection were associated with failure, whereas combination therapy was associated with a lower risk of failure. Antimicrobial-related adverse events were rare (3.2%). Conclusions: Our results support OPAT as an effective and safe strategy for managing P. aeruginosa infections in clinically stable patients. Patients with COPD, either as a comorbidity or during an exacerbation, and those with a higher Charlson score may require closer follow-up. Full article

Objectives: CD93, an angiogenesis-related transmembrane glycoprotein, is transcriptomically downregulated in uterine corpus endometrial carcinoma, yet circulating protein levels have not been clinically evaluated. This study aimed to evaluate serum CD93 as a diagnostic biomarker for EC and to examine its association with clinicopathological parameters. Methods: In this single-center case–control study, serum CD93 concentrations were measured by enzyme-linked immunosorbent assay in 46 patients with histologically confirmed primary EC and 35 controls with histologically verified benign gynecological pathology. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results: Serum CD93 was significantly lower in EC patients than controls (median 4.55 [IQR 3.51–6.97] vs. 10.24 [7.18–12.14] ng/mL; p < 0.001). In multivariable analysis adjusted for age and body mass index, lower CD93 remained independently associated with EC (OR = 0.521; 95% CI 0.061–0.720; p < 0.001). ROC analysis yielded an area under the curve of 0.845 (95% CI 0.759–0.921), with 82.6% sensitivity and 74.3% specificity at a cut-off of 7.338 ng/mL. CD93 levels showed no significant association with histological subtype, grade, lymphovascular space invasion, nodal metastasis, or recurrence. Conclusions: Serum CD93 is significantly reduced in EC and demonstrates independent diagnostic performance, supporting its prospective validation as a non-invasive biomarker in larger multicenter cohorts. Full article

Background: Body mass index (BMI) is a common nutritional marker, but admission-only measurements present limitations. Early dynamic BMI changes may better reflect metabolic stress and fluid balance. However, the clinical significance of early BMI trajectory during critical illness remains poorly understood. This study evaluated the impact of early BMI trajectory on mortality and ventilator weaning in critically ill patients. Methods: This retrospective cohort study included 1355 adult patients (ICU stay ≥ 7 days) admitted to the medical ICU between 2019 and 2025. BMI trajectory was defined as the percentage change from admission to day 7 and was categorized into three groups: decrease (>5% reduction), stable (±5%), and increase (>5% gain). Multivariable Cox proportional hazard and logistic regression analyses were performed to evaluate the association between BMI trajectory and clinical outcomes. Results: Of the 1355 patients, 15.9%, 57.7%, and 26.4% were in the decrease, stable, and increase groups, respectively. The increase group demonstrated significantly higher hospital mortality (52.5%) than the decrease (41.9%) and stable (40.0%) groups (p = 0.001). Multivariable analysis revealed that an increasing BMI trajectory was independently associated with higher hospital mortality (HR 1.25, 95% CI 1.05–1.48). A decreasing BMI trajectory strongly predicted successful ventilator weaning (OR 2.76, 95% CI 1.81–4.21). Conclusions: Early BMI trajectory significantly predicted ICU outcomes. Increasing and decreasing BMI were associated with higher mortality and improved ventilator weaning, respectively. These findings suggest that BMI trajectory may be a simple surrogate marker of metabolic stress, nutritional status, and fluid balance during early critical illness. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is a heterogeneous disease with substantial variability in clinical manifestations and outcomes, influenced by ethnic and geographical diversity. Remission is the optimal treatment target, while low lupus disease activity state is an accepted alternative goal. Although sustained remission has been associated with reduced organ damage, the impact of early attainment of treatment targets on subsequent damage accrual in SLE remains incompletely defined. To explore a potential window of opportunity, this study aimed to identify factors associated with achieving remission or low lupus disease activity state within the first year of SLE diagnosis and to examine their associations with organ damage. Methods: This retrospective study was conducted across 22 rheumatology centres in Malaysia and included patients with systemic lupus erythematosus (SLE) who had complete follow-up from diagnosis until attainment of treatment targets. Treatment targets were defined as achieving either early remission or a low disease activity state (LDAS). Given the retrospective nature of the study and the unavailability of complete Physician’s Global Assessment data, the definitions of early remission and LDAS were modified by excluding this component. Accordingly, treatment targets were defined as attainment of a clinical SLE Disease Activity Index (cSLEDAI) score of 0 with oral prednisolone doses of ≤5 mg/day and ≤7.5 mg/day, respectively, within 12 months of SLE onset. Multivariable Cox proportional hazards regression and logistic regression analyses were performed to determine factors associated with early remission and organ damage, respectively. Results: A total of 1599 patients were included, the majority of whom were female (92.5%). The cohort was predominantly Malay (68.7%), followed by Chinese (17.4%), Indigenous groups (10.8%) and Indian (3.0%). Early attainment of treatment targets was achieved in 45.7% of patients, while 54.3% experienced delayed attainment. In the multivariable cox regression model, the Malay and Chinese ethnic group demonstrated a significantly lower likelihood of achieving early remission compared to the Indigenous ethnic group. Patients with longer SLE duration, low C4 levels, presence of haematological and renal manifestations at the initial presentation, were identified as additional adverse factors associated with lower likelihood of early remission. Overall, 16.9% of patients accrued organ damage. Independent factors associated with organ damage included Indian ethnicity [OR 5.75, 95% CI 1.39–23.81, p = 0.02], delayed remission [OR 2.97, 95% CI 1.51–5.83) and absence of baseline hydroxychloroquine therapy [OR 4.13, 95% CI 1.21–14.07; p = 0.020]. Conclusions: Ethnic disparities were observed in the early attainment of the treatment targets, as well as in organ damage accrual within the Malaysian multi-ethnic SLE cohort. The significant association between the delay in achieving the treatment targets and organ damage underscores the importance of adopting an early treat-to-target approach in SLE management. Full article

Backgrounds/Objectives: Non-small cell lung cancer (NSCLC) exhibits substantial prognostic heterogeneity that is not fully captured by conventional anatomical staging, highlighting the need for individualized risk assessment. Radiomics enables non-invasive characterization of tumor phenotype, yet high dimensionality and inter-feature correlations often limit model stability and interpretability. Methods: To address these challenges, we developed a multimodal late-fusion framework integrating radiomic, clinical, and demographic information to predict patient-specific absolute risk in the Lung1 cohort (N = 398). Radomic features (N = 107) were extracted from primary tumor volumes and refined using a Group Lasso–penalized Cox model, preserving biological coherence and producing a parsimonious imaging signature. This signature was combined with clinical and demographic variables using five different late-fusion strategies: weighted averaging, Cox regression, logistic stacking, Random Survival Forests (RSF), and XGBoost. Model performance was evaluated using 5-fold cross-validation based on discrimination, calibration, and risk stratification metrics. Results: Using 5-fold cross validation, the radiomics-only model outperformed conventional clinical staging in patients’ risk prediction (C-index 0.5717 vs. 0.5350) and accuracy, demonstrating the prognostic value of imaging biomarkers. All fusion strategies improved risk prediction performance, with the Cox fusion model slightly better than other fusion methods with C-index of 0.58, time-dependent AUC of 0.60, and the distinct risk stratification with log-rank χ² of 22.85. Conclusions: These findings suggest that multimodal late fusion may provide robust and interpretable risk estimates with potential clinical relevance, supporting personalized risk prediction for informed decision-making in NSCLC. Full article

Background: To evaluate the association between glaucomatous visual field loss and self-reported driving limitation, and to explore potential threshold ranges of visual field loss associated with an increased likelihood of driving restriction. Methods: In this cross-sectional study, 100 patients with primary open-angle glaucoma underwent standard automated perimetry. Visual function was assessed using Mean Deviation (MD) and Visual Field Index (VFI) from the better eye. Driving status, driving limitation, and self-reported driving difficulties were assessed using a structured questionnaire. Multivariable logistic regression was performed to determine independent associations between visual field parameters and driving limitation, adjusting for age, sex, cataract status, and systemic comorbidities. Because MD and VFI are closely related indices of visual field loss, separate multivariable models were constructed for each parameter. Receiver operating characteristic (ROC) analysis was used to explore threshold values associated with driving limitation. Results: Driving limitation increased progressively with worsening functional severity, affecting 17% of participants with preserved function, 48% of those with borderline impairment, and 72% of those with definite impairment (p < 0.001). Reduced VFI was independently associated with driving limitation (OR = 0.972, 95% CI: 0.948–0.996; p = 0.021). In a separate model, more negative MD was also independently associated with driving limitation (OR = 0.924, 95% CI: 0.875–0.976; p = 0.004). Male sex was associated with a lower likelihood of driving limitation. ROC analysis identified threshold values of VFI ≤ 71% (AUC = 0.663) and MD ≤ −13.36 dB (AUC = 0.650), both characterized by high specificity but limited sensitivity. Participants who had ceased driving demonstrated worse visual field indices than active drivers, whereas never-drivers showed no consistent association with visual field loss. Conclusions: Glaucomatous visual field loss was significantly associated with self-reported driving limitation and behavioural self-regulation. Objective perimetric parameters, particularly VFI and MD in the better eye, may help identify patients more likely to report driving difficulties. The reported threshold values should be interpreted as exploratory reference points rather than clinically actionable criteria and require further validation before clinical application. Full article

Background/Objectives: The itch–scratch cycle is a key driver of exacerbation in atopic dermatitis (AD) and requires objective monitoring, yet patient-reported itch scores are often unreliable in children. This study aimed to evaluate smartwatch-derived nocturnal scratching metrics as digital biomarkers of disease activity and treatment response in pediatric AD. Methods: In this prospective observational study, 50 children (median age 9 years) with physician-diagnosed AD wore an Apple Watch with the Itch Tracker application for 5–14 nights during initiation of topical therapy. Three scratch metrics—scratch count rate (SCR), scratch duration ratio (SDR), and scratch burden index (SBI, duration × intensity)—were analyzed. Associations with clinical outcomes [Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM)], serum thymus and activation-regulated chemokine (TARC), and itch numerical rating scale (NRS) were examined. Logistic regression models were evaluated to examine whether these metrics could identify children who achieved clinically meaningful improvement, defined as EASI-50 plus ≥ 4-point POEM reduction. Results: All scratch metrics correlated with baseline EASI (r = 0.60–0.64, p < 0.001) and serum TARC (r = 0.58–0.60, p < 0.001). Reductions in scratching paralleled clinical improvement (r = 0.67–0.71, p < 0.0001). Among models, the SBI-based logistic regression demonstrated the best discriminative performance (AUC = 0.78, 95% CI: 0.64–0.92). Conclusions: Wearable-derived nocturnal scratching metrics showed moderate but consistent associations with disease severity and short-term improvement. Although predictive capability remains to be established, these metrics may serve as treatment-responsive digital measures. Given the cross-sectional nature of biomarker analyses and other study limitations, further prospective validation is required before clinical application in real-world pediatric AD monitoring. Full article

Background: Dentofacial deformities (DFDs) comprise heterogeneous sagittal, vertical, transverse, and asymmetry components, yet clinical severity is often summarized using isolated measurements. Objectives: To operationalize a reproducible composite DFD severity score and evaluate its cross-sectional associations with quality of life, function, airway-related screening indicators, and psychosocial burden. Methods: In this single-center cross-sectional study, consecutive adults assessed in an orthognathic surgery pathway underwent a prespecified 0–100 severity scoring framework integrating sagittal discrepancy (|Wits| and |ANB deviation|), vertical pattern (SN-MP angle), and asymmetry/transverse variables (chin deviation, asymmetry index, transverse discrepancy, and absolute overjet). Outcomes included the Oral Health Impact Profile-14 (OHIP-14), Orthognathic Quality of Life Questionnaire (OQLQ), FACE-Q facial appearance satisfaction scale, PHQ-9, GAD-7, STOP-Bang, functional testing, and CBCT-derived upper-airway metrics. Results: Severe DFDs had higher composite severity (62.9 ± 12.8 vs. 25.3 ± 10.9), larger sagittal discrepancy (|Wits| 6.3 ± 2.8 vs. 3.1 ± 1.8), and higher SN-MP angles (39.8 ± 7.4 vs. 34.7 ± 7.2) (all p < 0.001). Severe DFDs also had worse OQLQ (36.2 ± 6.2 vs. 24.1 ± 7.2), OHIP-14 (18.3 ± 4.2 vs. 12.4 ± 4.1), FACE-Q satisfaction (45.7 ± 10.3 vs. 67.6 ± 9.6), masticatory performance (59.4 ± 8.5 vs. 75.1 ± 7.5), and smaller airway area (126.7 ± 29.6 vs. 161.4 ± 27.7) (all p < 0.001). In multivariable logistic regression, |Wits|, SN-MP angle, asymmetry index, and lower airway area independently predicted severe status; PHQ-9 was associated with severity in unadjusted analyses but did not retain independent significance after multivariable adjustment. Model discrimination was high (AUC 0.91). Conclusions: This multidimensional severity framework captures clinically meaningful cross-sectional differences across morphologic, functional, airway-related, and psychosocial domains. Its interpretability remained stable in sensitivity analyses, but external and longitudinal validation is still required before broader implementation. Full article

Background: Reliable biomarkers that capture tumor–host interactions and predict treatment resistance in extensive-stage small cell lung cancer (SCLC) remain limited. We evaluated the prognostic and predictive value of the pretreatment lactate dehydrogenase-to-albumin ratio (LAR), an integrative biomarker reflecting metabolic activity, systemic inflammation, and host nutritional status. Methods: This multicenter, retrospective cohort study included patients with extensive-stage SCLC treated at five tertiary centers between 2016 and 2024. Pretreatment LAR was calculated using baseline serum lactate dehydrogenase and albumin levels and dichotomized using a Youden index-derived cut-off at the 12-month overall survival (OS) horizon. Time-dependent receiver operating characteristic (ROC) analyses using inverse probability weighting were performed to assess discriminative performance. Survival outcomes were evaluated using Kaplan–Meier estimates and Cox proportional hazards models. Associations with platinum resistance and lack of objective treatment benefit (defined as progressive disease as best response) were examined using logistic regression models. Results: A total of 223 patients were included. Elevated LAR was associated with inferior OS (median, 15.8 vs. 25.2 months; log-rank p < 0.001) and progression-free survival (7.9 vs. 11.5 months; p < 0.001). In multivariable analysis, LAR remained independently associated with OS (HR, 1.43; 95% CI, 1.04–1.95; p = 0.028). LAR demonstrated modest but consistently superior discriminative performance compared with other inflammatory indices for both 12-month OS (area under the curve [AUC], 0.692) and 6-month progression-free survival (PFS) (AUC, 0.646), with statistically significant differences in DeLong comparisons. Higher LAR was independently associated with increased odds of platinum resistance (adjusted odds ratio [aOR], 2.31; 95% CI, 1.41–3.81; p = 0.001) and lack of objective treatment benefit (adjusted OR, 2.04; 95% CI, 1.33–3.14; p = 0.001). Conclusions: Pretreatment LAR is a clinically accessible and biologically integrative biomarker associated with survival and treatment resistance in extensive-stage SCLC. By capturing tumor–host interactions, LAR may support risk stratification and identify patients at increased risk of early treatment failure. Prospective validation is warranted to define its role in biomarker-driven clinical decision-making. Full article