Search Results (12,056)

Feature importance analysis is essential for interpreting machine learning models in diabetes mellitus (DM) risk prediction; however, existing interpretability methods often produce inconsistent feature rankings across models. This study proposes a unified ODE-inspired interpretability framework and an algorithmic decision procedure for robust feature selection by integrating contribution-based (SHAP), perturbation-based (permutation importance), and sensitivity-based feature importance measures. Multiple supervised machine learning models, including Logistic Regression, Random Forest, Gradient Boosting, Histogram Gradient Boosting, and Multilayer Perceptron, were trained and evaluated on a longitudinal biochemical and demographic dataset comprising 200 patients with three repeated visits (N = 600 observations). To preserve longitudinal integrity and avoid patient-level information leakage, grouped cross-validation was applied. A sensitivity-based feature importance formulation using finite-difference approximations enabled model-agnostic comparison across heterogeneous machine learning architectures. Stability, normalization, and cross-method agreement analyses were additionally introduced to evaluate consistency of feature rankings across models and interpretability methods. Experimental results consistently identified HbA1c as the dominant predictor, followed by lipid-related variables, age, and body mass index. Strong agreement was observed between ODE-inspired feature importance and SHAP analysis, whereas permutation importance demonstrated comparatively weaker agreement with sensitivity-based methods. The proposed framework further enabled systematic analysis of ranking stability, cross-method agreement, longitudinal sensitivity dynamics, and the introduction of an agreement-weighted Consensus Interpretability Score (CIS) for unified feature ranking across heterogeneous interpretability methods. The results demonstrate that integrating ODE-inspired sensitivity analysis with machine learning provides a robust, interpretable, and computationally scalable framework for feature importance assessment in diabetes risk prediction. The proposed approach offers a principled solution to inconsistent feature importance estimation and supports more reliable interpretation of biomedical machine learning models. Full article

Background/Objectives: Pregnant women with obesity may experience a substantial burden of sleep disruption and obstetric risk, but prospective data integrating non-respiratory sleep symptoms, prescribed nutritional supplement exposure, and routinely collected hematological measures are limited. This single-center prospective pilot study aimed to describe longitudinal changes in anthropometry, non-respiratory sleep symptoms, prescribed nutritional supplement exposure, routine hematological and blood-count-derived inflammatory indices, and obstetric and neonatal outcomes, and to document study-accrual and data completeness metrics for a future controlled cohort. Methods: Seventeen adult women with singleton pregnancies and first-trimester body mass index (BMI) ≥ 30 kg/m² reached the sleep unit, and all consented to participate. Protocol-based assessments were performed in the first and third trimesters, whereas routine laboratory and treatment data were extracted from medical records. Nutritional exposure was defined solely by prescription status in routine records; doses, formulations, adherence, dietary intake, and serum micronutrient markers were unavailable. Analyses were endpoint-specific complete-case analyses. Results: Study accrual at the sleep unit occurred from 27 July 2023 to 14 March 2024 (17 participants over 7.6 months; approximately 2.2 participants/month). The number informed in Obstetrics and the number not reaching the sleep unit were not recorded. Paired anthropometry was available for 15/17 participants, paired Epworth and Insomnia Severity Index scores for 14/17, paired restless-legs scores for 13/17, and delivery outcomes for 16/17. Median paired changes were 6.0 kg (IQR 1.4–7.9) for weight and 2.3 kg/m² (IQR 0.5–3.1) for BMI. Hemoglobin decreased, and selected blood-count-derived indices varied across routine trimester measurements. Sleep scores showed no clear longitudinal change, although nocturnal awakenings and subclinical insomnia were frequent. Type III polygraphy was attempted in all 17 participants at T1 and was valid in 16; one participant declined a repeat study after a technically invalid recording. Polygraphy was valid in 15 participants at T3; a respiratory event index (REI) ≥5 events/h was observed in 6/16 (37.5%) and 8/15 (53.3%), respectively. Conclusions: This pilot provides feasibility, data completeness, and variability estimates for a larger controlled cohort. The small uncontrolled sample, non-standardized laboratory timing, treatment heterogeneity, and missing upstream referral logs prevent obesity-specific, mechanistic, or clinically actionable conclusions. Full article

Background: Despite evidence-based guidelines for cardiovascular risk management, many patients fail to achieve therapeutic targets. The relative contribution of medication non-adherence versus suboptimal treatment optimization to poor cardiovascular outcomes remains unclear in real-world primary care settings. The aim of this study was to describe changes in cardiovascular risk factor control following protocolized adherence reinforcement combined with physician-driven treatment optimization in high-risk patients. Methods: This multicenter, real-world longitudinal study included 789 participants with high or very high cardiovascular risk enrolled from primary care settings across 9 Spanish regions between 2023 and 2025. All participants received a protocolized intervention combining adherence reinforcement and physician-driven treatment optimization. This was a single-arm, pre–post study without a concurrent control group; observed changes therefore cannot be attributed to the intervention alone. Of 789 participants screened, all completed the baseline assessment, and 628 (79.6%) completed the 90-day follow-up. A total of 161 participants (20.4%) were lost to follow-up. Primary outcomes included changes in systolic and diastolic blood pressure, lipid parameters (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c], triglycerides [TG]), glucose, glycated hemoglobin (HbA1c), and body mass index (BMI) from baseline to 90-day follow-up. Changes were assessed using linear mixed models. Results: Among participants with complete paired data (n = 453–615 depending on the outcome), significant improvements were observed in most cardiovascular risk factors (HDL-c and HbA1c did not change significantly). Mean changes (95% confidence interval [CI]) were: systolic blood pressure, −9.24 mmHg (−10.41 to −8.06; p < 0.001); diastolic blood pressure, −4.75 mmHg (−5.49 to −4.01; p < 0.001); LDL-c, −22.29 mg/dL (−25.59 to −19.00; p < 0.001); TC, −23.24 mg/dL (−26.73 to −19.74; p < 0.001); TG, −16.75 mg/dL (−23.03 to −10.46; p < 0.001); fasting plasma glucose, −10.03 mg/dL (−12.61 to −7.46; p < 0.001); and BMI, −0.46 kg/m² (−0.58 to −0.35; p < 0.001). Linear mixed models including all available data (n = 628 at 90-day follow-up) confirmed these findings. No significant interactions were observed between assessment timepoint and sex, age, or overweight/obesity status for most outcomes, except for age-related differences in lipid responses. Conclusions: Protocolized adherence reinforcement combined with physician-driven treatment optimization was associated with clinically meaningful improvements in multiple cardiovascular risk factors in high-risk primary care patients. Given the single-arm pre–post design, the observed improvements are associative and cannot establish causality. Residual uncontrolled risk, particularly in lipid management and among older adults, persisted despite active treatment optimization (treatment was modified in 82.0% of participants), consistent with residual suboptimal treatment intensification even after adherence had been reinforced. These findings suggest that achieving optimal cardiovascular risk factor control requires addressing both medication adherence and treatment intensification, particularly in patients with multimorbidity. Full article

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the sacroiliac joints and spine and is associated with an increased risk of fractures due to persistent inflammation, reduced mobility and treatment-related factors. In radiographic axSpA (r-axSpA), assessment of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) may be limited by structural spinal changes. This cross-sectional study, conducted between March 2024 and June 2025, evaluated skeletal fragility in patients with r-axSpA using Radiofrequency Echographic Multi-Spectrometry (REMS)-derived Fragility Score (FS). Ninety patients with r-axSpA and sex-matched healthy controls underwent clinical assessment and REMS evaluation of lumbar spine and hip BMD, T-scores and spinal FS. Patients with r-axSpA had lower body mass index and higher rates of smoking, prior fractures and inflammatory markers compared with controls, while disease activity reflected a moderate burden. No significant differences in BMD or T-scores were observed between groups. However, FS was significantly higher in patients with r-axSpA (46.6 ± 15.4 vs. 31.2 ± 13.3, p = 0.004), corresponding to a higher fracture risk category, whereas correlations between FS and clinical parameters were not statistically significant. These findings suggest that REMS-derived FS may identify increased skeletal fragility in r-axSpA beyond conventional BMD measurements. Full article

Background/Objectives: The relationship between body composition (BC), sarcopenia, and multiple sclerosis (MS) remains poorly understood. A high body mass index (BMI) is associated with a higher risk of MS and brain atrophy. However, limited data are available on BC in patients in the early stages of the disease. This study investigates differences in BC and sarcopenia between early-diagnosed patients with MS (pwMS) and healthy controls (HC), while exploring correlations with brain atrophy and biomarkers of oxidative stress and axonal injury. Methods: This project is part of BPS-ARMS, a cross-sectional study conducted in 2019–2022 at Verona University involving 51 participants aged 18–40 years, diagnosed with MS in the last two years, and currently not taking disease-modifying drugs. Seventeen (69% females) pwMS consented to be enrolled in this sub-study, matched by age and body mass index (BMI) to 17 HC; BC was assessed using Dual-Energy X-ray Absorptiometry (DXA). Collected variables included BMI, fat and lean mass, and sarcopenia index (SI). A brain MRI scan was performed in pwMS between 6 months before and 1 month after inclusion, to assess T2 lesion, normalized brain (NBV), white matter (WMV) and gray matter (GMV) volumes, and presence of gadolinium-enhancing (Gd+) lesions. Biomarker analysis was performed on blood samples collected at baseline. Oxidative stress was assessed as plasma gluthatione (GSH) and gluthatione disulphide (GSSG) levels and STAT1 phosphorylation at Tyr 701 (pSTAT) in peripheral blood cells, while axonal damage was measured as serum neurofilament light chain (NfL) levels. Results: A significantly lower SI was found in pwMS compared to HC (p = 0.038), particularly in female cases. In the pwMS group, WMV was inversely correlated with SI (p = 0.028) and lean body mass (p = 0.016). BMI was inversely correlated with WMV (r = −0.658, p = 0.02). A significant inverse correlation of plasma GSSG level was found with SI (r = −0.546, p = 0.023) and lean mass (r = −0.585, p = 0.014); the ratio of GSH over GSSG (GSH/GSSG) was directly correlated with SI (r = 0.518, p = 0.036) and lean mass (r = 0.568, p = 0.017). Conclusions: Patients with early-stage untreated MS and low-grade disability are more prone to sarcopenia than HC. Moreover, MS subjects with higher BMI show lower brain white matter volume and a lower global brain volume. Full article

Diabetes mellitus is strongly associated with cardiovascular dysfunction and remains one of the leading contributors to morbidity and mortality worldwide. Early identification of diabetes-related cardiovascular alterations is essential for timely risk stratification and personalized clinical management. In the present study, an interpretable machine learning framework for diabetes classification in patients with cardiovascular disease was developed using routinely available clinical, biochemical, renal, and echocardiographic parameters. A retrospective dataset consisting of 131 cardiovascular patients was included in the final analysis, comprising 65 patients with diabetes mellitus and 66 patients without diabetes. Demographic, metabolic, renal, and cardiovascular variables, including age, body mass index (BMI), glycated hemoglobin (HbA1c), glucose concentration, estimated glomerular filtration rate (eGFR), troponin level, heart rate, and left ventricular ejection fraction (EF), were included in the analysis. Multiple supervised machine learning algorithms, including Logistic Regression, Support Vector Machine (SVM), Gradient Boosting, and Random Forest, were implemented and compared using repeated stratified cross-validation. Among the evaluated models, Random Forest demonstrated the highest classification performance, achieving a mean ROC AUC of 0.880 ± 0.050. Statistical analysis revealed significantly elevated HbA1c, glucose, and troponin levels together with reduced ejection fraction values in diabetic patients. Explainable artificial intelligence analysis using SHAP and partial dependence plots identified glucose concentration, HbA1c, age, and renal function as the dominant contributors to diabetes classification. Nonlinear relationships between metabolic and cardiovascular variables were additionally observed. The obtained findings demonstrate that interpretable machine learning approaches can provide effective discrimination between diabetic and non-diabetic cardiovascular patients while maintaining clinically meaningful interpretability. The proposed framework may contribute to future intelligent clinical decision-support systems and personalized cardiovascular risk assessment strategies. Full article

Background: Hydrogen breath testing is commonly used to assess intestinal fermentation and diagnose small intestinal bacterial overgrowth (SIBO). However, it remains unclear whether hydrogen production reflects systemic inflammatory or metabolic status. This study evaluated the relationship between hydrogen production dynamics and systemic biomarkers using a data-driven analytical approach. Methods: This cross-sectional study included 162 adults undergoing lactulose hydrogen breath testing. Hydrogen production was characterized using continuous measures, including area under the curve (AUC), early and late hydrogen responses, and unsupervised clustering-derived hydrogen response groups. Associations with serum 25-hydroxyvitamin D, C-reactive protein (CRP), leukocyte count, and interleukin-6 (IL-6) were assessed using multivariable regression models adjusted for age and body mass index (BMI). Results: Hydrogen production showed substantial interindividual variability. Unsupervised analysis identified low-, intermediate-, and high-hydrogen response groups. Differences between groups were driven mainly by overall fermentation intensity rather than distinct temporal response profiles. No significant associations were observed between hydrogen production metrics and systemic biomarkers. Hydrogen-related variables were not independently associated with vitamin D, CRP, leukocyte count, or IL-6 concentrations. In contrast, BMI was consistently associated with inflammatory markers, particularly CRP and IL-6. Correlation analyses demonstrated strong relationships among hydrogen-derived variables but weak associations with systemic parameters. Conclusions: Data-driven analysis revealed marked heterogeneity in intestinal hydrogen production but no detectable association with systemic inflammatory or metabolic markers within the present cohort. These findings suggest that hydrogen breath test metrics primarily reflect local intestinal fermentation rather than systemic physiological status. Hydrogen breath testing remains useful for assessing gastrointestinal function, but no evidence supporting its value as a marker of systemic inflammation was identified in the present cohort. Full article

Background and Objectives: Hysterectomy is one of the most frequently performed gynecological surgical procedures worldwide. It is well established that the laparoscopic approach offers better outcomes for patients compared to abdominal hysterectomy. However, the technique for vaginal cuff closure during laparoscopic hysterectomy (TLH) remains insufficiently standardized in the international literature. Based on our results, we aim to demonstrate that closure of the vaginal cuff using a figure-of-eight suture is a sufficient, reproducible, time-efficient and safe method during total laparoscopic hysterectomy. Materials and Methods: Our retrospective observational study analyzed 173 patients who underwent a TLH from January 2016 to December 2021 at the University of Debrecen, Department of Obstetrics and Gynecology. Standardized surgical steps were applied in all cases (ligation of the uterine arteries at their origin, fenestration of the broad ligament above the ureter), and the vaginal cuff was closed laparoscopically with an absorbable suture, incorporating vesicovaginal fascia, vaginal mucosa and uterosacral ligaments. Patient demographics, operative data, and perioperative outcomes were extracted and analyzed. Results: TLH was successfully performed in 173 cases, and no conversion to open surgery was necessary. The mean age of the patients was 51.4 (23–86) years, the median body mass index (BMI) was 26.9 (16.9–45) kg/m², and the operative time was 92 (35–240) minutes. The mean uterine weight was 151 (16–440) g. The mean hemoglobin drop was 15.8 (0–44) g/L after the surgery. Regarding complications, ureteral injuries occurred in two cases (1.2%). One patient (0.6%) required relaparotomy due to rectosigmoid perforation. Postoperative complications included vaginal cuff dehiscence in two cases (1.2%), with one patient (0.6%) requiring resuturing, fever in six cases (3.5%), vaginal discharge in four cases (2.3%), and vaginal bleeding in one case (0.6%). Pulmonary embolism occurred in one patient (0.6%). Three patients (1.7%) required blood transfusion based on postoperative blood counts. Conclusions: Our results demonstrate an acceptable operative time and a low rate of postoperative complications, suggesting that closing of the vaginal cuff with a figure-of-eight suture is a sufficient and safe technique. This method can be reliably reproduced and incorporated into the standardized steps of total laparoscopic hysterectomy. Full article

Background: Posterior malleolar fractures are commonly assessed using two-dimensional measurements and morphology-based classification systems. However, ankle fracture morphology is inherently three-dimensional, and the reproducibility of CT-based volumetric segmentation for malleolar fracture fragments has not been sufficiently established. Objectives: This study aimed to evaluate the relationship between lateral and posterior malleolar fragment volumes in homogeneous supination–external rotation (SER)-type trimalleolar ankle fractures and to assess the intraobserver and interobserver reproducibility of a manual CT-based three-dimensional volumetric segmentation workflow. Methods: This retrospective musculoskeletal imaging study included 71 patients with SER-type trimalleolar ankle fractures who underwent preoperative computed tomography (CT). Posterior and lateral malleolar fracture fragments were segmented on thin-slice axial CT images using a standardized manual contour-based slice-by-slice workflow. Fragment volumes were calculated using dedicated volumetric imaging software. The association between lateral and posterior malleolar fragment volumes was assessed using Spearman correlation and multivariable linear regression analyses. Measurement reproducibility was evaluated using intraclass correlation coefficients for absolute agreement [ICC(A,1)] and Bland–Altman analyses. Results: The median lateral and posterior malleolar fragment volumes were 8.63 cm³ (interquartile range [IQR], 7.18–10.71) and 2.64 cm³ (IQR, 1.88–4.24), respectively. A weak but statistically significant positive correlation was observed between lateral and posterior malleolar fragment volumes (Spearman rho = 0.313, p = 0.008). In multivariable linear regression analysis, lateral malleolar fragment volume remained independently associated with posterior malleolar fragment volume after adjustment for age, sex, and body mass index (B = 0.316, standardized β = 0.39, p = 0.002). Intraobserver and interobserver reproducibility were excellent for all volumetric measurements, with ICC(A,1) values ranging from 0.996 to 0.999. Bland–Altman analyses demonstrated low mean bias and narrow limits of agreement across all comparisons. Geometric agreement was also excellent, with Dice similarity coefficient values ranging from 0.93 to 0.96 across intraobserver and interobserver segmentation comparisons. Full article

Background/Objectives: Dietary adherence and physical activity are pivotal yet understudied behavioral components of self-management of type 2 diabetes mellitus (T2DM) in the Middle East and North Africa region. This study aimed to quantify dietary adherence and physical activity levels, examine their association, and identify sociodemographic and clinical factors independently associated with these outcomes among adults with T2DM in southwest Saudi Arabia—a region chronically underrepresented in the literature. Methods: A descriptive cross-sectional study (n = 257; December 2023–March 2024) was conducted at a specialist diabetes center. The Perceived Dietary Adherence Questionnaire (PDAQ; 0–56 after removal of the fat-avoidance item with near-zero item-total correlation) and General Practice Physical Activity Questionnaire (GPPAQ) were administered alongside body mass index (BMI) and glycated hemoglobin (HbA1c) extracted from medical records. Bonferroni-corrected non-parametric bivariate tests, multiple linear regression with variance inflation factor diagnostics, and binary logistic regression were applied. Results: Mean 8-item PDAQ was 20.44 ± 10.04/56 (36.5%); carbohydrate spacing was the critical deficit (16.4%). GPPAQ distribution: 10.1% inactive, 28.0% moderately inactive, 49.0% moderately active, and 12.8% active, with sensitivity analysis ranging 28.0–47.5% in the two lowest categories. PDAQ–GPPAQ correlation was weak (Spearman r = 0.18; 95% CI: 0.06–0.29; r² = 0.032). BMI alone accounted for 81.0% of PDAQ score variance (cross-sectional; direction of association not established; full model Adj. R² = 0.826; LOO-CV R² = 0.820, indicating model stability). Employment type showed the strongest cross-sectional association with GPPAQ-derived inactivity classification (housewife OR = 5.77; retired/seeking OR = 4.98 vs. employed), largely driven by the occupational component of the composite score. Conclusions: Dietary adherence was substantially below the maximum achievable score; BMI was the factor most strongly associated with PDAQ scores in cross-sectional analysis, though the direction of this relationship cannot be established. Physical activity levels were substantially associated with occupational patterns; housewives and retired/other participants faced approximately five-fold greater odds of being classified as inactive or moderately inactive compared with employed individuals. The weak PDAQ–GPPAQ correlation (r² = 0.032) suggests these behaviors are not strongly co-determined and points to the potential value of distinct, hypothesis-generating intervention approaches for dietary quality and leisure-time physical activity in T2DM populations. Full article

Background: Body image disturbance (BID) involves a distorted perception of one’s body, whereas body dissatisfaction (BDS) reflects negative affective evaluation of body appearance. Both are central features of eating disorders such as anorexia nervosa (AN), but their expression in siblings of affected individuals remains underexplored, particularly in younger populations. Methods: This cross-sectional preliminary study included 53 full sisters of adolescent patients with severe AN treated in a tertiary hospital. Participants underwent anthropometric assessment and completed standardized measures of BID, BDS, physical activity, eating-related attitudes, perfectionism, anxiety, and depressive symptoms. Results: Participants exhibited marked body size overestimation (mean relative BID = +45.2%), with 64.2% classified as high overestimators and 3.8% as underestimators. Overestimation was most pronounced in the waist, chest, and calves. BID was not significantly associated with BDS or with anthropometric measures, including body mass index. BDS showed significant positive correlations with depressive symptoms and self-oriented perfectionism, whereas BID was positively associated with physical activity. No significant associations were found between BID or BDS and age, socioeconomic status, or birth order. Conclusions: Sisters of adolescents with severe AN show substantial perceptual distortion of body size without corresponding levels of body dissatisfaction, suggesting partial independence between perceptual and affective components of body image. These findings identify a potentially vulnerable group and highlight the need for longitudinal studies to clarify mechanisms and inform preventive strategies. Full article

Background: Biologic therapies have transformed severe asthma management, but real-world evidence comparing phenotypes, lung function trajectories, and persistence across biologic classes remains limited. Objective: To characterize a real-world cohort of biologic-treated severe asthma patients, focusing on baseline phenotypes, longitudinal post-bronchodilator spirometry (including a spirometric surrogate suggestive of small airways involvement), and discontinuation/switching patterns. Methods: In this retrospective observational study at a tertiary referral center, adults with severe asthma treated with benralizumab, mepolizumab, omalizumab, or tezepelumab were included. Demographic, clinical, biomarker, and functional data were collected at baseline and follow-up. Post-bronchodilator FEV₁ and FEF25–75 (% predicted) were assessed at baseline, 6 months, 12 months, and 24–36 months when available. Longitudinal outcomes were analyzed using multivariable linear mixed-effects models; discontinuation and switching were recorded. Results: Eighty-seven patients were included (benralizumab n = 13, omalizumab n = 10, mepolizumab n = 30, tezepelumab n = 34), representing 10.9% of the clinic’s population. Most had long-standing disease, elevated body mass index, and a T2-high profile. Baseline characteristics were generally similar across groups, with expected differences in total IgE (p = 0.007) and blood eosinophils (p < 0.001). The primary endpoint (FEV₁ % predicted change from baseline to 12 months) showed adjusted mean changes of +12.46 (95% CI +1.63 to +19.29; p = 0.020) with benralizumab, +15.82 (+8.35 to +23.64; p < 0.001) with mepolizumab, +16.65 (+1.58 to +31.71; p < 0.001) with omalizumab, and +15.69 (+6.52 to +24.87; p = 0.030) with tezepelumab; trajectories differed by biologic class (time × biologic p = 0.019). Although the interaction term indicated heterogeneous temporal patterns, these adjusted findings should be interpreted as associative in the context of biomarker-driven treatment selection and not as evidence of comparative superiority of any biologic class. Discontinuation occurred in 15/87 (17.2%), with switching most commonly due to inadequate control. Conclusions: Real-world severe asthma patients demonstrate heterogeneous phenotypes and spirometric trajectories on biologics. Integrating biomarkers with longitudinal lung function monitoring, including small-airway spirometric surrogates, supports individualized management. Full article

Introduction: Previous research has suggested thiazolidinediones (TZDs) may be associated with certain solid tumors. We examined incidence rates over time for patients with solid tumors who received TZD treatment for diabetes. Methods: We identified medication use and diagnosis codes that were aggregated to phecode disease classifications derived from the nationwide Veterans Administration Health Record System from 2000 to 2021. We identified 148,139 patients who had ≥2 diabetes diagnoses and had no previous cancer diagnosis. Among these, 8981 subjects had ≥4 years of TZD exposure. We then identified subjects with ≥2 diagnosis codes for solid tumors including bladder (n = 3987), breast (n = 632), colorectal (n = 5139), esophageal (n = 482), glioma (n = 591), lung (n = 5142), melanoma (n = 1896), pancreatic (n = 726), prostate (n = 11,884), renal (n = 3145), testicular (n = 369), and thyroid (n = 513). We used multivariable Cox proportional hazards regressions to measure associations between TZD use and cancer incidence. TZD use was modeled as a time-varying covariate from the first to last prescription of TZD medication, and analyses were adjusted for age at diabetes diagnosis, self-reported race, self-reported ethnicity, sex, body mass index, and cancer site-specific polygenic risk scores. Results: Long-term (≥4 years) exposure to TZDs was significantly associated with increased risk of developing prostate cancer (HR = 1.24, p < 0.001) and decreased risk of developing lung (HR = 0.58, p < 0.001), bladder (HR = 0.51, p < 0.001), and renal cancer (HR = 0.75, p = 0.003). Conclusions: Decreased risk of developing several solid tumors (lung, bladder, and renal) indicate that TZDs may be strong candidates for drug repurposing strategies to manage these types of cancer. These results warrant replication attempts in external datasets. Full article

This study aimed to describe the upper-body bilateral deficit (BD) in recreational climbers and to examine its relationship with specific performance. Fifteen recreational climbers (11 men, 4 women; 25–45 years; ≥3 years of experience) performed unilateral and bilateral maximal isometric handgrip strength test (HGT), and unilateral and bilateral maximal isometric strength test using a climbing-specific fingerboard test (CSFT). The fatigue resistance index test (FRI) and the endurance capacity test (ECT) were used as performance tests. Paired Student’s T-tests were used to compare bilateral deficit results between CSFT and HGT. Pearson’s correlation was used to assess relationships between these variables with the level at 5%. The results showed a significant (p < 0.05) bilateral deficit in the CSFT (−2.53 ± 4.49%) and the HGT (−2.05 ± 3.29%), with no difference between methods. A positive correlation was found between bilateral deficit in the CSFT and the ECT (r = 0.53; p = 0.044), while no correlation was observed with the FRI. Relative bilateral strength to body mass was strongly associated with ECT (r = 0.92; p < 0.001). Greater bilateral deficit was associated with endurance capacity in climbers. In addition, the CSFT demonstrated good predictive accuracy and may be considered a specific and reliable tool for assessing BD in climbers. Full article

Background/Objectives: Serum 25-hydroxyvitamin D [25(OH)D] is a clinically used biomarker of vitamin D nutritional status, although it is also influenced by sunlight exposure, supplementation, season, and other host factors. Short-term functional status after extracorporeal shock wave therapy (ESWT) for lateral epicondylitis varies. We evaluated whether serum 25(OH)D level and status were associated with 12-week functional outcomes among ESWT-treated patients. Methods: This single-center retrospective cohort included 62 adults with lateral epicondylitis who received outpatient ESWT and had baseline and 12-week assessments. Baseline variables included grip strength ratio, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, serum 25(OH)D measured using the Architect 25-OH D vitamin kit, common extensor tendon (CET) thickness, age, sex, and body mass index. Multivariable linear regression was used in an analysis-of-covariance framework. Serum 25(OH)D was assessed continuously and as <20 versus ≥20 ng/mL in exploratory threshold analysis. Results: Serum 25(OH)D was 21.0 ± 8.4 ng/mL; 30 patients (48.4%) had <20 ng/mL, 22 (35.5%) had 20–29.9 ng/mL, and 10 (16.1%) had ≥30 ng/mL. QuickDASH decreased from 42.0 ± 17.4 to 27.0 ± 13.7, and grip strength ratio increased from 0.58 ± 0.14 to 0.76 ± 0.14. Higher serum 25(OH)D was associated with lower 12-week QuickDASH after adjustment (β per 10 ng/mL = −4.04, 95% CI −7.17 to −0.91; p = 0.012). Additionally, 25(OH)D <20 ng/mL was associated with higher 12-week QuickDASH (β = 6.43, 95% CI 1.17 to 11.69; p = 0.017). Serum 25(OH)D was not clearly associated with 12-week grip strength ratio. Conclusions: Lower serum 25(OH)D, interpreted as a vitamin D nutritional-status marker rather than as a nutrition-specific causal exposure, was associated with worse 12-week patient-reported function, but not grip strength ratio. The <20 ng/mL threshold analysis was exploratory and was not powered for subgroup inference. These findings should be interpreted as observational and hypothesis-generating. Full article