Medicine and Pharmacology

Abstract: Background: Inappropriate thyroid ultrasound (TUS) ordering by primary care providers (PCPs) is documented at academic centers but not in safety-net populations serving predominantly Hispanic patients. Objective: To quantify non-guideline TUS ordering, identify independent predictors, characterize indication-level concordance, and assess the association between guideline adherence and downstream diagnostic interventions. Design: Retrospective observational study (STROBE-compliant). Setting: Outpatient primary care clinics of a public safety-net hospital in Moreno Valley, California. Participants: 405 adults and children (age 7–86 years) who underwent PCP-ordered thyroid ultrasound between March 2023 and March 2024. Inpatient, specialist-ordered, and specialist-recommended TUS were excluded. Measurements: ATA guideline concordance (primary outcome) documented directed thyroid physical examination (PE), ICD-10 indication, and downstream outcomes (FNA, Bethesda cytology, thyroidectomy, pathology). Multivariable logistic regression, chi-square, and Fisher exact tests were used. Results: Of 405 orders, 178 (44.0%) were non-guideline. Patients were predominantly Hispanic (68.6%) and female (89.1%). Absence of directed PE independently predicted non-guideline ordering (OR, 4.67; 95% CI, 2.61–8.36; p< 0.001). Thyrotoxicosis/hyperthyroid and compressive-symptom indications had OR >38 versus nodule/follow-up. Biochemical indications had 95–100% non-guideline rates. Guideline-concordant TUS produced higher FNA rates (26.0% vs. 10.7%; p< 0.001) and 2.8-fold more Bethesda III–VI findings. Among 14 thyroidectomies, 71.4% occurred in patients without documented PE. Limitations: Single-center retrospective design; PE documentation may underestimate actual examination; causality cannot be established. Conclusion: Non-guideline TUS ordering is common in safety-net primary care, driven by biochemical indications and PE omission. Guideline-concordant TUS yields greater diagnostic value; targeted education and decision-support are needed.

Abstract: CYP17A1 inhibition suppresses adrenal androgen precursor production in advanced prostate cancer, but steroidal and non-steroidal inhibitors may differ in their selectivity towards 17α-hydroxylase and 17,20-lyase activities. Here we compare abiraterone and seviteronel using enzyme assays, adrenal steroidomics, structural analysis, molecular-dynamics simulations and prostate cancer cell models. Abiraterone was the more potent inhibitor of both CYP17A1 activities, whereas seviteronel showed weaker absolute potency but a higher lyase/hydroxylase selectivity index. In NCI-H295R cells, abiraterone caused marked pregnenolone and progesterone accumulation with broad depletion of downstream steroids. Seviteronel produced a more restricted shift, preserving partial 17α-hydroxylated flux while suppressing androgen output. Structural analysis showed that abiraterone combines heme coordination with a steroidal Asn202 anchor, whereas seviteronel uses Val482-backbone anchoring and a distinct non-steroidal contact distribution. Replicate simulations identified greater conformational heterogeneity of the central I-helix region in the seviteronel-bound system, although these dynamics do not establish the mechanism of catalytic selectivity. In prostate cancer models, both compounds preferentially reduced viability in androgen-responsive cells and increased sensitivity to ferroptosis-inducing lipid-peroxidation stress. These findings distinguish the endocrine, structural and redox pharmacology of two CYP17A1-targeted agents.

Abstract: Mesenteric panniculitis (MP) is an uncommon inflammatory disorder of mesenteric adipose tissue. Its pathophysiology remains unclear. Gut dysbiosis, intestinal barrier dysfunction, metabolic endotoxemia, glycemic variability (GV), and vascular dysfunction are involved in inflammatory and metabolic processes. These may also affect visceral and mesenteric adipose tissue. This narrative review examines the possible relationships among these mechanisms and mesenteric panniculitis and discusses their integration within a proposed gut–mesentery–metabolic axis. The literature was reviewed using PubMed, Scopus, Web of Science, and Google Scholar, including studies published between 2000 and 2026. We focus on recent evidence published between 2021 and 2026. Current data suggest that dysbiosis and impaired intestinal barrier function may facilitate microbial-product translocation and lipopolysaccharide-mediated inflammatory signaling, while GV may contribute to oxidative stress, endothelial dysfunction, and pro-inflammatory responses. Mesenteric vascular anatomy and impaired regional perfusion may represent additional factors influencing local tissue susceptibility. Recent randomized controlled trials of microbiome-targeted interventions in metabolic disorders have shown heterogeneous effects on glycemic, inflammatory, and microbiota-related outcomes. Future investigation of individualized microbiome-directed strategies is needed. Recent evidence demonstrating that these microbial, metabolic, or vascular mechanisms initiate or sustain MP remains limited. The proposed gut–mesentery–metabolic axis should be regarded as a hypothesis for further investigation. Prospective studies integrating microbiome profiling, metabolic biomarkers, glycemic variability assessment, vascular evaluation, and imaging phenotypes are needed to clarify if biological subgroups of MP can be identified.

Abstract: Background. Digital glucose technologies include continuous glucose monitoring (CGM), emerging sensing modalities, multi-vendor platforms, forecasting models and artificial-intelligence (AI) briefings. These components are already chained into one patient journey, yet they are still often judged by a single convenient metric, such as MARD, a fused curve, RMSE/R² or fluent text. Visual continuity across brands can look like a medical record while stack safety for care remains unevaluated. Risk can therefore propagate along the product stack.Framework and contributions. We propose a four-layer, stack-wise evaluation framework for digital glucose care comprising sensing (L1), platform interoperability and provenance (L2), forecasting (L3), and human–AI briefing (L4). The framework makes three contributions. First, it organises the glucose product stack as successive clinical gates and identifies the false reassurance associated with each layer, complementing horizontal multidomain AI tools. Second, it specifies the cross-brand longitudinal account as an informatics object and treats L2 provenance as the hinge on which L3 and L4 may inherit trust, with acceptance criteria independent of sensor MARD. Third, it translates the gates into a brand-switching cascade test (Figure 3), a Have-you checklist for procurement and ethics (Table 3), an evidence-bound briefing template (Figure 2), and constrained deployment modes.Findings. Synthesising public evaluation and interoperability literature, we show that silent L2 splicing can carry forward as unchanged L3 score thresholds and categorical L4 prose even when L1 labelled claims are individually acceptable; provenance-visible segments, forecast abstention and evidence-bound briefings interrupt that cascade. Tables 1–3 and Figures 1–3 operationalise the gates.Conclusion. Stack-wise gating, with L2 provenance as the hinge, makes readiness for care an evaluable claim before procurement. A visually continuous multi-vendor glucose curve remains an interface achievement until layer-wise warrants are in place.

Abstract: Diabetes mellitus is a worldwide metabolic disorder that can be debilitating to many if uncontrolled. Biomarkers, such as hemoglobin A1C and glycated albumin, are central to the effort to control diabetes. These each have their own advantages and disadvantages, and there is much ongoing research into development of improved biomarkers and biomarker measurement methods. Continuous glucose monitoring is also widely used to closely monitor diabetes in patients today. Increasing, however, there has been research into use of biomarkers in alternative mediums, such as tear fluid or saliva. This review efficiently summarizes the current biomarkers used clinically today, their advantages and disadvantages, as well as the biomarkers on the horizon that could advance how diabetes is treated in the future.

Abstract: Continuous glucose monitoring (CGM) has improved diabetes care, yet cost, wear burden, and reduced accuracy in the hypoglycemic range still motivate complementary, low-burden sensing. Consumer wearables that record electrocardiography (ECG), photoplethysmography (PPG), electrodermal activity (EDA), and related signals are widely available, and a growing literature maps them to glucose values, glycemic curves, or hypo-/hyperglycemia risk. Progress remains uneven: free-living signals are unstable, physiology-to-glucose mappings are indirect and non-deterministic, public multimodal datasets are small, evaluation protocols are heterogeneous, and cross-subject generalization is limited. Based on representative works in this field, this preprint contributes: (1) a three-task taxonomy (risk, value, curve) and how each aligns with wearable modalities; (2) a six-lineage evidence map with a qualitative exposure table of typical protocols and reporting gaps, treating CGM-only forecasting as a Task-A contrast baseline; (3) a synthesis of quality, uncertainty, and interpretability gaps plus a literature-derived minimal reporting checklist; and (4) an open-problem agenda. These deliverables clarify applicability and trust boundaries for wearable physiology as a glycemic decision aid under declared conditions, rather than as an undeclared CGM replacement.

Abstract: Diabetes mellitus is highly prevalent in the United States and increases the risk of severe illness in patients with COVID-19. We compared outcomes in hospitalized COVID-19 patients with and without diabetes using the National Inpatient Sample (2020-2022), adjusting for confounders via multivariable logistic regression. Among 5,934,565 hospitalizations for COVID-19, 2,155,978 (36.3%) had concomitant diabetes. The diabetes group had higher unadjusted in-hospital mortality (13.5% vs. 10.1%), but was not independently associated with mortality after adjustment (aOR 0.98; 95% CI 0.97-1.00). However, diabetes was independently associated with higher incidence of acute respiratory failure (46.1% vs 42.3%, aOR 1.29; 95% CI: 1.27-1.30), greater need for invasive mechanical ventilation (aOR 1.22; 95% CI 1.20-1.24) and non-invasive ventilation (aOR 1.27; 95% CI 1.25-1.29). These patients also had higher rates of ARDS, acute kidney injury, renal replacement therapy, sepsis, septic shock, and vasopressor use, along with longer length of hospital stay and higher total charges of hospitalization. Mortality among COVID-19 patients with diabetes declined through 2020-2022 (15.8% to 8.4%). Diabetes was not independently associated with in-hospital mortality but was associated with greater respiratory, renal, hemodynamic complications and hospital resource utilization. Early recognition and management of diabetes is warranted in patients with COVID-19.

Abstract: Childhood obesity is a major global health concern with a strong heritable component. While most cases are polygenic and environmentally driven, a subset of children present with rare genetic forms of obesity, including syndromic and monogenic disorders. Over the past three decades, advances in gene discovery—from candidate gene studies to genome-wide association studies (GWAS) and next-generation sequencing (NGS)—have significantly improved our understanding of the biological pathways regulating appetite and energy balance, particularly the leptin–melanocortin pathway. Early identification of genetic obesity is clinically relevant, as it allows tailored management, targeted pharmacological interventions, genetic counselling, and reduction of psychosocial stigma. However, distinguishing rare genetic obesity from common polygenic obesity remains challenging in clinical practice. This review summarizes the current knowledge on the genetic architecture of pediatric obesity, highlights red flags suggestive of monogenic and syndromic forms, discusses available diagnostic algorithms and genetic testing strategies, and explores the transition from gene discovery to precision medicine. The integration of genetic, epigenetic, and environmental data will be crucial to refine risk prediction and therapeutic strategies in the pediatric population.

Abstract: Background: Obesity is a primary driver of functional male hypogonadism, including male obesity-associated secondary hypogonadism (MOSH), for which weight loss remains the first-line intervention. However, the behavioral determinants of eating behavior in this population remain poorly characterized. This exploratory analysis examined whether lower total testosterone (TT) levels were associated with specific domains of the Eating Behavior Phenotype Scale (EFCA). Methods: A cross-sectional analysis was conducted using baseline data from a retrospective outpatient cohort of men with obesity who had available total testosterone measurements. Eating behavior was assessed using the validated 16-item EFCA. Associations were assessed primarily using Spearman’s rank correlation, with Kendall’s tau and leave-one-out analyses performed as sensitivity analyses. Results: Of the analytical sample (n = 10; mean BMI 38.8 kg/m² among the nine participants with available anthropometry), eight participants completed the EFCA. Total testosterone (TT) levels (mean 310.7 ng/dL) did not correlate with the hedonic, compulsive, hyperphagic, or emotional domains. A strong inverse correlation was observed between TT and the disorganized domain (Spearman’s rho = −0.914; p = 0.0015). This association remained significant after Bonferroni correction and was confirmed by Kendall’s tau and leave-one-out sensitivity analyses. Conclusions: Lower TT levels were selectively associated with increased eating disorganization. These hypothesis-generating findings warrant confirmation in prospective studies incorporating comprehensive androgen profiling, including measurements of free testosterone and sex hormone-binding globulin (SHBG).

Abstract: The remarkable evolution of incretin-based therapeutics from selective glucagon-like peptide-1 receptor agonists to dual, triple and emerging polyagonists has fundamentally expanded our understanding of metabolic regulation. Clinical trials have consistently demonstrated coordinated improvements in glycaemic control, hepatic steatosis, body composition, insulin sensitivity, cardiovascular and renal outcomes, inflammatory activity, mitochondrial metabolism and energy expenditure that extend well beyond the expected physiological effects of individual receptor activation. These observations suggest that the therapeutic efficacy of contemporary polyagonists cannot be adequately explained by isolated hormonal mechanisms but instead reflects modulation of an integrated physiological regulatory system. We propose the existence of an Entero–Pancreatico–Hepatico–Systemic Polyhormonal Metabolic Homeostasis Network (EPHS-PMHN), a dynamic endocrine, neural, immune and metabolic communication network in which gastrointestinal nutrient sensing initiates coordinated signaling through the enteroendocrine system, pancreatic islets, liver, central nervous system, adipose tissue, skeletal muscle, kidneys, cardiovascular system, immune system and peripheral mitochondria. Although incretin hormones constitute the principal initiating signals within this network, physiological regulation is ultimately achieved through integrated actions of both incretin and non-incretin mediators including insulin, glucagon, amylin, fibroblast growth factor-21, bile acid signaling pathways, adipokines, hepatokines, myokines, autonomic neural pathways, inflammatory mediators, circadian regulators and intracellular nutrient-sensing mechanisms. Within this framework, physiological variables traditionally regarded as independently regulated — including fasting and postprandial glycaemia, hepatic fat content, insulin-glucagon balance, hepatic gluconeogenesis, lipid oxidation, triglyceride synthesis, resting energy expenditure, metabolic flexibility, mitochondrial function and inflammatory tone — are interpreted as emergent properties of coordinated network behaviour rather than isolated homeostatic endpoints. Furthermore, neurobehavioral determinants including psychological stress, sleep architecture, cognitive function, emotional state, personality traits and environmental influences continuously modulate network activity, thereby contributing to the unique metabolic phenotype observed in each individual. Accordingly, obesity, type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, dyslipidaemia, sarcopenic obesity and cardio-renal-metabolic syndrome are viewed not as isolated disorders but as diverse clinical expressions of differential dysregulation within the same integrated metabolic network. This framework provides a mechanistic explanation for the superior efficacy of polyagonist therapies as network-restorative interventions rather than hormone replacement strategies and establishes a conceptual foundation for precision metabolic medicine based on characterization of network function instead of isolated biochemical abnormalities.

Abstract: Gut microbial metabolites serve as functional mediators of gut–brain communication, linking microbial alterations to neurodegenerative pathology. How metabolite profiles shift during disease progression and interact with host genetic susceptibility remains poorly characterized. This review centers on Alzheimer’s disease (AD) as the primary model, with Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) included for cross-disease comparison. Across the AD continuum, microbial metabolic remodeling features reduced protective metabolites and elevated inflammation-related metabolites. Short-chain fatty acids (SCFAs), particularly butyrate, and indole-derived metabolites are altered from early cognitive impairment to clinical dementia. Trimethylamine N-oxide (TMAO), kynurenine intermediates and abnormal bile acid profiles accumulate and drive neuroinflammatory and metabolic disturbances. Mechanistically, metabolic shifts affect AD pathology through three interrelated pathways. Tryptophan-derived metabolites regulate immune homeostasis via aryl hydrocarbon receptor (AhR) signaling. SCFAs modulate epigenetic processes linked to Aβ and tau lesions. Intestinal and blood-brain barrier damage allows peripheral metabolic and inflammatory signals to reach the central nervous system. APOE4 alters lipid metabolism and systemic inflammation to modify individual metabolic susceptibility. Shared metabolic abnormalities including SCFA loss and barrier damage exist in PD and ALS, alongside disease-specific metabolic changes. Existing data support associations among host factors, the microbiome, and metabolite profiles, but longitudinal target-engagement studies remain limited.

Abstract: Growth differentiation factor 15 (GDF15) is measured across two literatures that do not read each other. Clinical chemistry has established that it is a trait-like analyte with a stable set point: within-subject coefficients of variation of 6.3% and 7.6% in two independent cohorts against analytical variation below 1%, reference change values of 23% and 24.3% in tightly controlled healthy-volunteer protocols, and two specimens sufficient to estimate an individual’s homeostatic set point within ±10%. Exercise physiology has established that a single hour of submaximal cycling raises circulating GDF15 by 34% during exercise and 64% two hours after it ends, and that prolonged bouts raise it four- to fivefold. Read together, these yield a direct result: a single unrecorded bout of physiological load displaces GDF15 by 1.5 to 17 times the reference change value for the analyte. The stability of the set point is precisely what makes this consequential — a substantial transient is being injected into a quantity whose genuine within-person variation is under 8%, and within-subject variation is preserved across age strata (7.4% under 45 years, 7.9% at 45 and over). The problem is not confined to comparison against reference intervals. Where GDF15 is used as a continuous covariate or dichotomized at cohort-specific tertiles, unrecorded excursions produce misclassification, and where habitual activity differs between cases and controls that misclassification is directional rather than random. This paper formalizes the phasic–tonic distinction, derives its consequences for design and interpretation, reinterprets two unexplained findings in the fibromyalgia case-control literature, proposes a minimum reporting standard, and identifies the single measurement that would resolve the principal remaining uncertainty. No new primary data are presented.

Abstract: Diabetic wound healing is characterised by persistent inflammation, impaired angiogenesis, extracellular matrix (ECM) dysregulation, and defective tissue remodelling, frequently resulting in chronic wounds such as diabetic foot ulcers (DFUs). Fibrosis, characterised by excessive ECM deposition and sustained fibroblast activation, is increasingly recognised as an important barrier to effective wound repair in patients with diabetes. Emerging evidence suggests that glucocorticoid signalling, particularly through the stress hormone cortisol and its activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), may contribute to pathological and fibrotic changes in diabetic skin by altering inflammation, extracellular matrix turnover, angiogenesis, and cellular behaviour. In parallel, profibrotic mediators such as connective tissue growth factor (CTGF) and insulin-like growth factor binding protein-5 (IGFBP-5) have been implicated in fibroblast activation and fibrosis across multiple tissues, including skin. However, the interactions between cortisol signalling and these downstream pathways remain poorly understood. This review examines current evidence regarding the role of 11β-HSD1-mediated cortisol signalling in fibrosis and impaired diabetic wound healing, with particular emphasis on potential interactions with CTGF and IGFBP-5. Evidence from preclinical and early clinical studies suggests that inhibition of 11β-HSD1 may improve wound repair and tissue integrity; however, many existing studies rely on acute wound models and do not fully reflect the chronic inflammatory and fibrotic environment of diabetic wounds.

Abstract: Background/Objectives: Drug-associated vitamin B12 deficiency has emerged as a significant concern in clinical nutrition, as long-term use of metformin and proton pump inhibitors (PPIs) is common and may compromise cobalamin status through different physiological mechanisms. This narrative review summarizes mechanisms, risk profiles, diagnostic pitfalls, monitoring strategies and treatment options for vitamin B12 deficiency associated with chronic medication use. Methods: A narrative literature review was conducted by searching major biomedical databases and screening reference lists to identify relevant clinical studies, meta-analyses, narrative and systematic reviews, and clinical practice guidelines on vitamin B12 physiology, drug–nutrient interactions, biomarkers of cobalamin status, and supplementation strategies. Results: Metformin is consistently associated with lower serum vitamin B12 concentrations, particularly with high doses and prolonged exposure; PPIs may reduce the release of food-bound cobalamin through gastric acid suppression. Combined use may increase risk in older adults and in patients with restrictive diets, malabsorption or neurological symptoms. Serum vitamin B12 alone has limited diagnostic accuracy in borderline ranges; methylmalonic acid and homocysteine may help identify functional deficiency. High-dose oral vitamin B12 is effective in most clinical scenarios and may reduce healthcare burden compared with intramuscular therapy. Conclusions: A proactive, risk-based approach to monitoring and treatment may prevent hematological and neurological complications while preserving essential therapies such as metformin.

Abstract: Childhood overweight and obesity have been associated with earlier pubertal onset most commonly in girls than boys. An ever-increasing number of factors contributing to this association have been identified, including leptin, insulin, sirtuins, epigenetic factors and gut-derived molecules, such as short-chain fatty acids. This review aims to identify all the mechanisms involved in early puberty amongst children with increased weight and possibly help early detection and reduce any long-term related risks associated with precocious puberty in overweight children. Clarifying these links is clinically important for monitoring pubertal progression and cardiometabolic risk in children with obesity, and for informing prevention and early intervention aimed at reducing long term adverse outcome.

Abstract: Background: Endothelial deregulation (ED) manifests as a major secondary complication in clinical Diabetes mellitus (DM) which is established as the preliminary stage of vascular dysfunction. This study evaluates a broader repertoire of biomarkers that are relevant to diabetic - ED and the inflammatory potential of the high mobility group box-1 (HMGB1) nuclear protein in mitigating type-2 diabetes (T2D) -induced ED. Method: A total of 33 biomarkers were evaluated from retrospective metabolic and sociodemographic data in a forest plot following the PICOS study design. A total of 1830 entries published during the past 10 years ending on mid December 2023 from PUBMED, MEDLINE, SCOPUS, SPRINGER-LINK and WOS databases were screened using a variety of MESH terms. The results were generated using the RevMan and GraphPad Prism software. Modified Cochrane Organisation template for systematic reviews and meta-analyses was followed with data validated in PRISMA. The protocol of this study was registered at https://www.crd.york.ac.uk/Prospero/CRD42023493221. Results: Only 16 single case-control studies qualified for data extraction. 18 biomarkers were identified as having a significantly high risk of ED. IL-6 emerged as the biomarker having the highest effect size (SMD 5.20, 95% CI, 3.21, 7.18, p<0.00001, n=209). HMGB1 comprised the sixth highest standardized mean difference (SMD 2.86, 95% CI, 1.91, 3.81, p<0.00001, n=762) out of the eight highest biomarkers calculated. Conclusion: The biomarkers consisting of a mix of traditional and non-traditional markers carried a high risk in developing T2D-induced cardiovascular disease and it was concluded that HMGB1 provides us with a high-risk inflammatory metabolic target.

Abstract: Carbimazole is a widely used medication to treat Graves disease. Acquired aplastic anemia is a rare complication that happens in less than 0.01% of people. We had a 36-year-old woman. Who is on high-dose Carbimazole . who got high-grade fever; severe menorrhagia ; spontaneous epistaxis; and pancytopenia . Her bone marrow biopsy showed severe bone marrow failure with only 5% cellularity and trilineage hypoplasia. Other potential causes were rolled out. Immediate discontinuation of Carbimazole was done; and supportive care; including blood transfusions; broad-spectrum antibiotics; G-CSF; and eltrombopag; was started. The patient deteriorated during her hospital stay; developed neutropenic sepsis and acute respiratory failure from diffuse alveolar hemorrhage; which required intubation and pulse steroid therapy. She was stabilized and discharged; with a referral to a tertiary medical center for starting antithymocyte globulin (ATG) immunosuppressive therapy. This case serves as a stark reminder of how lethal thionamide-induced bone marrow failure can be; highlighting the vital need for immediate drug cessation; swift intensive care; and thorough patient education on early warning signs.

Abstract: Background/Objectives: Obesity is a chronic, multifactorial, and relapsing disease, and weight-loss outcomes should not be attributed solely to individual psychological characteristics. Psychological resilience has been proposed as a potential determinant of treatment adherence and weight-loss response, but prospective evidence in special-ized obesity care remains limited. This study investigated whether baseline psycholog-ical resilience predicts six-month weight loss among adults with obesity receiving spe-cialized outpatient care. Methods: We conducted a retrospective observational cohort study using real-world clinical data from the obesity outpatient service of a quaternary hospital in São Paulo, Brazil. The source cohort included 63 patients with six-month follow-up records. Baseline Resilience Scale for Adults (RSA) scores were available for 39 patients, of whom 35 had complete paired weight data and constituted the com-plete-case analytical cohort for the primary analysis. The primary outcome was six-month percent total body weight loss (%TBWL). Associations between baseline RSA score and %TBWL were evaluated using Spearman correlation and linear regression models, including adjustment for age, sex, and baseline body mass index. Results: In the complete-case analytical cohort, mean body weight decreased from 105.3 ± 23.0 kg at baseline to 102.4 ± 23.0 kg at six months. Mean absolute weight loss was 2.92 ± 5.72 kg, corresponding to 2.71 ± 5.64% TBWL. Weight reduction was statistically significant by paired t-test (95% CI 0.96 to 4.88 kg; p = 0.0048). Nine patients (25.7%) achieved ≥5% weight loss, and two patients (5.7%) achieved ≥10% weight loss. Baseline RSA score was not correlated with %TBWL (Spearman’s rho = −0.063; p = 0.718). In simple linear regression, each 10-point increase in RSA score was associated with a 0.03 per-centage-point change in %TBWL (95% CI −1.01 to 1.07; p = 0.953). Results remained non-significant after adjustment for age, sex, and baseline BMI (β = 0.14; 95% CI −1.01 to 1.30; p = 0.804). Conclusions: In this complete-case real-world cohort, baseline psy-chological resilience was not associated with six-month weight loss in adults with obe-sity receiving specialized outpatient care. These findings suggest that short-term weight-loss outcomes should not be attributed to baseline resilience or individual psy-chological characteristics alone. The substantial proportion of missing RSA data war-rants cautious interpretation and highlights the need for larger prospective studies evaluating resilience in relation to adherence, persistence, long-term maintenance, and weight regain.

Abstract: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine–metabolic disorder fre-quently associated with insulin resistance (IR) and increased cardiovascular risk. Soluble CD40 ligand (sCD40L) and soluble E-selectin (sE-selectin) are circulating biomarkers re-flecting immune activation and endothelial dysfunction, respectively. However, their dif-ferential associations with IR in PCOS, particularly in the context of central obesity, re-main incompletely understood. This cross-sectional study included 80 women with PCOS stratified according to waist-to-height ratio (WHtR > 0.50 vs. ≤ 0.50). Clinical, metabolic, hormonal, inflammatory, and endothelial parameters were evaluated. Correlation and multivariable regression analyses were performed to identify independent determinants of circulating sCD40L and sE-selectin. Women with central obesity exhibited significantly higher fasting insulin, HOMA-IR, triglycerides, non-HDL cholesterol, systolic blood pres-sure, and sE-selectin concentrations, together with lower HDL cholesterol. No significant differences were observed in TNF-α, IL-6, or sCD40L. In adjusted regression models, fast-ing glucose independently predicted sCD40L (β = 0.27, p = 0.02), whereas fasting insulin emerged as the strongest determinant of sE-selectin (β = 0.41, p < 0.001). These findings suggest distinct associations of immune and endothelial biomarkers with IR in PCOS. As-sessment of sCD40L and sE-selectin may provide complementary information for early cardiometabolic risk stratification in affected women.

Abstract: Background/Objectives: Hypovitaminosis-D is a highly prevalent condition worldwide, associated with adverse skeletal and extra-skeletal outcomes. Increasing demand for serum 25-hydroxyvitamin D (25(OH)D) testing points toward the need for simple tools to identify individuals at risk and optimize laboratory use. We aimed to develop and validate a clinical risk score for predicting hypovitaminosis-D based on easily assessable risk factors. Methods: This cross-sectional study included 1,408 adults across Italy. Demographic, clinical, lifestyle, and dietary data were collected through a standardized questionnaire. Univariable and multivariable logistic regression analyses identified predictors of 25(OH)D &lt;20 ng/mL and &lt;30 ng/mL. Risk scores were derived from models. Discriminative ability was assessed using ROC curves, and calibration by comparing predicted and observed probabilities. Results: Median age was 67 years, and 91.3% were female. Median 25(OH)D was 33.2 ng/mL; 9.8% had levels &lt;20 ng/mL. Independent predictors of hypovitaminosis-D (25(OH)D &lt;20 ng/mL) included higher body mass index, residence in Northern Italy, reduced summer sun exposure, sunscreen use, cardiovascular disease, glucocorticoid use, absence of cholecalciferol supplementation, and no prior vitamin D use. The score (range 9-18) showed good discrimination (Area under the curve; AUC: 79.1%, 95% CI 75.3-82.9) and excellent calibration (r=0.98, p&lt;0.001). A screening cut-off (10.3-10.7) ensured high sensitivity (87.0-92.7%), while 11.9-12.0 balanced sensitivity (~62%) and specificity (~80%). A second score for 25(OH)D &lt;30 ng/mL showed moderate discrimination (AUC: 69.6%). Performance remained stable across seasons and in untreated subjects (AUC: 72.7%). Conclusions: A simple, data-driven clinical risk score identifies individuals at risk of hypovitaminosis-D and may support targeted screening, reduce unnecessary testing, and improve cost-effectiveness in clinical practice.