As obesity and diabetes are on the verge of an alarming growth, so is the use of tirzepatide, a novel dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) and currently the most effective weight loss-drug. This research aimed to identify reporting patterns related to suboptimal therapeutic outcomes and tirzepatide-related drug-use issues, mining the EudraVigilance (EV).

Retrospective pharmacovigilance study using descriptive and disproportionality analyses of reports retrieved from the EV database.

Analysis of individual case safety reports involving tirzepatide in comparison with other GLP-1 RAs in the overall dataset (healthcare professionals (HP) and non-HP reports combined) and in the HP group.

Reporting ORs (RORs) with 95% CIs for selected Preferred Terms (PT) related to drug-use issues.

Among all analysed PTs, the most frequently reported were 'Off-label use' (n=1521), 'Drug ineffective' (n=425) and 'Off-label use device' (n=99). PTs in HP reports showed lower reporting odds compared with non-HP reports. In the overall dataset, reports involving tirzepatide showed lower reporting odds of the PT 'Drug ineffective' than those involving liraglutide (ROR 0.61, 95% CI 0.54 to 0.70), dulaglutide (ROR 0.72, 95% CI 0.63 to 0.82), exenatide (ROR 0.78, 95% CI 0.67 to 0.92) and semaglutide (ROR 0.81, 95% CI 0.72 to 0.91). However, in HP reports, no difference in reporting odds was observed between tirzepatide and semaglutide. A different pattern was observed for 'off-label use' in the full dataset, with higher reporting odds for tirzepatide vs lixisenatide, dulaglutide and liraglutide, but lower reporting odds vs semaglutide (ROR 0.52, 95% CI 0.49 to 0.55). In contrast, a higher reporting odd for the PT 'off-label use of device' was observed for tirzepatide versus semaglutide (ROR 43.47, 95% CI 16.00 to 118.13) in the overall reports; however, this finding should be interpreted with caution given the wide CI.

This study complements existing evidence from clinical trials and current clinical practice.

Genetic risk scores (GRSs) are summaries of genetic data that can improve prediction of disease risk and progression. GRSs are increasing available but rely on high-quality input data to produce good output results; with noisy or missing inputs the GRS may be inaccurate. We aimed to develop a method to produce a robust estimate of the GRS when input data are missing, noisy or both.

We developed a neural network approach, named masked-multi-layer perceptron (MLP), for robust GRS calculation trained on a set of GRS scores calculated on clean data. The masked-MLP includes additional input data and has noise inserted during training, both which make the model more robust.

A GRS for type 1 diabetes (T1D) calculated on input data with 10% of the data corrupted had a Spearman rank correlation to the clean GRS of 0.669 (0.665-0.674) while the equivalent for the masked-MLP was 0.951 (0.950-0.952). For the same data, the area under the receiver operating characteristic curve for separation of T1D from population samples fell from 0.919 (0.904-0.932) to 0.808 (0.787-0.827) for the GRS while the masked-MLP fell to 0.910 (0.895-0.924).

The masked-MLP was more robust to noise when calculating a GRS than using standard approaches. Our approach has the potential to enable GRS calculations which are more robust to noise.

The American Diabetes Association (ADA) recommends prescribing glucagon for people with diabetes (PWD) using insulin or at high risk of hypoglycemia; however, prescribing rates remain low. Few studies have examined practices and barriers to outpatient glucagon use from pharmacists' perspectives.

This study aimed to describe pharmacists' perspectives on current practices and barriers to outpatient glucagon use in PWD.

A voluntary, electronic survey questionnaire was distributed to 1,624 members of the American College of Clinical Pharmacy Ambulatory Care and Endocrine and Metabolism Practice and Research Networks. Categorical, Likert, and open-ended questions were used to evaluate practice scope, patient population, and knowledge and perceptions related to glucagon use. Statistical analyses were conducted using IBM SPSS Statistics and the Stats iQ function within the Qualtrics® platform.

Of the 186 respondents included, most pharmacists practiced in urban areas (58.2%) and primary care (83.1%), with a mean of 10.6 years of experience managing PWD. Respondents estimated that 23.5% of their patients with diabetes have an active glucagon prescription, and 42.1% fill their prescription. In hypothetical patients, respondents were most likely to recommend or prescribe glucagon for PWD with a history of hypoglycemia requiring medical attention (95.7%), recurrent hypoglycemia (89.6%), or using intensive insulin regimens, including continuous subcutaneous insulin infusion (82.3-93.9%). Respondents were less likely to do so for people with type 2 diabetes using basal insulin only (38.4%) or secretagogues (17.1%), or PWD with a history of an isolated hypoglycemic event (17.7%). The most frequently identified barriers to outpatient glucagon use were cost (75.5%), patient health literacy regarding when to use glucagon (71.7%), and insurance coverage (68.2%).

Current practices among pharmacists engaged in outpatient diabetes management may not fully align with recommendations for glucagon use, highlighting opportunities for pharmacists to support strategies that optimize appropriate glucagon prescribing for high-risk patients.

Peripheral artery disease (PAD) is a prevalent atherosclerotic disorder affecting over 113 million individuals worldwide, with its global burden projected to rise substantially amid population aging and increasing metabolic comorbidities, including type 2 diabetes mellitus (T2DM). Conventional diagnostic assessment, including the ankle-brachial index (ABI) as a non-invasive hemodynamic measurement and imaging-based techniques such as duplex ultrasonography, computed tomography angiography, magnetic resonance angiography, and digital subtraction angiography, has limited sensitivity for early disease detection and does not fully capture the multidimensional pathophysiological processes underlying disease progression, and ABI generates false-negative results in elderly and diabetic patients with medial arterial calcification, a critical unaddressed limitation in routine screening. Recent advances in multi-omics technologies have accelerated the discovery of circulating biomarkers that reflect distinct pathological axes-inflammation, oxidative stress, endothelial dysfunction, and metabolic dysregulation-underlying PAD pathogenesis. These novel biomarkers hold considerable promise for enhancing early diagnosis, risk stratification, prognostic assessment, therapeutic monitoring and postoperative restenosis prediction, and individualized precision intervention guidance. This review systematically summarizes the most recent advances in PAD biomarkers across these four pathophysiological categories, elucidating their mechanistic links to disease progression and critically evaluating their clinical utility and translational barriers; We further develop population-specific biomarker strategies for patients with diabetes mellitus, dialysis-dependent kidney disease, and chronic limb-threatening ischemia (CLTI), while considering disease-specific confounding factors and the current limitations of biomarker validation. We further discuss emerging biomarker classes, including extracellular vesicle-derived molecules and microRNAs, and highlight the superior diagnostic and predictive efficacy of multi-biomarker panels compared with single indicators, combined with machine learning modeling frameworks. Large-scale multi-center, multi-ethnic prospective validation studies, standardized pre-analytical and analytical detection protocols, and cost-effectiveness health economic evaluations remain essential prerequisites for full-scale clinical implementation.

BackgroundThe impact of Antidiabetic Agents on COPD Exacerbations remains uncertain. We conducted a comprehensive review to evaluate the impact Antidiabetic Agents on COPD Exacerbations in patients with T2DM.MethodsWe searched PubMed, Embase, and Web of Science from inception to January 15, 2026 for observational studies involving adults with T2DM and COPD. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models, treatments were ranked using the Surface Under the Cumulative Ranking Curve (SUCRA), and study quality was assessed using the Newcastle-Ottawa Scale.ResultsThirteen studies comprising 755,206 participants were included. Compared with sulfonylureas, SGLT-2 inhibitors were associated with the lowest risk of overall COPD exacerbations (RR 0.71, 95% CI 0.66-0.77), followed by GLP-1 receptor agonists (RR 0.77, 95% CI 0.71-0.84). Metformin demonstrated a near-neutral association (RR 0.89, 95% CI 0.79-1.00), whereas DPP-4 inhibitors (RR 1.05, 95% CI 0.97-1.13) and meglitinides (RR 1.13, 95% CI 0.93-1.36) showed no evidence of benefit. Similar findings were observed for severe exacerbations, with SGLT-2 inhibitors and GLP-1 receptor agonists demonstrating the strongest associations.ConclusionsSGLT-2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of COPD exacerbations than sulfonylureas, whereas metformin showed a near-neutral association and DPP-4 inhibitors and meglitinides showed no clear benefit.

Postoperative wound complications are an important cause of morbidity, and routinely available inflammatory markers may assist with early risk assessment. This study evaluated a newly proposed exploratory composite index, the Wound Inflammation-Nutrition Index (WINA), and its change between postoperative day 1 and postoperative day 3 (ΔWINA) in relation to postoperative wound complications.

This retrospective observational study included 86 patients who underwent general surgical procedures between January 2020 and December 2025. WINA was calculated by multiplying the C-reactive protein-to-albumin ratio by the neutrophil-to-lymphocyte ratio at postoperative days 1 and 3. ΔWINA was calculated as the POD3 value minus the POD1 value. Logistic regression, receiver operating characteristic analysis, model comparison, bootstrap internal validation, and sensitivity analyses were performed.

Postoperative wound complications occurred in 24 patients (27.9%). WINA values at POD1 and POD3 and ΔWINA were higher in patients with wound complications (all p < 0.001). In the parsimonious multivariable model, ΔWINA per 100-unit increase was associated with wound complications (adjusted OR: 2.12, 95% CI: 1.44-3.13, p = 0.001), together with diabetes mellitus (adjusted OR: 2.89, 95% CI: 1.01-8.29, p = 0.048) and operative time per 30-minute increase (adjusted OR: 1.67, 95% CI: 1.08-2.58, p = 0.021). ΔWINA had an AUC of 0.872 (95% CI: 0.789-0.941), with 83.3% sensitivity, 80.6% specificity, 62.5% positive predictive value, and 92.6% negative predictive value at a cut-off of 245.0. Its discrimination did not differ significantly from WINA at POD3. Adding ΔWINA to the clinical model increased the AUC from 0.772 to 0.903 (ΔAUC: 0.131, p = 0.003). The association remained after excluding complications diagnosed on or before POD3.

ΔWINA was associated with postoperative wound complications and improved the performance of a parsimonious clinical model. However, it did not outperform WINA measured at POD3, and the derived cut-off requires external validation before clinical use.

Tuberculosis remains a major cause of chronic respiratory morbidity in developing countries, including Indonesia. Persistent lung injury in tuberculosis is driven by chronic inflammation and cellular senescence, biological processes closely linked to telomere shortening. However, data on telomere length (TL) profiles and their association with clinical factors in tuberculosis patients remain limited. To characterize TL profiles and identify associated clinical factors among tuberculosis patients in Indonesia.

This cross-sectional study was conducted at Persahabatan National Respiratory Referral Hospital and Jakarta Islamic Hospital Cempaka Putih between October 2024 and March 2025. Adult patients with tuberculosis who met the inclusion criteria were enrolled. Relative telomere length (RTL) was measured from peripheral blood mononuclear cells using flow cytometry combined with fluorescence in situ hybridization.

A total of 64 tuberculosis patients were included, with a mean age of 41.36 ± 16.23 years, and the majority were male (68.7%). The mean RTL was 6.83 ± 1.36, with a median of 6.54. Shorter RTL was significantly associated with older age, higher body mass index (BMI), diabetes mellitus (DM), and the occurrence of drug-induced liver injury (DILI) ( P < 0.05). Among the evaluated clinical factors, age remained the strongest determinant of telomere shortening.

RTL was shorter with increasing age, higher BMI, DM, and the occurrence of DILI in tuberculosis patients. These findings highlight telomere alteration as a potential clinical health indicator that may assist in identifying risk profiles in diagnostic and treatment contexts.

Mortality among patients with drug-resistant tuberculosis (DR-TB) remains substantial despite advances in diagnosis and treatment. Individual studies have reported multiple prognostic factors for death, but findings remain heterogeneous. The objective of this study is to systematically review and quantitatively synthesize evidence on prognostic factors associated with mortality among patients with DR-TB using hazard ratios (HR) derived from survival analyses. A systematic search of PubMed, Scopus, and Web of Science was conducted to retrieve articles published from database inception to the final search date on March 31, 2026. Observational longitudinal studies involving patients with any form of DR-TB were included if they reported adjusted HR for all-cause mortality from survival models. Study selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline. Risk of bias was assessed using the Quality in Prognosis Studies tool. Fixed-effects and random-effects meta-analyses using restricted maximum likelihood were performed for prognostic factors reported in at least three comparable studies, whereas other factors were synthesized narratively. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) ID: CRD420261355163. A total of 34 studies published between 2006 and 2025 were included in the study. Most studies were retrospective cohort studies conducted mainly in Asia and Africa. The pooled analysis demonstrated that several factors were significantly associated with increased mortality including human immunodeficiency virus infection (pooled HR = 2.40; 95% confidence interval [CI] 1.73, 3.33), smoking (pooled HR = 2.07; 95% CI 1.48, 2.90), anemia (pooled HR = 1.79; 95% CI 1.51, 2.12), low body mass index or underweight (pooled HR = 2.08; 95% CI 1.69, 2.56), and diabetes mellitus (pooled HR = 1.77; 95% CI 1.29, 2.44). Gender was not significantly associated with mortality (pooled HR = 0.92; 95% CI 0.77, 1.11). Between-study heterogeneity ranged from low to substantial across the meta-analyses. Age, bacteriological positivity, previous TB treatment history, and drug resistance classification were synthesized narratively because of substantial heterogeneity in exposure definitions and comparator groups across studies. Mortality in DR-TB appears more consistently associated with clinical vulnerability and comorbidity rather than demographic characteristics or resistance profile alone. These findings support a risk-based approach to DR-TB care including early identification of high-risk patients, nutritional and comorbidity assessment and closer treatment monitoring.

to understand, in light of Social Representation Theory, the perceptions of people with Diabetes Mellitus after amputation regarding mental healthcare, exploring the meanings attributed to these practices in a high-complexity hospital.

a descriptive qualitative study conducted with ten participants undergoing outpatient follow-up after amputation. Data were collected through participant observation, semi-structured interviews, and field diary entries. Data analysis followed thematic content analysis.

three main thematic axes emerged: the invisible burden of diabetes; the ruptures and resignifications related to the disease; and the meanings attributed to mental healthcare.

the importance of the nursing team in mental healthcare is highlighted, being recognized as fundamental for the therapeutic relationship, health education, counseling and guidance, contributing to restoration of health from a holistic perspective.

Excess dietary sugar is a major contributor to metabolic disorders, including type 2 diabetes mellitus (T2DM). This study investigates the physiological, biochemical, behavioral, and molecular effects of high-sucrose diets in Drosophila melanogaster and evaluates the modulatory effects of metformin under these conditions.

Flies were reared on normal and high-sucrose diets (5% and 15%), with or without metformin treatment (5 mM and 15 mM). Pupation, survival, locomotor activity (negative geotaxis), trehalose levels, antioxidant enzyme activities (SOD, GST), and expression of stress-related genes (Mn-SOD, Cu/Zn-SOD, MTH, CAT, Hsp40, Hsp70) were assessed after 10 days of treatment. Gene expression levels were quantified relative to the normal control group using RpS20 as the housekeeping reference.

High-sucrose diets significantly reduced pupation and survival rates, impaired locomotor performance, increased trehalose levels, and decreased antioxidant enzyme activities. These diets were also associated with downregulation of stress- and antioxidant-related genes. Metformin treatment partially attenuated several of these alterations relative to the corresponding sucrose-treated groups, including improvements in pupation, survival, locomotor performance, metabolic parameters, antioxidant enzyme activity, and gene expression.

High-sucrose diets induced metabolic disturbances in Drosophila melanogaster, including impaired developmental progression and survival, functional locomotor impairment, carbohydrate imbalance, oxidative stress, and suppression of stress-related gene expression. Metformin partially attenuated several of these changes within the corresponding sucrose-treatment groups. These findings support the utility of Drosophila melanogaster as a tractable model for studying diet-induced metabolic dysfunction and evaluating pharmacological interventions.