Cognitive impairment, affecting people's ability to manage chronic diseases and perform daily tasks, is a growing global public health concern. No related research has been conducted in the Qassim region, Saudi Arabia.

This study aims to determine the prevalence of cognitive impairment and its associated factors among hemodialysis patients living in the Qassim region of Saudi Arabia.

A multicenter cross-sectional study was conducted among 210 hemodialysis patients in three dialysis centers in the region using an interview questionnaire and the patients' medical files. Data on sociodemographic, clinical, laboratory, and dialysis-related characteristics as well as the mini-mental state examination were obtained.

The participants' median age was 58 years, 56.2% were males, and the prevalence of cognitive impairment was 29.5%. The factors associated with cognitive impairment were female sex (adjusted odds ratio [AOR] =2.62; 95% confidence interval [CI]: 1.07-6.43; P = 0.035), inability to read and write (AOR = 12.44; 95% CI: 3.45-44.84; P < 0.001), diabetes (AOR = 3.29; 95% CI: 1.28-8.47; P = 0.013), and moderate anemia (AOR = 3.44; 95% CI: 1.00-11.82; P = 0.050).

Cognitive impairment is prevalent among hemodialysis patients. Early detection and management of cognitive impairment among hemodialysis patients are highly recommended, particularly for those with the four mentioned factors.

With one-third of the world's drug-resistant tuberculosis (DR-TB) cases, India is one of the nations with the highest number of patients. Limited treatment options, long duration of treatment, and associated toxicity adversely impact the physical and mental well-being of multidrug-resistant tuberculosis (MDR-TB) patients.

The study describes the challenges and psychosocial barriers faced by MDR-TB patients and their caregivers throughout the diagnosis and treatment process.

A mixed-method study was conducted among MDR-TB patients who are currently under treatment in Kancheepuram and Chengalpattu districts. A semistructured pretested questionnaire that had both quantitative and qualitative parts was used.

More than half of the patients (55.8%) had type II Diabetes Mellitus. The Patient Health Questionnaire-9 showed that 69.2% of the respondents had mild depressive symptoms. The challenges faced by the caregivers were: 19.2% felt an emotional rollercoaster, 32.8% had a financial burden, 25% had stress.

In light of the identified challenges among the patients and caregivers of MDR-TB such as emotional and financial strain, stigma along with smoking and alcohol abuse, it is essential to address the above issues through multifaceted and integrated approach.

Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has been shown to reduce cardiovascular (CV) and kidney events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We aimed to quantify the robustness of its CV benefits in phase 3 randomized controlled trials (RCTs) using fragility metrics coupled with conventional clinical effect measures.

We systematically searched MEDLINE and Scopus (from inception to June 2025) for phase 3 or 4 placebo-controlled RCTs of finerenone in T2DM and CKD reporting dichotomous CV outcomes. Three trials were included: FIDELIO-DKD, FIGARO-DKD, and the pooled FIDELITY analysis. We extracted hazard ratios (HRs), absolute risk reduction (ARR), relative risk reduction (RRR), number needed to treat (NNT), fragility index (FI), reverse fragility index (RFI), fragility quotient (FQ), and reverse fragility quotient (RFQ) for the primary composite CV outcome (CV death, non-fatal myocardial infarction [MI], non-fatal stroke, heart failure hospitalization [HFH]) and individual components. The primary composite outcome was significantly reduced in FIDELIO-DKD (HR 0.86, NNT 56; FI 4, FQ 0.0007) and FIDELITY (HR 0.86, NNT 59; FI 38, FQ 0.002), but not FIGARO-DKD (HR 0.87; RFI 7, RFQ 0.0009). Among individual outcomes, HFH showed the most consistent and robust benefit (FIDELITY HR 0.78, NNT 91; FI 23, FQ 0.001). Effects on CV death, MI, and stroke were numerically favorable but statistically non-significant, with low RFIs (mostly 1-3, and up to 9).

Finerenone significantly reduces HF hospitalization and modestly improves composite CV outcomes in T2DM with CKD, but effects on CV death, MI, and stroke are fragile. Combining fragility metrics with standard efficacy measures offers a clearer view of the reliability of trial results.

This meta-analysis aims to determine the prevalence of postoperative shoulder stiffness (PSS) after rotator cuff repair surgery and to explore its potential risk factors.

Search the PubMed, Embase, Web of Science, and Cochrane Library databases from their inception to July 1, 2025, for all studies reporting the prevalence of PSS after rotator cuff repair surgery and its associated risk factors. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies. Meta-analysis was performed using Stata 15.0 software.

Eight cohort studies involving 21,033 patients were included. The pooled prevalence of postoperative shoulder stiffness (PSS) after rotator cuff repair was 17% (95% CI: 9%-24%), with substantial heterogeneity (I² = 98.2%). Subgroup analysis by continent showed variation in reported prevalence estimates across regions, although these findings should be interpreted cautiously because some subgroups were based on a limited number of studies. Additional subgroup analyses according to sample size, publication year, and mean age were conducted to explore heterogeneity. In the sample size subgroup analysis, the pooled prevalence was 14% (95% CI: 2%-25%) in studies with a sample size ≥ 300 and 18% (95% CI: 15%-21%) in studies with a sample size < 300, with lower heterogeneity in the latter subgroup. By contrast, subgroup analyses by publication year and mean age did not materially reduce heterogeneity. In pooled analyses of adjusted effect estimates, age < 50 years (OR = 1.09, 95% CI: 1.03-1.15), female sex (OR = 1.66, 95% CI: 1.03-2.68), and diabetes mellitus (OR = 2.73, 95% CI: 1.75-4.26) were associated with PSS; however, the effect size for age < 50 years was small.

PSS after rotator cuff repair is not uncommon, but the pooled prevalence should be interpreted cautiously because of substantial heterogeneity and inconsistent diagnostic definitions across studies. Female sex and diabetes mellitus may be associated with PSS, whereas the clinical relevance of the association with age < 50 years appears limited. Further high-quality prospective studies are required.

Accurate risk prediction is essential for targeted prevention of type 2 diabetes mellitus (T2DM). However, the global applicability and methodological rigor of existing prediction models remain uncertain.

To systematically review and meta-analyze the geographic distribution, methodological quality, and predictive performance of all published T2DM risk prediction models.

PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang, and VIP were searched from inception to December 2025 (eAppendix S1 in the Supplement).

Studies that developed or validated a multivariable prediction model for incident T2DM in general adult populations and reported at least one performance measure.

Two reviewers independently extracted data and assessed risk of bias using the PROBAST tool. A random-effects meta-analysis was used to pool C-statistics. Heterogeneity was explored via subgroup analyses and meta-regression. The study followed TRIPOD-SRMA and PRISMA reporting guidelines.

The primary outcome was the geographic origin of models. Secondary outcomes included pooled measures of discrimination (C-statistic/AUC) stratified by region and an overall assessment of methodological quality (PROBAST).

A total of 65 studies comprising 97 distinct prediction models were included (eTable 1). Geographic distribution was highly skewed, with 70.1% of models developed in Asian populations (China: 47.4%; Japan: 13.4%; South Korea: 9.3%), while only 7.2% originated from the US and 4.1% from Europe. Logistic regression was used in 97.9% of models. External validation was performed for only 21 models (21.6%). According to PROBAST, 91.8% of models were at high risk of bias (eTable 2), primarily due to inadequate handling of missing data, lack of external validation, and poor calibration reporting. Meta-analysis revealed wide variation in discrimination by geographic region (eTable 7). US-based models achieved the highest pooled AUC (0.97; 95% CI, 0.94-0.99), but this finding is likely influenced by overfitting, small sample bias, and publication bias (see Discussion). European models showed a pooled AUC of 0.84 (0.81-0.87), while Chinese models showed the lowest performance (AUC, 0.79; 0.76-0.82). Due to very high heterogeneity (I² > 80% in most regions), these pooled estimates should be interpreted as descriptive summaries rather than precise estimates of true regional performance. Performance was lowest in prediabetic cohorts (AUC, 0.72; 0.68-0.76); however, this finding is preliminary due to the limited number of models and high heterogeneity. Funnel plot asymmetry suggested potential publication bias (Egger's test p=0.03); The most frequently included predictors were age (69.1%), body mass index (64.9%), family history of diabetes (44.3%), and waist circumference (39.2%) (eFigure 4 and eTable 3).

T2DM prediction models exhibit striking geographic inequity and poor methodological quality, with over 90% at high risk of bias. The substantial variation in performance by region and the lack of external validation critically limit their global clinical utility. These findings underscore an urgent need for rigorous external validation in diverse populations and de novo model development in under-represented regions, guided by PROBAST and TRIPOD standards.

Not applicable.

Not applicable.

Diffuse milky-white exudation (lipemic aqueous humor) in the anterior chamber is a rare ocular manifestation associated with metabolic disease-related microvascular dysfunction. Early-onset type 2 diabetes mellitus is characterized by severe metabolic disturbances (e.g., dyslipidemia) and early microvascular injury. We report a young female with poorly controlled hyperglycemia/hyperlipidemia presenting with pseudouveitis and marked milky-white anterior chamber exudation (lipemic aqueous humor), initially mimicking a corneal disorder.

A 33-year-old woman with 5-year type 2 diabetes (poor glycemic control), dyslipidemia, chronic sleep disturbances, and a high-fat/high-sugar diet developed acute left-eye pain, photophobia, and decreased vision during menstruation following travel-related fatigue. Slit-lamp examination showed massive homogeneous milky-white anterior chamber exudation (corneal porcelain-like appearance), and B-scan ultrasonography was unremarkable. Fasting blood tests revealed markedly elevated fasting glucose, triglycerides, and total cholesterol. She was diagnosed with pseudouveitis with anterior chamber lipid-protein exudation, and symptoms improved rapidly within 12 h of intensive topical/periocular corticosteroid therapy; intraocular inflammation largely resolved by day 6, with residual posterior synechiae.

Early-onset type 2 diabetes patients are prone to metabolic dysregulation under physiological/metabolic stress. Persistent hyperglycemia/hyperlipidemia may compromise microvascular integrity and increase permeability, potentially leading to lipid-protein leakage into the anterior chamber (lipemic aqueous humor)-a hypothetical association due to lack of aqueous humor biochemical analysis. This milky exudate is easily misdiagnosed as infectious keratitis, especially with normal B-scan findings. Meticulous slit-lamp examination, adjunctive AS-OCT/UBM, and systemic metabolic evaluation are crucial for accurate diagnosis. Clinicians should promptly assess serum glucose/lipid levels in young patients with milky anterior chamber opacities to avoid misdiagnosis and unnecessary interventions.

Pulmonary hypertension (PH) is highly prevalent and associated with increased mortality in patients undergoing maintenance hemodialysis (MHD). This study aimed to explore the disparities in the prevalence, risk factors, and prognostic impacts of PH between non-elderly and elderly MHD patients.

This study included 179 MHD patients with complete clinical records. All patients were evaluated using Doppler echocardiography, and PH was defined as a pulmonary artery systolic pressure > 35 mmHg.

The prevalence rates of PH were 24.8% in non-elderly patients and 33.8% in elderly patients. Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) was a predominant risk factor for PH in hemodialysis patients. A lower ratio of uric acid to high-density lipoprotein (UHR) was associated with PH among non-elderly patients, whereas diabetes mellitus served as a specific risk factor for elderly patients. The areas under the receiver operating characteristic curves of these risk factors identified in non-elderly and elderly patients were 0.86 (bootstrap 95% confidence interval (CI) 0.78-0.93) and 0.90 (bootstrap 95% CI 0.82-0.97), respectively. During a median follow-up duration of 32.90 (4.00-61.50) months, the presence of PH notably elevated the risk of all-cause mortality and cardiovascular hospitalization in both non-elderly and elderly patients. Meanwhile, it significantly augmented the risk of all-cause hospitalization (HR: 2.24, 95% CI 1.26-3.98, P = 0.006) in the non-elderly.

Distinct risk profiles for PH were identified between non-elderly and elderly MHD patients, offering valuable clinical data for the development of early detection and prevention strategies based on age stratification.

Patients with end-stage kidney disease (ESKD) have been largely excluded from randomized trials of sodium-glucose cotransporter-2 inhibitors (SGLT2is). Despite the lack of guideline recommendations, SGLT2i prescriptions occur in real-world clinical practice. We aimed to describe real-world associations between SGLT2i exposure and clinical outcomes among patients with type 2 diabetes mellitus (T2DM) coded with ESKD. We conducted a target trail emulation with retrospective, new-user, active-comparator cohort study using the TriNetX US Collaborative Network (2016-2023). Adults with T2DM and ESKD who initiated an SGLT2i or a dipeptidyl peptidase-4 inhibitor (DPP4i) were included. Propensity score matching (1:1) was used to balance baseline characteristics. The primary outcome was all-cause mortality; secondary outcomes included sepsis, pneumonia, major adverse cardiovascular events (MACE), all-cause hospitalization, and emergency department visits. Subgroup analyses were exploratory, and heterogeneity was assessed using Cochran's statistics. After matching, 5295 SGLT2i users were compared with 5295 DPP4i users. Over a follow-up of up to 4 years, SGLT2i exposure was associated with lower all-cause mortality (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.84-0.97), sepsis (HR 0.87, 95% CI 0.79-0.95), and all-cause hospitalization (HR 0.93, 95% CI 0.89-0.97). No significant associations were observed for MACE, pneumonia, or emergency department visits. Subgroup-specific estimates varied in magnitude, with no consistent evidence of heterogeneity. In this large real-world cohort of patients coded with ESKD, SGLT2i exposure was associated with favorable outcome patterns compared with DPP4i. Given the observational design, potential misclassification of kidney disease status, and off-label drug use, these findings should be interpreted as hypothesis-generating and do not establish causality.

Endoplasmic reticulum stress (ERS), caused by excessive buildup of misfolded proteins in the ER lumen, has emerged as a major contributor to diabetes mellitus (type-1 and type-2; T1DM and T2DM), leading to β-cell dysfunction, insulin resistance, and related comorbidities. In this review, we aim to characterize the signal transduction pathways in normal versus diseased conditions and their impact on the development of insulin-dependent and insulin-independent diabetes.

Evidence on ERS and diabetes were searched in MEDLINE and Google scholar databases using search strings that incorporated synonyms of ERS, diabetes, β-cell dysfunction and insulin resistance and their impact in disease progression. Our search was guided by the pertinent keywords as mentioned in the "keywords" section, that encompassed past twenty-five years of body of literature in this field as evident from Urano et al. 2000 till Sue et al. 2025.

Our results and conclusion are the distillation of past two and half decades of scientific research dedicated towards understanding the biology of ERS dependent diabetes. The ERS-induced Unfolded Protein Response (UPR), comprising of three signaling cascades, is pivotal in either protecting against or contributing to the pathophysiology of T1DM and T2DM. Clinically, ERS manifests as insulin resistance, heightened inflammation, and β-cell destruction. Consequently, ERS effectors and proteins involved in the UPR pathways have become attractive targets for pharmacological investigation. We also review some of the protein biomarkers of ERS dependent diabetes and relevant in vivo/ex vivo models used in clinical versus preclinical settings, as well as the latest state-of-the-art targeted molecular and cellular therapies that are currently being tried for the diabetic patients.

Diabetes mellitus-induced erectile dysfunction (DMED) is a highly prevalent complication among diabetic patients; however, its underlying pathogenic mechanisms remain incompletely understood. Metabolic disorder is a hallmark of diabetes, yet its precise contribution to DMED progression is not well defined. In this study, we demonstrate that metabolic disturbances, particularly elevated levels of palmitic acid (PA), induce ferroptosis in corpus cavernosum fibroblasts, thereby contributing to the development of erectile dysfunction. Mechanistically, we identified ZDHHC9, a palmitoyltransferase, to be aberrantly upregulated in DMED, where it catalyzes the S-palmitoylation of ACSL4 at cysteine 595. This post-translational modification enhances ACSL4 enzymatic activity, promotes lipid peroxidation, and drives ferroptosis in fibroblasts. Furthermore, we found that hyperactivation of the PI3K/AKT signaling pathway serves as a key upstream regulator of ZDHHC9 expression in this context. To explore the therapeutic potential of targeting this pathway, we developed siRNA against Zdhhc9 encapsulated in lipid nanoparticles (siZdhhc9-LNPs), which effectively suppressed Zdhhc9 expression in the corpus cavernosum and ameliorated erectile dysfunction in DMED mice. Collectively, our findings reveal a pathological cascade linking metabolic dysregulation to fibroblast ferroptosis via ZDHHC9-mediated ACSL4 palmitoylation, and establish ZDHHC9 as a promising therapeutic target for the treatment of DMED.