Tag: pubmed

World J Diabetes. 2025 Dec 15;16(12):112789. doi: 10.4239/wjd.v16.i12.112789.

ABSTRACT

BACKGROUND: Epigenetic regulation of leptin (LEP) plays a critical role in metabolic disorders, yet its promoter methylation patterns in lean diabetic populations remain poorly characterized. Emerging evidence suggests DNA methylation may precede clinical hyperglycemia, offering potential for early risk stratification. While obesity-associated LEP methylation is well-studied, lean Asian populations who exhibit high diabetes prevalence despite lower adiposity, represent an underexplored cohort. This study hypothesizes that LEP promoter methylation in peripheral leukocytes decreases progressively from normoglycemia to prediabetes and type 2 diabetes mellitus (T2DM), correlating inversely with serum LEP levels in lean Chinese adults [body mass index (BMI) < 24 kg/m²].

AIM: To investigate LEP promoter methylation status and its association with serum LEP levels across glycemic states in lean Chinese adults.

METHODS: We enrolled 392 participants including 120 normoglycemic controls, 94 prediabetes [44 impaired fasting glucose (IFG)/50 impaired glucose tolerance (IGT)], 178 T2DM aged 40-60 years with BMI < 24 kg/m². Genomic DNA from peripheral leukocytes underwent bisulfite conversion followed by methylation-specific PCR to assess CpG methylation in the LEP promoter. Serum LEP was quantified via enzyme-linked immunosorbent assay, with other parameters measured through standard assays. Statistical analyses included analysis of variance, χ² tests, and Pearson correlation (Bonferroni-corrected P value).

RESULTS: Methylation frequencies declined progressively: 59.2% (controls) reduced to 43.6% (prediabetes; IFG: 38.6%, IGT: 48%) reduced to 31.5% (T2DM) (all P < 0.05 vs controls; T2DM vs IGT: P = 0.030). Serum LEP levels increased significantly in T2DM (16.94 ± 4.19 μg/L) vs controls (11.33 ± 3.10 μg/L; P = 0.002), with intermediate values in prediabetes (IFG: 13.79 ± 3.32 μg/L; IGT: 12.62 ± 4.81 μg/L). A near-perfect inverse correlation between methylation and LEP levels was observed (r = -0.95, 95%CI: -0.97 to -0.92, P < 0.001), persisting after adjusting for age and BMI (β = -0.91, P < 0.001).

CONCLUSION: LEP promoter hypomethylation parallels worsening glycemic status in lean Chinese adults, suggesting its potential as a blood-based epigenetic biomarker for diabetes progression, pending validation in longitudinal cohorts.

PMID:41480608 | PMC:PMC12754086 | DOI:10.4239/wjd.v16.i12.112789

World J Diabetes. 2025 Dec 15;16(12):112830. doi: 10.4239/wjd.v16.i12.112830.

ABSTRACT

BACKGROUND: Cotadutide (MEDI0382) is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors. Several randomized controlled trials (RCTs) have been published evaluating the use of cotadutide in individuals with type 2 diabetes (T2D), showing promising results. However, the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.

AIM: To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.

METHODS: The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews (CRD42024511703), and the protocol summary can be accessed online. Several databases and registries, including MEDLINE (via PubMed), Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, were systematically searched using related terms from their inception to May 15, 2025, for RCTs involving individuals with T2D receiving cotadutide in the intervention group. Review Manager web was used to conduct meta-analysis using random-effects models. The co-primary outcomes of interest were the changes in glycated hemoglobin (HbA1c) and the percent changes in body weight from baseline. The results of the outcomes were expressed as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). The analysis of outcomes was stratified according to whether the control group received a placebo, denoted as the placebo control group (PCG), or an active comparator, referred to as the active control group (ACG).

RESULTS: Nine RCTs (mostly phase 2 RCTs, n = 1525) with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed; five studies had a low overall risk of bias, while the other four had some concerns. Compared to the PCG, greater reductions in HbA1c were achieved with cotadutide 100 μg (MD -0.77%, 95%CI: -1.06 to -0.47), 200 μg (MD -0.68%, 95%CI: -1.12 to -0.23), 300 μg (MD -0.67%, 95%CI: -0.79 to -0.56), and 600 μg (MD -0.69%, 95%CI: -0.97 to -0.41). Cotadutide 100 μg (MD -1.74%, 95%CI: -3.23 to -0.25), 200 μg (MD -2.56%, 95%CI: -3.37 to -1.75), 300 μg (MD -3.49%, 95%CI: -4.14 to -2.84), and 600 μg (MD -5.45%, 95%CI: -7.17 to -3.73) achieved greater percent reductions in body weight from baseline. However, the certainty of evidence for HbA1c and percent body weight reductions was very low to low. Cotadutide, at all doses, also outperformed PCG in reducing fasting plasma glucose and absolute body weight. The changes in HbA1c, percent body weight, fasting plasma glucose, and absolute body weight were similar between the cotadutide group and the ACG. Compared to PCG, pooled doses of cotadutide increased the risks of treatment-emergent adverse events (AEs), treatment-related AEs, and discontinuation of the study drug due to AEs, but not for serious AEs. More subjects experienced overall gastrointestinal AEs, dyspepsia, nausea, vomiting, constipation, and decreased appetite with cotadutide than with PCG. Compared to the ACG, none of the AEs showed increased risk in the cotadutide group.

CONCLUSION: Cotadutide demonstrated glycemic control and weight-loss benefits in short-term, small RCTs (mostly phase 2). However, small sample sizes, very low to low certainty of evidence, and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties, warranting cautious interpretation and further investigation in larger, longer-term trials to establish its safety and efficacy profile.

PMID:41480597 | PMC:PMC12754120 | DOI:10.4239/wjd.v16.i12.112830

NAR Genom Bioinform. 2025 Dec 31;7(4):lqaf205. doi: 10.1093/nargab/lqaf205. eCollection 2025 Dec.

ABSTRACT

Accurate identification of affected tissues of human diseases is important for the derivation of disease etiology and the development of new treatment strategies. In this study, we develop a logistic regression-based method named DEDUCE (disease tissue detection using logistic regression) that combines genomics big data and machine learning to address this important problem. The central hypothesis is that most disease-associated genes are expressed specifically in affected tissues. DEDUCE takes advantage of newly emerged data on disease-related genes as well as tissue-specific gene expression data. The unique feature of DEDUCE is that it takes into account the strength of gene-disease associations. When we applied DEDUCE to a total of 3261, 324 gene-disease associations collected from DisGeNET covering 30,170 diseases and 21,666 genes, we identified 216 significant tissue-disease pairs composed of 120 unique diseases and 37 unique tissues. Many of them shed light on potential explanations for disease pathogenesis. The results showed great consistency with previous findings and were proven effective by empirical plots and gene set enrichment analysis. Overall, DEDUCE has shown great potential in uncovering novel pathogenesis mechanisms of complex diseases. In-depth analysis and experimental validation were required to fully understand these discovered tissue-trait associations and their enriched genes.

PMID:41480592 | PMC:PMC12754781 | DOI:10.1093/nargab/lqaf205

IDCases. 2025 Dec 7;43:e02453. doi: 10.1016/j.idcr.2025.e02453. eCollection 2026.

ABSTRACT

BACKGROUND: In regions where hepatitis A virus (HAV) is endemic, the COVID-19 pandemic has introduced new challenges. While liver involvement in SARS-CoV-2 is well documented, the impact of HAV-COVID-19 coinfection remains unclear.

OBJECTIVE: Evaluate whether COVID-19 coinfection worsens clinical outcomes or liver injury in patients with HAV infection.

METHODS: We conducted a retrospective observational study at a tertiary care hospital in Lebanon, including 15 patients with confirmed HAV infection: 7 individuals were infected with COVID-19 (HAV-COVID coinfection group) and 8 with HAV alone (HAV-only group). Clinical characteristics, liver function tests, inflammatory markers, and recovery trends were assessed at admission (Day 1) and follow-up (Day 10) and remote follow-up extended up to 30 days. Group comparisons were made using Mann-Whitney U tests with effect sizes reported as rank-biserial correlations.

RESULTS: All patients experienced a mild disease course without hepatic complications or ICU admissions. CRP levels were significantly higher in the HAV-COVID group at both time points (Day 1 p = 0.04; Day 10 p < 0.001), but no statistically significant differences were seen in liver enzymes or recovery rates between the groups.

CONCLUSION: HAV-COVID-19 coinfection in otherwise healthy individuals does not appear to worsen liver injury or delay recovery compared to HAV alone. However, given isolated reports of fulminant hepatitis, clinicians should continue to screen for coinfection in patients presenting with liver injury during with COVID-19, especially in HAV-endemic regions. Larger studies are needed to confirm these findings and explore potential risk modifiers.

PMID:41480581 | PMC:PMC12754211 | DOI:10.1016/j.idcr.2025.e02453

J Hand Microsurg. 2025 Dec 5;18(1):100392. doi: 10.1016/j.jham.2025.100392. eCollection 2026 Jan.

ABSTRACT

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity. In addition to traditional open carpal tunnel release (OCTR), endoscopic (ECTR) and mini-open (MOCTR) approaches have been developed as minimally invasive alternatives. However, comparative evidence regarding their clinical efficacy and safety remains inconsistent.

METHODS: A systematic review and meta-analysis were performed according to PRISMA guidelines, including 44 comparative studies (38 comparing ECTR vs OCTR and 6 comparing ECTR vs MOCTR) involving adult patients with idiopathic CTS. Outcomes extracted included pain (VAS), functional scores (BCTQ-SSS, BCTQ-FSS, DASH), grip and pinch strength, sensory symptoms, and complications such as pillar pain, nerve injury, opioid use, and revision CTR.

RESULTS: Across all functional measures (DASH, BCTQ-FSS, BCTQ-SSS), pain, and sensory outcomes, pooled analyses demonstrated no statistically significant differences between ECTR, OCTR, and MOCTR. Grip and pinch strength were also comparable, indicating equivalent long-term motor recovery. Postoperative VAS pain scores did not differ significantly between ECTR and OCTR (p = 0.10). Nerve injury also showed no significant difference between techniques in the random-effects model (p = 0.56). Opioid prescription rates were similar across groups. Notably, ECTR demonstrated a significantly lower revision CTR rate compared with OCTR (risk ratio = 0.46, 95 % CI 0.29-0.73; p = 0.0009).

CONCLUSION: Open, mini-open, and endoscopic carpal tunnel release techniques provide comparable outcomes in pain relief, functional recovery, strength, sensory symptoms, and overall safety for idiopathic CTS. Although revision CTR occurred less frequently after ECTR in the pooled analysis, the clinical significance of this difference remains uncertain. Technique selection should therefore be individualized based on surgeon expertise, patient priorities, and resource availability.

PMID:41480575 | PMC:PMC12754214 | DOI:10.1016/j.jham.2025.100392

HRB Open Res. 2025 Nov 10;8:74. doi: 10.12688/hrbopenres.14154.2. eCollection 2025.

ABSTRACT

BACKGROUND: Evidence synthesis plays a vital role in healthcare research, informing clinical practice and policy. Increasingly, students are involved in reviews, yet their experiences, including the challenges and facilitators for participation, remain underexplored. This study aims to examine the barriers and opportunities encountered by novice student team members in evidence synthesis.

METHODS: This study is embedded within the Study Within A Review (SWAR) framework and will use a mixed-methods approach. Students in health-related disciplines engaged in or having just completed their first evidence synthesis will be recruited through academic networks and word of mouth. Data will be collected primarily via focus groups, in addition to a short, embedded survey. Thematic analysis will be employed to analyse qualitative data, while descriptive statistics will be used for survey responses.

RESULTS: The study aims to describe experiences of students involved in evidence synthesis, identifying barriers and facilitators related to their participation. Findings will inform recommendations for improving evidence synthesis training, mentorship, and student engagement strategies.

CONCLUSION: Understanding student experiences in evidence synthesis may inform the development of targeted training and support mechanisms. The findings will provide valuable insights for academic institutions and research teams seeking to optimise student involvement in evidence synthesis.

PMID:41480571 | PMC:PMC12754357 | DOI:10.12688/hrbopenres.14154.2

Sleep Sci. 2025 Dec 31;18(4):e436-e443. doi: 10.1055/s-0045-1811199. eCollection 2025 Dec.

ABSTRACT

INTRODUCTION: Patients with nasal obstruction due to chronic rhinosinusitis with nasal polyposis may present with altered sleep quality. Data on this subject in the literature remains scarce.

OBJECTIVES: To evaluate changes in sleep quality and polysomnographic parameters among patients who underwent functional endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis.

MATERIALS AND METHODS: A systematic review was performed in three databases: PubMed, Cochrane, and Embase. The following keywords were used: chronic rhinosinusitis, nasal polyposis, sleep quality, and nasosinusal endoscopic surgery. Studies evaluating adults with nasal polyposis who underwent endoscopic nasosinusal surgery were selected. A meta-analysis was conducted to compare mean scores for polysomnographic and subjective variables from before to after the operation.

RESULTS: A systematic review and meta-analysis of three studies were performed, only one of which was randomized. The total sample consisted of 64 patients. There was a decrease in the mean AHI score and improvements in mean and minimum saturation. The mean difference in percentage of stage N3 from before to after the operation was 1.12 with a 95% CI from -3.51 to 5.75, which was non-significant. There was a mean percentage increase in REM sleep duration and a decrease in PSQI scores, which were both statistically significant ( p < 0.05).

CONCLUSION: There were improvements in the quality of sleep and duration of REM sleep after surgery, with no improvement in polysomnographic respiratory parameters.

PMID:41480569 | PMC:PMC12755935 | DOI:10.1055/s-0045-1811199

Sleep Sci. 2025 Dec 31;18(4):e404-e409. doi: 10.1055/s-0045-1813729. eCollection 2025 Dec.

ABSTRACT

INTRODUCTION: Despite significant advancements in sleep medicine, its integration into formal medical education remains uneven. While structured programs exist in some regions, a standardized framework for postgraduate education is notably lacking in Latin America. This study assesses the availability of sleep medicine training programs, how specialists gain expertise, and the current clinical practice across the region.

METHODS: A descriptive, cross-sectional survey was conducted among Latin American sleep medicine specialists via a WhatsApp group of 443 professionals. The questionnaire covered formal education programs, training locations, and public and private healthcare coverage for sleep disorder treatments. Descriptive statistical analysis was performed.

RESULTS: Seventy-four physicians from 11 Latin American countries participated. Only four countries-Mexico, Brazil, Argentina, and Chile-had formal postgraduate programs, leading many specialists to seek training abroad. Mexico was the most cited destination for further education. Public healthcare coverage varied: five countries provided sleep surgeries, while others did not, and CPAP device access was inconsistent. Private insurance generally did not cover sleep disorder treatments, including DISE, which was only covered in Argentina and Colombia with mixed responses.

DISCUSSION: Significant disparities exist in sleep medicine education and healthcare access in Latin America. The lack of structured training limits local expertise development and increases reliance on international education. Raising awareness is a crucial step toward improving education and ensuring broader access to standardized sleep disorder care. Continued research is necessary to bridge existing gaps and enhance opportunities for specialized sleep medicine care.

PMID:41480558 | PMC:PMC12755934 | DOI:10.1055/s-0045-1813729

Front Med (Lausanne). 2025 Dec 17;12:1658982. doi: 10.3389/fmed.2025.1658982. eCollection 2025.

ABSTRACT

BACKGROUND: Fractures of the limbs are a common health problem among school-aged children and can cause severe pain as well as emotional issues. Traditional care may not fully meet the comprehensive needs of these children. Therefore, exploring more comprehensive intervention measures is of significant clinical importance.

OBJECTIVE: This research aimed to evaluate the clinical effect of Child Life intervention combined with a comprehensive nutrition intervention on pain management, nutritional status, and treatment compliance of school-age children with limb fractures.

METHODS: A total of 100 school-age children with limb fractures treated in our hospital from March 2024 to September 2024 were selected and randomly divided into a control group (CG) and an observation group (OG) using the random number table method, with 50 cases in each group. The CG received conventional nursing intervention, while the OG received Child Life intervention and comprehensive nutrition intervention on the basis of the CG. The pain scores, serum cortisol levels, treatment compliance, and nutritional status in both groups before and after surgery were compared.

RESULTS: At 12 h and 24 h after surgery, the FLACC scores in the OG were lower than those in the CG (p < 0.001, t = 5.042; p < 0.001, t = 4.836). At 12 h and 24 h after surgery, serum cortisol level in the OG exhibited depletion relative to that in the CG (p < 0.001, t = 6.049; p < 0.001, t = 11.662). After intervention, treatment compliance in the OG was higher than that in the CG, indicating statistical significance (p = 0.037, χ2 = 4.332; p = 0.017, χ2 = 5.741; p = 0.025, χ2 = 5.005). At 24 h after surgery, Lc, HGB, PA, and ALB levels in the OG were higher than those in the CG, indicating statistical significance (p < 0.01, t = 2.717; p < 0.001, t = 3.433; p < 0.001, t = 5.023; p < 0.001, t = 4.230).

CONCLUSION: A combination of Child Life intervention and comprehensive nutrition intervention can enhance the pain management effect in school-age children with limb fractures, attenuate their pain level, ameliorate their perioperative stress status, and improve their postoperative nutritional status, accelerating their recovery.

PMID:41480550 | PMC:PMC12753990 | DOI:10.3389/fmed.2025.1658982

Front Med (Lausanne). 2025 Dec 17;12:1658735. doi: 10.3389/fmed.2025.1658735. eCollection 2025.

ABSTRACT

OBJECTIVE: We aimed to characterize the prevalence and co-occurrence of social determinants of health among pregnant individuals during prenatal care in a single rural-based health system in the United States.

CONTEXT AND CASE: This community case study describes the implementation and findings of universal screening for social determinants of health among all individuals initiating prenatal care at four OB-GYN clinics in a single health system between January 2022 and December 2023. Antenatal sites spanned both small urban and rural settings, with a subset of deliveries occurring at a rural, tertiary care medical center. Social determinants, including financial stress, food insecurity, housing instability, transportation issues, social isolation, and health literacy, were assessed using a screening tool embedded in the electronic health record (EHR). We used descriptive statistics and UpSet Plots to describe these determinants and their co-occurrence patterns in relation to patient characteristics.

FINDINGS: Among 2,222 pregnant individuals who completed screening, 16.7% reported at least one social determinant, and 7.8% reported two or more. Among patients who screened positive for only one determinant, the most common concern was social isolation (38.9%), followed by financial stress (27.8%). Among those with two or more determinants, the most common items were financial stress (75.1%), food insecurity (67.6%), and housing instability (56.1%). Combinations of food insecurity, housing instability, and financial stress affected nearly one in 10 patients.

CONCLUSION: Social isolation emerged as a significant concern for non-urban pregnant women who had no other reported social determinants. However, determinants also co-occurred, particularly housing and food insecurity with financial stress. This descriptive analysis provides foundational data for future research examining associations between intersecting social determinants and maternal-infant health outcomes. Universal screening is critically important for identifying patients with high social risk.

PMID:41480546 | PMC:PMC12753359 | DOI:10.3389/fmed.2025.1658735