Background/Objectives: Type 2 diabetes mellitus (T2DM) is characterized by progressive β-cell dysfunction and insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may enhance β-cell function. Semaglutide, a long-acting GLP-1 RA, improves glycemic control and weight, but its direct effects on β-cell function remain uncertain. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251034071). PubMed, Embase, and Scopus were searched through April 2025 for randomized controlled trials evaluating semaglutide’s effects on β-cell function in adults with T2DM. Primary outcomes included HOMA-B, HOMA-IR, and the proinsulin/insulin ratio; secondary outcomes included insulin secretion rate, insulinogenic index, and C-peptide. Two reviewers independently performed data extraction and risk-of-bias assessment using the Cochrane RoB 1 tool. Random-effects models were used for pooling. Certainty of evidence was evaluated using GRADE. Results: Sixteen trials (n = 6591) met inclusion criteria, with nine included in the meta-analysis. Semaglutide improved β-cell function (HOMA-B log ratio of means 1.50, 95% confidence interval [CI]: 1.25–1.80) and reduced insulin resistance (HOMA-IR ratio 0.82, 95% CI: 0.73–0.94) compared with placebo or active comparators. The pooled treatment ratio for proinsulin/insulin was 0.70 (95% CI: 0.63–0.79). However, risk of bias was generally high due to open-label designs, and certainty of evidence for all primary outcomes was rated very low. Conclusions: Semaglutide appears to improve β-cell function and insulin sensitivity in adults with T2DM, but conclusions remain uncertain given the very low certainty of evidence and substantial heterogeneity. High-quality trials with standardized β-cell outcomes are needed to confirm these findings.

Introduction: Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent among the elderly, particularly women, and is characterized by complex pathophysiology driven by comorbidities such as hypertension, diabetes, and renal dysfunction. These overlapping mechanisms make diagnosis and prognosis challenging, highlighting the importance of circulating biomarkers that reflect key biological processes such as myocardial stretch, fibrosis, inflammation, and injury. Objective: This mini-review explores the diagnostic and prognostic roles of major cardiac biomarkers BNP/NT-proBNP, high-sensitivity troponins, soluble suppression of tumorigenicity 2 (sST2), and Galectin-3 in elderly patients with HFpEF. Results: BNP and NT-proBNP remain the cornerstone biomarkers for diagnosing HFpEF, reflecting ventricular wall stress and providing strong prognostic value, although their interpretation in older adults can be influenced by renal function, age, and comorbidities. High-sensitivity troponins indicate chronic myocardial injury and have emerged as reliable predictors of mortality and recurrent hospitalizations. sST2 reflects inflammatory and fibrotic remodeling; while limited diagnostically, it shows consistent association with adverse outcomes. Galectin-3 captures ongoing myocardial fibrosis and structural remodeling, offering particularly strong prognostic information in HFpEF compared to HFrEF. Conclusion: Collectively, these biomarkers represent complementary windows into the pathophysiology of HFpEF. A multimarker strategy that integrates markers of wall stress, injury, inflammation, and fibrosis may enhance diagnostic precision and risk stratification in elderly patients, guiding more personalized approaches to management.

Background: Thyroid nodules are common, yet only a small proportion are malignant. The independent role of nodule size in malignancy risk remains debated, particularly after adjustment for clinical, biochemical, and sonographic features. Methods: A retrospective cohort study was conducted on adult patients with thyroid nodules evaluated between 2018 and 2025 at a tertiary care center. Clinical, laboratory, ultrasound, cytology, and histopathology data were extracted. Thyroid-stimulating hormone (TSH), free thyroxine (free T4), and sonographic characteristics were analyzed. Univariable and multivariable logistic regression were performed. Missing ultrasound data were addressed using multiple imputation (m = 20), with pooled estimates derived using Rubin’s rules. The final multivariable model included 446 patients. Results: A total of 446 patients were included, of whom 91 (20.4%) had thyroid malignancy. Malignant nodules were significantly larger than benign nodules (2.30 [1.80] cm vs. 1.80 [1.13] cm; p = 0.015). In univariable analysis, TSH, free T4, and multiple ultrasound features were associated with malignancy. In multivariable analysis, nodule size remained the strongest independent predictor of malignancy (adjusted odds ratio [aOR] 1.51; p < 0.001). Hypoechogenicity (aOR 2.07; p = 0.020) and microcalcifications (aOR 1.86; p = 0.047) also remained independently significant, whereas thyroid function parameters were not associated with malignancy after adjustment. Conclusions: Thyroid nodule size is the strongest independent predictor of malignancy, with select ultrasound features retaining additional predictive value. These findings support incorporating nodule size more prominently into thyroid cancer risk stratification while maintaining key sonographic features.

Background:Polycystic Ovary Syndrome (PCOS) is commonly managed with metformin, a drug known to influence vitamin B12 and homocysteine levels. While these biochemical alterations are well-documented in diabetic populations, limited data exists on their relevance in PCOS patients. Objective:This systematic review and meta-analysis aimed to evaluate the impact of metformin on vitamin B12 and homocysteine levels in women diagnosed with PCOS. Methods:We systematically searched PubMed and other major databases for studies published between 2015 and 2025. Eligible studies included randomized controlled trials and observational studies comparing pre- and post-metformin levels of vitamin B12 and homocysteine in PCOS patients. Independent reviewers screened articles, extracted data, and assessed study quality. A random-effects meta-analysis was conducted to generate pooled effect estimates. Results:The analysis revealed no consistent effect of metformin on homocysteine levels, with moderate heterogeneity across studies (I² = 36%). Variations in study design, treatment duration, metformin dosage, and measurement techniques contributed to this heterogeneity. The impact on vitamin B12 levels was variably reported and could not be conclusively synthesized due to data limitations. Conclusion:Metformin’s effect on homocysteine levels in PCOS appears inconsistent and influenced by multiple factors. Further high-quality, standardized studies are needed to clarify its role in altering vitamin B12 and homocysteine profiles in this population.

BACKGROUND Avascular necrosis (AVN) is a disabling musculoskeletal complication of sickle cell disease (SCD), resulting from recurrent vaso-occlusive episodes and chronic microvascular ischemia. Although weight-bearing joints such as the femoral head are most commonly affected, humeral head involvement can lead to significant pain and functional limitation. Management of AVN in SCD remains challenging, and interest has grown in adjunctive therapies such as hyperbaric oxygen therapy (HBOT), which can enhance tissue oxygenation, promote angiogenesis, and support bone remodeling. Evidence regarding its role in non-weight-bearing joints remains limited. CASE REPORT A 32-year-old woman with homozygous SCD (HbSS) presented with a 2-month history of progressive bilateral shoulder pain and restricted motion. Magnetic resonance imaging (MRI) demonstrated stage II pre-collapse AVN of both humeral heads. Baseline laboratory evaluation showed stable chronic anemia consistent with SCD, without evidence of acute infection or inflammatory elevation. Following perioperative exchange transfusion to reduce hemoglobin S concentration, she underwent arthroscopic-assisted core decompression with ipsilateral fibular strut autografting of both shoulders in staged procedures. Postoperatively, she completed 40 sessions of HBOT at 2.5 atmospheres absolute for 60 min each, in addition to oral alendronate 70 mg weekly for 6 months. During clinical follow-up, she reported complete resolution of pain and restoration of full, pain-free range of motion bilaterally. Post-treatment MRI demonstrated preserved articular architecture with improvement in marrow signal. CONCLUSIONS This case report shows that a multimodal joint-preserving approach combining surgical decompression and adjunctive HBOT can be associated with meaningful clinical improvement in early-stage humeral head AVN secondary to SCD. However, as multiple concurrent interventions were employed, the independent contribution of HBOT cannot be determined. Larger studies are required to clarify its adjunctive role.