BACKGROUND Heart failure with preserved ejection fraction (HFpEF) is a growing global health burden with historically limited disease-modifying therapies. Patient-reported outcomes (PROs) and health-related quality of life (QoL) are central therapeutic targets, particularly in obesity-related HFpEF where symptom burden is substantial. Semaglutide, a once-weekly GLP-1 receptor agonist, has demonstrated weight loss and cardiometabolic benefits, prompting dedicated clinical trials using the Kansas City Cardiomyopathy Questionnaire (KCCQ) as the primary PRO instrument. However, a rigorous methodological appraisal comparing how PROs are measured, pooled, and interpreted across semaglutide studies in HFpEF has not been published. AIM To systematically review and quantitatively pool the evidence on PRO measurement and health-related QoL assessment in adults with HFpEF receiving semaglutide, and to critically appraise the methodological comparability of PRO instruments across included study designs, with specific attention to instrument psychometrics, missing data handling, minimal clinically important difference (MCID) rationale, and data collection standards. METHODS Following PRISMA 2020 guidelines, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception through January 2026. Eligible studies included randomised controlled trials (RCTs) and prospective cohort studies enrolling adults with HFpEF receiving semaglutide that reported validated QoL or PRO instruments. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool for RCTs and the ROBINS-I framework for the cohort study. A fixed-effects meta-analysis using inverse-variance weighting was performed for the two design-homogeneous RCTs (identical dose, endpoint, and follow-up). A qualitative synthesis additionally appraised the methodological comparability of PRO measurement across all included studies. RESULTS Three studies met inclusion criteria: Two double-blind, placebo-controlled, multicentre RCTs [semaglutide treatment effect in people with obesity and HFpEF (STEP-HFpEF), n = 529; STEP-HFpEF and diabetes mellitus, n = 616] and one prospective propensity score-matched cohort study (n = 406 after matching). Fixed-effects meta-analysis of the two RCTs yielded a pooled KCCQ-Clinical Summary Score (CSS) treatment effect of 7.36 points (95%CI: 5.32-9.40; P < 0.001; I ² = 0%), exceeding the 5-point MCID. The open-label observational cohort reported a 21-point absolute KCCQ-Total Symptom Score improvement, substantially larger than the RCT estimates-most plausibly attributable to expectation bias, residual confounding, subscale non-equivalence, and dose heterogeneity. Methodological evaluation revealed important gaps in KCCQ psychometric reporting, missing data handling, MCID justification, and standardisation of PRO data collection procedures. Generalisability is constrained by exclusive enrolment of obesity-related HFpEF phenotypes, predominantly White Western populations, and industry-sponsored trial designs. CONCLUSION Semaglutide produces consistent, clinically meaningful PRO improvements in obesity-related HFpEF. The pooled RCT effect of 7.36 KCCQ-CSS points constitutes the most methodologically reliable estimate of pharmacologic benefit. Significant methodological gaps remain across PRO instrument standardisation, psychometric reporting, population diversity, and prospective trial registration, which future HFpEF trials must address.
BACKGROUND Clubfoot is one of the most common musculoskeletal birth defects, compounded by the historical approach to managing idiopathic clubfeet in Pakistan with extensive surgical interventions till mid twenties. To keep pace with the global evidence-based shift from extensive surgical release to a Ponseti conservative management, the native orthopedic community manned a national initiative, “Pakistan Clubfoot Disability Prevention Program”. This review evaluates native literature published during the last 35 years, its effectiveness and outcomes, its comparison with global standards, and hypothesizes that Ponseti adoption reduced referral age and enhanced short-term success rates. Encouraging findings guide scaling clubfoot prevention and neonatal screening nationwide. AIM To evaluate the paradigm shift in clubfoot management strategies in Pakistan over 35 years and assess the Ponseti method outcomes. METHODS This meta-analysis includes studies conducted in Pakistan related to clubfoot management, published globally, between 1990 and June 2025. The study was carried out at Ziauddin University Hospital, Clifton, Karachi, after PROSPERO registration and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines 2020. The electronic databases search was made through multiple search engines and a manual search of the reference list from included studies and institutional repositories. The publications’ eligibility criteria included: Peer-reviewed studies carried at Pakistan, related to clubfoot management strategies and outcomes. RESULTS Of the 125 included studies, major surgical procedures were 26 (20.8%), conservative 76 (60.8%), and non-clinical procedures were 23 (18.4%). A clear shift occurred from surgical dominance in the pre-2005 era [87.5%; 95% confidence interval (CI): 61.2-96.8] to Ponseti-led conservative approaches in the post-2005 era (94.7% of conservative studies by 2025). Mean referral age declined from 52.3 months pre-2005 era to 6.3 months by 2024-2025. Publication activity peaked in 2020-2024 (58 studies; 70.7% conservative). Bracing non-compliance observed as 35%-69.5%. Pooled proportions were: Surgical 20.8% (95%CI: 14.9-28.2; I 2 = 93.7%); conservative 60.8% (95%CI: 52.2-68.7; I 2 = 95.2%), of which Ponseti comprised 94.7%. Ponseti success 87.2% (95%CI: 84.8-89.6; I 2 = 88%); vs Kite 69.1% (95%CI: 62.3-75.9; I 2 = 85%), risk ratio of 1.26 (95%CI: 1.18-1.35, P < 0.001), relapsed rate was18.4% (95%CI: 14.2-23.6), and percutaneous tenotomy rate 81.2%. High heterogeneity (I 2 > 90%) precluded reliable pooling; results are presented narratively. CONCLUSION Clubfoot management in Pakistan revealed a significant paradigm shift to Ponseti-dominant treatment, aligning with global standards and yielding high success, a progressive and significant decline in referral age and breaking the barriers.
BACKGROUND Obesity-related heart failure with preserved ejection fraction (HFpEF) is highly prevalent, symptomatically disabling, and lacks clearly disease-modifying pharmacotherapy. Glucagon-like peptide (GLP)-1-based incretin agonists-including GLP-1 receptor agonists (GLP-1 RAs; e.g. , semaglutide) and the dual GIP/GLP-1 RA tirzepatide-induce substantial weight loss and favorable cardiometabolic effects and have recently been evaluated in obese HFpEF populations. AIM To systematically evaluate the efficacy and safety of GLP-1–based incretin agonists (including GLP-1 RAs and the dual GIP/GLP-1 RA tirzepatide) in patients with obesity-related HFpEF and to quantify their effects through meta-analysis. METHODS PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, and Web of Science were searched from inception to October 2025 for randomized controlled trials (RCT) evaluating GLP-1–based incretin agonist therapy in adults with HFpEF and obesity. Outcomes included health status [Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS)], body weight, exercise capacity, heart failure events, and safety. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were performed for KCCQ-CSS and percentage body weight change. RESULTS Three RCTs (n = 1876) were included in quantitative synthesis: STEP-HFpEF (n = 529), STEP-HFpEF DM (n = 616), and SUMMIT (n = 731). GLP-1-based incretin agonist therapy significantly improved health status, with a pooled increase in KCCQ-CSS of +7.33 points [95% confidence interval (CI): 5.84 to 8.82; I ² = 0%]. Substantial weight loss was observed, with a pooled reduction of -9.56 percentage points (95%CI: -12.15 to -6.97; I ² = 58%). Tirzepatide significantly reduced the composite of cardiovascular (CV) death or worsening heart failure event (hazard ratio 0.62, 95%CI: 0.41-0.95; P = 0.026), while semaglutide trials demonstrated consistent favorable trends. Across trials, GLP-1-based therapies improved exercise capacity and were associated with fewer serious adverse events, with gastrointestinal symptoms being the most common side effect. CONCLUSION GLP-1-based incretin agonists produce clinically meaningful improvements in symptoms, functional capacity, and body weight in patients with obesity-related HFpEF, with consistent benefit across trials and acceptable safety. Meta-analysis confirms robust improvement in health status and substantial weight reduction, supporting this therapeutic class as a promising disease-modifying strategy for this high-risk HFpEF phenotype. Tirzepatide additionally reduced hard CV outcomes, providing proof of concept that targeting obesity can favorably alter HFpEF disease course.
BACKGROUND Ivermectin, an antiparasitic drug, has recently gained attention as a potential candidate for repurposing in cancer therapy. However, the clinical safety and implications of its use in this context remain inadequately explored. AIM To map existing preclinical evidence on ivermectin’s anticancer mechanisms, evaluate its therapeutic role in cancer treatment, and identify known or potential drug interactions relevant to oncology practice. METHODS A systematic search was conducted across PubMed and EMBASE, covering publications from January 2000 up to the present to identify studies eligible for inclusion in accordance with PRISMA extension for Scoping Reviews guidelines. RESULTS A total of 43 studies were included in this review. The data extracted from the studies covered ivermectin therapy across breast, colorectal, glioblastoma, and hematologic malignancies. Most studies showed that Ivermectin exerts its anticancer effects by inhibiting P-glycoprotein and tumor proliferation, mitochondrial dysfunction, and modulating various oncogenic molecular pathways. CONCLUSION Ivermectin shows potential as a repurposed anticancer agent, particularly as an adjunct to conventional therapies. However, robust clinical trials are needed to validate efficacy, optimize dosing, and ensure safety. This review provides a foundational framework for future translational and clinical research in oncology.
BACKGROUND Hashimoto’s thyroiditis (HT) is an autoimmune dysfunction caused by genetic and environmental changes that attack the thyroid gland. HT affects approximately 2% to 5% of the population, being more prevalent in women. It is diagnosed through a blood test (anti-thyroid peroxidase). Pharmacological treatment consists of daily administration of the synthetic hormone levothyroxine on an empty stomach. The most common signs and symptoms are: Tissue resistance to triiodothyronine T3, weight gain, dry skin, hair loss, tiredness/fatigue, and constipation, and nutritional therapy appears to help reduce these symptoms. AIM To analyze nutritional interventions for treating HT. METHODS This is an integrative review of original studies on nutritional interventions for treating Hashimoto’s disease. Articles were searched in the MEDLINE/PubMed and Latin American and Caribbean Literature on Health Sciences (LILACS) databases via virtual health library, using controlled vocabulary and free terms. A total of 70 articles were found: 67 from PubMed and 3 from LILACS. After exclusions, 9 articles met the eligibility criteria, including dietary interventions for maintaining and restoring the patient’s quality of life. RESULTS The reviewed articles evaluated the nutritional treatment of HT through supplementation of deficient micronutrients, anti-inflammatory diets, gluten-free diets, exclusion of foods that cause food sensitivities, lactose-free diet, paleo diet, and calorie restriction diets. However, some results were controversial regarding the beneficial effects of HT. CONCLUSION In general, it was observed that nutritional interventions for HT are based on the recovery of micronutrient deficiencies, treatment of the intestinal microbiota, diet rich in foods with anti-inflammatory properties, lifestyle changes, and encouragement of healthy habits.
BACKGROUND Intestinal ultrasound (IUS) has gained prominence as a safe, non-invasive imaging technique for managing Crohn’s disease (CD), offering real-time evaluation without radiation exposure. AIM To systematically review the role of IUS in diagnosing, monitoring disease progression, assessing treatment response, and managing complications in CD. METHODS A literature search of PubMed and Embase databases was conducted, identifying 207 original research articles published between 1953 and June 2024. The review focused on diagnostic accuracy, disease monitoring, therapeutic utility, and advancements in IUS applications. RESULTS IUS has shown high diagnostic accuracy for detecting inflammation, particularly in the ileum and colon, with limitations in jejunal and rectal regions. It is effective in assessing disease activity using parameters like bowel wall thickness (BWT) and vascularity and correlates well with endoscopy and magnetic resonance enterography. IUS can predict early response to biologics, with reductions in BWT serving as an important marker. In known CD, IUS influences clinical decisions during remission, flares, and therapy evaluations. It reliably detects strictures, fistulas, and therapy-related complications. Small intestinal contrast ultrasound (SICUS) can improve the detection of strictures particularly proximal ones. Techniques such as CE-IUS and elastography enhance stricture characterization but require further validation. IUS is also useful in special scenarios like perianal fistulas, pregnancy, post-operative CD, and guiding endoscopic therapy. CONCLUSION IUS is a patient-friendly, cost-effective imaging tool that significantly impacts CD management across various stages. Its integration into clinical practice supports early diagnosis, disease monitoring, and therapeutic adjustments. Further studies are warranted to refine advanced techniques and standardize its application for broader use.
BACKGROUND Trichotillomania is a challenging to treat psychiatric disorder, with limited evidence for pharmacotherapy. Treatment typically involves medication, cognitive behavioral therapy, and behavioral interventions. Recently, transcranial magnetic stimulation (TMS) has emerged as a potential treatment strategy. AIM To assess the role of TMS in treating trichotillomania. METHODS A systematic search using specific terms was done in PubMed and Scopus databases for articles published until May 17, 2024, related to trichotillomania and TMS. The search included randomized controlled trials, open-label studies, case series, case reports, and retrospective chart reviews, following the Preferred Items for Systematic Reviews and Meta-Analysis guideline. RESULTS We identified 32 articles (6 in PubMed and 26 in Scopus). After removing duplicates and articles that did not meet the selection criteria, we conducted a final analysis of four articles. These included one retrospective study, two case series, and one case study, with a total of 22 patients diagnosed with trichotillomania enrolled across all four studies. The brain areas targeted were the supplementary motor area (SMA), pre-SMA, and left dorsolateral prefrontal cortex. The studies reported an improvement in the severity of symptoms of trichotillomania in the majority of patients with negligible side effects. Nevertheless, it is important to note that the existing studies are mostly of low to moderate quality. CONCLUSION Early evidence suggests repetitive TMS and accelerated continuous theta burst stimulation can help treat trichotillomania adjunctively to other treatments.
BACKGROUND Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder presenting as symptoms of dysphagia, esophageal food impaction, chest pain, and heartburn. After an initial trial of proton pump inhibitor (PPI) therapy, swallowed topical corticosteroids (STC) are effective as induction therapy for EoE. However, outcome data for STC as a maintenance strategy is limited. AIM To systematically evaluate the long-term outcomes and safety of maintenance treatment with STC. METHODS A systematic search of PubMed, EMBASE, Cochrane, and Web of Science was performed from inception to January 2025 for studies comparing long term or maintenance treatment with STC for EoE compared to placebo. We included studies that investigated patients who underwent successful induction therapy. Pooled data was analyzed for histologic recurrence, symptom recurrence, need for repeat esophageal dilation, use of concomitant PPI, and candida infection rates. A random effects model was used, and the data was presented using odds ratios (OR) with 95% confidence intervals (CI). RESULTS Three randomized control trials and one observational study were included, involving 303 patients (189 in the STC group, 114 in the placebo-controlled group). Analysis showed that histologic recurrence was significantly lower with STC (OR: 0.04, 95%CI: 0.01-0.28, P < 0.00001, I 2 = 78%). Overall symptom recurrence was similar between groups (OR: 0.23, 95%CI: 0.02-3.54, P = 0.29, I 2 = 92%). On sensitivity analysis, symptom recurrence was significantly lower in the STC group (OR: 0.05, 95%CI: 0.02-0.17, P = 0.00001, I 2 = 39%). Odds of repeat dilation were significantly lower in the STC group (OR: 0.14, 95%CI: 0.02-0.91, P = 0.04, I 2 = 0%). Candida infection rates were similar between groups (OR: 6.13, 95%CI: 0.85-44.26, P = 0.07, I 2 = 24%). Proportion of concomitant PPI use was similar between groups (OR: 1.64, 95%CI: 0.83-3.21, P = 0.15, I 2 = 0%). CONCLUSION For patients who successfully achieved remission of EoE with STC induction therapy, maintaining treatment is effective in sustaining histologic remission, while newer regimens may be effective in preventing symptom recurrence compared to placebo. We found no significant difference for oropharyngeal/esophageal candidiasis with STC maintenance therapy. Future studies with longer follow-up periods are needed.
The causative agent for dengue is dengue virus (DENV), with humans and mosquitoes serving as vectors. The DENV (family = Flaviviridae ) is a positive-stranded RNA virus with four serotypes, DENV-1, DENV-2, DENV-3, and DENV-4. As of 2023, the disease had been reported in 80 countries with over 6.5 million cases and 7300 mortalities since then. Despite the concerning incidence and prevalence of this disease, less attention is given to the development of therapeutic remedies and preventive alternatives. The search for new antiviral bioactive compounds is therefore important and urgent. Marine organisms have been a source of diverse bioactive natural products. The large marine biodiversity and the structural diversity of their specialized metabolites provide an explorative opportunity for the discovery of novel antiviral specialized metabolites. Reported marine natural products with anti-DENV activities include fucoidan, scequinadoline A, indole derivatives, and others. Nevertheless, marine organisms are still largely underexplored as sources of antiviral drugs. With advances in metabolomics and computational screening, we may discover additional marine natural products to help with dengue treatment.
Hepatic encephalopathy (HE) remains a significant neuropsychiatric complication of liver disease, characterized by a spectrum of cognitive, behavioral, and motor impairments. Recent advances in the understanding of its pathophysiology have identified inflammation and gut-liver-brain axis interactions along with conventional theories on ammonia toxicity. Rifaximin and lactulose continue to be the first-line therapies. However, novel approaches like ammonia-lowering agents such as glycerol phenylbutyrate, ornithine phenylacetate, zinc and L-ornithine L-aspartate, gut microbiota modulation by probiotics, fecal microbiota transplantation, and anti-inflammatory drugs like rifamycin and its analogs started showing promising results in clinical trials. This review emphasizes the importance of a multidisciplinary approach in HE management, combining traditional and innovative therapies to enhance the patient’s quality of life and to reduce the healthcare burdens and also highlights the newer treatment strategies for future research and clinical application.
Inflammatory bowel disease (IBD) is an increasing global health issue that poses specific challenges in Nigeria. Although awareness of IBD is growing in the country, research and resources remain limited. This review aims to address this significant gap. To identify key gaps in IBD research within Nigeria and highlight opportunities for advancing future investigations to improve patient outcomes. A comprehensive review of the existing literature was conducted to evaluate current trends in IBD research, healthcare barriers, and potential areas for investigation specific to the Nigerian context. The analysis highlights significant deficiencies, including scarce epidemiological data, low levels of awareness among clinicians and patients, limited access to healthcare, and inadequate diagnostic and treatment resources. Additionally, there is a profound lack of localized research addressing genetic, environmental, and dietary factors relevant to the Nigerian population. Future investigations should prioritize epidemiological studies to assess IBD prevalence in Nigeria, establish specialized care centers for diagnosis and management, and launch public health initiatives to promote awareness and education. Strengthening collaboration between researchers, healthcare providers, and policymakers is imperative to achieving these goals. Bridging these research gaps presents an invaluable opportunity to enhance IBD healthcare delivery and patient outcomes in Nigeria. Collaborative, multidisciplinary efforts are essential for advancing knowledge, improving resources, and ultimately elevating the quality of life for individuals living with IBD in the country.
BACKGROUND Aortic root dilation, linked to bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV), risks aneurysm and dissection. Valve-sparing aortic root replacement (VSARR) preserves native valves, avoiding prosthetic valve complications. Long-term VSARR durability, especially in BAV patients, is debated. We hypothesize that VSARR outcomes differ between BAV and TAV patients in short-term and long-term settings. AIM To investigate short-term and long-term outcomes of VSARR in BAV vs TAV patients. METHODS This Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant meta-analysis included observational studies comparing VSARR in adult BAV vs TAV patients. PubMed, ScienceDirect, and EMBASE were searched from inception to June 2025. Outcomes included mortality, reintervention, and procedural times. Pooled relative risk (RR) and mean differences (MD) with 95%CI were calculated. Risk of bias was assessed using Risk of Bias in Non-randomized Studies of Interventions; evidence certainty via GRADE. RESULTS Thirteen observational studies involving 1419 BAV and 2349 TAV patients were included. In-hospital mortality (RR = 0.34, 95%CI: 0.10–1.14, P = 0.08) and reoperation (RR = 1.04, 95%CI: 0.64–1.69, P = 0.87) showed no significant differences. All-cause mortality risk was significantly lower in BAV patients (RR = 0.34, 95%CI: 0.13–0.86, P = 0.02). Overall reintervention risk was significantly greater in BAV patients (RR = 2.64, 95%CI: 1.96–3.55, P < 0.00001). Aortic cross-clamp (MD = 3.35 minutes, 95%CI: -5.06 to 11.76, P = 0.43) and cardiopulmonary bypass times (MD = 3.96 minutes, 95%CI: -10.26 to 18.18, P = 0.59) showed no significant differences but substantial heterogeneity. The certainty of evidence was moderate for reintervention, low for mortality risk and in-hospital reoperation, and very low for procedural times. CONCLUSION VSARR demonstrates comparable short-term safety between BAV and TAV patients. However, BAV patients face a significantly higher long-term reintervention risk, highlighting the need for tailored strategies and further research.
Neural stem cells (NSCs) play a fundamental role in generating diverse neuronal populations that contribute to the formation of intricate neural circuitry. Disturbances arising from intrinsic or extrinsic factors can alter the developmental behavior of NSCs and disrupt nervous system homeostasis. While intrinsic regulatory mechanisms have been elucidated extensively in invertebrate or vertebrate models, the regulatory mechanisms underlying extrinsic cues from the cellular environment remain poorly understood. This review synthesized recent research on cellular ambient effects, including the microenvironment, systemic environment and external factors, on NSCs in Drosophila . Key topics include spatial cues, NSC-glia interactions, long-distance regulation by tissues such as the fat body, and the external environmental stressors like irradiation or viral infection. By integrating these findings, this review provides new insights into how extrinsic signals shape NSCs and bridges gaps between foundational research and clinical translation.
BACKGROUND Clinical predictors of dengue fever are crucial for guiding timely management and avoiding life-threatening complications. While prognostic scores are available, a systematic evaluation of these tools is lacking. AIM To evaluate the performance and accuracy of various proposed dengue clinical prognostic scores. METHODS Three databases, PubMed, EMBASE and Cochrane, were searched for peer-reviewed studies published from inception to 4 September 2023. Studies either developing or validating a prognostic model relevant to dengue fever were included. A total of 29 studies (n = 17910) were included. RESULTS Most commonly studied outcomes were severe dengue (15 models) and mortality (8 models). For the paediatric population, Bedside Dengue Severity Score by Gayathri et al (specificity = 0.98) and the nomogram model by Nguyen et al (sensitivity = 0.87) performed better. For the adult population, the most specific model was reported by Leo et al (specificity = 0.98). The most sensitive score is shared between Warning Signs for Severe Dengue as reported by Leo et al and Model 2 by Lee et al (sensitivity = 1.00). CONCLUSION While several models demonstrated precision and reliability in predicting severe dengue and mortality, broader application across diverse geographic settings is needed to assess their external validity.
BACKGROUND Periodontitis is a chronic inflammatory disorder influenced by both behavioral and genetic factors. Among epigenetic regulators, the ANRIL gene has been proposed as a risk factor for periodontitis; however, findings on the association between ANRIL polymorphisms and disease susceptibility remain inconsistent. AIM To analyze the association between the rs1333048 genetic polymorphism in the ANRIL gene and periodontitis via meta-analysis. METHODS A literature search was performed for studies published before May 2, 2025. The Review Manager statistical program was used in analyses with calculations of heterogeneity index (I ²) and odds ratio (OR) with 95% of confidence intervals (CI). Begg’s test and the Egger’s linear regression test were used for publication bias evaluation using Comprehensive meta-analysis software. P < 0.05 was considered significant. RESULTS From 12 studies including 5489 participants across multiple ethnic groups, we observed a statistically significant association between ANRIL gene polymorphisms and periodontitis in the allelic contrast model (OR = 1.24 95%CI: 1.15-1.34, P < 0.00001). Conversely, the wild-type allele was significantly associated with the control group (OR = 0.80 95%CI: 0.75-0.87, P < 0.00001). Heterogeneity was low (I ² = 28%, P heterogeneity = 0.17), and no significant risk of publication bias was detected (P > 0.05). CONCLUSION In conclusion, this meta-analysis demonstrated a significant association between the rs1333048 polymorphism and periodontitis in the overall analysis and in stratified analyses of Caucasian populations, but in for mixed-race populations.
