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Role of genetics in early-onset cardiovascular disease
No full textGenetics increasingly comes to the front with early-onset cardiovascular disease (CVD) since researchers investigate the complex interplay of hereditary factors that promote an early manifestation of the disease. CVD is one of the most general causes of morbidity and mortality worldwide, presenting unique challenges when it arises in younger populations many times due to genetic predispositions. The various etiologies in the pathogenesis of early-onset CVD involve genetic factors, including the monogenic disorders of familial hypercholesterolemia (FH) and hypertrophic cardiomyopathy (HCM) of these diseases showing the simple Mendelian patterns of inheritance. These may be mediated through gene variations, including Low-Density Lipoprotein Receptor (LDLR), Apolipoprotein B (APOB), Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), and Myosin Heavy Chain 7 (MYH7). Disrupted lipid metabolism, myocardial function, or vascular integrity due to mutations could lead to adverse clinical consequences. Moreover, polygenic risk score (PRS) has now become helpful in identifying individuals who are at elevated risk due to the cumulative effect of several genetic variants. Knowledge about gene-environment interactions, epigenetic influences, and complex regulatory networks contributes to understanding the importance of genetic contributions to early-onset CVD. However, the genetic variation is population-specific and underlines the need for research inclusive of diverse genetic backgrounds in developing more inclusive and effective predictive models. Whole genome and exome sequencing have revolutionized early detection, making personalized treatment plans possible, including targeted therapeutic interventions like PCSK9 inhibitors. On the other hand, such scientific progress also provides a lot of ethical challenges, such as utilizing personal data, informed consent, and equal access to genetic services. This review summarizes the genetic basis underlying early-onset CVD, with detailed discussions of monogenic and polygenic contributions, important genetic pathways, and emerging advances in genetic testing and personalized medicine approaches. By highlighting the integration of genetic insights with preventive and therapeutic strategies, this review aims to bring into focus the use of genetic insight in the betterment of outcomes in patients and inform future research in cardiovascular genetics.https://www.cureus.com/articles/366279-role-of-genetics-in-early-onset-cardiovascular-disease#!
Effect of Digoxin versus Bisoprolol for heart rate control in atrial fibrillation with heart failure on quality of life: a prospective randomised comparative study.
No full textIntroduction Atrial fibrillation (AF) and heart failure (HF) often co-exist, exerting synergistic adverse effects on patients’ morbidity, quality of life (QOL) and mortality. This also poses a unique management challenge of heart failure in the AF population as compared to the sinus rhythm population. While beta blockers such as bisoprolol have been preferred treatment options for patients with heart failure, digoxin remains a cost-effective yet underrated alternative. However, its overall effect on QOL remains debated, especially in the South Asian population that carries a higher burden of heart failure than any other ethnicity. Objective The objective of this study was to compare the short-term effect of bisoprolol versus digoxin on quality of life in patients with permanent AF and concurrent HF in the South Asian population. Methods This single-centred prospective randomised comparative study was conducted at the outpatient department of Punjab Institute of Cardiology, Lahore, from March to September 2022. A total of 80 patients with permanent AF and established HF were enrolled and randomised in two groups to receive either digoxin (62.5-250 mcg/day) or bisoprolol (1.25-15 mg/day). The 36-Item Short Form Health Survey (SF-36) was administered at baseline and after three months to assess changes in QOL. Data were analysed using SPSS v25.0 (IBM Corp., Armonk, NY, USA), with significance at p ≤ 0.05. Results Both treatment groups significantly improved SF-36 QoL scores after three months (p < 0.001). However, the digoxin group reported significantly greater improvement compared to the bisoprolol group (mean QoL score: 76.68 ± 9.37 vs. 70.90 ± 8.00; p = 0.004). No serious adverse events or digoxin-related toxicities were reported in either group. Conclusion In patients with permanent AF and HF, digoxin resulted in a statistically significant improvement in short-term quality of life compared to bisoprolol. These findings suggest that digoxin may serve as a viable and possibly superior alternative to bisoprolol in patients with permanent AF and HF, with a potential role for digoxin as a first-line agent in select populations. It also highlights the need to re-evaluate current treatment preferences, especially in resource-limited settings. Further multicentric and multi-ethnic studies are needed to substantiate these findings and evaluate long-term clinical outcomes.https://www.cureus.com/articles/390007-effect-of-digoxin-versus-bisoprolol-for-heart-rate-control-in-atrial-fibrillation-with-heart-failure-on-quality-of-life-a-prospective-randomised-comparative-study#!
Assessing Morbidity and Malignancy Risk in Patients Presenting with Pulmonary Embolism in an Ambulatory Care Setting.
Get PDFObjectives: Venous thromboembolism (VTE), especially pulmonary embolism (PE), can be treated in an outpatient setting after appropriate risk assessment. However, front-door physicians may be resistant to follow this practice. The possibility of cancer-associated VTE complicates the outpatient management of PE. This study aimed to assess the morbidity and mortality in patients with PE who were managed in an emergency/acute medicine-led outpatient clinic as per risk stratification as well as detecting diagnoses of new cancer sites (NCSs) in these patients. Methods: This retrospective study included all patients with confirmed PE managed in an acute medicine outpatient setting at Queens Hospital, Burton-on-Trent, United Kingdom, from 2019 to 2022. Biochemical findings, radiological findings, mortality and morbidity rates, treatment administered, simplified Pulmonary Embolism Severity Index (sPESI) scores, complications and NCS diagnosis were obtained. Results: A total of 82 patients were included in this study; their mean age was 63.3 +/- 16.7 years and 56.1% (n = 46) were male. The two commonest presenting complaints were new shortness of breath (25.6%, n = 21) and pleuritic chest pain (19.5%, n = 16). Unprovoked PE was observed in 52.4% (n = 43) of patients. Increased sPESI scores were related to increased mortality rates; sPESI scores of 0 and 3 were associated with 0% and 50% mortality rates within 90 days, respectively. NCS was reported in 13.4% (n = 11). Statistical analyses using logistic regression and classification tree methods revealed that NCS can be predicted with 70.6% sensitivity and 97% specificity using 2 variables (history of cancer and age >73 years). Conclusion: The sPESI can help in the risk stratification of patients with PE showing poor outcomes; patients at a high risk of NCS development can be identified using the classification tree method
International Expert Consensus Recommendations for HER2 Reporting in Breast Cancer: Focus on HER2-low and Ultralow Categories.
Get PDFThe concept of "HER2-negative" breast cancer is evolving, with the recognition of HER2-low and HER2-ultralow subsets. These subsets are clinically relevant regarding treatment with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd), which has shown survival benefit in patients with metastatic carcinoma with minimal HER2 protein expression that lack HER2 gene amplification by in situ hybridisation (ISH). In clinical trials using T-DXd, HER2-low was defined as immunohistochemistry (IHC) score 1+ or IHC score 2+ without HER2 gene amplification. HER2-ultralow was defined as faint or barely perceptible, incomplete membrane staining in >0 to ≤10% of tumour cells (IHC score 0+/with membrane staining) and HER2-null as complete absence of staining (IHC score 0/absent membrane staining). These results now necessitate more detailed evaluation and reporting of traditional "HER2-negative" results to identify patients with metastatic breast cancer who may benefit from T-DXd therapy. Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have extended regulatory approval of T-DXd to patients with metastatic breast cancer showing HER2-low or HER2-ultralow expression. Updated clinical management guidelines now, therefore, incorporate the spectrum of HER2 results into treatment selection algorithms in the metastatic setting. To align histopathologic practice with these developments, the College of American Pathologists (CAP) has issued a new biomarker-reporting template that recommends explicit distinction between IHC 0/absent membrane staining and IHC 0+/with membrane staining. Key concerns among pathologists include assay variability, scoring reproducibility and quality assurance standards for accurately detecting such low levels of HER2 expression. This manuscript provides expert consensus, evidence-based practical recommendations for identifying and reporting tumours with HER2-low and HER2-ultralow expression. We emphasise standardised testing protocols, validated assays, robust internal and external controls, and focused training for pathologists. A universal structured pathology report is proposed to highlight the accurate distinction between IHC 0 (null), IHC 0+ (ultralow), and HER2-low expression
Carcinoid Heart Disease Revealing the Burden of a Neuroendocrine Tumour: A Case Report.
Get PDFCarcinoid heart disease (CHD) is a rare but serious complication of carcinoid syndrome (CS), typically arising in patients with metastatic neuroendocrine tumours (NETs). Prolonged exposure of the right side of the heart to vasoactive substances such as serotonin leads to progressive valvular fibrosis, predominantly affecting the tricuspid and pulmonary valves, and often culminates in right-sided heart failure. We report the case of a 67-year-old woman with a metastatic small bowel NET who developed CS and later presented with worsening exertional dyspnoea and peripheral oedema. Echocardiography demonstrated severe tricuspid regurgitation and moderate pulmonary regurgitation with preserved left ventricular systolic function. Despite aggressive diuretic therapy, her condition deteriorated, and she developed refractory right-sided heart failure with generalised anasarca. She was not a candidate for valve replacement or further disease-directed therapy due to advanced metastatic disease and frailty and was therefore managed palliatively until she passed away. This case highlights the severe burden of CHD in patients with serotonin-secreting NETs and emphasises the importance of early recognition and regular echocardiographic surveillance to facilitate timely intervention and potentially improve outcomes
Evaluating the Readability and Quality of Bladder Cancer Information from AI Chatbots: A Comparative Study Between ChatGPT, Google Gemini, Grok, Claude and DeepSeek.
Get PDFBackground/Objectives: Artificial Intelligence (AI)-based chatbots such as ChatGPT are easily available and are quickly becoming a source of information for patients as opposed to traditional Google searches. We assessed the quality of information on bladder cancer, provided by various AI chatbots such as ChatGPT 4o, Google Gemini 2.0 flash, Grok 3, Claude Sonnet 3.7 and DeepSeek R1. Their responses were analysed in terms of Readability Indices, and two consultant urologists rated the quality of information provided using the validated DISCERN tool. Methods: The top 10 most frequently asked questions about bladder cancer were identified using Google Trends. These questions were then provided to five different AI chatbots, and their responses were collected. No prompts were used, reflecting natural language queries that patients would use. The responses were analysed in terms of their readability using five validated indices: Flesch Reading Ease (FRE), the Flesch-Kincaid Reading Grade Level (FKRGL), the Gunning Fog Index, the Coleman-Liau Index and the SMOG index. Two consultant urologists then independently assessed the responses of various AI chatbots using the DISCERN tool, which rates the quality of the health information on a five-point LIKERT scale. Inter-rater agreement was calculated using Cohen's Kappa and the intraclass correlation coefficient (ICC). Results: ChatGPT 4o was the overall winner in readability scores, with the highest Flesch Reading Ease score (59.4) and the lowest average reading grade level (7.0) required to understand the material. Grok 3 was a close second (FRE 58.3, grade level 8.7). Claude 3.7 Sonnet used the most complex language in its answers and therefore scored the lowest FRE score of 44.9, with the highest grade level (9.5) and also the highest complexity on other indices. In the DISCERN analysis, Grok 3 received the highest average score (52.0), followed closely by ChatGPT 4o (50.5). The inter-rater agreement was highest for ChatGPT 4o (ICC: 0.791; Kappa: 0.437), while it was lowest for Grok 3 (ICC: 0.339, Kappa 0.0, Weighted Kappa 0.335). Conclusions: All AI chatbots can provide generally good-quality answers to questions about bladder cancer with zero hallucinations. ChatGPT 4o was the overall winner, with the best readability metrics, strong DISCERN ratings and highest inter-rater agreement.https://www.mdpi.com/2077-0383/14/21/780
Association Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Sarcopenia: A Systematic Review and Meta-analysis.
Get PDFThis systematic review and meta-analysis evaluated the prevalence of sarcopenia in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) compared to controls. A comprehensive search across PubMed, Embase, Cochrane Library, and Web of Science databases was conducted from January 2015 to August 2025, identifying studies that compared the prevalence of sarcopenia between MASLD patients and non-MASLD controls. Sixteen studies comprising diverse populations from Korea, China, the United States, Italy, the Netherlands, and the United Kingdom were included, with sample sizes ranging from 57 to 18,815 participants. Sarcopenia assessment methods varied across studies, including dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), computed tomography (CT), and functional tests. Statistical analyses were performed using RevMan 5.4 (The Cochrane Collaboration, London, England, UK) with random-effects models to calculate pooled odds ratios (ORs). The meta-analysis revealed a significantly higher prevalence of sarcopenia in MASLD patients (14.86%) compared to controls (6.49%), with a pooled OR of 2.24 (95% CI: 1.74-2.89, p < 0.001). Substantial heterogeneity was observed (I² = 95%) across studies. Subgroup analyses demonstrated stronger associations in cohort studies versus cross-sectional studies, in populations under 50 years of age, and in studies from Korea and the United States. The bidirectional relationship between MASLD and sarcopenia is supported by shared pathophysiological mechanisms, including insulin resistance, chronic inflammation, and altered protein metabolism. These findings suggest that MASLD patients should undergo routine sarcopenia screening, and interventions targeting muscle health may benefit both conditions. The substantial burden of sarcopenia in MASLD patients highlights the need for integrated management approaches addressing both hepatic and muscular manifestations
Comparative Effectiveness of the Proximal Femoral Nail and Dynamic Hip Screw Fixation in Intertrochanteric Femur Fractures: A Systematic Review and Meta-Analysis.
Get PDFThis systematic review and meta-analysis compared the clinical effectiveness of proximal femoral nail (PFN) versus dynamic hip screw (DHS) fixation in patients with intertrochanteric femur fractures. A comprehensive literature search was conducted across multiple databases from January 2010 to September 2025, identifying studies that directly compared PFN and DHS fixation outcomes. Thirty-three studies met the inclusion criteria, comprising randomized controlled trials, prospective cohorts, and retrospective comparative studies from diverse geographic regions. The pooled analysis demonstrated several significant advantages favoring PFN fixation. Operative time was significantly shorter with PFN compared to DHS (mean difference (MD): -12.30 minutes, 95% confidence interval (CI): -17.33 to -7.28), while intraoperative blood loss was substantially lower (MD: -115.01 mL, 95% CI: -132.05 to -97.98). Patients treated with PFN achieved full weight-bearing significantly earlier than those receiving DHS. Safety outcomes showed PFN was associated with significantly lower total complication rates (risk ratio (RR): 0.46, 95% CI: 0.31-0.68) and reduced infection risk. However, no significant differences were observed between groups regarding implant failure rates, mortality, or long-term functional outcomes, as measured by the Harris Hip Score. High heterogeneity was noted across most outcomes, reflecting variations in study populations and methodologies. These findings suggest that PFN offers superior perioperative outcomes and early recovery advantages compared to DHS, while maintaining comparable long-term functional results and survival rates in patients with intertrochanteric femur fracture
Surgical margins in breast conserving surgery for ductal carcinoma in situ of the breast and clinical outcomes: a national audit with long term follow-up.
Get PDFBACKGROUND: Optimal surgical margin width in breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is not established. The United Kingdom (UK) Association of Breast Surgery (ABS) recommended a 1 mm margin, whereas a minimum of 2 mm has been recommended in the United States of America (USA). This paper uses precise histological margin width data from UK national datasets to understand the impact of surgical margins on time to recurrence (TTR). METHODS: Patients were included if aged ≥45-years with a new diagnosis of DCIS alone, between 2003 and 2014, within the English National Health Service (NHS) Breast Screening Programme. Primary treatment included BCS and a minimum histological excision margin width recorded. Exclusion criteria included: prior history of DCIS; prior history of invasive cancer or its diagnosis within 3-months of initial surgical treatment for DCIS. Data was extracted from NHS England National Disease Registration Service (NDRS), ABS and Sloane Project audits. FINDINGS: 16,907 patients diagnosed with DCIS having definitive BCS surgery were identified between 2003 and 2014. TTR was found to be significantly shorter for patients with surgical margins <1 mm vs ≥ 1 mm (adjusted hazard ratio (aHR) = 1·32; 95% (confidence interval) CI:1·06-1·63; p = 0·012); <2 mm vs ≥ 2 mm (aHR = 1·19; 95% CI:1·05-1·35; p = 0·0062) and ≥1-<2 mm vs ≥ 2 mm (aHR = 1·18; 95% CI:1·01-1·38; p = 0·032). There was no evidence that increasing the surgical margin width beyond 2 mm significantly improved TTR (aHR = 0·96; 95% CI: 0·86-1·08; p = 0·52 for ≥5 mm vs ≥ 2-<5 mm). The rate of recurrence across 14 years following BCS + radiotherapy was 1·2% per annum, 2129 (13%) patients had a recurrence of which 78% were invasive breast cancers. INTERPRETATION: Patients with DCIS with histological margins of <2 mm, adjusted for other clinical factors, have significantly worse TTR compared to margins ≥2 mm. These findings may inform optimum treatment of patients with DCIS. FUNDING: An ABS grant covered the cost of data extraction by NHS England and medical writing assistance. The latter was provided by Edge Health, supervised by the co-authors
Comparative effectiveness of educational interventions in neurological disease for healthcare workers and students: a systematic review.
Get PDFOBJECTIVES: To assess the comparative effectiveness of educational interventions in neurological disease for healthcare workers and students. DESIGN: Systematic review. DATA SOURCES: Medline, Embase and Cochrane through to 1 June 2025. ELIGIBILITY CRITERIA: Studies evaluating neurological disease educational interventions with a comparator group (observational cohort/randomised controlled trial (RCT)) were included. DATA EXTRACTION AND SYNTHESIS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review was conducted (PROSPERO: CRD42023461838). Knowledge acquisition and educational methodologies were collected from each study. Study outcomes were classified using the Kirkpatrick and Kirkpatrick four-level model (learner reaction, knowledge acquisition, behavioural change, clinical outcome).1 Risk of bias was assessed using the Newcastle-Ottawa scale for non-randomised studies and the Cochrane Risk of Bias tool for RCTs.2 3 RESULTS: A total of 67 studies involving 4728 participants were included. Of these, 36 were RCTs, and 31 were observational studies. Virtual interventions were the most common (67.2%, n=45 studies), primarily targeting either medical students (46.3%, n=31 studies) or specialists (40.3%, n=27 studies). Overall, 70.1% (n=47) of studies demonstrated outcomes in favour of the intervention. However, few studies used K&K level 3/4 outcomes, with two studies evaluating behaviour change (level 3) and three assessing clinical outcomes (level 4 combined with other levels). No study exclusively assessed level 4 outcomes. Meta-analysis of 22 RCTs with calculable standardised mean differences (SMDs) (n=1748) showed a significant benefit of interventions (SMD 0.75, 95% CI 0.22 to 1.27, p=0.0056). CONCLUSIONS: This review highlights a growing body of research particularly focusing on virtual techniques, specialist audiences and treatment-oriented content. Few studies assessed changes in practice or patient care. Non-specialists remain underrepresented. Future studies should prioritise assessing the clinical impact of educational interventions within non-specialist audiences.https://bmjopen.bmj.com/content/15/11/e10747