Search Results (160)

Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological management of obstructive HCM (oHCM). This review offers an integrated and up-to-date synthesis of the cardiac myosin inhibitor class, with a focus on mavacamten, aficamten, and the broader landscape of emerging agents. It also highlights recent clinical trial outcomes, pharmacokinetic and pharmacogenetic considerations, and potential future directions in therapy. Furthermore, we incorporate the most recent data up to May 2025, including late-breaking trial results and real-world safety findings, aiming to provide clinicians with a practical and comprehensive perspective on this evolving drug class. A narrative review was conducted by systematically searching PubMed, Scopus, Google Scholar, and ClinicalTrials.gov for English-language articles and trials published between January 2016 and May 2025. Keywords included “cardiac myosin inhibitor”, mavacamten”, “aficamten”, “MYK-224”, and “hypertrophic cardiomyopathy.” Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. CMIs such as mavacamten and aficamten have demonstrated significant clinical benefits in reducing LVOT gradients, improving exercise capacity, and alleviating symptoms in patients with oHCM. Mavacamten is currently approved for clinical use, while aficamten is in advanced regulatory review. Comparative data suggest potential advantages of aficamten in the onset of action, pharmacokinetic profile, and tolerability. Emerging evidence supports the exploration of CMIs in pediatric populations, heart failure with preserved ejection fraction (HFpEF), and non-obstructive HCM (nHCM), although results are still preliminary. Cardiac myosin inhibitors offer a novel, pathophysiology-targeted approach to managing oHCM. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations. Full article

Background/Objectives: In the era of treat-to-target strategies in inflammatory bowel disease (IBD), transmural healing (TH) is gaining recognition as a promising therapeutic goal. TH has been associated with significantly better long-term outcomes, including reduced rates of hospitalization, surgery, and the need for therapy escalation. Cross-sectional imaging techniques, such as intestinal ultrasound (IUS), magnetic resonance imaging (MRI), and computed tomography enterography (CTE), offer a comprehensive, non-invasive means to assess this deeper level of healing. This review explores how TH is currently defined across various imaging modalities and evaluates the feasibility and cost-effectiveness of achieving TH with available therapies. Methods: A literature search was conducted across PubMed, Scopus, and Embase using keywords, including “transmural healing”, “intestinal ultrasonography”, “magnetic resonance imaging”, “computed tomography enterography”, “Crohn’s disease”, “ulcerative colitis”, and “inflammatory bowel disease”. Only English-language studies were considered. Results: Despite growing interest, there is no standardized definition of TH across imaging platforms. Among the modalities, IUS emerges as the most feasible and cost-effective tool, owing to its accessibility, accuracy (sensitivity 62–95.2%, specificity 61.5–100%), and real-time capabilities, though it does have limitations. Current advanced therapies induce TH in roughly 20–40% of patients, with no consistent differences observed between biologics and small molecules. However, TH has only been evaluated as a formal endpoint in a single randomized controlled trial to date. Conclusions: A unified and validated definition of transmural healing is critically needed to harmonize research and guide clinical decision-making. While TH holds promise as a meaningful treatment target linked to improved outcomes, existing therapies often fall short of achieving complete transmural resolution. Further studies are essential to clarify its role and optimize strategies for deep healing in IBD. Full article

Purpose: Pellucid Marginal Degeneration (PMD) is a rare ectatic corneal disorder characterized by inferior peripheral thinning and significant irregular astigmatism. Despite its clinical similarities to keratoconus, PMD presents unique diagnostic and therapeutic challenges. This review aims to provide a comprehensive update on the pathophysiology, clinical features, diagnostic approaches, and management strategies for PMD, emphasizing the latest advancements in treatment options. Methods: A systematic literature search was performed in MEDLINE (via PubMed), Google Scholar, and Scopus up to February 2025 using the terms: “pellucid marginal degeneration,” “PMD,” “ectatic corneal disorders,” “keratoplasty in PMD,” “corneal cross-linking in PMD,” “ICRS in PMD,” “toric IOL PMD” and their Boolean combinations (AND/OR). The search was restricted to English-language studies involving human subjects, including case reports, case series, retrospective studies, clinical trials, and systematic reviews. A total of 76 studies met the inclusion criteria addressing treatment outcomes in PMD. Results: PMD is characterized by a crescent-shaped band of inferior corneal thinning, leading to high irregular astigmatism and reduced visual acuity. Diagnosis relies on advanced imaging techniques such as Scheimpflug-based corneal tomography, which reveals the characteristic “crab-claw” pattern. Conservative management includes rigid gas-permeable (RGP) lenses and scleral lenses, which provide effective visual rehabilitation in mild to moderate cases. Surgical options, such as CXL, ICRS, and toric IOLs, are reserved for advanced cases, with varying degrees of success. Newer techniques such as CAIRS, employing donor tissue instead of synthetic rings, show promising outcomes in corneal remodeling with potentially improved biocompatibility. Penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) remain definitive treatments for severe PMD, though they are associated with significant risks, including graft rejection and postoperative astigmatism. Conclusions: PMD is a complex and progressive corneal disorder that requires a tailored approach to management. Early diagnosis and intervention are critical to optimizing visual outcomes. While conservative measures are effective in mild cases, surgical interventions offer promising results for advanced disease. Further research is needed to refine treatment protocols and improve long-term outcomes for patients with PMD. Full article

Background and Objectives: Congenital heart defects (CHD) affect around 1% of the population, making them the most common congenital disease worldwide. Thanks to advances in treatment, over 90% of affected children are able to reach adulthood, shifting focus to long-term outcomes such as disease-specific quality of life (DsQoL). To date, there has been no validated, standardized instrument for assessing DsQoL in young German CHD patients. This study introduces the Congenital Heart Disease Specific Inventory (CHDSI), the first freely available German-language instrument for measuring DsQoL in children and adolescents with CHD. Materials and Methods: The CHDSI was developed at the German Heart Center Munich in collaboration with affected children and adolescents and validated nationwide via the National Register for Congenital Heart Defects (NRCHD) with 1201 participants (46 kindergarten children, 530 children, 625 adolescents). Two age-specific versions (36/37 items) and a 31-item preschool version were created, alongside a 6-item short form (CHDSI-SF) for rapid screening. Reliability was assessed using Cronbach’s alpha and split-half methods; construct validity via confirmatory factor analysis (CFA) using DWLS; and score interpretation through standardized stanine scales. The small sample size of kindergarten children precluded a model test for this group. The standard values given for this subsample should therefore be interpreted with caution. Results: The CHDSI showed excellent internal consistency (Cronbach’s α = 0.856 to 0.900) and high split-half reliability (>0.95). CFA confirmed a robust six-factor structure with excellent model fit (CFI and TLI ≥ 0.991, RMSEA ≤ 0.05). Subscales showed strong discriminant validity, and significant differences were found by CHD severity and sex. Conclusions: The CHDSI is a psychometrically valid, age-appropriate, and freely available instrument for assessing DsQoL in children and adolescents with CHD. It provides valuable support for clinical decision-making and research. Further studies should explore international validation and cultural adaptation. Full article

Background/Objectives: Renal transplantation (RT) represents the optimal treatment for end-stage renal disease (ESRD), offering improved quality of life and restored fertility in women post-transplant. While post-transplant pregnancies are possible, they can lead to complications including pre-eclampsia, graft dysfunction, and other adverse outcomes. This study evaluates existing literature to assess pregnancy’s impact on kidney transplantation outcomes, specifically long-term graft function and survival. Methods: We conducted a systematic review of English-language literature from January 2000 to September 2023 across multiple databases, following PRISMA guidelines. We established inclusion criteria focusing on graft function and adverse events. Two independent reviewers performed data extraction, and we assessed risk of bias using the ROBINS-I tool. Results: From 4917 articles, we included 26 studies encompassing 1202 pregnancies in 902 kidney transplant recipients. Mean maternal age was 30.8 years, with an average interval of 52 months between transplant and pregnancy. Pre-pregnancy hypertension occurred in 54.2% of cases, and pre-eclampsia developed in 25.7%. The live birth rate reached 70.5%, while miscarriage, stillbirth, and neonatal death rates were 11.3%, 2.7%, and 2.5%, respectively. We noticed graft dysfunction during pregnancy in 20.2% of cases. Though kidney function often deteriorated temporarily, most patients recovered post-delivery. Discussion: Post-transplant pregnancies remain viable but high-risk, with elevated rates of obstetric complications. Our findings highlight the need for standardized data collection and reporting to better understand and manage pregnancy’s impact on graft outcomes. Conclusions: With appropriate management, pregnancy in kidney transplant recipients is feasible, though it carries elevated risks of obstetric complications. We recommend further multicenter studies with standardized data collection to improve understanding and outcomes. Full article

Background: Mycobacterium ulcerans causes Buruli ulcer (BU), a necrotizing skin disease endemic in over 30 countries. Its toxin, mycolactone, drives tissue destruction, and the infection is transmitted via environmental reservoirs or vectors. Disease patterns vary globally, and an improved understanding of their pathogenesis may enhance current antimicrobial and surgical treatments. Methods: A comprehensive literature search from 1901 to 2025 was conducted across major databases to explore antimicrobial and reconstructive surgical strategies for Mycobacterium ulcerans. Search terms included BU, key antibiotics, and surgical interventions. Relevant English-language studies on treatment outcomes were reviewed to summarize evolving management trends and emerging therapeutic approaches. Results and Discussion: This review highlights the importance of early diagnosis and timely antimicrobial therapy in preventing disease progression and limb loss. It reviews WHO-recommended antibiotic regimens and discusses the theoretical risk of drug resistance, although clinical resistance remains rare and unreported in Australia. Surgical interventions in select cases are crucial, with timing being a significant factor in functional outcomes. The review also covers pediatric-specific challenges, including growth preservation and psychosocial support for young patients. Reconstructive options focus on limb salvage and staged reconstructions, with multidisciplinary care essential for optimal outcomes. The paper advocates for RCTs to refine treatment protocols, surgical guidelines, and explore emerging antibiotic therapies such as telacebec. Conclusions: BU remains a global health challenge, requiring early diagnosis, timely antimicrobial therapy, and surgery in selected cases. Future research will refine treatment and reduce long-term impacts. Full article

Background/Objectives: Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. In cases of severe-to-profound SNHL, cochlear implantation (CI) is a widely used intervention, but outcomes remain variable due to possible neurodevelopmental comorbidities. This study aimed to evaluate the long-term auditory and language outcomes in children with cCMV after CI and to explore clinical and radiological predictors of post-CI performance. Methods: Fifty-three children with cCMV and bilateral severe-to-profound SNHL who underwent CI at five tertiary referral centers in Italy were included in the study. Auditory and language outcomes were assessed pre- and post-implantation using the Categories of Auditory Performance II (CAP-II) scale, the Nottingham 3-Level Classification, and the Bates Language Development Scale. Brain MRI abnormalities were classified according to the Alarcón classification. Correlations were explored between outcome scores and symptomatic status at birth, MRI findings, and neurodevelopmental comorbidities. Results: At birth, 40 children (75.5%) were symptomatic and 13 (24.5%) asymptomatic. Neurodevelopmental comorbidities were present in 19 children (35.8%). MRI was normal in 15 (28.3%), mildly abnormal in 26 (49%), and moderately to severely abnormal in 12 (22.6%). Auditory and language outcomes improved significantly post-CI (p < 0.001), though the outcomes varied widely. Twenty-five children (47%) reached CAP level ≥ 6, and thirteen (23%) reached Bates Level 6. Symptomatic status at birth correlated weakly with worse CAP (ρ = −0.291, p = 0.038) and Bates (ρ = −0.310, p = 0.028) scores. Higher Alarcón scores were significantly associated with neurodevelopmental comorbidities, though not directly with post-CI auditory and language outcomes. Finally, the presence of neurodevelopmental disabilities was generally associated with lower results, even if without statistical significance. Conclusions: CI provides substantial auditory and language benefit in children with cCMV, even in cases of severe neurodevelopmental comorbidities. MRI and developmental assessments, as well as perinatal history for clinical signs and symptoms, are helpful in guiding expectations and personalizing post-implantation support. Full article

Indigenous people possess unique health literacy issues and challenges with preventing infectious diseases. This research assessed the baseline knowledge and misinformation in the Semai indigenous subgroup in Perak state, Malaysia, and the impact of a culturally adapted health education intervention. A single-group pre-test/post-test design was used with 156 participants ranging from 7 to 69 years old, predominantly children. The survey addressed key issues of head lice, intestinal parasites, tuberculosis (TB), handwashing, and germ transmission. An interactive, multi-station health education session in the local language produced a significant increase in overall knowledge (mean score increased from 3.17 to 3.83 out of 5, p < 0.0001), with the largest increase among the adult group aged 31–50 years. This was most notable for handwashing knowledge, which had the greatest increase, and misconceptions about intestinal worms and head lice remained. Differences in outcome by age suggest the need for targeted educational strategies, particularly for teenagers and elderly individuals who achieved less gain. The results support the effectiveness of culturally tailored, community-based health education in promoting the awareness of disease among indigenous communities. The drawbacks are convenience sampling, the child dominance of the sample, and the short-term follow-up. Future emphasis should be placed on long-term, community-based intervention using culturally tailored content and digital media. Full article

Platinum-induced ototoxicity constitutes a significant adverse effect in pediatric oncology, frequently resulting in permanent hearing impairment with profound implications for quality of life, language acquisition, and scholastic performance. This comprehensive review critically evaluates contemporary ototoxicity monitoring practices across various pediatric oncology settings, analyzes current guideline recommendations, and formulates strategies for implementing standardized surveillance protocols. Through examination of recent literature—encompassing retrospective cohort investigations, international consensus recommendations, and functional outcome assessments—we present an integrated analysis of challenges and opportunities in managing chemotherapy-associated hearing loss among childhood cancer survivors. Our findings demonstrate marked heterogeneity in monitoring methodologies, substantial implementation obstacles, and considerable impact on survivors’ functional status across multiple domains. Particularly concerning is the persistent absence of an evidence-based consensus regarding the appropriate duration of audiological surveillance for this vulnerable population. We propose a structured framework for comprehensive ototoxicity management emphasizing prompt detection, standardized assessment techniques, and integrated long-term follow-up care to minimize the developmental consequences of platinum-induced hearing impairment. This approach addresses critical gaps in current practice while acknowledging resource limitations across diverse healthcare environments. Full article

Artificial intelligence (AI)-powered mental health chatbots have evolved quickly as scalable means for psychological support, bringing novel solutions through natural language processing (NLP), mobile accessibility, and generative AI. This systematic literature review (SLR), following PRISMA 2020 guidelines, collates evidence from 25 published, peer-reviewed studies between 2020 and 2025 and reviews therapeutic techniques, cultural adaptation, technical design, system assessment, and ethics. Studies were extracted from seven academic databases, screened against specific inclusion criteria, and thematically analyzed. Cognitive behavioral therapy (CBT) was the most common therapeutic model, featured in 15 systems, frequently being used jointly with journaling, mindfulness, and behavioral activation, followed by emotion-based approaches, which were featured in seven systems. Innovative techniques like GPT-based emotional processing, multimodal interaction (e.g., AR/VR), and LSTM-SVM classification models (greater than 94% accuracy) showed increased conversation flexibility but missed long-term clinical validation. Cultural adaptability was varied, and effective localization was seen in systems like XiaoE, okBot, and Luda Lee, while Western-oriented systems had restricted contextual adaptability. Accessibility and inclusivity are still major challenges, especially within low-resource settings, since digital literacy, support for multiple languages, and infrastructure deficits are still challenges. Ethical aspects—data privacy, explainability, and crisis plans—were under-evidenced for most deployments. This review is different from previous ones since it focuses on cultural adaptability, ethics, and hybrid public health incorporation and proposes a comprehensive approach for deploying AI mental health chatbots safely, effectively, and inclusively. Central to this review, symmetry is emphasized as a fundamental idea incorporated into frameworks for cultural adaptation, decision-making processes, and therapeutic structures. In particular, symmetry ensures equal cultural responsiveness, balanced user–chatbot interactions, and ethically aligned AI systems, all of which enhance the efficacy and dependability of mental health services. Recognizing these benefits, the review further underscores the necessity for more rigorous academic research into the development, deployment, and evaluation of mental health chatbots and apps, particularly to address cultural sensitivity, ethical accountability, and long-term clinical outcomes. Full article

Background/Objectives: Rho-associated coiled-coil-containing protein kinase inhibitors (ROCKis) have now become known as modulators of corneal endothelial wound repair and cell survival. However, evidence remains fragmented across laboratory and clinical reports. We performed a systematic review to synthesize preclinical and clinical data on ROCKis in corneal disease, assess their efficacy and safety, and identify research gaps. Methods: We searched PubMed, Web of Science, Scopus, and Google Scholar (until May 2025) for English-language original studies evaluating ROCKis in corneal models or patients. Inclusion criteria encompassed in vitro, ex vivo, in vivo, and clinical trials reporting functional outcomes (endothelial cell density, wound closure, visual acuity). Results: Thirty-one studies met criteria: 14 preclinical studies and 17 clinical studies. Preclinical models (rabbit, porcine, human explants) uniformly showed ROCKis (Y-27632, Ripasudil, Netarsudil, H-1152) accelerate corneal endothelial cell proliferation, migration, and restoration of a hexagonal monolayer with improved barrier and pump function over days to weeks. In 17 clinical investigations, topical Ripasudil or Netarsudil and cultured cell injections achieved significant corneal thinning, endothelial cell density and central corneal thickness changes, and visual acuity improvements (≥2 lines) with minimal adverse events. Overall bias was moderate in non-randomized studies and low in the RCTs. Conclusions: ROCKis demonstrate consistent pro-regenerative effects on corneal endothelium in multiple models and show promising clinical efficacy in Fuchs endothelial dystrophy and pseudophakic endothelial failure. Future work should explore novel delivery systems and larger controlled trials to optimize dosing, safety, and long-term outcomes. Full article

Background: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are prevalent conditions with overlapping clinical features and shared consequences on autonomic function. Heart rate variability (HRV), a non-invasive biomarker of autonomic nervous system activity, may offer diagnostic, prognostic, and therapeutic insights in this patient population. Methods: A comprehensive literature review was conducted using PubMed, Google Scholar, and MEDLINE to identify peer-reviewed English-language studies published between January 2015 and December 2024. Studies were included if they evaluated HRV parameters in individuals with OSA, COPD, or overlap syndrome, explored HRV as a marker of disease severity or progression. A total of 239 studies were identified; after screening, 41 met the inclusion criteria. Results: The analysis revealed consistent evidence linking reduced HRV with both OSA and COPD severity. HRV alterations were more pronounced in overlap syndrome, reflecting synergistic autonomic dysfunction. HRV showed potential in differentiating disease stages, predicting cardiovascular risk, and evaluating treatment efficacy, particularly for CPAP therapy in OSA. Short-term HRV was particularly sensitive to autonomic changes, while long-term recordings helped track disease progression. Emerging evidence supports the use of HRV derived from wearable technologies as a viable screening tool for health and wellness. Conclusion: HRV is a valuable, non-invasive tool for assessing autonomic dysfunction in OSA, COPD, and their overlap. It offers significant potential for early diagnosis, disease monitoring, and treatment evaluation. Integrating HRV into clinical practice, could enhance diagnostic efficiency, reduce healthcare burden, and improve outcomes in high-risk respiratory populations. Furthermore, longitudinal studies are warranted to standardise HRV thresholds and validate their use in routine screening protocols. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with the multifaceted nature of addiction by targeting both peripheral metabolic and central reward pathways. This review focused on the current clinical trials and real-world evidence regarding the effects of GLP-1RAs as novel therapeutics for AUD. We also discussed early but encouraging results from clinical trials in AUD, observational and real-world evidence, safety profiles, psychiatric considerations, and future directions leading beyond GLP-1RAs. Methods: A comprehensive English-language literature search was conducted per PRISMA guidelines across PubMed, Medline, Google Scholar, Web of Science, and trial registries. Using targeted keywords, we identified relevant clinical and observational studies on GLP-1RAs for alcohol use disorder, excluding off-topic or non-English works and assessing all studies for eligibility. Results: Out of 1080 records identified, seven studies met the inclusion criteria. The findings from recent clinical trials, large-scale observational studies, and real-world evidence suggest that GLP-1RAs may significantly reduce alcohol consumption, cravings, and alcohol-related hospitalizations. Their central effect on reward processing, coupled with a generally favorable safety profile, supports their potential therapeutic role beyond metabolic disorders. Conclusions: Emerging evidence positions GLP-1RAs as a promising new pharmacologic approach for managing AUD. Ongoing and future research should prioritize larger, longer-duration randomized controlled trials that include diverse populations, with specific attention to treatment motivation, co-occurring psychiatric conditions, and long-term outcomes. Full article

Background: Chronic diseases significantly burden healthcare systems due to the need for long-term treatment. Early diagnosis is critical for effective management and minimizing risk. The current traditional diagnostic approaches face various challenges regarding efficiency and cost. Digitized healthcare demonstrates several opportunities for reducing human errors, increasing clinical outcomes, tracing data, etc. Artificial Intelligence (AI) has emerged as a transformative tool in healthcare. Subsequently, the evolution of Generative AI represents a new wave. Large Language Models (LLMs), such as ChatGPT, are promising tools for enhancing diagnostic processes, but their potential in this domain remains underexplored. Methods: This study represents the first systematic evaluation of ChatGPT’s performance in chronic disease prediction, specifically targeting heart disease and diabetes. This study compares the effectiveness of zero-shot, few-shot, and CoT reasoning with feature selection techniques and prompt formulations in disease prediction tasks. The two latest versions of GPT4 (GPT-4o and GPT-4o-mini) are tested. Then, the results are evaluated against the best models from the literature. Results: The results indicate that GPT-4o significantly beat GPT-4o-mini in all scenarios regarding accuracy, precision, and F1-score. Moreover, a 5-shot learning strategy demonstrates superior performance to zero-shot, few-shot (3-shot and 10-shot), and various CoT reasoning strategies. The 5-shot learning strategy with GPT-4o achieved an accuracy of 77.07% in diabetes prediction using the Pima Indian Diabetes Dataset, 75.85% using the Frankfurt Hospital Diabetes Dataset, and 83.65% in heart disease prediction. Subsequently, refining prompt formulations resulted in notable improvements, particularly for the heart dataset (5% performance increase using GPT-4o), emphasizing the importance of prompt engineering. Conclusions: Even though ChatGPT does not outperform traditional machine learning and deep learning models, the findings highlight its potential as a complementary tool in disease prediction. Additionally, this work provides value by setting a clear performance baseline for future work on these tasks Full article

In the evolving landscape of China’s capital markets, the integration of Environmental, Social, and Governance (ESG) considerations has become increasingly crucial for investors and decision-makers. Traditional financial performance metrics often fall short in capturing the multidimensional and long-term impacts of ESG factors. This study introduces a novel computational framework that combines domain-adapted pre-trained language models with structured financial regression analysis, aiming to empirically assess the correlation between ESG disclosures and long-term financial performance. This approach allows for the simultaneous processing of both structured and unstructured ESG data, using graph-based modeling and reinforcement learning to guide sustainability aligned policy optimization. Our empirical results show that firms with consistent and well-structured ESG strategies exhibit significantly superior long-term financial outcomes compared to those with weak or inconsistent ESG engagement. This study not only confirms the value of ESG engagement in enhancing financial resilience but also offers practical recommendations for investors, regulators, and corporate decision-makers, emphasizing consistent disclosure, sector-aligned ESG investment, and proactive adaptation to policy shifts. Full article