Search Results (155)

Fibrotic disorders pose a significant global health burden due to limited treatment options, creating an urgent need for novel therapeutic strategies. Amphiregulin (AREG), a low-affinity ligand for the epidermal growth factor receptor (EGFR), has emerged as a key mediator of fibrogenesis through dual signaling pathways. Unlike high-affinity EGFR ligands, AREG induces sustained signaling that activates downstream effectors and promotes the integrin-mediated activation of transforming growth factor (TGF)-β. This enables both canonical and non-canonical EGFR signaling pathways that contribute to fibrosis. Elevated AREG expression correlates with disease severity across multiple organs, including the lungs, kidneys, liver, and heart. The therapeutic targeting of AREG has shown promising antifibrotic and anticancer effects, suggesting a dual-benefit strategy. The increasing recognition of the shared mechanisms between fibrosis and cancer further supports the development of unified treatment approaches. The inhibition of AREG has been shown to sensitize fibrotic tumor microenvironments to chemotherapy, enhancing combination therapy efficacy. Targeted therapies, such as Self-Assembled-Micelle inhibitory RNA (SAMiRNA)-AREG, have demonstrated enhanced specificity and favorable safety profiles in preclinical studies and early clinical trials. Personalized treatment based on AREG expression may improve clinical outcomes, establishing AREG as a promising precision medicine target for both fibrotic and malignant diseases. This review aims to provide a comprehensive understanding of AREG biology and evaluate its therapeutic potential in fibrosis and cancer. Full article

Aortic stenosis (AS), the most common valvular heart disease, is traditionally graded based on several echocardiographic quantitative parameters, such as aortic valve area (AVA), mean pressure gradient (MPG), and peak jet velocity (Vmax). This systematic review evaluates the clinical significance and prognostic implications of discordant high-gradient AS (DHG-AS), a distinct hemodynamic phenotype characterized by elevated MPG despite a preserved AVA (>1.0 cm²). Although often overlooked, DHG-AS presents unique diagnostic and therapeutic challenges, as high gradients remain a strong predictor of adverse outcomes despite moderately reduced AVA. Sixty-three studies were included following rigorous selection and quality assessment of the key studies. Prognostic outcomes across five key studies were discrepant: some showed better survival in DHG-AS compared to concordant high-gradient AS (CHG-AS), while others reported similar or worse outcomes. For instance, a retrospective observational study including 3209 patients with AS found higher mortality in CHG-AS (unadjusted HR: 1.4; 95% CI: 1.1 to 1.7), whereas another retrospective multicenter study including 2724 patients with AS observed worse outcomes in DHG-AS (adjusted HR: 1.59; 95% CI: 1.04 to 2.56). These discrepancies may stem from delays in intervention or heterogeneity in study populations. Despite the diagnostic ambiguity, the presence of high gradients warrants careful evaluation, aggressive risk stratification, and timely management. Current guidelines recommend a multimodal approach combining echocardiography, computed tomography (CT) calcium scoring, transesophageal echocardiography (TEE) planimetry, and, when needed, catheterization. Anatomic AVA assessment by TEE, CT, and cardiac magnetic resonance imaging (CMR) can improve diagnostic accuracy by directly visualizing valve morphology and planimetry-based AVA, helping to clarify the true severity in discordant cases. However, these modalities are limited by factors such as image quality (especially with TEE), radiation exposure and contrast use (in CT), and availability or contraindications (in CMR). Management remains largely based on CHG-AS protocols, with intervention primarily guided by transvalvular gradient and symptom burden. The variability among the different guidelines in defining severity and therapeutic thresholds highlights the need for tailored approaches in DHG-AS. DHG-AS is clinically relevant and associated with substantial prognostic uncertainty. Timely recognition and individualized treatment could improve outcomes in this complex subgroup. Full article

Background: Community-acquired bacterial pneumonia (CABP) is a common and costly cause of hospitalization. Although severe CABP (sCABP) occurs in 10–25% of all pneumonia hospitalizations, little generalizable data examine its characteristics and outcomes or hospital resource utilization. Methods: We conducted a retrospective single-group cohort study of adults within the IQVIA hospital Charge Data Master, 2018–2022. We identified CABP via an ICD-10 code algorithm and sCABP was defined as an episode requiring ICU care. We examined baseline characteristics and outcomes, including mortality, costs, and readmission rates. We developed models to identify risk factors associated with readmissions. Results: Among 24,149 patients with sCABP, 14,266 (58.4%) were ≥65 years old and 55.2% were male. The majority were hospitalized in large (300+ beds, 50.9%), urban (91.9%) teaching (62.7%) institutions in the US Southern region (52.3%). The mean (SD) Charlson Comorbidity Index was 1.35 (2.33). The most common comorbidities were hypertension (16.7%), diabetes mellitus (15.7%), and chronic obstructive pulmonary disease (COPD) (12.9%). Hospital mortality was 15.9%. The mean (SD) hospital length of stay (LOS) and costs were 13.6 (12.1) and USD 91,965 (USD 133,734), respectively. An amount of 20% required a readmission within 30 days. Readmission was most strongly associated with older age and the presence of select comorbidities (diabetes mellitus, congestive heart failure, and COPD), each with an odds ratio > 1.4 and 95% confidence intervals excluding 1.0. Conclusions: Patients with sCABP comprise a large population with high mortality and 30-day readmissions. The intrinsic factors related to the latter lend themselves to early recognition and aggressive efforts at reducing complications. Full article

Blood pressure is a vital indicator of cardiovascular health and plays a crucial role in the early detection and management of heart-related diseases. However, current practices for recording blood pressure readings are still largely manual, leading to inefficiencies and data inconsistencies. To address this challenge, we propose a deep learning-based method for automated digit recognition and measurement-type classification (systolic, diastolic, and pulse) from images of blood pressure monitors. A total of 2147 images were collected and expanded to 3649 images using data augmentation techniques. We developed and trained three YOLOv8 variants (small, medium, and large). Post-training quantization (PTQ) was employed to optimize the models for edge deployment in a mobile health (mHealth) application. The quantized INT8 YOLOv8-small (YOLOv8s) model emerged as the optimal model based on the trade-off between accuracy, inference time, and model size. The proposed model outperformed existing approaches, including the RT-DETR (Real-Time DEtection TRansformer) model, achieving 99.28% accuracy, 96.48% F1-score, 641.40 ms inference time, and a compact model size of 11 MB. The model was successfully integrated into the mHealth application, enabling accurate, fast, and automated blood pressure tracking. This end-to-end solution provides a scalable and practical approach for enhancing blood pressure monitoring via an accessible digital platform. Full article

Early detection and the rise of targeted cancer treatment have led to increased overall survival and decreased mortality among cancer patients. As the cancer survivor population ages, there is an increased risk for cardiovascular disease due to pre-existing comorbidities, deconditioning during therapy, or the natural progression of aging. Furthermore, with emerging oncologic therapies, there is an increased recognition of their potential cardiovascular toxicities. Indeed, heart disease is the leading cause of death in cancer survivors, which may reflect upon both the success of novel oncologic therapies and their potential cardiovascular toxicities. This recognition has driven the development of cardio-oncology, a multi-disciplinary field that involves collaboration between hematologists, oncologists, and cardiologists to screen, prevent, and manage cardiovascular disease in cancer patients and cancer survivors. The field focuses on early cardiovascular detection and prevention for these patients before, during, and after their oncologic treatment. As oncologic therapies evolve and our knowledge of short- and long-term adverse cardiovascular effects grows, it is critical for physicians to identify those at risk for increased morbidity and mortality, while also balancing the importance of their oncologic treatment plan. Multimodality cardiac imaging is the crux of the diagnosis and surveillance of these patients within cardio-oncology, and includes echocardiography, nuclear, computed tomography (CT), and cardiac magnetic resonance (CMR). Cardiac imaging is essential to establish the baseline function and assess various cardiotoxicities, including left ventricular dysfunction, heart failure, atherosclerosis, vascular injury, and arrhythmias. This review will discuss common oncologic therapies and their cardiotoxic profiles, the cardiac multimodality imaging modalities used in cardio-oncology, and the various approaches for the diagnosis and surveillance of this population. Full article

Systemic lupus erythematosus (SLE) is a pleiotropic disease that can present in numerous forms, ranging from mild mucocutaneous symptoms to severe manifestations affecting multiple organs. SLE has the potential to impact any segment of the respiratory system, exhibiting a range of severity levels throughout the different stages of the disease. Pulmonary manifestations in SLE patients can be classified as primary (i.e., directly related to SLE and to immune-mediated damage), secondary to other SLE manifestations (e.g., nephrotic syndrome, renal failure, congestive heart failure), and comorbidities (e.g., infections, cancers, overlapping primary respiratory diseases). Understanding and correctly managing lung involvement in SLE is crucial because pulmonary complications are common and can significantly impact morbidity and mortality in affected patients. Early recognition and appropriate treatment can prevent irreversible lung damage, improve quality of life, and reduce the risk of life-threatening complications. Treatment algorithms are based on the suppression of inflammation, with or without the need for dedicated, supportive care. According to disease severity, available treatments include nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants, and biological agents. In this review, we aim to summarize the current knowledge on lung involvement in SLE and then focus on the management and treatment approaches available for the different forms. Full article

Background: Activities of Daily Living (ADLs) are essential tasks performed at home and used in healthcare to monitor sedentary behavior, track rehabilitation therapy, and monitor chronic obstructive pulmonary disease. The Barthel Index, used by healthcare professionals, has limitations due to its subjectivity. Human activity recognition (HAR) is a more accurate method using Information and Communication Technologies (ICTs) to assess ADLs more accurately. This work aims to create a singular, adaptable, and heterogeneous ADL dataset that integrates information from various sources, ensuring a rich representation of different individuals and environments. Methods: A literature review was conducted in Scopus, the University of California Irvine (UCI) Machine Learning Repository, Google Dataset Search, and the University of Cauca Repository to obtain datasets related to ADLs. Inclusion criteria were defined, and a list of dataset characteristics was made to integrate multiple datasets. Twenty-nine datasets were identified, including data from various accelerometers, gyroscopes, inclinometers, and heart rate monitors. These datasets were classified and analyzed from the review. Tasks such as dataset selection, categorization, analysis, cleaning, normalization, and data integration were performed. Results: The resulting unified dataset contained 238,990 samples, 56 activities, and 52 columns. The integrated dataset features a wealth of information from diverse individuals and environments, improving its adaptability for various applications. Conclusions: In particular, it can be used in various data science projects related to ADL and HAR, and due to the integration of diverse data sources, it is potentially useful in addressing bias in and improving the generalizability of machine learning models. Full article

Background: Physical activity is vital for promoting health and rehabilitation, and ensuring cardiovascular safety during such activities is paramount. Electrocardiography (ECG) and its longitudinal monitoring remain crucial for the early detection of cardiac diseases. Recent advancements in nonlinear RR analysis and machine learning offer promising approaches to identifying subtle precursors of cardiac pathologies in monitoring systems using simple heart rate (HR) wearable sensors. Therefore, using HR sensors in human activity recognition (HAR) is recommendable. After defining fatigue in a cardiological context, and focusing on an AI-based methods suite for HAR, the main research question of this scoping review is as follows: “Can RR time series be successfully used as physiological biomarkers for the early detection of cardiac fatigue?” The reported data on assessment of fatigue are focused on the last two decades. The aim of this scoping review was to collect, present and discuss the existing literature on the effectiveness of AI-based methods for processing RR time series as a predictive biomarker for cardiac fatigue compared to commonly used questionnaires for this outcome in adult populations. Methods: Queries were conducted in the PubMed, Scopus and Google Scholar databases for the time period 2005–2025. Only research articles and review papers were considered suitable candidates. Results: Data from 10 papers were considered, related to the information researched. Conclusions: Information on HRV-based objective measures is quite scarce and there is an urgent need to adopt a multidisciplinary approach and to improve advanced AI-based nonlinear analyses to differentiate cardiac physiological status from cardiac pathological status. Full article

Chagas disease (CD) is endemic in Latin America, with its pathogenesis linked to Trypanosoma cruzi (Tc) persistence and autoimmune responses. This study investigates the role of LINE-1 (L1) activation in inflammation and loss of self-tolerance during Tc infection. In vitro assays evaluated the expression of genes involved in L1 regulation and interferon signaling under basal conditions and following L1 suppression via CRISPR/dCas9. In vivo analyses in a murine model included L1 and IFN expression profiling, autoantibody quantification, and histopathological assessments of liver, spleen, intestine, and heart. Tc infection induced L1 upregulation, correlating with an increased expression of its inhibitors, MOV-10 and APOBEC-3, suggesting host-driven regulatory mechanisms. L1 activation was also associated with the upregulation of DNA repair pathways (MMR and NHEJ) and RNA-sensing pathways (MDA-5 and RIG-I), leading to type I interferon responses. In the murine model, L1 expression was highest in the intestine and heart, independent of parasite burden, and correlated with increased interferon gene expression and autoantibody production. Our findings suggest that CD pathogenesis involves L1-induced chronic inflammation, which may contribute to late-stage symptoms. This highlights self-recognition mechanisms in disease severity and reveals potential therapeutic targets for novel treatments. Full article

Diuretics are a class of pharmacological agents that promote the renal excretion of water and electrolytes, increasing urine output and reducing fluid retention. They play a critical role in the management of edematous syndromes, irrespective of their etiology (cardiac, renal, or hepatic), as well as in the treatment of hypertension (HTA). The mechanism of action of diuretics can be classified as either renal, as seen with saluretic diuretics that inhibit sodium and water reabsorption at various segments of the nephron, or extrarenal, involving alterations in the glomerular filtration pressure or osmotic mechanisms. Based on their site of action and mechanism, diuretics are categorized into multiple classes, including loop diuretics, thiazide and thiazide-like diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, and osmotic diuretics. These agents are frequently used in combination with other antihypertensive or heart failure medications to optimize therapeutic efficacy. By reducing the blood volume and peripheral vascular resistance, diuretics improve cardiac function, lower blood pressure, and enhance exercise tolerance. Additionally, they are employed in managing chronic kidney disease (CKD), electrolyte imbalances, and specific metabolic disorders. Given the potential for adverse effects such as electrolyte disturbances and renal dysfunction, diuretic therapy should be individualized, with the careful monitoring of the dosage, patient response, and comorbid conditions. Patient education on adherence, lifestyle modifications, and the recognition of side effects is essential for optimizing the therapeutic outcomes and minimizing the risks associated with diuretic therapy. Full article

Secondary dilated cardiomyopathy (DCM) refers to left ventricular dilation and impaired systolic function arising from identifiable extrinsic causes, such as ischemia, hypertension, toxins, infections, systemic diseases, or metabolic disorders. Unlike primary DCM, which is predominantly genetic, secondary DCM represents a diverse spectrum of pathophysiological mechanisms linked to external insults on myocardial structure and function. The increasing prevalence of conditions such as alcohol use disorder, chemotherapy-induced cardiotoxicity, and viral myocarditis underscores the need for heightened awareness and early recognition of secondary DCM. A comprehensive analysis of clinical trial data and observational studies involving secondary dilative cardiomyopathy was conducted, with a focus on mortality, symptom relief, and major adverse events. A systematic literature review was performed using databases, including PubMed, Embase, and ClinicalTrials.gov, following PRISMA guidelines for study selection. Data were extracted on patient demographics, etiology of dilation, trial design, outcomes, and follow-up duration. Advances in diagnostic modalities have refined the ability to identify underlying causes of secondary DCM. For example, high-sensitivity troponin and cardiac magnetic resonance imaging are pivotal in diagnosing myocarditis and differentiating it from ischemic cardiomyopathy. Novel insights into toxin-induced cardiomyopathies, such as those related to anthracyclines and immune checkpoint inhibitors, have highlighted pathways of mitochondrial dysfunction and oxidative stress. Treatment strategies emphasize the management of the causing condition alongside standard heart failure therapies, including RAAS inhibitors and beta-blockers. Emerging therapies, such as myocardial recovery protocols in peripartum cardiomyopathy and immune-modulating treatments in myocarditis, are promising in reversing myocardial dysfunction. Secondary DCM encompasses a heterogeneous group of disorders that require a precise etiological diagnosis for effective management. Timely identification and treatment of the underlying cause, combined with optimized heart failure therapies, can significantly improve outcomes. Future research focuses on developing targeted therapies and exploring the role of biomarkers and precision medicine in tailoring treatment strategies for secondary DCM. Full article

The recognition and treatment of scabies has been incorporated into Australian guidelines for the prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). The incidence of both diagnosed ARF and RHD is increasing in Far North Queensland (FNQ) in northeast tropical Australia, but the local burden of scabies is incompletely defined. We reviewed the results of every skin scraping collected in FNQ’s public health system between 2000 and 2023; 121/4345 (2.8%) scrapings were positive, including 19/1071 (1.8%) in the last 5 years of the study; the proportion of scrapings that were positive for scabies declined over the study period. Individuals who tested positive for scabies were no more likely to have had a prior diagnosis of ARF or RHD compared to the matched controls (1/101 (1%) versus 3/101 (3%), p = 1.0). During a median of 14.7 years of follow-up, individuals who tested positive for scabies were also no more likely to have a diagnosis of ARF or RHD than matched controls (2/100 (2%) versus 6/98 (6%); hazard ratio (95% confidence interval): 0.30 (0.06–1.50) p = 0.14). Microbiologically confirmed scabies is uncommon in FNQ and appears to make a limited contribution to the local incidence of ARF and RHD. Full article

Background: High-intensity interval training (HIIT) has gained recognition for its positive impacts on cardiovascular (CV) health, metabolic outcomes, mental health, and quality of life (QoL). This narrative review aims to comprehensively evaluate the efficacy of HIIT in enhancing CV health and preventing CV disease (CVD). Methods: A comprehensive search of PubMed identified 257 articles, of which 39 studies met predefined inclusion and exclusion criteria for quality assessment. Key metrics evaluated included blood pressure, vascular function, lipid profiles, body composition, and CRF. Results: HIIT significantly improved vascular function, evidenced by reductions in systolic and diastolic blood pressure and enhanced flow-mediated dilation. Improvements in cardiac function were observed through increased cardiac output and heart rate variability. Additionally, HIIT positively influenced lipid profiles, decreasing low-density lipoprotein and triglycerides while increasing high-density lipoprotein. Significant reductions in body fat and improvements in VO₂peak were noted, contributing to enhanced CRF. HIIT also positively impacted mental health and QoL, reducing anxiety and depressive symptoms. Importantly, HIIT was safely and effectively applied to high-risk populations—individuals with obesity, metabolic syndrome, CVD, and cancer survivors—with a low incidence of adverse effects. Conclusions: This review highlights HIIT as an effective and safe exercise modality for improving CV health, metabolic indicators, mental health, and QoL. Future research should focus on developing tailored HIIT protocols to optimize adherence and efficacy across diverse populations, considering variations in age, sex, health status, and underlying medical conditions. Full article

Background/Objectives: Fecal calprotectin (FC) is a biomarker of intestinal inflammation widely used in the assessment of gastrointestinal disorders. However, its role in chronic kidney disease (CKD) remains unclear. Given the growing recognition of the gut–kidney axis in CKD pathophysiology, this study aimed to investigate the association between FC levels, systemic inflammation, renal outcomes, and mortality in CKD patients. Methods: We enrolled a total of 515 CKD patients who underwent fecal calprotectin measurement between 2016 and 2023. After applying the exclusion criteria (inflammatory bowel disease, ongoing renal replacement therapy, or incomplete laboratory data), 260 patients were included in the final analysis and stratified into low-FC (<102 μg/g, n = 130) and high-FC (≥102 μg/g, n = 130) groups based on the median FC value. Factors associated with kidney disease progression and patient survival were analyzed. Results: Patients in the high-FC group (≥102 μg/g) were significantly older (72.8 ± 14.63 vs. 64.02 ± 18.15 years, p < 0.0001) and had a higher prevalence of diabetes mellitus (55.38% vs. 42.31%, p = 0.0349), heart failure (21.54% vs. 7.69%, p = 0.0016), and history of acute kidney injury (33.85% vs. 18.46%, p = 0.0048). Elevated FC was independently associated with increased mortality risk (hazards ratio [HR] 1.658, 95% confidence interval [CI] 1.034–2.658, p = 0.0357) with higher mortality rates (48.36 vs. 18.46 per 100,000 person-years). Subgroup analyses revealed stronger associations between FC and mortality in males (HR 2.160, 95% CI 1.046–4.463, p = 0.0375), elderly patients (≥75 years) (HR 2.122, 95% CI 1.209–3.725, p = 0.0088), and non-diabetic patients (HR 2.487, 95% CI 1.141–5.421, p = 0.0219). While FC was not significantly associated with end-stage kidney disease (ESKD) progression (odds ratio [OR] 1.289, 95% CI 0.455–3.650, p = 0.6323), higher FC levels paradoxically predicted slower estimated glomerular filtration rate (eGFR) decline (OR 2.763, 95% CI 1.139–6.699, p = 0.0245). Combined analysis revealed patients with both elevated FC and high-sensitivity C-reactive protein (hs-CRP) had the highest mortality risk (HR 3.504, 95% CI 1.163–10.554, p < 0.0001) compared to those with low levels of both markers. Conclusions: FC is a potential prognostic biomarker for mortality in CKD patients, independently of traditional inflammatory markers. Further research is warranted to elucidate the mechanisms underlying its paradoxical relationship with renal outcomes and its potential role in risk stratification and therapeutic targeting in CKD. Full article

Study Objectives: This review aims to explore the epidemiology, pathophysiology, risk factors, and diagnostic approaches of obstructive sleep apnea syndrome and small airway disease, emphasizing their interrelationship and implications for clinical management. Methods: A comprehensive analysis of the literature was conducted to examine shared and distinct characteristics of obstructive sleep apnea syndrome and small airway disease. Risk factors, clinical presentations, diagnostic tools, and management strategies were reviewed to identify potential areas for improvement in care. Results: Obstructive sleep apnea syndrome, characterized by intermittent upper airway obstruction during sleep, contributes to fragmented sleep and systemic diseases. Small airway disease involves inflammation and obstruction of the small airways, impairing airflow and gas exchange. Shared risk factors, such as obesity, smoking, and age, were identified as contributors to the development and progression of both conditions. The co-occurrence of obstructive sleep apnea syndrome and small airway disease exacerbates respiratory symptoms and increases the risk of comorbidities, such as pulmonary hypertension, heart failure, and respiratory failure. Recognition of their interplay highlights the need for integrated diagnostic and therapeutic strategies. Conclusions: The interrelationship between obstructive sleep apnea syndrome and small airway disease underscores the importance of integrated management approaches to improve patient outcomes. Addressing shared risk factors and understanding the interplay between these conditions are crucial for optimizing care. This review identifies key knowledge gaps, including the need for precise diagnostic tools and targeted therapies, which are essential for advancing personalized treatment strategies for individuals with obstructive sleep apnea syndrome and small airway disease. Full article