Search Results (41)

Background: Endothelial dysfunction and renal injury are emerging as a common feature of long COVID, especially in those with hypertension. It is not yet well characterised whether SARS-CoV-2 infection exacerbates podocyte dysfunction, fibrotic signalling and renal hemodynamic remodelling, over and above the effects of hypertension alone and there are no reliable early biomarkers in this population. Methods: We conducted a comparative cross-sectional study with prospective 6-month treatment response follow-up in 120 adult patients (aged 30–60 years) with essential hypertension (Stage I, II or III; n = 40 per stage), at Bukhara Regional Multidisciplinary Hospital. Each stage subgroup was further divided into post-COVID (3–6 months after recovery; n = 20) and non-COVID (n = 20) strata. Patients with diabetes, known chronic kidney disease, previous myocardial infarction or stroke and other major comorbidities were excluded. Serum cystatin-C, creatinine, aldosterone, TGF-β1 and VEGF-A; urinary nephrin and microalbumin; cystatin-C-derived eGFR (CKD-EPI) and oral protein-loaded renal functional reserve (RFR); and renal Doppler indices (Vps, Ved, RI, PI) of the main, segmental and interlobar arteries were assessed before and after 6 months of guideline-based renin–angiotensin–aldosterone system (RAAS) blockade (enalapril 5–10 mg or azilsartan 40–80 mg, ±eplerenone). Comparisons were made by Student’s t-test—associations by Pearson correlation. Results: At baseline, post-COVID hypertensive patients exhibited consistently higher endothelial–podocyte injury markers than non-COVID counterparts. Urinary nephrin was elevated across all stages (Stage I: 126.5 ± 9.1 vs. 91.9 ± 8.3 pg/mL, p < 0.01; Stage III: 203.3 ± 11.2 vs. 164.5 ± 9.7 pg/mL, p < 0.05), as were VEGF-A (Stage III: 286.1 ± 16.4 vs. 223.2 ± 12.6 pg/mL, p < 0.01) and TGF-β1 (Stage III: 186.4 ± 10.1 pg/mL, 1.3-fold higher; p < 0.01). The detection of microalbuminuria was 100% in Stage III post-COVID patients and 85% in non-COVID controls. The post-COVID groups had selective loss of renal functional reserve (7.8 ± 1.1% in Stage III compared to 12.5 ± 1.6% in non-COVID controls, p < 0.001). Nephrinuria correlated strongly with RFR (r = −0.824, p < 0.001), eGFR (r = −0.797, p < 0.001) and aldosterone (r = 0.613, p < 0.001). Six months of RAAS blockade reduced nephrinuria, microalbuminuria and TGF-β1 in both arms but the magnitude of biomarker reduction appeared smaller in the post-COVID group, particularly in Stage III. Conclusions: Long COVID appears to be associated with persistent endothelial dysfunction and podocyte injury in hypertensive patients. These results indicate that nephrinuria, VEGF-A, TGF-β1 and renal functional reserve are potential exploratory markers of endothelial and renal abnormalities in hypertensive patients following COVID-19. Before clinical utility can be determined, larger studies with multivariable modelling, diagnostic-performance analyses and correction for multiple testing are needed. The differences in biomarker response between groups observed in this study need to be confirmed in larger prospective studies with multivariable modelling and formal interaction analyses. Full article

Selenium (Se) is an essential micronutrient required for redox regulation and metabolic homeostasis. Altered biomarkers of Se status have been linked with obesity and metabolic syndrome, yet its role in these conditions, particularly in a sex-specific context, is not well defined. This study investigated the impact of suboptimal Se intake on metabolic risk profiles in male and female mice with pre-existing diet-induced obesity. C57BL/6N mice were fed either a standard diet with adequate Se (SD-ASe), a Western diet with adequate Se (WD-ASe), or WD-ASe followed by a Western diet containing suboptimal Se levels (WD-SOSe). Metabolic parameters, adipokine profiles, tissue Se distribution, and gene expression in visceral white adipose tissue (vWAT) were assessed. Both sexes exhibited increased weight gain and adiposity in response to a Western diet; however, only males developed hypertension and elevated non-fasted blood glucose levels. Suboptimal Se intake elicited marked sex-dependent effects. In females, it induced elevated non-fasted blood glucose levels and circulating leptin, and further dysregulated circulating adipokine profiles, accompanied by pronounced alterations in selenoprotein expression and redox-related pathways in vWAT. In contrast, male mice exhibited a partial adaptation, including reduced glucose levels and minimal alterations in gene expression. Tissue Se distribution also appeared to be influenced by biological sex. These findings demonstrate that suboptimal Se intake may exacerbate obesity-related metabolic dysfunction in a sex-specific manner, with females showing greater susceptibility, underscoring the importance of micronutrient status and sex differences in metabolic disorders. Full article

Background: Maternal mortality remains a major global health challenge, disproportionately affecting black and Indigenous women. Hypertensive disorders of pregnancy and postpartum hemorrhage are the leading direct causes of maternal death. Artificial intelligence (AI) tools have emerged as potential strategies for predicting these complications, yet concerns persist about their equity and validation across racial groups. Methods: A rapid review was conducted in five databases, PubMed, EMBASE, Web of Science, Scopus and LILACS, to synthesize recent evidence on the use of AI for preventing maternal mortality due to hypertension and postpartum hemorrhage. Studies published in the last five years that included racial or ethnic data were selected and analyzed narratively. Results: Ten studies met the inclusion criteria, showing high predictive accuracy of AI models (AUROC often >0.95) for severe maternal outcomes. However, few models incorporated racial variables or underwent external validation in racially diverse or low-resource populations. Evidence suggests that unrepresentative datasets may perpetuate or exacerbate existing health inequities. Conclusions: AI demonstrates strong technical performance in predicting maternal complications but limited equity in application. Broader racial representation, external validation, and ethical governance are essential for ensuring that AI-based tools reduce rather than reinforce racial disparities in maternal mortality. Full article

Background: Right heart failure (HF) and tricuspid regurgitation (TR) are closely interrelated conditions, linked by a bidirectional and self-perpetuating pathophysiological relationship. Alterations in right-ventricular (RV) loading conditions, pulmonary vascular impedance, and ventriculo-arterial (VA) coupling play a central role in the development and progression of TR, which in turn exacerbates RV volume overload and end-organ dysfunction. Methods: This review provides a comprehensive overview of the pathophysiology of right HF and TR, focusing on the mechanisms underlying RV dysfunction, pressure–volume (PV) relationships, and pulmonary vascular load. We further examine the clinical implications of this interaction and summarize current strategies for risk stratification, with particular emphasis on disease-specific risk models. Results: TR emerges both as a consequence and a driver of RHF. Conditions such as pulmonary hypertension (PH) and left-sided heart disease promote annular dilation and leaflet tethering, leading to functional TR. Conversely, TR increases RV volume overload, worsening chamber dilation, reducing effective forward stroke volume (SV), and accelerating disease progression. This vicious cycle results in progressive RV impairment, impaired left-ventricular filling through ventricular interdependence, and systemic venous congestion affecting renal and hepatic function. Traditional risk scores fail to capture this complex pathophysiology. In this context, TRISCORE integrates clinical, biological, and echocardiographic (TTE) parameters reflecting RV dysfunction and systemic involvement, providing a more comprehensive assessment of disease severity and prognosis. Conclusions: TR should be considered not only a marker but also a key determinant of right HF progression. A multiparametric approach integrating pathophysiology and disease-specific risk stratification is essential to identifying the optimal therapeutic window and guiding clinical decision making. Full article

Background and Clinical Significance: Vascular lesions of the face, particularly arteriovenous malformations (AVM) and mixed hemangiomas (MH), pose significant diagnostic and therapeutic challenges because of their complex anatomy, unpredictable behavior, and high risk of bleeding. Surgical planning should be individualized and often requires a staged approach with meticulous interdisciplinary coordination to ensure patient safety. The presence of a concomitant odontogenic infection further complicates management, as local inflammation may exacerbate vascular instability and increase the risk of life-threatening complications. Local inflammation and infection might cause some life-threatening conditions, especially when an abscess occurs in the area of any vascular lesion. Ensuring that the oral cavity is free from potential odontogenic infections is a particularly important issue in many complex cases, especially in patients treated for oral, head, and neck cancer or in those with other coexisting morbidities affecting the oral and facial regions. Case Presentation: A 72-year-old man was referred for management of a severe odontogenic infection associated with an extensive facial vascular lesion. The patient’s medical history was significant for arterial hypertension and chronic liver dysfunction (CLD) of unclear etiology. Complete blood testing, including coagulation assessment and liver ultrasonography, was performed, with no contraindication to surgery identified. The scope of odontogenic-related infections was scheduled for simultaneous removal during initial surgery. Preparation for surgery included the local application of sclerotherapy agents. Conclusions: Quite often, a routine panoramic radiograph can help in assessing the status of bone and dentition to undertake all necessary treatment. Severe odontogenic disease, including multiple retained roots, periapical infections, and odontogenic cystic lesions in the context of poor oral hygiene, may lead to the occurrence of possible inflammation. In case of any vascular lesion, a careful diagnostic and therapeutic strategy is needed. This case report highlights that maintaining an infection-free oral environment is a critical component of care in patients with complex facial MH and should be regarded as an essential element of overall treatment planning. Full article

Nitric oxide (NO) functions as a master integrative regulator of cardiovascular–kidney–metabolic (CKM) homeostasis, yet it displays a profound Janus face, defined by concentration- and context-dependent roles in both health and disease. This narrative review examines NO signaling from a life-course perspective, beginning with fetal programming, during which the NO–asymmetric dimethylarginine (ADMA) axis orchestrates placental development and nephron endowment. Perturbations during this critical window—such as maternal ADMA elevation—can imprint a maladaptive trajectory toward adult-onset hypertension and chronic kidney disease. In adulthood, this initially silent dysregulation of NO signaling is amplified by Western dietary patterns and environmental pollutants, culminating in the clinical manifestation of the CKM triad. This pathological transition is driven by eNOS uncoupling and ADMA accumulation, which shift redox balance toward peroxynitrite formation and precipitate mitochondrial bioenergetic failure. Moreover, while constitutive NO production is essential for vascular homeostasis, pathological induction of inducible NOS generates excessive NO fluxes that promote insulin resistance and tissue injury. With advancing age, a progressive loss of NO resilience further exacerbates multi-organ vulnerability. To mitigate the cumulative burden of CKM disease, this review highlights developmental reprogramming strategies—such as perinatal L-citrulline supplementation and ADMA-lowering interventions—as interventions to restore physiological NO signaling. Integrating such early-life strategies with contemporary pharmacological therapies offers a coherent framework for maintaining NO bioavailability and extending health span across the life course. Full article

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Arterial hypertension represents the leading modifiable risk factor for cardiovascular morbidity and mortality globally. Their coexistence is frequent, affecting approximately 40–60% of adults with HCM, yet the implications of this overlap remain insufficiently investigated. Methods: We conducted a narrative review of the existing literature addressing the clinical profile and management strategies in patients with concomitant HCM and hypertension. Particular emphasis was placed on pharmacologic treatment and the role of emerging therapies for this population. Results: Patients with both conditions are generally older, with more cardiometabolic comorbidities and greater functional limitation than those with isolated HCM. Hypertension may confound diagnosis and is linked to a higher prevalence of atrial fibrillation and stroke. Its effect on ventricular arrhythmias, sudden cardiac death and mortality is less clear. Management is challenging, as vasodilatory antihypertensives can exacerbate left ventricular outflow tract obstruction. β-blockers and non-dihydropyridine calcium channel blockers are preferred, while novel agents such as myosin inhibitors and SGLT2 inhibitors show potential but require further study. Conclusions: The coexistence of HCM and hypertension is frequent but insufficiently studied, with major implications for diagnosis and treatment. Further research is essential to optimize management and outcomes. Full article

Preeclampsia (PE) is an obstetric disorder with significant risks to both maternal and fetal health, characterized by hypertension and multi-organ dysfunction. Central to its pathogenesis is the impaired differentiation and function of trophoblast cells, leading to abnormal placental development and defective uterine vascular remodeling. This dysfunctional placentation triggers a cascade of oxidative stress, systemic inflammation, and immune dysregulation, collectively exacerbating disease severity. The trophoblast regulates maternal–fetal interactions through complex and tightly controlled gene expression networks, in which non-coding RNAs such as microRNAs (miRNAs) and circular RNAs (circRNAs) play essential regulatory roles. Here, we summarize current findings on transcriptomic alterations associated with trophoblast anomalies in PE and discuss their potential translational applications. Understanding these molecular mechanisms may enhance early diagnosis, improve clinical outcomes, and pave the way for precision medicine and individualized therapeutic strategies in PE. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and atrial fibrillation (AF) are two highly prevalent conditions that share overlapping cardiometabolic risk factors, including obesity, type 2 diabetes, hypertension, and dyslipidemia. Growing evidence suggests that these two disease entities are pathophysiologically linked through systemic inflammation, oxidative stress, and structural remodeling. Population-based studies and meta-analyses report an association between steatotic liver disease and both incident and recurrent AF. While several analyses observe persistence of this association after adjustment for cardiometabolic risk factors, residual confounding and limitations of observational designs preclude firm causal inference. Conversely, heart rhythm disturbances may exacerbate hepatic fibrosis and dysfunction. Lifestyle interventions—particularly sustained weight loss—have demonstrated significant benefits in both conditions. Emerging pharmacological options, including incretin mimetics, flozins, statins, and thiazolidinediones, show promise in addressing the liver–heart axis, while appropriate anticoagulation remains essential in AF management. This review summarizes current epidemiological data, mechanistic insights, diagnostic approaches, and therapeutic strategies related to the coexistence of MASLD and AF. Emphasis is placed on shared pathogenic pathways, non-invasive diagnostic tools, and integrated management options. Full article

Background: Combined Pulmonary Fibrosis and Emphysema (CPFE) is a distinct syndrome characterized by upper-lobe emphysema and lower-lobe fibrosis, predominantly in older male smokers. Despite often preserved spirometric volumes, patients exhibit severely reduced diffusing capacity and high susceptibility to complications, including pulmonary hypertension (PH), acute exacerbations, and lung cancer, contributing to poor prognosis. Purpose: This review aims to synthesize current evidence on CPFE, focusing on clinical phenotype, functional impairment, differential diagnosis, complications, and emerging management strategies, highlighting distinctions from idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Methods: A narrative review of observational cohorts, retrospective series, and clinical studies examining CPFE patients was performed. Data on demographics, smoking history, symptomatology, pulmonary function, radiology, comorbidities, complications, and treatment approaches were extracted and integrated. Results: CPFE affects mainly males aged 65–70, with >90% reporting > 40 pack–years smoking history. Dyspnea is the cardinal symptom (>95%), often disproportionate to preserved FVC and TLC, accompanied by chronic cough in 30–70%. Exercise-induced desaturation is frequent, correlating with PH, observed in 47–90% of patients. Pulmonary function tests reveal preserved volumes, normal or near-normal FEV1/FVC, and severely reduced DLCO (35–45%), distinguishing CPFE from COPD and IPF. HRCT confirms the combined emphysematous and fibrotic pattern, critical for differential diagnosis. Acute exacerbations occur in 20–28% of cases, lung cancer in 22–46% (mostly squamous cell), and long-term oxygen therapy is required in >70%. Five-year survival is 35–55%, lower than emphysema alone and comparable or worse than IPF. Management focuses on smoking cessation, antifibrotics, oxygen therapy, and complication-specific treatments, and selected patients may undergo lung transplantation. Conclusions: CPFE is a clinically and functionally unique entity with a high burden of pulmonary and systemic complications. Accurate recognition using HRCT and DLCO, along with early intervention and tailored management, is essential to improve patient outcomes and guide prognostic stratification. Full article

Endothelial dysfunction plays a central role in the pathogenesis of cardiovascular diseases, driven by a complex interplay of oxidative stress, metabolic imbalances, and adipokine dysregulation. Excessive reactive oxygen species reduce nitric oxide bioavailability by impairing endothelial nitric oxide synthase function, leading to vascular inflammation and impaired vasodilation. Adipose tissue-derived hormones such as leptin, adiponectin, and resistin exert opposing effects on vascular homeostasis, influencing inflammation and oxidative stress in obesity and metabolic syndrome. Dyslipidemia, particularly through oxidized LDL, initiates endothelial injury and foam cell formation, accelerating atherosclerosis. Furthermore, hypertension and obesity exacerbate vascular dysfunction by disrupting the balance between vasodilators and vasoconstrictors, enhancing oxidative stress, and altering perivascular adipose tissue function. These interrelated mechanisms contribute to the progression of atherosclerotic cardiovascular disease and diabetic vascular complications. A deeper understanding of these processes is essential for developing targeted interventions to restore endothelial health and reduce cardiometabolic risk. Full article

Background: Hypertension remains the leading global risk factor for cardiovascular morbidity and mortality, with suboptimal control rates despite guideline-directed therapies. Digital health and artificial intelligence (AI) technologies offer novel approaches for improving diagnosis, monitoring, and individualized treatment of hypertension. Objectives: To critically review the current landscape of AI-enabled digital tools for hypertension management, including emerging applications, implementation challenges, and future directions. Methods: A narrative review of recent PubMed-indexed studies (2019–2024) was conducted, focusing on clinical applications of AI and digital health technologies in hypertension. Emphasis was placed on real-world deployment, algorithmic explainability, digital biomarkers, and ethical/regulatory frameworks. Priority was given to high-quality randomized trials, systematic reviews, and expert consensus statements. Results: AI-supported platforms—including remote blood pressure monitoring, machine learning titration algorithms, and digital twins—have demonstrated early promise in improving hypertension control. Explainable AI (XAI) is critical for clinician trust and integration into decision-making. Equity-focused design and regulatory oversight are essential to prevent exacerbation of health disparities. Emerging implementation strategies, such as federated learning and co-design frameworks, may enhance scalability and generalizability across diverse care settings. Conclusions: AI-guided titration and digital twin approaches appear most promising for reducing therapeutic inertia, whereas cuffless blood pressure monitoring remains the least mature. Future work should prioritize pragmatic trials with equity and cost-effectiveness endpoints, supported by safeguards against bias, accountability gaps, and privacy risks. Full article

A psoriasis vulgaris flare is characterized by a rapid intensification of symptoms, which is often triggered by various factors that can worsen the condition. The risk factors for these exacerbations are numerous and include obesity, antihypertensive drugs, and psychological stress. Moreover, links have been documented between type II diabetes, hypertension, and psoriasis vulgaris. The present case report describes a 52-year-old female patient who presented at the clinic with disseminated erythematous-squamous plaques and patches covered by thick, white-pearly, easily detachable scales, along with stress, fatigue, anxiety, severe pruritus, irritability, insomnia, and decreased self-esteem. Her past medical regimen included various conventional topical options, including calcipotriol combined with betamethasone, clobetasol, betamethasone combined with salicylic acid, and betamethasone combined with gentamicin, yet the condition remained refractory, with periodic flare-ups. The integrated and personalized therapeutic approach aimed to target both the dermatological issues and the associated systemic and psychological factors contributing to the condition. The therapeutic strategy implemented in this case combined psychological counseling sessions, a very low-calorie ketogenic diet, oral supplementation with anti-inflammatory and antioxidant vitamins and minerals, topical treatments utilizing urea and Dead Sea-mineral-based formulations, and rosemary extract-based scalp care, without requiring additional conventional treatment. This comprehensive approach led to significant improvement, ultimately achieving complete remission of the patient’s psoriasis. The associated comorbidities were well controlled with the specified medication, without any further complications. Thus, the importance of alternative options was emphasized, particularly in the context of an incurable disease, along with the need for continued research to improve the ongoing therapeutic management of psoriasis vulgaris. Such approaches are essential to reducing the risk of flare-ups and to achieving better management of associated risk factors. Full article

Objective: To systematically review the scientific literature on lysergic acid amide (LSA), focusing on its physical, neurobiological, and social effects, as well as its potential risks and therapeutic uses. Methods: A systematic review was conducted across PubMed, Google Scholar, and Web of Science up to December 2023, using keywords such as “ergine,” “lysergic acid amide,” and “legal high.” Studies were included if they reported original human data on the physical, neurobiological, psychological, or social effects of LSA; seventeen studies were included. Animal studies, in vitro research, and non-original articles were excluded. Two independent reviewers screened and selected the studies, with a third resolving discrepancies. Data were extracted using a standardized form. The review followed PRISMA guidelines and was prospectively registered on the Open Science Framework. Results: LSA is primarily consumed through preparations made from the seeds of Convolvulaceae plants. Reported effects include euphoria, hallucinations, nausea, and anxiety. Severe adverse outcomes, such as psychosis, hypertension, and hospitalization, have also been documented. Some evidence suggests its potential therapeutic application for cluster headaches. However, variability in dosing and misinformation on digital platforms heighten the risks associated with LSA use. Conclusions: LSA poses significant health risks, exacerbated by online misinformation and variability in its effects, and a lack of scientific studies. Further research is essential to clarify its pharmacological profile, establish guidelines for safe use, and raise public awareness about its dangers. Full article

Hypertension-induced cardiac remodeling is a complex process driven by interconnected molecular and cellular mechanisms that culminate in hypertensive myocardium, characterized by ventricular hypertrophy, fibrosis, impaired angiogenesis, and myocardial dysfunction. This review discusses the histomorphometric changes in capillary density, fibrosis, and mast cells in the hypertensive myocardium and delves into the roles of key regulatory systems, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathways, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling in the pathogenesis of hypertensive heart disease (HHD). Capillary rarefaction, a hallmark of HHD, contributes to myocardial ischemia and fibrosis, underscoring the importance of maintaining vascular integrity. Targeting capillary density (CD) through antihypertensive therapy or angiogenic interventions could significantly improve cardiac outcomes. Myocardial fibrosis, mediated by excessive collagen deposition and influenced by fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-β), plays a pivotal role in the structural remodeling of hypertensive myocardium. While renin–angiotensin–aldosterone system (RAAS) inhibitors show anti-fibrotic effects, more targeted therapies are needed to address fibrosis directly. Mast cells, though less studied in humans, emerge as critical regulators of cardiac remodeling through their release of pro-fibrotic mediators such as histamine, tryptase, and FGF-2. The apelinergic system emerges as a promising therapeutic target due to its vasodilatory, anti-fibrotic, and cardioprotective properties. The system counteracts the deleterious effects of the RAAS and has demonstrated efficacy in preclinical models of hypertension-induced cardiac damage. Despite its potential, human studies on apelin analogs remain limited, warranting further exploration to evaluate their clinical utility. VEGF signaling plays a dual role, facilitating angiogenesis and compensatory remodeling during the early stages of arterial hypertension (AH) but contributing to maladaptive changes when dysregulated. Modulating VEGF signaling through exercise or pharmacological interventions has shown promise in improving CD and mitigating hypertensive cardiac damage. However, VEGF inhibitors, commonly used in oncology, can exacerbate AH and endothelial dysfunction, highlighting the need for therapeutic caution. The NO/NOS pathway is essential for vascular homeostasis and the prevention of oxidative stress. Dysregulation of this pathway, particularly endothelial NOS (eNOS) uncoupling and inducible NOS (iNOS) overexpression, leads to endothelial dysfunction and nitrosative stress in hypertensive myocardium. Strategies to restore NO bioavailability, such as tetrahydrobiopterin (BH₄) supplementation and antioxidants, hold potential for therapeutic application but require further validation. Future studies should adopt a multidisciplinary approach to integrate molecular insights with clinical applications, paving the way for more personalized and effective treatments for HHD. Addressing these challenges will not only enhance the understanding of hypertensive myocardium but also improve patient outcomes and quality of life. Full article