Search Results (2,129)

Pulmonary hypertension (PH) can be defined as a mean pulmonary artery pressure (mPAP) greater than 20 mm Hg at rest during right heart catheterization (RHC). The reported prevalence of PH throughout the globe has been estimated to impact approximately 1% of the total population, with a majority of those afflicted being women more than men. Numerous etiologies give rise to the pathophysiology of PH, including heart disease (i.e., left-sided heart failure), lung diseases, and other unclear causes related to chronic stages and complications surrounding long-standing pulmonary thromboembolisms, side effects of certain medications, and genetic and environmental factors. Untreated PH can lead to severe morbidities such as cardio-renal syndrome and congestive hepatopathy (cardiac cirrhosis). Management of PH focuses on decreasing pulmonary pressures by using vasodilators such as prostanoids, and phosphodiesterase type 5 (PDE-5) inhibitors, as well as newer treatments such as sotatercept, which inhibits activin signaling, thereby inhibiting excessive cell growth in the pulmonary artery vasculature and down-regulating the pro-proliferative pathways. Full article

Pulmonary arterial hypertension (PAH) is a severe and progressive cardiopulmonary disorder with limited treatment options. Camellia petelotii (Merr.) Sealy (CP) contains multiple flavonoids and other phytochemicals, but its active compounds and molecular mechanisms in PAH remain unclear. Active compounds of CP were screened by comprehensive literature mining and absorption, distribution, metabolism, and excretion (ADME) evaluation. PAH-related hub targets were identified from transcriptomic data using weighted gene co-expression network analysis (WGCNA), machine learning, and external validation. Functional enrichment, immune infiltration, and single-cell RNA-sequencing analyses were performed to characterize their biological roles and cellular localization. Molecular docking and molecular dynamics simulations assessed compound–target interactions. The effects of CP were further evaluated in hypoxia-induced rat pulmonary artery smooth muscle cells (RPASMCs). Five core bioactive compounds were identified, among which luteolin and quercetin were prioritized for further analysis. HSP90AA1 and ROCK2 were screened as hub targets. Bioinformatic analyses suggested that these targets were mainly associated with the “Lipid and atherosclerosis” pathway, metabolic reprogramming, and modulation of the immune microenvironment. Single-cell analysis showed broad expression of HSP90AA1 and enrichment of ROCK2 in fibroblasts and endothelial cells. Molecular docking and molecular dynamics simulations supported stable binding of luteolin to HSP90AA1. In vitro, CP extract inhibited hypoxia-induced hyperproliferation of RPASMCs and reduced HSP90AA1 protein expression. HSP90AA1 may represent a candidate molecular mediator of CP in PAH, and CP inhibited hypoxia-induced RPASMC proliferation in association with downregulation of HSP90AA1. Full article

Background and Objectives: Pulmonary hypertension (PH) is a major contributor to morbidity and mortality in sickle cell disease (SCD), yet reliable and accessible biomarkers for cardiopulmonary risk stratification remain limited. This study aimed to evaluate whether the platelet-to-neutrophil ratio (PNR) is independently associated with echo-estimated PH (ePH) in adolescents and adults with SCD and to compare its predictive value with hemoglobin composition and genotype. Materials and Methods: A retrospective cohort study was conducted at King Fahd Hospital of the University, Al Khobar, Saudi Arabia (January 2019–January 2025). Clinical, laboratory, and echocardiographic data from 114 patients with confirmed SCD who underwent transthoracic echocardiography (TTE) were analyzed. ePH was defined as tricuspid regurgitant velocity (TRV) ≥ 2.5 m/s or pulmonary artery acceleration time (PAAT) ≤ 105 ms. Multivariable logistic and linear regression models were used to assess associations between PNR, hemoglobin fractions, genotype, and pulmonary pressure estimates. Results: Overall, 43% of patients met the criteria for ePH. PNR was not independently associated with ePH or TRV in adjusted analyses. In contrast, higher fetal hemoglobin (HbF) levels were independently associated with lower odds of ePH (adjusted OR 0.92 per 1% increase, 95% CI 0.86–0.98) and lower TRV values. The HbS/β⁰ genotype was significantly associated with increased odds of ePH (adjusted OR 5.44, 95% CI 1.37–24.0). Exploratory analyses demonstrated an inverse association between PNR and lactate dehydrogenase, suggesting that PNR reflects hemolytic activity rather than pulmonary vascular involvement. Conclusions: In this retrospective cohort of patients with SCD, PNR was not independently associated with ePH or TRV after multivariable adjustment. In contrast, hemoglobin composition and genotype, particularly higher HbF and the HbS/β⁰ genotype, were significantly associated with pulmonary pressure estimates. Full article

Background/Objective: Continuous blood pressure (BP) monitoring is essential in clinical settings, where rapid hemodynamic changes influence patient management. While intra-arterial measurement remains the reference standard, non-invasive volume-clamp systems offer a potential alternative. We assessed the accuracy of finger-cuff-based continuous BP monitoring compared to invasive measurement in patients with pulmonary hypertension (PH). Methods: This post hoc analysis from a crossover RCT included PH patients who underwent repetitive hemodynamic assessments at rest and during exercise. The participants had simultaneous invasive BP monitoring via the radial artery and a non-invasive finger-cuff device (Finapres^® NOVA Basic). The mean blood pressure (mBP) was compared at rest, 50% of the maximal workload, and at the end of exercise using Bland–Altman and Taffé analysis. Results: In the study, 24 patients (seven female; 59 ± 14 years) contributed 385 paired mBP measurements. The invasive and non-invasive methods showed similar values at rest (96.1 ± 16.7 vs. 96.4 ± 17.2 mmHg) and during maximal exercise (106.8 ± 18.6 vs. 111.8 ± 21.6 mmHg). The overall Bland–Altman bias was 2.8 mmHg with wide limits of agreement (−39.6 to 45.3 mmHg), which remained broad across all exercise intensities. The Taffé analysis revealed a non-uniform, directionally dependent bias: the non-invasive system overestimated the mBP at low pressures and underestimated it at higher pressures. The measurement variability was substantially greater for the non-invasive method than for the invasive reference. Conclusions: In PH patients, finger-cuff-based continuous BP monitoring demonstrated acceptable group-level agreement but insufficient individual-level accuracy for clinical decision-making. Full article

Background: The global demographic shift towards an aging population has driven a steady, exponential increase in the utilization of cardiac implantable electronic devices (CIEDs). Consequently, device-related infectious complications have emerged as a leading cause of morbidity and healthcare expenditure. Patients in their eighth decade of life—octogenarians (aged 80–90 years)—represent an exceptionally high-risk demographic due to the compounding factors of physiological frailty, immunosenescence, and complex multi-morbidity. Despite this growing demographic, their specific clinical presentations, microbiological profiles, and procedural outcomes following infection remain poorly defined in the current literature. This study aimed to comprehensively compare the clinical characteristics, pathogen distribution, and in-hospital outcomes of CIED infections in an octogenarian cohort against a younger patient population. Methods: We conducted a robust retrospective cohort analysis of 383 consecutive patients treated for confirmed CIED infections at one major tertiary referral center (Heidelberg University Hospital) between January 2002 and December 2022. The cohort was stratified by age into octogenarians (n = 76) and a younger control group (n = 307). We systematically extracted and compared data regarding baseline clinical presentation, chronic comorbidities, detailed microbiological cultures (pocket, blood, and extracted leads), and definitive in-hospital outcomes, primarily mortality and length of stay. Results: The octogenarian cohort exhibited a significantly heavier comorbidity burden, notably higher rates of coronary artery disease (51.3% vs. 29.6%, p < 0.001), systemic hypertension (55.3% vs. 38.1%, p = 0.007), and chronic obstructive pulmonary disease (7.9% vs. 1.6%, p = 0.003). Furthermore, therapeutic systemic anticoagulant use was substantially more prevalent in the elderly group (60.5% vs. 45.0%, p = 0.015). Octogenarians presented overwhelmingly with localized generator pocket infections (73.0% vs. 30.0%, p < 0.001) but paradoxically also demonstrated higher rates of systemic bacteremia and sepsis (26.3% vs. 15.0%, p = 0.019). Microbiological analysis revealed a unique pathogen profile, with Staphylococcus capitis found with significantly higher frequency in the generator pockets of the elderly cohort. Remarkably, despite possessing a higher average lead burden (2.1 vs. 1.2 leads) and extreme comorbidity profiles, octogenarians demonstrated no statistically significant differences in in-hospital mortality (3.9% vs. 4.2%, p = 1.000) or overall length of hospital stay (14.7 vs. 17.2 days, p = 0.386) when compared to the younger cohort. Conclusions: Octogenarians suffering from CIED infections display highly distinct clinical and microbiological profiles, characterized predominantly by elevated rates of localized pocket infections, specific opportunistic pathogens, and a severe underlying comorbidity burden. Crucially, our findings indicate that with the application of modern extraction and management protocols, advanced age alone does not intrinsically correlate with increased in-hospital mortality. Future prevention and perioperative management strategies tailored to this rapidly expanding demographic must heavily prioritize the mitigation of pocket-related complications, particularly considering the high prevalence of concurrent anticoagulation therapy. Full article

Cirrhosis is no longer viewed solely as an isolated hepatic disorder but rather as a complex multisystemic disease that affects cardiovascular, renal, pulmonary, metabolic, and immune systems. One of its most clinically relevant but under-recognized consequences is cardiac dysfunction, manifesting as cirrhotic cardiomyopathy, portopulmonary hypertension, right ventricular (RV) failure, and impaired myocardial strain. Oxidative stress (OS) has recently emerged as a fundamental mechanistic link between hepatic fibrogenesis and myocardial remodeling, acting through mitochondrial injury, NADPH oxidase activation, nitric oxide dysregulation, iron-mediated ferroptosis, and inflammatory cytokines. These alterations lead to diastolic dysfunction, autonomic imbalance, myocardial fibrosis, electrophysiological abnormalities (including QTc prolongation), and impaired RV–pulmonary artery coupling. Redox biomarkers such as malondialdehyde (MDA), NOX2-derived peptides, GSH/GSSG ratio, sST2, NT-proBNP, and 8-isoprostanes hold promise in detecting early subclinical cardiac involvement in cirrhosis. Novel antioxidant therapies, including mitochondrial-targeted molecules, NOX inhibitors, and ferroptosis blockers, may improve myocardial remodeling and hemodynamic stability. This review explores the central role of redox imbalance in the cardiohepatic syndrome and its potential utility in diagnosis, monitoring, and therapy. Full article

Hemorrhagic shock remains one of the leading causes of preventable death for both civilian and military trauma. Fluid resuscitation is the primary treatment but requires constant monitoring, particularly for volume non-responsive patients susceptible to fluid overload, pulmonary edema, and other life-threatening conditions. To overcome fluid non-responsiveness, vasoactive drugs or vasopressors can be necessary adjuvants to fluid therapy but require tedious titrations that can be difficult to manage during mass-casualty situations. This study developed and evaluated automated closed-loop vasopressor controllers for hemorrhage scenarios. Ten physiological closed-loop controller (PCLC) configurations with different underlying functionalities were tuned to be either more aggressive or conservative to reach the target mean arterial pressure. A hardware-in-loop test platform with fluid-pressure responsiveness, derived from animal data, tested each controller across three different starting pressure scenarios. The platform successfully differentiated controller designs based on performance metrics. While some configurations overshot the target and others could not reach the target pressure, strong-performing PCLCs consistently reached and maintained the target quickly. Three candidate PCLCs outperformed the rest and will be evaluated across wider scenarios to develop a robust controller design. This work accelerates PCLC-driven vasopressor administration development, providing a necessary fluid resuscitation adjuvant for precise hemodynamic management in hemorrhagic trauma. Full article

The lung–kidney axis forms an important physiologically integrated system which controls multiple essential functions of the body. An important observation of this interaction is tissue oxygenation and erythropoiesis, a vital process that involves erythropoietin (EPO) release by the kidney to bring red cell production into the bone, while pulmonary gas exchange ensures adequate oxygen delivery to the cells. Subsequently, the lung–kidney activation of the renin angiotensin system (RAS) influences vascular tone, blood pressure, and tissue perfusion, influencing the delivery of oxygen and the body’s requirement for erythropoietin. Additionally, beyond oxygen sensing, studies have evidenced the role of hypoxia-inducible factors (HIFs), inflammatory mediators, endothelial signaling pathways and iron availability. These modulate erythropoietin production, which enhances the process of erythropoiesis and arterial oxygen balance. Localized variations in renal oxygen levels together with hemodynamic control mechanisms enable the body to produce erythropoietin independently from systemic hypoxia conditions. This concept emerged to include the renal oxygen extraction fraction (OFE) and intrarenal microvascular shunting with perfusion oxygen coupling in governing EPO production. The present review refines the traditional knowledge to further expand our understanding of the lung–kidney axis regulating the process of erythropoiesis and arterial oxygen content. The integrative framework demonstrates that pulmonary arterial oxygenation and renal oxygen sensing together with bone hematopoietic responses operate as a unified system which maintains both oxygen equilibrium and hematopoietic balance throughout the body. Full article

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO₂) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017–2024) was conducted in preterm infants < 32 weeks’ gestation who required > 24 h of invasive ventilation within the first 3 days of life. Perinatal–neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary–venous) and the maximum and minimum PCO₂ in the first 72 h were evaluated. Normocapnia was defined as PCO₂ 35–45 mmHg, hypocapnia as < 35 mmHg, and hypercapnia as > 45 mmHg. Primary outcomes were the incidence of PCO₂ abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age < 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age < 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO₂ values and greater PCO₂ variability, although these were not independent predictors of SBI or death. Conclusions: PCO₂ instability is highly prevalent in ventilated preterm infants, underscoring the need for individualized ventilation strategies. Extreme prematurity emerged as the primary risk factor for adverse outcomes, while hypercapnia was independently associated with BPD. Full article

High-altitude workers in the Los Andes Mountains, known as “the Chilean miner model,” are exposed to chronic intermittent hypobaric hypoxia (CIHH). This intermittent condition differs from other models of chronic hypoxia, mainly due to the hypoxic pattern and the cardiovascular and pulmonary effects. There are reports of cardiopulmonary dysfunction and remodeling in human and animal models. However, research on some mechanisms of vascular function and the consequences of lung remodeling induced by CIHH is still lacking. Therefore, this study aims to characterize the effects of CIHH exposure on lung structure and redox status in a rat model of the Chilean miner, involving intermittent exposure to chronic cycles of normoxia/hypobaric hypoxia (96 h/96 h) in an experimental hypoxic chamber. Our results demonstrate that CIHH acts as a primary driver of pulmonary vascular remodeling by significantly increasing the medial wall thickness of small pulmonary arteries (<100 μm) and promoting a shift toward a more muscularized phenotype in previously non-muscularized vessels. Structurally, this was characterized by a marked reduction in alveolar space and a significant increase in the thickness of the alveolar-capillary barrier, suggesting impaired gas exchange capacity. These structural changes were strongly associated with a pro-oxidant state, evidenced by increased lipid peroxidation (malondialdehyde levels) and a concomitant reduction in antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase (CAT), in lung tissue. In conclusion, the CIHH model effectively replicates the complex interplay between chronic oxidative damage and structural lung remodeling, identifying the thickening of the arterial medial wall and alveolar septa as key pathological features of probably CIHH-induced pulmonary hypertension. Full article

Background/Objectives: Dual-energy CT (DECT) enables iodine quantification as a snapshot perfusion indicator. Understanding pulmonary iodine distribution in lung-healthy individuals is crucial for clinical applications. This study aimed to automate iodine quantification and assess demographic effects in a lung-healthy reference cohort. Methods: This retrospective cohort study included 112 adults (53% female, mean age 60.3 ± 16.6 years) who underwent repeated portal venous phase chest DECT on a spectral detector dual-layer scanner between 2016 and 2019 at an academic medical center. Patients had dermato-oncological diseases but no visible thoracic tumors. Automatic lung volumetry was merged with reconstructed iodine maps to assess volume and mean iodine concentrations of each lung lobe. Pulmonary iodine perfusion ratios (PIPRs) were calculated by normalizing the pulmonary iodine density against iodine concentration in the portal vein and the main pulmonary artery (mPA). Results: Mean lung volume (f: 3.9 L vs. m: 5.2 L) and iodine concentration (f: 0.87 mg/mL vs. m: 0.69 mg/mL) differed between ages. However, no difference was observed when comparing PIPRs after normalizing against the iodine level in the mPA. PIPR_mPA were consistent across two timepoints (r = 0.88) and decreased with increasing age (≤50 years: 0.18 vs. ≥70 years: 0.15). Conclusions: This study demonstrates that automated pulmonary iodine quantification is feasible. Normalized pulmonary iodine concentration is a more reliable and effective method for evaluating iodine distribution. Our study also highlights the need to account for sex and age variations in future research and clinical applications. Full article

Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is an important but under-recognised complication in neuromuscular diseases. In adults, emerging epidemiological data suggests increased VTE occurrence in conditions such as Amyotrophic Lateral Sclerosis, myotonic dystrophy, myasthenia gravis, inflammatory neuropathies, inflammatory myopathies, and POEMS syndrome. This heightened risk reflects not only disease-related immobility but also disorder-specific biological mechanisms, including inflammation, endothelial dysfunction and cardiomyopathy-related stasis. Therapies such as corticosteroids, IVIG-related hyperviscosity, long-term central venous access, perioperative immobility, critical illness, and complex orthopaedic procedures have prothrombotic effects. Despite this multifactorial risk profile, disease-specific guidance for thromboprophylaxis is lacking, and current practice relies heavily on extrapolation from general medical and surgical recommendations rather than data derived from neuromuscular cohorts. In children and adolescents, the VTE burden is less well-characterised, but events have been reported in Duchenne and Becker muscular dystrophy, congenital myopathies, and spinal muscular atrophy particularly with advanced motor impairment, severe cardiomyopathy, ventilatory insufficiency, and prolonged hospitalisation. Beyond venous events, selected neuromuscular disorders also exhibit increased arterial thrombosis risk. Myotonic dystrophy and dystrophinopathies are associated with cardiomyopathy and arrhythmia that predispose to systemic embolism and stroke, while inflammatory myopathies may demonstrate arterial events related to vasculitic or endothelial processes, although overall evidence remains limited. This review summarises available empirical and epidemiological evidence on venous and arterial thrombosis across adult and paediatric neuromuscular disorders, outlines disease-specific mechanistic pathways, examines treatment-related contributors, and highlights key evidence gaps that must be addressed to guide rational and targeted prophylaxis strategies in this complex, heterogeneous population. Full article

Background/Objectives: Since 2015, pulmonary arterial hypertension (PAH)-specific medications have been fully reimbursed in Lithuania. To describe the current situation of PAH treatment in the country and to determine survival during different PAH treatment regimens. Methods: The data from the Institute of Hygiene and the State Data Agency of Lithuania cases with administrative codes I27.0 and I27.8 have been evaluated. Results: In 2025, 225 confirmed cases of PAH were treated with PAH-specific medications in two PH centers. At least one PAH-specific medication was prescribed to 163 (72.4%) female and 62 (27.6%) male patients. Among these, 96 (42.7%) received sildenafil monotherapy, 82 (36.4%) received a combination of sildenafil and an ERA, 36 (16.0%) were on triple PAH-specific therapy (including selexipag or treprostinil), and 11 (4.9%) received other regimens due to specific medical considerations. The age of adults treated with sildenafil monotherapy vs. other therapies was 63.9 ± 14.8 (n = 117) and 51.5 ± 17.3 (n = 116) years, respectively (p < 0.05). A total of 191 PAH patients who received targeted therapy died during the observational period 2017–2025. Of these, 105 received monotherapy, 57 sildenafil and endothelin receptor antagonist and 29 triple therapies (treprostinil [n = 19], selexipag [n = 6], or inhaled iloprost [n = 4] were prescribed as the third drug). Patients who died and received triple therapy were younger than those on mono- and dual therapy (age at diagnosis 45.0 ± 21.6, 67.2 ± 14.7 and 61.6 ± 16.3 years, respectively, p < 0.01). Survival was longer in patients on dual therapy compared with monotherapy (43.1 ± 28.1 vs. 31.7 ± 25.0 months, p = 0.04), and the longest was in those receiving triple therapy (59.9 ± 29.4 months; p < 0.05). Conclusions: The availability of reimbursed medications dramatically increased the number of treated PAH cases in Lithuania. In 2025, most of the PAH patients received sildenafil monotherapy. Patients treated with sildenafil only were significantly older than the rest of cohort. In the survival analysis, combination PAH therapies were more often prescribed to younger patients and were associated with longer duration of life than monotherapy. Full article

Background: Cardiovascular diseases are the main cause of mortality and morbidity in Portugal, with coronary artery bypass grafting (CABG) being one of the most performed surgeries in cardiothoracic centers. After cardiac surgery, patients often experience a decrease in physical capacity, which results in an increased risk of mortality or hospitalization expenditures. The objective of this systematic review was to characterize changes in respiratory function in patients undergoing CABG. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Web of Science, Pubmed, SCOPUS, and Sport Discus were searched using a predefined research strategy to identify relevant original studies published until August 2025. To be included, studies must have assessed adult patients submitted to CABG who evaluated the respiratory function before and after cardiac surgery. Studies that reported other types of cardiac surgery were excluded. The Risk of Bias in Non-randomized Studies-of-Exposure and the Cochrane risk-of-bias tool for randomized trials were used to analyze the risk of bias of the selected studies. Results: After screening 1184 potential articles, six studies met the inclusion criteria. The studies included participants who underwent CABG (n = 324), with a mean age ranging from 54.05 ± 13.6 to 67 ± 10 years. Conclusions: All included studies reported significant postoperative reductions in respiratory function following CABG, including forced vital capacity, forced expiratory volume in one second, maximal inspiratory pressure, and maximal expiratory pressure. Although these findings consistently indicate a decline in pulmonary function, the limited number of available studies limits the strength of the conclusions. This systematic review suggests that monitoring respiratory impairments after CABG may be clinically relevant to improve health-related quality of life. Full article

Background: While previous studies indicate an association between chest pain and favorable clinical outcomes in patients with pulmonary embolism (PE), the extent and underlying mechanisms of this effect remain inadequately defined. Methods: We investigated the prognostic value of chest pain with regard to in-hospital adverse outcomes and the association of chest pain with age and sex in consecutive patients with confirmed PE enrolled in a single-center registry between 2008 and 2019. Results: Of 858 patients (52% female) included in this study, 435 (51%) had chest pain at presentation. Chest pain was more prevalent in younger individuals aged 18–34 years (74%) compared to patients >34 years (46%). The prevalence of coronary artery disease (CAD) was similar in patients with and without chest pain (17.0% vs. 16.1%). Chest pain patients less frequently presented with elevated troponin levels (p < 0.001) or signs of right heart strain (RHS; p = 0.007) but more frequently exhibited imaging signs of pulmonary infarction (p = 0.001). Chest pain was associated with lower risk of adverse outcome (OR 0.35 [95% CI: 0.19–0.65]) and in-hospital mortality (OR 0.31 [95% CI: 0.13–0.74]). Multivariable models confirmed a prognostic effect independent of sex, comorbidities and results of risk stratification algorithms. Conclusions: In acute PE, chest pain is a favorable prognostic marker irrespective of sex. Chest pain patients are less likely to suffer from myocardial ischemia or show signs of RHS but more frequently show imaging signs of pulmonary infarction, suggesting pleuritic irritation rather than myocardial ischemia as the likely cause of pain. Full article