Search Results (364)

Background and Objectives: Heart failure (HF) represents a clinical syndrome characterized by symptoms and signs such as fatigue, dyspnea, edema of the lower limb, or pulmonary rales. It usually occurs in elderly individuals due to decreased cardiac pumping function and/or increased diastolic ventricular filling pressures. The COVID-19 pandemic deeply altered many daily life habits, and one of the most affected groups of people were those with chronic diseases because of their need for regular medical follow-up. Furthermore, SARS-CoV-2 infection itself has been shown to exacerbate cardiovascular diseases (CVDs). Materials and Methods: This retrospective, observational, and comparative study aimed to characterize and compare patients with chronic heart failure hospitalized in the Cardiology Department of Medical Clinic II, Mureș County Emergency Clinical Hospital, in Târgu Mureș, Romania, between January and December 2019 (pre-pandemic), January and December 2021 (pandemic), and January and December 2023 (post-pandemic). Results: A total of 406 patients were analyzed: 202 patients hospitalized in 2019, 101 patients hospitalized in 2021, and 103 patients hospitalized in 2023. Women with HF were significantly older (median age 72 years) than men (median age 65 years; p < 0.001). During the pandemic, the median length of hospitalization increased (8 days vs. 7 days in the other periods). The pandemic period was also associated with a decrease in left ventricular ejection fraction (LVEF), as reflected by a higher incidence of patients with HF with reduced ejection fraction (42% during the pandemic; p < 0.01). Conclusions: During and after the pandemic, men exhibited significantly higher rates of right and left bundle branch blocks, as well as chronic obliterating artery disease of the lower limb. Left ventricular function declined during the pandemic in both men and women. Throughout the years, we observed distinct patterns between male and female patients regarding associated diseases or behaviours, suggesting lifestyle and psychological changes due to the COVID-19 pandemic. Full article

Left-sided congestive heart failure (CHF) is a common cause of acute respiratory distress in cats, and echocardiographic assessment of left atrial (LA) size is an important test to differentiate it from respiratory diseases that cause similar clinical signs. Furosemide, a potent loop diuretic, is the first-line therapy for cardiogenic pulmonary edema, but its effect on LA size has not been systematically investigated in cats. Some dyspneic cats are referred after having received high doses of furosemide by the referring veterinarian without prior point-of-care ultrasound (POCUS). This can make the diagnosis of CHF challenging. If furosemide significantly reduces left atrial size, it could potentially lead to misdiagnosis, by erroneously categorizing these cats as not having CHF. This prospective, observational multicenter study enrolled 25 cats with acute left-sided CHF. Point-of-care ultrasound was used to assess LA to aortic ratio (LA:Ao) and maximal LA diameter (LAD) at admission and three hours after furosemide administration. Significant reductions were observed in LA:Ao (2.48 ± 0.35 to 2.17 ± 0.40; p < 0.001), LAD (21.0 ± 2.8 mm to 18.4 ± 3.2 mm; p < 0.001), and respiratory rate (64 ± 30 to 40 ± 14 breaths/min; p < 0.001). Normalization of respiratory rate occurred in 50% of cats, while normalization of maximum LAD occurred in 32%. One cat achieved normalization of LA:Ao. We found that furosemide induced rapid reduction in LA size and respiratory rate in cats with left-sided CHF. Clinicians should be aware that severe LA dilation can be absent in referred dyspneic cats that had already received furosemide. Full article

Exposure to hypoxia may cause lung injury characterized by hydrostatic pulmonary edema (PE), inflammation and oxidative stress. Norepinephrine (NE) infusion can also induce lung injury with similar pathogenetic characteristics. The main questions of this study were (i) whether NE infusion aggravates hypoxia-induced pulmonary injury; (ii) whether inflammation and oxidative stress deteriorate the hypoxic PE; and (iii) whether PE and inflammation recede after three days of normoxic recovery. Ninety-eight female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl or NE. Some of these animals were transferred to a three-day normoxic recovery period thereafter. We performed histological and immunohistochemical analyses of the lung, determined protein concentrations in pleural fluid (PF) and bronchoalveolar lavage fluid (BALF), and evaluated hemodynamic parameters. While inflammation and oxidative stress receded after 3 days of normoxic recovery, PE did not resolve. Increased protein concentrations in PF and BALF indicated that capillary stress failure increased even further during the normoxic recovery phase, particularly in animals that had previously received an NE infusion. These results highlight the fact that inflammation does not play a causal role in the development of hypoxic PE. Full article

This review reappraises the anti-inflammatory potential of the contact activation system (CAS) in intensive care through an evolutionary lens. The authors propose that coagulation factor XII (FXII) and related components evolved in terrestrial animals as a “foreign-surface sensing–immunothrombosis” module, helping to explain the minimal bleeding phenotype of FXII deficiency and the secondary loss of F12 in marine mammals. CAS shares components with the kallikrein–kinin system (KKS): alpha-coagulation factor XIIa (α-FXIIa) drives coagulation factor XI (FXI) activation to amplify coagulation, whereas betacoagulation factor XIIa (β-FXIIa) activates the KKS to generate bradykinin, promoting vasodilation and vascular leak. Beyond proteolysis, zymogen FXII signals via urokinase-type plasminogen activator receptor (uPAR) to induce neutrophil extracellular trap formation (NETosis), thereby amplifying immunothrombosis. Clinically, the relevance spans sepsis and extracorporeal organ support: pathogens can hijack CAS/KKS to facilitate invasion, and artificial surfaces such as extracorporeal membrane oxygenation (ECMO) circuits chronically trigger contact activation. In animal models, selective inhibition of FXII/FXI prolongs circuit life and attenuates pulmonary edema and inflammation without materially increasing bleeding. The review also catalogs “non-coagulation” roles of CAS members: Activated coagulation factor XI (FXIa) modulates endothelial permeability and smooth-muscle migration, and the FXII heavy chain exhibits direct antimicrobial activity—underscoring CAS as a nexus for coagulation, inflammation, and host defense. Overall, CAS inhibitors may couple “safe anticoagulation” with “cascade-level anti-inflammation,” offering a testable translational path for organ protection in the ICU alongside infection control and informing combined, precision strategies for anticoagulation and anti-inflammatory therapy. Full article

Subarachnoid hemorrhage (SAH), often resulting from aneurysmal rupture, remains a life-threatening cerebrovascular disorder with high morbidity and mortality. While previous research has focused primarily on cerebral damage and neurological outcomes, growing evidence suggests that SAH also causes systemic complications, including pulmonary dysfunction. The underlying mechanisms linking SAH to lung injury, however, are not fully understood. The glymphatic system, a perivascular network that facilitates the clearance of cerebrospinal fluid (CSF) and interstitial waste from the brain, plays a critical role in maintaining central nervous system (CNS) homeostasis. Aquaporin-4 (AQP4) water channels, predominantly expressed in astrocytic end feet, are essential for efficient glymphatic flow. Emerging studies have shown that SAH impairs glymphatic function by disrupting AQP4 polarity and CSF circulation, resulting in the accumulation of neurotoxic substances and neuroinflammation. Recent findings further suggest that glymphatic dysfunction may exert systemic effects beyond the CNS, contributing to a breakdown of the brain–lung axis. The release of pro-inflammatory cytokines, blood degradation products, and damage-associated molecular patterns (DAMPs) into systemic circulation can promote pulmonary endothelial injury and trigger immune responses in the lungs. This phenomenon is exacerbated by impaired clearance via the glymphatic system, amplifying systemic inflammation and increasing the risk of acute lung injury (ALI) or neurogenic pulmonary edema (NPE). This review proposes a novel perspective linking glymphatic impairment with pulmonary complications after SAH. Understanding this connection could open new therapeutic avenues—such as targeting AQP4 function, enhancing CSF circulation, or modulating the inflammatory response—to mitigate both neurological and respiratory sequelae in SAH patients. Full article

Background/Objectives: Lithocarpus litseifolius (Hance) Chun, also known as sweet tea, is a traditional Chinese tea-making plant. Acute lung injury (ALI), a life-threatening syndrome with symptoms like hypoxemia and dyspnea, can be triggered by infection or trauma, with high morbidity and mortality. Whether the water extract of Lithocarpus litseifolius (WEL) has therapeutic effects on ALI remains unclear. This study aimed to analyze WEL’s components, establish in vitro cellular inflammation and mouse ALI models, and investigate WEL’s protective effects against LPS-induced ALI. Methods: LC-MS analysis identified 42 compounds in WEL and quantified three key ones. In an LPS-induced mouse ALI model, WEL significantly reduced lung injury severity, lung wet-to-dry ratio, pulmonary edema, and levels of NO, ROS, IL-1β, TNF-α, and MPO in lung tissues and bronchial alveolar lavage fluid. Immunohistochemical analysis showed WEL pretreatment inhibited the upregulation of NLRP3, Caspase-1, and GSDMD-NT expression, mitigated tissue oxidative stress and cell pyroptosis, and alleviated ALI severity in mice. Cellular experiments confirmed WEL’s protective effects via anti-inflammatory, antioxidant actions, and inhibiting cell pyroptosis, with phlorizin and trilobatin as potential key active ingredients. Conclusions: This research demonstrates sweet tea’s significant protective effects against ALI and its potential to alleviate inflammation by inhibiting pyroptosis, providing a theoretical basis for developing new health-promoting functions of sweet tea. Full article

Background/Objectives: Acute spinal cord injury (ASCI) often leads to pulmonary complications, yet reliable, non-invasive assessment tools are limited. This study aimed to evaluate the utility of lung ultrasound (LUS) in assessing lung injury following ASCI in a rat model. Methods: Fifty-four female Sprague Dawley rats were randomized into sham (n = 27) or ASCI (n = 27) groups. LUS was performed at 12 h, 48 h, and 1 week post-injury, with lung injury quantified using a modified B-line score (BLS). Pulmonary function was assessed non-invasively, and histopathological evaluation and wet-to-dry (W/D) weight ratios were conducted post-mortem. Correlations between BLS and functional and pathological parameters were analyzed. Results: Histological analysis revealed progressive pulmonary hemorrhage, edema, and inflammatory infiltration peaking at 48 h post-injury, with residual hemorrhage and fibroplasia at 1 week. LUS findings evolved from narrow-based B-lines at 12 h to confluent B-lines with pleural abnormalities by 1 week. ASCI rats showed significant reductions in respiratory frequency, peak inspiratory and expiratory flow, and EF₅₀ at all time points (p < 0.05). Tidal volume and minute volume decreased initially, with partial recovery at 1 week. BLS negatively correlated with all pulmonary function parameters and positively with the histological score and W/D ratio (p < 0.001). Conclusions: LUS reliably detects and tracks lung injury after ASCI, correlating well with physiological and pathological indicators. These findings support its potential as a non-invasive monitoring tool. Future refinement of ultrasound scoring may improve clinical applicability in ASCI-related pulmonary assessment. Full article

Background and Clinical Significance: Idiopathic pulmonary arterial hypertension is a rare disorder, often linked to genetic predisposition. Canonical pulmonary arterial hypertension genes such as BMPR2, KCNK3, and TBX4 are well described, but novel associations continue to emerge. Glomulin (GLMN) encodes a protein essential for vascular smooth-muscle biology, classically implicated in glomuvenous malformations, yet not previously associated with pulmonary arterial hypertension. Case Presentation: We present a 49-year-old woman with progressive dyspnea, edema, and persistent hypercapnic respiratory failure. Right-heart catheterization confirmed precapillary pulmonary hypertension. Comprehensive evaluation, including ventilation/perfusion scanning, autoimmune panel, polysomnography, and high-resolution computed tomography, excluded secondary causes. Respiratory assessment revealed diaphragmatic weakness and reduced respiratory muscle pressures, consistent with primary myopathy and explaining the unusual hypercapnic profile. Whole-genome sequencing identified a heterozygous pathogenic GLMN nonsense variant, while canonical pulmonary arterial hypertension genes were negative. No cutaneous or mucosal glomuvenous malformations were found. The patient was treated with oxygen therapy, diuretics, non-invasive ventilation, and dual oral pulmonary arterial hypertension therapy (ambrisentan and tadalafil), with stabilization but persistent hypercapnia. Conclusions: To our knowledge, this is the first reported co-occurrence of idiopathic pulmonary arterial hypertension and a pathogenic GLMN variant. While causality cannot be inferred, glomulin’s role in vascular smooth-muscle maturation provides a plausible link to pulmonary vascular remodeling. This case underscores the importance of assessing respiratory muscle function in idiopathic pulmonary arterial hypertension patients with hypercapnia and highlights the potential relevance of extended genetic testing in rare pulmonary vascular disease. Full article

Patients undergoing thoracic surgery or intensive care are frequently exposed to high-voltage electric fields generated by medical devices; however, the duration-dependent effects of such exposure on lung tissue remain unclear. This study aimed to investigate the histopathological and immunoinflammatory effects of exposure to a uniform 10 kV/m electric field for varying durations using a rat model. Thirty-five adult female Wistar rats were randomly assigned to five groups (n = 7): control, and 1, 5, 15, and 30 min exposure groups. Lung tissues were analyzed histologically with hematoxylin and eosin staining, and the immunohistochemical expression of IL-1β, RANKL, and TNF-α was semi-quantitatively assessed. Histopathological examination revealed a duration-dependent increase in lung injury, with the 30 min group showing marked epithelial loss, mononuclear infiltration, edema, and vascular congestion (p < 0.001). The expression of IL-1β, RANKL, and TNF-α remained minimal in the 1–15 min groups but was significantly elevated in the 30 min group (p < 0.001). These findings suggest that prolonged exposure to high-voltage electric fields induces substantial pulmonary inflammation and tissue damage, indicating the presence of a threshold beyond which inflammatory pathways are abruptly activated. These results highlight the importance of establishing safety guidelines for electric field exposure in clinical settings. Full article

Background: Acute lung injury (ALI) is a life-threatening respiratory condition and one of the leading causes of mortality worldwide, accounting for approximately 20% of global annual deaths. Despite its high prevalence and severity, effective therapeutic options remain limited. Eupatorium lindleyanum DC., a traditional medicinal herb, has demonstrated therapeutic potential against pulmonary diseases, particularly ALI, in both clinical and experimental settings. However, the protective effects and underlying mechanisms of its characteristic sesquiterpene lactone components against ALI remain unclear. Objective: This study aimed to evaluate the protective effects of sesquiterpene lactones from Eupatorium lindleyanum DC. (SLEL) against lipopolysaccharide (LPS)-induced ALI both in vivo and in vitro. Furthermore, it sought to elucidate the underlying mechanisms by integrating network pharmacology, multi-omics approaches (transcriptomics, metabolomics, and 16S rRNA sequencing), and various molecular biology techniques. Results: SLEL significantly attenuated inflammatory injury in alveolar epithelial cells and alleviated pulmonary edema, hemorrhage, and inflammatory infiltration in rats, accompanied by reduced TNF-α, IL-6, and IL-1β levels and improved lung injury indices. Mechanistically, SLEL exerted dual suppression of the PI3K-Akt and MAPK-NF-κB pathways. Network pharmacology, molecular docking, and UPLC-MS analyses identified Eupalinolide A and Eupalinolide K as potential bioactive constituents, which were further validated to inhibit phosphorylation of key signaling proteins, thereby partially accounting for SLEL’s pharmacological effects. Multi-omics integration further revealed that SLEL restored bile acid metabolism, reshaped gut microbial diversity, and reconstructed the microbiota–metabolite–inflammatory cytokine network, thereby maintaining gut–lung axis homeostasis and enhancing anti-inflammatory effects. Conclusions: SLEL alleviates ALI through multi-component synergistic actions that suppress pro-inflammatory signaling and modulate the gut–lung axis. These findings highlight the potential of SLEL as a promising therapeutic candidate for the treatment of ALI. Full article

Methods: Using the most recent pre-COVID National Inpatient Sample (2016–2019), we evaluated inpatient mortality and economic impact after elective primary total hip arthroplasty (THA) across 327,123 cases (1,635,615 weighted discharges).Results: Overall inpatient mortality was 0.04%, but was higher in patients ≥ 80 years (0.15%), with weekend admissions (0.10%), and with surgical delay ≥ 1 day (0.17%). Comorbidities with the greatest mortality association included congestive heart failure and chronic kidney disease (both with markedly elevated odds), and acute in-hospital complications (e.g., pulmonary embolism) carried substantial risk. Complications also increased resource use; for example, heart failure, pulmonary edema, and acute coronary artery disease were each associated with significantly higher costs and prolonged length of stay. Conclusion: These findings provide a contemporary, pre-pandemic national baseline that quantifies high-risk subgroups and the economic footprint of adverse events, supporting targeted perioperative strategies and hospital planning for elective THA. Full article

Sepsis is a life-threatening condition driven by a dysregulated host response to infection, with high mortality and few treatment options. Decades of failed drug development underscore the urgent need for therapies with novel mechanisms of action. Vimentin, an intermediate filament protein, acts as a network hub that senses and integrates cellular signals. Its involvement in key sepsis pathologies, including infection, hyperinflammation, immunosuppression, coagulopathy and metabolic dysregulation, positions it as a potential therapeutic target. This study evaluated the efficacy of ALD-R491, a novel small-molecule vimentin modulator, in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice received ALD-R491 prophylactically or therapeutically, alone or with ceftriaxone. The treatment significantly reduced serum levels of key biomarkers of sepsis, including C-reactive protein (CRP), lactate (Lac), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and dose-dependently improved the survival of septic mice. Organ-specific analysis confirmed the effects of ALD-R491 in mitigating hyperinflammation and multi-organ injury. The treatment reduced pulmonary edema and inflammation; preserved liver tissue architecture and improved hepatic function with lowered alanine aminotransferase/aspartate aminotransferase (ALT/AST); decreased kidney tubular damage; and improved renal function with lowered creatinine/blood urea nitrogen (BUN). These preclinical findings indicate that the vimentin-targeting agent ALD-R491 represents a promising therapeutic candidate for sepsis and merits further clinical investigation. Full article

Introduction: Twelve-lead electrocardiography (ECG) remains an essential diagnostic tool for patients presenting with chest pain. Timely recognition of specific electrocardiographic patterns is critical for guiding reperfusion strategies and predicting adverse outcomes. Among these, Wellens’ pattern is a high-risk marker of critical left anterior descending (LAD) artery stenosis and an impending anterior myocardial infarction. Although typically described in clinically stable patients without heart failure, its occurrence in the setting of acute decompensation is rare. Case Report: We report the case of a 66-year-old male with hypertension, obesity, and active smoking who presented with exertional chest pain, dyspnea, and signs of acute heart failure. Initial ECG revealed biphasic T waves in V2–V4, consistent with type A Wellens’ pattern. Laboratory evaluation demonstrated elevated troponin I, while point-of-care ultrasound (POCUS) identified systolic and diastolic dysfunction, lateral wall hypokinesia, pericardial effusion, and cardiogenic pulmonary edema. The patient received acute management with antiplatelet therapy, statins, diuretics, and anticoagulation, followed by referral for coronary angiography. This revealed critical stenosis (>90%) of the proximal LAD, successfully treated with percutaneous coronary intervention and drug-eluting stent implantation. The in-hospital course was uneventful, and guideline-directed medical therapy was optimized at discharge, including dual antiplatelet therapy, beta-blocker, renin–angiotensin system inhibitor, and SGLT2 inhibitor. Conclusions: This case highlights the need for early recognition of Wellens’ pattern, even in atypical contexts such as acute heart failure. Integrating ECG interpretation with bedside POCUS facilitated diagnostic accuracy and guided an early invasive strategy, preventing extensive myocardial infarction. In resource-limited settings, strengthening frontline diagnostic capabilities and referral networks is crucial to improving patient outcomes. Full article

Acute lung injury (ALI) is a severe pulmonary disorder characterized by the disruption of the alveolar–capillary barrier, leading to impaired oxygenation and pulmonary edema. Current pharmacological interventions primarily involve the use of steroid drugs, oxygen radical scavengers, and bronchodilators. However, the therapeutic efficacy of these interventions remains inconsistent. Canthin-6-ones, a class of tryptophan-derived alkaloids, exhibit anti-inflammatory, antioxidant, and immunomodulatory properties. In this study, we synthesized a novel Canthin-6-one derivative, namely HCX3, and evaluated its potential beneficial effects and underlying mechanisms on ALI. Prior to the experimental study, network pharmacology analysis revealed that HCX3 may exert anti-inflammatory effects in the context of ALI through the regulation of multiple signaling pathways, including the NF-κB pathways. To validate these findings, Lipopolysaccharide (LPS) was employed to stimulate RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) to construct cellular models of inflammatory response associated with ALI. Our data demonstrated that exposure to HCX3 significantly inhibited the transcription and the secretion of multiple pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α, in a dose-dependent manner. Additionally, HCX3 reduced LPS-induced phosphorylation levels of p65 and IκB-α in macrophages, indicating an inhibitory effect of the compound on the activation of NF-κB signaling pathway. Collectively, our data suggest that HCX3 exhibits significant anti-inflammatory effects by inhibiting NF-κB-related signaling pathways, providing new insights for ALI treatment. Full article

Endothelial dysfunction (characterized by reduced vasodilation or vasoconstriction, oxidative stress, inflammation, and pro-thrombotic condition) is a critical factor in the pathophysiology of various cardiovascular conditions, and the application of anesthetics can affect this dysfunction. Patients undergoing major surgery, especially cardiovascular surgery, are at increased risk of endothelial dysfunction. The impact of anesthetics on endothelial function can vary depending on the specific agent, dosage, duration of exposure, comorbidities, etc. Certain anesthetics, especially at higher doses, may increase the production of reactive oxygen species (ROS), leading to oxidative stress and endothelial dysfunction through reduced nitric oxid (NO) availability. Some anesthetics can modulate inflammatory responses, either by suppressing or exacerbating inflammation, or may affect the permeability of the endothelium, potentially leading to pulmonary edema and disruption of the blood-brain barrier. Anesthetics can influence endothelial glycocalyx. Understanding anesthetics effects is crucial for optimizing anesthetic management, particularly in patients with pre-existing cardiovascular issues. Therefore, the aim of this review is to critically evaluate the effects of different classes of anesthetics on endothelial function and oxidative stress. Specifically, we address how anesthetics influence NO bioavailability, endothelial glycocalyx integrity, inflammatory and oxidative pathways, and clinical outcomes in surgical patients. By summarizing current evidence, we aim to highlight mechanistic insights and identify potential perioperative strategies to minimize endothelial dysfunction. Full article