Search Results (2,977)

Acute ischemic stroke (AIS) is characterized by complex interactions among vascular occlusion, endothelial injury, and inflammatory activation, which collectively influence clinical outcomes. Increasing attention has focused on the endothelial glycocalyx, a critical regulator of vascular permeability, mechanotransduction, and inflammatory signaling. Disruption of the endothelial glycocalyx during ischemia and subsequent reperfusion contributes to blood–brain barrier (BBB) dysfunction and secondary brain injury. Mechanical thrombectomy has emerged as the reference standard treatment for large vessel occlusion in AIS. This review synthesizes current evidence on endothelial glycocalyx degradation and associated inflammatory cascades in cute ischemic stroke, with particular emphasis on patients undergoing mechanical thrombectomy. We examine the mechanisms underlying endothelial and BBB injury, ischemia–reperfusion-mediated vascular dysfunction, and systemic inflammatory responses (SIRS). In addition, the potential clinical relevance of circulating biomarkers indicative of endothelial glycocalyx shedding and endothelial damage is discussed. By integrating molecular pathophysiology with contemporary reperfusion strategies, this review highlights the importance of endothelial protection as a potential adjunct to mechanical thrombectomy. While mechanical thrombectomy remains the gold standard therapy for AIS due to large vessel occlusion, targeting endothelial glycocalyx integrity and post-reperfusion inflammation may represent a promising approach to optimizing neurological outcomes and reducing complications. Further research is required to elucidate specific pathophysiological mechanisms and to develop targeted therapeutic strategies aimed at reducing stroke-related morbidity and mortality. Full article

Background: New therapies like intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) for acute ischemic stroke (AIS) can significantly impact outcomes and complication rates. This study examines the nationwide impact of MT implementation on decompressive hemicraniectomy (DH) in Germany, accounting for the effects of the COVID-19 pandemic. Methods: Annual treatment numbers (2015 to 2023) for IVT, MT, DH, cranioplasty (CP), and Computer-Aided Design CP (CAD CP) were extracted using the Operation and Procedure Codes (OPS). Age and sex distributions were analysed in four age groups (0–39, 40–59, 60–79, ≥80 years). Hospitalizations for AIS, subarachnoid haemorrhage (SAH), and intracranial haemorrhage (ICH) were included. Annual treatment rates were calculated. Results: In 2015 250,802 patients with ACI, 11,082 patients with SAH and 47,336 patients with ICH were documented. Overall, AIS hospitalizations declined slightly by 1.1%, whereas SAH and ICH decreased more markedly by 15.6% and 14.3%, respectively, with the most pronounced reductions observed during the COVID-19 pandemic. Among AIS patients, intravenous thrombolysis increased from 16% to 20%, while mechanical thrombectomy rates increased from 3% to 9%. Both reperfusion therapies showed increasing use particularly among patients aged ≥80 years (IVT: +35%; MT: +42%). DH remained overall stable (+2.82%), with a predominance in men (60%). In contrast, CP procedures declined by 25.3%, whereas CAD CP increased by 35% during the observation period. Conclusions: Long-term increasing trends in reperfusion therapies, especially mechanical thrombectomy, were largely unaffected by the COVID-19 pandemic and—contrary to expectation—obviously had no influence on the emergence of decompressive hemicraniectomy in our descriptive analysis. Full article

Bilirubin, historically recognized solely as a waste product of heme catabolism, has recently gained attention for its potential protective role in the cardiovascular system. Experimental and clinical studies suggest that bilirubin exhibits potent antioxidant, anti-inflammatory, anti-apoptotic, and cytoprotective properties that may protect the heart against oxidative stress, ischemia–reperfusion injury, and the progression of cardiovascular diseases, such as heart failure. As an endogenous hormone, bilirubin activates peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor that controls energy balance and lipid metabolism. Moderately elevated circulating bilirubin levels have been associated with a reduced risk of coronary artery disease, heart failure, and myocardial infarction; however, the mechanisms underlying bilirubin’s protective effects remain incompletely understood. Conversely, the gut microbiota’s metabolism of bilirubin to urobilin is detrimental, given urobilin’s association with cardiometabolic dysfunction. The therapeutic potential of bilirubin in the management of cardiovascular disease is becoming increasingly apparent, supported by preclinical research and emerging technologies that enhance bilirubin delivery via nanoparticles and methods to elevate plasma bilirubin levels. Collectively, these scientific advancements position bilirubin as a promising, biologically plausible endogenous therapeutic for the prevention and treatment of heart disease. Full article

Background/Objectives: Acute carotid tandem lesions (TLs), defined by concurrent cervical internal carotid artery (ICA) stenosis or occlusion and intracranial large vessel occlusion, occur in 10–20% of patients undergoing mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Optimal periprocedural antiplatelet management during emergent carotid artery stenting (eCAS) remains uncertain, particularly regarding the balance between preventing stent thrombosis and avoiding hemorrhagic complications. Methods: A narrative review was conducted using PubMed and Scopus (until 6 March 2026) to identify English-language studies evaluating antiplatelet therapies during eCAS for TLs. We included seven real-world studies and registry analyses. Data on study design, patient characteristics, procedural strategies, angiographic results, functional outcomes, and safety metrics were extracted. Results: No randomized controlled trials (RCTs) were identified. The available evidence is derived exclusively from observational studies. Across these cohorts, glycoprotein IIb/IIIa inhibitors (GPIs), particularly tirofiban, were generally associated with lower rates of in-stent thrombosis and higher reperfusion success, with symptomatic intracranial hemorrhage (sICH) rates that appeared comparable to or lower than those reported with acetylsalicylic acid (ASA). Cangrelor, an intravenous (IV) P2Y₁₂ inhibitor, was associated with improved stent patency and increased likelihood of complete reperfusion, although reported effects on clinical outcomes were inconsistent when compared with GPIs or ASA. Aside from abciximab, potent IV antiplatelet agents did not consistently show an increased sICH signal. Oral dual antiplatelet therapy was also associated with improved technical outcomes without a clear excess in bleeding complications. Conclusions: Current real-world observational data suggest that rapid-acting IV antiplatelet agents—particularly GPIs and, increasingly, cangrelor—may represent feasible periprocedural options during eCAS for TLs, with potential benefits for technical success and no consistent evidence of increased hemorrhagic risk. However, interpretation is limited by study heterogeneity and non-randomized designs. The absence of RCTs highlights the need for prospective comparative studies and standardized periprocedural antiplatelet protocols. Full article

Sickle cell anemia (SCA) is a genetic disorder characterized by chronic hemolysis, primarily driven by red blood cell lysis. Its pathophysiology is centered, though not exclusively, on the increased release of intracellular components, such as hemoglobin degradation products, which are known to stimulate innate immune responses and promote prothrombotic states. Current therapies alleviate symptoms, yet patients remain exposed to a chronic inflammatory milieu punctuated by episodes of acute pain. The recurrence of these crises can be life-threatening due to ischemia–reperfusion injury, hypercoagulability, and respiratory complications. Central mechanisms are marked by elevated hemolysis, heightened inflammatory signaling, and increased procoagulant activity, largely driven by soluble molecules released into the plasma, such as hemoglobin, nuclear molecules and other products. These compounds are recognized from sensors on immune and endothelial cells, named Pattern Recognition Receptors (PRRs), and constitute canonical pathways for intracellular activation. Four main types have been extensively studied in the literature over recent years in both infectious and sterile inflammatory contexts; still, only a few have elucidated the mechanisms underlying acute and chronic inflammation in patients with SCA. Although Toll receptors were shown to be major in triggering immunity, other receptors were found to be important regarding this function, which suggested a multifactorial mechanism for this triggering. Therefore, here, we propose a comprehensive review of previously published findings regarding the expression, activation, and dynamics of Toll-like, NOD-like, and RIG-I–like receptors in the progression of SCA and its associated inflammatory features. Full article

Acute kidney injury (AKI) continues to pose a significant clinical challenge due to its high morbidity rates and limited therapeutic options. Recent evidence suggests that natural compounds may provide renoprotective benefits by modulating oxidative stress and inflammation. This study examines the protective effects of a novel polysaccharide peptide extracted from Ganoderma lucidum (GL-PPQ1) against renal ischemia–reperfusion (I/R) injury, with particular emphasis on the integrin β3/Fibronectin 1 (Fn1) signaling axis. A murine model of renal I/R injury was established, and GL-PPQ1 was administered orally for seven days before surgery. The assessment included renal function, histopathology, oxidative stress markers, and inflammatory cytokines. Additionally, transcriptomic profiling and protein expression analyses were conducted to elucidate the underlying mechanisms. The results revealed that GL-PPQ1 pretreatment significantly reduced renal tubular damage, lowered serum creatinine and blood urea nitrogen levels, and diminished oxidative stress and inflammatory responses. RNA sequencing revealed that GL-PPQ1 affected gene sets associated with extracellular matrix remodeling and cell adhesion. Western blot and immunohistochemistry further confirmed that GL-PPQ1 decreased the expression of integrin β3 and Fn1, suggesting a regulatory effect on their interaction during I/R injury. These findings demonstrate that GL-PPQ1 offers substantial kidney protection by mitigating oxidative stress, inflammation, and dysregulation of the integrin β3/Fn1 signaling pathway. Thus, this study supports that polysaccharide peptides derived from Ganoderma lucidum could have the potential to serve as both a dietary supplement and a therapeutic agent in the treatment of AKI. Full article

Liver transplantation is the definitive therapy for end-stage liver disease, yet persistent organ shortages result in approximately 10% of recovered livers being discarded, with markedly higher discard rates among marginal grafts from elderly donors, donation after circulatory death (DCD), and those with macrovesicular steatosis. Machine perfusion (MP) has emerged as a paradigm-shifting preservation strategy with the potential to safely expand the usable donor pool. This narrative review examines the current evidence for three MP modalities—hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), and normothermic regional perfusion (NRP)—across various marginal donor populations, including elderly donors, steatotic grafts, donors with infectious diseases, and split liver transplantation. Current evidence demonstrates that MP significantly increases utilization of steatotic grafts with up to an eightfold rise in usage of severely steatotic organs. HMP consistently reduces non-anastomotic biliary strictures and early allograft dysfunction across donor types, while NMP enables real-time viability assessment and reduces post-reperfusion syndrome in steatotic grafts. NRP shows particular benefit in DCD organs, reducing biliary complications and improving one-year survival. Additionally, MP extends preservation times enabling next-day split liver transplantation and shows promise as a platform for ex situ antiviral therapy. Despite compelling evidence supporting MP in marginal grafts, widespread adoption remains constrained by high costs, logistical complexity, and the absence of standardized protocols. Future progress will require multicenter studies evaluating long-term outcomes alongside consensus-driven implementation frameworks. Full article

Ischemic stroke promotes monocyte recruitment to the injured brain and their differentiation into monocyte-derived macrophages (MDMs). These cells contribute to debris clearance but may also exacerbate neuroinflammation. However, the heterogeneity of MDM subsets and the phenotypic transitions that shape MDM functional states during the subacute phase of stroke remain incompletely characterized. To address this, we first performed single-cell RNA sequencing (scRNA-seq) to define the transcriptional landscape of the mouse brain 48 h after transient middle cerebral artery occlusion/reperfusion compared with sham controls. Reclustering of macrophage-lineage cells identified multiple MDM subsets, including a distinct Cd68^hi/Ctsd^hi MDM subset enriched for lysosomal and lipid-processing gene expression programs. Cell trajectory inference supported a transition from early recruited MDMs toward the Cd68^hi/Ctsd^hi state, accompanied by induction of transcriptomic networks that drive MDM function to favor a clearance-competent phenotype in response to ischemic stroke. Complementary single-cell ATAC sequencing (scATAC-seq) demonstrated cell type-specific chromatin remodeling after stroke and revealed MDM subclusters with accessibility at key loci regulating lysosomal function and lipid metabolism. Together, our findings define a cellular and regulatory framework of the subacute post-stroke brain and identify a lysosome-enriched Cd68^hi/Ctsd^hi MDM trajectory, highlighting endolysosomal and lipid-processing programs during early stroke recovery. Full article

Severe accidental hypothermia represents a unique and potentially reversible cause of cardiac arrest in which prolonged resuscitation may still result in favorable neurological recovery. Unlike normothermic cardiac arrest, hypothermic cardiac arrest (HCA) is characterized by profound metabolic suppression and temperature-mediated myocardial instability, requiring a fundamentally different therapeutic paradigm. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) provides not only circulatory support but also controlled reperfusion and rewarming, positioning it as the cornerstone of modern management. Recent international guidelines have clarified indications for extracorporeal life support (ECLS) in HCA and have contributed to improved standardization of care. Building upon these recommendations, this narrative review focuses on physiological principles underlying extracorporeal rewarming and their implications for bedside management. We examine mechanisms of ischemia–reperfusion injury, rewarming-associated hemodynamic instability and myocardial stunning, discuss dynamic risk assessment beyond statistical thresholds such as the HOPE score and summarize practical considerations regarding cannulation strategies, differential hypoxia, left ventricular unloading and neurologic evaluation. By integrating current evidence with pathophysiological insight and organizational considerations, this review proposes a clinically oriented framework to support decision-making in hypothermic cardiac arrest and to optimize meaningful neurological recovery. Full article

Background: Post-cardiac arrest syndrome (PCAS) following out-of-hospital cardiac arrest (OHCA) is driven by global ischemia–reperfusion injury, endothelial dysfunction, and a dysregulated inflammatory response. This cascade frequently culminates in profound vasoplegia and multiorgan failure, even when guideline-directed post-resuscitation management is applied. Hemoadsorption using the CytoSorb device may attenuate hyperinflammation and vasoplegia by removing circulating inflammatory and injury-related mediators. Methods: This single-centre, retrospective cohort study compared adults with PCAS following OHCA who received hemoadsorption with propensity score-matched controls (1:1 matching; n = 50 per group). For patients treated with hemoadsorption, data were analyzed within predefined intervals covering the 24 h preceding therapy initiation (T1) and the 24 h following the completion of the hemoadsorption treatment period (T2). Controls were evaluated at time points aligned to those of their matched hemoadsorption counterparts. Hemodynamic, metabolic, respiratory, and organ injury markers were assessed. Results: Formal between-group comparisons of temporal change between T1 and T2 showed no statistically significant differences between hemoadsorption-treated patients and matched controls across key parameters, including VIS (Δ −18.7 vs. −7.7; p = 0.183) and lactate (Δ −1.8 vs. −1.25 mmol/L; p = 0.780), as well as markers of organ injury, pH, and oxygenation. In exploratory ANCOVA models, only base excess was associated with treatment group (p = 0.035). Survival to hospital discharge was comparable (48% vs. 40%; p = 0.423), with similar neurological outcomes. Within the hemoadsorption group, pre–post comparisons around hemoadsorption initiation (T1–T2) demonstrated marked improvements, including reduced vasoactive support (VIS 70.0 to 12.1; p = 0.039), substantial lactate clearance (4.1 to 1.1 mmol/L; p < 0.001), and declines in organ injury markers (AST, ALT, LDH, myoglobin), alongside more pronounced platelet reduction compared with controls (129 to 57 × 10³/µL vs. 189 to 123 × 10³/µL). However, adjusted analyses indicated that these changes were primarily driven by baseline shock severity rather than a treatment-specific effect. Conclusions: In this propensity score-matched cohort of PCAS patients after OHCA, hemoadsorption was associated with within-group physiological changes but showed no detectable advantage over matched controls, with similar survival. These findings are hypothesis-generating and warrant prospective studies with standardized timing and phenotype-guided patient selection. Full article

Ischemic stroke (IS) remains a major cause of global disability and mortality. While exogenous H₂S has demonstrated neuroprotective potential, the role of endogenous H₂S generated by cystathionine β-synthase (CBS) in cerebral ischemia–reperfusion injury (CIRI) remains incompletely elucidated. L-Cysteine (L-Cys), as a substrate for CBS, serves as a key precursor for endogenous H₂S. Using the established pre-clinical model of CIRI—middle cerebral artery occlusion/reperfusion (MCAO/R) in rats—we investigated the neuroprotective effects of brain-derived CBS-generated H₂S through neurological function scoring, 2,3,5-triphenylchlorotetrazole (TTC) staining, enzyme-linked immunosorbent assay (ELISA), and histopathological examination. Immunofluorescence, Western blot, and laser speckle contrast imaging were utilized to analyze the protein expression of ZO-1, claudin-5, CBS, vascular endothelial growth factor receptor-2 (VEGFR₂) and CD31, as well as cerebral blood flux changes. L-Cys treatment ameliorated neurological deficits, reduced cerebral infarct volume, decreased serum lactate dehydrogenase (LDH) and neuron-specific enolase (NSE) levels, attenuated histopathological damage, alleviated cerebral edema, and restored blood–brain barrier integrity via upregulation of tight junction proteins ZO-1 and claudin-5. Additionally, L-Cys improved MCAO/R-induced cognitive impairment and behavioral deficits. Furthermore, L-Cys upregulated CBS and VEGFR₂ expression, enhanced endogenous H₂S production, promoted post-ischemic cerebral angiogenesis, and improved cerebral blood flux recovery. CBS-derived H₂S promoted post-ischemic angiogenesis mediated by VEGFR₂, enhances cerebral reperfusion flux, and consequently ameliorated MCAO/R-induced CIRI in rats, providing experimental evidence for clinical translation. Full article

Background/Objectives: Myocardial ischemia–reperfusion injury (MIRI) remains an ever-growing threat in the field of cardiology, as it has become a major risk factor for unfavorable outcomes following reperfusion therapies. Oxidative stress and inflammation remain the key pathophysiological mechanisms underlying MIRI, and the presently available treatments fail to prevent this process effectively. This systematic review aimed to summarize and critically assess the latest preclinical research (2020–2026) on nanocarrier-based interventions targeting oxidative stress in MIRI, highlighting the potential of the new nanostructures in cardioprotection. Methods: A total of 24 studies meeting the PRISMA criteria have been found through a literature search of PubMed, Embase, and Web of Science databases published between 2020 and 2026. The studies eligible for inclusion had focused on the efficacy of nanocarrier-based interventions in preclinical studies of MIRI. Results: Of the 24 included studies, all investigated nanocarrier-based interventions in preclinical models of MIRI. In vitro, ex vivo, and in vivo models were diverse, with most studies being a combination of both in vitro and in vivo models. Commonly studied were lipid-based nanocarriers, polymeric nanoparticles, and biomimetic nanocarriers. Across studies assessed for this review, treatments with nanocarriers were seen to suppress inflammatory and oxidative stress pathways, with a few studies showing a suppression of cardiomyocyte apoptosis. Cardiac function was restored as determined by echocardiography analyses or ex vivo models of the myocardium, thus validating that the nanocarrier-mediated therapies are effective against MIRI. Conclusions: The analyzed preclinical studies indicate that the described therapies could provide a promising basis for future clinical trials in the treatment of MIRI, provided their safety and efficacy are confirmed in clinical trials. Full article

Background/Objectives: Percutaneous coronary intervention (PCI) effectively restores coronary flow in acute myocardial infarction (AMI), but myocardial ischemia–reperfusion injury (MIRI) remains a major prognostic determinant. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown cardiovascular protective effects, yet its association with MIRI is unclear. This study aimed to investigate the relationship between serum MOTS-c levels and MIRI in AMI patients. Methods: Seventy-two AMI patients undergoing PCI were enrolled and divided into MIRI (n = 34) and non-MIRI (n = 38) groups. Clinical data and MOTS-c levels in peripheral serum and intracoronary blood were compared. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were performed to identify MIRI predictors. Results: The MIRI group exhibited lower systolic blood pressure, preoperative thrombolysis in myocardial infarction (TIMI) grade, and HDL-C, but higher total ischemic time, door-to-balloon time, culprit vessel stenosis severity, Killip grade and adverse event incidence (all p < 0.05). Postoperative peripheral serum MOTS-c levels were significantly lower in the MIRI group than in the non-MIRI group (p < 0.05), while preoperative peripheral and intracoronary MOTS-c levels showed no significant differences between groups. Multivariate logistic regression identified postoperative peripheral MOTS-c levels (OR = 0.986, 95%CI: 0.976–0.996) and preoperative TIMI grade ≥ 1 (OR = 0.036, 95%CI: 0.004–0.309) as independent protective factors for MIRI, whereas serum creatinine was identified as an independent risk factor. ROC analysis demonstrated that postoperative peripheral MOTS-c levels predicted MIRI with an area under the curve of 0.648. Conclusions: Postoperative peripheral serum MOTS-c levels represent an independent protective factor against MIRI in patients with acute myocardial infarction and suggest a potential predictive value for MIRI, although its clinical utility as a standalone predictor requires further validation through dynamic monitoring and larger-scale studies. This finding may offer a potential novel biomarker and therapeutic direction for MIRI. Full article

Acute pulmonary embolism (PE) is increasingly managed as a dynamic risk continuum in which imaging findings guide therapeutic escalation rather than merely confirm diagnosis. The principal challenge still remains normotensive patients with intermediate–high-risk features, where early right ventricular (RV) dysfunction may precede overt hemodynamic collapse. New trends focus on a trajectory-based model by integrating clinical, laboratory, and standardized imaging parameters into severity categorization. This review critically examines how imaging-derived markers influence risk stratification, escalation timing, and endovascular decision pathways in contemporary PE management. A structured narrative review was conducted focusing on the literature published between January 2020 and January 2026. PubMed/MEDLINE, Scopus, and Web of Science were searched for studies addressing imaging-based risk assessment, catheter-based reperfusion strategies, randomized trials, prospective registries, and guideline documents. Contemporary data consistently demonstrate that catheter directed therapies (CDTs) lead to rapid improvement in RV imaging surrogates and hemodynamic parameters. However, short-term mortality differences are uncommon in predominantly normotensive cohorts. Clinically meaningful signals instead emerge in the reduction in early clinical deterioration, the need for rescue escalation, bleeding optimization, and healthcare resource utilization. Imaging, as standardized reporting of RV strain on computed tomography pulmonary angiography and echocardiography, should be further embedded into escalation algorithms. In modern PE care, imaging functions as a trigger for escalation within multidisciplinary pathways rather than as a passive prognostic marker. CDTs should be interpreted as tools for trajectory modulation in selected intermediate-risk patients rather than mortality-reduction strategies. Future research should integrate imaging phenotyping, dynamic reassessment models, and organizational variables to refine patient selection and optimize outcome-relevant endpoints. Full article

Myocardial ischemia–reperfusion injury (MIRI) significantly limits the clinical benefits of reperfusion therapy, underscoring a pressing need for effective interventions. This study examines the cardioprotective effects and underlying mechanisms of the natural amide alkaloid N-p-trans-Coumaroyltyramine (p-CT). Using hypoxia/reoxygenation (H/R) models in neonatal rat cardiomyocytes and in vivo rat MIRI models, we assessed p-CT pretreatment on cell viability, cardiac function, serum injury markers (lactate dehydrogenase, creatine kinase-MB, cardiac troponin T, and myoglobin), myocardial histopathology, ultrastructural alterations, and infarct size. The systematic screening and validation of potential targets were conducted via label-free quantitative proteomics, molecular docking, and Western blot. The results demonstrated that p-CT pretreatment dose-dependently mitigated H/R-induced cellular injury, improved cardiac function in MIRI rats, reduced serum markers of myocardial damage, alleviated pathological and ultrastructural injury in myocardial tissue, and significantly diminished infarct size. Proteomic analysis revealed 19 differentially expressed proteins specifically reversed by p-CT, with Titin-cap (Tcap) exhibiting the most pronounced downregulation in the MIRI model—a change effectively restored by p-CT pretreatment. Molecular docking indicated strong binding affinity between p-CT and Tcap protein. In summary, p-CT represents a promising cardioprotective agent, likely exerting its effects by targeting Tcap protein and upregulating its expression, thereby helping preserve cardiomyocyte structural and functional integrity. Full article