Metabolic syndrome (MS) is a multifaceted condition characterised by insulin resistance, dyslipidemia, central obesity and hypertension, significantly elevating the risks of cardiovascular diseases and type 2 diabetes. This review aims to elucidate the bidirectional interplay between anaesthetic agents and MS, highlighting the mutual influence on metabolic regulation and anaesthetic efficacy. Accumulating evidence underscores the disruptive impact of anaesthetic agents on metabolic pathways. General anaesthetics can impair insulin signalling, thereby influencing insulin sensitivity, while local anaesthetics may indirectly affect systemic metabolism via alterations in local metabolic processes and blood flow. For instance, lidocaine interferes with the overall metabolism in the body by inhibiting tissue perfusion and local metabolic processes such as insulin signalling pathways. Conversely, MS can modulate the metabolism and efficacy of anaesthetic drugs, further complicating their clinical application. This review systematically explores the intricate relationship between anaesthetic agents and MS. It begins by delineating the primary features of MS and its potential impact on anaesthetic pharmacology. Subsequently, it examines the effects of diverse anaesthetic agents on components of MS, including insulin resistance, lipid metabolism and blood pressure regulation. Lastly, the review addresses how MS influences the metabolism and pharmacodynamics of anaesthetic drugs, offering insights into future research and clinical strategies to enhance anaesthetic management in MS patients.

The molecular features of coronary atherosclerosis progression remain incompletely understood. A comprehensive characterization of coronary proteome dynamics during atherosclerosis progression could facilitate the identification of novel biomarkers for early detection of plaque initiation and risk assessment of plaque destabilization. We performed proteomics on human coronary artery specimens representing five progressive histopathologic stages of atherosclerosis according to the modified AHA classification, including adaptive intimal thickening (AIT), pathological intimal thickening (PIT), fibroatheroma (FA), thin cap fibroatheroma (TCFA), and ruptured plaque (RP). The results revealed progressive dysregulation of complement and coagulation cascades and extracellular matrix (ECM) organization during histopathologic progression, particularly in plaque initiation and destabilization. Integrated single-cell RNA sequencing data showed that complement and coagulation pathways were predominantly upregulated in fibroblasts and macrophages, while ECM organization was elevated in fibroblasts and smooth muscle cells. Plasma proteomics in a discovery cohort identified THBS1, ECM2, and C1R proteins as robust diagnostic biomarkers from among the overlapping complement and ECM proteins found in the tissue proteomics. The combination of these biomarkers achieved area under the curve (AUC) values of 0.831 in the training set and 0.764 in the test set for identifying coronary artery disease (CAD). In both the discovery cohort and the external validation cohort, this biomarker panel distinguished stable CAD from non-stenosis controls (AUC: 0.765 and 0.841, respectively) and identified ACS patients (AUC: 0.786 and 0.822, respectively). These findings elucidate the proteomic landscape of atherosclerosis progression and establish a three-protein biomarker panel with potential for CAD diagnosis.

Internal jugular venous catheterization is an invasive procedure, and there are life-threatening complications that require urgent intervention. In this study, we present a young patient who developed myocardial injury due to internal jugular catheterization.

The patient underwent middle lobectomy for bronchiectasis. Right internal jugular venous catheterization was performed. In the fourth postoperative hour, resuscitation was initiated due to sudden hypotension, tachycardia, and altered consciousness. Bedside echocardiography, performed to evaluate the etiology of the acute presentation, revealed diffuse fluid accumulation in the pericardial cavity. Following fluid drainage, hemodynamic stability was achieved.

Possible complications can be life-threatening, and rapid diagnosis along with prompt treatment may be life-saving.

Immune checkpoint inhibitors targeting programmed cell death ligand 1 (PD-L1) have transformed cancer therapy but have been linked to increased cardiovascular risk, particularly atherosclerosis (AS). This study hypothesized that anti-PD-L1 therapy promotes atherosclerosis progression by modulating macrophage phenotypes and enhancing foam cell formation via gene-level changes. Single-cell RNA sequencing (scRNA-seq) analysis of macrophages post-anti-PD-L1 immunotherapy was conducted using the GSE169246 dataset. Differential expression, GO/KEGG enrichment, and transcription factor analyses were performed. Cellular communication patterns were examined, and in vitro validation included foam cell assays and protein-level assessments. Anti-PD-L1 treatment promoted a shift toward pro-inflammatory M1 macrophages, increased foam cell formation, and upregulated EGR1 and HSP90AB1. These gene changes correlated with altered cellular interaction patterns, particularly between macrophages and endothelial cells. PD-L1 inhibition reprograms macrophage behavior through EGR1 and HSP90AB1-mediated pathways, driving M1 polarization and foam cell development. These findings reveal a mechanistic link between immunotherapy and AS progression and underscore the need for cardiovascular monitoring in patients undergoing PD-L1 blockade.

Advanced glycation end products, systemic and vascular inflammation, and oxidative stress are risk factors for cardiovascular disease in peritoneal dialysis (PD) patients. No studies have examined the effects of melatonin on these risk factors in PD patients. This study was a randomized clinical trial. Forty-four PD patients were randomly assigned to either the melatonin or the placebo group. Participants in the melatonin group received 5 mg melatonin for 10 weeks, while the placebo group received a corresponding placebo. In this study, serum pentosidine, carboxymethyl lysine (CML), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), malondialdehyde (MDA), and glucose were measured. Serum MDA showed a significant reduction in the melatonin group (P = 0.001), and the reduction was significant compared to the placebo group (P = 0.03). Serum hs-CRP decreased in the melatonin group, and this reduction was significant compared to the placebo group (P = 0.04). Significant reductions were observed in serum sICAM-1 (P = 0.02) and pentosidine (P = 0.03) in the melatonin group. Serum CML and glucose did not show significant changes within each group. This study indicates that nightly administration of 5 mg melatonin reduces MDA, hs-CRP, sICAM-1 and pentosidine, which are cardiovascular risk factors in PD patients. ClinicalTrials.gov: NCT06096558 (23/10/2023).

Brugada syndrome (BrS) is an inherited cardiac disorder characterized by electrical disturbances. Pathogenic variants in the SCN5A gene are implicated in 25-30% of probands. Although loss-of-function mutations in SCN5A gene drive clinical severity, incomplete penetrance and interindividual susceptibility suggest additional contributing factors. Emerging evidence highlights the role of microRNAs (miRNAs), short non-coding nucleotides involved in post-transcriptional gene regulation, in cardiovascular pathophysiology. We sought to identify differences in circulating miRNAs in SCN5A gene mutation carriers according to their phenotype. 27 patients from 10 families with SCN5A gene mutations were included. Among them, 15 had a confirmed diagnosis of BrS by spontaneous or induced electrocardiographic pattern 1, while the other 12 were asymptomatic mutation carriers. Circulating miRNAs profile differences were identified by using miScript miRNA PCR-Arrays and validated by qPCR-Taqman assay. Gene set enrichment analyses (GSEA) were performed. miScript miRNA screening showed statistical differences in 10 of 84 analyzed miRNAs. Taqman analysis verified a significant downregulation of miR-320a in SCN5A mutation carriers associated with BrS phenotype. GSEA revealed a wide range of signaling pathways, including cellular adhesion and actin cytoskeleton regulatory pathways. Receiver operating characteristic curve analysis indicates that dysregulated miR-320a may help predict phenotypic differences in SCN5A mutation carriers, supporting the potential of circulating miRNAs, particularly reduced miR-320a levels, as possible predictive biomarkers for the manifestation of BrS. Additionally, our results indicate that phenotype might depend on epigenetic regulation of the electromechanical properties of the heart.

Myocardial infarction (MI) contributes to significant morbidity and mortality globally. Platelet derived growth factor-AB (PDGF-AB) is potentially a novel translational therapeutic for improving cardiac function post-MI, which we assess here using a 60 day porcine left anterior descending artery occlusion ischemia-reperfusion model. MI was induced in 10 female Landrace swine, with 5 controls, 5 receiving PDGF-AB treatment and 2 additional shams. PDGF-AB improved left ventricular ejection fraction 58 days after MI, without affecting overall infarct scar size, as shown using serial cardiac magnetic resonance imaging. Preserved infarct zone microvascular function and increased vessel maturity was also observed. Multi-omic analyses showed that PDGF-AB treatment altered the expression of proteins, metabolites, and lipids that are known to be involved in myocardial energetics and redox balance. Novel therapeutics such as PDGF-AB may lead to more sustained salvage of cardiac function by modulating the post-MI microvasculature, myocardium and extracellular matrix.

Children are particularly vulnerable to landscape fire sourced fine particulate matter (LFS PM_2.5), yet evidence on its health effects remains limited. Here we show that short-term exposure to LFS PM_2.5 is associated with increased hospital admissions for multiple diseases in children and adolescents. We analysed daily hospital admission data from 1012 communities in seven countries/territories, linked to a high-resolution LFS PM_2.5 dataset. Each 10 μg/m³ increase in LFS PM_2.5 was associated with elevated risks for all-cause (1.1%), respiratory (1.9%), infectious (1.5%), cardiovascular (2.9%), neurological (2.8%), diabetes (3.7%), cancer (1.5%), and digestive (0.8%) hospital admissions. Risks for respiratory, infectious, and neurological conditions increased even at low exposure, while others rose only above 15-20 μg/m³. Children aged 5-9 years and those in lower socioeconomic areas were especially affected. These findings highlight the health burden of LFS PM_2.5 in young people and the urgent need to reduce exposure and protect vulnerable populations.

Induced hypothermia after cardiac arrest is neuroprotective in several animal models of cardiac arrest, but few high-quality studies have been conducted in larger animals. Recent clinical trials have questioned the beneficial effects of post-ischemic hypothermia. This study investigated whether immediate cooling or a 2-h delay in cooling to 33 °C after cardiac arrest was neuroprotective compared to controlled normothermia in large animals.

Young adult female swine were anesthetized and kept at normothermia (38 °C). All animals were subject to 10 min of cardiac arrest by ventricular fibrillation, followed by 4 min of cardiopulmonary resuscitation, before the first countershock. At 10 min of return of spontaneous circulation (ROSC), animals were included and randomized to receive immediate hypothermia (33 °C), 2-h delayed hypothermia (33 °C), or normothermia for 30 h, including both cooling and rewarming time. Animals were extubated and assessed for 7 days. The primary outcome was brain histopathology using a modified Histology Damage Score. Secondary outcomes were neurocognitive testing, neurologic deficit score, and biomarkers of brain injury.

Among 42 animals, 33 were included; 11 in each arm, 23 survived until day 7. The modified Histology Damage Score was not significantly different between groups (p = 0.29). Neither neurocognitive testing nor neurologic deficit scores showed significant differences between the groups (p = 0.11 and p = 0.67, respectively). Neurofilament light chain (NfL) levels were significantly lower in the immediate hypothermia group at 48 h and on day 7 compared to the normothermia group (p = 0.0087, p = 0.012), but not in the delayed hypothermia group (p = 0.075, p = 0.33).

Our experimental model in large swine showed no neuropathological or functional protective effect of induced hypothermia after cardiac arrest, but NfL levels were lower in animals receiving immediately induced hypothermia, suggesting mitigation of neuronal injury.

Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.

An 11-year-old boy presented with erythematous plaques over the bilateral mandibular and mental regions for 2 years, accompanied by cough and dyspnea for more than 2 months. Chest computed tomography angiography revealed marked stenosis of the right pulmonary artery, irregular aortic caliber, and aortic wall thickening. Histopathological examination of the skin lesion, including immunohistochemistry and special stains, confirmed a chronic suppurative inflammation. Whole-exome sequencing was negative. A final diagnosis of granuloma faciale and Takayasu arteritis was established. Combination therapy with systemic tocilizumab, prednisone, and methotrexate, along with topical 0.1% tacrolimus ointment, resulted in a favorable clinical response. This report summarizes the clinical features of a pediatric case of granuloma faciale and Takayasu arteritis and reviews the etiology, diagnostic approach, and current treatment strategies for the disorders, aiming to enhance clinicians' understanding of these conditions.