The role of iron overload and ferroptosis in arrhythmia pathogenesis.

Ferroptosis is a newly discovered form of programmed cell death triggered by intracellular iron overload, which leads to the accumulation of lipid peroxides in various cells. It has been implicated in the pathogenesis and progression of various diseases, including tumors, neurological disorders, and cardiovascular diseases. The intricate mechanism underlying ferroptosis involves an imbalance between the oxidation and antioxidant systems, disturbances in iron metabolism, membrane lipid peroxidation, and dysregulation of amino acid metabolism. We highlight the key molecular mechanisms governing iron overload and ferroptosis, and discuss potential molecular pathways linking ferroptosis with arrhythmias.

Associations between ticagrelor use and the risk of infections: A Mendelian randomization study.

AIMS: We conducted a Mendelian randomization (MR) study to elucidate the anti-infective effects of ticagrelor. METHODS AND RESULTS: Single-nucleotide polymorphisms (SNPs) associated with serum levels of ticagrelor or its major metabolite AR-C124910XX (ARC) in the PLATelet inhibition and patient Outcomes trial were selected as genetic proxies for ticagrelor exposure. Positive control analyses indicated that genetically surrogated serum ticagrelor levels (six SNPs) but not ARC levels (two SNPs) were significantly associated with lower risks of coronary heart disease. Therefore, the six SNPs were used as genetic instruments for ticagrelor exposure, and the genome-wide association study data for five infection outcomes were derived from the UK Biobank and FinnGen consortium. The two-sample MR analyses based on inverse variance-weighted methods indicated that genetic liability to ticagrelor exposure could reduce the risk of bacterial pneumonia (odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.71-0.95, P = 8.75E-03) and sepsis (OR: 0.83, 95% CI: 0.73-0.94, P = 3.69E-03); however, no causal relationship between ticagrelor exposure and upper respiratory infection, pneumonia, and urinary tract infection was detected. Extensive sensitivity analyses corroborated these findings. CONCLUSION: Our MR study provides further evidence for the preventive effects of ticagrelor on bacterial pneumonia and sepsis.

Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection.

BACKGROUND: Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated. METHODS: We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups. RESULTS: Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001). CONCLUSION: CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.

Risk factors for electrical storms following percutaneous coronary intervention in patients with acute myocardial infarction: A meta-analysis.

Electrical storms (ESs) following percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients pose a significant challenge, affecting prognostic outcomes and increasing mortality. This meta-analysis synthesized data from 11 studies involving 9,666 AMI patients to identify risk factors associated with ES following PCI. Our findings revealed an average ES incidence of 7.70%, with identified risk factors including low thrombolysis in myocardial infarction (TIMI) flow grades (0-1), elevated cardiac troponin I levels, persistent hypotension, reperfusion arrhythmias, the right coronary artery being the infarct-related artery, increased diameter of the infarct-related artery, renal dysfunction, elevated creatine kinase-MB, and bradycardia. Notably, the use of ß-blockers was found to significantly reduce the risk of ES. The study underscores the importance of early identification and management of these risk factors in AMI patients undergoing PCI to prevent the occurrence of ES, highlighting the protective role of ß-blockers. This research provides a foundation for future strategies aimed at reducing the incidence and improving the prognosis of ES in this patient population.

Breakfast skipping and traits of cardiometabolic health: A mendelian randomization study.

BACKGROUND: Breakfast skipping has been linked to poor cardiometabolic health in observational studies, but the causality remains unknown. Herein, we used Mendelian randomization (MR) approach to elucidate the potential causal effects of breakfast skipping on cardiometabolic traits. METHODS: Genetic association estimates for breakfast skipping, cardiometabolic diseases, and cardiometabolic risk factors were extracted from the UK Biobank and several large genome-wide association studies. Two-sample MR analyses were performed primarily using the inverse variance weighted method, followed by sensitivity analysis to test the reliability of results. RESULTS: MR results indicated no causal relationship between breakfast shipping with coronary heart disease (odds ratio [OR]: 1.079, 95 % confidence interval [CI]: 0.817-1.426; p = 0.591), stroke (OR: 0.877, 95 % CI: 0.680-1.131; p = 0.311), and type 2 diabetes mellitus (OR: 1.114, 95 % CI: 0.631-1.970; p = 0.709). However, genetically predicted breakfast skipping was significantly associated with increased body mass index (ß: 0.250, standard error [SE]: 0.079; p = 0.001), waist-to-hip ratio (ß: 0.177, SE: 0.076; p = 0.019), and low-density lipoprotein cholesterol (ß: 0.260, SE: 0.115; p = 0.024). We found no evidence of association of genetic liability to breakfast skipping with blood pressure, glycemic traits, and other blood lipids. Sensitivity analysis supported the above results. CONCLUSION: Our study suggested that breakfast skipping is causally linked to weight gain and higher serum low-density lipoprotein cholesterol, which may mediate the increased risk of cardiometabolic diseases reported in epidemiological studies.

Prevalence of Primary Drug Resistance Among Newly Diagnosed HIV-1-Infected Individuals in Hunan Province, China.

At present, research on the prevalence of primary drug resistance (PDR) in Hunan Province is limited. Therefore, we explored the current status of HIV-1 PDR in Hunan to provide a basis for antiretroviral therapy (ART) and a theoretical foundation for prevention and control of the HIV/AIDS epidemic. Three hundred seventy newly diagnosed HIV-1-infected individuals who had not received ART in Hunan province, China, were enrolled in the study. Plasma samples were collected, RNA was extracted, two rounds of gene amplification were carried out with the in-house method, and subtype analysis and drug resistance analysis were carried out with relevant software. We found that the most prevalent subtypes of HIV-1 in Hunan Province are CRF_01AE (126/359, 35.1%) and CRF07_BC (85/359, 23.7%). The PDR rate among newly diagnosed HIV/AIDS patients was 10.0% (36/359). Among them, the drug resistance rates of protease inhibitors, nucleotide reverse transcriptase inhibitors, non-nucleotide reverse transcriptase inhibitors, and integrase inhibitors were 0.3% (1/359), 3.3% (12/359), 8.36% (30/359), and 0.6% (2/359), respectively. The distribution of HIV-1 subtypes in Hunan Province is diverse and complex, and the PDR rate has exceeded the low-level warning line set by the World Health Organization (<5%). Therefore, we should conduct pretreatment drug resistance assays to determine the optimal primary ART so that patients can obtain better antiretroviral treatment outcomes and transmission of drug-resistant strains in the population can be blocked.

Impacts of ainuovirine-based and efavirenz-based antiretroviral therapies on the lipid profile of HIV/AIDS patients in southern China: a real-world study.

Background: The newly approved third-generation oral anti-HIV-1 drug, ainuovirine (ANV), was used in combination with nucleoside reverse transcriptase inhibitors (NRTIs) in our study, and its effects on the lipid profile of antiretroviral-experienced HIV/AIDS patients are unclear. Objectives: This study aimed to examine the effects of antiretroviral agents on the lipid profile in patients with HIV/AIDS. Methods: We conducted a real-world prospective study involving treatment-naive and treatment-experienced adult participants living with HIV-1 infection provided with ANV- or efavirenz (EFV)-based regimens. The primary endpoint was the proportion of participants with an HIV-1 RNA level of <50 copies/mL at week 24 of treatment. Secondary endpoints included the change from baseline in CD4+ T-cell count and lipid profile. Results: A total of 60 treatment-naive and 47 treatment-experienced participants received an ANV-based regimen, while 88 treatment-naive and 47 treatment-experienced participants receiving an EFV-based regimen were, respectively, matched as controls. At week 24 following treatment, the proportion of participants with an HIV-1 RNA level of <50 copies/mL and the mean changes of CD4+ T-cell counts from baseline were significantly higher in naive-ANV group than those in naive-EFV group (p < 0.01). Compared with the EFV group, both naive and experienced ANV groups exhibited a favorable lipid profile, including constant changes in total cholesterol and triglycerides, a significant decrease in LDL-cholesterol (p < 0.0001), and a dramatic increase in HDL-cholesterol (p < 0.001). Conclusion: The efficacy of ANV was non-inferior to EFV when combined with two NRTIs. Patients receiving ANV-based regimens had a decreased prevalence of dyslipidemia.

Olive oil consumption and risk of cardiovascular disease and all-cause mortality: A meta-analysis of prospective cohort studies.

Background: Epidemiological studies have shown the preventive effects of olive oil consumption against cardiovascular events and all-cause deaths, but the results remain inconsistent. Herein, we performed a meta-analysis to elucidate this association. Materials and methods: A systematical literature search was conducted in online databases (PubMed and Scopus) through July 31, 2022. Prospective cohort studies providing the risk of total cardiovascular disease (CVD) or all-cause mortality for olive oil consumption were included. Relative risks (RRs) and 95% confidence intervals (CIs) were aggregated using random-effect model. Results: This meta-analysis included 13 studies comprising a total of 13 prospective cohorts. Compared with lower consumption, higher consumption of olive oil conferred a significantly reduced risk in CVD (RR: 0.85, 95% CI: 0.77-0.93, p < 0.001) and all-cause mortality (RR: 0.83, 95% CI: 0.77-0.90, p < 0.001). This beneficial effect was not modified by the potential confounders such as study country, sample size, follow-up duration, gender, and type of olive oil consumed. In dose-response meta-analysis, the summary RR of per 5-g/days increase in olive oil intake was 0.96 (95% CI: 0.93-0.99, p = 0.005) for CVD and 0.96 (95% CI: 0.95-0.96, p < 0.001) for all-cause mortality. Non-linear associations of olive oil intake with CVD and all-cause mortality were also identified (both p for non-linearity < 0.001), with little additional or no risk reduction observed beyond the consumption of approximately 20 g/days. Conclusion: Olive oil consumption is inversely related to the risk of CVD and all-cause mortality. Such benefits seem to be obtained with an intake of olive oil up to 20 g/days, which deserves further exploration in future studies.