Monoclonal antibodies for dyslipidemia in adults: a focus on vulnerable patients groups.

INTRODUCTION: Dyslipidemia significantly contributes to atherosclerotic cardiovascular disease (ASCVD). Patients with lipid-rich vulnerable plaques are particularly susceptible to cardiovascular complications. Despite available lipid-lowering therapies (LLTs), challenges in effective lipid management remain. AREAS COVERED: This article reviews monoclonal antibody (mAb) therapy in dyslipidemia, particularly focusing on vulnerable plaques and patients. We have reviewed the definitions of vulnerable plaques and patients, outlined the efficacy of traditional LLTs, and discussed in-depth the mAbs targeting PCSK9. We extensively discuss the potential mechanisms, intracoronary imaging, and clinical evidence of PCSK9mAbs in vulnerable plaques and patients. A brief overview of promising mAbs targeting other targets such as ANGPTL3 is also provided. EXPERT OPINION: Research consistently supports the potential of mAb therapies in treating adult dyslipidemia, particularly in vulnerable patients. PCSK9mAbs are effective in regulating lipid parameters, such as LDL-C and Lp(a), and exhibit anti-inflammatory and anti-thrombotic properties. These antibodies also maintain endothelial and smooth muscle health, contributing to the stabilization of vulnerable plaques and reduction in adverse cardiovascular events. Future research aims to further understand PCSK9 and other targets like ANGPTL3, focusing on vulnerable groups. Overall, mAbs are emerging as a promising and superior approach in dyslipidemia management and cardiovascular disease prevention.

Intravenous immunoglobulin for treatment of hospitalized COVID-19 patients: an evidence mapping and meta-analysis.

BACKGROUND: The clinical efficacy and safety of intravenous immunoglobulin (IVIg) treatment for COVID-19 remain controversial. This study aimed to map the current status and gaps of available evidence, and conduct a meta-analysis to further investigate the benefit of IVIg in COVID-19 patients. METHODS: Electronic databases were searched for systematic reviews/meta-analyses (SR/MAs), primary studies with control groups, reporting on the use of IVIg in patients with COVID-19. A random-effects meta-analysis with subgroup analyses regarding study design and patient disease severity was performed. Our outcomes of interest determined by the evidence mapping, were mortality, length of hospitalization (days), length of intensive care unit (ICU) stay (days), number of patients requiring mechanical ventilation, and adverse events. RESULTS: We included 34 studies (12 SR/MAs, 8 prospective and 14 retrospective studies). A total of 5571 hospitalized patients were involved in 22 primary studies. Random-effects meta-analyses of very low to moderate evidence showed that there was little or no difference between IVIg and standard care or placebo in reducing mortality (relative risk [RR] 0.91; 95% CI 0.78-1.06; risk difference [RD] 3.3% fewer), length of hospital (mean difference [MD] 0.37; 95% CI - 2.56, 3.31) and ICU (MD 0.36; 95% CI - 0.81, 1.53) stays, mechanical ventilation use (RR 0.92; 95% CI 0.68-1.24; RD 2.8% fewer), and adverse events (RR 0.98; 95% CI 0.84-1.14; RD 0.5% fewer) of patients with COVID-19. Sensitivity analysis using a fixed-effects model indicated that IVIg may reduce mortality (RR 0.76; 95% CI 0.60-0.97), and increase length of hospital stay (MD 0.68; 95% CI 0.09-1.28). CONCLUSION: Very low to moderate certainty of evidence indicated IVIg may not improve the clinical outcomes of hospitalized patients with COVID-19. Given the discrepancy between the random- and fixed-effects model results, further large-scale and well-designed RCTs are warranted.

Sex and age disparities in the influence of tobacco smoking on depression: Evidence from the Taiwan Biobank.

INTRODUCTION: The global tobacco epidemic poses a notable challenge to global health due to its association with various tobacco-related diseases. Although tobacco smoking is associated with depression, the exact mechanism by which tobacco smoking increases the risk of depression is unclear. This study explored the potential effects of tobacco smoking on depression. METHODS: We used data in the analysis from the Taiwan Biobank of 27916 individuals recruited from 2015 to 2020. To investigate the associations between tobacco use and depression, the results of the depression-measuring subscale of the Patient Health Questionnaire-4 as well as data on participants' tobacco consumption and other relevant covariates, were analyzed. RESULTS: Participants who smoked were more likely to report depression than those who did not smoke (AOR=1.50; 95% CI: 1.21-1.86). Furthermore, depression was significantly higher in women who smoked than in their male counterparts (females: AOR=1.68; 95% CI: 1.27-2.23, and males: AOR=1.32; 95% CI: 0.96-1.80). Women aged <55 years and who smoked were more likely to report depression, whereas this trend was not observed in those aged ≥55 years (<55 years: AOR=1.75; 95% CI: 1.23-2.48), and ≥55 years: AOR=1.58; 95% CI: 0.97-2.56). CONCLUSIONS: Tobacco smoking is a significant factor associated with depression, particularly in younger women. The increasing prevalence of tobacco use for years among younger women in Taiwan might contribute to shifts in the associations between depression and tobacco use in women.

The Association between Statins and Liver Cancer Risk in Patients with Heart Failure: A Nationwide Population-Based Cohort Study.

Heart failure (HF) and cancer have similar risk factors. HMG-CoA reductase inhibitors, also known as statins, are chemoprotective agents against carcinogenesis. We aimed to evaluate the chemoprotective effects of statins against liver cancer in patients with HF. This cohort study enrolled patients with HF aged ≥20 years between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database in Taiwan. Each patient was followed to assess liver cancer risk. A total of 25,853 patients with HF were followed for a 12-year period; 7364 patients used statins and 18,489 did not. The liver cancer risk decreased in statin users versus non-users (adjusted hazard ratio (aHR) = 0.26, 95% confidence interval (CI): 0.20-0.33) in the entire cohort in the multivariate regression analysis. In addition, both lipophilic and hydrophilic statins reduced the liver cancer risk in patients with HF (aHR 0.34, 95% CI: 0.26-0.44 and aHR 0.42, 95% CI: 0.28-0.54, respectively). In the sensitivity analysis, statin users in all dose-stratified subgroups had a reduced liver cancer risk regardless of age, sex, comorbidity, or other concomitant drug use. In conclusion, statins may decrease liver cancer risk in patients with HF.

Influence of Sex Differences on Serum Lipid Profiles among Habitual Coffee Drinkers: Evidence from 23,072 Taiwan Biobank Participants.

The bioactive compounds of coffee are involved in lipid metabolism, and sex differences may play an important role. This study aimed to evaluate the influence of sex differences on serum lipid profiles among habitual coffee drinkers. We conducted a nationwide cross-sectional study of 23,628 adults using data obtained from the Taiwan Biobank database. Adults who drank more than one cup of coffee per day and those who drank less than one cup per day were compared with non-drinkers. After adjusting for baseline demographics and lifestyle, a generalized linear model was used to estimate the change in serum lipid profiles in men and women and in postmenopausal and premenopausal women among different coffee-drinking behaviors. We found that habitual coffee consumption changed the serum lipid profiles of men and women. Further, coffee drinkers had higher serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lower serum triglyceride levels than non-drinkers. Compared with premenopausal women, both men and postmenopausal women had increased serum total cholesterol and low-density lipoprotein cholesterol levels. Menopausal status may play an important role in modulating the effect of habitual coffee intake on dyslipidemia. Moreover, premenopausal women potentially benefit more from habitual coffee drinking than men and postmenopausal women.

Coronary Stent Off-Wire Dislodgement: Case Report of a Rare Complication.

Although several techniques have been reported for managing an on-wire dislodged stent in the coronary artery, very few reports have focused on the much rarer complication of an off-wire dislodged stent. In a 73-year-old man who experienced an off-wire dislodged coronary stent, the proximal elongated segment was lodged in the left main coronary artery, and the distal segment was floating in the aorta like a wind sock. After a failed attempt at retrieval using a gooseneck microsnare, the dislodged stent was successfully removed using a 3-loop vascular snare via the left radial artery. There was no obvious vascular injury. This novel technique for removing a partially floating dislodged stent was successful after conventional retrieval techniques failed.

The Relationship between Habitual Coffee Drinking and the Prevalence of Metabolic Syndrome in Taiwanese Adults: Evidence from the Taiwan Biobank Database.

Previous studies revealed inconsistent results between coffee drinking and metabolic syndrome (MetS). The aim of the study was to evaluate the relationship between habitual coffee drinking and the prevalence of MetS among men and women. We conducted a nationwide, cross-sectional study using 23,073 adults obtained from the Taiwan Biobank database (mean ± SD (range) age, 54.57 ± 0.07 (30-79) years; 8341 men and 14,731 (63.8%) women). Adults who drank more than one cup of coffee per day (n = 5118) and those who drank less than one cup per day (n = 4515) were compared with nondrinkers (n = 13,439). Multivariate logistic regression models were used to evaluate the risk of MetS between the two groups. Separate models were also estimated for sex-stratified and habitual coffee-type-stratified (black coffee (BC), coffee with creamer (CC), and coffee with milk (CM)) subgroup analyses. The MetS diagnosis was based on at least three of the five metabolic abnormalities. Coffee drinkers (≥1 cup/day) had a significantly lower prevalence of MetS than nondrinkers (AOR (95% CI): 0.80 (0.73-0.87)). Women who drank any amount of coffee and any type of coffee were more likely to have a significantly lower prevalence of MetS than nondrinkers. Only men who drank more than one cup of coffee per day or black coffee drinkers were more likely to have a lower prevalence of MetS. Our study results indicate that adults with habitual coffee drinking behaviors of more than one cup per day were associated with a lower prevalence of MetS. Moreover, women could benefit from habitual coffee drinking of all three coffee types, whereas men could only benefit from drinking BC.

Association between sleep disorder and atrial fibrillation: A nationwide population-based cohort study.

OBJECTIVES: Sleep disorder (SD), especially sleep apnea, and its effect on atrial fibrillation (AF) are gathering attention. However, other SDs may also play an essential role in AF. The aim of the study is to investigate the effects of other SDs on the risk of atrial fibrillation development. METHODS: This study investigated the risk of AF in people diagnosed with SD compared with that in age and sex-matched unaffected individuals. This longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) of individuals diagnosed with SD from January 1, 2001, to December 31, 2012. RESULTS: The sample consisted of 193,288 people with the SD, which include of 4406 people with sleep apnea, 73,704 people with insomnia, 107,395 people with sleep disturbance, 7,783 people with other SD, and 193,288 matched controls. A Cox proportional hazard regression was used to compute the risk of AF in people with SD and subgroup of SD, relative to that in people without SD. The AF incidences were 1.21-fold higher (95% CI 1.15-1.27) in the SD cohort, 1.19-fold higher (95% CI 0.91-1.56) in the sleep apnea cohort, 1.26-fold higher (95% CI 1.19-1.34) in the insomnia cohort, 1.15-fold higher (95% CI 1.08-1.22) in the sleep disturbance cohort, and 1.30-fold higher (95% CI 1.11-1.53) in other SDs, than in the control cohort, after age, sex, and comorbidities were adjusted. CONCLUSIONS: This nationwide population-based cohort study indicates a strong relationship between SD and incident AF, and insomnia has a higher impact on AF compared with other SD.

Myocardial Ischemic Syndromes, Heart Failure Syndromes, Electrocardiographic Abnormalities, Arrhythmic Syndromes and Angiographic Diagnosis of Coronary Artery Spasm: Literature Review.

In coronary artery spasm (CAS), an excess coronary vasoconstriction causing total or subtotal vessel occlusion could lead to syncope, heart failure syndromes, arrhythmic syndromes, and myocardial ischemic syndromes including asymptomatic myocardial ischemia, stable and unstable angina, acute myocardial infarction, and sudden cardiac death. Although the clinical significance of CAS has been underrated because of the frequent absence of symptoms, affected patients appear to be at higher risk of syncope, serious arrhythmias, and sudden death than those with classic Heberden's angina pectoris. Therefore, a prompt diagnosis has important therapeutic implications, and is needed to avoid CAS-related complications. While a definitive diagnosis is based mainly on coronary angiography and provocative testing, clinical features may help guide decision-making. We perform a literature review to assess the past and current state of knowledge regarding the clinical features, electrocardiographic abnormalities and angiographic diagnosis of CAS, while a discussion of mechanisms is beyond the scope of this review.

Mitochondrial DNA somatic mutation burden and heteroplasmy are associated with chronological age, smoking, and HIV infection.

The gradual accumulation of mitochondrial DNA (mtDNA) mutations is implicated in aging and may contribute to the accelerated aging phenotype seen with tobacco smoking and HIV infection. mtDNA mutations are thought to arise from oxidative damage; however, recent reports implicate polymerase γ errors during mtDNA replication. Investigations of somatic mtDNA mutations have been hampered by technical challenges in measuring low-frequency mutations. We use primer ID-based next-generation sequencing to quantify both somatic and heteroplasmic blood mtDNA point mutations within the D-loop, in 164 women and girls aged 2-72 years, of whom 35% were smokers and 56% were HIV-positive. Somatic mutations and the occurrence of heteroplasmic mutations increased with age. While transitions are theorized to result from polymerase γ errors, transversions are believed to arise from DNA oxidative damage. In our study, both transition and transversion mutations were associated with age. However, transition somatic mutations were more prevalent than transversions, and no heteroplasmic transversions were observed. We also measured elevated somatic mutations, but not heteroplasmy, in association with high peak HIV viremia. Conversely, heteroplasmy was higher among smokers, but somatic mutations were not, suggesting that smoking promotes the expansion of preexisting mutations rather than de novo mutations. Taken together, our results are consistent with blood mtDNA mutations increasing with age, inferring a greater contribution of polymerase γ errors in mtDNA mutagenesis. We further suggest that smoking and HIV infection both contribute to the accumulation of mtDNA mutations, though in different ways.

Seco-sativene and Seco-longifolene Sesquiterpenoids from Cultures of Endophytic Fungus Bipolaris eleusines.

Two new seco-sativene sesquiterpenoids, bipolenins D (1) and E (2), a new seco-longifolene sesquiterpenoid, bipolenin F (3), together with three known analogues (4-6), were obtained from cultures of endophytic fungus Bipolaris eleusines. Their structures were established by MS and NMR data. Compounds 1-6 showed no activity to five human cancer cell lines.

N(6)-(2-Hydroxyethyl)adenosine in the Medicinal Mushroom Cordyceps cicadae Attenuates Lipopolysaccharide-Stimulated Pro-inflammatory Responses by Suppressing TLR4-Mediated NF-κB Signaling Pathways.

Natural products play an important role in promoting health with relation to the prevention of chronic inflammation. N(6)-(2-Hydroxyethyl)adenosine (HEA), a physiologically active compound in the medicinal mushroom Cordyceps cicadae, has been identified as a Ca(2+) antagonist and shown to control circulation and possess sedative activity in pharmacological tests. The fruiting body of C. cicadae has been widely applied in Chinese medicine. However, neither the anti-inflammatory activities of HEA nor the fruiting bodies of C. cicadae have been carefully examined. In this study, we first cultured the fruiting bodies of C. cicadae and then investigated the anti-inflammatory activities of water and methanol extracts of wild and artificially cultured C. cicadae fruiting bodies. Next, we determined the amount of three bioactive compounds, adenosine, cordycepin, and HEA, in the extracts and evaluated their synergistic anti-inflammatory effects. Moreover, the possible mechanism involved in anti-inflammatory action of HEA isolated from C. cicadae was investigated. The results indicate that cordycepin is more potent than adenosine and HEA in suppressing the lipopolysaccharide (LPS)-stimulated release of pro-inflammatory cytokines by RAW 264.7 macrophages; however, no synergistic effect was observed with these three compounds. HEA attenuated the LPS-induced pro-inflammatory responses by suppressing the toll-like receptor (TLR)4-mediated nuclear factor-κB (NF-κB) signaling pathway. This result will support the use of HEA as an anti-inflammatory agent and C. cicadae fruiting bodies as an anti-inflammatory mushroom.