👤 Mark Atallah

People with HIV (PWH) and undetectable virus experience elevated cardiovascular risk independent of traditional risk factors. Vascular inflammation may contribute to this residual risk. The perivascular fat attenuation index (FAI), derived from coronary computed tomography angiography (CCTA), is a biomarker of coronary inflammation. Lipoprotein(a) [Lp(a)] carries oxidized phospholipids that may promote inflammation. Statins have demonstrated cardiovascular benefit in PWH, including pleiotropic anti-inflammatory effects. This study assessed the associations of Lp(a) and of statin use with coronary inflammation (FAI) in men with HIV (MWH). We analysed FAI of the left anterior descending (LAD) and the right coronary arteries (RCA) in 583 men from the Multicenter AIDS Cohort Study, a prospective, multicentre cohort study, including 280 with undetectable HIV RNA, <50 copies/ml. Associations between log Lp(a) was associated with increased coronary inflammation, independent of traditional cardiovascular risk factors, in MWH with undetectable virus. Statin therapy did not modify the relationship between coronary inflammation and Lp(a). Show less

Ultrasound (US)-guided supine percutaneous nephrolithotomy (PCNL) is increasingly being adopted. The aim of this study was to assess the safety of lower vs non-lower pole access (non-LPa) in supine US-guided PCNL. This study was a retrospective cohort analysis of 228 patients who underwent single-access US-guided supine PCNL between March 2023 and June 2024 and were categorized into lower (n = 162), interpolar (n = 42), and upper pole (n = 21) access categories. Baseline demographics, stone characteristics, and intraoperative details were analyzed and compared between the groups. Safety outcomes, including 30-day postoperative total and major complications (based on Clavien-Dindo classification), as well as pain scores, were compared between lower pole access (LPa) and non-LPa. Baseline clinical and stone characteristics were comparable between the groups. Non-LPa was more frequently performed on the right side ( When performing US-guided supine PCNL, LPa has a superior safety profile, resulting in fewer major and total complications compared with non-LPa. Show less

Lipoprotein(a) [Lp(a)] is a primarily genetically determined, causal and independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) levels are stable, unaffected by lifestyle, and best measured using isoform-insensitive, molar-based assays. Current guidelines from the European Atherosclerosis Society and U.S. National Lipid Association recommend a one-time Lp(a) measurement in all adults. Cascade testing is advised in affected families. Elevated Lp(a) levels are associated with increased risk of coronary artery disease, myocardial infarction incidence and recurrence, and aortic stenosis onset and progression. In cerebrovascular disease, high Lp(a) is linked to large artery ischemic stroke incidence and recurrence, as well as poor functional outcomes. Associations with venous thromboembolism are limited to prothrombotic states and extreme Lp(a) concentrations. Elevated levels (≥50 mg/dL or ≥125 nmol/L) should prompt intensified risk factor modification. There are no currently approved lipid-lowering therapies that substantially reduce Lp(a) levels. Novel agents to lower Lp(a) include antisense oligonucleotides, small interfering ribonucleic acid and small molecules, all of which have shown promising results in phase 2 trials. Ongoing phase 3 trials will evaluate the causal relationship between Lp(a) and ASCVD, and whether lowering Lp(a) reduces cardiovascular outcomes. Show less

Lipoprotein(a) [Lp(a)] is a primarily genetically determined, low-density lipoprotein-like particle that plays an important role in atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). Despite optimal control of traditional lipid levels, elevated lipoprotein(a) [Lp(a)] remains a significant contributor to residual cardiovascular risk, affecting up to 20% of the global population. We performed a literature search of PubMed/Medline and Google Scholar until July 2025 to provide a comprehensive overview of the genetics, structure, metabolism, and molecular mechanisms underlying Lp(a)'s pathogenicity. Structurally, Lp(a) consists of an LDL-like core covalently bound to apolipoprotein(a) [apo(a)], a polymorphic glycoprotein characterized by kringle IV type 2 (KIV-2) repeat variability. This copy number variation is the primary determinant of apo(a) isoform size and plasma Lp(a) levels. Small isoforms are produced more efficiently, resulting in higher concentrations. Lp(a) is synthesized in hepatocytes, and its plasma levels are predominantly governed by production rather than clearance. It carries a high burden of oxidized phospholipids (OxPLs), which confer pro-inflammatory and pro-atherogenic properties. Lp(a) promotes arterial inflammation, endothelial dysfunction, monocyte activation and impaired fibrinolysis via competition with plasminogen. It also plays a direct pathogenic role in valvular calcification by delivering OxPLs and autotaxin to valve interstitial cells, triggering osteogenic signaling cascades. While environmental factors such as inflammation and hormonal status can transiently modulate levels, genetic variation overwhelmingly dictates lifelong Lp(a) burden. As novel agents targeting Lp(a) enter late-stage clinical trials, mechanistic insights into Lp(a) biology will be essential to risk stratification and future clinical management. Show less

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by repetitive behaviors and a lack of social communication. The role of probiotics, phytochemicals and their combination phytochemicals as treatment options for ASD is still under study. This study aimed to evaluate the associated molecular pathways and explore the impact of Fifty 3-week-old male albino rat pups were randomly distributed into five groups. The groups included a control group, a PA-induced ASD group, in which PA (250 mg/kg, p.o.) was administered for 3 days, and three other groups that received PA (250 mg/kg, p.o.) for 3 days along with either Compared with the group administered only PA, treatment with Our results suggest that Show less

The peri- and early post-infarction period carries an increased risk of recurrent ischemic events. Oxidized phospholipids (OxPLs) are pro-inflammatory and contribute to plaque instability and thrombosis. This study aimed to: (1) assess changes, during the early post-MI period in OxPL-apo(a) and OxPL-apoB, (2) evaluate the effect of PCSK9 inhibition on these changes, and (3) explore their relationships with the changes in Lp(a) and LDL-C. Ninety-six participants with NSTEMI or STEMI were randomized to receive placebo (n = 48) or 420 mg subcutaneous evolocumab (n = 48) within 24 h of admission. OxPL-apo(a), OxPL-apoB, Lp(a), and LDL-C levels were measured at baseline and 30 days post-MI. In the placebo group, OxPL-apo(a) increased from 52.6 [19.3, 106.5] nmol/L at baseline to 61.7 [31.5, 116.9] nmol/L at 30 days (p = 0.014), and OxPL-apoB rose from 6.7 [3.1, 21] nmol/L to 8.8 [3.7, 23] nmol/L (p = 0.0045). In contrast, no significant changes were observed for OxPL-apo(a) (p = 0.17) or OxPL-apoB (p = 0.058) in the evolocumab group. OxPL-apo(a) correlated strongly with Lp(a) at baseline (r = 0.93, p < 0.001) and 30 days (r = 0.94, p < 0.001), and OxPL-apoB correlated similarly (baseline: r = 0.92, p < 0.001; 30 days: r = 0.93, p < 0.001). No correlation was observed between OxPLs and LDL-C. OxPL-apo(a) and OxPL-apoB levels were strongly correlated with Lp(a) and increased during the early post-infarction period. This increase was prevented by in-hospital administration of a PCSK9 inhibitor. These findings provide new insights into early changes in OxPLs following acute MI and suggest a protective role for PCSK9 inhibition during this critical period. Show less

MYBPC3 is the most frequently mutated gene in hypertrophic cardiomyopathy (HCM). Several loss-of-function founder variants have been reported in MYBPC3 from various geographic regions, altogether suggestive of a modest or absent effect of these variants on reproductive fitness. One of them, a MYBPC3 splice variant, NM₀₀₀₂₅₆.3:c.3330+2T > G, was first described in homozygous state in newborns presenting with a severe, recessive form of HCM among the Amish population and was later associated with adult-onset dominant HCM in heterozygous carriers. We here report this splice variant in heterozygous state in eight unrelated Swiss families with HCM, making it the most prevalent cardiomyopathy variant in western Switzerland. This variant was identified in patients using targeted (n = 5) or full-genome sequencing (n = 3). Given the prevalence of this variant in the Old Order Amish, Mennonites and Swiss populations, and given that both Amish and Mennonites founders originated from the Bern Canton in Switzerland, the MYBPC3, NM₀₀₀₂₅₆.3:c.3330+2T > G variant appears to be of Swiss origin. Neighboring regions that hosted the first Amish settlements (Alsace, South Germany) should be on the lookout for that variant. The existence of MYBPC3 founder variants in different populations suggests that individuals with early-onset clinical disease may be the tip of the iceberg of a much larger number of asymptomatic carriers. Alternatively, reproductive fitness could even be slightly increased in some variant carriers to compensate for the reduction of fitness in the more severely affected ones, but this remains to be investigated. Show less