Lipoprotein(a) screening in young and middle-aged patients presenting with acute coronary syndrome

Background: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). However, its role in real-world practice and implications for clinical care remains limited. Under investigation herein, are the clinical characteristics associated with increased Lp(a) levels in patients presenting with acute coronary syndrome (ACS). Methods: Lp(a) was measured at admission in patients ≤ 65 years of age presenting with ACS in a single center. Logistic regression model was used to determine the independent association of clinical characteristics with elevated Lp(a). Results: A total of 134 patients were screened for Lp(a); 83% males, mean age 52 ± 8 years. Median Lp(a) level was 46 nmol/L (interquartile range [IQR] 13–91). Elevated Lp(a) > 72 nmol/L (30 mg/dL) was documented in 32% and associated with younger age at CAD diagnosis. In a multiple logistic regression model, premature CAD (odds ratio [OR] 3.85, 95% confidence interval [CI] 1.48–10.07, p = 0.06), previous revascularization (OR 2.56, 95% CI 1.17–5.59, p = 0.019) and probable/definite familial hypercholesterolemia (FH) (OR 3.18, 95% CI 1.10–9.21, p = 0.033), were independently associated with elevated Lp(a). In contrast, Lp(a) levels were not associated with other traditional cardiovascular risk factors, previous statin treatment, C-reactive protein level or ACS type. Conclusions: In young and middle-aged patients presenting with ACS, premature CAD, previous revascularization and FH were independently associated with elevated Lp(a), indicating progressive CAD and higher cardiovascular risk. These results, are in accordance with guideline based recommendations for Lp(a) screening, and may be of importance in addressing residual cardiovascular risk in young ACS patients, in light of the novel emerging therapies targeting Lp(a)

Development of Autoantibodies Following BNT162b2 mRNA COVID-19 Vaccination and Their Association with Disease Flares in Adult Patients with Autoimmune Inflammatory Rheumatic Diseases (AIIRD) and the General Population: Results of 1-Year Prospective Follow-Up Study

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed

Genetic analysis of p38 MAP kinases in myogenesis: fundamental role of p38α in abrogating myoblast proliferation

The p38 mitogen-activated protein kinase (MAPK) pathway plays a critical role in skeletal muscle differentiation. However, the relative contribution of the four p38 MAPKs (p38α, p38β, p38γ and p38δ) to this process is unknown. Here we show that myoblasts lacking p38α, but not those lacking p38β or p38δ, are unable to differentiate and form multinucleated myotubes, whereas p38γ-deficient myoblasts exhibit an attenuated fusion capacity. The defective myogenesis in the absence of p38α is caused by delayed cell-cycle exit and continuous proliferation in differentiation-promoting conditions. Indeed, activation of JNK/cJun was enhanced in p38α-deficient myoblasts leading to increased cyclin D1 transcription, whereas inhibition of JNK activity rescued the proliferation phenotype. Thus, p38α controls myogenesis by antagonizing the activation of the JNK proliferation-promoting pathway, before its direct effect on muscle differentiation-specific gene transcription. More importantly, in agreement with the defective myogenesis of cultured p38α(Δ/Δ) myoblasts, neonatal muscle deficient in p38α shows cellular hyperproliferation and delayed maturation. This study provides novel evidence of a fundamental role of p38α in muscle formation in vitro and in vivo