We describe a case of Streptococcus viridans endocarditis in a 17-year-old female with congenital ventricular septal defect, that followed shortly after performing naval piercing. She was eventually treated with penicillin with complete recovery. We review other cases from the literature of piercing-associated endocarditis, and suggest that individuals at particularly high risk might be considered for antibiotic prophylaxis prior to such procedures.

Background—Various antidepressant agents are metabolized by the CYP2C19 enzyme, including Citalopram and Escitalopram. Variation in CYP2C19 expression might give rise to different plasma concentrations of the active metabolites, potentially affecting both drugs’ efficacy and tolerability. Aim—The aim of this study was to evaluate differences in the Escitalopram and Citalopram efficacy and tolerability between different CYP2C19 genotype-based metabolizing categories in outpatients suffering from major depressive disorder (MDD). Methods—In a retrospective, longitudinal cohort study of electronic medical-record data, 283 patients with MDD who were prescribed Escitalopram or Citalopram with the available CYP2C19-genotyping test were enrolled. The primary efficacy end point was adverse drug reactions recorded in the medical files. A proportional-odds, multilevel-regression model for longitudinal ordinal data was used to estimate the relation between the CYP2C19 genotype and adverse drug reactions, adjusting for potential confounding variables and other explanatory variables. Latent-class analysis (LCA) was utilized to detect the presence of clinically significant subgroups and their relation to an individual’s metabolizing status for CYP2D6/CYP2C19. Results—With poor CYP2C19 metabolizers as a reference, for each unit difference in the activity score of the CYP2C19 phenotype, the odds ratio for drug intolerability was lowered by 0.73 (95% credible intervals: 0.56–0.89), adjusting for significant covariates. In addition, applying LCA, we identified two qualitatively different subgroups: the first group (61.85%) exhibited multiple side effects, low compliance, and frequent treatment changes, whereas the second group (38.15%) demonstrated fewer side effects, good adherence, and fewer treatment changes. The CYP2C19 phenotype was substantially associated with the group membership. Conclusions—We found a positive association between the CYP2C19 activity scores, as inferred from the genotype, and both the efficacy of and tolerability to both Es/Citalopram. LCA enabled valuable insights into the underlying structure of the population; the CYP2C19 phenotype has a predictive value that discriminates between low-adherence, low-drug-tolerance, and low-response patients and high-adherence, high-drug-tolerance, and high-response patients. Personalized medicine based on CYP2C19 genotyping could evolve as a promising new avenue towards mitigating Escitalopram and Citalopram therapy and the associated side effects and enhancing treatment success.

Objective: Vaccines against COVID-19 induce specific antibodies whose titer is perceived as a reliable correlate of protection. Vitamin D confers complex regulatory effects on the innate and adaptive immunity. In this study, we explored a plausible impact of baseline vitamin D content on achieved immunity following COVID-19 vaccination. Methods: A retrospective observational study comprising 73,254 naïve subjects insured by the Leumit Health Service HMO, who were vaccinated between 1 February 2020 and 30 January 2022, with one available vitamin D level prior to vaccination, was performed. The association between 25(OH) vitamin D levels, SARS-CoV-2 antibody titer, and post-vaccination PCR results were evaluated. Results: Of the study population, 5026 (6.9%) tested positive for COVID-19. The proportion of low 25(OH)D levels (<30 ng/mL) was significantly higher in the PCR-positive group (81.5% vs. 79%, p < 0.001). Multivariate analysis showed a higher incidence of breakthrough infection among non-smokers [1.37 (95% CI 1.22–1.54, p < 0.001)] and lower incidences among subjects with sufficient 25(OH)D levels (>30 ng/mL) [0.87 (95% CI 0.79–0.95, p—0.004)], hyperlipidemia [0.84 (95% CI 0.76–0.93, p < 0.001], depression [OR-0.87 (95% CI: 0.79–0.96, p < 0.005], socio-economic status >10 [0.67 (95% CI 0.61–0.73, p < 0.001)], and age >44 years. SARS-CoV-2 antibody titers were available in 3659 vaccinated individuals. The prevalence of antibody titers (<50 AU) among PCR-positive subjects was 42% compared to 28% among PCR-negative subjects (p < 0.001). Baseline 25(OH)D levels showed an inverse relation to total antibody titers. However, no association was found with an antibody titer <50 AU/mL fraction. Conclusion Baseline 25(OH)D levels correlated with the vaccination-associated protective COVID-19 immunity. Antibody titers <50 AU/mL were significantly linked to breakthrough infection but did not correlate with 25(OH)D levels.

Background and Objectives: The neutrophilic peptide, alpha-defensin, is considered an evolving risk factor intimately linked with lipid mobilization. It was previously linked to augmented liver fibrosis. Here, we assess a potential association between alpha-defensin and fatty liver. Materials and Methods: A cohort of transgenic C57BL/6JDef^+/+ male mice that overexpress the human neutrophil-derived alpha-defensin in their polymorphonuclear neutrophils (PMNs) were assessed for liver steatosis and fibrosis development. Wild type (C57BL/6JDef.Wt) and transgenic (C57BL/6JDef^+/+) mice were maintained on a standard rodent chow diet for 8.5 months. At the termination of the experiment, systemic metabolic indices and hepatic immunological cell profiling were assessed. Results: The Def^+/+ transgenic mice exhibited lower body and liver weights, lower serum fasting glucose and cholesterol, and significantly lower liver fat content. These results were associated with impaired liver lymphocytes count and function (lower CD8, NK cells, and killing marker CD107a). The metabolic cage demonstrated dominant fat utilization with a comparable food intake in the Def^+/+ mice. Conclusions: Chronic physiological expression of alpha-defensin induces favorable blood metabolic profile, increased systemic lipolysis, and decreased hepatic fat accumulation. Further studies are needed to characterize the defensin net liver effect.

Objective: Inflammation is associated with atherogenesis. Although a higher neutrophil count is associated with the plaque burden, the role of neutrophil activation is unclear. Human neutrophil peptides 1–3 (HNP1–3) are a risk factor for atherogenesis in bench models and are elevated in human atheromas. This study aimed to examine the association between skin HNP1–3 deposition and the severity of coronary artery disease (CAD), including long-term outcomes. Methods: HNP1–3 levels were immunohistochemically quantified in skin biopsies, which were prospectively taken from 599 consecutive patients before clinically indicated coronary angiography. Established cardiovascular risk factors and blood markers for atheroinflammation were obtained. CAD severity and the incidence of repeat revascularization and mortality at 48 months of follow-up were assessed in relation to HNP1–3 levels. Results: The risk of CAD was independently associated with age and HNP1–3 in the entire cohort (F = 0.71 and F = 7.4, respectively). Additionally, HNP1–3 levels were significantly associated with myocardial necrosis (R = 0.26). At the follow-up, high HNP1–3 levels negatively affected mortality (19.54%) and recurrent revascularization (8.05%). Conclusion: HNP1–3 tissue deposition is positively associated with the severity of CAD, myonecrosis, and long-term sequelae. HNP1–3 levels may be suppressed using colchicine.

Background: Diabetes mellitus (DM) significantly impacts cardiovascular outcomes, particularly in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). The presence of polyvascular disease further complicates the prognosis due to the increased burden of atherosclerosis and comorbidities. This study was designed to investigate the combined impact of DM and polyvascular disease on outcomes in patients with AMI and CS. Method: Using the National Inpatient Sample database, we analyzed 39,140 patients with AMI complicated by CS and known polyvascular disease. The patients were stratified by diabetes status. The study assessed in-hospital major adverse cardiovascular and cerebrovascular events (MACCE), mortality, cerebrovascular accident (CVA) and major bleeding. Multivariable logistic regression models were used to examine the association between in-hospital outcomes and diabetes, adjusting for baseline differences. Results: Of the study population, 54% had DM. The patients with DM were younger (69.5 vs. 72.1 years, p < 0.001) and more likely to be female (36.7% vs. 34.2%, p < 0.001). After adjustment, the patients with DM showed a 17% increased mortality risk (aOR 1.17, 95% CI: 1.11–1.23, p < 0.001) and a higher risk of major adverse cardiovascular and cerebrovascular events (aOR 1.05, 95% CI: 1.01–1.10, p = 0.020). Conclusions: DM significantly impacts outcomes in patients with AMI complicated by CS and polyvascular disease, leading to increased mortality risk, longer hospital stays, and higher healthcare costs. These findings underscore the need for targeted interventions and specialized care strategies for this high-risk population.