Global metabolomic profiling of uterine leiomyomas

Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy. Results: A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data. Conclusions: The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.Peer reviewe

The Impact of Acculturation on Diabetes Risk Among Arab Americans in Southeastern Louisiana.

Purpose. This study was conducted to investigate the relationship between acculturation and diabetes risk among Arab Americans in Southeastern Louisiana. The secondary objective was to identify the prevalence of diabetes, hypertension, hyperlipidemia, and cardiovascular disease in the same population. Background. Research suggests that Arab Americans report disproportionate rates of diabetes and other chronic diseases. Methods. A cross-sectional study of 181 Arab Americans was conducted in Louisiana. Interviewers recruited participants to answer a 37-item survey with a five-dimension acculturation assessment and abridged National Institute of Health Survey and American Diabetes Association (2010) diabetes tool. Results were analyzed using factor analysis and Spearman’s correlation. Results. A negative correlation was found between Arab acculturation variables and diabetes risk among males (r=−.216, p=.044) and American acculturation variables among females (r=−.222, p=.032). Twelve percent reported being diagnosed with Type II diabetes by a primary care physician

Concordance of Vancomycin Population-Predicted Pharmacokinetics with Patient-Specific Pharmacokinetics in Adult Hospitalized Patients: A Case Series.

Background: Vancomycin empiric therapy is commonly dosed using clinical algorithms adapted from population-predicted pharmacokinetic parameters. However, precise dosing of vancomycin can be designed using patient-specific pharmacokinetic calculations. Objective: The objective of this study is to assess the correlational fit between vancomycin population-predicted and patient-specific pharmacokinetic parameters [elimination rate constant (Ke) and half-life (t1/2)] in a case series of adult hospitalized patients. Methods: This is a single-center case series of hospitalized adult patients who received vancomycin, had creatinine clearance calculation for derivation of population-predicted pharmacokinetic parameters, and had two vancomycin concentrations for calculation of patient-specific pharmacokinetic parameters. The primary objective of this case series is to evaluate the correlation between population-predicted and patient-specific pharmacokinetic parameters. The secondary objectives of this study are to evaluate the mean bias and precision between the population-predicted and patient-specific pharmacokinetic parameters and to assess the correlation between population-predicted and patient-specific pharmacokinetic parameters in special population subgroups (obese patients with body mass index ≥ 30 kg/m2 and patients with renal dysfunction). All correlation analyses were performed on the population-predicted pharmacokinetics using diverse methods of estimating renal function (Salazar–Corcoran and Cockcroft–Gault methods using either ideal, actual, or adjusted body weights). All significance testing was set at an α of \u3c 0.05. IBM SPSS Statistics version 25 and SAS version 9.4 were used to conduct all statistical analyses. Results: A total of 30 patients were included in the study; 33.3% (10/30) of the patients were obese and 56.7% (17/30) had renal dysfunction. In all patients in the study, the calculated population-predicted Ke and t1/2 using all four creatinine clearance estimation methods were each significantly correlated with patient-specific Ke and t1/2 (all Pearson correlation coefficients [r]: \u3e + 0.7, p \u3c 0.001). The population-predicted Ke and t1/2 calculated using Cockcroft–Gault creatinine clearance using adjusted body weight showed the strongest association with patient-specific Ke and t1/2. In the subgroup analyses, all the population-predicted Ke and t1/2 using four creatinine clearance estimation methods were each significantly correlated with patient-specific Ke and t1/2. The exception was the population-predicted t1/2 derived from Cockcroft–Gault creatinine clearance using actual body weight that did not show a significant correlation with patient-specific t1/2 in obese patients. Conclusions: In this case series, population-predicted pharmacokinetic parameters were strongly correlated with patient-specific pharmacokinetic parameters. The vancomycin population-predicted pharmacokinetic formula can be used safely to predict a patient’s vancomycin pharmacokinetic disposition and can be maintained as an empiric dosing strategy in various hospitalized adult patients

Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2–Related Multisystem Inflammatory Syndrome in Children With Shock

NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5–11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35–45%), 261 ng/mL (131–390 ng/mL), and 3.2 mmol/L (2–4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5–28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814–11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987–192,499 pg/mL]), von Willebrand factor antigen (344% [288–378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472–1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms

Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood-longitudinal analysis of BMI data from birth to age 46 in cases of PCOS

Background: Adiposity rebound (AR), the second BMI rise in childhood at around the age of 6 years, is associated with obesity and metabolic alteration in later life. Given that polycystic ovary syndrome (PCOS) has a strong metabolic component, early life growth patterns could reveal a risk of PCOS. Thus, we aimed to investigate the associations between age at AR and PCOS diagnosis and BMI later in life. Materials and methods: This study is part of a prospective, population-based longitudinal study, where women with PCOS diagnosis by age 46 (n = 280) were compared with asymptomatic women (CTRLs, n = 1573). Weight and height data from birth to age 13 years, at age at menarche, and at ages 31 and 46 years were analyzed Results: Women with PCOS had lower birth weight (3357 +/- 477 vs. 3 445 +/- 505 g, p <0.001), earlier age at AR (5.2 +/- 1.0 vs. 5.6 +/- 0.90 years, p <0.001) and higher BMI from AR onwards compared with controls. Early timing of AR was associated with PCOS diagnosis independently of BMI (OR 1.62, 95% CI 1.37-1.92). Women with PCOS and early AR had higher BMI at 31 and 46 years when compared to controls with early AR. The age at AR did not associate with T levels at ages 31 or 46 years. Conclusions: Early AR was associated with PCOS diagnosis and high BMI in adulthood. Adolescent girls with early AR and persisting obesity should be screened for PCOS symptoms, such as persistent irregular cycles and hirsutism.Peer reviewe