Methicillin-Resistant Staphylococcus capitis with Reduced Vancomycin Susceptibility Causes Late-Onset Sepsis in Intensive Care Neonates

isolated from the blood of NICU infants and compared these data to adult patients. element, and constantly showed either vancomycin resistance (37.5%) or heteroresistance (62.5%). Conversely, the isolates that were collected outside of the NICU were genetically diverse and displayed much lower rates of vancomycin resistance and heteroresistance (7.7% and 23.1%, respectively). strains has spread into several French NICUs. These isolates exhibit reduced susceptibility to vancomycin, which is the most widely used antimicrobial agent in the NICU setting

Testosterone-to-estradiol ratio and platelet thromboxane release in ischemic heart disease: the EVA project

Background Data on the interplay between sexual hormones balance, platelet function and clinical outcomes of adults with ischemic heart disease (IHD) are still lacking. Objective To assess the association between the Testosterone (T)-to-Estradiol (E2) Ratio (T/E2) and platelet activation biomarkers in IHD and its predictive value on adverse outcomes. Methods The EVA study is a prospective observational study of consecutive hospitalized adults with IHD undergoing coronary angiography and/or percutaneous coronary interventions. Serum T/E2 ratios E2, levels of thromboxane B-2 (TxB(2)) and nitrates (NO), were measured at admission and major adverse events, including all-cause mortality, were collected during a long-term follow-up. Results Among 509 adults with IHD (mean age 67 +/- 11 years, 30% females), males were older with a more adverse cluster of cardiovascular risk factors than females. Acute coronary syndrome and non-obstructive coronary artery disease were more prevalent in females versus males. The lower sex-specific T/E2 ratios identified adults with the highest level of serum TxB(2) and the lowest NO levels. During a median follow-up of 23.7 months, the lower sex-specific T/E2 was associated with higher all-cause mortality (HR 3.49; 95% CI 1.24-9.80; p = 0.018). In in vitro, platelets incubated with T/E2 ratios comparable to those measured in vivo in the lowest quartile showed increased platelet activation as indicated by higher levels of aggregation and TxB(2) production. Conclusion Among adults with IHD, higher T/E2 ratio was associated with a lower long-term risk of fatal events. The effect of sex hormones on the platelet thromboxane release may partially explain such finding

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Vancomycin MICs are higher in <i>Staphylococcus capitis</i> pulsotype NRCS-A than in other pulsotypes.

<p>Vancomycin MICs were determined by the E-Test method. The mean vancomycin MIC was significantly higher in pulsotype NRCS-A isolates (2.8 mg/L) than in pulsotypes NRCS-B to –M isolates (1.7 mg/L), as illustrated by the shift toward the higher values of the MIC distribution curve (<i>P</i><0.01, two-tailed Mann-Whitney <i>U</i>-test).</p

A species distribution comparison of <i>Staphylococcus</i> spp. isolates from the positive blood cultures of patients in neonatal intensive care units (NICUs) and adult ICUs, 2004–2009.

a<p>The differences between the groups were tested for statistical significance using a two-tailed Fisher's exact test. <i>P</i> values were corrected for multiple testing using the Holm-Bonferroni method.</p

A retrospective comparison of the antimicrobial resistance profiles of methicillin-resistant and methicillin-susceptible <i>Staphylococcus capitis</i> bloodstream isolates from patients in neonatal intensive care units, 2004–2009.

a<p>The differences between the groups were tested for statistical significance using a two-tailed Fisher's exact test. <i>P</i> values were corrected for multiple testing using the Holm-Bonferroni method.</p>b<p>NC, not calculable.</p

Flow diagram of case selection.

<p>(N)ICU, (neonatal) intensive care unit; CoNS, coagulase-negative staphylococci; BC, blood culture. ^aIn NICU infants, a single CoNS-positive blood culture was interpreted as possible bacteremia and included in the analysis. The CoNS-positive results that were excluded were explicitly recorded as a contaminant in the microbiology record. ^bIn adult patients, a single CoNS-positive blood culture was interpreted as a contaminant and excluded from the analysis. ^cRecords were excluded when antimicrobial susceptibility results were not available.</p

A retrospective comparison of the antimicrobial resistance profiles of <i>Staphylococcus capitis</i> bloodstream isolates from patients in neonatal intensive care units (NICUs) and adult ICUs, 2004–2009.

a<p>The differences between the groups were tested for statistical significance using a two-tailed Fisher's exact test. <i>P</i> values were corrected for multiple testing using the Holm-Bonferroni method.</p

<i>Staphylococcus capitis</i> isolates from distant neonatal intensive care units (NICUs) are clonal.

<p>Pulsed-field gel electrophoresis (PFGE) was applied to 53 bloodstream isolates of <i>S. capitis</i> that were collected from NICU infants and adult patients from cities spanning the French territory. The PFGE dendrogram was generated using the GelCompar software version 4.1. The isolates were assigned to pulsotypes using >80% similarity (vertical dashed line). Staphylococcal chromosomal cassette <i>mec</i> (SCC<i>mec</i>) typing was applied to 23 methicillin-resistant isolates representative of each pulsotype and geographic origin. All methicillin-resistant isolates from the different NICUs belonged to the same pulsotype and shared a type V-related SCC<i>mec</i> element, whereas methicillin-susceptible and/or non-NICU isolates were genetically diverse. <i>ccr</i>, chromosomal cassette recombinase; unkn., unknown (a combination of the <i>mec</i> complex and <i>ccr</i> genes has not been assigned to an SCC<i>mec</i> type so far).</p