Sex differences influencing micro- and macrovascular endothelial phenotype in vitro

Key points: Endothelial dysfunction is an early hallmark of multiple disease states that also display sex differences with respect to age of onset, frequency and severity. Results of in vivo studies of basal and stimulated microvascular barrier function revealed sex differences that are difficult to ascribe to specific cells or environmental factors. The present study evaluated endothelial cells (EC) isolated from macro- and/or microvessels of reproductively mature rats under the controlled conditions of low-passage culture aiming to test the assumption that EC phenotype would be sex independent. The primary finding was that EC, regardless of where they are derived, retain a sex-bias in low-passage culture, independent of varying levels of reproductive hormones. The implications of the present study include the fallacy of expecting a universal set of mechanisms derived from study of EC from one sex and/or one vascular origin to apply uniformly to all EC under unstimulated conditions, and no less in disease. Abstract: Vascular endothelial cells (EC) are heterogeneous with respect to phenotype, reflecting at least the organ of origin, location within the vascular network and physical forces. As an independent influence on EC functions in health or aetiology, susceptibility, and progression of dysfunction in numerous disease states, sex has been largely ignored. The present study focussed on EC isolated from aorta (macrovascular) and skeletal muscle vessels (microvascular) of age-matched male and female rats under identical conditions of short-term (passage 4) culture. We tested the hypothesis that genomic sex would not influence endothelial growth, wound healing, morphology, lactate production, or messenger RNA and protein expression of key proteins (sex hormone receptors for androgen and oestrogens α and β; platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin mediating barrier function; αvβ3 and N-cadherin influencing matrix interactions; intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 mediating EC/white cell adhesion). The hypothesis was rejected because the EC origin (macro- vs. microvessel) and sex influenced multiple phenotypic characteristics. Statistical model analysis of EC growth demonstrated an hierarchy of variable importance, recapitulated for other phenotypic characteristics, with predictions assuming EC homogeneity \u3c sex \u3c vessel origin \u3c sex and vessel origin. Furthermore, patterns of EC mRNA expression by vessel origin and by sex did not predict protein expression. Overall, the present study demonstrated that accurate assessment of sex-linked EC dysfunction first requires an understanding of EC function by position in the vascular tree and by sex. The results from a single EC tissue source/species/sex cannot provide universal insight into the mechanisms regulating in vivo endothelial function in health, and no less in disease

Plasma‐derived biomarkers of Alzheimer\u27s disease and neuropsychiatric symptoms: A community‐based study

INTRODUCTION: We examined associations between plasma-derived biomarkers of Alzheimer\u27s disease (AD) and neuropsychiatric symptoms (NPS) in community-dwelling older adults. METHODS: Cross-sectional study involving 1005 persons ≥50 years of age (mean 74 years, 564 male, 118 cognitively impaired), who completed plasma-derived biomarker (amyloid beta 42 [Aβ42]/Aβ40, phosphorylated tau 181 [p-tau181], p-tau217, total tau [t-tau], neurofilament light [NfL]), and NPS assessment. RESULTS: P-tau181 (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.41–3.00, p < 0.001), p-tau217 (OR 1.70, 95% CI 1.10–2.61, p = 0.016), and t-tau (OR 1.44, 95% CI 1.08–1.92, p = 0.012) were associated with appetite change. We also found that p-tau181 and p-tau217 were associated with increased symptoms of agitation (OR 1.93, 95% CI 1.20–3.11, p = 0.007 and OR 2.04, 95% CI 1.21–3.42, p = 0.007, respectively), and disinhibition (OR 2.39, 95% CI 1.45–3.93, p = 0.001 and OR 2.30, 95% CI 1.33–3.98, p = 0.003, respectively). Aβ42/Aβ40 and NfL were not associated with NPS. CONCLUSION: Higher plasma-derived p-tau181 and p-tau217 levels are associated with increased symptoms of appetite change, agitation, and disinhibition. These findings may support the validity of plasma tau biomarkers for predicting behavioral symptoms that often accompany cognitive impairment. HIGHLIGHTS - We studied 1005 community-dwelling persons aged ≥ 50 years - Higher plasma tau levels are associated with increased neuropsychiatric symptoms - Aβ42/Aβ40 and NfL are not associated with neuropsychiatric symptoms - Clinicians should treat neuropsychiatric symptoms in persons with high plasma-derived ta

Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objective: To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). Study design: Infants with sBPD in the Children's Hospitals Neonatal Database who had echocardiograms 34-44 weeks' postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. Results: Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/missing, RVSP 20% vs. 9% normal/missing, both p < 0.01) in unadjusted and multivariable models, adjusted for significant covariates (SP OR 1.9, 95% CI 1.2-3.0; RVSP OR 2.2, 95% CI 1.1-4.7). Abnormal parameters had high specificity (SP 82%; RVSP 94%), and negative predictive value (SP 94%, NPV 91%) for mortality. Conclusions: Abnormal SP or RVSP is independently associated with mortality in sBPD infants. Negative predictive values distinguish infants most likely to survive

Comparing Feedback Techniques in Bilobe Flap Simulation Using 3D‐Printed Facial Models

Abstract Objective To compare live versus delayed feedback on trainee performance of bilobe flaps using 3‐dimensional (3D)‐printed facial simulators and determine whether these effects are sustained on repeat performance. Study Design Cohort study. Setting University of Arkansas for Medical Sciences. Methods 3D‐printed facial models with a nasal ala defect were provided to 18 subjects. Subjects were stratified and randomized based on their training level into 1 of 3 groups corresponding to live feedback (Group 1), delayed feedback (Group 2), and no feedback (Group 3). Subjects performed a bilobe flap following a structured lecture. Four weeks later, subjects independently repeated the exercise on the contralateral ala. Likert surveys were used to assess subjective parameters. Objective grading was performed by a plastic surgeon, which included a point system and score for the overall appearance. Results Following exercise 1, Group 1 reported a significant improvement in knowledge (P < .001), which was sustained after exercise 2 (P < .001); Group 2 reported a significant improvement after exercise 1 (P = .03) but was not sustained (P = .435). After the second exercise, Group 1 and Group 2 improved their confidence in bilobed repair (P = .001 and P = .003, respectively), but this was greater for Group 1. Group 1 showed a significant improvement in their design time following exercise 2 (P = .007). There were no significant differences between groups on total time for repair, total score, and appearance. Conclusion 3D‐printed models are valuable in teaching the bilobe flap for nasal defects, with live feedback providing the greatest level of improvement in self‐reported knowledge and confidence

Home Oxygen Use and 1-Year Readmission among Infants Born Preterm with Bronchopulmonary Dysplasia Discharged from Children's Hospital Neonatal Intensive Care Units

Objective: To determine associations between home oxygen use and 1-year readmissions for preterm infants with bronchopulmonary dysplasia (BPD) discharged from regional neonatal intensive care units. Study design: We performed a secondary analysis of the Children's Hospitals Neonatal Database, with readmission data via the Pediatric Hospital Information System and demographics using ZIP-code-linked census data. We included infants born <32 weeks of gestation with BPD, excluding those with anomalies and tracheostomies. Our primary outcome was readmission by 1 year corrected age; secondary outcomes included readmission duration, mortality, and readmission diagnosis-related group codes. A staged multivariable logistic regression was adjusted for center, clinical, and social risk factors; at each stage we included variables associated at P < .1 in bivariable analysis with home oxygen use or readmission. Results: Home oxygen was used in 1906 of 3574 infants (53%) in 22 neonatal intensive care units. Readmission occurred in 34%. Earlier gestational age, male sex, gastrostomy tube, surgical necrotizing enterocolitis, lower median income, nonprivate insurance, and shorter hospital-to-home distance were associated with readmission. Home oxygen was not associated with odds of readmission (OR, 1.2; 95% CI, 0.98-1.56), readmission duration, or mortality. Readmissions for infants with home oxygen were more often coded as BPD (16% vs 4%); readmissions for infants on room air were more often gastrointestinal (29% vs 22%; P < .001). Clinical risk factors explained 72% of center variance in readmission. Conclusions: Home oxygen use is not associated with readmission for infants with BPD in regional neonatal intensive care units. Center variation in home oxygen use does not impact readmission risk. Nonrespiratory problems are important contributors to readmission risk for infants with BPD

Emergency management and asthma risk in young Medicaid-enrolled children with recurrent wheeze

To describe clinical characteristics of young children presenting to the emergency department (ED) for early recurrent wheeze, and determine factors associated with subsequent persistent wheeze and risk for early childhood asthma. Retrospective cohort study of Medicaid-enrolled children 0–3 years old with an index ED visit for wheeze (e.g. bronchiolitis, reactive airway disease) from 2009 to 2013, and at least one prior documented episode of wheeze at an ED or primary care visit. The primary outcome was persistent wheeze between 4 and 6 years of age. Demographics and clinical characteristics were collected from the index ED visit. Logistic regression was used to estimate the association between potential risk factors and subsequent persistent wheeze. During the study period, 41,710 children presented to the ED for recurrent wheeze. Mean age was 1.3 years; 59% were male, 42% Black, and 6% Hispanic. At index ED visits, the most common diagnosis was acute bronchiolitis (40%); 77% of children received an oral corticosteroid prescription. Between 4 and 6 years of age, 11,708 (28%) children had persistent wheeze. A greater number of wheezing episodes was associated with an increased odds of ED treatment with asthma medications. Subsequent persistent wheeze was associated with male sex, Black race, atopy, prescription for bronchodilators or corticosteroids, and greater number of visits for wheeze. Young children with persistent wheeze are at risk for childhood asthma. Thus, identification of risk factors associated with persistent wheeze in young children with recurrent wheeze might aid in early detection of asthma and initiation of preventative therapies.</p

Pediatric septic shock collaborative improves emergency department sepsis care in children

Objectives: The pediatric emergency department (ED)-based Pediatric Septic Shock Collaborative (PSSC) aimed to improve mortality and key care processes among children with presumed septic shock. Methods: This was a multicenter learning and improvement collaborative of 19 pediatric EDs from November 2013 to May 2016 with shared screening and patient identification recommendations, bundles of care, and educational materials. Process metrics included minutes to initial vital sign assessment and to first and third fluid bolus and antibiotic administration. Outcomes included 3- and 30-day all-cause in-hospital mortality, hospital and ICU lengths of stay, hours on increased ventilation (including new and increases from chronic baseline in invasive and noninvasive ventilation), and hours on vasoactive agent support. Analysis used statistical process control charts and included both the overall sample and an ICU subgroup. Results: Process improvements were noted in timely vital sign assessment and receipt of antibiotics in the overall group. Timely first bolus and antibiotics improved in the ICU subgroup. There was a decrease in 30-day all-cause in-hospital mortality in the overall sample. Conclusions: A multicenter pediatric ED improvement collaborative showed improvement in key processes for early sepsis management and demonstrated that a bundled quality impr