Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge.

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4-), and, to a lower extent, in B-cells from healthy controls. Notably, IDE's surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE's surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4- T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4- T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.

Systems of care among children and youth with special health care needs with and without adverse childhood events: National Survey of Children's Health 2016-2017.

BACKGROUND: Knowledge of adverse childhood events (ACEs), the associated access to healthcare and unmet needs among children and youth with special health care needs (CYSHCN) is limited. OBJECTIVES: Our objectives were to compare the likelihood of CYSHCN versus non-CYSHCN experiencing one or more ACEs and document differences in receipt of recommended and needed health care among CYSHCN with and without ACEs. METHODS: We combined two years of data from the 2016 and 2017 National Survey of Children's Health (N = 71,181), providing a sample of 16,304 CYSHCN. Our primary outcome measures included eight adverse childhood events, compared to singular and aggregated ACEs among non-CYSHCN. We calculated associations between ACEs and secondary outcome measures for six components of well-functioning systems of care and unmet need for different types of health care using bivariate and multivariate analyses. RESULTS: CYSHCN were more likely to have each of the ACEs measured and were likelier to experience aggregated levels of ACEs compared to non-CYSHCN. The likelihood of CYSHCN having a medical home with family-centered and coordinated care decreased with increased ACEs, while one or more ACES increased the likelihood of having unmet needs for mental health care. CONCLUSION: The findings of the current study extend our understanding of the additional adverse event burden associated with special health care needs status, the accompanying limitations in access to family-centered and coordinated care in a medical home and unmet need for mental health care, indicating that much work remains in establishing appropriate care systems for this very vulnerable population.

Healthcare provider-child-parent communication in the preoperative surgical setting.

OBJECTIVES: Although preoperative preparation programs were once common, most children currently undergoing outpatient surgery are first exposed to the hospital on the day of the procedure. It is advocated that these outpatient children undergo the preparation just prior to surgery. AIM: To assess the amount of time that healthcare providers spend with children and families on the day of surgery in the preoperative area. MATERIALS AND METHODS: The study used video infrastructure in the preoperative holding area of Yale New Haven Children's Hospital to record all interactions between children, families, and healthcare providers. Videotapes were coded to characterize and quantify behaviors of healthcare professionals. RESULTS: On the day of surgery, healthcare providers spent medians of 2.75-4.81 min interacting with children and parents in the preoperative area. Families spent a median of 46.5 min in the preoperative area. Healthcare professionals spent the most time in medical talk (averages of 42.5-48.2% of time spent with family) and little time was spent in nonmedical talk (range of 6.2-6.9% of time spent with family). Anesthesiologists and surgeons spent 28% and 18% of the interview in talk to children; admitting nurses spent more of the interview talking to children (43%). CONCLUSIONS: Families interact with healthcare providers for only a small proportion of the time they spent in the preoperative area. This is likely to be a result of increased production pressure in the perioperative settings and has implications for providing preparation for surgery on the morning of the procedure.