Pediatric Surgical Reentry Strategy Following the COVID-19 Pandemic: A Tiered and Balanced Approach.

BACKGROUND: In response to the COVID-19 pandemic, children's hospitals across the country postponed elective surgery beginning in March 2020. As projective curves flattened, administrators and surgeons sought to develop strategies to safely resume non-emergent surgery. This article reviews challenges and solutions specific to a children's hospital related to the resumption of elective pediatric surgeries. We present our tiered reentry approach for pediatric surgery as well as report early data for surgical volume and tracking COVID-19 cases during reentry. METHODS: The experience of shutdown, protocol development, and early reentry of elective pediatric surgery are reported from Levine's Children's Hospital (LCH), a free-leaning children's hospital in Charlotte, North Carolina. Data reported were obtained from de-identified hospital databases. RESULTS: Pediatric surgery experienced a dramatic decrease in case volumes at LCH during the shutdown, variable by specialty. A tiered and balanced reentry strategy was implemented with steady resumption of elective surgery following strict pre-procedural screening and testing. Early outcomes showed a steady thorough fluctuating increase in elective case volumes without evidence of a surgery-associated positive spread through periprocedural tracking. CONCLUSION: Reentry of non-emergent pediatric surgical care requires unique considerations including the impact of COVID-19 on children, each children hospital structure and resources, and preventing undue delay in intervention for age- and disease-specific pediatric conditions. A carefully balanced strategy has been critical for safe reentry following the anticipated surge. Ongoing tracking of resource utilization, operative volumes, and testing results will remain vital as community spread continues to fluctuate across the country.

Leading countries in global science increasingly receive more citations than other countries doing similar research.

Citations and text analysis are both used to study the distribution and flow of ideas between researchers, fields and countries, but the resulting flows are rarely equal. We argue that the differences in these two flows capture a growing global inequality in the production of scientific knowledge. We offer a framework called 'citational lensing' to identify where citations should appear between countries but are absent given that what is embedded in their published abstract texts is highly similar. This framework also identifies where citations are overabundant given lower similarity. Our data come from nearly 20 million papers across nearly 35 years and 150 fields from the Microsoft Academic Graph. We find that scientific communities increasingly centre research from highly active countries while overlooking work from peripheral countries. This inequality is likely to pose substantial challenges to the growth of novel ideas.

A neonatal mouse model of intestinal perforation: investigating the harmful synergism between glucocorticoids and indomethacin.

BACKGROUND: Early postnatal steroids and indomethacin in combination have been shown to increase the risk of spontaneous intestinal perforation (SIP) in infants with extremely low birth weight (ELBW), but the mechanism behind this synergistic effect is unknown. MATERIALS AND METHODS: Based on literature in a variety of models suggesting that glucocorticoids and nonsteroidal antiinflammatory agents diminish complementary isoforms of nitric oxide synthase (NOS), we hypothesized that perturbations in NO metabolism contribute to SIP. RESULTS: Our results using newborn wild-type (WT) and endothelial NOS-knockout (eNOS KO) mice treated with dexamethasone and/or indomethacin indicate that indomethacin treatment diminishes ileal eNOS abundance; dexamethasone treatment diminishes ileal inducible NOS and neuronal NOS (nNOS); 100% of dexamethasone-treated eNOS KO mice die after 3 days; eNOS KO mice treated for 2 days with dexamethasone develop acute pyloric stenosis in association with reduced expression of pyloric nNOS; and isolated ileum from eNOS KO mice treated for 2 days with dexamethasone exhibit a significant decrease in spontaneous peristalsis, decreased circumference, and decreased capacitance for forced volume before ileal perforation compared with ileum from untreated controls. CONCLUSIONS: Our findings suggest that eNOS and nNOS display functional overlap in the newborn mouse gastrointestinal tract and that simultaneous reduction in the activity of both NOS isoforms may be a risk factor for neonatal ileal perforation. If this holds true in human infants, then it provides a plausible etiologic explanation for the strong temporal association between SIP and the simultaneous treatment of ELBW infants with glucocorticoids and indomethacin.

Igf-I accelerates ileal epithelial cell migration in culture and newborn mice and may be a mediator of steroid-induced maturation.

We have previously hypothesized that IGF-I is a mediator of dexamethasone (DEX) effect in the newborn mouse ileum-a model designed to mimic the precocious mucosal maturation associated with spontaneous ileal perforations in extremely premature neonates. We have further investigated this hypothesis using in vivo and in vitro models of accelerated epithelial migration (a transient property, temporally associated with mucosal maturation). These experiments include a steroid-treatment model comparing IGF-I immunolocalization with bromo-deoxyuridine (BrdU)-pulse-labeling, as a means of assessing epithelial cell migration, within the ileum of newborn mice that received either daily intraperitoneal injections of DEX (1 microg/gm) or vehicle. Likewise, a transgenic newborn mouse model was used to compare the effect of IGF-I overexpression upon the clearance of BrdU-pulse-labeled epithelial cells traveling up the villus during the same time period. For our in vitro model, rat ileal epithelial cells (IEC-18) were cultured to confluence in serum-free media then treated with DEX, a stable IGF-I agonist, or nothing before being subjected to linear scarification. Serial photomicrographs of migrating cells were taken over time and the average speed was determined for each treatment condition. Our data demonstrate that IGF-I accelerates ileal epithelial cell migration in every model. However, DEX was only associated with accelerated epithelial cell migration in models where IGF-I (or a synthetic agonist) was highly abundant. In contrast, DEX by itself slowed migration speed in cell culture. These findings suggest that IGF-I may be a mediator of steroid effect during precocious maturation of the ileal mucosa.

Insulin-like growth factor-I governs submucosal growth and thickness in the newborn mouse ileum.

Spontaneous intestinal perforations in extremely premature infants are associated with glucocorticoid-induced thinning of the ileal bowel wall. We have previously demonstrated that insulin-like growth factor-1 (IGF-1) is abundant within the submucosa of the newborn mouse ileum but is diminished by glucocorticoid exposure, concomitant with bowel wall thinning. These findings prompted us to hypothesize that IGF-I governs submucosal growth during neonatal gut development and that diminished IGF-I abundance results in submucosal thinning. Heterozygous IGF-I knockout, wild type and homozygous IGF-I over-expresser newborn mice were euthanized at 3 d of life. Additionally, wild type newborn mice received daily dexamethasone (DEX) (1microg/gm/d) or vehicle control on days of life 1 and 2 and were also euthanized at 3 d of life. Their ileums were harvested, fixed and the resulting sections were processed in parallel for IGF-I immunohistochemistry and morphometric measurements of submucosal thickness and bowel diameter. Immunolocalization of IGF-I in each genotype was also compared with that seen in DEX-treated and control mice euthanized at the same time of life. IGF-I heterozygous knockouts had diminished submucosal IGF-I immunolocalization (similar to that seen in DEX-treated newborn mice) whereas homozygous IGF-I over-expressers exceeded that seen within wild type mice. IGF-I genotype and submucosal abundance was positively correlated with ileal submucosal thickness. DEX treatment of newborn mice diminished IGF-I and caused significant thinning of the submucosa compared with controls. Submucosal growth and thickness in the neonatal mouse ileum is governed by IGF-I and is diminished by dexamethasone treatment.