Impact of maternal factors, environmental factors, and race on necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a complex disease with a multifactorial etiology. As the leading cause of intestinal morbidity and mortality among premature infants, many resources are being dedicated to neonatal care and molecular targets in the newborn intestine. However, NEC is heavily influenced by maternal and perinatal factors as well. Given its nature, preventive approaches to NEC are more likely to improve outcomes than new treatment strategies. Therefore, this review focuses on maternal, environmental, and racial factors associated with the development of NEC, with an emphasis on those that may be modifiable to decrease the incidence of the disease.

Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. CONCLUSIONS: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.

Perforated Appendicitis During a Pandemic: The Downstream Effect of COVID-19 in Children.

INTRODUCTION: Coronavirus Disease-19 (COVID-19) was declared a pandemic in March 2020. States issued stay-at-home orders and hospitals cancelled non-emergent surgeries. During this time, we anecdotally noticed more admissions for perforated appendicitis. Therefore, we hypothesized that during the months following the COVID-19 pandemic declaration, more children were presenting with perforated appendicitis. MATERIALS AND METHODS: This is a retrospective cohort study reviewing pediatric patients admitted at a single institution with acute and/or perforated appendicitis between October 2019 to May 2020. Interval appendectomies were excluded. COVID-19 months were designated as March, April, and May 2020. Additional analysis of March, April, and May 2019 was performed for comparison purposes. Analyzed data included demographics, symptoms, white blood cell count, imaging findings, procedures performed, and perforation status. Statistical analysis was performed. RESULTS: During the study period, 285 patients were admitted with the diagnosis of acute appendicitis with 95 patients being perforated. We identified a significant increase in perforated appendicitis cases in the three COVID-19 months compared with the preceding five months (45.6% vs 26.4%; P <0.001). In addition, a similar significant increase was identified when comparing to the same months a year prior (P = 0.003). No significant difference in duration of pain was identified (P=0.926). CONCLUSION: The COVID-19 pandemic and its associated stay-at-home orders have had downstream effects on healthcare. Our review has demonstrated a significant increase in the number of children presenting with perforated appendicitis following these stay-at-home ordinances. These results demonstrate that further investigations into the issues surrounding access to healthcare, especially during this pandemic, are warranted.

Stress and the Gut-Brain Axis: Implications for Cancer, Inflammation and Sepsis.

BACKGROUND: The gut-brain axis has been discussed, directly or indirectly, for centuries, with the ideas of the gut affecting anything from moods to overall physiology being discussed across the centuries. With a recent explosion in research that looks to the microbiota as a mechanistic link between the gut and the brain, one sees that the gut-brain axis has various means of communication, such as through the vagus nerve and the enteric nervous system and can use the metabolites in the gut to communicate to the brain. METHODS: The purpose of this review is to view the gut-brain axis through the lens of stress and how stress, from the prenatal period all the way through adulthood can impact the physiology of a human being. Studies have shown multiple mechanisms of measurable change with disruption in the microbiota that lead to behavioral changes. There are also effects of gut inflammation on the brain and the corresponding systemic response observed. CONCLUSION: The overall literature is encouraging that the more understanding of the gut-brain axis, the greater ability to wield that understanding for therapeutic benefits.

Effectiveness of a central line associated blood stream infection protocol in a pediatric population.

BACKGROUND: Central line associated bloodstream infections are a common cause of bacteremia and sepsis in pediatric patients with intestinal failure, secondary to long-term CVC use. METHODS: An IRB approved retrospective chart review was conducted on TPN-dependent patients with IF who had an identified CLABSI and presented to Children's of Alabama's emergency department (ED) and were admitted to the hospital. RESULTS: Forty-four patients were included in the study, 28 in the first 18-month period and 26 in the second, with 10 in both populations. After implementation, mean time from ED presentation to antibiotic ordered and ED admission to antibiotic administered were lower. Mean time between antibiotic administration and admission to the floor was greater, and number of infectious disease consultations was greater. Floor-ICU transfers were lower, readmissions within 30 days was similar, and mean length of stay was similar. CONCLUSION: A collaborative, multidiscipline-supported protocol for the care of patients with IF presenting to the ED enhances efficiency of antibiotic ordering/administration, as well as reduces the number of unplanned floor-ICU transfers.

Reassessing career pathways of surgical leaders: An examination of surgical leaders' early accomplishments.

BACKGROUND: The American College of Surgeon (ACS), American Surgical Association (ASA), Association of Women Surgeons (AWS), and Society of Black Academic Surgeons (SBAS) partnered to gain insight into whether inequities found in surgical society presidents may be present earlier. METHODS: ACS, ASA, AWS, and SBAS presidents' CVs were assessed for demographics and scholastic achievements at the time of first faculty appointment. Regression analyses controlling for age were performed to determine relative differences across societies. RESULTS: 66 of the 68 presidents' CVs were received and assessed (97% response rate). 50% of AWS future presidents were hired as Instructors rather than Assistant professors, compared to 29.4% of SBAS, 25% of ASA and 29.4% of ACS. The future ACS, ASA, and SBAS presidents had more total publications than the AWS presidents, but similar numbers of 1st and Sr. author publications. CONCLUSION: Gender inequities in academic surgeon hiring practices and perceived scholastic success may be present at first hire.

A Novel Use of Artificial Intelligence to Examine Diversity and Hospital Performance.

BACKGROUND: The US population is becoming more racially and ethnically diverse. Research suggests that cultural diversity within organizations can increase team potency and performance, yet this theory has not been explored in the field of surgery. Furthermore, when surveyed, patients express a desire for their care provider to mirror their own race and ethnicity. In the present study, we hypothesize that there is a positive correlation between a high ranking by the US News and World Report for gastroenterology and gastrointestinal (GI) surgery and greater racial, ethnic, and gender diversity among the physicians and surgeons. METHODS: We used the 2019 US News and World Report rankings for best hospitals by specialty to categorize gastroenterology and GI surgery departments into 2 groups: 1-50 and 51-100. Hospital websites of these top 100 were viewed to determine if racial diversity and inclusion were highlighted in the hospitals' core values or mission statements. To determine the rates of diversity within departments, Betaface (Betaface.com) facial analysis software was used to analyze photos taken from the hospitals' websites. This software was able to determine the race, ethnicity, and gender of the care providers. We examined the racial and ethnic makeup of the populations served by these hospitals to see if the gastroenterologists and surgeons adequately represented the state population. We then ran the independent samples t-test to determine if there was a difference in rankings of more diverse departments. RESULTS: Hospitals with gastroenterology and GI surgery departments in the top 50 were more likely to mention diversity on their websites compared with hospitals that ranked from 51-100 (76% versus 56%; P = 0.035). The top 50 hospitals had a statistically significant higher percentage of underrepresented minority GI physicians and surgeons (7.01% versus 4.04%; P < 0.001). In the 31 states where these hospitals were located, there were more African Americans (13% versus 3%; P < 0.001) and Hispanics (12% versus 2%; P < 0.001), while there were fewer Asians (4% versus 21%; P < 0.001) in the population compared with the faculty. CONCLUSIONS: We used artificial intelligence software to determine the degree of racial and ethnic diversity in gastroenterology and GI surgery departments across the county. Higher ranking hospitals had a greater degree of diversity of their faculty and were more likely to emphasize diversity in their mission statements. Hospitals stress the importance of having a culturally diverse staff, yet their care providers may not adequately reflect the populations they serve. Further work is needed to prospectively track diversity rates over time and correlate these changes with measurable outcomes.

Trending diversity: Reviewing four-decades of graduating fellows and the current leadership in pediatric surgery.

PURPOSE: Diversity in the physician workforce remains a priority in healthcare as it has been shown to improve outcomes. Decisions for choosing specific fields in medicine are partly influenced by mentors, which tend to be the same sex or ethnicity. Females are starting to outnumber males in medical school and minorities are targeted for recruitment. We hypothesized that diversity in pediatric surgery has increased over time. METHODS: The recently published A Genealogy of North American Pediatric Surgery was utilized to identify graduating pediatric surgery fellows from 1981 to 2018. Organization websites were used to identify past and current leaders. A web-based analysis, including online facial recognition software, was performed. A year-to-year and decade-to-decade demographic comparison was completed. RESULTS: 1217 pediatric surgery fellows graduated between 1981 and 2018. When comparing graduates from the first and last decades, an increase from 16.9% to 39.5% for female graduates was observed (p = 0.046). A significant increase in nonwhite graduates was seen for all races (p < 0.05). Representation in leadership was White and male dominant. CONCLUSION: There was a significant increase in diversity in pediatric surgery fellowship graduates. There were increasing trends in female graduates and all nonwhite racial groups. Focusing on enhancing the pipeline and mentoring underrepresented minorities will continue to enhance this trend for the field of pediatric surgery. LEVEL OF EVIDENCE: III; Retrospective Review.

Effect of the COVID-19 Pandemic on Pediatric Intestinal Failure Healthcare Delivery.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has influenced how healthcare is being provided, particularly in patients whose diagnoses require multidisciplinary care, such as pediatric intestinal failure (IF). We sought to ascertain the effects of the COVID-19 pandemic on healthcare delivery for pediatric patients with IF. METHODS: A 20-question survey was administered to members of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Intestinal Rehabilitation (IR) Special Interest Group. Input values were "yes" and "no," along with a free-text response. Following a 10-day open survey period, data were divided into cohorts based on patient population size and disease burden by state. Analysis was then performed using the χ2 test application. RESULTS: Responses from 29 centers were included in analysis. Centers that followed >50 patients on parenteral nutrition (PN) were more likely to have social workers present in telemedicine visits and observed more central line difficulties among families. Centers located in states with <40,000 reported cases of COVID-19 saw patients less frequently and were more likely to withhold changes to PN prescriptions. Additionally, the survey revealed a significant degree of financial hardship and food insecurity among families. CONCLUSION: Many aspects of pediatric IF healthcare delivery have been impacted by the COVID-19 pandemic, both for care providers and caregivers. Despite the availability of telemedicine, IR centers should remain attentive to the global needs of the pediatric IF patient, as well as their families.

New directions in necrotizing enterocolitis with early-stage investigators.

The 2019 Necrotizing Enterocolitis (NEC) Symposium expanded upon the NEC Society's goals of bringing stakeholders together to discuss cutting-edge science, potential therapeutics and preventative measures, as well as the patient-family perspectives of NEC. The Symposium facilitated discussions and shared knowledge with the overarching goal of creating "A World Without NEC." To accomplish this goal, new research to advance the state of the science is necessary. Over the last decade, several established investigators have significantly improved our understanding of the pathophysiology of NEC and they have paved the way for the next generation of clinician-scientists funded to perform NEC research. This article will serve to highlight the contributions of these young clinician-scientists that seek to elucidate how immune, microbial and nervous system dysregulation contributes to the pathophysiology of NEC.

RNASeq analysis reveals upregulation of complement C3 in the offspring gut following prenatal stress in mice.

Dysregulated activation of inflammatory signaling by the immature neonatal immune system could lead to the development of many pediatric diseases including necrotizing enterocolitis (NEC). While the mechanism(s) of pathogenesis is unknown, NEC is believed to have multifactorial causes. Microbial dysbiosis and intestinal immaturity have been implicated as potential triggers for this disease. We hypothesized that psychological stress during pregnancy negatively impacts the development of intestinal tissues in offspring and contributes to development of NEC. Consistent with this hypothesis, we previously observed shorter villi and a decrease in total surface area in the small intestine of pups derived from mice that were chronically stressed during gestation. In this study, we performed RNASeq analysis to determine the gene expression changes in the offspring gut following prenatal stress in pregnant mice and identified several differentially expressed genes (DEGs) and biological pathways. Notably, C3 was upregulated in the small intestine and contributed to a higher tissue injury score in a mesenteric ischemia model compared to unstressed controls. We discuss the potential implications of these stress-induced genes expression changes and their contribution to development of intestinal inflammation.

Prenatal stress increases IgA coating of offspring microbiota and exacerbates necrotizing enterocolitis-like injury in a sex-dependent manner.

Necrotizing enterocolitis (NEC) is an intestinal inflammatory disease with high morbidity and mortality that affects almost exclusively premature infants. Breast milk feeding is known to substantially lower NEC incidence, and specific components of breast milk, such as immunoglobulin (Ig) A, have been identified as mediating this protective effect. On the other hand, accumulating evidence suggests dysbiosis of the neonatal intestinal microbiome contributes to NEC pathogenesis. In mice, neonates can inherit a dysbiotic microbiome from dams that experience stress during pregnancy. Here we show that while prenatal stress lowers fecal IgA levels in pregnant mice, it does not result in lower levels of IgA in the breast milk. Nevertheless, coating of female, but not male, offspring microbiota by IgA is increased by prenatal stress. Accordingly, prenatal stress was found to alter the bacterial community composition in female neonates but not male neonates. Furthermore, female, but not male, offspring of prenatally stressed mothers exhibited more severe colonic tissue damage in a NEC-like injury model compared to offspring with non-stressed mothers. Our results point to prenatal stress as a possible novel risk factor for NEC and potentially reveal new avenues in NEC prevention and therapy.

Benchmarking Accomplishments of Leaders in American Surgery and Justification for Enhancing Diversity and Inclusion.

OBJECTIVE: To comprehensively assess the level of achievement and demographics of national surgical society presidents. BACKGROUND: Data on the accomplishments needed to rise to positions of national surgical leadership is scarce and merit alone does not always yield such opportunities. Recognizing the shortcomings of sex and ethnic diversity within academic surgical leadership, the American College of Surgeon (ACS), American Surgical Association (ASA), Association of Women Surgeons (AWS), and the Society of Black Academic Surgeons (SBAS) partnered to address these challenges by performing a comprehensive assessment of their presidents over the last 16 years. METHODS: ACS, ASA, AWS, and SBAS presidents' CVs, at the time of their presidential term, were assessed for demographics and scholastic achievements. Regression analyses controlling for age were performed to determine relative differences across societies. RESULTS: A total of 62 of the 64 presidents' CVs were received and assessed (97% response rate). There was a large discrepancy in the average age in years of ACS (70) and ASA (66) presidents compared to the AWS (51) and SBAS (53) presidents. For the ACS and ASA cohort, 87% were male and 83% were White, collectively. After controlling for age (52), the AWS and SBAS presidents' scholastic achievements were comparable to the ACS (and ASA) cohort in 9 and 12 of the 15 accessed metrics, respectively. CONCLUSION: The ACS and ASA presidents' CVs displayed unsurpassed scholastic achievement, and although not equivalent, both the AWS and the SBAS presidents had comparable attainment. These findings further substantiate that women and ethnic minority surgeons are deserving of additional national leadership consideration as organized medicine pursues a more diverse and reflective physician workforce.

The Society of Black Academic Surgeons CV benchmarking initiative: Early career trends of academic surgical leaders.

BACKGROUND: Surgeons from under-represented backgrounds are less likely to receive academic tenure and obtain leadership positions. Our objective was to query the curriculum vitaes (CVs) of SBAS leadership to develop a benchmarking tool to promote and guide careers in academic surgery. METHODS: CVs from academic leaders were reviewed for academic productivity at early career stages-the first 5-and 10-years. Variables queried: peer-reviewed publications, grant funding, surgical societal involvement, invited lectureships and visiting professorships. RESULTS: Of 20 CVs, 41 leadership positions including 13 SBAS Presidents were identified. At 5- and 10-years, respectively, the academic productivity increased: 20.6 and 52.3 publications; 4.7 and 9.7 grants; 18 and 42.6 lectures/professorships. CONCLUSION: The CV benchmarking tool may be a useful framework for aspiring academic surgeons to track their progress relative to successful SBAS members. Creative strategies like these, paired with faculty mentorship and sponsorship are necessary to improve the ethnic diversity in academic surgery.