Disparities in Utilization of Same-Day Discharge Following Appendectomy in Children.

INTRODUCTION: Disparities in the delivery of pediatric surgical care exist for racial and ethnic minority groups. Utilization of same-day discharge (SDD) following appendectomy for acute, uncomplicated appendicitis is increasing; however, rates among diverse populations have not been explored to evaluate equitable care delivery and healthcare utilization. Our objective was to determine whether race and ethnicity are associated with rates of SDD and postdischarge healthcare utilization. We hypothesized that racial and ethnic minority groups would have lower rates of SDD. METHODS: This retrospective cohort study used data from the 2015-2019 American College of Surgeons National Surgical Quality Improvement Program-Pediatric clinical registry and included children who underwent appendectomy. Patients with complicated appendicitis were excluded. Primary exposure was racial or ethnic group. The primary outcome was SDD, and secondary outcomes included postdischarge emergency department visits and hospital readmissions. RESULTS: Of 37,579 simple appendicitis patients, SDD after appendectomy occurred in 10,012 (26.6%). On multivariable analysis, Black or African American race was associated with lower likelihood of SDD (adjusted odds ratio [aOR]: 0.85; 95% confidence interval [95% CI]:0.79-0.92; P < 0.0001). Hispanic ethnicity was associated with higher likelihood of SDD (aOR: 1.19; 95% CI: 1.12-1.25; P < 0.0001). Likelihood of postoperative emergency department visits was higher in Black or African American patients (aOR: 1.36; 95% CI: 1.14-1.62; P < 0.001) and Hispanic patients (aOR: 1.37; 95% CI: 1.12-1.58; P < 0.0001). Hospital readmission rates were similar across groups. CONCLUSIONS: Rates of SDD following appendectomy vary among racial and ethnic groups. Interventions to achieve equitable healthcare delivery including SDD after appendectomy are needed.

Postoperative Complications and Risk of Mortality after Laparotomy in a Resource-Limited Setting.

BACKGROUND: Despite increases in surgical capacity in Malawi, minimal data exist on postoperative complications. Identifying surgical management gaps and targeting quality improvement requires detailed, longitudinal complications, and outcome data that assess surgical safety and efficacy. METHODS: We conducted a 6-mo prospective, observational study of patients >12 y after laparotomy at a tertiary hospital in Lilongwe, Malawi. Outcomes included postoperative complications and mortality. The seniormost rounding physician determined complication diagnoses. Bivariate and Poisson regression analyses identified predictors of mortality. RESULTS: Only patients undergoing emergent laparotomy (77.8%) died before discharge, so analysis excluded elective cases. Of 189 patients included, the median age was 33.5 y (IQR 22-50.5), 22 (12.2%) had prior abdominal surgery, and 11 (12.1%) were human immunodeficiency virus-positive. Gastrointestinal perforation was the most common diagnosis (35.5%). The most common procedures were primary gastrointestinal repair (24.9%), diverting ostomy (21.2%), and bowel resection with anastomosis (16.4%). Overall postoperative mortality was 14.8%. Intra-abdominal complication occurred in 17 (9.0%) patients, of whom 8 (47.1%) died. Older age (RR 1.05, 95% CI 1.02-1.08, P < 0.001) and intra-abdominal complication (RR 2.88, 95% CI 1.28-6.46, P = 0.01) increased the relative risk of mortality. Preoperative diagnosis, surgical intervention type, and symptom-to-surgery time did not increase the relative risk of mortality. CONCLUSIONS: The incidence of complications and mortality after laparotomy at a large referral hospital in Malawi is high. Older age and intra-abdominal complications increase the risk of death. Strategies to improve operative mortality in Malawi should prioritize postoperative surveillance and management and continued outcomes reporting.

Outcomes Following Intensive Care Unit Admission in a Pediatric Cohort in Malawi.

INTRODUCTION: The burden of critical illness in low- and middle-income countries (LMICs) is high; however, there is a paucity of data describing pediatric critical care outcomes in this setting. METHODS: We performed a prospective observational study of the pediatric (≤18 years) intensive care population in Malawi, from August 2016 to May 2018. Data collected include patient demographics and clinical data, admission criteria and outcome. A multivariate Poisson regression was performed to determine risk factors for mortality. RESULTS: Over the study period, 499 patients were admitted to the intensive care unit (ICU) and 105 (21.0%) were children. The average age was 10.6 ± 5.4 years. Primary indications for ICU admission were sepsis (n = 30, 30.3%) and traumatic brain injury (TBI, n = 23, 23.2%). Of those who died, sepsis (n = 18, 32.7%), acute respiratory failure (n = 11, 20.0%) and TBI (n = 11, 20.0%) were the primary admission diagnoses. Overall, ICU mortality was 54.3% (n = 57). Multivariate regression for increased ICU mortality revealed: age ≤5 years [risk ratio (RR) 1.96, 95% CI 1.10-2.26, p < 0.001], hemoglobin < 10 g/dl (RR 1.58, 95% CI 1.08-2.01, p = 0.01) and shock requiring epinephrine support (RR 2.76, 95% CI 1.80-4.23, p < 0.001). CONCLUSIONS: Pediatric ICU mortality is high. Predictors of mortality were age ≤5 years, anemia at ICU admission and the need for epinephrine support. Training of pediatric intensive care specialists and increased blood product availability may attenuate the high mortality for critically ill children in Malawi.

Alvarado Scores Predict Additive Value of Magnetic Resonance Imaging in Workup of Suspected Appendicitis in Children.

BACKGROUND: The presentation of appendicitis in pediatrics is variable, and diagnostic imaging is often used. Magnetic resonance imaging (MRI) is replacing computed tomography in some centers, particularly after a nondiagnostic ultrasound (NDUS). Nonetheless, MRI is not widely used in this setting because of cost, procedure time, institutional capacity, and high rates of negative scans. We hypothesized that the Alvarado Score (AS) could be used to determine the additive diagnostic value of MRI after an NDUS. MATERIALS AND METHODS: Retrospective review of patients aged ≤18 y at a single tertiary care children's hospital who received an ultrasound for suspected appendicitis during 10 consecutive months in 2017. NDUS were defined as nonvisualization of the appendix or secondary signs without radiologic diagnosis. AS were retrospectively calculated from the electronic medical record. Primary outcomes were pathology-confirmed appendicitis, appendectomy, and perforation. RESULTS: AS was determined for 352 patients out of 463 who met inclusion criteria (76%). Sixty-two percent had an NDUS, and 45% of these patients received MRI. Patients with high-risk AS were significantly more likely to have MRI diagnostic of appendicitis (P = 0.0015), and low-risk AS patients were more likely to have a negative or equivocal MRI (P = 0.0169). Twenty-one MRI scans were required per each additional diagnosis of appendicitis in patients with low AS after NDUS versus 4.2 in intermediate-risk AS patients and 2.1 in high-risk AS patients. CONCLUSIONS: Risk stratification with AS can help assess the additive diagnostic utility of MRI after NDUS. MRI may be overutilized for diagnosing acute appendicitis in pediatric patients with low-risk AS.

miR-30 Family Controls Proliferation and Differentiation of Intestinal Epithelial Cell Models by Directing a Broad Gene Expression Program That Includes SOX9 and the Ubiquitin Ligase Pathway.

Proliferation and differentiation of intestinal epithelial cells (IECs) occur in part through precise regulation of key transcription factors, such as SOX9. MicroRNAs (miRNAs) have emerged as prominent fine-tuners of transcription factor expression and activity. We hypothesized that miRNAs, in part through the regulation of SOX9, may mediate IEC homeostasis. Bioinformatic analyses of the SOX9 3'-UTR revealed highly conserved target sites for nine different miRNAs. Of these, only the miR-30 family members were both robustly and variably expressed across functionally distinct cell types of the murine jejunal epithelium. Inhibition of miR-30 using complementary locked nucleic acids (LNA30bcd) in both human IECs and human colorectal adenocarcinoma-derived Caco-2 cells resulted in significant up-regulation of SOX9 mRNA but, interestingly, significant down-regulation of SOX9 protein. To gain mechanistic insight into this non-intuitive finding, we performed RNA sequencing on LNA30bcd-treated human IECs and found 2440 significantly increased genes and 2651 significantly decreased genes across three time points. The up-regulated genes are highly enriched for both predicted miR-30 targets, as well as genes in the ubiquitin-proteasome pathway. Chemical suppression of the proteasome rescued the effect of LNA30bcd on SOX9 protein levels, indicating that the regulation of SOX9 protein by miR-30 is largely indirect through the proteasome pathway. Inhibition of the miR-30 family led to significantly reduced IEC proliferation and a dramatic increase in markers of enterocyte differentiation. This in-depth analysis of a complex miRNA regulatory program in intestinal epithelial cell models provides novel evidence that the miR-30 family likely plays an important role in IEC homeostasis.

Indocyanine green (ICG) fluorescence-enhanced applications in pediatric surgery.

The breadth of pediatric surgical practice and variety of anatomic anomalies that characterize surgical disease in children and neonates require a unique level of operative mastery and versatility. Intraoperative navigation of small, complex, and often abnormal anatomy presents a particular challenge for pediatric surgeons. Clinical experience with fluorescent tissue dye, specifically indocyanine green (ICG), is quickly gaining widespread incorporation into adult surgical practice as a safe, non-toxic means of accurately visualizing tissue perfusion, lymphatic flow, and biliary anatomy to enhance operative speed, safety, and patient outcomes. Experience in pediatric surgery, however, remains limited. ICG-fluorescence guided surgery is poised to address the challenges of pediatric and neonatal operations for a growing breadth of surgical pathology. Fluorescent angiography has permitted intraoperative visualization of colorectal flap perfusion for complex pelvic reconstruction and anastomotic perfusion after esophageal atresia repair, while its hepatic absorption and biliary excretion has made it an excellent agent for delineating the dissection plane in the Kasai portoenterostomy and identifying both primary and metastatic hepatoblastoma lesions. Subcutaneous and intra-lymphatic ICG injection can identify iatrogenic chylous leaks and improved yields in sentinel lymph node biopsies. ICG-guided surgery holds promise for more widespread use in pediatric surgical conditions, and continued evaluation of efficacy will be necessary to better inform clinical practice and identify where to focus and develop this technical resource.

Cost Analysis of Early vs Delayed Outpatient Repair of Inguinal Hernias in Premature Infants.

INTRODUCTION: Premature infants treated for inguinal hernias after hospital discharge require overnight post-operative observation for apnea monitoring until 50-60 weeks adjusted gestational age (AGA). This study aimed to compare costs associated with early (at time of diagnosis) versus delayed (at AGA not requiring overnight observation) repair of inguinal hernia in premature infants. METHODS: Costs were estimated using the average hospital charges at a single institution for three scenarios: 1) delayed repair 2) early repair requiring overnight observation, and 3) incarcerated inguinal hernia reduced but requiring delayed repair at 48 h. A decision analysis model was used to estimate the cost for premature infants undergoing delayed repair of inguinal hernia while considering the risk of incarceration and associated costs. The base model used 50 weeks AGA for delayed repair and an incarceration rate of 0.5%/week. Sensitivity analyses varied incarceration rate from 0.1 to 4%/week and delayed repair to 55 and 60 weeks AGA. RESULTS: In the base model, delayed repair incurred lower estimated costs than early repair at all time points of diagnosis. In sensitivity analyses, estimated cost for delayed repair only rose above the estimated cost for early repair when estimated incarceration risk reached 3%/week with repair at 60 weeks AGA (if repair before 38 weeks AGA) or 4%/week with repair at 55 weeks AGA (if repair before 39 weeks AGA). CONCLUSIONS: Using solely cost as a deciding factor, repair of premature inguinal hernias diagnosed as an outpatient should be delayed until overnight observation is no longer necessary. TYPE OF STUDY: Decision Analysis model. LEVEL OF EVIDENCE: III.

Preoperative anemia and surgical outcomes following laparotomy in a resource-limited setting.

INTRODUCTION: Anemia is a common and potentially modifiable condition in sub-Saharan Africa. We sought to determine the role of preoperative anemia on post laparotomy abdominal complications. METHODS: We conducted a six-month prospective, observational study of patients age >12 years following laparotomy at a tertiary hospital in Malawi. The outcome was the occurrence of abdominal complications. Poisson regression analyses estimated the risk of abdominal complications in patients with moderate/severe anemia. RESULTS: Of 280 patients, most were male (76.4%) with median age of 35 years (IQR 24-50). Abdominal complications developed in 34 patients (15.2%). Of the 224 patients with known preoperative hemoglobin 54 (20.7%) were moderately or severely anemic at the time of surgery. Patients with moderate-to-severe anemia had an increased risk of abdominal complications (RR 4.44, 95% CI 2.0-9.6). CONCLUSION: Anemia is a common but modifiable comorbidity among laparotomy patients and independently increases the risk of abdominal complications.

The effect of burn mechanism on pediatric mortality in Malawi: A propensity weighted analysis.

INTRODUCTION: The burden of global trauma disproportionately affects low- and middle-income countries, with a high incidence in children. Thermal injury represents one of the most severe forms of trauma and is associated with remarkable morbidity and mortality. The predictors of burn mortality have been well described (age, % total body surface area burn [TBSA], and presence of inhalation injury). However, the contribution of the burn mechanism as a predictor of burn mortality is not well delineated. METHODS: This is a retrospective analysis of prospectively collected data, utilizing the Kamuzu Central Hospital (KCH) Burn Surveillance Registry from May 2011 to August 2019. Pediatric patients (≤12 years) with flame and scald burns were included in the study. Basic demographic variables including sex, age, time to presentation, %TBSA, surgical intervention, burn mechanism, and in-hospital mortality outcome was collected. Bivariate analysis comparing demographic, burn characteristics, surgical intervention, and patient outcomes were performed. Standardized estimates were adjusted using inverse-probability of treatment weights (IPTW) to account for confounding. Following weighting, logistic regression modeling was performed to determine the odds of in-hospital mortality based on burn mechanism. RESULTS: During the study period, 2364 patients presented to KCH for burns and included in the database with 1794 (75.9%) pediatric patients. Of these, 488 (27.6%) and 1280 (72.4%) were injured by flame and scald burns, respectively. Males were 47.2% (n = 230) and 59.2% (n = 755) of the flame and scald burn cohorts, respectively (p < 0.001.) Patients presenting with flame burns compared to scald burns were older (4. 7 ± 3.1 vs. 2.7 ± 2.3 years, p < 0.001) with greater %TBSA burns (17.8 [IQR 10-28] vs 12 [IQR 7-20], p < 0.001). Surgery was performed for 42.2% (n = 206) and 19.9% (n = 140) of the flame and scald burn cohorts, respectively (p < 0.001.) Flame burns had a 2.6x greater odds of in-hospital mortality compared to scald burns (p < 0.001) after controlling for sex, %TBSA, age, time to presentation, and surgical status. CONCLUSION: In this propensity-weighted analysis, we show that burn mechanism, specifically flame burns, resulted in a nearly 3-fold increase in odds of in-hospital mortality compared to scald burns. Our results emphasize flame and scald burns have major differences in the inflammatory response, metabolic profile over time, and outcomes. We may further utilize these differences to develop specialized treatments for each burn mechanism to potentially prevent metabolic dysfunction and improve clinical outcomes.

Improving Use of a Hospital Transitional Care Clinic.

BACKGROUND: In response to Medicare readmission penalties, some hospitals have introduced transitional care clinics (TCCs) to meet the care needs of patients recently discharged from the emergency room or inpatient setting. This study was undertaken to increase the proportion of low-income, medically complex patients using a TCC at a large academic medical center, Northwestern Medical Group Transitional Care Clinic (NMG-TC). METHODS: This quality improvement study combined interviews and quantitative data analysis to determine how to increase use of NMG-TC. Physicians and patients were interviewed and surveyed to identify opportunities to expand clinic use. Logistic regression analysis of electronic health record (EHR) data was used to identify sociodemographic and clinical conditions influencing the TCC appointment show rate. RESULTS: Provider surveys and interviews suggested that referrals would likely increase via automation of referral guidelines and enhanced transitional care education. Patient interviews indicated that better communication of NMG-TC purpose, emphasizing nonmedical offerings, and warm handoffs could increase engagement. EHR analyses revealed that patients least likely to attend appointments were male, uninsured, non-Hispanic black, or homeless; had documented substance use; or lived > 50 miles from the clinic. Conversely, patients with heart failure, anxiety, or malignancy were more likely to attend appointments. CONCLUSION: TCC show rates could be improved with better communication of NMG-TC benefits to both patients and referring providers, as well as warm appointment handoffs, particularly for patients least likely to attend scheduled visits.

Caveolin 1 is Associated with Upregulated Claudin 2 in Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency of neonates. Epithelial tight junction (TJ) proteins, such as claudins, are essential for regulation and function of the intestinal barrier. Rho kinase (ROCK) affects cellular permeability and TJ regulation. We hypothesized that TJ protein changes would correlate with increased permeability in experimental NEC, and ROCK inhibitors would be protective against NEC by regulation of key claudin proteins. We tested this hypothesis using an in vivo rat pup model, an in vitro model of experimental NEC, and human intestinal samples from patients with and without NEC. Experimental NEC was induced in rats via hypoxia and bacteria-containing formula, and in Caco-2 cells by media inoculated with LPS. The expression of claudins was measured by gene and protein analysis. Experimental NEC in rat pups and Caco-2 cells had increased permeability compared to controls. Gene and protein expression of claudin 2 was increased in experimental NEC. Sub-cellular fractionation localized increased claudin 2 protein to the cytoskeleton. ROCK inhibition was associated with normalization of these alterations and decreased severity of experimental NEC. Co-immunoprecipitation of caveolin-1 with claudin 2 suggests that caveolin-1 may act as a shuttle for the internalization of claudin 2 seen in experimental NEC. In conclusion, NEC is associated with intestinal permeability and increased expression of claudin 2, increased binding of caveolin-1 and claudin 2, and increased trafficking of claudin 2 to the cytoskeleton.