Stephanie Papillon

The role of the intestinal microbiota in the pathogenesis of necrotizing enterocolitis.

Abstract Development of necrotizing enterocolitis (NEC) requires a susceptible host, typically a premature infant or an infant with congenital heart disease, enteral feedings and bacterial colonization. Although there is little doubt that microbes are critically involved in the pathogenesis of NEC, the identity of specific causative pathogens remains elusive. Unlike established normal adult gut microbiota, which is quite complex, uniform, and stable, early postnatal bacterial populations are simple, diverse, and fluid. These properties complicate studies aimed at elucidating characteristics of the gut microbiome that may play a role in the pathogenesis of NEC. A broad variety of bacterial, viral, and fungal species have been implicated in both clinical and experimental NEC. Frequently, however, the same species have also been found in physiologically matched healthy individuals. Clustered outbreaks of NEC, in which the same strain of a suspected pathogen is detected in several patients suggest, but do not prove, a causative relationship between the specific pathogen and the disease. Studies in Cronobacter sakazakii, the best characterized NEC pathogen, have demonstrated that virulence is not a property of a bacterial species as a whole, but rather a characteristic of certain strains, which may explain why the same species can be pathogenic or non-pathogenic. The fact that a given microbe may be innocuous in a full-term, yet pathogenic in a pre-term infant has led to the idea of opportunistic pathogens in NEC. Progress in understanding the infectious nature of NEC may require identifying specific pathogenic strains and unambiguously establishing their virulence in animal models.

Percutaneous liver biopsy: pathologic diagnosis and complications in children.

Objective: The aim of this study was to determine patient factors that predict diagnostic failure or increased risk of bleeding complications following percutaneous liver biopsy in children. Methods: A retrospective review of all children undergoing percutaneous liver biopsy at a single institution between July 2008 and July 2011 was performed. Demographics, comorbid conditions, preprocedural diagnoses/indications, procedural details, laboratory data, pathologic diagnosis, and complications were recorded. Continuous data were analyzed by Wilcoxon test and categorical data by Fisher exact test to determine statistical significance. Results: Two hundred thirteen children (104 girls) with a median age of 7 years (range 1 week–22 years) underwent 328 percutaneous liver biopsies. Nine (4.2%) experienced a decrease in hemoglobin >2 g/dL, 7 required transfusion (3.3%), and 1 patient died (0.5%). Younger age (1.8 vs 84 months, P = 0.05) and lower preprocedural hematocrit (29.3 vs 34.3, P = 0.05) predicted bleeding complications, whereas the number of biopsies, comorbid conditions, and coagulopathy did not. Sixty-three (19.2%) biopsies were insufficient for definitive histologic evaluation on initial biopsy in 57 patients. Twenty-one of 57 patients (37%) underwent repeat percutaneous biopsy and 3 of 57 (8%) underwent surgical biopsy. Biopsy provided definitive diagnosis in 86% of cases when repeat biopsy was performed. Shorter specimen length (1.4 vs 1.7 cm, P < 0.01) and biopsies performed for unexplained elevation of liver function tests (34.9% vs 16.7%, P < 0.01) were predictive of nondiagnosis. Conclusions: Percutaneous liver biopsy is safe with a low rate of bleeding-related complications. Ensuring adequate sample length and careful patient selection may further increase the diagnostic yield.

Late onset of necrotizing enterocolitis in the full-term infant is associated with increased mortality: Results from a two-center analysis

PURPOSE The effect of timing of onset of necrotizing enterocolitis (NEC) on outcomes has not been determined for the full-term infant. In this study we aimed to characterize the full-term NEC population and to evaluate onset of NEC. METHODS We performed a two-center retrospective review of all full-term infants (≥ 37weeks) with a diagnosis of NEC between 1990 and 2012. Patients were identified by ICD-9 and age. Early onset for NEC was ≤7days and late onset after 7days of life. Demographics, comorbidities, maternal factors, clinical factors, surgical intervention, complications, and mortality were evaluated. Wilcoxons test was performed on continuous variables and Fishers exact test on categorical data. A p-value<0.05 was considered significant. Univariate outcomes with a p-value<0.1 were selected for multivariable analysis. RESULTS Thirty-nine patients (24 boys, 15 girls) with median EGA of 39weeks were identified. Overall mortality was 18%. Univariate predictors of mortality included congenital heart disease and placement of an umbilical artery (UA) catheter. Multivariate analysis revealed late onset of NEC to be an independent predictor of mortality (OR 90.8, 95% CI 2.6-3121). CONCLUSION Full-term infants who develop NEC after 7days of life, have congenital heart disease, and/or need UA catheterization have increased mortality.

Low doses of Celecoxib attenuate gut barrier failure during experimental peritonitis

The intestinal barrier becomes compromised during systemic inflammation, leading to the entry of luminal bacteria into the host and gut origin sepsis. Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study, we examined the role of cyclooxygenase-2 (COX-2), a key enzyme in the production of inflammatory prostanoids, in gut barrier failure during experimental peritonitis in mice. I.p. injection of LPS or cecal ligation and puncture (CLP) increased the levels of COX-2 and its product prostaglandin E2 (PGE2) in the ileal mucosa, caused pathologic sloughing of the intestinal epithelium, increased passage of FITC-dextran and bacterial translocation across the barrier, and increased internalization of the tight junction (TJ)-associated proteins junction-associated molecule-A and zonula occludens-1. Luminal instillation of PGE2 in an isolated ileal loop increased transepithelial passage of FITC-dextran. Low doses (0.5–1 mg/kg), but not a higher dose (5 mg/kg) of the specific COX-2 inhibitor Celecoxib partially ameliorated the inflammatory gut barrier failure. These results demonstrate that high levels of COX-2-derived PGE2 seen in the mucosa during peritonitis contribute to gut barrier failure, presumably by compromising TJs. Low doses of specific COX-2 inhibitors may blunt this effect while preserving the homeostatic function of COX-2-derived prostanoids. Low doses of COX-2 inhibitors may find use as an adjunct barrier-protecting therapy in critically ill patients.

Colonization with Escherichia coli EC 25 protects neonatal rats from necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality in premature infants; yet its pathogenesis remains poorly understood. To evaluate the role of intestinal bacteria in protection against NEC, we assessed the ability of naturally occurring intestinal colonizer E. coli EC25 to influence composition of intestinal microbiota and NEC pathology in the neonatal rat model. Experimental NEC was induced in neonatal rats by formula feeding/hypoxia, and graded histologically. Bacterial populations were characterized by plating on blood agar, scoring colony classes, and identifying each class by sequencing 16S rDNA. Binding of bacteria to, and induction of apoptosis in IEC-6 enterocytes were examined by plating on blood agar and fluorescent staining for fragmented DNA. E. coli EC 25, which was originally isolated from healthy rats, efficiently colonized the intestine and protected from NEC following introduction to newborn rats with formula at 106 or 108 cfu. Protection did not depend significantly on EC25 inoculum size or load in the intestine, but positively correlated with the fraction of EC25 in the microbiome. Introduction of EC25 did not prevent colonization with other bacteria and did not significantly alter bacterial diversity. EC25 neither induced cultured enterocyte apoptosis, nor protected from apoptosis induced by an enteropathogenic strain of Cronobacter muytjensii. Our results show that E. coli EC25 is a commensal strain that efficiently colonizes the neonatal intestine and protects from NEC.

The biological prosthesis is a viable option for abdominal wall reconstruction in pediatric high risk defects

BACKGROUND Our aim was to explore the indications for and outcome of biological prostheses to repair high risk abdominal wall defects in children. METHODS A retrospective chart review was performed of all cases of abdominal wall reconstruction in a single institution between 2007 and 2015. Demographic and clinical variables, technique and complications were described and compared between prosthesis types. RESULTS A total of 23 patients underwent abdominal wall reconstruction using a biological prosthesis including 17 neonates. The main indication was gastroschisis (17 patients) followed by ruptured omphalocele and miscellaneous conditions. Alloderm™ was most commonly used followed by Surgisis™, Strattice™, Flex-HD™ and Permacol™. In 22 cases wounds were contaminated or infected. Open bowel/stomas were present in 9 cases. Skin was not closed in 11 cases. Post-operative complication rate was 30% and hernia recurrence rate was 17% after a mean follow-up time of 16 months. CONCLUSIONS The use of a biological prosthesis may offer advantages over a synthetic mesh in pediatric high risk abdominal wall defects. The surgeon should be ready to consider its use in selected cases.

Pediatric trauma-associated acute respiratory distress syndrome: Incidence, risk factors, and outcomes

BACKGROUND/PURPOSE Acute Respiratory Distress Syndrome (ARDS) results in significant morbidity and mortality in pediatric trauma victims. The objective of this study was to determine risk factors and outcomes specifically related to pediatric trauma-associated ARDS (PT-ARDS). METHODS A retrospective cohort (2007-2014) of children ≤18 years old from the American College of Surgeons National Trauma Data Bank (NTDB) was used to analyze incidence, risk factors, and outcomes related to PT-ARDS. RESULTS PT-ARDS was identified in 0.5% (2660/488,381) of the analysis cohort, with an associated mortality of 18.6% (494/2660). Mortality in patients with PT-ARDS most commonly occurred in the first week after injury. Risk factors associated with the development of PTARDS included nonaccidental trauma, near drowning, severe injury (AIS ≥ 3) to the head or chest, pneumonia, sepsis, thoracotomy, laparotomy, transfusion, and total parenteral nutrition use. After adjustment for age, injury complexity, injury mechanism, and physiologic variables, PT-ARDS was found to be independently associated with higher mortality (adjusted OR 1.33, 95% CI 1.18-1.51, p < 0.001). CONCLUSIONS PT-ARDS is a rare complication in pediatric trauma patients, but is associated with substantial mortality within 7 days of injury. Recognition and initiation of lung-protective measures early in the postinjury course may represent the best opportunity to change outcomes. LEVEL OF EVIDENCE Level 3 - Epidemiologic.

Use of the Harmonic Blade Scalpel as a Novel Technique for Thoracoscopic Resection of Pediatric Paraspinal Masses in Children

INTRODUCTION Data support use of video-assisted thoracoscopic surgery (VATS) for safe and effective resection of paraspinal masses in children. Our aim was to describe outcomes following this operation using a novel technique and to compare its use with that of other established techniques. SUBJECTS AND METHODS We performed a retrospective chart review of all children (<18 years old) undergoing thoracoscopic resection of paraspinal masses in 2000-2011. Demographics, operative details, and clinical outcomes were summarized and compared between those undergoing resection using a Harmonic (Ethicon Endo-Surgery, Blue Ash, OH) blade scalpel (HBS) and those who did not. RESULTS Sixteen cases were identified (median age, 57.5 months; range, 2-204 months). Six cases (37%) underwent VATS with use of the HBS, and 10 (63%) did not. Demographic and clinical factors were well matched. Median tumor diameter was larger in the HBS group (49.2 cm(3) versus 18.7 cm(3); P=.07). Operative time was similar between groups (121 versus 138 minutes; P=.25), as was the estimated blood loss (10 mL versus 30 mL; P=.91) and chest tube duration (2.1 versus 1.8 days; P=.78). Three cases of Horners syndrome developed in the standard resection group, and one complication occurred in the HBS group. CONCLUSIONS The Harmonic blade scalpel can be used as a simple alternative to standard dissection techniques for thoracoscopic resection of paraspinal masses in children.