Necrotizing Enterocolitis: Using Regulatory Science and Drug Development to Improve Outcomes

Caplan, Michael S.; Underwood, Mark A.; Modi, Neena; Patel, Ravi; Gordon, Phillip V.; Sylvester, Karl G.; McElroy, Steven J.; Manzoni, Paolo; Gephart, Sheila M.; Chwals, Walter J.; Turner, Mark A.; Allen, Marilee C; Baer, Gerri; Besner, Gail E.; Canvasser, Jennifer; Chaaban, Hala; Clay, Robert; Connolly, Eamonn; Davis, Jonathan M.; Duchon, Jennifer; Eklund, Wakako; Ferguson, Joanne; Good, Misty; Grogan, Cristal; Hudson, Lynn D.; Khashu, Minesh; Kim, Jae; Lotze, Andrea; Mangili, Alexandra; Markel, Troy A.; Martin, Laura Y.; Miyazawa, Tokuo; Neu, Josef; Noel, Gary J.; Portman, Ron; Rosito, Simone; Schwartz, Ann G.; Scottoline, Brian; Seo, Suna; Stromberg, Staffan; Treem, William R.; Umberger, Erin; Warren, Tracy; West, Alicia

doi:10.1016/j.jpeds.2019.05.032

Cited by 43 publications

(24 citation statements)

References 46 publications

(15 reference statements)

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“…However, if tissue is not available, as is often the case when a peritoneal drain is placed instead of performing an open laparotomy, it may be difficult to differentiate SIP from perforated-NEC since their clinical features often overlap 29 . In the absence of a universally accepted clinical definition of NEC and SIP, the International Neonatal Consortium NEC Workgroup recently recommended that research studies use case-based definitions of NEC and SIP that are comprised of the individual components of the definition 30 . Therefore, we defined SIP and perforated-NEC based on the presence or absence of 5 predetermined clinical, radiographic and pathologic criteria (see Table 1 ): a) duration of clinical deterioration (presence of new onset metabolic acidosis, hypotension requiring dopamine, hyperglycemia, thrombocytopenia, and/or leukopenia) prior to the perforation; b) duration of abnormal abdominal radiographs (fixed isolated or stacked dilated intestinal loops, edematous bowel wall, or gasless abdomen) prior to the perforation; c) pneumatosis intestinalis and or portal venous gas; d) presence of a small perforation in the intestinal wall, without signs of inflammation, ischemia, or septic necrosis on surgical pathology or observed at the time of laparotomy; and, e) presence of single or multiple perforations with necrosis, inflammation and ischemia on surgical pathology or observed at the time of laparotomy ( Table 1 ).…”

Section: Methodsmentioning

confidence: 99%

A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis

2020

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Objective: To examine the relationship between intestinal perforations (caused by either spontaneous perforation (SIP) or necrotizing enterocolitis (NEC)) and the outcome “death due to intestinal perforation”. Methods: Multivariable logistic regression analyses were used to compare infants <28 weeks’ gestation with SIP (n=32) and perforated-NEC (n=45) for the outcome perforation-related death. Results: In univariate analyses the incidence of death due to perforation was higher among infants with perforated-NEC (36%) than infants with SIP (13%). However, infants with perforated-NEC were more likely to be older than 10 days and have bacteremia/fungemia with non-coagulase negative staphylococci (non-CONS) organisms than infants with SIP. After adjusting for confounding the only variable that was significantly associated with mortality due to perforation was the presence of non-CONS bacteremia/fungemia at the onset of perforation. Conclusions: The apparent association between death and perforated-NEC could be explained by the higher incidence of non-CONS bacteremia/fungemia among infants with perforated-NEC.

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Section: Methodsmentioning

confidence: 99%

A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis

2020

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“…However, the exact etiologic mechanisms and pathophysiology of NEC is still incomplete. In addition, the NEC phenotype may actually be the result of a final common pathway starting from multiple inciting events that results in an imbalance between mucosal injury and epithelial defense and repair, with activation of an unchecked pro-inflammatory cascade (103). As a disease process, NEC is unique in the Neonatal Intensive Care Unit (NICU) population.…”

Section: Paneth Cells and Necrotizing Enterocolitis (Nec)mentioning

confidence: 99%

The Paneth Cell: The Curator and Defender of the Immature Small Intestine

2020

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Paneth cells were first described in the late 19th century by Gustav Schwalbe and Josef Paneth as columnar epithelial cells possessing prominent eosinophilic granules in their cytoplasm. Decades later there is continued interest in Paneth cells as they play an integral role in maintaining intestinal homeostasis and modulating the physiology of the small intestine and its associated microbial flora. Paneth cells are highly specialized secretory epithelial cells located in the small intestinal crypts of Lieberkühn. The dense granules produced by Paneth cells contain an abundance of antimicrobial peptides and immunomodulating proteins that function to regulate the composition of the intestinal flora. This in turn plays a significant role in secondary regulation of the host microvasculature, the normal injury and repair mechanisms of the intestinal epithelial layer, and the levels of intestinal inflammation. These critical functions may have even more importance in the immature intestine of premature infants. While Paneth cells begin to develop in the middle of human gestation, they do not become immune competent or reach their adult density until closer to term gestation. This leaves preterm infants deficient in normal Paneth cell biology during the greatest window of susceptibility to develop intestinal pathology such as necrotizing enterocolitis (NEC). As 10% of infants worldwide are currently born prematurely, there is a significant population of infants contending with an inadequate cohort of Paneth cells. Infants who have developed NEC have decreased Paneth cell numbers compared to age-matched controls, and ablation of murine Paneth cells results in a NEC-like phenotype suggesting again that Paneth cell function is critical to homeostasis to the immature intestine. This review will provide an up to date and comprehensive look at Paneth cell ontogeny, the impact Paneth cells have on the host-microbial axis in the immature intestine, and the repercussions of Paneth cell dysfunction or loss on injury and repair mechanisms in the immature gut.

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“…As many as 19% of all cases of necrotizing enterocolitis treated with surgery and necrotizing enterocolitis causing death were pan-necrotizing enterocolitis. 9 In some obstructive colitis cases, few present with fulminating gangrene of the colon which is known as 'necrotizing colitis'. The exact etiology, however, is yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

Acute necrotizing enterocolitis due to sigmoid colon cancer: a rare entity case report

et al. 2021

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Adult necrotizing enterocolitis and non-occlusive mesenteric ischemia are rare causes of acute abdomen. Necrotising enterocolitis usually affects children and only few cases have been described in adults especially in geriatric patient. We report a rare case of acute necrotizing colitis of a 61 years old male patient. X-ray abdomen led to bowel dilatation. We performed emergency laparotomy under general anaesthesia and revealed that the dilatation of intestines and colon was caused by obstructive colitis due to sigmoid tumour. The digestive system was expanded proximally and the mucosae was seen turning black from the sigmoid colon to 80 cm proximal to the terminal ileum, from the findings we concluded that the patient was suffering from acute necrosis without significant vessel occlusion. The occlusion from the tumour may increase intraluminal pressure that affect colonic blood flow, and in closed-loop colonic obstruction without perforation, mucosal ischemia may be the primary event leading to massive colonic gangrene. Necrotising enterocolitis usually affects children and only few cases have been described in adults especially in geriatric patient. We performed complete colectomy with 90 cm resection of terminal ileum and ileostomy to remove the necrotic colon during surgery. Hartmann procedure was performed to distal part of rectum. The surgery was successful and patient was stable after the surgery.

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Necrotizing Enterocolitis: Using Regulatory Science and Drug Development to Improve Outcomes

Cited by 43 publications

References 46 publications

A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis

A role for neonatal bacteremia in deaths due to intestinal perforation: spontaneous intestinal perforation compared with perforated necrotizing enterocolitis

The Paneth Cell: The Curator and Defender of the Immature Small Intestine

Acute necrotizing enterocolitis due to sigmoid colon cancer: a rare entity case report

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