Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. Some strains of the probiotic Lactobacillus reuteri (L. reuteri) have both antimicrobial and anti-inflammatory properties that may be exploited for the treatment and prevention of different gastrointestinal diseases, including necrotizing enterocolitis (NEC) and Clostridioides difficile (C. difficile) infection. Our laboratory has developed a new delivery system for L. reuteri in which the probiotic is incubated with biocompatible, semipermeable, porous dextranomer microspheres (DM) that can be loaded with beneficial and diffusible cargo. L. reuteri can be induced to form a biofilm by incubating the bacteria on the surface of these microspheres, which enhances the efficacy of the probiotic. Loading the DM with sucrose or maltose induces L. reuteri to produce more biofilm, further increasing the efficacy of the probiotic. Using a rat model of NEC, L. reuteri administered in its biofilm state significantly increases animal survival, reduces the incidence of NEC, preserves gut barrier function, and decreases intestinal inflammation. In a murine model of Clostridiodes difficile infection, L. reuteri administered in its biofilm state decreases colitis when administered either before or after C. difficile induction, demonstrating both prophylactic and therapeutic efficacy. There are currently no FDA-approved probiotic preparations for human use. An FDA-approved phase I clinical trial of L. reuteri in its biofilm state in healthy adults is currently underway. The results of this trial will be used to support a phase 1 clinical trial in neonates, with the goal of utilizing L. reuteri in its biofilm state to prevent NEC in premature neonates in the future.

IntroductionNecrotizing enterocolitis (NEC) is a complex inflammatory disorder of the human intestine that most often occurs in premature newborns. Animal models of NEC typically use mice or rats; however, pigs have emerged as a viable alternative given their similar size, intestinal development, and physiology compared to humans. While most piglet NEC models initially administer total parenteral nutrition prior to enteral feeds, here we describe an enteral-feed only piglet model of NEC that recapitulates the microbiome abnormalities present in neonates that develop NEC and introduce a novel multifactorial definitive NEC (D-NEC) scoring system to assess disease severity.MethodsPremature piglets were delivered via Caesarean section. Piglets in the colostrum-fed group received bovine colostrum feeds only throughout the experiment. Piglets in the formula-fed group received colostrum for the first 24 h of life, followed by Neocate Junior to induce intestinal injury. The presence of at least 3 of the following 4 criteria were required to diagnose D-NEC: (1) gross injury score ≥4 of 6; (2) histologic injury score ≥3 of 5; (3) a newly developed clinical sickness score ≥5 of 8 within the last 12 h of life; and (4) bacterial translocation to ≥2 internal organs. Quantitative reverse transcription polymerase chain reaction was performed to confirm intestinal inflammation in the small intestine and colon. 16S rRNA sequencing was performed to evaluate the intestinal microbiome.ResultsCompared to the colostrum-fed group, the formula-fed group had lower survival, higher clinical sickness scores, and more severe gross and histologic intestinal injury. There was significantly increased bacterial translocation, D-NEC, and expression of IL-1α and IL-10 in the colon of formula-fed compared to colostrum-fed piglets. Intestinal microbiome analysis of piglets with D-NEC demonstrated lower microbial diversity and increased Gammaproteobacteria and Enterobacteriaceae.ConclusionsWe have developed a clinical sickness score and a new multifactorial D-NEC scoring system to accurately evaluate an enteral feed-only piglet model of NEC. Piglets with D-NEC had microbiome changes consistent with those seen in preterm infants with NEC. This model can be used to test future novel therapies to treat and prevent this devastating disease.

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Introduction The management of Kommerell’s Diverticulum (KD) has evolved from open surgical resection and graft replacement of the aorta, to endovascular repair in asymptomatic patients due to its recognized possible sequelae – aortic rupture and dissection. Despite these technical advances, standard indications for intervention and treatment algorithms remain unclear. We will present our single-center experience in the treatment of KD, supporting a multidisciplinary endovascular-first approach. Methods All patients who underwent thoracic endovascular aortic repair (TEVAR) for KD between 2017 and 2020 were retrospectively identified from a prospectively maintained institutional surgery database. Chart review was used to characterize presenting symptoms, interventions, technical results, and complications. Revascularization was performed using carotid-axillary bypass. Routine endovascular subclavian artery occlusion was employed to eliminate retrograde diverticulum perfusion and avoid open ligation. Results 8 patients were identified, including 6 females and 2 males between the ages of 44-76. Patients presented with dysphagia (n = 3), acute embolic stroke (n = 1), transient ischemic attack (TIA) (n = 1), upper extremity embolization (n = 1), and acute type B aortic dissection (n = 1). One patient had a prior incomplete open repair that was successfully treated endovascularly. Another patient had a mediastinal neoplasm infiltrating an incidental aberrant subclavian artery and KD. All cases had symptomatic improvement and successful endovascular repair as demonstrated on post-operative imaging. Perioperative complications included percutaneous access site pseudoaneurysm (n = 2), stroke (n = 1), and subclavian artery rupture immediately recognized and treated (n = 1). There was no perioperative mortality. Conclusion Endovascular techniques have resulted in technical success and symptomatic improvement for KD without open thoracotomy or sternotomy. Significant rates of endovascular complications and paucity of long-term durability data should be considered. Until formal criteria for repair are established, early application of TEVAR using a consistent multi-specialty approach may mitigate the risk of unpredictable aortic complications in these patients while avoiding the accepted morbidity and mortality of open surgery.