Gut Microbiome-Brain Axis as an Explanation for the Risk of Poor Neurodevelopment Outcome in Preterm Infants with Necrotizing Enterocolitis.

Necrotizing Enterocolitis (NEC) is characterized by an inflammation of intestinal tissue that primarily affects premature infants. It is the most common and devastating gastrointestinal morbidity of prematurity, but beyond intestinal morbidity, this condition has also been associated with an increased risk of neurodevelopmental delays that persist beyond infancy. Prematurity, enteral feeding, bacterial colonization, and prolonged exposure to antibiotics are all risk factors that predispose preterm infants to NEC. Interestingly, these factors are all also associated with the gut microbiome. However, whether or not there is a connection between the microbiome and the risk of neurodevelopmental delays in infants after NEC is still an emerging area of research. Furthermore, how microbes in the gut could impact a distant organ such as the brain is also poorly understood. In this review, we discuss the current understanding of NEC and the role of the gut microbiome-brain axis in neurodevelopmental outcomes after NEC. Understanding the potential role of the microbiome in neurodevelopmental outcomes is important as the microbiome is modifiable and thus offers the hope of improved therapeutic options. We highlight the progress and limitations in this field. Insights into the gut microbiome-brain axis may offer potential therapeutic approaches to improve the long-term outcomes of premature infants.

An Algorithmic Approach for the MIS Repair of Ventral Midline Hernias Associated With Diastasis of the Rectus Abdominis Muscle.

Purpose: We present our algorithmic approach for symptomatic ventral hernias with Diastasis of the Rectus Abdominis Muscle (DRAM). Methods: Retrospective analysis of patients with symptomatic ventral hernias and DRAM undergoing hernia repair and plication of DRAM from July 2018-March 2021 was conducted. Based on our algorithm, patients were selected for an Endoscopic Onlay Repair (ENDOR) or a Robotic Extended Totally Extraperitoneal Ventral Repair (R-eTEP). Results: We performed a R-eTEP in fifty-seven patients and an ENDOR in twenty-four patients. In the R-eTEP group, thirty-seven (65%) patients were female, the mean age was 54.8 (±10.6), and the mean BMI was 32 (±4.8). Fifty patients (87.7%) had multiple defects, of which 19 (38%) were recurrent hernias and 31 (62%) were incisional hernias. The mean operative time was 200 (±62.4) minutes, with two cases requiring a hybrid approach. The median length of stay was 1 day (0-12), and the median follow-up was 103 days. Twenty-four patients underwent an ENDOR, 19 females (79.2%), the mean age was 45.7 years (±11.7) and the mean BMI was 28 (±3.6). 13 patients had isolated umbilical or epigastric hernias. The mean operative time was 146.2 min (±51.1). Fibrin sealant and suture was the predominant method for mesh fixation, and most cases were performed in an ambulatory setting. Four patients developed post-operative seromas; one requiring drainage due to infection. The Median follow-up was 48.5 days (10-523), with two reported hernia recurrences. Conclusion: An algorithmic approach for adequate patient selection was shown to be safe for treating ventral hernias with DRAM.

Distinct, sex-dependent miRNA signatures in piglet hippocampus induced by a clinically relevant isoflurane exposure: a pilot study.

PURPOSE: To evaluate the effects of sex on miRNA expression in the hippocampus after isoflurane anesthesia in a neonatal piglet model. METHODS: Six male and 6 female piglets, aged 3-5 days, were anesthetized with 2% isoflurane in room air for 3 h. Full physiologic monitoring was observed. Untreated animals (6 male, 6 female) served as controls. Expression of miRNAs in hippocampus was assessed. RESULTS: In controls, miRNA expression in the hippocampus was highly conserved between males and females. However, 17/326 displayed sex-dependent differences: 10 miRNAs were more highly expressed in males; 7 showed lower expression in males than females. Isoflurane was associated with changes in the expression of distinct subsets of miRNAs in both males and females. In females, 14/326 miRNAs were significantly changed (3 downregulated; 11 upregulated); in males, 17/326 miRNAs were changed (7 downregulated; 10 upregulated). There was no overlap in significantly changed miRNAs between isoflurane-exposed males and females. CONCLUSIONS: In the neonatal piglet hippocampus, miRNA expression was highly conserved. There was no overlap in miRNA expression between isoflurane-exposed males and females, suggesting sex differences in isoflurane-induced miRNA expression. These results support the hypothesis that a clinically relevant exposure to isoflurane induces distinct miRNA signatures in the hippocampus of neonatal male and female piglets. Their functional relevance in anesthesia-induced neurotoxicity remains unknown, although changes in specific miRNAs may either contribute to or protect against anesthesia-induced neurotoxicity.

Selective induction of IL-1ß after a brief isoflurane anesthetic in children undergoing MRI examination.

PURPOSE: To determine if isoflurane anesthesia without surgery causes systemic inflammation in children. Inflammation is targeted as responsible for the development of many neurologic pathologies. The effect will be evaluated by measuring serum cytokine levels before and after isoflurane anesthesia. The possible neurotoxic effect of anesthetic agents is a concern in pediatric anesthesia. Questions remain as to the true effects of anesthesia alone on systemic inflammation. The current study assesses systemic inflammatory response to general anesthesia in children not exposed to surgical stress. METHODS: Twenty-five patients, aged 6 months to 11 years undergoing MRI scanning were recruited. Patients with ASA Physical Status Classification >II, known neurologic disease, prematurity, recent infection, or current treatment with anti-inflammatory medications were excluded. Each patient received a sevoflurane induction, peripheral intravenous catheterization, and laryngeal mask airway placement. Isoflurane was titrated to ensure adequate depth of anesthesia. Two peripheral blood samples were obtained: one immediately after placement of the PIV and one upon arrival to the post-anesthesia care unit. Serum cytokine levels were compared between pre- and post-isoflurane time points using paired t tests. RESULTS: For all patients, interleukin-1ß increased after isoflurane when compared to pre-isoflurane samples (pre = 25.97 ± 9.01, post = 38.53 ± 16.56, p = 0.0002). Serum levels of IL-6 (pre = 2.28 ± 2.27, post = 2.04 ± 2.15, p = 0.146) and tumor necrosis factor-α (pre = 94.26 ± 18.07, post = 85.84 ± 12.12, p = 0.057) were not significantly changed. Interleukin-10 and vascular endothelial growth factor were undetectable in pre- and post-isoflurane samples at a minimum detection threshold of 6.6 and 10 pg/ml, respectively. CONCLUSIONS: A brief (approximately 60 min) exposure to isoflurane general anesthesia, without induced surgical stress, significantly increased serum IL-1ß, a selective activation marker of systemic inflammation (IL-1ß pathway).