Gut microbiota promotes stem cell differentiation through macrophage and mesenchymal niches in early postnatal development.

Intestinal stem cell maturation and development coincide with gut microbiota exposure after birth. Here, we investigated how early life microbial exposure, and disruption of this process, impacts the intestinal stem cell niche and development. Single-cell transcriptional analysis revealed impaired stem cell differentiation into Paneth cells and macrophage specification upon antibiotic treatment in early life. Mouse genetic and organoid co-culture experiments demonstrated that a CD206+ subset of intestinal macrophages secreted Wnt ligands, which maintained the mesenchymal niche cells important for Paneth cell differentiation. Antibiotics and reduced numbers of Paneth cells are associated with the deadly infant disease, necrotizing enterocolitis (NEC). We showed that colonization with Lactobacillus or transfer of CD206+ macrophages promoted Paneth cell differentiation and reduced NEC severity. Together, our work defines the gut microbiota-mediated regulation of stem cell niches during early postnatal development.

Risk factors for glioblastoma in adults in Japan: an exploratory cohort study based on the Shizuoka Kokuho Database, the Shizuoka study.

PURPOSE: To elucidate the risk factors associated with the onset of glioblastoma (GBM) utilizing a comprehensive administrative claims database from a major governmental district in Japan. METHODS: Using the Shizuoka Kokuho Database (SKDB) for the period from April 2012 to September 2021, we conducted a retrospective analysis of 1,465,353 participants, identifying GBM cases using specific Japanese disease codes in conjunction with associated treatments. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models. RESULTS: Within the cohort, 182 participants (0.012%) received a GBM diagnosis during the study period, resulting in an incidence rate of 2.1 per 100,000 person-years. The multivariable analysis revealed that older age, male sex, and peripheral vascular disease (PVD) significantly influenced the risk of GBM onset. No clear link was found between allergic conditions and GBM risk, in contrast to some previous research. CONCLUSION: Employing a robust health insurance database, this study revealed significant associations between GBM and factors such as age, male sex, and PVD within the Japanese population. It provides key insights into GBM epidemiology and underscores the potential of health insurance databases for large-scale oncological research.

Risk factors, treatment and survival rates of late-onset acquired haemophilia A: A cohort study from the Shizuoka Kokuho Database.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare disease. The risk factors have yet to be studied. AIM: We aimed to identify risk factors for late-onset AHA in Japan. METHODS: A population-based cohort study was conducted using data from the Shizuoka Kokuho Database. The study population was defined as individuals aged ≥60 years. Cause-specific Cox regression analysis was performed to calculate hazard ratios. RESULTS: Of 1,160,934 registrants, there were 34 patients with newly diagnosed AHA. The mean follow-up period was 5.6 years, and the incidence of AHA was 5.21 per million person-years. Myocardial infarction, diabetes mellitus, solid tumors, antimicrobial agents, phenytoin and anti-dementia drugs, which showed significant differences in the univariate analysis, were excluded from the multivariable analysis because of the small number of cases. Multivariable regression analysis showed that the presence of Alzheimer's disease (hazard ratio [HR]:4.28, 95% confidence interval [CI]:1.67-10.97) and rheumatic disease (HR:4.65, 95% CI:1.79-12.12) increased the risk of AHA development. CONCLUSION: We found that comorbid Alzheimer's disease is a risk factor of AHA incidence in the general population. Our findings provide insight into the etiology of AHA, and the proof of the coexistence of Alzheimer's disease may support the recent notion that Alzheimer disease is an autoimmune disease.

Mortality and neurodevelopmental outcomes in very low birth weight infants with esophageal atresia.

PURPOSE: Very low birth weight infants (VLBWIs) have been thought as risk of bad outcomes in the patients with esophageal atresia (EA). However, detailed outcomes of EA within VLBWIs were not fully understood. We aimed to reveal short- and long-term outcomes in VLBWIs with EA. METHODS: Clinical data regarding VLBWIs with EA registered in Neonatal Research Network Japan, a multicenter research database in Japan, were collected. Patients with chromosomal abnormality were excluded. Short term outcome was survival discharge from NICU and long-term outcome was neurodevelopmental impairment (NDI) at 3 years. RESULTS: A total of 103 patients were analyzed. the overall survival discharge rate from NICU was 68.0% (70/103). The risk of death was increased as the birth weight got reduced. The presence of associated anomaly increased the risk of death. Three-year neurodevelopmental information was available in 32.9% (23/70) of patients. Of the 23 included patients for 3-year follow-up, 34.8% had NDI. The risk of NDI was increased as the birth weight reduced. CONCLUSIONS: In VLBWIs with EA, survival discharge from NICU was still not high. More immature patients and patients with an associated anomaly had worse outcomes. Among patients who survived, NDI was confirmed in a certain number of patients.

Safety evaluation of a stepwise tracheostomy decannulation program in pediatric patients.

PURPOSE: In the event of failed tracheostomy decannulation, patients might have a tragic course of events. We retrospectively evaluated our stepwise tracheostomy decannulation program and examined its safety. METHODS: A 12-year retrospective study of pediatric patients was conducted. The decannulation program was performed on patients who had airway patency by laryngobronchoscopy and whose cannula could be capped during the day. A stepwise decannulation program was performed: continuous 48-h capping trial during hospitalization (Phase 1), removal of the tracheostomy tube for 48 h during hospitalization (Phase 2), and outpatient observation (Phase 3). If a persistent tracheocutaneous fistula existed, the fistula was closed by surgery (Phase 4). RESULTS: The 77 patients in the study underwent 86 trials. The age at the first time of the decannulation program was 6.5 ± 3.6 years. Sixteen trials failed (18.6%): 8 trials in Phase 1, 2 trials in Phase 2, 4 trials in Phase 3, and 2 trials in Phase 4. Most decannulation failures were due to desaturation in Phase 1/2 and dyspnea in Phase 3/4. The time to reintubation after decannulation was 15-383 days in Phase 3/4. CONCLUSIONS: Patients could fail at every phase of the program, suggesting that a stepwise decannulation program contributes to safety.

Bovine milk-derived exosomes attenuate NLRP3 inflammasome and NF-κB signaling in the lung during neonatal necrotizing enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC), an inflammatory intestinal disease common in premature infants, has been associated with the development of lung damage. Toll-like receptor 4 has been shown to regulate inflammation in the NEC lungs, however, other important inflammatory mechanisms have not been thoroughly investigated. In addition, we reported that milk-derived exosomes were able to attenuate intestinal injury and inflammation in experimental NEC. This study aims to (i) investigate the role of the NLRP3 inflammasome and NF-κB pathway in regulating lung damage during experimental NEC; and (ii) evaluate the therapeutic potential of bovine milk exosomes in reducing lung inflammation and injury during NEC. METHODS: NEC was induced by gavage feeding of hyperosmolar formula, hypoxia, and lipopolysaccharide administration in neonatal mice from postnatal days 5-9. Exosomes were obtained by ultracentrifugation of bovine milk and administered during each formula feed. RESULTS: The lung of NEC pups showed increased inflammation, tissue damage, NLRP3 inflammasome expression, and NF-κB pathway activation, which were attenuated upon exosome administration. CONCLUSION: Our findings suggest that the lung undergoes significant inflammation and injury following experimental NEC which are attenuated by bovine milk-derived exosomes. This emphasizes the therapeutic potential of exosomes not just on the intestine but also on the lung.

Intestinal epithelial tight junctions and permeability can be rescued through the regulation of endoplasmic reticulum stress by amniotic fluid stem cells during necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is one of the most severe gastrointestinal diseases affecting premature infants. It has been shown that NEC is associated with disrupted intestinal barrier and dysregulated endoplasmic reticulum (ER)-stress response. It has also been shown that stem cells derived from amniotic fluid (AFSC) rescued intestinal injury in experimental NEC. Herein, we hypothesized that the beneficial effects of AFSC in the injured intestine are due to the restoration of intestinal barrier function. We evaluated intestinal barrier function using an ex vivo intestinal organoid model of NEC. We found that AFSC restored the expression and localization of tight junction proteins in intestinal organoids, and subsequently decreased epithelial permeability. AFSC rescued tight junction expression by inducing a protective ER stress response that prevents epithelial cell apoptosis in injured intestinal organoids. Finally, we validated these results in our experimental mouse model of NEC and confirmed that AFSC induced sustained ER stress and prevented intestinal apoptosis. This response led to the restoration of tight junction expression and localization, which subsequently reduced intestinal permeability in NEC pups. These findings confirm that intestinal barrier function is disrupted during NEC intestinal injury, and further demonstrate the disruption can be reversed by the administration of AFSC through the activation of the ER stress pathway. This study provides insight into the pathogenesis of NEC and highlights potential therapeutic targets for the treatment of NEC.

Amniotic fluid stem cell administration can prevent epithelial injury from necrotizing enterocolitis.

BACKGROUND: Stem cell therapy has been proven to rescue intestinal injury and stimulate intestinal regeneration in necrotizing enterocolitis (NEC). Specifically, stem cells derived from amniotic fluid (AFSCs) and mesenchymal stem cells (MSCs) derived from bone marrow have shown promising results in the treatment of experimental NEC. This study aims to examine the effects of AFSCs and MSCs on the prevention of intestinal injury during experimental NEC. METHODS: Supernatants from AFSC and MSC cultures were collected to perform proteomic analysis. Prior to NEC induction, mice received intraperitoneal injections of phosphate-buffered saline (PBS), 2 × 106 AFSCs, or 2 × 106 MSCs. RESULTS: We found that AFSCs grew faster than MSCs. Proteomic analysis indicated that AFSCs are primarily involved in cell development and growth, while MSCs are involved in immune regulation. Administering AFSCs before NEC induction decreased NEC severity and mucosal inflammation. Intestinal proliferation and endogenous stem cell activation were increased after AFSC administration. However, administering MSCs before NEC induction had no beneficial effects. CONCLUSIONS: This study demonstrated that AFSCs and MSCs have different protein release profiles. AFSCs can potentially be used as a preventative strategy for neonates at risk of NEC, while MSCs cannot be used. IMPACT: AFSCs and MSCs have distinct protein secretory profiles, and AFSCs are primarily involved in cell development and growth, while MSCs are involved in immune regulation. AFSCs are unique in transiently enhancing healthy intestinal epithelial cell growth, which offers protection against the development of experimental NEC. The prevention of NEC via the administration of AFSCs should be evaluated in infants at great risk of developing NEC or in infants with early signs of NEC.

Pancreaticobiliary maljunction without biliary dilatation in pediatric patients.

PURPOSE: Pancreaticobiliary maljunction (PBM) without biliary dilatation is a condition in which dilatation of the bile duct is not seen in patients with PBM. Recently, the Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) published new diagnostic criteria for PBM. In these criteria, biliary dilatation is defined according to the standard diameter at each age. We reviewed cases of pediatric patients with PBM without biliary dilatation. METHODS: From 1992 to 2019, 134 patients with PBM were treated in our institution. Among these, 7 patients were retrospectively diagnosed with PBM without biliary dilatation. The clinical information was retrospectively assessed in these patients. RESULTS: Of the seven patients, six were female. All patients had symptoms similar to those of patients with congenital biliary dilatation. In all seven patients, the diagnosis of PBM was made before definitive surgery. Six patients had type B PBM, and one had type D PBM. All patients underwent extrahepatic bile duct resection and hepaticojejunostomy, and their symptoms resolved. One patient experienced postoperative complications of anastomotic leakage followed by anastomotic stricture. CONCLUSION: The present report revealed important clinical features of this entity. However, there are still some issues that need to be discussed, and further research is needed.

Hepatic oxidative injury: role of mitochondrial dysfunction in necrotizing enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC) is a severe neonatal gastrointestinal disease that can cause damage to remote organs. Previous studies have shown that inflammatory and oxidative injury occur in the liver during NEC. Mitochondrial DNA (mtDNA) plays an important role in hepatic injuries of many other diseases. We aimed to investigate the mechanism of mitochondrial dysfunction in hepatic oxidative injury during NEC. METHODS: NEC was induced in C57BL/6 mice (approval: 44032) by hypoxia, gavage feeding with hyperosmolar formula, and lipopolysaccharide administration from postnatal days 5 to 9 (n = 15). Two additional groups with hypoxia only (n = 10) and hypoxia and hyperosmolar formula (n = 13) were also examined. Breastfed pups were used as control (n = 15). Liver was harvested on postnatal day 9. Gene expressions of mtDNA markers cytochrome c oxidase subunit 3 (COX3), cytochrome b (CYTB) and NADH-ubiquinone oxidoreductase chain 1 (ND1) were measured by real-time qPCR. Mitochondrial morphology marker HSP60 and oxidative stress marker NRF2 were detected by immunofluorescence staining and compared between NEC and control. Data were presented as mean ± SD and compared using Student's t test; p < 0.05 was considered significant. RESULTS: Gene expression of mtDNA markers (COX3, CYTB, and ND1) were significantly decreased in the liver of NEC mice relative to control, hypoxia alone, and hypoxia with hyperosmolar formula. Immunofluorescence showed depletion of HSP60 indicating decreased mitochondria in NEC liver relative to control. Furthermore, a higher protein expression of NRF2 was observed indicating higher oxidative stress in NEC liver relative to control. CONCLUSIONS: Intestinal injury in experimental NEC leads to a systemic inflammatory response affecting the liver. Hepatic oxidative injury in NEC is characterized by decreased mitochondria and mtDNA depletion. This study provides insight into the mechanism of liver injury in NEC.

Risk factors of dumping syndrome after fundoplication for gastroesophageal reflux in children.

PURPOSE: In postoperative cases of fundoplication, the gastric emptying ability is promoted and sometimes exhibits dumping syndrome. Dumping syndrome often goes unrecognized in children. Furthermore, the risk factors for postoperative dumping syndrome are unknown. This study aimed to investigate the risk factors of developing dumping syndrome after fundoplication. METHODS: A retrospective chart review of all consecutive patients between January 2003 and March 2018 (190 patients) who had fundoplication at our clinic was conducted. Regarding the risk factors of dumping syndrome, gender, age and body weight at the time of surgery, neurological impairment, severe scoliosis, microgastria, chromosomal abnormalities, complex cardiac anomalies, gastrostomy, and laparoscopic surgery were retrospectively studied. RESULTS: 17 patients (9%) developed dumping syndrome post-operatively. Multivariate analysis showed that significant risk factors for dumping syndrome included: undergoing surgery within 12 months of age (adjusted OR 10.3, 95% CI 2.6-45.2), severe scoliosis (adjusted OR 19.3, 95% CI 4.4-91.1), and microgastria (adjusted OR 26.5, 95% CI 1.4-896.4). CONCLUSIONS: We identified that: age at fundoplication being within 12 months of age, severe scoliosis, and microgastria were risk factors for dumping syndrome after fundoplication, and that this information should be explaining to the family before conducting the fundoplication.

Long-Term Outcomes After Pediatric Tracheostomy-Candidates for and Timing of Decannulation.

BACKGROUND: Although pediatric tracheostomy has been a widely performed, life-saving procedure, its long-term outcomes have remained unclear. This study aimed to review outcomes after tracheostomy at a Japanese tertiary hospital and clarify candidates for and timing of decannulation. MATERIALS AND METHODS: Hospital records of critically ill children who underwent tracheostomy from 2001 to 2014 were retrospectively reviewed, subsequently analyzing outcomes according to demographics, complications, and decannulation. After excluding those who were lost to follow-up or had irreversible neuromuscular impairment, the remaining patients were divided into the decannulation (D group) and nondecannulation (ND group) groups and compared. RESULTS: In total, 184 patients who underwent tracheostomy were analyzed (median age at operation: 0.5 y). The major indication for tracheostomy was irreversible neuromuscular impairment (46%). Surgery-related and overall mortality rates were 1% and 25%, respectively, while the successful decannulation rate was 21%. No significant difference in surgical indications or comorbidities was observed between the D (n = 39) and ND (n = 50) groups, except for infection (7 in D group versus 0 in ND group; P = 0.002) and chromosome-gene disorder (15% versus 34%; P = 0.04). The ND group had a significantly higher mortality rate than the D group (46% versus 3%; P < 0.0001). The median time to decannulation was 3.6 years, while that for infection was 0.7 y. CONCLUSIONS: Patients who underwent tracheostomy at our institution due to temporary infections achieved more successful and earlier decannulation compared to other indications. Chromosome-gene disorder as a comorbidity can negatively affect decannulation.

The effect of pre- and post-remote ischemic conditioning reduces the injury associated with intestinal ischemia/reperfusion.

PURPOSE: Midgut volvulus is associated with intestinal ischemia/reperfusion (IR) injury and can progress to severe intestinal damage. Remote ischemic conditioning (RIC) reduces IR-induced injury in distant organs. The aim of this study was to investigate whether RIC protects the intestine from IR injury. METHODS: We investigated intestinal IR injury in 3 weeks old SD rats. Animals underwent: (i) sham laparotomy, (ii) intestinal IR injury, (iii) intestinal IR + RIC during ischemia, or (iv) intestinal IR + RIC after reperfusion. Intestinal IR injury was achieved by 45 min occlusion of superior mesenteric artery followed by de-occlusion. RIC was administered via four cycles of 5 min of hind limb ischemia followed by 5 min reperfusion. Animals were sacrificed 24 h after surgery and the ileum was harvested for evaluation. RESULTS: Intestinal injury was present after IR. However, this injury was reduced in both IR + RIC groups. Expression of inflammatory cytokine IL6 was lower in IR + RIC groups compared to IR alone. Carbonyl protein was also significantly lower in IR + RIC compared to IR, indicating lower oxidative stress in both IR + RIC groups. CONCLUSION: Remote ischemic conditioning attenuated intestinal injury, inflammation, and oxidative stress in experimental intestinal ischemia/reperfusion injury. Remote ischemic conditioning may be useful in children with midgut volvulus to reduce the intestinal injury. LEVEL OF EVIDENCE: Experimental study. TYPE OF STUDY: Animal experiment.

Human breast milk exosomes attenuate intestinal damage.

BACKGROUND: Human breast milk (HBM), which contains an abundant supply of exosomes, is known to prevent necrotizing enterocolitis (NEC). Preterm infants are commonly given pasteurized donor milk when HBM is unavailable. However, pasteurization can disrupt its components. This study investigates the effects of both raw and pasteurized HBM-derived exosomes on intestinal inflammation. METHODS: HBM exosomes were isolated and characterized by positive CD63 and negative calnexin markers from western blot, nanoparticle tracking analysis and transmission electron microscopy. Mouse intestine organoids were established and treated with exosomes from raw or pasteurized HBM in healthy and injury conditions. Following ethical approval (#44032), mice pups were randomly assigned to (1) breastfed control; (2) NEC; (3) NEC receiving raw HBM exosomes; (4) NEC receiving pasteurized HBM exosomes. NEC was induced by hypoxia, gavage feeding and lipopolysaccharide (LPS). Ileum was evaluated. Data were analyzed using one-way ANOVA with Bonferroni post-test. RESULTS: Both raw and pasteurized HBM exosomes decreased inflammation in hypoxia and LPS-treated organoids compared to control. In vivo, NEC-induced mucosal injury, inflammation and mucous production were improved by raw and pasteurized HBM-derived exosomes. CONCLUSIONS: Exosomes derived from raw and pasteurized HBM equally reduced intestinal damage. Exosome administration in clinical practice requires further investigation.

Safety and usefulness of plastic closure in infants with gastroschisis: a systematic review and meta-analysis.

PURPOSE: Recently, plastic closure of abdominal defect in infants with gastroschisis has been used. Timing of gastroschisis closure can be mainly divided into two groups: primary closure and delayed closure after silo forming. Safety and usefulness of plastic closure in gastroschisis remains unclear. We aimed to evaluate the current evidence for plastic closure in infants with gastroschisis. METHODS: The analysis was done for primary closure as well as closure after silo. Outcomes were mortality, wound infection, duration of ventilation, time to feeding, and length of hospital stay (LOS). The quality of evidence was summarized using the GRADE approach. RESULTS: In the "primary" group, there was no significant difference in mortality, time to feeding initiation and LOS. In the "silo" group, wound infection was significantly lower in plastic closure (Odds ratio 0.24, 95%CI 0.09-0.69, p = 0.008). Duration of ventilation, time to feeding initiation and LOS were significantly shorter after plastic closure (Ventilation; mean difference (MD) - 5.76, p = 0.03. Feeding initiation; MD - 9.42, p < 0.0001. LOS; MD - 14.06, p = 0.002). Quality of evidence was very low for all outcomes. CONCLUSIONS: Current results suggest that plastic closure may be beneficial for infants with gastroschisis requiring silo formation. However, this evidence is suboptimal and further studies are needed.

Neonatal intestinal organoids as an ex vivo approach to study early intestinal epithelial disorders.

BACKGROUND: Adult intestinal organoids have been used to study ex vivo intestinal injury in adulthood. However, the neonatal intestinal epithelium has many unique features that are different from adult mature intestine. Establishing a neonatal ex vivo organoid model is essential to study the epithelial physiology in early postnatal development and to investigate derangements associated with disease processes during the neonatal period like necrotizing enterocolitis (NEC). METHODS: Fresh and frozen terminal ileum was harvested from mice pups on postnatal day 9. Crypts were isolated and organoids were cultured. Organoids were exposed to hypoxia and lipopolysaccharide (LPS) for 48 h to induce epithelial injury. Inflammatory cytokines and tight junction proteins were evaluated. RESULTS: Robust intestinal organoids can be formed from both fresh and frozen intestinal tissue of neonatal mice pups. Hypoxia and LPS administration induced intestinal inflammation and disrupted tight junctions in these neonatal intestinal organoids. CONCLUSIONS: We have established a novel method to grow organoids from neonatal intestine. We demonstrated that these organoids respond to the injury occurring during neonatal intestinal diseases such as NEC by increasing the organoid inflammation and by disrupting the organoid barrier function. Organoids provide an ex vivo platform to study intestinal physiology and pathology during the neonatal period.

Endothelin receptor B affects the perfusion of newborn intestine: possible mechanism of necrotizing enterocolitis development.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most severe gastrointestinal diseases in infancy. Hypoxia is known as one of the major risk factors for the development of NEC. Endothelin, known to regulate vasoconstriction, has two receptors (A and B). However, the role of endothelin receptor B (EDNRB) in neonatal intestinal injury remains unclear. We aimed to investigate whether EDNRB is involved in NEC pathophysiology. METHODS: Following ethical approval (#44032), EDNRB hetero knockout mice pups (EDNRB±) and their wild-type (WT) littermates were studied. NEC was induced from postnatal day 5-9 (P5-P9) by hypoxia, gavage feeding of formula and administration of lipopolysaccharide. On P9, the ileum was harvested. RESULTS: NEC induction in WT mice was associated with mucosal injury. However, EDNRB± NEC mice had reduced mucosal injury. Similarly, EDNRB± mice had significantly lower expression of IL-6 mRNA compared to WT NEC mice. Pimonidazole immunostaining was also significantly lower in EDNRB± compared to WT NEC, suggesting reduced tissue hypoxia. CONCLUSIONS: Partial knockout of EDNRB results in reduced NEC severity and reduced tissue hypoxia. Intestinal perfusion and hypoxia are important elements of NEC pathogenesis. These findings are relevant to the understanding of NEC pathophysiology and to the development of novel preventive strategies for NEC.

Unexpected gap between intraoperative caliber change of the intestine and normoganglia in patients with intestinal aganglionosis.

PURPOSE: Intestinal aganglionosis (IA) is so rare that the entity remains unclear. The aim of the present study was to compare the outcomes of patients with IA and those with total colonic aganglionosis (TCA). METHODS: The hospital records were retrospectively reviewed from 1977 to 2018. Outcomes were analyzed for the IA group and the TCA group, including clinical presentation, initial management, and operative details. RESULTS: There were six patients were managed in IA (all male) and seven patients in TCA (4 male). The median age at the first operation was significantly younger in IA than TCA (2 days vs 24 days, p = 0.01). The gap between the intraoperative caliber change (CC) of the intestine and the initial stoma location was not significantly different (7.5 cm vs 12 cm, p = 0.61), but the rate of stoma dysfunction was significantly higher in IA (83% vs 0%, p = 0.005). The gap between the CC and the ganglionated bowel was significantly longer in IA (85 cm vs 10 cm, p = 0.003). CONCLUSION: Patients with IA appear to have a high risk for stoma dysfunction after the first operation because of the unexpected gap between the CC and normoganglia. The initial location of the stoma requires careful consideration.

Post-operative paralysis and elective ventilation reduces anastomotic complications in esophageal atresia: a systematic review and meta-analysis.

AIM OF STUDY: The repair of esophageal atresia (EA) carries an increased risk of anastomotic leak and stricture formation, especially in patients with anastomotic tension. To minimize this risk, pediatric surgeons perform elective post-operative muscle paralysis, positive-pressure ventilation, and head flexion (PVF) to reduce movement and tension at the anastomosis. We systematically reviewed and analyzed the effect of post-operative PVF on reducing anastomotic complications. METHODS: Embase, MEDLINE, Web of Science, and PubMed databases were used to conduct searches. Articles reporting pediatric EA undergoing primary anastomosis, anastomotic complications, and comparisons between patients who received post-operative PVF to those who did not were included. Odds ratios (OR) for all post-operative anastomotic complications were calculated using random effects modelling. MAIN RESULTS: Three of the 2268 papers retrieved met inclusion criteria (all retrospective cohort studies). There were no randomized controlled trials. Post-operative PVF showed a significant reduction in anastomotic leak (OR 0.07; 95% CI 0.01-0.35) when compared to no PVF. Stricture formation was not statistically different between groups. Potential sources of bias include patient allocation. CONCLUSIONS: Based on available data, our analysis indicates PVF may reduce anastomotic post-operative leak. To confirm these results, a prospective study with clearer definitions of treatment allocation should be performed.