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Objective: : To develop an international Core Outcome Set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children.Summary Background Data: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS.Methods: The development process consisted of four phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a two-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS.Results: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (eight countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with ten outcomes emerging with consensus. After two young peoples’ focus groups, two additional outcomes were added to the final COS (12): mortality, bowel obstruction, intra-abdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications.Conclusion: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment of simple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.

To evaluate neurodevelopment and growth in extremely preterm infants with or without necrotizing enterocolitis or spontaneous intestinal perforation.We conducted a retrospective cohort study of infants admitted to Canadian neonatal intensive care units in 2010 to 2011. We assessed outcomes at 18 to 24 months' corrected ages for preterm infants29 weeks of gestational age at birth with spontaneous intestinal perforation or non-perforated or perforated necrotizing enterocolitis, and for preterm infants with none of these gastrointestinal complications. The primary outcome was a composite of death or significant neurodevelopmental impairment at 18 to 24 months' corrected age. We used multivariable logistic regression models to adjust for gestational age, small for gestational age, prenatal steroids, cesarean section, multiple gestations, and SNAP-II score.Of 2,019 infants total, 39 (1.9%) had spontaneous intestinal perforation, 61 (3%) had perforated necrotizing enterocolitis, and 115 (5.7%) had non-perforated necrotizing enterocolitis. Infants with spontaneous intestinal perforation (aOR 2.11; 95% CI 1.01-4.42), necrotizing enterocolitis (aOR 2.58; 95% CI 1.81-3.68), or any bowel perforation (aOR 3.97; CI 2.43-6.48) had higher odds of death or significant neurodevelopmental impairment compared to infants with none of these bowel diseases.Spontaneous intestinal perforation, necrotizing enterocolitis, or any bowel perforation are risk factors for death or significant neurodevelopmental impairment in extremely preterm infants.Study type: prognosis study (cohort study: retrospective) LEVEL OF EVIDENCE RATING: II.

Purpose To determine the global prevalence for congenital diaphragmatic hernia (CDH) and identify CDH-related risk factors. Methods Using a defined strategy, a systematic review of the literature was conducted according to PRISMA guidelines, searching for population-based epidemiological studies to evaluate the prevalence of CDH globally and per country. Studies containing overlapping populations or timeframes were excluded. CDH-related risk factors were calculated by meta-analysis using RevMan5.3 and expressed as risk ratio and 95% confidence interval. Results Prevalence: Of 8230 abstracts screened, 30 full-text articles published between 1980 and 2019 were included. The overall prevalence of CDH was 2.3 in 10,000 births (16,710 CDH babies in 73,663,758 livebirths). Risk factors: From 9 studies we found that male sex [RR 1.38 (1.05–1.80), p = 0.02] and maternal age > 35 years [RR 1.69 (1.26–2.25), p = 0.0004] were associated with CDH. Conversely, maternal black ethnicity resulted as a protective factor [RR 0.82 (0.77–0.89, p Conclusion This study reveals that there is a worldwide paucity of population-based studies, and those studies that report on prevalence and risk factors come from a small number of countries. The prevalence of CDH varies within and across geographical world regions. The main risk factors for CDH identified are male sex and older maternal age. More epidemiological studies, involving more world regions, are needed to identify possible strategies to help strengthen our understanding of the risk factors, provide clinicians with the tools necessary for prenatal and postnatal counseling, and inform policy makers on how to strategize CDH care in different parts of the world. Type of study Systematic review and meta-analysis. Level of evidence Level III.

The clinical and plain radiographic differentiation of congenital intrinsic duodenal anomalies (atresia, web, stenosis) from intestinal malrotation is not always clear. Although sonography has been documented as an important diagnostic tool in the differentiation of these two entities, its role is still not widely appreciated and it is still not universally utilized in this clinical setting. To assess the usefulness of sonographic features of the duodenal and gastric wall in the differentiation of congenital intrinsic duodenal anomalies from midgut malrotation in a large series of neonates and to compare them with other features on abdominal radiographs, ultrasound and upper gastrointestinal series. Using the surgical database at our tertiary pediatric hospital, we identified neonates who had surgically proven congenital intrinsic duodenal anomalies or malrotation over a period of 15 years (2000–2015). We reviewed imaging findings in both groups of neonates (blinded to the final diagnosis) with attention to the echogenicity and thickness of the wall of the duodenum and stomach, the relationship between the superior mesenteric artery and vein, the position of the third portion of the duodenum and the presence of the whirlpool sign. Findings were compared between the groups using the unpaired t-test and Fisher exact test. We included 107 neonates in the study, 40 with a congenital intrinsic duodenal anomaly, 49 with malrotation (36 with volvulus) and 18 with a combination of both. Duodenal and gastric wall thickening and hyperechogenicity were significantly more common in the group with a congenital intrinsic duodenal anomaly compared to those with malrotation (P

The novel coronavirus disease 2019 (COVID-19) pandemic has impacted our way of living in an unprecedented manner. Medical professionals at all levels have been forced to adapt to the novel virus. The delivery of surgical services and the subsequent learning opportunities for surgical residents have especially been disrupted and the pediatric surgical community has not been exempted by this. This article highlights the challenges imposed by the pandemic and outlines the various learning modalities that can be implemented to ensure continued learning opportunities throughout the pandemic and beyond. Furthermore, it aims to show how the utilization and expansion of technologies maintain and further increase the communication, as well as the exchange of and access to knowledge among peers. Virtual education-, application-, and simulation-based learning and social media, as well as telemedicine and online conferences, will play a considerable role in the future of surgical specialties and surgical education.

Necrotizing enterocolitis (NEC) is a devastating neonatal disease characterized by acute intestinal injury. Intestinal stem cell (ISC) renewal is required for gut regeneration in response to acute injury. The Wnt/β-catenin pathway is essential for intestinal renewal and ISC maintenance. We found that ISC expression, Wnt activity and intestinal regeneration were all decreased in both mice with experimental NEC and in infants with acute active NEC. Moreover, intestinal organoids derived from NEC-injured intestine of both mice and humans failed to maintain proliferation and presented more differentiation. Administration of Wnt7b reversed these changes and promoted growth of intestinal organoids. Additionally, administration of exogenous Wnt7b rescued intestinal injury, restored ISC, and reestablished intestinal epithelial homeostasis in mice with NEC. Our findings demonstrate that during NEC, Wnt/β-catenin signaling is decreased, ISC activity is impaired, and intestinal regeneration is defective. Administration of Wnt resulted in the maintenance of intestinal epithelial homeostasis and avoidance of NEC intestinal injury. ispartof: Cell Death & Disease vol:10 issue:10 ispartof: location:England status: published

Appendiceal carcinoid (neuroendocrine tumor or NET) is a rare neuroendocrine neoplasm often found incidentally following appendectomy for appendicitis. Surgery for appendicitis is currently under scrutiny and children are increasingly managed conservatively with antibiotics alone. Herein, we aimed to review our experience with the management of appendiceal carcinoids at our institution. Following ethical approval, we reviewed the charts of all patients who underwent appendectomy for appendicitis at our institution between 2000 and 2018. The pathology registry was consulted to identify children diagnosed with appendiceal carcinoid. Outcome measures included incidence, demographics, and management. During the study period, 32 children (23 female) had an appendiceal carcinoid confirmed at pathology. Of these, 13 were initially treated with appendectomy (total of 5,059 appendectomies: 0.3% incidence). The other 19 had an appendectomy elsewhere by an adult general surgeon and were referred to our institution for further management. Overall, the mean age at diagnosis was 13 ± 2.7 years and all patient had a preoperative diagnosis of appendicitis, none of suspected carcinoid. Most children (75%) had acute non-perforated appendicitis. The overall mean size of the lesion was 1 ± 0.9 cm, with a > 2 cm lesion in 3 patients. Following diagnosis, 12 children (38%) underwent an ileocolic resection, due to carcinoid size, invasiveness, and margin clearance. In our cohort, the incidence of appendiceal carcinoid among children with appendicitis is very low. Most carcinoids are small, located at the tip, associated with non-perforated appendicitis, and present in girls. Most were treated with appendectomy alone, with more extensive surgery performed in one third of children.

Introduction Inguinal hernia repair represents the most common operation in childhood; however, consensus about the optimal management is lacking. Hence, recommendations for clinical practice are needed. This study assesses the available evidence and compiles recommendations on pediatric inguinal hernia. Materials and Methods The European Pediatric Surgeons' Association Evidence and Guideline Committee addressed six questions on pediatric inguinal hernia repair with the following topics: (1) open versus laparoscopic repair, (2) extraperitoneal versus transperitoneal repair, (3) contralateral exploration, (4) surgical timing, (5) anesthesia technique in preterm infants, and (6) operation urgency in girls with irreducible ovarian hernia. Systematic literature searches were performed using PubMed, MEDLINE, Embase (Ovid), and The Cochrane Library. Reviews and meta-analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Results Seventy-two out of 5,173 articles were included, 27 in the meta-analyses. Laparoscopic repair shortens bilateral operation time compared with open repair. In preterm infants, hernia repair after neonatal intensive care unit (NICU)/hospital discharge is associated with less respiratory difficulties and recurrences, regional anesthesia is associated with a decrease of postoperative apnea and pain. The review regarding operation urgency for irreducible ovarian hernia gained insufficient evidence of low quality. Conclusion Laparoscopic repair may be beneficial for children with bilateral hernia and preterm infants may benefit using regional anesthesia and postponing surgery. However, no definite superiority was found and available evidence was of moderate-to-low quality. Evidence for other topics was less conclusive. For the optimal management of inguinal hernia repair, a tailored approach is recommended taking into account the local facilities, resources, and expertise of the medical team involved.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease. Amniotic fluid stem cells (AFSC) improve NEC injury but human translation remains difficult. We aimed to evaluate the use of extracellular vesicles (EV) derived from human AFSC. Human AFSC (hAFSC) were cultured according to the protocol (Celprogen Inc., California, U.S.A.). Conditioned medium was obtained, ultra-centrifuged, and EV were suspended in phosphate-buffered saline (PBS). C57BL/6 pups were grouped into: (1) breast-fed (Control, n = 11); (2) NEC + placebo (NEC + PBS; n = 10); and (3) NEC + treatment (NEC + EV; n = 11). NEC was induced post-natal days P5-9 by (A) gavage feeding hyperosmolar formula; (B) hypoxia for 10 min; and (C) lipopolysaccharide. Intra-peritoneal injections of PBS or hAFSC-EV were given on P6-7. All animals were sacrificed on P9 and terminal ileum harvested. hAFSC-EV administration reduced intestinal injury (p = 0.0048), NEC incidence (score ≥ 2), and intestinal inflammation (IL-6 p

Congenital diaphragmatic hernia (CDH) is characterized by the herniation of abdominal organs into the fetal chest through a diaphragmatic defect. The mortality and morbidity rates of babies with CDH remain high, and are directly related to the degree of pulmonary hypoplasia (lung underdevelopment) and the severity of pulmonary hypertension. CDH is typically diagnosed antenatally and observed/expected lung-to-head ratio is a common prenatal prognostic marker of pulmonary hypoplasia. Newborns with CDH often have life-threatening respiratory distress for which immediate intubation at birth is recommended. Moreover, they are usually managed with gentle ventilation, which allows permissive hypercapnia and aims to provide adequate tissue oxygenation, while avoiding barotrauma. Some patients are managed with extracorporeal membrane oxygenation (ECMO) that provides rest to the hypoplastic lungs, allowing them to grow and avoiding ventilation-induced barotrauma. When the neonate is clinically stable, the diaphragmatic repair is performed either from the abdomen (laparotomy or laparoscopy) or from the chest (thoracotomy or thoracoscopy). Large defects that cannot be closed primarily are closed with a synthetic or natural patch. CDH is associated with short- and long-term morbidities; the latter are better addressed in a dedicated multidisciplinary clinic.

Severe COVID-19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors. Most patients with severe COVID-19 infections who died had developed ARDS. Currently, ARDS is treated with supportive measures, but regenerative medicine approaches including extracellular vesicle (EV)-based therapies have shown promise. Herein, we aimed to analyse whether EV-based therapies could be effective in treating severe pulmonary conditions that affect COVID-19 patients and to understand their relevance for an eventual therapeutic application to human patients. Using a defined search strategy, we conducted a systematic review of the literature and found 39 articles (2014–2020) that reported effects of EVs, mainly derived from stem cells, in lung injury models (one large animal study, none in human). EV treatment resulted in: (1) attenuation of inflammation (reduction of pro-inflammatory cytokines and neutrophil infiltration, M2 macrophage polarization); (2) regeneration of alveolar epithelium (decreased apoptosis and stimulation of surfactant production); (3) repair of microvascular permeability (increased endothelial cell junction proteins); (4) prevention of fibrosis (reduced fibrin production). These effects were mediated by the release of EV cargo and identified factors including miRs-126, −30b-3p, −145, −27a-3p, syndecan-1, hepatocyte growth factor and angiopoietin-1. This review indicates that EV-based therapies hold great potential for COVID-19 related lung injuries as they target multiple pathways and enhance tissue regeneration. However, before translating EV therapies into human clinical trials, efforts should be directed at developing good manufacturing practice solutions for EVs and testing optimal dosage and administration route in large animal models.

Aim:Controversies exist on the optimal diagnostic workup for neonates with esophageal atresia (EA) with/without tracheoesophageal fistula (TEF). Aim of this study was to describe the current diagnostic policies in EA/TEF patients enrolled in an International multicenter registry. Methods:All patients consecutively registered from July 2014 to December 2017 in the EUPSA Esophageal Atresia Registry (EUPSA-EAR) were included in the study. Data related to diagnostic investigations among Centers forming the EUPSA-EAR were analyzed. Main Results:During the study period, 374 consecutive patients were recorded by 23 Centers. The majority of patients underwent chest X-rays, echocardiography, abdominal ultrasound, and abdominal X-rays. Preoperative bronchoscopy and esophageal gap measurement were performed in one third of the patients. Conclusions:Present data from a large cohort of patients from the EUPSA-EAR show both inter-institutional and intra-institutional variability in diagnostic workup of patients with EA/TEF. Efforts should be made to develop guidelines on the diagnostic workup for EA/TEF patients.

Incomplete lung development, also known as pulmonary hypoplasia, is a recognized cause of neonatal death and poor outcome for survivors. To date, there is no effective treatment that promotes fetal lung growth and maturation. Herein, we describe a novel stem cell-based approach that enhances fetal lung development via the administration of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs). In experimental models of pulmonary hypoplasia, administration of AFSC-EVs promoted lung branching morphogenesis and alveolarization, and stimulated pulmonary epithelial cell and fibroblast differentiation. This regenerative ability was confirmed in two models of injured human lung cells, where human AFSC-EVs obtained following good manufacturing practices restored pulmonary epithelial homeostasis. AFSC-EV beneficial effects were exerted via the release of RNA cargo, primarily miRNAs, that regulate the expression of genes involved in fetal lung development. Our findings suggest that AFSC-EVs hold regenerative ability for underdeveloped fetal lungs, demonstrating potential for therapeutic application.One Sentence SummaryFetal lung regeneration via administration of extracellular vesicles derived from amniotic fluid stem cells

To describe the postnatal outcome of fetal meconium peritonitis and identify prenatal predictors of neonatal surgery. We retrospectively reviewed all fetuses with ultrasound findings suspicious for meconium peritonitis at a single center over a 10-year period. A systematic review and meta-analysis were then performed pooling our results with previous studies assessing prenatally diagnosed meconium peritonitis and postnatal outcome. Prenatal sonographic findings were analyzed to identify predictors for postnatal surgery. 34 cases suggestive of meconium peritonitis were diagnosed at our center. These were pooled with cases from 14 other studies yielding a total of 244 cases. Postnatal abdominal surgery was required in two thirds of case (66.5 %). The strongest predictor of neonatal surgery was meconium pseudocyst (OR [95 % CI] 6.75 [2.53-18.01]), followed by bowel dilation (OR [95 % CI] 4.17 [1.93-9.05]) and ascites (OR [95 % CI] 2.57 [1.07-5.24]). The most common cause of intestinal perforation and meconium peritonitis, found in 52.2 % of the cases, was small bowel atresia. Cystic fibrosis was diagnosed in 9.8 % of cases. Short-term neonatal outcomes were favorable, with a post-operative mortality rate of 8.1 % and a survival rate of 100 % in neonates not requiring surgery. Meconium pseudocysts, bowel dilation, and ascites are prenatal predictors of neonatal surgery in cases of meconium peritonitis. Fetuses with these findings should be delivered in centers with pediatric surgery services. Though the prognosis is favorable, cystic fibrosis complicates postnatal outcomes.ZIEL: Beschreibung des postnatalen Outcomes der fetalen Mekoniumperitonitis und Identifizierung pränataler Prädiktoren für die neonatale Chirurgie. Wir untersuchten an einem einzigen Zentrum über 10 Jahre hinweg retrospektiv alle Föten mit Ultraschallbefunden, bei denen der Verdacht einer Mekoniumperitonitis bestand. Eine systematische Übersicht und eine Metaanalyse wurden daraufhin durchgeführt, um unsere Ergebnisse mit früheren Studien zur Beurteilung der pränatalen Mekoniumperitonitis und des postnatalen Outcomes zusammenzufassen. Die pränatalen sonografischen Befunde wurden analysiert, um Prädiktoren für die postnatale Chirurgie zu identifizieren. In unserem Zentrum gab es 34 Fälle mit Verdachtsdiagnose Mekoniumperitonitis. Diese wurden mit Fällen aus 14 anderen Studien zusammengefasst, sodass sich insgesamt 244 Fälle ergaben. In 2 Drittel der Fälle (66,5 %) war eine postnatale abdominale Operation erforderlich. Der stärkste Prädiktor für die neonatale Chirurgie war eine Mekonium-Pseudozyste (OR 6,75; 95 %-KI 2,53–18,01), gefolgt von Darmdilatation (OR 4,17; 95 %-KI 1,93–9,05) und Aszites (OR 2,57; 95 %-KI 1,07–5,24). Die häufigste Ursache für Darmperforation und Mekoniumperitonitis, die in 52,2 % der Fälle gefunden wurde, war die Dünndarmatresie. Mukoviszidose wurde in 9,8 % der Fälle diagnostiziert. Das Kurzzeit-Outcome bei Neugeborenen war günstig, mit einer postoperativen Mortalitätsrate von 8,1 % und einer Überlebensrate von 100 % bei Neugeborenen, die nicht operiert werden mussten. Mekonium-Pseudozysten, Darmdilatation und Aszites sind pränatale Prädiktoren für eine neonatale Chirurgie bei Mekoniumperitonitis. Bei Föten mit diesen Befunden sollte die Entbindung in Zentren mit dem Schwerpunkt Neugeborenenchirurgie erfolgen. Obwohl die Prognose günstig ist, erschwert Mukoviszidose das postnatale Outcome.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm neonates and causing high morbidity, high mortality, and huge costs for the family and society. The treatment and the outcome of the disease have not changed in recent decades. Emerging evidence has shown that stimulating the Wnt/β-catenin pathway and enhancing intestinal regeneration are beneficial in experimental NEC, and that they could potentially be used as a novel treatment. Amniotic fluid stem cells (AFSC) and AFSC-derived extracellular vesicles (EV) can be used to improve intestinal injury in experimental NEC. However, the mechanisms by which they affect the Wnt/β-catenin pathway and intestinal regeneration are unknown. In our current study, we demonstrated that AFSC and EV attenuate NEC intestinal injury by activating the Wnt signaling pathway. AFSC and EV stimulate intestinal recovery from NEC by increasing cellular proliferation, reducing inflammation and ultimately regenerating a normal intestinal epithelium. EV administration has a rescuing effect on intestinal injury when given during NEC induction; however, it failed to prevent injury when given prior to NEC induction. AFSC-derived EV administration is thus a potential emergent novel treatment strategy for NEC. ispartof: CELL DEATH & DISEASE vol:11 issue:9 ispartof: location:England status: published

To study pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH), investigators have been employing a fetal rat model based on nitrofen administration to dams. Herein, we aimed to: (1) investigate the validity of the model, and (2) synthesize the main biological pathways implicated in the development of PH associated with CDH. Using a defined strategy, we conducted a systematic review of the literature searching for studies reporting the incidence of CDH or factors involved in PH development. We also searched for PH factor interactions, relevance to lung development and to human PH. Of 335 full-text articles, 116 reported the incidence of CDH after nitrofen exposure or dysregulated factors in the lungs of nitrofen-exposed rat fetuses. CDH incidence: 54% (27–85%) fetuses developed a diaphragmatic defect, whereas the whole litter had PH in varying degrees. Downregulated signaling pathways included FGF/FGFR, BMP/BMPR, Sonic Hedgehog and retinoid acid signaling pathway, resulting in a delay in early epithelial differentiation, immature distal epithelium and dysfunctional mesenchyme. The nitrofen model effectively reproduces PH as it disrupts pathways that are critical for lung branching morphogenesis and alveolar differentiation. The low CDH rate confirms that PH is an associated phenomenon rather than the result of mechanical compression alone.

Females with recto-vestibular fistula (RVF) can be managed either by one-stage sagittal anorectoplasty (SARP) or by conventional multi-stage approach with colostomy followed by SARP. Our aim was to define which approach, one-stage or multi-stage, is safer and more beneficial. Using a defined search strategy, two investigators identified all comparative studies on the mentioned procedures. The study was conducted under PRISMA guidelines. The meta-analysis was performed using RevMan 5.3. Data are mean ± SD. Of 649 titles/abstracts screened, 13 full-text articles were analyzed. Three studies were included (156 females). One-stage SARP was associated with increased risk of wound infection (24.3 ± 8.7%) compared to multi-stage approach (10.9 ± 2.5%; p

Aim The American College of Surgeons has developed a registry, the National Quality Improvement Program Pediatric (NSQIP-P), that provides participating centers with high-quality surgical outcome data for children. Herein, we aimed to analyze for the first time the short-term outcomes of live-born infants with congenital diaphragmatic hernia (CDH) registered on this large North American database. Methods During 2015 to 2016, up to 101 participating centers uploaded 95 perioperative data points on the NSQIP-P database for patients that underwent surgical repair of CDH. The demographics, peri-, and post-operative data (up to 30 days following surgical repair) of infants with CDH were reviewed. Binary logistic regression was performed to test associations between risk factors and mortality. Main Results There were 432 (61% male) infants, who underwent CDH surgical repair during the study period. The prematurity rate (gestational age Conclusion This is the first report on CDH outcomes from the NSQIP-P database. Utilization of ECMO was low compared with single-center studies from North America. The early postoperative mortality rate of babies with CDH considered suitable for surgery remains high.

The laparoscopic repair of Morgagni's hernia (MH) has been reported to be safe and feasible. However, it is still unclear whether laparoscopy is superior to open surgery in repairing MH.Using a defined search strategy, three investigators independently identified all comparative studies reporting data on open and laparoscopic MH repair in patients18 years of age. Case reports and opinion articles were excluded. Meta-analysis was conducted according to PRISMA guidelines and using RevMan 5.3. Data are expressed as mean ± SD.Systematic review - Of 774 titles/abstracts screened, 51 full-text articles were analyzed. Three studies were included (92 patients), with 53 (58%) open approaches and 39 (42%) laparoscopy. Meta-analysis - The length of surgery was shorter in laparoscopy (50.5 ± 17.0 min) than in open procedure (90.0 ± 15.0 min; P .00001). Laparoscopy shortened the length of hospital stay (2.1 ± 1.4 days) versus open surgery (4.5 ± 2.1 days; P .00001). There was no difference with regards to complications (laparoscopy: 8.8% ± 5.5%, open: 9.4% ± 1.6%; P = .087) and recurrences (laparoscopy: 2.9% ± 5.0%, open: 5.7% ± 1.8%; P = .84).Comparative studies indicate that laparoscopic MH repair can be performed in infants and children. Laparoscopy is associated with shortened length of surgery and hospital stay in comparison to open procedure. Prospective randomized studies would be needed to confirm present data.

Background To describe the spectrum of noniatrogenic pediatric vascular injuries and their outcomes at a large tertiary pediatric hospital. Methods Retrospective review of a prospectively-maintained trauma database, identifying children with noniatrogenic vascular injuries managed between 1994 and 2014. Results A total of 198 patients were identified. Those patients with a digital or intracerebral vascular injury (92/198) were excluded from further analysis. The remaining 106 patients represented 1.2% of all traumas managed at our institution during the 21-year study period. The majority were male (75%), and between 1 and 12years of age (71% of all patients). Median time from trauma scene to any hospital was 48min (range 0–132), and most patients were transferred from another hospital (64%). Three patients were declared dead upon arrival (3%). Penetrating injuries accounted for most injuries (72%), while blunt injuries accounted for the remainder. Ulnar, radial, or brachial artery trauma accounted for 47% of injuries. Most vessels were treated operatively, by primary repair (49%), vessel ligation (15%), or interposition graft (12%). Fourteen patients (13%) were managed nonoperatively and most patients (74%) experienced no complications in hospital or during follow-up. Conclusion Noniatrogenic pediatric vascular injuries are rare and represent a highly heterogeneous population. Most children recover well, with minimal perioperative complications. Level of evidence IV (case series with no comparison group).

Aim To define current management of congenital pulmonary airway malformation (CPAM). Methods A total of 181 European Pediatric Surgeons' Association members (91% senior) from 48 countries completed an online questionnaire. Main Results Prenatal: 93% respondents work in centers with prenatal diagnosis facilities, and 27% in centers offering in utero surgery. Prenatal counseling is performed by 86% respondents, 22% of whom see >10 cases per year. Risk of single pre-/postnatal complications is deemed low (Postnatal: 75% respondents operate on asymptomatic patients, 18% before 6 months of age, 62% between 6 and 12 months of age, and 20% after 12 months of age. Risk of infection (86%), cancer (63%), and symptoms development (62%) are indications for surgery in asymptomatic CPAM. Sixty-three percent prefer a thoracotomy. Lobectomy is the preferred procedure (58% respondents). Motivations against surgery include lesion Conclusion Current pre- and postnatal management of CPAM lacks uniformity, particularly for surgical indication, timing, and approach. Efforts should be made toward standardization. Risk of CPAM-associated cancer is not clear.

Introduction Several authors have reported the use of atropine as an alternative treatment to pyloromyotomy in infants with hypertrophic pyloric stenosis (HPS). Our aims were to review the efficacy of atropine in treating HPS and to compare atropine therapy versus pyloromyotomy. Materials and Methods Using a defined search strategy (PubMed, MEDLINE, OVID, Embase, Cochrane databases), two investigators independently identified studies reporting the use of atropine for HPS. Case reports and opinion articles were excluded. Outcome measures included success rate, side effects, and length of hospital stay. Maneuvers were compared using Fisher's exact test, and meta-analysis was conducted using RevMan 5.3. Data are expressed as mean ± standard deviation. Results Systematic review: of 2,524 abstracts screened, 51 full-text articles were analyzed. There were no prospective or randomized studies. Twelve articles (508 infants) reported HPS resolution using atropine in 402 (79.1%) patients. Atropine side effects were documented in 38/251 (15.1%) infants and included tachycardia, increased transaminases, and flushed skin. Meta-analysis: five studies compared atropine treatment (293 infants) with pyloromyotomy (537 infants). Pyloromyotomy had higher success rate (100%) than atropine (80.8%; p Conclusion Comparative but nonrandomized studies indicate that atropine is less effective than pyloromyotomy to treat infants with HPS. Currently, there is no evidence-based literature to support atropine treatment in these infants. To our knowledge, atropine should be reserved for patients unfit for general anesthesia or surgery.

SummaryBackground Intraoperative hypercapnia and acidosis have been associated with thoracoscopic repair of both congenital diaphragmatic hernia and esophageal atresia/tracheoesophageal fistula. Aim The aim of the present study was to investigate whether thoracoscopic repair of congenital diaphragmatic hernia or esophageal atresia/tracheoesophageal fistula was associated with acidosis and hypercapnia in a large group of neonates, and to analyze the effects of acidosis and hypercapnia on early postoperative outcomes. Methods We reviewed the charts of neonates who underwent open or thoracoscopic congenital diaphragmatic hernia or esophageal atresia/tracheoesophageal fistula repair (2004-2014). Patients with available intraoperative arterial gas values were included. Data (PaCO2: mm Hg) were compared using paired/unpaired tests and are reported as difference [95% confidence interval]. Results Congenital diaphragmatic hernia: 187 neonates underwent open (n=153) or thoracoscopic (n=34) repair. Intraoperative arterial gas values were recorded in 96 open and in 23 thoracoscopic operations. Both groups had similar preoperative pH and PaCO2, and developed intraoperative acidosis (open −0.08 [−0.11, −0.05] P

As appendicitis in children can be managed differently according to the severity of the disease, we investigated whether commonly used serum biomarkers on admission could distinguish between simple and complicated appendicitis.Admission white blood cell (WBC), neutrophil (NEU), and C-reactive protein (CRP) levels were analysed by ROC curve, and Kruskal-Wallis and contingency tests. Patients were divided according to age and histology [normal appendix (NA), simple appendicitis (SA), complicated appendicitis (CA)].Of 1197 children (NA = 186, SA = 685, CA = 326), 7% were5 years, 55% 5-12, 38% 13-17. CA patients had higher CRP and WBC levels than NA and SA (p 0.0001). NEU levels were lower in NA compared to SA or CA (p 0.0001), but were similar between SA and CA (p = 0.6). CA patients had higher CRP and WBC levels than SA patients in 5-12- (p 0.0001) and 13-17-year groups (p = 0.0075, p = 0.005), but not in5-year group (p = 0.72, p = 0.81). We found CRP40 mg/L in 58% CA and 37% SA (p 0.0001), and WBC15 × 10Admission CRP and WBC levels may help the clinician predict complicated appendicitis in children older than 5 years of age. Early distinction of appendicitis severity using these tests may guide caregivers in the preoperative decision-making process.

Purpose Oxidative stress has been implicated in the pathogenesis of various neonatal diseases involving the intestine. Hydrogen sulfide (H 2 S) has been shown to protect against oxidative stress. We hypothesized that administration of sodium hydrosulfide (NaHS), an H 2 S donor, to neonatal mice can decrease the intestinal epithelial injury associated with maternal separation (MS). Methods C57BL/6 mice received either intraperitoneal phosphate buffered saline (PBS; n=10) or NaHS (1mg/kg/day; n=10), followed by MS for 3h daily between postnatal day P5 and P9. Control neonatal mice were untreated and were not exposed to MS (n=10). Proximal colon was harvested and analyzed for crypt length, goblet cell number per crypt, oxidative stress and inflammation. Groups were compared using one-way ANOVA with Bonferroni post-test. Results Compared to controls, MS+PBS mice had shorter crypt lengths, fewer goblet cells per crypt, reduced glutathione peroxidase activity, increased expression of thiobarbituric acid reactive substances and inducible nitric oxide synthase mRNA, as well as increased IL-6 , TNFα and myeloperoxidase. Administration of NaHS significantly counteracted these negative effects of MS. Conclusions H 2 S protects the colon from the epithelial damage, oxidative stress and inflammation caused by maternal separation. This study provides insights on the pathogenesis of neonatal bowel diseases and indicates the potential for a pharmacological intervention to rescue the colonic epithelium. Level of evidence n/a – animal and laboratory study.

Aim Isolated oesophageal perforation in neonates is a rare but potentially life-threatening condition. Although management has historically been operative, conservative management (antibiotics, bowel rest, parenteral nutrition) is now more routinely used. The aim of this study was to evaluate the management of this condition in two large neonatal surgical centres. Methods A retrospective cohort study was conducted for neonates admitted to The Hospital for Sick Children (Toronto, Canada) or The Royal Children's Hospital (Melbourne, Australia) with a diagnosis of oesophageal perforation, from 2006 to 2016. Patients with oesophageal atresia or tracheo-oesophageal fistula were excluded. Data were collected from chart review regarding demographics, clinical course, management and outcomes. Results Eleven neonates with oesophageal perforation were identified over a 10-year period at the two centres. Median gestational age at birth was 25.3 weeks (interquartile range 24.2-28.8) and the majority (7/11, 64%) of neonates were extremely low birthweight. Diagnosis was made on day 1 of life for 9 of 11 (81%) neonates and was secondary to nasogastric tube insertion in 10 of 11 (91%) neonates. Only four (36%) neonates had symptomatic complications. All neonates were managed with bowel rest and intravenous antibiotics for a median of 7 days (interquartile range 7-10); two patients required operative intervention. Three neonates (27%) developed chronic lung disease and two (19%) died prior to discharge. Conclusions Oesophageal perforation is severe complication secondary to instrumentation of the upper gastrointestinal tract in neonates. Prompt and accurate diagnosis is crucial. Non-operative management is effective for the majority, though morbidity is common.

Congenital Diaphragmatic Hernia (CDH) is a birth defect that is characterized by lung hypoplasia, pulmonary hypertension and a diaphragmatic defect that allows herniation of abdominal organs into the thoracic cavity. Although widely unknown to the public, it occurs as frequently as cystic fibrosis (1:2500). There is no monogenetic cause, but different animal models revealed various biological processes and epigenetic factors involved in the pathogenesis. However, the pathobiology of CDH is not sufficiently understood and its mortality still ranges between 30 and 50%. Future collaborative initiatives are required to improve our basic knowledge and advance novel strategies to (prenatally) treat the abnormal lung development. This review focusses on the genetic, epigenetic and protein background and the latest advances in basic and translational aspects of CDH research.

Purpose: Surgical site infections (SSI) contribute to postoperative morbidity and mortality in children. Our aim was to evaluate the prevalence and identify risk factors for SSI in neonates. Methods: Using a defined strategy, three investigators searched articles on neonatal SSI published since 2000. Studies on neonates and/or patients admitted to neonatal intensive care unit following cervical/thoracic/abdominal surgery were included. Risk factors were identified from comparative studies. Meta-analysis was conducted according to PRISMA guidelines using RevMan 5.3. Data are (mean ± SD) prevalence. Results: Systematic review—of 885 abstracts screened, 48 studies (27,760 neonates) were included. The incidence of SSI was 5.6% (1,564 patients). SSI was more frequent in males (61.8%), premature babies (77.4%), and following gastrointestinal surgery (95.4%). Meta-analysis—10 comparative studies (16,442 neonates; 946 SSI 5.7%) showed that predictive factors for SSI development were gestational age, birth weight, age at surgery, length of surgical procedure, number of procedure per patient, length of preoperative hospital stay, and preoperative sepsis. Conversely, preoperative antibiotic use was not significantly associated with development of SSI. Conclusions: Younger neonates and those undergoing abdominal procedures are at higher risk for SSI. Given the lack of evidence-based literature, prospective studies may help determine the risk factors for SSI in neonates.

The sonographic whirlpool sign of volvulus due to midgut malrotation is well recognized. However, variations of the whirlpool sign may be seen in other conditions, but this observation has received little attention in the literature. This study presents a series of neonates with a variety of causes of congenital intestinal obstruction, all associated with a whirlpool sign (unrelated to midgut volvulus), which was correctly recognized preoperatively on sonography. We also emphasize the pivotal role of sonography in managing congenital obstruction of the intestinal tract in neonates. This is a retrospective analysis of clinical, imaging and surgical findings in 11 neonates with congenital intestinal obstruction associated with a whirlpool sign (unrelated to midgut volvulus) that was recognized preoperatively on sonography and in whom the cause for the whirlpool was documented at surgery. Eleven neonates (eight male, three female) had clinical and radiographic evidence of intestinal obstruction in whom sonography depicted a whirlpool sign, which was recognized on the initial sonogram in nine and on a repeat sonogram in two. The whirlpool was located in the upper abdomen in only two, mid-abdomen in five and right lower quadrant in four. The whirlpool was only 1–2 cm in diameter. An upper gastrointestinal series in three neonates failed to depict the cause of obstruction. Contrast enema in three cases had findings suggesting the site of obstruction was in the ileum but none depicted the exact cause of the obstruction. At surgery, the whirlpool sign correlated with a segmental volvulus of the small intestine in eight neonates and with the coiled distal small intestine associated with apple-peel atresia in the other three. This study illustrates neonates in whom a whirlpool sign (unrelated to midgut volvulus) was correctly recognized on sonography before surgery. Sonography proved more useful than an upper gastrointestinal series or contrast enema in depicting the exact cause of the obstruction. Pediatric radiologists must make the effort to search throughout the entire abdomen and pelvis for a small whirlpool sign on sonography, even in the absence of midgut malrotation, in neonates with congenital intestinal obstruction. Its recognition preoperatively will facilitate a rapid diagnosis and will obviate the necessity for contrast examinations of the gastrointestinal tract, which require ionizing radiation.

To evaluate neurodevelopmental impairment (NDI) in children born with congenital diaphragmatic hernia (CDH).Using a defined search strategy, a systematic review was conducted to define the incidence and types of NDI, to report abnormal neuroimaging findings and to evaluate possible NDI predictors. A meta-analysis was performed on comparative studies reporting risk factors for NDI, using RevMan 5.3.Of 3541 CDH children (33 studies), 829 (23%) had NDI, with a higher incidence in CDH survivors who received ECMO treatment (49%) vs. those who had no ECMO (22%; p0.00001). NDI included neuromuscular hypotonia (42%), hearing (13%) and visual (8%) impairment, neurobehavioral issues (20%), and learning difficulties (31%). Of 288 survivors that had postnatal neuroimaging, 49% had abnormal findings. The main risk factors for NDI were severe pulmonary hypoplasia, large defect size, ECMO use.NDI is a relevant problem for CDH survivors, affecting 1 in 4. The spectrum of NDI covers all developmental domains and ranges from motor and sensory (hearing, visual) deficits to cognitive, language, and behavioral impairment. Further studies should be designed to better understand the pathophysiology of NDI in CDH children and to longitudinally monitor infants born with CDH to correct risk factors that can be modifiable.Level III.

Aim To define patterns in the management of pediatric appendicitis. Methods A total of 169 delegates from 42 (24 European) countries completed a validated survey administered at the EUPSA 2017 annual congress. Results In the work-up of children with suspected acute appendicitis, most surgeons rely on full blood count (92%), C-reactive protein (82%), and abdominal ultrasonography (76%), but rarely on computed tomography scans or magnetic resonance imaging. In suspected simple appendicitis, most surgeons (76%) do not perform appendectomy at night in clinically stable patients and start antibiotic preoperatively (64%), but only 15% offer antibiotic therapy alone (no appendectomy). In suspected perforated appendicitis, 96% start antibiotic preoperatively, and 92% perform an appendectomy. Presence of phlegmon/abscess is the main contraindication to immediate surgery. In case of appendix mass, most responders (75%) favor a conservative approach and perform interval appendectomy always (56%) or in selected cases (38%) between 2 and 6 months from the first episode (81%). Children with large intraperitoneal abscesses are managed by percutaneous drainage (59% responders) and by surgery (37% responders). Laparoscopy is the preferred surgical approach for both simple (89%) and perforated appendicitis (81%). Most surgeons send the appendix for histology (96%) and pus for microbiology, if present (78%). At the end of the operation, 58% irrigate the abdominal cavity only if contaminated using saline solution (93%). In selected cases, 52% leave a drain in situ. Conclusion Some aspects of appendicitis management lack consensus, particularly appendix mass and intraperitoneal abscess. Evidence-based guidelines should be developed, which may help standardize care and improve clinical outcomes.

Hyperinsulinism as a cause of persistent hypoglycaemia in infancy and childhood is very uncommon (1:50,000). The importance of preventing hypoglycaemia (and reducing the likelihood of neurologic damage) by the administration of adequate quantities of carbohydrate cannot be overstressed.

We sought to assess the magnitude of functional decline and the natural history of the operated kidney residual function after zero-ischemia nephron-sparing surgery (Z-NSS) in children with unilateral renal tumor (URT).50 children were treated for URT at our surgical unit between 1992 and 2016. Of these 12 who underwent Z-NSS were available for the current analysis. Operated kidney function was assessed by 99mTc-dimercapto-succinic acid (DMSA) renal scintigraphy. Operated kidney volume was assessed by renal ultrasonography.A positive correlation between split renal function and split renal volume was found (P = 0.001). The subset of patients with ≥40% preservation of operated kidney function/volume (OKF/V) had no-time dependent changes during adolescence. The subset of patients with40% OKF/V preservation had a catch-up growth that after puberty reached values not much different from those with ≥40% OKF/V preservation. At 5 years of follow-up, 3 of 5 patients with baseline dysfunction (eGFR between 40.8 and 89.4 ml/min/1.73 mIn children with URT who underwent Z-NSS, the pattern of OKF/V recovery suggests that compensatory catch-up growth capacity during childhood minimizes OKF/V decline more than Z-NSS.Level I prognosis study - prospective cohort study with80% follow-up and all patients enrolled at same time point in disease.

A term female infant, born after an uneventful pregnancy with normal antenatal ultrasonography, presented at 2 hours of life with respiratory distress, requiring mechanical ventilation. Her initial chest X-ray was unremarkable (figure 1A). The blood culture at birth was positive for group B streptococcus (GBS). She improved with antibiotics, allowing extubation to continuous positive airway pressure (CPAP) on day-of-life (DOL)-4. Weaning from CPAP failed on several occasions. An ultrasound (DOL-19) showed normal function of both hemidiaphragms, but a chest X-ray showed right lung hyperdensity with pleural effusion (figure …

The surgical management of neonates with duodenal atresia (DA) involves re-establishment of intestinal continuity, either by duodeno-duodenostomy (DD) or by duodeno-jejunostomy (DJ). Although the majority of pediatric surgeons perform DD repair preferentially, we aimed to analyze the outcome of DA neonates treated with either surgical technique. Following ethical approval (REB:1000047737), we retrospectively reviewed the charts of all patients who underwent DA repair between 2004 and 2014. Patients with associated esophageal/intestinal atresias and/or anorectal malformations were excluded. Outcome measures included demographics (gender, gestational age, and birth weight), length of mechanical ventilation, time to first and full feed, length of hospital admission, weight at discharge (z-scores), and postoperative complications (anastomotic stricture/leak, adhesive obstruction, and need for re-laparotomy). Both DD and DJ groups were compared using parametric or non-parametric tests, with data presented as mean ± SD or median (interquartile range). During the study period, 92 neonates met the inclusion criteria. Of these, 47 (51%) had DD and 45 (49%) DJ repair. All procedures were performed open, apart from one laparoscopic DJ. Overall, DD and DJ groups had similar demographics. Likewise, we found no differences between the two groups for length of ventilation (p = 0.6), time to first feed (p = 0.5), time to full feed (p = 0.4), length of admission (p = 0.6), prokinetic use (p = 0.5), nor weight at discharge (p = 0.1). When the 30/92 (33%) patients with trisomy-21 (DD = 16, DJ = 14) were excluded from analysis, the groups still had similar weight at discharge (p = 0.2). Postoperative complication rate was not different between the two groups. One patient per group died, due to respiratory failure (DD) and sepsis (DJ). This study demonstrates that in neonates with duodenal atresia, duodeno-duodenostomy and duodeno-jejunostomy have similar outcomes. These findings are relevant for surgeons who repair duodenal atresia laparoscopically, as duodeno-jejunostomy had equal clinical outcomes and may be easier to perform.

Administration of hyperosmolar formula is regarded as a risk factor for the development of necrotizing enterocolitis (NEC). However, there are limited number of reports about the relationship between formula osmolality and NEC. The aim of this study is to evaluate the effects of formula concentration in an experimental model of NEC. We studied experimental NEC in C57BL/6 mice. NEC was induced by giving hypoxia, gavage administration of lipopolysaccharide and gavage formula feeding from postnatal day 5–9. We used two types of formula: (1) hyperosmolar formula (HF): 15 g Similac + 75 ml Esbilac (849 mOsm/kg); (2) diluted formula (DF): dilute hyperosmolar formula with an equal amount of water (325 mOsm/kg). Controls were fed by the mother. On postnatal day 9, the ileum was harvested and evaluated for severity of mucosal injury (hematoxylin/eosin staining) and inflammation (PCR for IL6 and TNFα mRNA expression). The incidence of NEC was same in both HF and DF (80%). The intestinal inflammatory response was similar between HF and DF (IL6: p = 0.26, TNFα: p = 0.69). This study indicates the osmolality of enteral formula does not affect incidence of experimental NEC. This experimental study provides new insights into the relationship between formula feeding and NEC.

Maternal separation (MS) leads to intestinal barrier dysfunction in neonatal mice. Endoplasmic reticulum (ER) stress is associated with apoptosis and pro-inflammatory response induction. We hypothesized that MS induced gut damage is associated with ER stress and that administration of an ER stress inhibitor protects gut damage.C57BL/6 mice received intraperitoneal PBS (n=10) or Salubrinal (1mg/kg/day, n=10). MS was performed soon after treatment for 3h daily between P5 and P9. Ten untreated neonatal mice served as control. The colon was harvested on P9 and analyzed for ER stress markers (BiP, CHOP), apoptosis (CC3), goblet cell number per crypt and crypt length (Alcian blue, hematoxylin/eosin), and transcellular permeability (Ussing chamber). Groups were compared using one-way ANOVA with Bonferroni post-test.Compared to controls, MS mice had higher relative protein expression of ER stress and apoptosis markers (p0.05) and reduced goblet cell number per crypt and crypt length (p0.001). In comparison to PBS mice, Salubrinal treated mice had higher goblet cell number (p0.05), crypt length (p0.001), and lower transcellular permeability (p0.05).Maternal separation induces ER stress and causes colon damage, but ER stress inhibitor protects morphology and permeability. This provides insights on bowel pathogenesis and potential novel treatments for diseases such as necrotizing enterocolitis.

Pentalogy of Cantrell is a rare syndrome that is characterized by varying degrees of midline wall defects and congenital cardiac anomalies. A left ventricular diverticulum (LVD) is defined as partial ectopia cordis, can be part of the pentalogy of Cantrell, and can put the patient at risk of severe complications. Early diagnosis and ligation/resection of the LVD is important to prevent complications. We report on a case of pentalogy of Cantrell, in which a LVD was diagnosed only at 2 months of age despite preceding pre- and postnatal echocardiography. We conclude that in the suspicion of pentalogy of Cantrell, either complete or incomplete, cardiac magnetic resonance imaging should be performed, when possible, to avoid the potential complication of a herniating ventricular diverticulum.

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is characterized by pulmonary hypoplasia and pulmonary hypertension (PHTN). PHTN secondary to CDH is a result of vascular remodeling, a structural alteration in the pulmonary vessel wall that occurs in the fetus. Factors involved in vascular remodeling have been reported in several studies, but their interactions remain unclear. To help understand PHTN pathophysiology and design novel preventative and treatment strategies, we have conducted a systematic review of the literature and comprehensively analyzed all factors and pathways involved in the pathogenesis of pulmonary vascular remodeling secondary to CDH in the nitrofen model. Moreover, we have linked the dysregulated factors with pathways involved in human CDH. Of the 358 full-text articles screened, 75 studies reported factors that play a critical role in vascular remodeling secondary to CDH. Overall, the impairment of epithelial homeostasis present in pulmonary hypoplasia results in altered signaling to endothelial cells, leading to endothelial dysfunction. This causes an impairment of the crosstalk between endothelial cells and pulmonary artery smooth muscle cells, resulting in increased smooth muscle cell proliferation, resistance to apoptosis, and vasoconstriction, which clinically translate into PHTN.

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired epithelial homeostasis. Recently, amniotic fluid stem cells (AFSCs) have been shown to promote growth in hypoplastic lungs of rat fetuses with CDH. Herein, we investigated whether CDH hypoplastic lungs mount an endoplasmic reticulum (ER) stress response and whether AFSCs could re-establish pulmonary epithelial homeostasis. Primary epithelial cells were isolated from fetal rat lungs at E14.5 from control and nitrofen-exposed dams at E9.5. Nitrofen-exposed epithelial cells were grown in medium alone or co-cultured with AFSCs. Epithelial cell cultures were compared for apoptosis (TUNEL), cytotoxicity (LIVE/DEAD assay), proliferation (5′EdU), and ER stress (CHOP, Bcl-2) using one-way ANOVA (Dunn’s post-test). Compared to control, nitrofen-exposed epithelial cells had increased cytotoxicity and apoptosis, reduced proliferation, and activated ER stress. AFSCs restored apoptosis, proliferation, and ER stress back to control levels, and significantly reduced cytotoxicity. This study shows for the first time that ER stress-induced apoptosis is activated in the pulmonary epithelium of hypoplastic lungs from fetuses with CDH. AFSC treatment restores epithelial cellular homeostasis by attenuating the ER stress response and apoptosis, by increasing proliferation and migration ability, and by reducing cytotoxicity.

To determine the true incidence of associated intestinal atresia (AIA) in infants with duodenal atresia (DA) and to analyze whether the surgical approach, open versus laparoscopic, would impact on patient outcome when AIA is present. Cohort study We review all DA infants treated at our institution (2001–2016) and analyzed the outcome of those with AIA. Systematic review/meta-analysis Using a defined search strategy and according to PRISMA guidelines, two investigators independently identified all studies on DA and searched cases of AIA to determine its incidence. Data are mean ± SD. Cohort study Of 140 DA infants, 10 (7%) had AIA (4 type I, 4 type III, 2 type II). All type I AIA (webs) were found in the duodenum. Systematic review/meta-analysis Of 840 studies, 18 were included (2026 infants). The incidence of AIA was 2.8 ± 1.6%. The incidence of missed AIA was 0.8 ± 2.4%. Three comparative studies (759 infants) showed higher risk of missed AIA following laparoscopic (2.9 ± 2.4%) than open repair (0.3 ± 0.1%; p

Aim The main purpose of this study was to investigate if necrotizing enterocolitis (NEC) has a different presentation and outcome in patients with congenital heart defect (CHD) (cardiogenic NEC) from those without (classical NEC). Materials and Methods A systematic review of the literature on the characteristics of infants with NEC and CHD was performed by three independent investigators using a defined strategy (PubMed, Cochrane, Embase, and Web of Science). A meta-analysis was conducted on studies comparing NEC in infants with CHD and non-CHD infants using RevMan 5.3. Results Systematic review: Of 7,291 abstracts screened, 126 full-text articles were analyzed and 51 studies were included. NEC had an incidence of 5.1% in CHD infants (7,728/151,046, range 0–24%) and 0.8% in non-CHD infants (26,430/3,256,891, range 0.1–8.9%; p Conclusion This is the first evidence-based study showing that infants with cardiogenic NEC have different demographics and outcomes than those with classical NEC. The risk of developing NEC and the mortality rate are higher among infants with CHD than in those without. Conversely, the need for intestinal surgery is lower in babies with cardiogenic NEC than in those with classical NEC. Further studies are needed to establish preventative and management interventions that are specific to infants with or at risk of developing cardiogenic NEC.

Neurologically impaired children (NIC) suffer severe gastroesophageal reflux (GER) with poor fundoplication outcome. Aims of the study were: (1) to determine the recurrence of GER after fundoplication in NIC; (2) to compare fundoplication versus gastro-jejunal tube feeding insertion (GJ) and fundoplication versus total esophagogastric dissociation (TEGD) in primarily treating GER in NIC. Using defined search strategy, two investigators identified all comparative studies reporting the mentioned procedures to primarily treat GER in NIC. The study was conducted under PRISMA guidelines. The meta-analysis was performed using RevMan 5.3. Data are mean ± SD. Of 3840 titles/abstracts screened, 14 studies on fundoplication (2716 pts.) reported a recurrence/persistence of GER higher in NIC (14.2 ± 8.3%) than in neurologically normal (9.4 ± 5.2%; p = 0.0001), with an increased incidence of re-do fundoplication (12.6 ± 7.0% versus 9.1 ± 4.5%; p

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal surgical emergency in preterm neonates. Over the last five decades, a variety of experimental models have been developed to study the pathophysiology of this disease and to test the effectiveness of novel therapeutic strategies. Experimental NEC is mainly modeled in neonatal rats, mice and piglets. In this review, we focus on these experimental models and discuss the major advantages and disadvantages of each. We also briefly discuss other models that are not as widely used but have contributed to our current knowledge of NEC.