BACKGROUND:Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in the ZNF148 gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far. METHODS:As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals. RESULTS:The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of the ZNF148 gene. Heterozygous deletion including the entire ZNF148 gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families. CONCLUSION:The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term 'GDACCF syndrome' with 'ZNF148-related neurodevelopmental disorder'.

The Summary Background Data: EA is the most frequent congenital esophageal malformation. Long gap EA remains a therapeutic challenge for pediatric surgeons. A case case-control prospective study from a multi-institutional national French data base was performed to assess the outcome, at age of 1 and 6 years, of long gap esophageal atresia (EA) compared with non-long gap EA/tracheo-esophageal fistula (TEF). The secondary aim was to assess whether initial treatment (delayed primary anastomosis of native esophagus vs. esophageal replacement) influenced mortality and morbidity at ages 1 and 6 years. Methods: A multicentric population-based prospective study was performed and included all patients who underwent EA surgery in France from January 1, 2008 to December 31, 2010. A comparative study was performed with non-long gap EA/TEF patients. Morbidity at birth, 1 year, and 6 years was assessed. Results: Thirty-one patients with long gap EA were compared with 62 non-long gap EA/TEF patients. At age 1 year, the long gap EA group had longer parenteral nutrition support and longer hospital stay and were significantly more likely to have complications both early post-operatively and before age 1 year compared with the non-long gap EA/TEF group. At 6 years, digestive complications were more frequent in long gap compared to non-long gap EA/TEF patients. Tracheomalacia was the only respiratory complication that differed between the groups. Spine deformation was less frequent in the long gap group. There were no differences between conservative and replacement groups at ages 1 and 6 years except feeding difficulties that were more common in the native esophagus group. Conclusions: Long gap strongly influenced digestive morbidity at age 6 years. (c) 2022 Elsevier Inc. All rights reserved.

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

Background and ObjectivesPatients with Hirschsprung's disease are at risk of developing Hirschsprung-associated enterocolitis, especially in the first 2 years of life. The pathophysiology of this inflammatory disease remains unclear, and intestinal dysbiosis has been proposed in the last decade. The primary objective of this study was to evaluate in a large cohort if Hirschsprung-associated enterocolitis was associated with alterations of fecal bacterial composition compared with HD without enterocolitis in different age groups.MethodsWe analyzed the fecal microbiota structure of 103 Hirschsprung patients from 3 months to 16 years of age, all of whom had completed definitive surgery for rectosigmoid Hirschsprung. 16S rRNA gene sequencing allowed us to compare the microbiota composition between Hirschsprung's disease patients with (HAEC group) or without enterocolitis (HD group) in different age groups (0–2, 2–6, 6–12, and 12–16 years).ResultsRichness and diversity increased with age group but did not differ between HD and HAEC patients, irrespective of the age group. Relative abundance of Actinobacteria was lower in HAEC than in HD patients under 2 years of age (−66%, P = 0.045). Multivariate analysis by linear models (MaAsLin) considering sex, medications, birth mode, breast-feeding, and the Bristol stool scale, as well as surgery parameters, highlighted Flavonifractor plautii and Eggerthella lenta, as well as Ruminococcus gnavus group, as positively associated with Hirschsprung-associated enterocolitis in the 0–2 years age group.ConclusionHirschsprung-associated enterocolitis was associated with features of intestinal dysbiosis in infants (0–2 years) but not in older patients. This could explain the highest rate of enterocolitis in this age group.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02857205, MICROPRUNG, NCT02857205, 02/08/2016.

In Hirschsprung’s disease (HSCR), postoperative course remains unpredictable. Our aim was to define predictive factors of the main postoperative complications: obstructive symptoms (OS) and Hirschsprung-associated enterocolitis (HAEC). In this prospective multicentre cohort study, samples of resected bowel were collected at time of surgery in 18 neonates with short-segment HSCR in tertiary care hospitals. OS and HAEC were noted during postoperative follow-up. We assessed the enteric nervous system and the intestinal epithelial barrier (IEB) in ganglionic segments by combining immunohistochemical, proteomic and transcriptomic approaches, with functional ex vivo analysis of motility and para/transcellular permeability. Ten HSCR patients presented postoperative complications (median follow-up 23.5 months): 6 OS, 4 HAEC (2 with OS), 2 diarrhoea (without OS/HAEC). Immunohistochemical analysis showed a significant 41% and 60% decrease in median number of nNOS-IR myenteric neurons per ganglion in HSCR with OS as compared to HSCR with HAEC/diarrhoea (without OS) and HSCR without complications ( p = 0.0095; p = 0.002, respectively). Paracellular and transcellular permeability was significantly increased in HSCR with HAEC as compared to HSCR with OS/diarrhoea without HAEC ( p = 0.016; p = 0.009) and HSCR without complications ( p = 0.029; p = 0.017). This pilot study supports the hypothesis that modulating neuronal phenotype and enhancing IEB permeability may treat or prevent postoperative complications in HSCR.

INTRODUCTION:Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.METHODS:A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).RESULTS:Of 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.CONCLUSION:The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.

OBJECTIVES:The objective of this study was to assess whether the laterality of congenital diaphragmatic hernia (CDH) was a prognostic factor for neonatal survival. METHODS:This was a cohort study using the French national database of the Reference Center for Diaphragmatic Hernias. The principal endpoint was survival after hospitalization in intensive care. We made a comparative study between right CDH and left CDH by univariate and multivariate analysis. Terminations and stillbirths were excluded from analyses of neonatal outcomes. RESULTS:A total of 506 CDH were included with 67 (13%) right CDH and 439 left CDH (87%). Rate of survival was 49% for right CDH and 74% for left CDH (P < .01). Multivariate analysis showed two factors significantly associated with mortality: thoracic herniation of liver (OR 2.27; IC 95% [1.07-4.76]; P = .03) and lung-to-head-ratio over under expected (OR 2.99; IC 95% [1.41-6.36]; P < .01). Side of CDH was not significantly associated with mortality (OR 1.87; IC 95% [0.61-5.51], P = .26). CONCLUSION:Rate of right CDH mortality is more important than left CDH. Nevertheless after adjusting for lung-to-head-ratio and thoracic herniation of liver, right CDH does not have a higher risk of mortality than left CDH.

Abstract Introduction Long-gap esophageal atresia (LGEA) leads to multifactorial morbidity. The aim of this study is to analyze midterm gastrointestinal and respiratory morbidities with special assessment of feeding difficulties. Secondary goals were to determine risk factors of malnutrition and the impact of surgical techniques on morbidity. Methods We conducted a prospective observational national study. Using French national database, we reviewed medical charts of every patient treated for LGEA between 2008 and 2010 in France. Phone contact was proposed to assess orality disorders using Functional Oral Intake Scale (FOIS). Patients with complete data were included. We compared conservative management with esophageal replacement. Results We included 31 cases with a median age of follow-up of 9 years [7–10]. Median z-score for weight was −0.97 [−3.52–2.50], Conclusion Midterm morbidity in LGEA concerns 80% of our population. Gastrointestinal morbidity includes mainly dysphagia, GER, and orality disorders. This study suggests that conservative management provides more orality disorders. Other studies are mandatory to confirm it.

Objective To identify predictors of and factors associated with the performance of antireflux surgery during the first year of life in children born with esophageal atresia. Study design All patients were included in a French registry for esophageal atresia. All 38 multidisciplinary French centers completed questionnaires about perinatal characteristics and one-year outcome for children born with esophageal atresia. Results Of 835 infants with esophageal atresia born in France from 2010 to 2014, 682 patients, excluding those with long-gap esophageal atresia, were included. Three patients had type I, 669 had type III, and 10 had type IV esophageal atresia. Fifty-three children (7.8%) received fundoplication during the first year of life. The median age at the time of the end-to-end esophageal anastomosis was 1.1 day (range 0-15). Multivariate analysis identified three perioperative factors that predicted the need for early antireflux surgery: anastomotic tension (P = .004), associated malformations (P = .019), and low birth weight (P = .018). Six other factors, measured during the first year of life, were associated with the need for antireflux surgery: gastroesophageal reflux (P < .001), anastomotic stricture (P < .001), gastrostomy (P < .001), acute life-threatening event (P = .002), respiratory complications (P = .045), and poor nutritional status (P < .001). Conclusions Gastroesophageal reflux disease, low birth weight, poor nutrition, and surgical anastomosis difficulties predicted the performance of antireflux surgery in the first year of life in infants with esophageal atresia.

Answer: Onchocerciasis. The elements corresponded to a visualization of adult worms (see Fig. 1A in the photo quiz). Each worm was surrounded by a dense cuticle with a discrete annealing, which was most patent on longitudinal sections. Under the cuticle, the muscle was thin and had 6 to 10

A 9-year-old female child was referred to the hospital by her general practitioner for an anterior abdominal nodule. On admission, clinical examination showed a painful hardened nodule not visible to the naked eye. The nodule was about 1 cm long and was localized 6 cm above the navel. The lesion

TVF is a simple and reproductive technique for UCF repair, with a high success rate. The risk of testicular atrophy has to be considered in case of associated undescended testis surgery, and careful attention must be given to the TVF dissection. This technique should be considered as first choice treatment for any UCF.

Objective With the replacement of karyotyping by chromosomal microarray (CMA) in invasive prenatal diagnosis, new challenges have arisen. By building a national database, we standardize the classification and reporting of prenatally detected copy number variants (CNVs) across Belgian genetic centers. This database, which will link genetic and ultrasound findings with postnatal development, forms a unique resource to investigate the pathogenicity of variants of uncertain significance and to refine the phenotypic spectrum of pathogenic and susceptibility CNVs. Methods The Belgian MicroArray Prenatal (BEMAPRE) consortium is a collaboration of all genetic centers in Belgium. We collected data from all invasive prenatal procedures performed between May 2013 and July 2016. Results In this three-year period, 13 266 prenatal CMAs were performed. By national agreement, a limited number of susceptibility CNVs and no variants of uncertain significance were reported. Added values for using CMA versus conventional karyotyping were 1.8% in the general invasive population and 2.7% in cases with an ultrasound anomaly. Of the reported CNVs, 31.5% would have remained undetected with non-invasive prenatal test as the first-tier test. Conclusion The establishment of a national database for prenatal CNV data allows for a uniform reporting policy and the investigation of the prenatal and postnatal genotype-phenotype correlation.

INoEA is the International Network of Esophageal Atresia and consists of a broad spectrum of pediatric specialties and patient societies. The working group on long-gap esophageal atresia (LGEA) set out to develop guidelines regarding the definition of LGEA, the best diagnostic and treatment strategies, and highlight the necessity of experience and communication in the management of these challenging patients. Review of the literature and expert discussion concluded that LGEA should be defined as any esophageal atresia (EA) that has no intra-abdominal air, realizing that this defines EA with no distal tracheoesophageal fistula (TEF). LGEA is considerably more complex than EA with distal TEFs and should be referred to a center of expertise. The first choice is to preserve the native esophagus and pursue primary repair, delayed primary anastomosis, or traction/growth techniques to achieve anastomosis. A cervical esophagostomy should be avoided if possible. Only if primary anastomosis is not possible, replacement techniques should be used. Jejunal interposition is proposed as the best option among the major EA centers. In light of the infrequent occurrence of LGEA and the technically demanding techniques involved to achieve esophageal continuity, it is strongly advised to develop regional or national centers of expertise for the management and follow-up of these very complex patients.

Maternal uniparental disomy of chromosome 14 (upd(14)mat) is responsible for a Prader-Willi-like syndrome with precocious puberty. Although upd(14) is often hypothesized to result from trisomy rescue mechanism, T14 cell lines are usually not found with postnatal cytogenetic investigations. We report the coexistence of both chromosomal abnormalities in a 15-year-old girl.

Introduction. Meckel's diverticulum is a common malformation in children, usually asymptomatic, with complications in only 20% of cases. Exceptionally, a tumor can develop in Meckel's diverticulum in children, particularly Burkitt's lymphoma; in adults it can develop into a gastrointestinal stromal tumor, a leiomyosarcoma, or a neuroendocrine tumor such as a carcinoid tumor. The diagnosis of inflammatory pseudotumor following an insidious perforation is rare.Observation. We report the case of a 14-month-old boy who presented with fever, asthenia, food refusal, and digestive complaints such as vomiting and tender abdomen suggesting appendicitis. Computed tomography showed an ileal mass of 3 cm in diameter, which led to the suspicion of Burkitt's lymphoma. Laparoscopy showed Meckel's diverticulum with a mass of 3 x 2.8 x 2 cm. Histological examination confirmed the diagnosis of Meckel's diverticulum with gastric heterotopia and showed a proliferation of spindle cells in a myxoid background, with an inflammatory infiltrate made of lymphocytes and plasmocytes. Immunostaining ruled out a malignant tumor. The diagnosis of an inflammatory pseudotumor developing on a Meckel diverticulum with gastric heterotopias was made. The outcome was favorable after surgical resection.Conclusion. While perforation of a Meckel diverticulum with gastric heterotopia is a common finding, the discovery of an inflammatory pseudotumor following a perforation is rare; the differential diagnosis should include Burkitt's lymphoma. (C) 2016 Elsevier Masson SAS. All rights reserved.

Several areas of the management of children with esophageal atresia (EA) remain controversial. To investigate practice variation in the management of EA in France. A survey was sent to each of the thirty-eight centers that treat EA in France. Thirty-five centers (92%) responded. If EA has been suspected prenatally, most centers would recommend prenatal MRI (82%). At birth, selective (symptoms or EA suspected prenatally) or systematic diagnostic test with a nasogastric tube was recommended by 30% and 70% of centers respectively. Preoperative echocardiography was almost always recommended (88%). Routine per or preoperative tracheobronchosopy was recommended by 64% of centers. For EA with distal fistula, 72% of centers recommended thoracotomy, whereas 27% would use thoracoscopy in selected cases. Although 94% of centers recommended placement of a nasogastric tube through the anastomosis, duration and time to initiate enteral or oral feeding were highly diverse. Routine post-operative imaging study of the esophagus was recommended by 64% of centers. The most commonly recommended operation for “long-gap” EA, was delayed anastomosis (88%). If delayed anastomosis was still unachievable, most centers would recommend esophageal replacement (39%) rather than gastric interposition (Spitz) or growth by traction (Foker) (6% and 9% respectively). The preferred technique for esophageal replacement was colonic interposition (73%). This national survey demonstrates that variations exist in the management of EA in France. Variations may represent legitimate decision for varying clinical situation; however it may indicate a lack of clear evidence to guide management or represent heterogeneous standards of care.

To describe current management and mid-term outcomes for patients with Long Gap Esophageal Atresia (LGEA) in France. We retrospectively analyzed the whole medical charts of all LGEA cases identified in the French Esophageal Atresia (EA) Registry and managed between 2008 and 2010. We included all infants born with an EA in whom primary anastomosis could not be achieved before 1 month of life because of the length of the gap. Forty-nine children were included, 37 type I, 5 type II, 6 type III and 1 type IV according to Ladd's classification. The median gestational age and weight at birth were respectively 36 weeks (26.8–41) and 2060 g (550–3740). A surgical gastrostomy was performed in all cases, combined with closure of tracheoesophageal fistula (n = 8), esophagostomy (n = 4) or Foker's technique (n = 2). Twenty children experienced a complication of whom two died. EA repair was performed either by delayed anastomosis (n = 33, 70%) or esophageal replacement (n = 14, 30%) at a median age and weight of 87 days (19–454) and 4250 g (2400–8300) respectively. The esophageal replacement techniques were gastric transposition (n = 8), gastric tube (n = 3), colon interposition (n = 2) and Collis-Nissen procedure (n = 1). Ninety complications were reported in thirty-eight patients (81%) including 22 anastomotic leaks and 28 anastomotic strictures. At the end of the follow up, the mortality rate was 12%. Most of the french surgeons management strategies favored a delayed anastomosis for LGEA. Despite a good survival rate of 88%, the morbidity remained high and diverse, highlighting the need for multidisciplinary management.

Background: The background is to review our experience with laparoscopic repair of congenital duodenal atresia or stenosis (CDAS) and compare postoperative outcome with a group control of laparotomy repair.Methods: Retrospective chart review of all cases of CDAS undergoing laparoscopic surgery at our institution between July 2013 and May 2014 and comparison with a group control of open operation performed between 2007 and 2010. Data were compared using Fisher's exact test for qualitative values and Mann-Whitney test for quantitative values. P values less than 0,05 were considered statistically significant.Results: Ten consecutive cases were identified in laparoscopic group (7 duodenoduodenostomy and 3 duodenojejunostomy) and 19 cases in laparotomy group (16 duodenoduodenostomy and 3 web excision). Median birth weight was lower in laparoscopic group (2125 grams Vs 2777 grams p = 0.04). In laparoscopic group, there was no conversion and no intraoperative complication. Median duration of surgery was 90 minutes (80-150). In both groups, the surgical morbidity rate was 10%. Median time to initiation of oral feeding was significatively shorter in laparotomy group (8 days Vs 4 p=0.009). Median time to full oral feeding and length of stay were shorter in laparotomy but not statistically different. (36 days Vs 16,5 p = 0.14 and 45,5 days Vs 25,5 p = 0.09 respectively) After a median follow up of 149,5 days (24-355) in laparoscopic group, 8 children had a full oral intake. Five children had a weight below the 10th percentile.Conclusion: The laparoscopic approach for CDAS is safe and reproducible with outcomes similar to open repair even in the beginning of a learning curve for pediatric surgeons with appropriate laparoscopic skills. In this small series, laparoscopy did not appear to decrease time to full oral intake or length of stay. Larger studies are suggested to provide more conclusive results. (C) 2015 Elsevier Inc. All rights reserved.