Complications after Heller myotomy in children: a national multicenter study on the impact of prior endoscopic dilatation and identification of risk factors.

BACKGROUND: Although esophageal achalasia has been historically treated by Heller myotomy, endoscopic esophageal dilatations are nowadays often the first-line treatment in children. The aim was to assess whether performing an endoscopic dilatation before a Heller myotomy is associated with higher risks of esophageal perforation in children. METHODS: A retrospective multicentric study was performed, including children that underwent a Heller myotomy (2000-2022, 10 centers). Two groups were compared based on the history of previous dilatation before myotomy. Outcomes esophageal perforation (intra-operative or secondary) and post-operative complications requiring surgery (Clavien-Dindo III). Statistics Comparisons using contingency tables or Kruskal-Wallis when appropriate. Statistical significance: p-value < 0.05. RESULTS: A Heller myotomy was performed in 77 children (median age: 11.8 years), with prior endoscopic dilatation in 53% (n = 41). A laparoscopic approach was used in 90%, with associated fundoplication in 95%. Esophageal perforation occurred in 19% of children (n = 15), including 12 patients with intra-operative mucosal tear and 3 with post-operative complications related to an unnoticed esophageal perforation. Previous endoscopic dilatation did not increase the risk of esophageal perforation (22% vs 17%, OR: 1.4, 95%CI: 0.43-4.69). Post-operative complications occurred in 8% (n = 6), with similar rates regardless of prior endoscopic dilatation. Intra-operative mucosal tear was the only risk factor for post-operative complications, increasing the risk of complications from 5 to 25% (OR: 6.89, 95%CI: 1.38-31.87). CONCLUSIONS: Prior endoscopic dilatations did not increase the risk of esophageal perforation or postoperative complications of Heller myotomy in this cohort of children with achalasia. Mucosal tear was identified as a risk factor for post-operative complications.

Long-Term Functional Outcomes of an Anorectal Malformation French National Cohort.

OBJECTIVES: The present study aimed to assess long-term functional outcomes of children with anorectal malformations (ARMs) across a network of expert centers in France. METHODS: Retrospective cross-sectional study of patients ages 6-30 years that had been surgically treated for ARM. Patient and ARM characteristics (eg, level, surgical approach) and functional outcomes were assessed in the different age groups. RESULTS: Among 367 patients, there were 155 females (42.2%) and 212 males (57.8%), 188 (51.2%) cases with, and 179 (48.8%) higher forms without, perineal fistula. Univariate and multivariate statistical analyses with logistic regression showed correlation between the level of the rectal blind pouch and voluntary bowel movements (odds ratio [OR] = 1.84 [1.31-2.57], P < 0.001), or soiling (OR = 1.72 [1.31-2.25], P < 0.001), which was also associated with the inability to discriminate between stool and gas (OR = 2.45 [1.28-4.67], P = 0.007) and the presence of constipation (OR = 2.97 [1.74-5.08], P < 0.001). Risk factors for constipation were sacral abnormalities [OR = 2.26 [1.23-4.25], P = 0.01) and surgical procedures without an abdominal approach (OR = 2.98 [1.29-6.87], P = 0.01). Only the holding of voluntary bowel movements and soiling rates improved with age. CONCLUSION: This cross-sectional study confirms a strong association between anatomical status and functional outcomes in patients surgically treated for ARM. It specifically highlights the need for long-term follow-up of all patients to help them with supportive care.

Pathophysiological adaptations of resistance arteries in rat offspring exposed in utero to maternal obesity is associated with sex-specific epigenetic alterations.

BACKGROUND/OBJECTIVES: Maternal obesity impacts vascular functions linked to metabolic disorders in offspring, leading to cardiovascular diseases during adulthood. Even if the relation between prenatal conditioning of cardiovascular diseases by maternal obesity and vascular function begins to be documented, little is known about resistance arteries. They are of particular interest because of their specific role in the regulation of local blood flow. Then our study aims to determine if maternal obesity can directly program fetal vascular dysfunction of resistance arteries, independently of metabolic disorders. METHODS: With a model of rats exposed in utero to mild maternal diet-induced obesity (OMO), we investigated third-order mesenteric arteries of 4-month old rats in absence of metabolic disorders. The methylation profile of these vessels was determined by reduced representation bisulfite sequencing (RRBS). Vascular structure and reactivity were investigated using histomorphometry analysis and wire-myography. The metabolic function was evaluated by insulin and glucose tolerance tests, plasma lipid profile, and adipose tissue analysis. RESULTS: At 4 months of age, small mesenteric arteries of OMO presented specific epigenetic modulations of matrix metalloproteinases (MMPs), collagens, and potassium channels genes in association with an outward remodeling and perturbations in the endothelium-dependent vasodilation pathways (greater contribution of EDHFs pathway in OMO males compared to control rats, and greater implication of PGI2 in OMO females compared to control rats). These vascular modifications were detected in absence of metabolic disorders. CONCLUSIONS: Our study reports a specific methylation profile of resistance arteries associated with vascular remodeling and vasodilation balance perturbations in offspring exposed in utero to maternal obesity, in absence of metabolic dysfunctions.

Risk Factors of Early Mortality and Morbidity in Esophageal Atresia with Distal Tracheoesophageal Fistula: A Population-Based Cohort Study.

OBJECTIVE: To identify the risk factors for early mortality and morbidity in a population with distal esophageal atresia (EA)-tracheoesophageal fistula. STUDY DESIGN: Cohort study from a national register. Main outcomes and measures included early mortality, hospital length of stay (LoS), need for nutritional support at 1 year of age as a proxy measure of morbidity, and complications during the first year of life. RESULTS: In total, 1008 patients with a lower esophageal fistula were included from January 1, 2008, to December 31, 2014. The survival rate at 3 months was 94.9%. The cumulative hospital LoS was 31.0 (17.0-64.0) days. Multivariate analysis showed that intrahospital mortality at 3 months was associated with low birth weight (OR 0.52, 95% CI [0.38-0.72], P < .001), associated cardiac abnormalities (OR 6.09 [1.96-18.89], P = .002), and prenatal diagnosis (OR 2.96 [1.08-8.08], P = .034). LoS was associated with low birth weight (-0.225 ± 0.035, P < .001), associated malformations (0.082 ± 0.118, P < .001), surgical difficulties (0.270 ± 0.107, P < .001), and complications (0.535 ± 0.099, P < .001) during the first year of life. Predictive factors for dependency on nutrition support at 1 year of age were complications before 1 year (OR 3.28 [1.23-8.76], P < .02) and initial hospital LoS (OR 1.96 [1.15-3.33], P < .01). CONCLUSIONS: EA has a low rate of early mortality, but morbidity is high during the first year of life. Identifying factors associated with morbidity may help to improve neonatal care of this population.

Concomitant gastrostomy tube insertion during laparoscopic Nissen fundoplication for gastro-esophageal reflux disease: analysis of risk factors for fundoplication failure.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) and gastrostomy tube (GT) placement may be performed concomitantly in children with gastro-esophageal reflux disease (GERD) and failure to thrive. We aimed to evaluate the rate and risk factors for LNF failure in children undergoing concomitant LNF/GT. METHODS: A retrospective multi-institutional cohort study was conducted, reviewing patients that underwent LNF (2005-2014). Data collected included patient demographics, comorbidities, and type of GT (laparoscopy- or endoscopy-assisted). The primary outcome measure was LNF failure. Data was compared using contingency tables or Mann-Whitney tests, when appropriate. An exploratory analysis by Kaplan-Meier survival and Cox proportional hazards analysis was performed to determine predictors of time to LNF failure after LNF/GT. RESULTS: Of 189 children that underwent LNF, 99 (52%) had a concomitant GT (55% laparoscopy-, 45% endoscopy-assisted). LNF failed in 15% after LNF/GT and in 17% after LNF alone (p = 0.84), at a median age of 23 months (IQR 8-41). Using univariate analysis, we found that a younger age at the time of surgery (p = 0.05), prematurity (p = 0.0018), esophageal atresia (p = 0.01), and endoscopy-assisted GT (p = 0.02) were potential predictors of LNF failure after LNF/GT. After multivariate regression analysis, prematurity (p = 0.007) remained significantly associated with LNF failure after LNF/GT. No predictive factors for LNF failure after LNF alone were identified. CONCLUSIONS: Concomitant GT insertion and LNF is a common practice, as half of the children that undergo LNF also received GT insertion. Children born preterm or with esophageal atresia comprise a fragile population at high-risk of LNF failure after LNF/GT. Prospective, multicentric studies are needed to evaluate the best GT technique to use in children undergoing LNF.

Predictors of the Performance of Early Antireflux Surgery in Esophageal Atresia.

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.

What prenatal ultrasound features are predictable of complex or vanishing gastroschisis? A retrospective study.

OBJECTIVE: To evaluate prenatal ultrasound parameters as prognostic factors for complex and vanishing gastroschisis. METHODS: Retrospective multicentre study of 200 gastroschisis over 13 years (2000-2013). Collection of prenatal ultrasound evaluation on maternal and fetal growth parameters, intra- and extra-abdominal bowel and stomach dilation, abdominal wall defect diameter and changes in bowel appearance. Correlation of these factors with the presence of mechanical intestinal complications at birth, named 'complex gastroschisis'. RESULTS: Fifty-two patients (26%) had complex gastroschisis (CG), including ten vanishing gastroschisis. The presence of intra-abdominal bowel dilation at the second (T2) or third (T3) trimester ultrasound was predictive for CG, with odds ratios at 6.69 (95%CI 2.41-18.55) and 4.72 (95%CI 2.16-10.28), respectively, with a cut-off value at the last examination of >19 mm. A small abdominal wall defect diameter was also predictive for CG, with cut-off values of <9.2 mm at T2 and <12.5 mm at T3. Vanishing gastroschisis recorded earlier intra-abdominal bowel dilation diagnosis, associated with a small wall defect and no extra-abdominal dilation. CONCLUSION: Intra-abdominal bowel dilation and a small abdominal wall defect diameter accurately predict CG and could be a first sign of vanishing gastroschisis when they occur early. © 2016 John Wiley & Sons, Ltd.

DPY19L2 deletion as a major cause of globozoospermia.

Globozoospermia, characterized by round-headed spermatozoa, is a rare (< 0.1% in male infertile patients) and severe teratozoospermia consisting primarily of spermatozoa lacking an acrosome. Studying a Jordanian consanguineous family in which five brothers were diagnosed with complete globozoospermia, we showed that the four out of five analyzed infertile brothers carried a homozygous deletion of 200 kb on chromosome 12 encompassing only DPY19L2. Very similar deletions were found in three additional unrelated patients, suggesting that DPY19L2 deletion is a major cause of globozoospermia, given that 19% (4 of 21) of the analyzed patients had such deletion. The deletion is most probably due to a nonallelic homologous recombination (NAHR), because the gene is surrounded by two low copy repeats (LCRs). We found DPY19L2 deletion in patients from three different origins and two different breakpoints, strongly suggesting that the deletion results from recurrent events linked to the specific architectural feature of this locus rather than from a founder effect, without fully excluding a recent founder effect. DPY19L2 is associated with a complete form of globozoospermia, as is the case for the first two genes found to be associated with globozoospermia, SPATA16 or PICK1. However, in contrast to SPATA16, for which no pregnancy was reported, pregnancies were achieved, via intracytoplasmic sperm injection, for two patients with DPY19L2 deletion, who then fathered three children.

Staged gastroschisis closure using Alexis wound retractor: first experiences.

INTRODUCTION: The aim of this study is to analyze the effectiveness of an Alexis wound retractor (AWR) device for staged gastroschisis closures. PATIENTS AND METHODS: AWR device was used to cover unreduced viscera of a gastroschisis when primary abdominal wall closure was not convenient. The eviscerated organs were covered with one of the two spring-loaded rings of the AWR inserted underneath the abdominal wall. Gradual reduction was guaranteed through careful traction on the external ring. We retrospectively analyzed the prenatal, post-natal and operative data of the first patients treated with AWR and report their post-operative outcomes. RESULTS: The AWR device was used for staged closure in eight cases. Complete reduction and fascial closure were performed at a median of 3.5 ± 1.6 days. Ventilatory support was necessary for 4.0 ± 3 days and full parenteral feeds for 7.5 ± 6.1 days after fascial closure. Median full enteral feeding was observed at 18 ± 12.5 days after closure allowing discharge in a median period of 30.5 ± 15.6 days after closure. CONCLUSION: The AWR device is not only a safe and efficient silo for a progressive reduction of severe gastroschisis, but also an interesting tool for continuous stretching leading to an increase of the peritoneal cavity volume, enhancing the equalizing of the viscero-abdominal disproportion.

Congenital Diaphragmatic Eventration: Should we Maintain Surgical Treatment? A Retrospective Multicentric Cohort Study.

BACKGROUND: The aims of this study were to describe the characteristics of children with congenital diaphragmatic eventration (CDE) and compare the outcomes of surgical and conservative treatment of pediatric CDE in France. METHODS: Retrospective study on cohort data conducted in 22 paediatric surgery departments, including patients less than 16 years of age diagnosed with CDE between 2010 and 2021. Patients with surgical or conservative treatment were compared. RESULTS: 139 patients were included, with a median age of 8 [1-16] months. CDE occurred in boys in 68.3% and was right-sided in 66.7% of the cases. Indication for treatment depended essentially on respiratory symptoms and level of the diaphragmatic dome. The initial treatment was a surgical, with a diaphragmatic plication, in 87 cases (62%) and conservative, consisting of clinical follow-up in 52 children (38%). Of the latter, 25 children underwent surgery secondarily. Intra- and early post-operative complications occurred in 32 children (29%) and eventration recurrence in 8 children (7%). With a median follow-up of 28 months, the median level of diaphragmatic dome improved from the 6th to the 9th back rib, and the rate of respiratory symptoms decreased from 64% to 14% in the overall cohort of patients. CONCLUSIONS: Diaphragmatic plication is effective in symptomatic patients with a dome level above the 6th posterior rib, but is associated with a 29% complication rate and 7% of recurrence. CLINICALTRIALS: NCT04862494, April 28, 2021. LEVEL OF EVIDENCE: level III treatment study.

Factors Associated With Weight Loss After Laparoscopic Adjustable Gastric Banding in Adolescents With Severe Obesity.

Childhood obesity is associated with many comorbidities. Bariatric surgery is known to be efficient for reducing weight in adolescents. Objectives: The primary outcome was to identify somatic or psychosocial factors associated with success at 24 months after a laparoscopic adjustable gastric banding (LAGB) procedure in our cohort of adolescents with severe obesity. Secondary endpoints were to describe weight loss outcomes, comorbidity resolution, and complications. Methods: We have retrospectively reviewed medical records of patients who had LAGB placed between 2007 and 2017. Factors associated with success at 24 months after LAGB were researched, with success being defined as positive percentage of excess weight loss (%EWL) at 24 months. Results: Forty-two adolescents underwent a LAGB procedure, the mean %EWL was 34.1% at 24 months, with improvement in most comorbidities and without major complications. Having lost weight before surgery was associated with success, whereas a high body mass index at surgery was associated with a higher risk of failure. No other factor was found to be associated with success. Conclusion: Comorbidities mostly improved 24 months after LAGB and no major complication occurred. Having lost weight before surgery was associated with a successful surgery, whereas a high body mass index at surgery increases the risk of failure.

Efficient pathway for men fertility preservation in testicular cancer or lymphoma: a cross-sectional study of national 2018 data.

BACKGROUND: In 15-49 years-old men, the main cancers are testicular cancer (TC) and lymphomas (L): freezing of ejaculated sperm is primarily used for male fertility preservation (FP) before cancer treatment. Our objective was to analyze the French FP rate in 15-49 years-old men diagnosed with TC or L in 2018. We designed a national descriptive cross-sectional study of sperm banking rate in men with a diagnosis of TC, Hodgkin L (HL) or non-Hodgkin L (NHL). From the French National Cancer Institute (INCa) 2018 data, we extracted the estimated incidence of TC and L in metropolitan France. From the 2018 activity report of CECOS network (Centers for Study and Banking of Eggs and Sperm), we extracted the number of men with TC or L who banked ejaculated sperm. We estimated the proportion of 15-49 years-old men diagnosed with TC or L who banked sperm. RESULTS: Among 15-49 years-old men, INCa estimated 38,048 new cancer diagnoses in metropolitan France in 2018: 2,630 TC and 3,913 L (943 HL and 2,970 NHL). The CECOS network provided data from 26/27 metropolitan centers (96% response rate): 1,079 sperm banking for men with TC, 375 for HL and 211 for NHL. We estimated that the 2018 sperm banking rate in France was 41% for TC, 40% for HL, and 7% for NHL. CONCLUSIONS: To our knowledge, our paper is the first cross-sectional study with multicenter and national data analyzing FP rate in cancer men: it suggests an efficient pathway for men to FP before cancer treatment, compared to previously published studies. Although sperm banking rate in 15-49 years-old men could definitely be improved, further studies should evaluate the information given to patients before gonadotoxic treatments, the factors associated with the absence of sperm banking and whether this lack of referral induces a loss of chance for these men.

RéSUMé: CONTEXTE: Chez les hommes de 15 à 49 ans, les principaux cancers sont le cancer du testicule (CT) et les lymhomes (L): la congélation de spermatozoïdes éjaculés est utilisée en première intention pour leur préservation de fertilité (PF) avant traitement du cancer. Notre objectif était d'analyser le taux de PF chez les hommes de 15 à 49 ans diagnostiqués avec un CT ou un L en 2018 en France. Nous avons réalisé une étude nationale transversale descriptive du taux de congelation de spermatozoïdes chez les hommes âgés de 15 à 49 ans diagnostiqués avec un CT, un L de Hodgkin (LH) ou un L non-Hodgkinien (LNH). A partir des données de l'Institut National du Cancer (INCa) de 2018, nous avons extrait l'incidence estimée de CT et de L en France métropolitaine. A partir des données du bilan d'activité 2018 de la Federation Française des CECOS (Centre d'Etude et de Conservation des Oeufs et du Sperme), nous avons extrait le nombre d'hommes avec un CT ou un L qui ont congelé leurs spermatozoïdes. Nous avons enfin estimé la proportion d'hommes de 15 à 49 ans diagnostiqués avec un CT ou un L qui ont congelé leurs spermatozoïdes. RéSULTATS: Chez les hommes de 15 à 49 ans, l'INCa a estimé en 2018 38 048 nouveaux cas de cancers diagnostiqués en France métropolitaine en 2018: 2 630 CT et 3 913 L (943 LH et 2 970 LNH). Le réseau des CECOS a produit les résultats issus de 26/27 centres métropolitains (taux de réponse de 96%): 1 079 congélations de sperme pour des hommes atteints de CT, 375 pour LH et 211 pour LNH. Nous avons estimé que le taux de congelation de spermatozoïdes de 2018 en France était de 41% pour le CT, 40% pour le LH et 7% pour le LNH. CONCLUSIONS: A notre connaissance, notre travail est la première étude transversale multicentrique de données nationales analysant le taux de PF chez les hommes atteints de cancer: il suggère un parcours patient efficace pour la PF des hommes avant traitement d'un cancer, par rapport aux études précédemment publiées. Bien que le taux de PF chez les hommes puisse certainemen être amélioré, des études futures devraient évaluer l'information donnée aux patients avant traitement gonadotoxique, les facteurs associés à l'absence de PF et si le défaut d'adressage au CECOS induit un perte de chance pour ces hommes. MOTS-CLéS: Chimiothérapie, Radiothérapie, Oncofertiité, Azoospermia, Paternité.

Tolerance and efficacy of preventive gastrostomy feeding in pediatric oncology.

BACKGROUND: Malnutrition in pediatric oncology remains underestimated, although having a negative impact on outcome. Enteral nutrition (EN) using percutaneous endoscopic gastrostomy (PEG) may prevent or reverse malnutrition consequences. We aimed to evaluate both efficacy and safety of early EN during tumors treatment in children. PROCEDURES: Medical records of pediatric patients having a PEG tube inserted between 1995 and 2009 were retrospectively reviewed. We compared type and incidence of complications in Group 1, including 74 patients suffering from cancer, and control Group 2, including 57 patients with neurological impairment. Efficacy of EN was evaluated through nutritional parameters [Z-scores weight for height (W/H) and height for age (H/A)], post-operative complications and relapse rates. Statistical significance was set for P < 0.05. RESULTS: PEG tolerance was similar in both groups, as shown by comparable complication rates (62% vs. 76%, NS). EN allowed improvement or stabilization of Z-score W/H in 76% of oncologic patients. The final height loss was lower (-0.5 vs. -1.2 SD of Z-scores H/A) when EN was started at the beginning of the oncologic treatment. In bone tumors, EN prevented weight loss during chemotherapy, and tended to lessen surgical complications, relapses and deaths. CONCLUSIONS: Early gastrostomy feeding represents a relatively safe way to prevent malnutrition in children with cancer, and might play a role in bone tumors oncological outcome. Further prospective studies are needed to confirm these results and assess the impact of EN and PEG on quality of life.

Different Fecal Microbiota in Hirschsprung's Patients With and Without Associated Enterocolitis.

Background and Objectives: Patients 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. Methods: We 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). Results: Richness 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. Conclusion: Hirschsprung-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 Registration: https://clinicaltrials.gov/ct2/show/NCT02857205, MICROPRUNG, NCT02857205, 02/08/2016.

Nutritional status at age 1 year in patients born with esophageal atresia: A population-based, prospective cohort study.

Objective: Despite recent progress in caring for patients born with esophageal atresia (EA), undernutrition and stunting remain common. Our study objective was to assess nutritional status in the first year after birth with EA and to identify factors associated with growth failure. Study design: We conducted a population-based study of all infants born in France with EA between 2010 and 2016. Through the national EA register, we collected prenatal to 1 year follow-up data. We used body mass index and length-for-age ratio Z scores to define patients who were undernourished and stunted, respectively. Factors with P < 0.20 in univariate analyses were retained in a logistic regression model. Results: Among 1,154 patients born with EA, body mass index and length-for-age ratio Z scores at 1 year were available for about 61%. Among these, 15.2% were undernourished and 19% were stunted at the age of 1 year. There was no significant catch-up between ages 6 months and 1 year. Patients born preterm (41%), small for gestational age (17%), or with associated abnormalities (55%) were at higher risk of undernutrition and stunting at age 1 year (P < 0.05). Neither EA type nor surgical treatment was associated with growth failure. Conclusion: Undernutrition and stunting are common during the first year after birth in patients born with EA. These outcomes are significantly influenced by early factors, regardless of EA type or surgical management. Identifying high-risk patient groups with EA (i.e., those born preterm, small for gestational age, and/or with associated abnormalities) may guide early nutritional support strategies.

Anti-reflux surgery in children with congenital diaphragmatic hernia: A prospective cohort study on a controversial practice.

INTRODUCTION: Gastro-esophageal reflux disease (GERD) is the most frequent long-term morbidity of congenital diaphragmatic hernia (CDH) survivors. Performing a preventive fundoplication during CDH repair remains controversial. This study aimed to: (1) Analyze the variability in practices regarding preventive fundoplication; (2) Identify predictive factors for fundoplication. (3) Evaluate the impact of preventive fundoplication on gastro-intestinal outcomes in children with a CDH patch repair; METHODS: This prospective multi-institutional cohort study (French CDH Registry) included CDH neonates born in France between January 1st, 2010-December 31st, 2018. Patch CDH was defined as need for synthetic patch or muscle flap repair. Main outcome measures included need for curative fundoplication, tube feed supplementation, failure to thrive, and oral aversion. RESULTS: Of 762 CDH neonates included, 81 underwent fundoplication (10.6%), either preventive or curative. Median follow-up was 3.0 years (IQR: 1.0-5.0). (1) Preventive fundoplication is considered in only 31% of centers. The rates of both curative fundoplication (9% vs 3%, p = 0.01) and overall fundoplication (20% vs 3%, p < 0.0001) are higher in centers that perform preventive fundoplication compared to those that do not. (2) Predictive factors for preventive fundoplication were: prenatal diagnosis (p = 0.006), intra-thoracic liver (p = 0.005), fetal tracheal occlusion (p = 0.002), CDH-grade C-D (p < 0.0001), patch repair (p < 0.0001). After CDH repair, 8% (n = 51) required curative fundoplication (median age: 101 days), for which a patch repair was the only independent predictive factors identified upon multivariate analysis. (3) In neonates with patch CDH, preventive fundoplication did not decrease the need for curative fundoplication (15% vs 11%, p = 0.53), and was associated with higher rates of failure to thrive (discharge: 81% vs 51%, p = 0.03; 6-months: 81% vs 45%, p = 0.008), tube feeds (6-months: 50% vs 21%, p = 0.02; 2-years: 65% vs 26%, p = 0.004), and oral aversion (6-months: 67% vs 37%, p = 0.02; 1-year: 71% vs 40%, p = 0.03). CONCLUSIONS: Children undergoing a CDH patch repair are at high risk of requiring a curative fundoplication. However, preventive fundoplication during a patch repair does not decrease the need for curative fundoplication and is associated with worse gastro-intestinal outcomes in children. LEVEL OF EVIDENCE: II - Prospective Study.

Lentiviral vectors that express UGT1A1 in liver and contain miR-142 target sequences normalize hyperbilirubinemia in Gunn rats.

BACKGROUND & AIMS: Crigler-Najjar type 1 (CN-I) is an inherited liver disease caused by an absence of bilirubin-uridine 5'-diphosphate-glucuronosyltransferase (UGT1A1) activity. It results in life-threatening levels of unconjugated bilirubin, and therapeutic options are limited. We used adult Gunn rats (an animal model of the disease) to evaluate the efficiency of lentiviral-based gene therapy to express UGT1A1 in liver. METHODS: Gunn rats were given intraportal injections of VSVG-pseudotyped lentiviral vectors that encode UGT1A1 under the control of a liver-specific transthyretin promoter (mTTR.hUGT1A1); this vector does not contain target sequences for miR-142, a microRNA that is expressed specifically in hematopoietic cells. Rats were also injected with the vector mTTR.hUGT1A1.142T, which contains 4 copies of the miR-142 target sequences; its messenger RNA should be degraded in antigen-presenting cells. Bilirubinemia was monitored, and the presence of transduced hepatocytes was analyzed by quantitative polymerase chain reaction. Vector expression was tested in vitro in rat hematopoietic cells. RESULTS: In Gunn rats, bilirubin levels normalized 2 weeks after administration of mTTR.hUGT1A1. However, hyperbilirubinemia resumed 8 weeks after vector administration, concomitant with the induction of an immune response. In contrast, in rats injected with mTTR-UGT1A1.142T, bilirubin levels normalized for up to 6 months and transduced cells were not eliminated. CONCLUSIONS: Lentiviral vectors that express UGT1A1 reduce hyperbilirubinemia in immunocompetent Gunn rats for at least 6 months. The immune response against virally expressed UGT1A1 can be circumvented by inclusion of miR-142 target sequences, which reduce vector expression in antigen-presenting cells. This lentiviral-based gene therapy approach might be developed to treat patients with CN-I.

[The virtual slide: a new tool for the External Quality Control for the spermatozoid assessment morphology]. / La lame virtuelle : un nouvel outil pour le contrôle externe de qualité de l'analyse morphologique des spermatozoïdes.

As part of the accreditation procedures, External Quality Control (EQC) must be performed for all biological determinations. In the exploration of male infertility, the spermocytogram is very important because it is often used as first line and an error of interpretation may have dramatic consequences. Alongside the EQC which usely consists of carrying out preparation slides (stained or not), we tested the use of a slide scanned from a stained specimen ("virtual slide"). All participants (n = 57) received a sample of the following supports: an unstained slide, a stained one and a virtual slide, all of them from a single human ejaculate. The required tests were the proportion of typical forms of spermatozoa and the degree of teratozoospermia using the Multiple Abnomalities Index (MAI) according to David's criteria. Results showed that for the two examinations, the dispersion of results remains similar regardless of the support. Furthermore, results seemed no to be influenced by the staining technique. This indicates that the discrepancy between results came from the quality of the observer. Moreover, the numerical values of half the participants were situated in the interval mean of ±â€Š30% for the evaluation of typical forms and ±â€Š15% for MAI. We recommend the virtual slide for EQC spermocytogram to evaluate and improve the reading ability. In addition, we propose to retain an interval of acceptability of ±â€Š30% for the evaluation of typical forms and ±â€Š15% for MAI.

Fertility preservation and sperm donation in transgender individuals: The current situation within the French CECOS network.

BACKGROUND: Many studies reported that reproductive desire could be high among transgender individuals. In France, fertility preservation and sperm donation were very little proposed to transgender individuals until recently, mainly because the Bioethics Law allows the use of assisted reproductive technologies only in infertile couples and prohibits surrogacy. OBJECTIVES: To evaluate the distribution of care on the French territory concerning fertility preservation and sperm donation in transgender individuals. MATERIALS AND METHODS: A multicentric national survey was carried out between January 2019 and October 2020 in 28 assisted reproductive technology centres of the French CECOS (Centres d'Etudes et de Conservation des Oeufs et du Sperme) network. Each centre was questioned to find out how many transgender individuals came, were informed and cared for fertility preservation and sperm donation. RESULTS: Concerning fertility preservation, 71.4% of centres received transgender individuals and performed gamete cryopreservation; 581 transgender individuals consulted for fertility preservation. Transgender women were more likely to desire (p < 0.0001) and achieve (p < 0.0001) fertility preservation than transgender men. Concerning sperm donation in couples including a transgender man, 68% of centres offer the complete course from the first consultation to the completion of the assisted reproductive technology cycles; 122 offsprings have been conceived with sperm donation in couples including a transgender man since 1999. DISCUSSION: Our results showed that even if all centres do not propose fertility preservation or sperm donation in transgender individuals, these assisted reproductive technologies are present throughout the French territory. The major point is that both fertility preservation and sperm donation in transgender individuals have grown significantly and that the care of these patients is improving year after year. CONCLUSION: In France, most of CECOS centres can take care of transgender individuals for fertility preservation and sperm donation. The French Bioethics Law allows these latter, and transgender individuals can benefit from a financial support of the national health care insurance for fertility preservation and sperm donation.

Esophageal Atresia and Respiratory Morbidity.

BACKGROUND AND OBJECTIVES: Respiratory diseases are common in children with esophageal atresia (EA), leading to increased morbidity and mortality in the first year. The primary study objective was to identify the factors associated with readmissions for respiratory causes in the first year in EA children. METHODS: A population-based study. We included all children born between 2008 and 2016 with available data and analyzed factors at birth and 1 year follow-up. Factors with a P value <.10 in univariate analyses were retained in logistic regression models. RESULTS: Among 1460 patients born with EA, 97 (7%) were deceased before the age of 1 year, and follow-up data were available for 1287 patients, who constituted our study population. EAs were Ladd classification type III or IV in 89%, preterm birth was observed in 38%, and associated malformations were observed in 52%. Collectively, 61% were readmitted after initial discharge in the first year, 31% for a respiratory cause. Among these, respiratory infections occurred in 64%, and 35% received a respiratory treatment. In logistic regression models, factors associated with readmission for a respiratory cause were recurrence of tracheoesophageal fistula, aortopexy, antireflux surgery, and tube feeding; factors associated with respiratory treatment were male sex and laryngeal cleft. CONCLUSIONS: Respiratory morbidity in the first year after EA repair is frequent, accounting for >50% of readmissions. Identifying high risk groups of EA patients (ie, those with chronic aspiration, anomalies of the respiratory tract, and need for tube feeding) may guide follow-up strategies.