Jean Breaud

Esophageal atresia: Data from a national cohort

PURPOSE A prospective national register was established in 2008 to record all new cases of live-birth newborns with esophageal atresia (EA). This epidemiological survey was recommended as part of a national rare diseases plan. METHODS All 38 national centers treating EA participated by completing for each patient at first discharge a questionnaire validated by a national committee of experts. Data were centralized by the national reference center for esophageal anomalies. Quantitative and qualitative analyses were performed, with P-values of less than 0.05 considered statistically significant. Results of the 2008-2009 data collection are presented in this report. RESULTS Three hundred seven new living cases of EA were recorded between January 1, 2008, and December 31, 2009. The male/female sex ratio was 1.3, and the live-birth prevalence of EA was 1.8 per 10,000 births. Major characteristics were comparable to those reported in the literature. Survival was 95%, and no correlation with caseload was noted. CONCLUSIONS Epidemiologic surveys of congenital anomalies such as EA, which is a rare disease, provide valuable data for public health authorities and fulfill one important mission of reference centers. When compared with previous epidemiological data, this national population-based registry suggests that the incidence of EA remains stable.

Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect

BACKGROUND Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions. OBJECTIVE To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias. DESIGN, SETTING, AND PARTICIPANTS A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009-2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS In patients without AR, SRD5A2, and MAMLD1 mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed. RESULTS Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11-4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%, p=0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%, p=0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%, p<0.00005). Association of occupational and environmental exposures increases this risk. CONCLUSIONS This multicenter prospective controlled study with a homogeneous cohort of hypospadiac boys without genetic defects strongly suggests that EDCs are a risk factor for hypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk. PATIENT SUMMARY Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical products increase the risk of hypospadias in children.

Minor Hypospadias: The “Tip of the Iceberg” of the Partial Androgen Insensitivity Syndrome

Background Androgens are critical in male external genital development. Alterations in the androgen sensitivity pathway have been identified in severely undermasculinized boys, and mutations of the androgen receptor gene (AR) are usually found in partial or complete androgen insensitivity syndrome (AIS). Objective The aim of this study was to determine whether even the most minor forms of isolated hypospadias are associated with AR mutations and thus whether all types of hypospadias warrant molecular analysis of the AR. Materials and Methods Two hundred and ninety-two Caucasian children presenting with isolated hypospadias without micropenis or cryptorchidism and 345 controls were included prospectively. Mutational analysis of the AR through direct sequencing (exons 1–8) was performed. In silico and luciferase functional assays were performed for unreported variants. Results Five missense mutations of the AR were identified in 9 patients with glandular or penile anterior (n = 5), penile midshaft (n = 2) and penile posterior (n = 2) hypospadias, i.e., 3%: p.Q58L (c.173A>T), 4 cases of p.P392S (c.1174C>T), 2 cases of p.A475V (c.1424C>T), p.D551H (c.1651G>C) and p.Q799E (c.2395C>G). None of these mutations was present in the control group. One mutation has never been reported to date (p.D551H). It was predicted to be damaging based on 6 in silico models, and in vitro functional studies confirmed the lowered transactivation function of the mutated protein. Three mutations have never been reported in patients with genital malformation but only in isolated infertility: p.Q58L, p.P392S, and p.A475V. It is notable that micropenis, a cardinal sign of AIS, was not present in any patient. Conclusion AR mutations may play a role in the cause of isolated hypospadias, even in the most minor forms. Identification of this underlying genetic alteration may be important for proper diagnosis and longer follow-up is necessary to find out if the mutations cause differences in sexual function and fertility later in life.

Does prenatal diagnosis modify neonatal treatment and early outcome of children with esophageal atresia

OBJECTIVE Our study aimed at (1) evaluating neonatal treatment and outcome of neonates with either a prenatal or a postnatal diagnosis of esophageal atresia (EA) and (2) analyzing the impact of prenatal diagnosis on outcome based on the type of EA. STUDY DESIGN We conducted a population-based study using data from the French National Register for infants with EA born from 2008-2010. We compared prenatal, maternal, and neonatal characteristics among children with prenatal vs postnatal diagnosis and EA types I and III. We defined a composite variable of morbidity (anastomotic esophageal leaks, recurrent fistula, stenosis) and death at 1 year. RESULTS Four hundred sixty-nine live births with EA were recorded with a prenatal diagnosis rate of 24.3%; 82.2% of EA type I were diagnosed prenatally compared with 17.9% of EA type III (P < .001). Transfer after birth was lower in case of prenatal diagnosis (25.6% vs 82.5%; P < .001). The delay between birth and first intervention did not differ significantly among groups. The defect size was longer among the prenatal diagnosis group (2.61 vs 1.48 cm; P < .001). The composite variables were higher in prenatal diagnosis subset (44% vs 27.6%; P = .003) and in EA type I than in type III (58.1% vs 28.3%; P < .001). CONCLUSION Despite the excellent survival rate of EA, cases with antenatal detection have a higher morbidity rate related to the EA type (type I and/or long gap). Even though it does not modify neonatal treatment and the 1-year outcome, prenatal diagnosis allows antenatal parental counselling and avoids postnatal transfers.

Inguinal hernia in premature boys: Should we systematically explore the contralateral side?☆ , ☆☆

OBJECTIVE Bilateral surgery has been largely advocated in premature boys with unilateral inguinal hernia owing to the high incidence of contralateral patent processus vaginalis. Recently, the potential morbidity of herniotomy in low birth-weight babies and the progress in pediatric anesthesia questioned this attitude. This study aims to evaluate the incidence of contralateral metachronous hernia in a large series of premature boys and to compare the morbidity of preventive versus elective surgery. METHODS This retrospective multicenter analysis of 964 premature boys presenting with unilateral inguinal hernia operated from 1998 to 2012 included 557 infants who benefited from a unilateral herniotomy and 407 from a bilateral herniotomy (median follow-up 12months). RESULTS Contralateral metachronous hernia after unilateral surgery occurred in 11% (n=60) without significant difference according to the initial symptomatic side (9.5% on right vs 13% on left, p>0.05). Postoperative morbidity on the contralateral side was higher after preventive surgery than elective surgery with metachronous hernia (2.45% versus 0.9%, p=0.05) especially for secondary cryptorchidism (1% vs 0%, p=0.03). Despite the risk of metachronous incarcerated hernia, elective surgery did not increase the rate of testicular hypotrophy on the opposite side (0.7%, vs 0.7%, p>0.05). CONCLUSION Systematic bilateral herniotomy is unnecessary in almost 90% of patients and has a significant morbidity. Secondary surgery for metachronous hernia does not increase the risk of testicular lesion and even reduces the risk of secondary cryptorchidism. These results, along with the risk of hypofertility reported after bilateral surgery, may justify treating only the symptomatic side in premature boys.

Blunt abdominal aortic trauma in paediatric patients.

BACKGROUND Blunt abdominal aortic trauma (BAAT) is a very rare occurrence in children, with significant morbidity and mortality. Varied clinical presentations and sparse literature evidence make it difficult to define the proper management policy for paediatric patients. METHOD We report our centres data on three consecutive children with BAAT managed between 2006 and 2010. A Medline search was also performed for relevant publications since 1966, together with a review of references in retrieved publications. RESULTS Forty children (range 1-16 years) were included in our final analysis. Motor vehicle crashes (MVC) were the leading cause of injury (65%). The in-hospital mortality rate was 7.5% (3/40). Nine patients (22.5%) ended up with residual sequelae. Main primary aortic lesions were complete wall rupture (12.5%), intimal transection (70%) and pseudoaneurysm (15%). Twenty-eight children underwent aortic surgical repair (70%). Among the 12 non-operatively managed patients, 41.6% had complications, including one death. CONCLUSION Symptomatic lesions and complete ruptures should undergo immediate surgical repair. Circumferential intimal transections are at high risk of complication and should also receive intervention. Partial intimal transections and delayed pseudoaneurysms can be initially observed by clinical examination and imaging. Patients with these latter pathologies should be operated on at any sign of deterioration.

In Situ Intestinal Ischemia-Reperfusion Injury in the Pig: A Model Using the First Jejunal Artery for Flushing

BackgroundWe describe a new surgical technique of in situ intestinal ischemia–reperfusion injury in the pig, which includes transection of the small bowel, extrinsic autonomic denervation, lymphatic disruption, and finally in-situ cold ischemia of the graft by flushing through the first jejunal artery.Material and methodsTen female pigs were used for the study. All neural and lymphatic connections to the jejunoileum were transected. The stripped superior mesenteric vessels remained as the only connections. The skeletonized mesenteric vessels were clamped and the superior mesenteric artery was cannulated through the first jejunal artery. The isolated jejunoileum was flushed with cold IGL-1 solution. A small incision on the superior mesenteric vein was made to allow outflow of the effluent. After the flushing process was complete, the small incision in the superior mesenteric vein was closed and the vascular clamps were removed. The proximal 70% of the graft was resected.ResultsThe mean preoperative weight of the animals was 25.8 ±7.6 kg. The mean duration of the operation was 242.0 ± 28.6 min. The mean cold ischemia time was 47.6 ± 3.9 min. All animals survived the procedure and were sacrificed at day 8. At sacrifice, there were no adhesions. The small bowel appeared normal. On intestinal histology, there were no significant changes between specimens obtained from the animal immediately at the end of cold flushing (T0), 2 h after reperfusion (T1), and at sacrifice (T2).ConclusionsThis novel technique for intestinal ischemia–reperfusion injury in the pig provides an extremely useful model for experimental studies of immunological and cold ischemia–reperfusion injury of transplanted small bowels.

Troubles mictionnels de l’enfant : de la physiologie à la symptomatologie clinique

Micturition is a natural event occurring several times a day, the result of a complex and partially unknown physiology. It involves different muscles (striated and smooth) as well as the central and autonomic nervous systems in an innate voiding reflex. This reflex is controlled after 2 years of age. If there is a failure or dysfunction of one of these elements, a miction disorder may appear. Two types of miction disorders are identified: neuromuscular disorders of the bladder and defective central control. Multiple factors such as constipation, bladder irritation, or an increase in abdominal pressure can interfere with the voiding reflex. The new international definitions and classifications of voiding disorders allow an easier clinical approach through careful and complete questioning and a simple clinical exam, efficient enough in most cases to provide the diagnosis and adapted treatment.

Terrorist attack in Nice: the central role of a children's hospital

www.thelancet.com Vol 389 March 11, 2017 1007 2 Aylwin CJ, König TC, Brennan NW, et al. Reduction in critical mortality in urban mass casualty incidents. Lancet 2006; 368: 2219–25. 3 Gregory TM, Bihel T, Guigui P, et al. Terrorist attacks in Paris: surgical trauma experience in a referral center. Injury 2016; 47: 2122–26. 4 Tobert D, von Keudell A, Rodriguez EK. Lessons from the Boston Marathon bombing: an orthopaedic perspective on preparing for high-volume trauma in an urban academic center. J Orthop Trauma 2015; 29 (suppl 10): S7–10. 5 Weil YA, Peleg K, Givon A, Israeli Trauma Group, Mosheiff R. Musculoskeletal injuries in terrorist attacks—a comparison between the injuries sustained and those related to motor vehicle accidents, based on a national registry database. Injury 2008; 39: 1359–64. order to keep reserve staff at home was given, resulting in strong feelings of frustration among those people. 44 patients were admitted in 2 h (appendix). Of these, 12 were adults: five were in critical condition, of whom four died quickly. The remaining 32 patients were children: eight were in critical condition, of whom two died later. The trauma leader assigned the patients to the operating room, resuscitation room, or for a CT scan. The CT scanner was made immediately available, performing 15 scans during the night. Six patients needed surgery during the first 24 h. All elective surgeries scheduled for July 15, 2016, were postponed, and team rotations were reorganised to allow rest. Injuries were typical of road crashes, differing from those caused by bomb or bullets, but similar to injuries observed in Israel. Cause of death was mainly haemorrhagic shock after multiple traumas including pelvic disjunction, head trauma, and trunk crush. During the night, child psychiatrists took care of victims, parents, witnesses, and staff. Stress disorder and dissociative symptomatology were observed—more prominently in adults than in children— and resulted in two transfers to the psychiatric emergency department at Pasteur Hospital and in disorganisation and sick leave for affected hospital staff. Multiple debriefing meetings, both technical and psychological, were necessary and profitable for all hospital staff. Our experience confirms that every hospital, regardless of level and specialty, should be prepared to receive patients of all ages, with all types of severities and lesions.

A prospective study into the benefits of simulation training in teaching obstetric vaginal examination

To assess the benefits of incorporating simulations in obstetric vaginal‐examination training.