Spatial analysis of hypospadias cases in northern France: taking clinical data into account.

BACKGROUND: Strong evidence for a causal role of environmental factors in a congenital anomaly is still difficult to produce. The collection of statistical data is crucial for gaining a better understanding of the epidemiology and pathophysiology of these anomalies. We aimed to evaluate spatial variations in hypospadias within our region and it's association to socioeconomic and ecological factors, taking clinical data into account. METHODS: All boys with hypospadias born in northern France and seen in Lille University Medical Center (Lille, France) between 1999 and 2012 were included in the analysis. We retrospectively collected geographic data, clinical data (especially known confounding factors associated with an elevated risk of hypospadias), and demographic, socio-economic and ecological data. We analyzed the entire study population and subsequently the subset of boys lacking confounding factors. RESULTS: The study sample of 975 cases of hypospadias over the 13-year period resulted in an incidence of 25.4/10,000 male births, and was characterized by significant spatial heterogeneity (p < 0.005) and autocorrelation (p < 0.001). We detected two high-incidence clusters that differed with regard to their land use. After the exclusion of 221 patients with confounding factors, two high-incidence clusters with significant disease risks (1.65 and 1.75, respectively; p < 0.001) and a significant difference in land use (p < 0.001) again appeared. The first cluster contained a higher median [interquartile range] proportion of artificialized land (0.40 [0.22;0.47]) than the remaining "neutral areas" (0.19 [0.08;0.53]) did (p < 0.001). Conversely, the second cluster contained a higher median proportion of rural land (0.90 [0.78;0.96]) than the "neutral areas" (0.81 [0.47;0.92]) did (p < 0.001). The median deprivation index was significantly lower in the urban cluster (0.47 [0.42;0.55]) and significantly higher in the rural cluster (0.69 [0.56;0.73]) (p < 0.001). CONCLUSIONS: Our results evidenced the heterogeneous spatial distribution of cases of hypospadias in northern France. We identified two clusters with different environmental and social patterns - even after the exclusion of known confounding factors.

Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats.

Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O2, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O2 (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O2 (n = 30), PUFA ω-3/air (n = 30), control/O2 (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O2 (n = 30) or to the control/O2 (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.

Changes in the clinical management of 5α-reductase type 2 and 17ß-hydroxysteroid dehydrogenase type 3 deficiencies in France.

Objectives: To examine the changes in diagnostic practices and clinical management of patients with 5α-reductase type 2 (SRD5A2) or 17ß-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency since molecular diagnoses became available. Methods: Clinical, laboratory, and therapeutic data were retrieved from the medical records of 52 patients with a molecular diagnosis of SRD5A2 (n = 31) or HSD17B3 (n = 21) deficiency. Temporal trends regarding age at assessment and initial sex assignment over 1994-2020 were qualitatively analyzed. Age at molecular diagnosis was compared between two subgroups of patients according to their year of birth. Results: Fifty-eight percent (n = 30) patients were diagnosed during the perinatal period, 33% (n = 17) during infancy, and 9% (n = 5) during adolescence or adulthood. Over the studied period, the patients' age at initial assessment and diagnosis frankly decreased. The median (range) age at diagnostic confirmation was 10.5 (0-53.2) years for patients born before 2007 and 0.4 (0-9.3) years for those born in 2007 or later (P = 0.029). Genetic testing identified 27 different variants for the SRD5A2 gene (30% novel, n = 8) and 18 for the HSD17B3 gene (44% novel, n = 8). Before 2002, most patients were initially assigned as females (95%, n = 19), but this proportion dropped for those born later (44%, n = 14; P < 0.001). The influence of initial genital appearance on these decisions seemingly decreased in the most recent years. Therapeutic interventions differed according to the sex of rearing. Ten percent (n = 2) patients requested female-to-male reassignment during adulthood. Conclusion: This study showed, over the past two decades, a clear trend toward earlier diagnosis and assignment of affected newborns as males.

"Re-Materialized" Medical Data: Paper-Based Transmission of Structured Medical Data Using QR-Code, for Medical Imaging Reports.

Although paper-based transmission of medical information might seem outdated, it has proven efficient, and remains structurally safe from massive data leaks. As part of the ICIPEMIR project for improving medical imaging report, we explored the idea of structured data storage within a medical report, by embedding the data themselves in a QR-Code (and no URL-to-the-data). Three different datasets from ICIPEMIR were serialized, then encoded in a QR-Code. We compared 4 compression algorithms to reduce file size before QR-Encoding. YAML was the most concise format (character sparing), and allowed for embedding of a 2633-character serialized file within a QR-Code. The best compression rate was obtained with gzip, with a compression ratio of 2.32 in 15.7ms. Data were easily extracted and decompressed from a digital QR-Code using a simple command line. YAML file was also successfully recovered from the printed QR-Code with both Android and iOS smartphone. Minimal detected size was 3*3cm.

ICIPEMIR: Improving the Completeness, Interoperability and Patient Explanations of Medical Imaging Reports.

INTRODUCTION: Although electronic health records have been facilitating the management of medical information, there is still room for improvement in daily production of medical report. Possible areas for improvement would be: to improve reports quality (by increasing exhaustivity), to improve patients' understanding (by mean of a graphical display), to save physicians' time (by helping reports writing), and to improve sharing and storage (by enhancing interoperability). We set up the ICIPEMIR project (Improving the completeness, interoperability and patients explanation of medical imaging reports) as an academic solution to optimize medical imaging reports production. Such a project requires two layers: one engineering layer to build the automation process, and a second medical layer to determine domain-specific data models for each type of report. We describe here the medical layer of this project. METHODS: We designed a reproducible methodology to identify -for a given medical imaging exam- mandatory fields, and describe a corresponding simple data model using validated formats. The mandatory fields had to meet legal requirements, domain-specific guidelines, and results of a bibliographic review on clinical studies. An UML representation, a JSON Schema, and a YAML instance dataset were defined. Based on this data model a form was created using Goupile, an open source eCRF script-based editor. In addition, a graphical display was designed and mapped with the data model, as well as a text template to automatically produce a free-text report. Finally, the YAML instance was encoded in a QR-Code to allow offline paper-based transmission of structured data. RESULTS: We tested this methodology in a specific domain: computed tomography for urolithiasis. We successfully extracted 73 fields, and transformed them into a simple data model, with mapping to a simple graphical display, and textual report template. The offline QR-code transmission of a 2,615 characters YAML file was successful with simple smartphone QR-Code scanner. CONCLUSION: Although automated production of medical report requires domain-specific data model and mapping, these can be defined using a reproducible methodology. Hopefully this proof of concept will lead to a computer solution to optimize medical imaging reports, driven by academic research.

Quality of life in adults with bladder exstrophy-epispadias complex.

PURPOSE: We evaluated quality of life in adults with bladder exstrophy-epispadias complex to improve patient and parent counseling. MATERIALS AND METHODS: We evaluated quality of life in a multicenter study using the SF-36® Medical Outcome Study questionnaire and a local questionnaire. A total of 47 patients born in 1957 to 1990 were followed due to bladder exstrophy-epispadias complex at the 4 participating hospitals. RESULTS: Nine women and 16 men were included in analysis, including 15 who underwent staged reconstruction for bladder exstrophy-epispadias complex and 10 who underwent primary or secondary urinary diversion. Nine patients were married and 2 were in a long-term partnership. A total of 22 patients achieved a high school degree with examination success and 17 worked full time. Six women and 12 men achieved penetrative intercourse. A total of 13 children were born to 3 women and 7 men. Quality of life scores in our patients were less than the norm based scores on 2 of the 8 health concepts, including limitations in physical activity due to health problems and general health perception. Results were statistically different among patients depending on dryness, voiding and urinary reconstruction/diversion. Patient scores did not differ in regard to gender, number of interventions, sexual life, cosmesis or renal function. CONCLUSIONS: Patient scores were less than norm based scores on only 2 health concepts and patients were generally well integrated into society. Urinary diversion was usually well tolerated. It remains a therapeutic option when incontinence interferes with social life or renal function is compromised.

Vasodilator effects of dehydroepiandrosterone (DHEA) on fetal pulmonary circulation: An experimental study in pregnant sheep.

Persistent pulmonary hypertension (PPHN) remains a severe complication of the transition to extra-uterine life with significant morbidity and mortality in the newborns. Dehydroepiandrosterone (DHEA) represents a new pharmacological agent with vascular effects, including improvement of PPHN in several animal models. We hypothesized that DHEA could decrease pulmonary vascular resistance (PVR) in the pulmonary circulation of fetal sheep. We studied the effect of intravenous infusion of DHEA in fetal lambs using chronically instrumented sheep at 128 days of gestation. PVR was computed before and after intravenous infusion of increasing doses of DHEA. We assessed pre-treatment by L-nitroarginine, an inhibitor of NO production. Blood gases and doses of DHEA were measured in both sheep and fetus before/after DHEA infusion. Intravenous infusion of DHEA had a vasodilator effect with a significant decrease in PVR (respectively -11%, -14% and -36% after infusion of 6, 12 and 24 mg DHEA, p<0.01) without damaging effects on systemic circulation or on blood gases. The inhibitory effect of pre-treatment with L-nitroarginine resulted in a significant increase in PVR. We demonstrated a potent vasodilator effect of DHEA on fetal pulmonary circulation without deleterious effects. DHEA might represent a new treatment for PPHN.

Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs.

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E- (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E- (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.

[Complexity of pathological interpretation in megacystis-microcolon-intestinal hypoperistalsis syndrome]. / Complexité de l'interprétation anatomopathologique dans le syndrome mégavessie-microcôlon-hypopéristaltisme intestinal.

Megacystis-microcolon-intestinal hypoperistalsis syndrome is very rare, and is the most severe of the chronic intestinal pseudoobstructions. Diagnosis is usually made in the neonatal period, is clinical and radiological, and is confirmed by manometric studies. Microscopic abnormalities are variable, inconstant and nonspecific. They involve the smooth muscle more often than the intrinsic innervation of the gut and the bladder. A girl, currently seven years old, presented with megacystis observed on prenatal ultrasound at 21 weeks of gestation. At first, amniotic fluid volume was appropriate for gestational age, and then hydramnios appeared at 30 weeks of gestation. Microcolon was discovered at birth, with microileum, dilatation of the duodenum and proximal jejunum, intestinal malposition, and severe hypoperistalsis of the entire gastrointestinal tract, which indicated enterostomy and total parenteral nutrition from birth. At pathological examination, rectal biopsy and enteric nervous plexuses were normal. There was hypoplasia of the external longitudinal layer of the muscularis propria in the colon and ileum. Cajal cells could not be demonstrated immunohistochemically in the colon. This case highlights the complexity and difficulties of pathological interpretation in this syndrome, and the necessity of a large study of controls at different ages and different levels of the digestive tract and the bladder.

[Synaptophysin expression abnormalities in Hirschsprung's disease]. / Anomalies d'expression de la synaptophysine dans la maladie de Hirschsprung.

Hirschsprung's disease is defined by the congenital absence of ganglion cells in enteric plexuses. Immunostaining of synaptophysin after formalin fixation may be used to identify hyperplasia of nerve fibers and rarefaction of neuromuscular junctions in Hirschsprung's disease. The aim of the study was to evaluate semi-quantitatively the expression of synaptophysin in Hirschsprung's disease, in correlation with morphologic features. This retrospective study included 3 controls, 42 surgical rectal biopsies performed for suspicion of Hirschsprung's disease in children presenting with lower digestive occlusion or severe chronic constipation, including 18 Hirschsprung's disease, and 23 surgical specimens of Hirschsprung's disease. In the absence of Hirschsprung's disease, synaptophysin-positive fibers were numerous but thin in the muscularis mucosae, thin and scarce in the mucosa and submucosa. Neuromuscular junctions were thin and numerous in the muscularis propria. In Hirschsprung's disease, synaptophysin-positive fibers were coarse, and increased in number on each side of the muscularis mucosae. Plexuses were enlarged, weakly stained, and associated in the connective tissue of the muscularis propria with coarse and intensely stained fibers. In conclusion, staining for synaptophysin could be useful to demonstrate abnormalities of enteric innervation in rectal biopsies performed for suspected Hirschsprung's disease in the absence of acetylcholinesterase staining on frozen sections, in transmural biopsies performed for guiding surgery in Hirschsprung's disease, and in cases of extensive Hirschsprung's disease.

Advantages of intraoperative semiquantitative evaluation of myenteric nervous plexuses in patients with Hirschsprung disease.

BACKGROUND: The reappearance of an occlusive syndrome after surgical treatment of patients with Hirschsprung disease is often caused by incomplete resection of the affected segment. Intraoperative examination of frozen biopsies assists surgery, but interpretation of biopsies in the transitional zone is difficult. METHODS: We performed retrospective semiquantitative evaluations of myenteric nervous plexuses at the proximal limits of resection specimens from 41 children who were treated for rectocolic Hirschsprung disease using intraoperative examination of transparietal biopsies. The results of the evaluations were correlated with the postoperative courses of the children. RESULTS: After formalin fixation, the mean length of the aganglionic segments was 8.9 cm (range, 1-37.5 cm). At the proximal limit, the percentage of the circumference of the muscularis propria that was composed of plexuses with ganglion cells was more than 95% in 7 children, 90% to 95% in 21 children, 40% to 80% in 6 children, and 30% or less in 7 children (17%), 4 of whom subsequently developed occlusive syndromes. CONCLUSIONS: Semiquantitative intraoperative examination of the entire circumference of resected segments facilitates precise evaluation of intrinsic innervation at the level of the anastomosis and may reduce the frequency of recurrence of occlusive symptoms after surgery.

Biofeedback therapy in the treatment of bladder overactivity, vesico-ureteral reflux and urinary tract infection.

OBJECTIVE: Voiding disorders are commonly encountered in paediatric urology practice. Urinary incontinence often leads to the impairment of self-esteem but can also cause renal damage, when recurrent urinary tract infection (UTI) or vesico-ureteral reflux (VUR) exists. The aim of this study was to assess the efficacy of a biofeedback training program in children with a long history of voiding disorders. PATIENTS AND METHODS: Between 1998 and 2002, 60 children with voiding disorders without neuropathic disease, aged 5-14, were treated. There were 48 girls and 12 boys. The main symptoms were daytime incontinence for 90%, urge syndrome for 78%, and night-time incontinence for 60%. UTIs were noted in 62% of the children, for 37% of them in association with a VUR. Ten weekly sessions were planned for all the children. They were given instructions on toilet behaviour and posture, and pelvic floor training. They had to supervise their voiding frequency and liquid intake at home using a chart. Biofeedback procedure used surface perineal electrodes. The exercises focused on relaxation of the perineum. RESULTS: The first results were recorded 6 months after the last session: 96% of the children with daytime incontinence and 83% of the children with night-time incontinence were cured or improved; 84% of the children were free from infection and VUR was cured in 50% of cases. After a mean follow-up of 21 months, 8% of the children with daytime incontinence and 33% with night-time incontinence relapsed, with a significant difference between primary and secondary enuresis. A breakthrough UTI was observed in 19% of cases. CONCLUSION: This non-invasive training program was effective in the treatment of daytime incontinence, UTI and VUR. There was an improvement in secondary but not primary enuresis. To prevent relapse, additional support sessions seem to be necessary.