[Outpatient surgery for penile hypospadias in pediatric urology: A monocentric experience with a mean follow-up of 3 years]. / Chirurgie ambulatoire de l'hypospade pénien pédiatrique : expérience monocentrique avec un recul moyen de 3 ans.

INTRODUCTION: Hypospadias is one of the most common congenital anomalies in men. Outpatient surgery has been proposed but is not widespread. The aim of this study was to evaluate our experience of outpatient surgery for penile hypospadias repair and to specify the constraints for a result similar to a conventional inpatient procedure. PATIENTS AND METHODS: Observational, retrospective and single-center study, including all the patients operated on hypospadias for the first time by one of the 3 senior surgeons, between January 2011 and March 2018. Peno-scrotal and perineal hypospadias were excluded because systematically hospitalized. RESULTS: One hundred sixty-six patients were included. 67 patients (40,4%) were treated on an outpatient basis. The mean age at the time of procedure was 15.6 (6-51) months. Forms with curvature were almost exclusively hospitalized (1 vs. 25, P<0.001). There was no significant difference for anterior penile forms (60 vs. 81, P=0.06). Middle and posterior hypospadias were more often hospitalized, although outpatient experience exists. There were no more complications in the outpatient group. CONCLUSION: Outpatient hypospadias surgery seems to be achievable in most of the cases, provided that medical care is standardized and multidisciplinary, the staff is trained and involved and a specific organization is put in place in the department. Evaluation of the socio-family environment is therefore fundamental.

Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment.

Here we investigated the role of murine mast cell protease 4 (MCPT4), the functional counterpart of human mast cell chymase, in an experimental model of renal ischemia reperfusion injury, a major cause of acute kidney injury. MCPT4-deficient mice had worsened kidney function compared to wildtype mice. MCPT4 absence exacerbated pathologic neutrophil infiltration in the kidney and increased kidney myeloperoxidase expression, cell death and necrosis. In kidneys with ischemia reperfusion injury, when compared to wildtype mice, MCPT4-deficient mice showed increased surface expression of adhesion molecules necessary for leukocyte extravasation including neutrophil CD162 and endothelial cell CD54. In vitro, human chymase mediated the cleavage of neutrophil expressed CD162 and also CD54, P- and E-Selectin expressed on human glomerular endothelial cells. MCPT4 also dampened systemic neutrophil activation after renal ischemia reperfusion injury as neutrophils expressed more CD11b integrin and produced more reactive oxygen species in MCPT4-deficient mice. Accordingly, after renal injury, neutrophil migration to an inflammatory site distal from the kidney was increased in MCPT4-deficient versus wildtype mice. Thus, contrary to the described overall aggravating role of mast cells, one granule-released mediator, the MCPT4 chymase, exhibits a potent anti-inflammatory function in renal ischemia reperfusion injury by controlling neutrophil extravasation and activation thereby limiting associated damage.

Renal parenchyma impairment characterization in partial unilateral ureteral obstruction in mice with intravoxel incoherent motion-MRI.

Ureteropelvic junction obstruction constitutes a major cause of progressive pediatric renal disease. The biological mechanisms underlying the renal response to obstruction can be investigated using a clinically relevant mouse model of partial unilateral ureteral obstruction (pUUO). Renal function and kidney morphology data can be evaluated using renal ultrasound, scintigraphy and uro-magnetic resonance imaging (uro-MRI), but these methods are poorly linked to histological change and not all are quantitative. Here, we propose to investigate pUUO for the first time using an intravoxel incoherent motion diffusion sequence. The aim of this study was to quantitatively characterize impairment of the kidney parenchyma in the pUUO model. This quantitative MRI method was able to assess the perfusion and microstructure of the kidney without requiring the injection of a contrast agent. The results suggest that a perfusion fraction (f) reduction is associated with a decrease in the volume of the renal parenchyma, which could be related to decreased renal vascularization. The latter may occur before impairment by fibrosis and the findings are in accordance with the literature using the UUO mice model and, more specifically, on pUUO. Further investigation is required before this technique can be made available for the diagnosis and management of children with antenatal hydronephrosis and to select the optimal timing of surgery if required.

DeepMPTB: a vaginal microbiome-based deep neural network as artificial intelligence strategy for efficient preterm birth prediction.

In recent decades, preterm birth (PTB) has become a significant research focus in the healthcare field, as it is a leading cause of neonatal mortality worldwide. Using five independent study cohorts including 1290 vaginal samples from 561 pregnant women who delivered at term (n = 1029) or prematurely (n = 261), we analysed vaginal metagenomics data for precise microbiome structure characterization. Then, a deep neural network (DNN) was trained to predict term birth (TB) and PTB with an accuracy of 84.10% and an area under the receiver operating characteristic curve (AUROC) of 0.875 ± 0.11. During a benchmarking process, we demonstrated that our DL model outperformed seven currently used machine learning algorithms. Finally, our results indicate that overall diversity of the vaginal microbiota should be taken in account to predict PTB and not specific species. This artificial-intelligence based strategy should be highly helpful for clinicians in predicting preterm birth risk, allowing personalized assistance to address various health issues. DeepMPTB is open source and free for academic use. It is licensed under a GNU Affero General Public License 3.0 and is available at https://deepmptb.streamlit.app/ . Source code is available at https://github.com/oschakoory/DeepMPTB and can be easily installed using Docker ( https://www.docker.com/ ).

[Calprotectin levels in meconium measured with an automated immunoassay (Liaison® XL)]. / Valeurs de référence de la calprotectine méconiale (immuno-dosage Liaison® XL).

A threshold of 50 µg fecal calprotectin per g stool sample (µg/g) is commonly used to diagnose chronic inflammatory bowel disease in adult patients and children over 4 years of age. In younger children, fecal calprotectin values are physiologically increased. For the first time, the objective of our study was to establish reference ranges in newborns for the measurement of meconium calprotectin with an automated assay (Liaison® XL, DiaSorin). A prospective study was conducted in 2022 in the Maternity Unit of the Clermont-Ferrand University Hospital, with the inclusion of full-term newborns without intestinal involvement. The quantitative automated Liaison® XL calprotectin assay was assessed on a panel of meconium samples. In our cohort of 132 term neonates, calprotectin values ranged from 21 to 855 µg/g of meconium (2,5th to 97.5th percentile) and the median value was 194 µg/g. In our cohort, only sex-related differences were observed for calprotectin values. No significant differences were found for the other factors studied (maternal or neonatal). Because of inter-individual variability, a sequential measurement of newborn calprotectin from meconium should be considered.

Influence of Perinatal Factors on Blood Tryptase and Fecal Calprotectin Levels in Newborns.

BACKGROUND: Blood tryptase and fecal calprotectin levels may serve as biomarkers of necrotizing enterocolitis. However, their interpretation may be hindered by the little-known effects of perinatal factors. The aim of this study was to compare the tryptase and calprotectin levels in newborns according to their term, trophicity, and sex. METHOD: One hundred and fifty-seven premature newborns and 157 full-term newborns were included. Blood tryptase and fecal calprotectin were assayed. RESULTS: Blood tryptase levels were higher in premature than in full-term newborns (6.4 vs. 5.2 µg/L; p < 0.001). In situations of antenatal use of corticosteroids (p = 0.007) and non-exclusive use of human milk (p = 0.02), these levels were also higher. However, in multiple linear regression analyses, only prematurity significantly influenced tryptase levels. Fecal calprotectin levels were extremely wide-ranging and were much higher in female than in male newborns (300.5 vs. 110.5 µg/g; p < 0.001). CONCLUSIONS: The differences in tryptase levels according to term could be linked to early aggression of the still-immature digestive wall in premature newborns, in particular, by enteral feeding started early. The unexpected influence of sex on fecal calprotectin levels remains unexplained.

Case reports of large and symptomatic abdominal tumors in newborns: Pitfalls, difficulties in management, and surgical decision making.

BACKGROUND: Large and rapidly growing abdominal tumors may result in fatal outcomes in newborns. In some cases, a rapidly worsening clinical condition requires surgical decision-making despite the absence of a precise histological diagnosis. In these situations, there is neither a guide nor consensus. CASE: We highlight our experience with five patients with large abdominal tumors and assess the available literature for the best possible management of a rare condition. CONCLUSION: In these cases, laparostomy should be considered as a life-saving procedure. If the liver is involved and coagulopathy is present, prognosis is often compromised.

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.

Management of lower urinary tract fibroepithelial polyps in children.

INTRODUCTION: Fibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date. OBJECTIVE: The aim of this study was to address the experience of FEP management in children. STUDY DESIGN: A retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed. RESULTS: A total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1-48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1-10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1-34) months. DISCUSSION: The main limitation of our study is the retrospective design, although it is the largest one for this pathology. CONCLUSION: This series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences. LEVEL OF EVIDENCE: Level V.

Mast Cells and MCPT4 Chymase Promote Renal Impairment after Partial Ureteral Obstruction.

Obstructive nephropathy constitutes a major cause of pediatric renal progressive disease. The mechanisms leading to disease progression are still poorly understood. Kidney fibrotic lesions are reproduced using a model of partial unilateral ureteral obstruction (pUUO) in newborn mice. Based on data showing significant mast cell (MC) infiltration in patients, we investigated the role of MC and murine MCPT4, a MC-released chymase, in pUUO using MC- (Wsh/sh), MCPT4-deficient (Mcpt4-/-), and wild-type (WT) mice. Measurement of kidney length and volume by magnetic resonance imaging (MRI) as well as postmortem kidney weight revealed hypotrophy of operated right kidneys (RKs) and compensatory hypertrophy of left kidneys. Differences between kidneys were major for WT, minimal for Wsh/sh, and intermediate for Mcpt4-/- mice. Fibrosis development was focal and increased only in WT-obstructed kidneys. No differences were noticed for local inflammatory responses, but serum CCL2 was significantly higher in WT versus Mcpt4-/- and Wsh/sh mice. Alpha-smooth muscle actin (αSMA) expression, a marker of epithelial-mesenchymal transition (EMT), was high in WT, minimal for Wsh/sh, and intermediate for Mcpt4-/- RK. Supernatants of activated MC induced αSMA in co-culture experiments with proximal tubular epithelial cells. Our results support a role of MC in EMT and parenchyma lesions after pUUO involving, at least partly, MCPT4 chymase. They confirm the importance of morphologic impairment evaluation by MRI in pUUO.

The function of mast cells in autoimmune glomerulonephritis.

Immune-mediated glomerulonephritis is caused by deposition of immune complexes on the glomerular basement membrane or of autoantibodies directed against the glomerular basement membrane. Depositions lead to an inflammatory response that can ultimately destroy renal function and lead to chronic kidney disease. However, the pathological processes leading to the development of renal injury and disease progression remain poorly understood. To investigate the mechanisms of disease development in glomerulonephritis various animal models have been developed, which include as the most popular one the induction of glomerulonephritis by the injection of heterologous antibodies directed to the glomerular basement membrane. The role of mast cells and mast cell-derived mediators has been evaluated in these models. In this chapter we describe the methods that allow to set up and study the disease parameters of immune-mediated glomerulonephritis development.

Laparoscopic Mitrofanoff procedure in children: critical analysis of difficulties and benefits.

OBJECTIVES: The Mitrofanoff principle is an accepted continent urinary diversion. We studied the feasibility and the possible benefits of using a laparoscopic approach in children with significant bladder dysfunction associated with difficulty doing efficient urethral catheterization. PATIENTS AND METHODS: A fully laparoscopic Mitrofanoff continent cystostomy was attempted in 15 children with a median age of 9 years (IQR 6), between 2003 and 2013. Before the Mitrofanoff procedure was considered, urodynamic evaluation was done for each patient, to study bladder compliance, detrusor activity, and bladder capacity. The procedure was performed using a transperitoneal four-port approach. A 30-degree down camera angle was optimal for viewing the appendix and the posterior wall of the bladder. The operative steps of the open procedure were replicated laparoscopically. The proximal end of the appendix was spatulated and anastomosed to the posterior wall of the bladder, providing an antireflux mechanism by an extramucosal tunnel. The distal end of the appendix was brought out as the cutaneous umbilical stoma. Some modifications were done because of the high rate of conversion due to early opening of the mucosa (harmonic hook) or difficult anastomosis: (a) use of 5-mm trocars to change the laparoscope position from the left to right subcostal area to better visualize the anastomosis, (b) the anastomosis was suspended at its two ends during suturing; a trans-abdominal traction suture of the bladder was inserted for better exposure of the anastomosis (hitch stitch) and to stabilize the anastomotic line during suturing, (c) use of a monopolar hook to cut the detrusor muscle fibers, to avoid incidental opening of the mucosa, and (d) the window between the appendix and the peritoneum was closed to avoid internal hernia. RESULTS: The procedure was totally completed by laparoscopy in 12 cases. Three were converted to an open procedure due to tearing of bladder mucosa (n = 2) or appendix ischemia (n = 1). Median operative time for fully laparoscopic Mitrofanoff was 255 min (IQR 52). Median follow-up was 18 months (IQR 35). No patient required stomal revision. Seven patients were continent, five experienced urinary leakage from urethra n = 1 and/or stoma n = 5. Three patients with stomal urinary leakage were successfully managed by Deflux (dextranomer-based implants) injection in the catheterizable channel. Two patients required an open revision of the appendicovesical anastomosis. The patient with both stomal and urethral urinary leakage also required the implantation of an artificial urinary sphincter 1.5 years after Mitrofanoff. One patient had bladder augmentation. CONCLUSION: Although our results of laparoscopic Mitrofanoff procedure in children are unsatisfying in cases of high-pressure bladders in terms of incontinent stoma, we still believe that it is justified to develop this challenging technique with more refinement and improvement, to provide a minimal invasive procedure that may postpone or even avoid bladder augmentation in pediatric age.

Mast cells in renal inflammation and fibrosis: lessons learnt from animal studies.

Mast cells are hematopoietic cells involved in inflammation and immunity and have been recognized also as important effector cells in kidney inflammation. In humans, only a few mast cells reside in kidneys constitutively but in progressive renal diseases their numbers increase substantially representing an essential part of the interstitial infiltrate of inflammatory cells. Recent data obtained in experimental animal models have emphasized a complex role of these cells and the mediators they release as they have been shown both to promote, but also to protect from disease and fibrosis development. Sometimes conflicting results have been reported in similar models suggesting a very narrow window between these activities depending on the pathophysiological context. Interestingly in mice, mast cell or mast cell mediator specific actions became also apparent in the absence of significant mast cell kidney infiltration supporting systemic or regional actions via draining lymph nodes or kidney capsules. Many of their activities rely on the capacity of mast cells to release, in a timely controlled manner, a wide range of inflammatory mediators, which can promote anti-inflammatory actions and repair activities that contribute to healing, but in some circumstances or in case of inappropriate regulation may also promote kidney disease.