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La promontofixation cœlioscopique est considérée comme le traitement de choix du prolapsus de la femme jeune car elle associe les avantages de la chirurgie prothétique par voie abdominale, avec celles d'une technique mini-invasive. De nombreuses variantes se sont développées autour de cette intervention et rendent parfois difficile l'analyse des résultats. L'objectif de cet article est de faire une mise au point sur les différents aspects de la technique chirurgicale. Description et recommandations sur les différents aspects de la technique chirurgicale fondée l'expérience des auteurs (trucs et astuces) mais aussi à partir des données de la littérature. Nous décrirons les différents temps de la double promontofixation cœlioscopique avec conservation utérine. Bien qu'il n'existe pas de données comparatives concernant les sites et modes de fixation des prothèses, il convient de se référer aux résultats des grandes séries et de privilégier de la fixation des prothèses à l'aide de fils, en avant sur l'isthme utérin et la paroi vaginale antérieure et en arrière sur les muscles releveurs. De même, il est conseillé de fixer sans tension excessive les prothèses sur le promontoire à l'aide de fils non résorbables et d'effectuer une péritonisation de ces prothèses. Il n'est pas recommandé de mettre systématiquement une prothèse postérieure inter recto-vaginale en prévention de rectocèle secondaire. L'utilisation de prothèses non résorbables par voie haute (promontofixation) permet de traiter les prolapsus des organes pelviens avec des bons résultats et peu de complications y compris en termes d'exposition et d'infection de prothèses. Elle est considérée à ce titre comme la technique chirurgicale de référence et les différents aspects de la technique chirurgicale doivent donc à ce titre être bien codifiés. Laparoscopic sacrocolpopexy is considered as the gold standard for the surgical treatment for urogenital prolapse because it combines the advantages of abdominal route for prosthetic prolapse repair with those of a minimally invasive technique. Many variants have been described and make results difficult to analyze. The purpose of this article is to focus on the different technical aspects of this surgery. Description and recommendations on different aspects of the surgical technique based on the experience of the authors (tips and tricks) but also from the data of the literature. We will describe the different steps of laparoscopic sacrocolpopexy with two mesh and with uterine preservation. Although there are no comparative data on sites and methods of fixation of prostheses, we have to refer to the results of large series. There is a consensus on fixation of prostheses with the help of threads, forward on uterine isthmus and the anterior vaginal wall and back on the levator muscles. Similarly consensus is to fix prostheses on the promontory without excessive tension and with non-absorbable thread and close the peritoneum on these prostheses. It is not recommended to systematically put an inter-recto-vaginal prosthesis in prevention of secondary rectocele. Laparoscopic sacrocolpopexy with non-resorbable prostheses can treat pelvic organ prolapse with good results and few complications including in terms of prothetic exposure or infection. Considered as the reference surgical technique for prolapse repair, the various aspects of this procedure must therefore be well codified. [ABSTRACT FROM AUTHOR]

An abstract of the article "A contraction stress test before induction of labour for small-for-gestational age fetuses: does it decrease the rate of Caesarean during labour?," by M. Chesnais and colleagues is presented.

Pathogenic variants in the MED13L gene are associated with the autosomal dominant MED13L syndrome, which is characterised by global developmental delay and cardiac malformations. We investigated two heterozygous MED13L variants located at the canonical donor splice site motif of exon 7: c.1009+1G>C and c.1009+5G>C. We report that in silico predictions suggested two possible outcomes: exon 7 skipping, resulting in loss of the phosphodegron motif essential for MED13L regulation, or activation of a cryptic donor site in intron 7, leading to intron retention. RNA analysis confirmed that both variants affected the exon 7 splice donor site, resulting in the retention of 73 bp of intron 7. This retention caused a frameshift and premature translation termination, consistent with haploinsufficiency. Our results highlight the importance of combining predictive and experimental approaches to understand the functional impact of splice site variants. These insights into the molecular consequences of MED13L variants provide a deeper understanding of the genetic basis of MED13L syndrome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Cutaneous stoma stenosis represents a frequent complication associated with continent catheterizable channel, often necessitating recurrent patients' consultation, hospital admission, and repetitive surgical interventions. Management strategies encompass dilatation, incision, and, in case of refractory stenosis, invasive surgical revision., Objectives: In this study, we aimed to assess the efficacy of buccal mucosa graft as an alternative therapeutic approach for managing cutaneous catheterizable channel stenosis., Methods: We conducted a retrospective analysis of all patients referred to our two specialized tertiary reconstructive urology centers due to continent catheterizable cutaneous channel stenosis between January 2015 and June 2023. The study cohort comprises patients who had undergone either a Mitrofanoff, an ileal continent catheterizable channel (Monti or Casal) or a Malone antegrade colonic enema procedure (MACE), all of whom exhibited stoma stenosis., Results: We identified 14 patients who underwent a total of 15 buccal mucosa graft augmentation repairs for stenosis. Following a mean follow-up duration of 30 months, 11 out of 15 procedures (73%) demonstrated successful outcomes. Notably, no complication was observed, except in the 4 cases classified as failures. These failures were attributed to either stenosis recurrence (3 cases) or fleshy bud persistence (1 case). Importantly, patients did not report any concerns regarding esthetic or functional complains., Conclusions: Buccal mucosa graft emerges as a minimally invasive alternative for repairing continent catheterizable channel stenosis, yielding a promising success rate and an exceptionally low incidence rate of complications., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: The objective of the CUROPF and CTMH was to establish recommendations about ketamine induced uropathy management., Methods: A systematic review of the literature was conducted on Pubmed/Medline by the members of the French committees of female urology and male lower urinary tract symptoms focusing on the epidemiology, pathophysiology, diagnosis and treatment of ketamine induced uropathy, evaluating references and level of evidence., Results: Recommendations include epidemiology, pathophysiology, diagnosis and treatment of ketamine induced uropathy. It represents a rising healthcare issue, with major augmentation of ketamine consumers and new patients across the world. Several pathophysiology pathways are suspected and need clinical validation. The diagnosis is clinical, with hyperactive bladder symptoms mostly including pollakiuria, but also lower urinary tract symptoms, and histological, requiring bladder biopsies to rule out carcinoma and show specific features and inflammation. Therapeutics are currently limited and non-specific, combining abstinence, hydrodistension, pentosane polysulfate and Botox injections. Complex reconstructive surgeries should be avoided and be considered as a last resort., Conclusion: These guidelines should provide tools to help every physician confronted to ketamine induced uropathy patients, which represents a growing issue. Hopefully, this work will allow the improvement of the screening, management and care of ketamine induced uropathy in the future., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Recent advances in the understanding of infantile developmental epileptic encephalopathies (IDEE) have revealed the association of biallelic pathogenic variants in UGDH. In this study, we report two novel combinations identified by exome sequencing: p.(Arg135Trp) with p.(Arg65*) and p.(Arg102Trp) with p.(Arg65*). Both combinations share a common pathogenic nonsense variant, with the missense variants strategically located in the NAD-binding domain of the UGDH protein, predicted in structural models to create new interactions with the central domain. The first patient exhibited the typical UGDH-related disease phenotype and progressive microcephaly, a rarely reported feature. In contrast, the second patient presented an atypical phenotype, including absence of seizure, severe intellectual disability, ataxic gait, and abnormal eye movements. This comprehensive analysis extends the phenotypic spectrum of UGDH syndrome beyond early infantile intractable encephalopathy to include intellectual disability without epilepsy., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

In this study, we investigated the role of a newly identified homozygous variant (c.1245 + 6T > C) in the CFAP61 gene in the development of multiple morphologically abnormal flagella (MMAF) in an infertile patient. Using exome sequencing, we identified this variant, which led to exon 12 skipping and the production of a truncated CFAP61 protein. Transmission electron microscopy analysis of the patient's spermatozoa revealed various flagellar abnormalities, including defective nuclear chromatin condensation, axoneme disorganization, and mitochondria embedded in residual cytoplasmic droplets. Despite a fertilization rate of 83.3% through ICSI, there was no successful pregnancy due to poor embryo quality.Our findings suggest a link between the identified CFAP61 variant and MMAF, indicating potential disruption in radial spokes' assembly or function crucial for normal ciliary motility. Furthermore, nearly half of the observed sperm heads displayed chromatin condensation defects, possibly contributing to the low blastulation rate. This case underscores the significance of genetic counseling and testing, particularly for couples dealing with infertility and MMAF. Early identification of such genetic variants can guide appropriate interventions and improve reproductive outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Sacral nerve neuromodulation (SNM) is a safe and effective therapy for the management of fecal and/or urinary incontinence. The generators InterStim™ and InterStim™ II (Medtronic™) are non-rechargeable active implantable medical devices with a limited lifespan. The aims of this study were to assess the generators' median lifespan for all indications and the long-term hospital costs of the therapy., Methods: This was a retrospective monocentric study that included 215 patients aged over 18 years who were treated by SNM for fecal incontinence and/or urinary incontinence. Lifespan was considered as the amount of time between definitive implantation and observed battery depletion by the surgeon and was assessed by the Kaplan-Meier method. Costs were assessed according to the activity-based pricing of the French public health care system., Results: The median observed lifetime of stimulators implanted in our center was 7.29 years and 5.9 years for InterStim™ and InterStim™ II, respectively. The difference observed between the two generations was statistically significant. The modelling of primary implantation and renewal costs allowed us to observe that the decrease in the lifetime of Interstim™ II is associated with an increase in hospital costs over time. The retrospective study design is one limitation and we did not take into consideration stimulation's settings., Conclusions: The InterStim™ II lifespan is shorter than the first-generation device. This is associated with an increase of the long-term hospital costs. Additional information about the new neuromodulator will be required to choose the most appropriate IPG for the patient while optimizing the costs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to seek predictive factors and develop a predictive tool for sacral nerve modulation (SNM) implantation in patients with non-obstructive urinary retention and/or slow urinary stream (NOUR/SS)., Methods: This study was designed as a retrospective study including all patients who have undergone a two-stage SNM for NOUR/SS between 2000 and 2021 in 11 academic hospitals. The primary outcome was defined as the implantation rate. Secondary outcomes included changes in bladder emptying parameters. Univariate and multivariable logistic regression analysis were performed and determined odds ratio for IPG implantation to build a predictive tool. The performance of the multivariable model discrimination was evaluated using the c-statistics and an internal validation was performed using bootstrap resampling., Results: Of the 357 patients included, 210 (58.8%) were finally implanted. After multivariable logistic regression, 4 predictive factors were found, including age (≤ 52 yo; OR = 3.31 CI95% [1.79; 6.14]), gender (female; OR = 2.62 CI95% [1.39; 4.92]), maximal urethral closure pressure (≥ 70 cmH 2 O; OR: 2.36 CI95% [1.17; 4.74]), and the absence of an underlying neurological disease affecting the lower motor neuron (OR = 2.25 CI95% [1.07; 4.76]). Combining these factors, we established 16 response profiles with distinct IPG implantation rates, ranging from 8.7 to 81.5%. Internal validation found a good discrimination value (c-statistic, 0.724; 95% CI 0.660-0.789) with a low optimism bias (0.013). This allowed us to develop a predictive tool ( https://predictivetool.wixsite.com/void )., Conclusion: The present study identified 4 predictive factors, allowing to develop a predictive tool for SNM implantation in NOUR/SS patients, that may help in guiding therapeutic decision-making. External validation of the tool is warranted., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Transcutaneous posterior tibial nerve stimulation (TC-PTNS) is a validated option for lower urinary tract symptoms (LUTS) management, with a short-term success rate of around 60% and few adverse events. Our goal was to report the efficacy and safety results of TC-PTNS using the newly issued device TENSI+ for LUTS management., Patients and Methods: A multicenter, retrospective study was conducted in 7 urology departments in France. All patients treated with TC-PTNS for LUTS using the TENSI+ device between September 2021 and February 2022 were included. All patients received supervised at-home training by a specialized nurse. All patients were asked to do daily, 20minutes sessions of TC-PTNS. Patient demographics, history, initial symptoms and previous treatment were collected at inclusion. A follow-up visit was scheduled at 3 months. Efficacy was evaluated through treatment persistence at 3 months and PGI-I (Patient Global Impression of Improvement) score. Adverse events were recorded., Results: One hundred and three patients (86 women and 17 men) were included. All patients had overactive bladder symptoms, 64 suffered from urgency incontinence, and 24 had associated voiding symptoms. Eighteen patients had neurogenic background, and 30 previously received anticholinergics. After a median follow-up of 12 [10-21]weeks, 70 patients were still using the device (68%). PGI-I score reflected an improvement in 70.9% and was 1, 2 and 3 in 28, 26 and 19 patients respectively, while 24 were unchanged and 6 were worse. No clinical baseline parameter was predictive of success. Adverse events included pain at stimulation site (two cases) and pelvic pain (two patients), which rapidly resolved after treatment interruption., Conclusions: TC-PTNS with TENSI+ device is an effective option for LUTS management, with results that seem similar to other TC-PTNS approaches. Adverse events were mild and reversible after treatment interruption., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: We assess the efficacy, safety, and predictive factors for failure of synthetic mid-urethral slings for the treatment of urinary incontinence in a large cohort of women with neurogenic lower urinary tract dysfunction., Materials and Methods: Women aged 18 years or older who received a synthetic mid-urethral sling for stress urinary incontinence or mixed urinary incontinence in 3 centers between 2004 and 2019 and who had a neurological disorder were included. Exclusion criteria were less than 1 year of follow-up, concomitant pelvic organ prolapse repair, previous synthetic sling implantation, and no baseline urodynamics. The primary outcome was surgical failure, defined as recurrence of stress urinary incontinence during follow-up. Kaplan-Meier analysis was used to estimate the 5-year failure rate. Adjusted Cox proportional hazard model was used to identify factors associated with surgical failure. Complications and reoperations during the follow-up have also been reported., Results: A total of 115 women with a median age of 53 years were included . The median follow-up duration was 75 months. The 5-year failure rate was 48% (95 CI 46%-57%). Age above 50 years, negative tension-free vaginal tape test and transobturator route were associated with surgical failure. Thirty-six patients (31.3%) underwent at least 1 reoperation for complications or failure, and 2 required definitive intermittent catheterization., Conclusions: Synthetic mid-urethral slings may be an acceptable alternative to autologous slings or artificial urinary sphincters for the treatment of stress urinary incontinence in a selected group of patients with neurogenic lower urinary tract dysfunction.

When a patient presents with symptoms suggestive of pelvic organ prolapse (POP), clinical evaluation should include an assessment of symptoms, their impact on daily life and rule out other pelvic pathologies. The prolapse should be described compartment by compartment, indicating the extent of the externalization for each. The diagnosis of POP is clinical. Additional exams may be requested to explore the symptoms associated or not explained by the observed prolapse. Pelvic floor muscle training and pessaries are non-surgical conservative treatment options recommended as first-line therapy for pelvic organ prolapse. They can be offered in combination and be associated with the management of modifiable risk factors for prolapse. If the conservative therapeutic options do not meet the patient's expectations, surgery should be proposed if the symptoms are disabling, related to pelvic organ prolapse, detected on clinical examination and significant (stage 2 or more of the POP-Q classification). Surgical routes for POP repair can be abdominal with mesh placement, or vaginal with autologous tissue. Laparoscopic sacrocolpopexy is recommended for cases of apical and anterior prolapse. Autologous vaginal surgery (including colpocleisis) is a recommended option for elderly and fragile patients. For cases of isolated rectocele, the posterior vaginal route with autologous tissue should be preferentially performed over the transanal route. The decision to place a mesh must be made in consultation with a multidisciplinary team. After the surgery, the patient should be reassessed by the surgeon, even in the absence of symptoms or complications, and in the long term by a primary care or specialist doctor., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: Determine if head-perineum distance (HPD) measurement before vacuum extraction (VE) was predictive of an obstetric anal sphincter injury (OASIS) occurrence., Methods: Retrospective, bicentric (Lille and Poissy, France) cohort study conducted from January 2019 to June 2020. All VE in singleton pregnancies of ≥34 weeks were included. HPD measurement was performed without compression of the tissues before each VE. The judgment criterion was the occurrence of an OASIS., Results: Of 12 568 deliveries, VE was performed in 1093 (8.6%). Among these 1093 women undergoing VE, 675 (61.7%) with HPD measurement were included. OASIS was found in 6.5% of women (n = 44; 95% CI 4.5-8.7). HPD was not associated with OASIS (38.5 ± 12.6 mm in women with OASIS vs 37.4 ± 12.0 mm in women without; adjusted OR [aOR] per 5 mm increase = 0.92; 95% CI 0.79-1.06). Increased HPD was associated with higher risk of sequential extraction (aOR = 1.19; 95% CI 1.06-1.32), extraction duration >10 min (aOR = 1.12; 95% CI 1.02-1.23) and shoulder dystocia (aOR = 1.20; 95% CI 1.03-1.40)., Conclusion: Ultrasound-measured head-perineum distance does not predict the occurrence of obstetric anal sphincter injury during a VE. The interest of HPD is more about predicting the success or difficulty of VE rather its specific complications., (© 2022 International Federation of Gynecology and Obstetrics.)

TRIT1 encodes a tRNA isopentenyl transferase that allows a strong interaction between the mini helix and the codon. Recent reports support the TRIT1 bi-allelic alterations as the cause of an autosomal recessive disorder, named combined oxydative phophorylation deficiency 35, with microcephaly, developmental disability, and epilepsy. The phenotype is due to decreased mitochondrial function, with deficit of i6A37 in cytosolic and mitochondrial tRNA. Only 10 patients have been reported. We report on two new patients with four novel variants, and confirm the published clinical TRIT1 deficient phenotype stressing the possibility of both very severe, with generalized pharmaco-resistant seizures, and mild phenotypes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome., Methods: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076., Findings: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia., Interpretation: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction., Funding: French Ministry of Health., Competing Interests: Declaration of interests TS reports receiving consulting fees from Dilafor. LS reports receiving consulting fees from Dilafor; lecture fees from Bayer, GlaxoSmithKline, and Sigvaris; and lecture and consulting fees from Ferring Pharmaceuticals. AJV reprts receiving consulting fees from Norgine. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction and Hypothesis: The aim of our study was to evaluate the efficiency and safety of synthetic mid-urethral slings (sMUS) for the treatment of stress urinary incontinence (SUI) in women with neurogenic lower urinary tract dysfunction (NLUTD)., Methods: A systematic review was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. MEDLINE, Embase and Cochrane controlled trials databases were systematically searched from January 1995 to April 2021. Studies including adult women with NLUTD who had a sMUS for SUI were considered for inclusion. Primary outcome was success of the surgery according to study criteria. Secondary outcomes were complications, especially de novo urgency, urinary retention, tape exposure and revision for complications., Results: A total of 752 abstracts were screened and 9 studies were included, representing 298 patients. The mean age was 52 years and median follow-up was 41.3 months. sMUS insertion was successful in 237 patients (79.5%). The median rate of de novo urgency was 15.7% (range 8.3-30%). In patients with spontaneous voiding, the median rate of retention was 19.3% (range 0-46.7%) and 21 out of 26 patients required intermittent self-catheterisation. Four cases of tape exposure were reported, and 8 patients underwent a revision for complications., Conclusions: This review suggests that sMUS might offer interesting success rates and acceptable morbidity and could be considered for the treatment of SUI in women with NLUTD. Further studies are required to define which patients would be more likely to benefit from this intervention, as well as its place among the other surgical treatments for SUI., (© 2021. The International Urogynecological Association.)

SHANK2 code a scaffolding protein located at the postsynaptic membrane of glutamatergic neurons. To date, only nine patients were reported with a SHANK2-variation or microdeletion. Molecular anomalies were identified through screening of large cohorts of patients, but only poor patient clinical descriptions were available. However, this information is crucial for patient care. Here, we describe two additional unrelated patients carrying a SHANK2 de novo variant, improving the delineation of the condition. Phenotypic analysis of these 11 patients identified as major features of the condition: mild to moderate intellectual disability, speech delay, poor language skills, and autism spectrum disorders., (Copyright © 2020. Published by Elsevier Masson SAS.)

Purpose: Missing heritability in human diseases represents a major challenge, and this is particularly true for ABCA4-associated Stargardt disease (STGD1). We aimed to elucidate the genomic and transcriptomic variation in 1054 unsolved STGD and STGD-like probands., Methods: Sequencing of the complete 128-kb ABCA4 gene was performed using single-molecule molecular inversion probes (smMIPs), based on a semiautomated and cost-effective method. Structural variants (SVs) were identified using relative read coverage analyses and putative splice defects were studied using in vitro assays., Results: In 448 biallelic probands 14 known and 13 novel deep-intronic variants were found, resulting in pseudoexon (PE) insertions or exon elongations in 105 alleles. Intriguingly, intron 13 variants c.1938-621G>A and c.1938-514G>A resulted in dual PE insertions consisting of the same upstream, but different downstream PEs. The intron 44 variant c.6148-84A>T resulted in two PE insertions and flanking exon deletions. Eleven distinct large deletions were found, two of which contained small inverted segments. Uniparental isodisomy of chromosome 1 was identified in one proband., Conclusion: Deep sequencing of ABCA4 and midigene-based splice assays allowed the identification of SVs and causal deep-intronic variants in 25% of biallelic STGD1 cases, which represents a model study that can be applied to other inherited diseases.

X-linked intellectual disability (XLID) is a genetically heterogeneous condition involving more than 100 genes. To date, 35 pathogenic variants have been reported in the lysine specific demethylase 5C (KDM5C) gene. KDM5C variants are one of the major causes of moderate to severe XLID. Affected males present with short stature, distinctive facial features, behavioral disorders, epilepsy, and spasticity. For most of these variants, related female carriers have been reported, but phenotypic descriptions were poor. Here, we present clinical and molecular features of 19 females carrying 10 novel heterozygous variants affecting KDM5C function, including five probands with de novo variants. Four heterozygous females were asymptomatic. All affected individuals presented with learning disabilities or ID (mostly moderate), and four also had a language impairment mainly affecting expression. Behavioral disturbances were frequent, and endocrine disorders were more frequent in females. In conclusion, our findings provide evidence of the role of KDM5C in ID in females highlighting the increasing implication of XLID genes in females, even in sporadic affected individuals. Disease expression of XLID in females should be taken into consideration for genetic counseling., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cellular stress response contributes to epithelial defense in adaptation to environment changes. Galectins play a pivotal role in the regulation of this response in malignant cells. However, precise underlying mechanisms are largely unknown. Here we demonstrate that Galectin-3, a pro and anti-apoptotic lectin, is required for setting up a correct cellular response to stress by orchestrating several effects. First, Galectin-3 constitutes a key post-transcriptional regulator of stress-related mRNA regulons coordinating the cell metabolism, the mTORC1 complex or the unfolded protein response (UPR). Moreover, we demonstrated the presence of Galectin-3 with mitochondria-associated membranes (MAM), and its interaction with proteins located at the ER or mitochondrial membranes. There Galectin-3 prevents the activation and recruitment at the mitochondria of the regulator of mitochondria fission DRP-1. Accordingly, loss of Galectin-3 impairs mitochondrial morphology, with more fragmented and round mitochondria, and dynamics both in normal and cancer epithelial cells in basal conditions. Importantly, Galectin-3 deficient cells also display changes of the activity of the mitochondrial respiratory chain complexes, of the mTORC1/S6RP/4EBP1 translation pathway and reactive oxygen species levels. Regarding the ER, Galectin-3 did not modify the activities of the 3 branches of the UPR in basal conditions. However, Galectin-3 favours an adaptative UPR following ER stress induction by Thapsigargin treatment. Altogether, at the ER-mitochondria interface, Galectin-3 coordinates the functioning of the ER and mitochondria, preserves the integrity of mitochondrial network and modulates the ER stress response.

Microdeletions encompassing 14q11.2 locus, involving SUPT16H and CHD8, were shown to cause developmental delay, intellectual disability, autism spectrum disorders and macrocephaly. Variations leading to CHD8 haploinsufficiency or loss of function were also shown to lead to a similar phenotype. Recently, a 14q11.2 microduplication syndrome, encompassing CHD8 and SUPT16H, has been described, highlighting the importance of a tight control of at least CHD8 gene-dosage for a normal development. There have been only a few reports of 14q11.2 microduplications. Patients showed variable neurodevelopmental issues of variable severity. Breakpoints of the microduplications were non-recurrent, making interpretation of the CNV and determination of their clinical relevance difficult. Here, we report on two patients with 14q11.2 microduplication encompassing CHD8 and SUPT16H, one of whom had normal intelligence. Review of previous reports describing patients with comparable microduplications allowed for a more precise delineation of the condition and widening of the phenotypic spectrum.

Background: Lower urinary tract symptoms related to benign prostatic obstruction (BPO) are frequent in men aged > 50 years. Based on the use of innovative medical devices, a number of transurethral ablative techniques have recently been developed for the surgical treatment of BPO. In recent years, GreenLight photoselective vaporization of the prostate (PVP) has been considered as a non-inferior alternative to transurethral resection of the prostate. The GreenLight PVP is usually considered as an interesting surgical option for patients treated via oral anticoagulants (OACs) with regard to its haemostatic properties. The aim of this study was to assess the impact of maintaining OAC treatment in patients undergoing PVP., Methods: This study is a multicentre, open-label, randomized controlled trial (RCT) designed to show the non-inferiority of PVP surgery in patients with BPO treated with OACs. This study is designed to enrol 386 OAC-treated patients (treated with vitamin K antagonists and direct oral anticoagulants) who are undergoing PVP for BPO. Patients will be randomized (1:1) to either maintain or stop OAC treatment during the perioperative course. The intervention group will maintain OAC treatment until the day before surgery and resume OAC treatment the day after surgery, whereas the control group will stop OAC treatment (with or without low-molecular-weight heparin bridging therapy) according to the anaesthesia guidelines. The primary outcome of interest to be assessed is the 30-day complications rate according to the Clavien-Dindo classification. The secondary endpoint will examine the 30-day rate of haemorrhagic and thrombotic events. This study will provide 80% power to show non-inferiority, defined as not worse than a 10% (non-inferiority margin) inferior change in the proportion of patients with good outcomes (Clavien-Dindo score < 2), using two-tailed 95% confidence intervals., Discussion: This first multicentre RCT in the field is underway to evaluate the safety and efficacy of PVP in patients with ongoing OAC therapy. The study results could influence the perioperative management of OACs in BPO surgery with a high level of evidence., Trial Registration: ClinicalTrials.gov, NCT03297281 . Registered on 29 September 2017.

Helsmoortel-van der Aa (SWI/SNF autism-related or ADNP syndrome) is an autosomal dominant monogenic syndrome caused by de novo variants in the last exon of ADNP gene and no deletions have been documented to date. We report the first case of a 3 years and 10 months old boy exhibiting typical features of ADNP syndrome, including intellectual disability, autistic traits, facial dysmorphism, hyperlaxity, mood disorder, behavioral problems, and severe chronic constipation. 60K Agilent array-comparative genomic hybridization (CGH) identified a heterozygous interstitial microdeletion at 20q13.13 chromosome region, encompassing ADNP and DPM1. Taking into account the clinical phenotype of previously reported cases with ADNP single-point variants, genotype-phenotype correlation in the proband was established and the diagnosis of Helsmoortel-van der Aa syndrome was made. Our report thus confirms that ADNP haploinsufficiency is associated with Helsmoortel-van der Aa syndrome as well as highlights the utility of whole-genome array-CGH for detection of unbalanced submicroscopic chromosomal rearrangements in routine clinical setting in patients with unexplained intellectual disability and/or syndromic autism.

Background: The dramatic rise in cesarean delivery rates worldwide in recent decades, without evidence of a concomitant decrease in cerebral palsy rates, has raised concerns about its potential negative consequences for maternal and infant health. In 2014, the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine jointly published an Obstetric Care Consensus for safe prevention of the primary cesarean delivery., Objective: We sought to assess whether modification of our protocol to implement these recommendations helped to decrease our primary cesarean delivery rate safely., Study Design: This is a before-and-after retrospective cohort study at a university referral hospital. In March 2014, the threshold for defining active labor changed from 4 to >6 cm and arrest of first-stage labor from lack of cervical change despite regular contractions after 3 hours of oxytocin administration with amniotomy and epidural anesthesia to no change after 4 hours of adequate or 6 hours of inadequate contractions in women with an epidural. The definition of second-stage arrest of labor changed simultaneously from lack of progress for 3 hours with adequate contractions in women with epidural anesthesia to no progress for ≥4 hours in nulliparas or 3 hours in multiparas with an epidural. We compared maternal and neonatal outcomes over two 1 year periods: from March 2013 to February 2014 (before, preguideline) and from June 2014 to May 2015 (after, postguideline). We included all women with singleton pregnancies at ≥37 weeks' gestation, in vertex presentation, in spontaneous or induced labor, and with epidural anesthesia. We excluded women with an elective or previous cesarean delivery and those with obstetric or fetal complications., Results: This study included 3283 and 3068 women in the before and after periods, respectively. The groups had similar general and obstetric characteristics. The global cesarean delivery rate decreased significantly from 9.4% in the preguideline to 6.9% in the postguideline period (odds ratio, 0.71; 95% confidence interval, 0.59-0.85; P < .01). The cesarean delivery rate for arrest of first-stage labor fell by half, from 1.8% to 0.9% (odds ratio, 0.51; 95% confidence interval, 0.31-0.81; P < .01) but was significant only among nulliparous women. The cesarean delivery rate for second-stage arrest of labor decreased but not significantly between periods (1.3% vs 1.0%; odds ratio, 0.73; 95% confidence interval, 0.44-1.22; P = .2), and the cesarean delivery rate for failure of induction remained similar (3.7% vs 3.5%; odds ratio, 1.06; 95% confidence interval, 0.06-13.24; P = .88). The median duration of labor before cesarean delivery also became significantly longer among nulliparous women during the later period. Maternal and neonatal outcomes did not differ between the 2 periods, except that the rate of 1 minute Apgar score <7 fell significantly in the later period (8.4% vs 6.9%; odds ratio, 0.80; 95% confidence interval, 0.66-0.97; P = .02)., Conclusion: The modification of our protocol by implementing the new consensus recommendations was associated with a reduction of the rate of primary cesarean delivery performed for arrest of labor with no apparent increase in immediate adverse neonatal outcomes in nulliparous women at term with singleton pregnancies in vertex presentation and with epidural anesthesia. Further studies are needed to assess the long-term maternal and neonatal safety of these policies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The management of major renal trauma has shifted in the last decade in favor of a nonoperative approach. Our level 1 trauma center promotes this approach with the objective of renal function preservation. However, certain situations still require surgery. In this study we analyze predictors of surgery and long-term outcomes after conservative management., Materials and Methods: From January 2004 to March 2015 we prospectively collected data from all patients admitted to our institution for high grade blunt renal trauma (grades IV and V). Nonoperative management was considered successful when patients did not undergo surgical exploration, regardless of angioembolization or endoscopic treatment., Results: Of 306 patients with renal trauma 151 presented with major injuries, including 124 grade IV and 27 grade V. Nonoperative management was successful in 110 (89%) cases of grade IV and 14 (52%) cases of grade V lesions. Deceleration mechanism (p=0.03), associated lesions (p=0.001), percentage of devitalized parenchyma (p=0.012), angioembolization (p <0.001), hemodynamic instability (p <0.001) and low hemoglobin (p=0.001) were more frequent in patients treated surgically. On multivariate analysis grade (OR 7.36, p=0.01) and hemodynamic instability (OR 4.18, p=0.04) were the only independent predictors of surgical treatment. Long-term followup of preserved kidneys revealed a remaining 40% and 0% relative renal function after grade IV and V injuries, respectively. Only devascularized parenchyma greater than 25% predicted the decline of long-term renal function., Conclusions: Nonoperative management can and should be performed safely in cases of grade IV injuries whenever possible, with valuable long-term renal function. It can also be initiated in grade V cases. However, surgeons should consider nephrectomy with the onset of any suspicious symptoms., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To predict the outcomes of a non-operative approach to managing urinary extravasation after blunt renal trauma., Patients and Methods: A prospective observational study was conducted between January 2004 and October 2011. First-line non-operative management was proposed for 99 patients presenting with a grade IV blunt renal injury according to the revised American Association for the Surgery of Trauma (AAST) classification. Among them, 72 patients presented with a urinary extravasation. Management and outcomes were recorded and compared between patients presenting and those who did not present with urinary leakage. Relative postoperative renal function was assessed 6 months after the trauma using dimercapto-succinic acid renal scintigraphy. Predictors of the need for endoscopic or surgical management and long-term renal function were evaluated on multivariate analysis., Results: Among patients with urinary leakage, endoscopic ureteric stent placement and open surgery were required in 37% and 15%, respectively. On multivariate analysis, fever of >38.5 °C and ureteric clot obstruction were independent predictors of the need for ureteric stent placement. The only predictor of open surgery was the percentage of devitalised parenchyma. Long-term renal function loss was correlated to the percentage of devitalised parenchyma and associated visceral lesions. Urinary extravasation did not predict surgical intervention or long-term renal function loss., Conclusions: Urinary extravasation after blunt renal trauma can be successfully managed conservatively and does not predict long-term decreased renal function or surgery requirement. A devascularised parenchyma volume of >25% predicts a higher rate of surgery and poorer renal function., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Purpose: The management of high grade blunt renal injury has evolved with time to become increasingly conservative with the ultimate objective of renal preservation. We evaluated relative renal function with dimercapto-succinic acid renal scintigraphy 6 months after major renal trauma (grade IV or V)., Materials and Methods: This prospective observational study was done between January 2004 and April 2010. All patients who presented with grade IV or V renal trauma and were treated conservatively were included in analysis. Patient and trauma characteristics, and initial management were recorded. Relative renal function was evaluated by dimercapto-succinic acid renal scintigraphy 6 months after trauma., Results: A total of 88 patients were included in the study. Conservative management was possible in 79 patients (90%), including 69 and 10 with grade IV and V trauma, respectively. Dimercapto-succinic acid renal scintigraphy was done at 6 months for 22 patients (28%). Mean relative renal function for grade IV and V injuries was 39% and 11%, respectively (p=0.0041). The percent of devascularized parenchyma (p=0.0033) and the vascular subtype of grade IV injuries (p=0.0194) also correlated with decreased renal function. No complication or de novo arterial hypertension was noted., Conclusions: Conservative treatment achieves the objective of renal function preservation for grade IV lesions. Grade V and specific subtypes of grade IV injury have a poor functional outcome. Further study must be performed to determine which patients will benefit from conservative treatment vs early nephrectomy to avoid a longer hospital stay and useless procedures., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Malaria may be complicated by development of thrombocytopenia, elevated liver enzymes, and/or hemolysis, which may be difficult to distinguish from HELLP (hemolytic anemia; elevated liver enzymes; low platelet count) syndrome in a pregnant patient. A 33-year-old woman developed a HELLP-like syndrome and persistent fever postpartum without symptoms of preeclampsia. A malaria blood smear was performed and was positive for Plasmodium falciparum. The patient was immediately treated with quinine. The follow-up was uneventful with total disappearance of fever and prompt resolution of biochemical signs of HELLP-like syndrome 3 days later. Malaria in a pregnant woman can masquerade as HELLP syndrome. The wide overlap in symptoms (headache, malaise, digestive symptoms) does not suggest that symptoms would be effective in differentiating malaria and preeclampsia. A recent travel in endemic area, associated with malaria blood smear and clinic examination, should be the key of the differential diagnosis., (Thieme Medical Publishers.)

Background: Portal vein cavernoma (PVC) is a rare disease resulting from extrahepatic portal vein thrombosis and development of collateral venous circulation. The management of pregnancy and delivery in woman with PVC has rarely been described., Cases: Two primiparous women are presented to illustrate the management of PVC during pregnancy and discuss the delivery route according to the symptoms and the PVC complications. The first patient presented PVC associated with large jejunal varices and high anticardiolipid antibodies. She was treated with beta-blocker therapy and low molecular weight heparin during pregnancy, and delivered by cesarean section. The second patient presented protein S deficiency complicated by PVC and thrombocytopenia and delivered vaginally without complications., Conclusion: Many issues should be considered when counseling women with PVC, including the management before and during pregnancy according to symptoms and PVC complications. A multidisciplinary approach seems to be key to the management of delivery. Our advice to caregivers is that elective cesarean section seems necessary in cases with digestive varices. Vaginal delivery, with a passive second stage, seems to be relatively safe and less morbid in women without digestive varices, when maternal and fetal tolerance permits.