Response to Snodgrass and Bush

We sincerely appreciate the comments made by Warren Snodgrass and Nicol Bush regarding our paper. First of all, we need to clarify that of our population of 130 patients only 66 have already reached pubertal development (55 in the preputial flap group and 11 in the staged repair). The aim of the published paper, as already clearly stated in our discussion, was limited to a retrospective analysis of the potential risk of development of megalourethra and fistula in this population. We fully agree that there is indeed a potential large amount of very important data retained in these series which may help to better understand some of the still unresolved questions on long-term outcome of hypospadias repair. Unfortunately we will need a few more years of follow-up before we will be able to fulfill these requests. Regarding the multiple questions mentioned we will try to provide some specific answers

A Case of Hypotonia-Cystinuria Syndrome With Genito-Urinary Malformations and Extrarenal Involvement

Hypotonia-Cystinuria syndrome (HCS) is a rare disease, caused by a mutation in two contiguous genes (SLC3A1 and PREPL) localized on chromosome 2p21, and it is characterized by both renal involvement with cystine stones and nervous involvement with hypotonia. We here describe a 2 years old child with HCS associated with other clinical features as congenital anomalies of kidney and urinary tract (primary obstructed megaureter, POM), cryptorchidism and cardiac involvement (patent foramen ovale with atrial septum aneurysm). To the best of our knowledge, cryporchidism and POM have never been reported before in patients with HCS. Moreover, a cardiac involvement has been described only in another case of HCS that, interestingly, presents the same genetic abnormalities as our patient. The diagnosis of HCS can be difficult because neurological signs are aspecific and kidney stones are commonly absent during the first months of life. A better understanding of the complete clinical scenario associated with HCS can help clinicians suspect, diagnose and treat HCS earlier with a positive influence on both neurological and renal outcome

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc

Long term outcomes in terms of sexual function and relational aspects in primary cases born with Bladder Exstrophy

Introduction and purpose Bladder exstrophy (BE) is a rare malformation that involves not only the bladder, urethra and genital organs but also all of the pelvic floor and bones. Its prevalence is about 1/25.000-40.000 born in Italy and about 15 new cases are estimated each year. The disease affects males and females with a ratio of 2:1. The etiology is unknown. The effect of this malformation, affecting the urogenital complex, can be reflected on urinary continence and sexual life. These aspects can influence strongly the social life of patients. We evaluated both psychosexual and psychosocial aspects and sexual dysfunctional in adult with BE using a validated instrument. Materials and methods We conducted a survey using SESAMO (Sexuality Evaluation Schedule Assessment Monitoring). We evaluated a group of patients (cases) and a group of controls. All are invited to complete the male or female, single or partnership version of the instrument. The questionnaires are loaded into the program SESAME-Win and processed by the software SESAME-R. Both cases and the controls are analyzed in general and by sex and by emotional situation (single or partnership). We investigated the Areas found to be significant in the group of cases and not in the corresponding group of controls; in these Areas we analyzed individually every Items, highlighting the percentage of significant responses. We also assessed the state of continence about patients. Results This questionnaire is being distributed to 45 patients with BE, including 30 men (M) and 15 women (W) and 40 controls, 20 M and 20 W. 26 cases (17 M and 9 W), with a response rate of 57.7%, and 35 controls (18 M and 17 W) with a response rate of 87.5%, were finally included in analysis. With regard to the cases 16 (11 M and 5 W), completed the questionnaire as situation of “partnership” and 10 (6 M and 4 W) as "single". In group of controls 26 (14 M and 12 W) completed the questionnaire as situation of "partnership" and 9 (4 M and 5 W) as "single". Median age was 28 years in the Cases group and 30.5 in Controls. Environmental psychology and Lived Body Areas were significant in all groups of Cases (except in Females Total about Lived Body) and never in groups of controls. Desire Area is significant only in females Cases. Pleasure Areas are significant only in the groups of Controls and never in Cases. Remote Masturbation is significant, both in the group of Cases that Controls Females. Previous Experiential and the Sexual and Medical History are significant in all groups (except in the group of females controls about this last Area). Patients had a continence rate of 80, 7%. Conclusions Patients with bladder exstrophy have a tendency toward obsessive-compulsive disorder towards sexuality. They are dissatisfied about their free time, but they reached a satisfactory social position. They have a critical relationship with their parents and especially with mother, certainly more present in the clinical pathway. Especially with female patients, there is a lack of communication about sexuality. They present a difficulty to express and share their experiences, particularly sexuality, which they define like frustration experience. The body perception was very critical, more critical in single cases than in partnership. The areas of the body affected by the malformation are hated by themselves. Sexual dysfunction affects a high percentage of both sexes and the women seem to have more difficulty in having a satisfying sexual relationship. Sexuality appear a pathological experience in both single and partnership group. Singles are not satisfied with their emotional situation and even the frequency of sexual intercourse. Patients who live in a partnership use frequently masturbation not for his own pleasure but as act that substitute a complete sexual intercourse.Introduzione e scopo dello studio L’Estrofia Vescicale-Epispadia (EV) è una rara patologia congenita caratterizzata da uno sviluppo incompleto della vescica e dell’uretra. La sua prevalenza varia da 1/25.000 a 1/40.000 nati ed in Italia si stima un'incidenza di circa 15 nuovi casi ogni anno. La patologia colpisce maschi e femmine con un rapporto di 2:1. L’etiologia non è nota. La patologia, colpendo l’apparato uro-genitale si riflette su elementi di primaria importanza, vale a dire la continenza urinaria e la vita sessuale. Tali aspetti possono condizionare fortemente la vita di relazione dei soggetti affetti. Scopo dello studio è stato quello di identificare sia gli aspetti psicosessuali e psicosociali che gli aspetti disfunzionali sessuali in soggetti affetti da EV. Materiali e metodi Abbiamo eseguito un’indagine strutturata mediante il questionario SESAMO (Sexuality Evaluation Schedule Assessment Monitoring - Boccadoro, Perillo 1996). Sono stati individuati due gruppi d’indagine: un gruppo di pazienti (casi) e uno di soggetti non portatori della patologia (controlli). Tutti i soggetti sono stati invitati a rispondere alla versione maschile o femminile, single o di coppia del questionario. I questionari sono stati caricati nel programma SESAMO-Win ed elaborati dal software SESAMO-R. Sia i Casi che i controlli sono stati analizzati sia in generale che divisi per sesso e situazione affettiva single/coppia. Sono state indagate le Aree risultate significative nel gruppo dei Casi e non nel corrispettivo gruppo dei Controlli; di tali Aree sono stati analizzati singolarmente i vari Item che le componevano, evidenziando la percentuale di risposte significative. Abbiamo inoltre valutato lo stato di continenza dei pazienti. Risultati Il questionario è stato consegnato a 45 pazienti affetti da EV di cui 30 maschi (M) e 15 femmine (F) e 40 controlli, di cui 20 M e 20 F. Hanno aderito allo studio 26 casi (17 M e 9 F), con un tasso di risposta di 57,7%, e 35 controlli (18 M e 17 F) con un tasso di risposta di 87,5%. In particolare per quanto riguarda i casi, 16 (61,5%) di cui 11 M e 5 F, hanno compilato il questionario come situazione affettiva di “coppia” e 10 (38,5%) di cui 6 M e 4 F come “single”; riguardo i controlli 26 (74,5%) (14 M e 12 F) hanno compilato il questionario come situazione affettiva di “coppia” e 9 (25,5) (4 M e 5 F) come “single”. L’età mediana è stata di 28 anni nel gruppo dei casi e 30,5 nei controlli. Le Aree Relati psicoambientali e Vissuto corporeo sono risultate significative in tutti i gruppi dei Casi (eccetto nei Casi Femmine totali per quanto riguarda il vissuto corporeo) e mai nei gruppi dei Controlli. L’Area Desiderio è significativa solo nei Casi Femmine. Gli Ambiti del piacere sono significativi solo nei gruppi dei Controlli e mai nei Casi. La Masturbazione remota è significativa sia nel gruppo dei Casi che dei Controlli Femmine. L’Esperienziale pregresso e l’ Anamnesi Medica e Sessuale sono significative in tutti i gruppi (eccetto nel gruppo dei Controlli Femmine per quest’ultima Area). I pazienti hanno presentato un tasso di continenza dell’80,7%. Conclusioni I pazienti affetti da estrofia vescicale presentano una spiccata tendenza all’ossessività che si manifesta sia nelle pratiche quotidiane che nei confronti della sessualità. Sono insoddisfatti del loro tempo libero ma circa la metà di essi ha raggiunto una condizione sociale soddisfacente. Presentano un rapporto critico con i propri genitori e in particolar modo con la madre, figura sicuramente più presente nel percorso clinico; specialmente nelle pazienti di sesso femminile si riscontra una carente comunicazione intrafamiliare riguardo alla sessualità. E’ emersa inoltre una difficoltà ad esprimere e raccontare le loro esperienze, in particolare quelle sessuali che definiscono frustranti. L’attenzione rivolta al “se’ corporeo” è risultata molto critica, più nei casi in situazione di coppia che nei single; le zone interessate dalla malattia e di conseguenza coinvolte negli interventi chirurgici sono le più odiate da essi. Le disfunzioni sessuali colpiscono in alta percentuale entrambi i sessi e nel complesso le donne sembrano avere più difficoltà ad avere un rapporto sessuale soddisfacente. La sessualità è vissuta in maniera patologica sia nel gruppo dei pazienti “single” che “coppie”. I pazienti single non sono soddisfatti della loro situazione affettiva e neppure della frequenza dei rapporti sessuali. I pazienti che vivono una situazione di coppia sono spinti ad attuare con maggiore frequenza la masturbazione non per proprio piacere ma come atto sostitutivo al rapporto sessuale completo

Resultant hypospadias after epispadias repair in bladder exstrophy patients: A difficult surgical task with high complication rate

BACKGROUND/PURPOSE: The aim of this study was to analyze the complication rate in male bladder exstrophy (BE) patients undergoing flap or graft urethroplasty for the repair of resultant hypospadias after epispadias repair. METHODS: We retrospectively reviewed the charts of 22 male BE patients who underwent 24 urethroplasties for resultant hypospadias between 2000 and 2009. Median patient age was 4.2 (range, 1.5-26.5) years, and median follow-up was 7.5 (range, 0.8-10.3) years. Meatal location after epispadias repair was midshaft in 6 cases and proximal shaft in 15. Complications were compared in relation to meatal position, type of urethroplasty (no graft vs graft), use of second-layer coverage of the urethroplasty, and use of suprapubic diversion. RESULTS: Overall, complications developed in 12 (50%) patients, including 10 urethrocutaneous fistulas and 2 urethroplasty dehiscence. Univariate analysis failed to show any differences between complicated and uncomplicated cases in all the variables. Only the 3 cases undergoing a 2-stage repair had fully successful outcomes. CONCLUSIONS: Urethroplasty in patients with BE has a high complication rate. Quality of local tissue and presence of scarring are possibly the 2 major determinants of a poor outcome. A staged repair seems the safest, although this commits the patient to 2 procedures

Exposition to chickenpox of two children with autonflammatory syndrome under treatment with anakinra

We report two children with autoinflammatory syndromes treated with anakinra who came in contact with the varicella-zoster virus after being exposed accidentally to infected children: both cases were managed prophylactically with specific antichickenpox intravenous immunoglobulins and anakinra temporary suspension; neither adverse events nor complications related to the natural course of chickenpox were experienced by the two patients. The risk of developing infectious events should be closely monitored, because of the absence of data concerning long-term safety of biological agents in the pediatric age, and prevention strategies should be highly encouraged before they are started

Substitution Phalloplasty in Patients With Bladder Exstrophy-Epispadias Complex: A Systematic Review of Techniques, Complications and Outcomes

BACKGROUND: Males born with bladder exstrophy-epispadias complex generally have a shorter phallus, split corpora with dorsal curvature, and a scarred and flattened glans, so substitution phalloplasty is often required.AIM: The aim of this study was to review the techniques, complications, and outcomes of substitution phalloplasty in bladder exstrophy-epispadias complex patients to determine the ideal surgical procedure and gauge the risks and benefits for the patient.METHODS: A systematic review of the literature was performed using PubMed/MEDLINE and the Cochrane Library with the following terms: ("phalloplasty"); (("epispadias") OR ("bladder exstrophy") OR ("cloacal exstrophy")). We included only full-text articles reporting data about techniques and outcomes of substitution phalloplasty in patients with bladder exstrophy-epispadias complex.OUTCOMES: To determine whether patients with bladder exstrophy-epispadias complex might benefit from substitution phalloplasty.RESULTS: We selected 7 studies involving 47 patients. All the studies were characterized by a low level of evidence and a heterogeneous approach during treatment and outcome assessment. The free radial forearm flap was the most commonly performed technique (89%) with an overall complication rate of 15%. Urethroplasty was performed in 22 of 47 (47%) patients, and in most cases (20/22) a "tube-within-the-tube" technique was performed simultaneously with the phalloplasty (20/47). Urethroplasty complications were recorded in 12 of 22 (54%) patients with 6 fistulae and 6 stenoses. A penile prosthesis was implanted in 32 of 47 (68%) patients and complications occurred in 8 of 32 (25%) patients with 6 erosion. Aesthetic, sexual, and psychological outcomes were satisfactory, but none of the studies used validated instruments for the final assessment.CLINICAL IMPLICATIONS: It was not possible to formulate any recommendations based on a high level of evidence regarding substitution phalloplasty in patients with bladder exstrophy-epispadias complex.STRENGTH & LIMITATION: To our knowledge, this is the first review to address bladder exstrophy-epispadias complex patients only. The limitations are mainly represented by the small number of cases because of the rarity of this disease and by the fact that no studies used validated instruments.CONCLUSION: Substitution phalloplasty in patients with bladder exstrophy-epispadias complex can achieve good functional, aesthetic, psychological, and sexual outcomes. It requires multiple procedures and carries a high complication rate. Multicentric studies including the assessment of patients by means of a validated questionnaire which investigates both sexual function and psychosexual satisfaction are required. Berrettini A, Sampogna G, Gnech M, etal. Substitution Phalloplasty in Patients With Bladder Exstrophy-Epispadias Complex: A Systematic Review of Techniques, Complications, and Outcomes. J Sex Med 2020;XX:XXX-XXX

Fluorescence-Guided Surgery and Novel Innovative Technologies for Improved Visualization in Pediatric Urology

Fluorescence-guided surgery (FGS), three-dimensional (3D) imaging technologies, and other innovative devices are rapidly revolutionizing the field of urology, providing surgeons with powerful tools for a more complete understanding of patient-specific anatomy. Today, several new intraoperative imaging technologies and cutting-edge devices are available in adult urology to assist surgeons in delivering personalized interventions. Their applications are also gradually growing in general pediatric surgery, where the detailed visualization of normal and pathological structures has the potential to significantly minimize perioperative complications and improve surgical outcomes. In the field of pediatric urology, FGS, 3D reconstructions and printing technologies, augmented reality (AR) devices, contrast-enhanced ultrasound (CEUS), and intraoperative magnetic resonance imaging (iMRI) have been increasingly adopted for a more realistic understanding of the normal and abnormal anatomy, providing a valuable insight to deliver customized treatments in real time. This narrative review aims to illustrate the main applications of these new technologies and imaging devices in the clinical setting of pediatric urology by selecting, with a strict methodology, the most promising articles published in the international scientific literature on this topic. The purpose is to favor early adoption and stimulate more research on this topic for the benefit of children