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Context Neurourological patients often encounter bacteriuria without any symptoms or may experience symptoms suspicious of urinary tract infections (UTIs). However, there is a lack of guidelines that unequivocally state the definition of UTIs in this specific patient group. Objective To present all used definitions of UTIs in neurourological patients. Evidence acquisition This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were identified by electronic search of Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov without a time limitation (last search September 2020) and by screening of reference lists and reviews. The occurrences of the various UTI definitions were counted and the frequencies calculated. Evidence synthesis After screening 7164 abstracts, we included 32 studies enrolling a total of 8488 patients with a neurourological disorder who took part in an interventional clinical study. UTI definitions were heterogeneous. The concordance to predefined definitions was low. Conclusions Interventional clinical studies rarely report specific definitions for UTIs, and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed. Patient summary Patients suffering from neurological disorders often experience symptoms in their lower urinary tract that resemble urinary tract infections. Furthermore, they can have positive urine cultures without symptoms (the so-called asymptomatic bacteriuria). However, clinical studies rarely report specific definitions for urinary tract infections, and when it is done, they are heterogeneous. A generally accepted urinary tract infection definition for neurourological patients is urgently needed. Take Home Message Interventional clinical studies on neurourological patients rarely report specific definitions for urinary tract infections (UTIs), and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.

Context Controversy still exists regarding the balance of benefits and harms for the different surgical options for neurogenic stress urinary incontinence (N-SUI). Objective To identify which surgical option for N-SUI offers the highest cure rate and best safety without compromising urinary tract function and bladder management. Evidence acquisition A systematic review was performed under the auspices of the European Association of Urology Guidelines Office and the European Association of Urology Neuro-Urology Guidelines Panel according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Evidence synthesis A total of 32 studies were included. Overall, 852 neurourological patients were surgically treated for N-SUI. The treatment offered most often (13/32 studies) was an artificial urinary sphincter (AUS; 49%, 416/852) and was associated with a need for reintervention in one-third of patients. More than 200 surgical revisions were described. Overall, 146/852 patients (17%) received concomitant bladder augmentation, mainly during placement of an AUS (42%, 62/146) or autologous sling (34% of women and 14% of men). Following pubovaginal sling placement, dryness was achieved in 83% of cases. A significant improvement in N-SUI was observed in 87% (82/94) of women following placement of a synthetic midurethral sling. Efficacy after insertion of an adjustable continence therapy device (ACT 40%, proACT 60%) was reported for 38/128 cases (30%). The cure rate for bulking agents was 35% (9/25) according to 2/32 studies, mainly among men (90%). The risk of bias was highly relevant. Baseline and postoperative cystometry were missing in 13 and 28 studies, respectively. Conclusions The evidence is mainly reported in retrospective studies. More than one intervention is often required to achieve continence because of coexisting neurogenic detrusor overactivity, low compliance, or the onset of complications in the medium and long term. Urodynamic data are needed to better clarify the success of N-SUI treatment with the different techniques. Patient summary Our review shows that insertion of an artificial urinary sphincter for urinary incontinence is effective but is highly associated with a need for repeat surgery. Other surgical options may have lower continence rates or a risk of requiring intermittent catheterization, which patients should be informed about before deciding on surgery for their incontinence.

Aims To determine the bleeding risk in patients taking anticoagulants (AC) and antiplatelets (AP) before onabotulinumtoxinA (BoNT-A) injections and improve peri-operative decision making and counseling. Methods We performed a retrospective review of patients having intravesical BoNT-A in three teaching hospitals from January 2016 to July 2018. Demographic data, indication for intravesical BoNT-A injection, and side-effects of significant bleeding requiring intervention were recorded. Results Five hundred and thirty-two patients had intravesical BoNT-A injections during this time. Sixty-three patients of mean age 69 years (range 19-89) had a total of 114 separate rounds of BoNT-A injections whilst on treatment dose AC/AP therapy. Of the 63, there were 33 males, with 46 having idiopatic detrusor overactivity and 17 with neurogenic detrusor overactivity. Each patient had between 1 and 7 repeat injections during the studied period. AC/AP use across the 114 episodes included; aspirin 44, clopidogrel 37, warfarin 19, and NOAC (novel/non-vitamin K oral anticoagulant) 14. Patients on warfarin who had point of care testing all had international normalized ratio less than 3. BoNT-A dose varied from 100U to 300U-modal dosage was 200U.1/114(0.88%) injection episodes resulted in postinjection hematuria requiring overnight admission. This resolved spontaneously, with an overnight catheter. This patient was on rivaroxaban and had 300U of BoNT-A injected through 20 sites, on a background of previous prostate radiotherapy and self-catheterization. Conclusions Continuation of AP/AC therapy during intravesical BoNT-A injection treatment appears to be safe-with a 0.88% rate of spontaneously resolving hematuria.

We aim to determine the presentation of and immediate and longer-term outcomes of vaginal surgical excision of urethral extrusion of mid-urethral tape (MUT). We performed a retrospective analysis of all patients with urethral extrusion of MUT having vaginal surgical excision between 2007 and 2018. The MUT was removed either partially (via vaginal approach) or completely (via combined vaginal and laparoscopic approach). Functional outcomes and any re-interventions are described. Thirty-four patients of median age 53 (range 34–82) years were identified. Preoperative symptomatic recurrent/persistent urinary incontinence was present in 29/34(85%) with 24/34(71%) women having recurrent/persistent stress urinary incontinence (SUI) or stress predominant mixed urinary incontinence (s-MUI) on urodynamics. Vaginal surgical excision was performed alone in 33/34(97%) women and in combination with laparoscopic removal of abdominopelvic MUT in 1/34(3%) woman. In the longer term vaginal/urethral pain resolved or improved in all 15/15(100%) patients presenting with this complaint whilst patient reported poor flow resolved in 8/9 (89%) women. Twenty-eight of 34 women (82%) had persistent/recurrent SUI or s-MUI following MUT excision. Twenty-four of 34 women (71%) had further SUI surgery with cure or improvement of SUI in 20/24 (83%) patients. The outcome of vaginal surgical excision of the MUT was cure or improvement of pain in 100% and resolution of poor flow in 89% women. Recurrent/persistent SUI or s-MUI was present in 82% following removal as compared to 71% women prior to removal. Of the 71% of women electing to have further surgery for recurrent/persistent SUI/s-MUI, 83% were dry or improved afterwards.

Purpose The NIH Undiagnosed Diseases Network (UDN) evaluates participants with disorders that have defied diagnosis, applying personalized clinical and genomic evaluations and innovative research. The clinical sites of the UDN are essential to advancing the UDN mission; this study assesses their contributions relative to standard clinical practices. Methods We analyzed retrospective data from four UDN clinical sites, from July 2015 to September 2019, for diagnoses, new disease gene discoveries and the underlying investigative methods. Results Of 791 evaluated individuals, 231 received 240 diagnoses and 17 new disease-gene associations were recognized. Straightforward diagnoses on UDN exome and genome sequencing occurred in 35% (84/240). We considered these tractable in standard clinical practice, although genome sequencing is not yet widely available clinically. The majority (156/240, 65%) required additional UDN-driven investigations, including 90 diagnoses that occurred after prior nondiagnostic exome sequencing and 45 diagnoses (19%) that were nongenetic. The UDN-driven investigations included complementary/supplementary phenotyping, innovative analyses of genomic variants, and collaborative science for functional assays and animal modeling. Conclusion Investigations driven by the clinical sites identified diagnostic and research paradigms that surpass standard diagnostic processes. The new diagnoses, disease gene discoveries, and delineation of novel disorders represent a model for genomic medicine and science.

Lower urinary tract dysfunction is a major cause of morbidity in patients with neurogenic conditions. One of the significant issues in this group is urinary tract infections. In this review, the causes of bacteriuria along with the symptoms, diagnosis, prevention and treatment options will be discussed. As in other areas of neuro-urology there is a lack of randomized controlled trials in this field. Most of the evidence is from retrospective cohort studies. Nonetheless, there are a number of guidelines and consensus statements from international organizations to standardize the treatment of recurrent urinary infections in this complex group of patients. The management of recurrent urinary infections symptoms in neurogenic patients is challenging as these patients do not always exhibit classical signs and symptoms. The evidence base is not so strong for treatment pathways. We need structured randomized control studies to better understand and manage this complex condition in this cohort of patients.

Introduction In the development of terminology of the lower urinary tract (LUT), due to its increasing complexity, the terminology for male LUT surgery needs to be updated using a male-specific approach and via a clinically-based consensus report. Methods This report combines the input of members of the Standardization Committee of the International Continence Society in a Working Group with recognized experts in the field, assisted by many external referees. Appropriate core clinical categories and a subclassification were developed to give a numeric coding to each definition. An extensive process of 14 rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). Results A Terminology Report for male LUT and pelvic floor surgery, encompassing 149 separate definitions/descriptors, has been developed. It is clinically-based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in male LUT surgery. Figures have not been included to avoid any preference or bias towards a specific procedure. Conclusions A consensus-based Terminology Report for male LUT surgery has been produced aimed at being a significant aid to clinical practice and a stimulus for research.

AIMS To investigate typical pad weight gain (PWG) in asymptomatic women who have never reported any episodes of urinary incontinence. METHODS An observational study was performed by measuring the increase in weight of small sanitary pads worn by 35 healthy, female volunteers of a median age 36 (range, 23-56) years. Each pad was worn for a minimum of 5 h which is the typical maximum duration of an ambulatory urodynamics study. RESULTS The median duration of pad wear was 6 h (interquartile range [IQR], 5-8). The median PWG was 0.111 g (IQR, 0.047-0.255). The maximum recorded PWG was 0.621 g and the minimum was 0.012 g. PWG was not significantly affected by age, parity, years since last delivery, body mass index, or menopausal status. CONCLUSIONS PWG over a median duration of 6 h (IQR, 5-8) is typically

Introduction and hypothesis In randomized clinical trials onabotulinumtoxinA was demonstrated to be an effective and well-tolerated treatment for overactive bladder (OAB) with urinary incontinence (UI). However, data reporting onabotulinumtoxinA use in everyday clinical practice are limited. Here, we present the results from a large, first-of-its-kind real-world study in patients with OAB. Methods This was a prospective, observational, multinational study (GRACE; ClinicalTrials.gov, NCT02161159) performed in four European countries. Patients (N = 504) aged ≥ 18 years with OAB inadequately managed with ≥ 1 anticholinergic received onabotulinumtoxinA per their physician’s normal clinical practice. Results Physicians primarily used rigid cystoscopes for onabotulinumtoxinA injection; anesthesia/analgesia was utilized during most treatment procedures. Significant reductions in UI episodes/day from baseline to weeks 1 and 12 were observed as well as in micturition, urgency, and nocturia episodes/day. These improvements in urinary symptoms corresponded to higher scores on the treatment benefit scale at week 12. The use of other OAB medications dropped from baseline to weeks 1 and 12 and was sustained to week 52, which paralleled a reduction in the number of incontinence products used during that time frame. Adverse reactions were reported in 2.6% of patients throughout the study. Conclusions In this real-world study, significant improvements in urinary symptoms were seen following onabotulinumtoxinA treatment as early as week 1 and sustained to at least week 12. This was accompanied by a reduced reliance upon incontinence products and reduction in concomitant OAB medication use. OnabotulinumtoxinA was well tolerated with no new safety signals.

Aims To investigate the role of onabotulinumtoxinA (BTX-A) injections in patients with failed augmentation cystoplasty for neuropathic or idiopathic detrusor overactivity (NDO or IDO). Methods A retrospective review of all cystoplasty patients who underwent onabotulinumtoxinA injection at a tertiary center between 2008 and 2019 was performed. Details including indications and time from cystoplasty, video-urodynamic parameters, onabotulinumtoxinA dose, and clinical outcomes were analyzed. Telephone interview was performed for patients that requested repeat onabotulinumtoxinA injections. The interview included a modified PGIC7 and UDI6 questionnaires. A positive clinical response was considered improvement of overactive symptoms sufficient to merit repeat onabotulinumtoxinA injection and a modified PGIC7 of four or above. Results Thirty patients were identified (11 men and 19 women). The indications for augmentation were IDO (n = 18) or NDO (n = 12). Mean age at the time of cystoplasty was 42 years (range, 10-61). Interval between cystoplasty and initial onabotulinumtoxinA was 98 months (range, 3-271). Video-urodynamics before onabotulinumtoxinA revealed low compliance in 13 patients, DO in 22 patients, and combined low compliance/DO in 10. The median maximum cystometric bladder capacity was 338 mL (range, 77-570 mL). Thirteen patients responded to onabotulinumtoxinA injections. Higher peak DO pressure was associated with a significantly higher chance that the patient would experience benefit from the injections P = .026). The patients that responded to onabotulinumtoxin A underwent a total of 115 procedures (mean, 8.8 injections) over a mean 88 months (range, 20-157 months). Conclusions Forty-three percent of patients responded well to intra-detrusor onabotulinumtoxinA injections. This avoided the need for more invasive surgery and had a positive impact on their quality of life.

Objectives: To evaluate the efficacy of ultrasonography and colour and power Doppler ultrasonography for diagnosis of intraosseous lesions of the jaws and to correlate the contents of the lesion with the histological findings. Materials and Methods: 30 patients with intraosseous jaw lesions in the maxilla or mandible were included in the study. Ultrasonographic examinations were performed and, according to the ultrasonography findings, the jaw lesions were classified into three groups: cystic, semisolid and solid. Further, colour Doppler ultrasonographic examination was performed to evaluate blood flow in all patients following which surgical treatment was done. The correlation between ultrasonography and Doppler ultrasonography findings of the lesions and histological findings was investigated. Results: Thirty intra-osseous lesions from twenty nine patients were evaluated in this study. Twenty two lesions were located in the mandible and eight were in the maxilla. Of the thirty lesions, the ultrasound examination was inconclusive in one lesion because of the thick cortical vestibular bone plate and for two lesions histopathology was not available. Conclusions: Information regarding the content of intraosseous jaw lesions can be obtained using ultrasound before any surgical procedure. Further, vascularization of the lesion can be assessed via Doppler ultrasonography. Also, there was a correlation between the ultrasound findings and the definitive histological diagnosis. Keywords: Intraosseous, Ultrasonography, Doppler ultrasonography, Histopathology.

While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify the limitations of ES, we investigated the diagnostic yield of genetic tests beyond ES in our Undiagnosed Diseases Network (UDN) participants. We reviewed the yield of additional genetic testing including genome sequencing (GS), copy number variant (CNV), noncoding variant (NCV), repeat expansion (RE), or methylation testing in UDN cases with nondiagnostic ES results. Overall, 36/54 (67%) of total diagnoses were based on clinical findings and coding variants found by ES and 3/54 (6%) were based on clinical findings only. The remaining 15/54 (28%) required testing beyond ES. Of these, 7/15 (47%) had NCV, 6/15 (40%) CNV, and 2/15 (13%) had a RE or a DNA methylation disorder. Thus 18/54 (33%) of diagnoses were not solved exclusively by ES. Several methods were needed to detect and/or confirm the functional effects of the variants missed by ES, and in some cases by GS. These results indicate that tests to detect elusive variants should be considered after nondiagnostic preliminary steps. Further studies are needed to determine the cost-effectiveness of tests beyond ES that provide diagnoses and insights to possible treatment.

Vesicovaginal fistulae (VVF) repair success rates for simple surgical fistulae are high, but constitute a significantly greater challenge when occurring in a radiotherapy field. We aim to evaluate the causes, assessment, closure rates and functional outcomes of VVF surgery in patients with previous radiotherapy. Data on all VVF repairs were collected prospectively. A retrospective review of outcomes in those with VVF performed between 2009 and 2018 was carried out. Details including time from radiotherapy, pre-operative assessments, approach to surgery and functional outcome were analysed. Twenty women with VVFs were identified. The mean age was 59 (range 25–88) years. Primary malignancy was cervical in 16 women, with the remaining 4 women having ovarian, urethral, endometrial and rectal cancer respectively. All women had external beam radiotherapy with 6 (30%) undergoing boosted brachytherapy. Mean interval between radiotherapy and fistula repair was 19 (range 0–40) years. Fistulae arose spontaneously in 14 patients, whereas 6 occurred following a further surgical intervention.Closure was attempted vaginally in 7 women and abdominally in 1, whereas 12 had a primary diversion owing to significant bladder contracture and ureteric involvement. The closure rate in those attempted was 62.5%, 40% in those with spontaneous fistulae compared with 100% for post-surgical fistulae, but only 20% for the total cohort. Closure of VVF is a significant challenge, with an initial success rate of 20% and an overall success rate of only 25%. Seventy percent required primary or secondary urinary diversion. Vaginal surgery was utilised in the majority to try to avoid a hostile pelvis, but the surgical approach should be tailored to individual circumstances.

Inflammatory cells contribute to irreversible damage in pulmonary arterial hypertension (PAH). We hypothesized that in PAH, dysfunctional BMPR2 signaling in macrophages contributes to pulmonary vascular injury and phenotypic changes via proinflammatory cytokine production. Studies were conducted in: (1) Rosa26-rtTA2 3 X TetO7-Bmpr2delx4 FVB/N mice (mutant Bmpr2 is universally expressed, BMPR2 delx4 mice) given a weekly intra-tracheal liposomal clodronate injections for four weeks; and (2) LysM-Cre X floxed BMPR2 X floxed eGFP monocyte lineage-specific BMPR2 knockout (KO) mouse model (Bmpr2 gene expression knockdown in monocytic lineage cells) (BMPR2 KO ) following three weeks of sugen/hypoxia treatment. In the BMPR2 delx4 mice, increased right ventricular systolic pressure (RVSP; P

INTRODUCTION AND OBJECTIVE:Urethroplasty for female urethral stricture (FUS) is becoming increasingly popular however there is little to guide choice of technique as all series to date contain smal...

Leukodystrophies are a group of genetically determined disorders that affect development or maintenance of central nervous system myelin. Leukodystrophies have an incidence of at least 1 in 4700 live births and significant morbidity and elevated risk of early death. This report includes a discussion of the types of leukodystrophies; their prevalence, clinical presentation, symptoms, and diagnosis; and current and future treatments. Leukodystrophies can present at any age from infancy to adulthood, with variability in disease progression and clinical presentation, ranging from developmental delay to seizures to spasticity. Diagnosis is based on a combination of history, examination, and radiologic and laboratory findings, including genetic testing. Although there are few cures, there are significant opportunities for care and improvements in patient well-being. Rapid advances in imaging and diagnosis, the emergence of and requirement for timely treatments, and the addition of leukodystrophy screening to newborn screening, make an understanding of the leukodystrophies necessary for pediatricians and other care providers for children.

Huntington disease (HD) is caused by a pathologic cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. Typical adult-onset disease occurs with a minimum of 40 repeats. With more than 60 CAG repeats, patients can have juvenile-onset disease (jHD), with symptom onset by the age of 20 years. We report a case of a boy with extreme early onset, paternally inherited jHD, with symptom onset between 18 and 24 months. He was found to have 250 to 350 CAG repeats, one of the largest repeat expansions published to date. At initial presentation, he had an ataxic gait, truncal titubation, and speech delay. Magnetic resonance imaging showed cerebellar atrophy. Over time, he continued to regress and became nonverbal, wheelchair-bound, gastrostomy-tube dependent, and increasingly rigid. His young age at presentation and the ethical concerns regarding HD testing in minors delayed his diagnosis.

Mutations in the torsinA-interacting protein 1 (TOR1AIP1) gene result in a severe muscular dystrophy with minimal literature in the pediatric population. We review a case of TOR1AIP1 gene mutation in a 16-year-old Caucasian female with a long history of muscle weakness. Extensive clinical workup was performed and MRI at time of initial presentation demonstrated no significant muscular atrophy with heterogenous STIR hyperintensity of the lower extremity muscles. MRI findings seven years later included extensive atrophy of the lower extremities, with severe progression, including the gluteal muscles, iliopsoas, rectus femoris, and obturator internus. There was also significant atrophy of the rectus abdominis and internal and external oblique muscles, and iliacus muscles. The MRI findings showed more proximal involvement of lower extremities and no atrophy of the tibialis anterior, making TOR1AIP1 the more likely genetic cause. Muscle biopsy findings supported TOR1AIP1 limb-girdle muscular dystrophy. Though rare, TOR1AIP1 gene mutation occurs in pediatric patients and MRI can aid in diagnosis and help differentiate from other types of muscular dystrophy. Genetic and pathology workup is also crucial to accurate diagnosis and possible treatment of these patients.

Aims An updated literature review on outcomes in men treated with currently commercially available bulking agents was performed to determine whether this is a reasonable option in selected patients. Methods The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework of systematic reviews. A comprehensive search of PubMed, Medline, and Embase was undertaken. Abstracts were independently screened by two investigators to include men with stress urinary incontinence treated with a peri-urethral injection of bulking agents currently available in the market. Results Only eight original articles met the inclusion criteria. The bulking agents used were Macroplastique in five studies (total 123 patients), Opsys, Durasphere, and Urolastic in one study each (10, 7, and 2 patients, respectively). Only one study was randomized; Macroplastique vs AUS in men with mild or total incontinence. The included populations were heterogeneous and encompassed endoscopic, perineal, abdominal and laparoscopic prostate surgery as well as spinal cord injuries and urethral sphincter insufficiency. Significant dissimilarity was evident for the duration of incontinence (9-108 months), mean volume of bulking agent used (2.3-13.5 mL), number of cushions (1-5), depth and position of the cushions. The outcomes varied significantly, with reported dry rates between 0% and 83%. Outcomes were limited by relatively short follow-up in most studies. Conclusion Following initial enthusiasm and then dismay with collagen-based compounds, sparse and heterogeneous literature data were produced on newer non-migrating and nonabsorbable bulking agents. Some studies have suggested encouraging, if short term outcomes, however, future studies are needed in this field to support recommendations for widespread use.

AIMS To assess the incidence and management of urodynamic stress urinary incontinence (USUI) in women undergoing transvaginal excision of a urethral diverticulum (UD) at our institution. METHODS A prospective database, capturing patients undergoing urethral diverticulectomy over a 9-year period (May 2007 to August 2016), was reviewed focusing on USUI and subsequent management. RESULTS One hundred patients underwent UD excision (with modified Martius labial fat-pad flap interposition). Preoperative magnetic resonance imaging data, available in 90 patients, demonstrated that 80% had complex diverticula. Complete urodynamic data were available for 93 patients. Preoperatively, 27 patients (29%) had USUI of which 16 patients resolved with either UD excision alone (n = 8) or 3 months of pelvic floor muscle therapy (PFMT) (n = 8). All 11 with persistent postoperative USUI had video urodynamics (VUDs) confirming Blaivas type 3 USUI. Six patients had a rectus fascial pubovaginal sling (RFPVS) with success in five (83.3%) while five had a mid-urethral obturator tape (MUT-O) with 100% success. Sixteen patients developed de novo stress urinary incontinence (SUI) postoperatively, with resolution after PFMT in 12 (75%). VUDS identified USUI (Blaivas type 3) in two (of the remaining four) patients, managed successfully with MUT-O (n = 1) and RFPVS (n = 1). CONCLUSION Preoperative USUI is present in 29% with UD. Postoperatively, 35.5% (n = 33) have pre-existing (19) or de novo (14) SUI, of which 60.6% (n = 20) resolves after 12 months of conservative management. Surgery for USUI is required in 13 (13.9%), with cure in 92.3%. This supports our practice to excise UD primarily and delay USUI surgery, therefore, avoiding overtreatment for the majority.

Introduction and hypothesis The objective was to assess the comparative provider costs of vaginal and open abdominal repair of vesicovaginal fistula (VVF) and to determine the most cost-effective means of managing VVF. Methods A prospectively acquired database of all women undergoing VVF repair by a single surgeon between 2007 and 2015 was retrospectively reviewed to determine operating time, perioperative complications, inpatient stay and 30-day readmissions. The success and cost of the VVF repair were identified. Statistical analysis was by unpaired t test, Chi-squared test and Mann–Whitney U test. Results Forty-seven consecutive women of mean age 51 years (range 21–88) undergoing a first attempt at VVF repair at our institution were included; 32(68%) had vaginal repair with Martius fat pad interposition and 15 (32%) had open abdominal repair with omental interposition. There were no perioperative complications or 30-day readmissions in either group. Mean operative time was longer for open abdominal (223.4 min) than vaginal repair (196.9 min). Median inpatient stay was longer for an open abdominal (8 days) than for a vaginal approach (4 days). Successful anatomical closure was achieved in 91% of vaginal and 86% of open abdominal repairs at first attempt, and in 100% after second repair, where required. Mean/median costs for an abdominal repair were significantly higher, at £4,608.69/£4,169.20 than for vaginal repair at £3,381.50/£3,009.24 (P

Objectives To evaluate functional outcomes of surgery in patients with ectopic ureters diagnosed in adulthood; to review the world literature. Patients and methods Patients were referred over 10 years. Data including surgical history, presenting symptoms, diagnostic modalities, interventions and functional outcomes were collected; and the world literature reviewed. Results 9 women and 1 man had a mean age of 37 (range 20-58). All women were referred with lifelong leakage. The man was referred with storage LUTS. Three women had heminephrectomy/nephrectomy with the distal ureter left in-situ prior to referral. MRI was the predominant diagnostic tool but often took senior review to confirm the diagnosis. Excision of the ectopic ureter was performed with bladder neck reconstruction in 6 women, with concomitant rectus fascial sling in one patient. 4 of 6 (67%) women were cured of their stress incontinence with the bladder neck reconstruction alone, whilst two required further intervention. Three women had nephroureterectomy alone as primary treatment of which two were cured. The single male had heminephrectomy and excision of seminal vesicle. Conclusions Ectopic ureter is a rare diagnosis in adults but should be considered in patients who describe lifelong incontinence. Fine slice MRI is the imaging of choice. Excision of the ureter with bladder neck reconstruction alone was successful in two-thirds of patients, whilst further stress urinary incontinence surgery was required in one-third. Malignancy in ureteric remnants is described in 8% of the world literature. Patients should be counselled of this risk if the ureter is left in-situ.

Introduction In the development of terminology of the lower urinary tract, due to its increasing complexity, the terminology for male lower urinary tract and pelvic floor symptoms and dysfunction needs to be updated using a male-specific approach and via a clinically-based consensus report. Methods This report combines the input of members of the Standardisation Committee of the International Continence Society (ICS) in a Working Group with recognized experts in the field, assisted by many external referees. Appropriate core clinical categories and a subclassification were developed to give a numeric coding to each definition. An extensive process of 22 rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). Results A Terminology Report for male lower urinary tract and pelvic floor symptoms and dysfunction, encompassing around 390 separate definitions/descriptors, has been developed. It is clinically-based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in male lower urinary tract and pelvic floor dysfunction. Male-specific imaging (ultrasound, radiology, CT, and MRI) has been a major addition whilst appropriate figures have been included to supplement and help clarify the text. Conclusions A consensus-based Terminology Report for male lower urinary tract and pelvic floor symptoms and dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research.

Angiokeratomas consist of ectasias of dermal capillaries associated with an acanthotic and hyperkeratotic overlying epidermis. These dark red-to-purple, papular vascular anomalies can vary considerably in size, depth, and location. It is a skin disorder that rarely involves oral cavity. It can occur in localized or generalized form and is often associated with underlying metabolic disorder such as Fabry's disease and fucosidosis. It has many clinical variants with the same underlying histopathology. Mucosal involvement, including the oral cavity, is occasionally found either as a component of the systemic variety, called angiokeratoma corporis diffusum, or associated with cutaneous lesions in more locations. Isolated oral involvement seems to be rather infrequent, and only eighteen cases have been described in the world literature thus far. Isolated multiple angiokeratomas of tongue without plaque formation have been reported only four times before this. Here, we report a fifth case of isolated multiple angiokeratomas of tongue in a 16-year-old female which was confirmed by immunohistochemical pattern in consonance with a blood vessel origin, with expression of CD31, CD34, and von Willebrand factor. The lesion did not express D2-40 and CD45. No other malformation or metabolic disorder was found in the patient.

Introduction: About 40% of women suffer pelvic organ prolapse (POP) in a lifetime. The current standard intervention for vault prolapse is a mesh sacrocolpopexy or sacrohysteropexy. However, patients and surgeons are increasingly hesitant to use mesh given recent the UK and Food and Drug Administration warnings and litigation. A possible alternative is to use autologous tissue to support the vault, as a mesh-free solution. We report the outcomes from an initial series of autologous rectus fascia sheath (RFS) sacrocolpopexy and sacrohysteropexy in patients with complex pelvic floor dysfunction. Patients and Methods: All patients had previous, multiple urological/gynecological surgery and declined standard mesh repairs. All had preoperative videourodynamics and defecating magnetic resonance imaging evaluation. The autologous POP repair was performed using 10–18 cm of rectus sheath with a similar technique to that employing mesh to support the anterior-posterior vaginal walls or encircle the cervix and secured to the sacral promontory. Results: Seven patients with a mean age of 52 (33–64) years underwent autologous RFS POP repair between 2014 and 2017. Mean follow-up is 16 (range 2–33) months. All patients have durable result at last follow-up. No significant complications are reported. Conclusions: This is the first report of patients with complex pelvic floor dysfunction and apical POP being managed with autologous RFS sacrocolpopexy/sacrohysteropexy, and only the second report of a free graft being utilized with success. Autologous RFS sacrocolpopexy/sacrohysteropexy avoids the 10%–15% risks of mesh-related complications. Further studies of long-term durability are needed.

Injuries to the bladder and ureter are uncommon but usually require prompt urological management. Due to their infrequent nature, Urologists maybe unfamiliar with managing these acute problems and may not work in specialist centres with readily available expertise in open and abdominal surgery. We aim to provide advice in the form of a consensus statement led by the Female, Neurological and Urodynamic Urology (FNUU) Section of the British Association of Urological Surgeons (BAUS), in consultation with BAUS members and consultants working in units throughout the UK, to create a comprehensive management pathway and a series of statements to aid clinicians.

Objective To look at best evidence and expert opinion to provide advice in the form of a consensus statement lead by Female, Neurological and Urodynamic Urology (FNUU) section of the British Association of Urological Surgeons (BAUS) in conjunction with the British Association of Urological Nurses (BAUN). Methods Initially a literature search was performed with incorporation of aspects of the existing guidance and further informed by UK best practice by core members of the group. The document then underwent reviews by the FNUU Executive Committee members, the BAUN executive committee, a separate experienced urologist and presented at the BAUS annual meeting 2020 to ensure wider feedback was incorporated in the document. Results Complications of long-term indwelling catheters include catheter-associated urinary tract infections (CAUTI), purple urine bag syndrome, catheter blockages, bladder spasms (causing pain and urinary leakage), loss of bladder capacity, urethral erosion ("catheter hypospadias")/dilatation of bladder outlet and chronic inflammation (metaplasia and cancer risk). Conclusions We have provided a list of recommendations and a troubleshooting table to help with the management of the complications of long term catheters.

Purpose To investigate pre-operative urodynamic parameters in male sling patients to ascertain whether this might better predict surgical outcomes and facilitate patient selection. Methods We performed a retrospective, case notes and video-urodynamics, review of men who underwent AdVanceXP male sling in three London hospitals between 2012 and 2019. Urodynamics were performed in all centres, while retrograde leak point pressure (RLPP) was performed in one centre. Results Successful outcome was seen in 99/130 (76%) of men who required one pad or less per day. The dry rate was 51%. Pad usage was linked to worse surgical outcomes, mean 2.6 (range 1–6.5) for success vs 3.6 (range 1–10) although the ranges were wide (p = 0.002). 24 h pad weight also reached statistical significance (p = 0.05), with a mean of 181 g for success group versus 475 g for the non-successful group. The incidence of DO in the non-successful group was significantly higher than in successful group (55% versus 29%, p = 0.0009). Bladder capacity less than 250 ml was also associated with worse outcomes (p = 0.003). Reduced compliance was not correlated with outcomes (31% for success groups vs 45% for non-successful group, p = 0.15). Preoperative RLPP was performed in 60/130 patients but did not independently reach statistical significance (p = 0.25). Conclusion Urodynamic parameters related to bladder function—detrusor overactivity and reduced maximum cystometric capacity predict male sling outcomes and may help in patient selection for male sling (or sphincter) surgery; whereas urodynamic parameters of sphincter incompetency (RLPP) were not predictive. Further larger scale studies are required to confirm these findings.

Objectives To report the British Association of Urological Surgeon's (BAUS) guidance on the assessment and management of female voiding dysfunction. Methods A contemporary literature search was conducted to identify the evidence base. The BAUS Section of Female, Neurological and Urodynamic Urology (FNUU) Executive Committee formed a guideline development group to draw up and review the recommendations. Where there was no supporting evidence, expert opinion of the BAUS FNUU executive committee, FNUU Section and BAUS members, including urology consultants working in units throughout the UK, was used. Results Female patients with voiding dysfunction can present with mixed urinary symptoms or urinary retention in both elective and emergency settings. Voiding dysfunction is caused by a wide range of conditions which can be categorized into bladder outlet obstruction (attributable to functional or anatomical causes) or detrusor underactivity. Guidance on the assessment, investigation and treatment of women with voiding dysfunction and urinary retention, in the absence of a known underlying neurological condition, is provided. Conclusion Wa have produced a BAUS approved consensus on the management pathway for female voiding dysfunction with the aim to optimize assessment and treatment pathways for patients.

BackgroundMany thousands of patients with a suspected Mendelian disease have their exomes/genomes sequenced every year, but only about 30% receive a definitive diagnosis. Since a novel Mendelian gene-disease association is published on average every business day, thousands of undiagnosed patient cases could receive a diagnosis each year if their genomes were regularly compared to the latest literature. With millions of genomes expected to be sequenced for rare disease analysis by 2025, and considering the current publication rate of 1.1 million new articles per annum in PubMed, manually reanalyzing the growing cases of undiagnosed patients is not sustainable.MethodsWe describe a fully automated reanalysis framework for patients with suspected, but undiagnosed, Mendelian disorders. The presented framework was tested by automatically parsing all ∼100,000 newly published peer reviewed papers every month and matching them on genotype and phenotype with all stored undiagnosed patients. If a new article contains a possible diagnosis for an undiagnosed patient, the system provides notification. We test the accuracy of the automatic reanalysis system on 110 patients, including 61 with available trio data.ResultsEven when trained only on older data, our system identifies 80% of reanalysis diagnoses, while sending only 0.5-1 alerts per patient per year, a 100-1,000-fold efficiency gain over manual literature surveillance of equivalent yield.ConclusionWe show that automatic reanalysis of patients with suspected Mendelian disease is feasible and has the potential to greatly streamline diagnosis. Our system is not intended to replace clinical judgment. Rather, clinical diagnostic services could greatly benefit from a modest re-allocation of time from manual literature exploration to review of automated reanalysis alerts. Our system additionally supports a new paradigm for medical IT systems: proactive, continuously learning and consequently able to autonomously identify valuable insights as they emerge in digital health records. We have launched automated patient reanalysis, trained on the latest data, with user accounts and daily literature updates at https://AMELIE.stanford.edu.

Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a fatty acid oxidation disorder in which the patient is unable to break down fats to produce energy. This disorder places children at risk for metabolic decompensation during periods of stress, such as routine childhood illnesses. The intent of this clinical report is to provide pediatricians with additional information regarding the acute clinical care of patients with MCADD. Although each patient with MCADD will still be expected to have a primary metabolic physician, the involvement of the primary care provider is crucial as well. Appropriate treatment of children with MCADD can lead to avoidance of morbidity and mortality.

International audience; Purpose:CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results:Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.Conclusion:We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome.

Background Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. Methods During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. Results 500 patients underwent surgery with median age 62.5 (IQR 51–71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. Conclusion It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration., Highlights • Priority surgeries are being cancelled every week due to the COVID-19 pandemic. • A multicentre surgical referral network was set up as part of an NHS England approach to continuing safe surgery • The referral network consisted of 14 NHS trusts and surgery was performed at a single COVID-19 ‘cold site’. • After 500 surgeries performed, there was a 0% 30-day mortality from COVID-19. • It is safe to continue cancer and priority surgery during the COVID-19 pandemic with appropriate service reconfiguration.

Purpose Overactive Bladder (OAB) is a common condition that is known to have a significant impact on Health Related Quality of Life (HRQoL). Whilst all patients will initially benefit from lifestyle modifications and behavioural therapy in the first instance drug therapy remains integral in management pathways. The purpose of this review paper is to reappraise the evidence based approach to the management of OAB in addition to exploring a new treatment algorithm for the escalation of treatment in those patients with refractory symptoms. Design Literature Review RESULTS: Antimuscarinic drugs are currently the most commonly used medication although the introduction of mirabegron, a β3 agonist, has provided an alternative and also allowed combination therapy in those patients who have failed to improve on primary therapy or who have troublesome side effects. For those patients with symptoms of refractory OAB more invasive therapies including OnabotulinumtoxinA, sacral neuromodulation and Percutaneous Tibial Nerve Stimulation (PTNS) may be indicated. Conclusion We propose a new, evidence based, treatment algorithm for the management of OAB in patients who remain refractory to first line therapy.

Coronavirus disease‐2019 (COVID‐19) pandemic significantly altered our daily life as well as our professional practice. COVID‐19 has disrupted our lives both professionally and personally. We know the urological management in a neurogenic patient needs to be tailored to the individual circumstances, this is even more pertinent during these uncertain times. International Continence Society is the premier international organization in functional urology. Lately, it has established an institute to facilitate teaching and training opportunities all over the world. The School of Neurourology teamed with the School of Modern Technology and set up a Webinar—“How to manage the neuro‐urological patients in the current pandemic.” This was set up as a case‐based discussion to deliberate the management of our patients in the present climate and examine the role of modern technology in overcoming the current barriers.

STUDY DESIGN: A prospective interventional pilot study using within-individual comparisons. OBJECTIVES: To assess the effect of dorsal genital nerve stimulation (DGNS) on urine-storage parameters in participants with spinal cord injury (SCI) and neurogenic detrusor overactivity (NDO) during natural bladder filling. SETTING: The London Spinal Cord Injuries Centre at the Royal National Orthopaedic Hospital, Stanmore, UK. METHODS: Ambulatory urodynamic monitoring (AUM) was carried out with and without DGNS, before and after a week of using DGNS at home. DGNS was applied on-demand by four participants with bladder sensation, and both continuously and intermittently by one participant with absent sensation. A Wilcoxon sign-rank test was used to test paired results of changes within an AUM session. RESULTS: Urodynamic outcomes were improved using DGNS. Bladder capacity was increased from 244 ± 59 to 346 ± 61 ml (p = 0.0078), a mean change of 46 ± 25%. Maximum detrusor pressure was decreased from 58 ± 18 to 47 ± 18 cmH(2)O (p = 0.0156), a change of 17 ± 13%, and average peak detrusor pressure was decreased from 56 ± 16 to 31 ± 128 cmH(2)O (p = 0.0156), a mean reduction of 50 ± 19%. There was an increase in the number of detrusor contractions from the first involuntary detrusor contraction to a strong desire, urgency or incontinence, from 1.5 ± 1.4 to 4.3 ± 1.7, and an increase in time of 23 ± 22 min. There were no changes in baseline outcomes following home use of DGNS. CONCLUSIONS: DGNS may be applied on-demand, intermittently or continuously, to increase bladder capacity, decrease storage pressures and provide extra time. Improvements were made in addition to existing antimuscarinic medication regimes.

Contains fulltext : 220648.pdf (Publisher’s version ) (Closed access) The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.

INTRODUCTION AND OBJECTIVE:Video urodynamics (VUDS) enables delineation of site and cause of bladder outlet obstruction and/or incontinence as well as additional findings such as vesico-ureteric re...

INTRODUCTION AND OBJECTIVE:Patients who fail all minimally invasive therapies for idiopathic (IDO) or neuropathic detrusor overactivity (NDO) undergo augmentation cystoplasty as a last resort. Whil...

INTRODUCTION AND OBJECTIVE:The surgical options for post prostatectomy incontinence are implantation of an artificial sphincter or male sling. Outcomes for artificial sphincters, and predictive val...

Aim Bladder outflow in women (bladder outlet obstruction [BOO]) has no well-accepted defining diagnostic criteria. Various nomograms exist based on flow rates, pressure-flow data, and fluoroscopy. We have prospectively evaluated the Solomon-Greenwell bladder outflow obstruction nomogram (SG BOO nomogram) as a measurement of BOO resolution following targeted surgical intervention. Methods The routine posttreatment urodynamics of 21 unselected women with an original urodynamic diagnosis of BOO on fluoroscopy and the SG BOO nomogram (BOO boundary defined as Qmax > 2.2 Pdet.Qmax + 5) were reviewed. All women had symptomatic BOO secondary to anterior pelvic organ prolapse (aPOP), urethrovaginal fistula (UVF), previous stress urinary incontinence (SUI) surgery, urethral stricture (US), or urethral diverticulum (U Div). Following treatment, all presenting symptoms resolved and simple urodynamics were performed as part of routine follow-up. Results The urodynamic findings preoperatively and postoperatively showed statistically significant changes posttreatment in mean flow rate which increased from 9.38 to 14.71 mL/s, mean Pdet.Qmax which decreased from 38 to 18.38 cmH2 O, and mean SG BOO nomogram probability (PBOO) which reduced from PBOO = 0.68 to 0.08. Mean SG BOO nomogram PBOO was significantly reduced posttreatment in all individual categories except UVF where a nonsignificant reduction from PBOO = 0.55 to 0.05 occurred. Conclusions All urodynamic parameters significantly improve in women who become asymptomatic following surgical treatment of BOO. This improvement is best demonstrated by the change in probability of BOO according to the Solomon-Greenwell nomogram. These findings underline the validity of the Solomon-Greenwell female BOO nomogram for diagnosing and monitoring BOO in women.

Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH). Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH. Methods: Patients with Group 1 PAH were included from two national registries with genome-wide data and two local cohorts, and further incorporated in a global meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for transplant-free, all-cause mortality in Hispanic patients with non-Hispanic white (NHW) patients as the reference group. Odds ratios (ORs) for inpatient-specific mortality in patients with PAH were also calculated for race/ethnic groups from an additional National Inpatient Sample dataset not included in the meta-analysis. Measurements and Main Results: After covariate adjustment, self-reported Hispanic patients (n = 290) exhibited significantly reduced mortality versus NHW patients (n = 1,970) after global meta-analysis (HR, 0.60 [95% CI, 0.41–0.87]; P = 0.008). Although not significant, increasing Native American genetic ancestry appeared to account for part of the observed mortality benefit (HR, 0.48 [95% CI, 0.23–1.01]; P = 0.053) in the two national registries. Finally, in the National Inpatient Sample, an inpatient mortality benefit was also observed for Hispanic patients (n = 1,524) versus NHW patients (n = 8,829; OR, 0.65 [95% CI, 0.50–0.84]; P = 0.001). An inpatient mortality benefit was observed for Native American patients (n = 185; OR, 0.38 [95% CI, 0.15–0.93]; P = 0.034). Conclusions: This study demonstrates a reproducible survival benefit for Hispanic patients with Group 1 PAH in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.

PURPOSE: Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, and more rarely in PPP2R1A. Here, we aimed to better understand the latter by characterizing 30 individuals with de novo and often recurrent variants in this PP2A scaffolding Aα subunit. METHODS: Most cases were identified through routine clinical diagnostics. Variants were biochemically characterized for phosphatase activity and interaction with other PP2A subunits. RESULTS: We describe 30 individuals with 16 different variants in PPP2R1A, 21 of whom had variants not previously reported. The severity of developmental delay ranged from mild learning problems to severe intellectual disability (ID) with or without epilepsy. Common features were language delay, hypotonia, and hypermobile joints. Macrocephaly was only seen in individuals without B55α subunit-binding deficit, and these patients had less severe ID and no seizures. Biochemically more disruptive variants with impaired B55α but increased striatin binding were associated with profound ID, epilepsy, corpus callosum hypoplasia, and sometimes microcephaly. CONCLUSION: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported. ispartof: Genetics In Medicine vol:23 issue:2 ispartof: location:United States status: Published online

Purpose With advances in treatment modalities and medical knowledge, girls with congenital urologic disorders are living well into adulthood. Although, sexual and reproductive function in this population is still poorly understood. The aim is to review existing literature about fertility and sexuality in women with congenital genitourinary disorders, including spina bifida (SB), bladder exstrophy-epispadias complex (BEEC) and congenital adrenal hyperplasia (CAH). Methods This review represents the joint SIU-ICUD (Societe Internationale d'Urologie-International Consultation on Urological Disease) consultation on congenital lifelong urology. The results of this analysis were first presented at a joint consultation of the SIU and ICUD at the 2018 SIU annual conference in Seoul, South Korea. Appropriate experts were asked to write specific sections regarding sexuality and reproductive function in female patients with these complex congenital urogenital disorders. Each expert performed their own literature review which was reviewed by GDW, AFS, Hadley M. Wood and Dan Wood. Expert opinion was obtained where data are non-existent. Results Only about half of the individuals with SB express a satisfactory sex life. In women with BEEC, cosmetic concerns surrounding genital appearance and function may increase psychological distress, including severe depression, suicide and sexual dysfunction. Professional health care is key for improving self-esteem and to interact in the biopsychosocial model of the quality of life. Patients with SB and BEEC should be informed about all the potential risks and difficulties before, during and after pregnancy. Screening for pelvic organ prolapse is important as it can exacerbate their already existing sexual dysfunction, difficulties achieving pregnancy and challenges with clean intermittent catheterization. Conclusions Lifelong multidisciplinary follow-up and management are complex but necessary. As these patients grow into their adolescence, they may have the desire to become involved in personal relationships and have sexual interactions. Their healthcare team needs to be increasingly sensitive to these aspects.

Aims The complexity of urethral diverticulectomy depends on location, size, and degree of circumferential involvement. MRI features were examined to predict functional outcome after surgery for urethral diverticulum (UD). Methods A prospectively acquired database was of all patients who have had surgical excision of UD at a tertiary center since 2004 was reviewed. Particular focus was pre- and post-operative urodynamically proven stress urinary incontinence (USUI), and pre-operative MRI features. MRI parameters included diverticular volume, degree of circumferential involvement around the urethra, distance of the Os of UD to bladder neck and urethral length. Students t-test and Mann-Whitney U-test were used to compare rates of de novo USUI. Results There were 100 patients (mean age 45.8 yrs), who had excision of UD since 2004, with a minimum follow-up of 10 months (range 10-112 months). Full MRI data was available for 83 patients. Fourteen were of simple configuration (16.8%), 32 were horseshoe (38.6%), and 37 (44.6%) were circumferential. Twenty-five (25%) patients had pre-operative USUI, while 12 (12%) patients developed de novo USUI post-excision. While, the majority of patients with de novo USUI (67%) had >270° circumferential involvement of urethra, the pre-operative diverticular volume did not predict the likelihood of USUI developing (P = 0.3). A shorter urethral length was associated with pre-operative USUI. Conclusions 25% of all patients had pre-op USUI, and diverticular volume and urethral length was significantly smaller in this group. The majority of patients with de novo USUI had complex diverticula configuration with higher baseline circumferential angle around urethra, with 67% of angle's between 270 and 360°.

Background Pulmonary arterial hypertension (PAH) is a rare disease characterized by distinctive changes in pulmonary arterioles that lead to progressive pulmonary arterial pressures, right-sided heart failure, and a high mortality rate. Up to 30% of adult and 75% of pediatric PAH cases are associated with congenital heart disease (PAH-CHD), and the underlying etiology is largely unknown. There are no known major risk genes for PAH-CHD. Methods To identify novel genetic causes of PAH-CHD, we performed whole exome sequencing in 256 PAH-CHD patients. We performed a case-control gene-based association test of rare deleterious variants using 7509 gnomAD whole genome sequencing population controls. We then screened a separate cohort of 413 idiopathic and familial PAH patients without CHD for rare deleterious variants in the top association gene. Results We identified SOX17 as a novel candidate risk gene (p = 5.5e−7). SOX17 is highly constrained and encodes a transcription factor involved in Wnt/β-catenin and Notch signaling during development. We estimate that rare deleterious variants contribute to approximately 3.2% of PAH-CHD cases. The coding variants identified include likely gene-disrupting (LGD) and deleterious missense, with most of the missense variants occurring in a highly conserved HMG-box protein domain. We further observed an enrichment of rare deleterious variants in putative targets of SOX17, many of which are highly expressed in developing heart and pulmonary vasculature. In the cohort of PAH without CHD, rare deleterious variants of SOX17 were observed in 0.7% of cases. Conclusions These data strongly implicate SOX17 as a new risk gene contributing to PAH-CHD as well as idiopathic/familial PAH. Replication in other PAH cohorts and further characterization of the clinical phenotype will be important to confirm the precise role of SOX17 and better estimate the contribution of genes regulated by SOX17. Electronic supplementary material The online version of this article (10.1186/s13073-018-0566-x) contains supplementary material, which is available to authorized users.