Identification of Novel Genetic Risk Variants Associated with Hidradenitis Suppurativa in an Exome Sequencing Cohort of 92,455 Individuals.

INTRODUCTION: Hidradenitis suppurativa (HS) is a prevalent and persistent inflammatory skin disorder, lacking a known cure or effective biomarkers for early diagnosis at present. The genetic determinants of HS have not been fully documented, but it is believed to result from a combination of genetic and environmental factors. METHODS: To identify relevant HS gene variants in sporadic HS patients, this study utilized longitudinal electronic health records (EHRs) and whole-exome sequencing. DNA exome sequencing data from 92,455 participant samples in the MyCode biobank, linked to Geisinger's EHR, were analyzed. This cohort included 1,092 HS cases and 91,363 healthy controls. The MyCode EHR has a median longitudinal follow-up of 15 years per participant, with an average of 87 clinical encounters, 687 laboratory tests, and 7 procedures. RESULTS: There were 1,092 (901 females and 191 males) participants aged 14-89 years (median 47 years) with HS (L73.2), indicating a 1.18% prevalence and accounting for a 4.7:1 female-to-male ratio among the individuals presenting for clinical care. γ-secretase complex, syndromic, and autoinflammatory gene variants were assessed. Potential pathogenic variants were identified among 66 individuals in the HS genes studied. Molecularly, the estimated HS variant prevalence was 1:1,400 in the cohort, 12.3% of variant carriers had HS diagnosis in EHR. CONCLUSIONS: Using longitudinal EHR data, genomic screening identified HS-associated gene variants in a defined group of sporadic HS patients to augment the clinical diagnosis, particularly in cases of ambiguity. Based on this study, the field of skin disorders can benefit from a personalized approach to HS diagnosis using large-scale sequencing.

Does antithrombotic use enable earlier diagnosis of bladder cancer? A brief institutional assessment.

INTRODUCTION: Wallis et al (JAMA 2017) demonstrated use of antithrombotic medications (ATMs) is associated with increased prevalence of hematuria-related complications and subsequent bladder cancer diagnosis within 6 months. Stage of diagnosis was lacking in this highly publicized study. This study examined the association of ATM use on bladder cancer stage at the time of diagnosis. MATERIALS AND METHODS: We completed a retrospective chart review of patients with a bladder cancer diagnosis at our institution. Patient demographics and bladder cancer work up information were assessed. Patients were stratified based on use of ATMs at time diagnosis. Descriptive statistics were completed to identify association between ATM use and stage of bladder cancer diagnosis, as stratified by non-muscle invasive bladder cancer (NMIBC) versus muscle invasive bladder cancer (MIBC). RESULTS: A total of 1052 patient charts were reviewed. Eight hundred and forty-four were included and 208 excluded due to unavailability of diagnosis history. At diagnosis, 357 (42.3%) patients were taking ATMs. Patients on ATMs presented with NMIBC at similar rates as patients not taking ATMs (81.2% vs. 77.8%, p = 0.23). Subgroup analysis by ATM class similarly demonstrated no statistically significant differences in staging. CONCLUSION: While Wallis et al established that patients on blood thinners who present with hematuria are more likely to be diagnosed with genitourinary pathology, this factor does not appear to enable an earlier diagnosis of bladder cancer. Future study may assess hematuria at presentation (gross, microscopic), type of blood thinners, and low versus high risk NMIBC presentation.

Evaluation and management of female urinary incontinence.

INTRODUCTION Urinary incontinence (UI) is a common condition in all demographics of women and consists of stress UI (SUI), Urgency UI (UUI), and mixed UI (MUI). Treatment includes lifestyle modifications, medical treatment, and surgery depending on the type of UI and severity of symptoms. This review is an update on the evaluation and management of UI in women. MATERIALS AND METHODS: This review article covers the evaluation and management options for UI in women and includes the most recent guidelines from the American Urological Association (AUA) as well as recently published literature on the management of UI. RESULTS: Any evaluation of UI should include a thorough targeted history and physical, and counseling for treatment should consider patient goals and desired outcomes. For both SUI and UUI, behavioral therapy and lifestyle modifications are effective first line treatments. Patients with UUI can benefit from medical therapy which includes anticholinergics and ß3-agonist medications, as well as neuromodulation in treatment refractory patients. SUI patients may further benefit from mechanical inserts which prevent leaks, urethral bulking agents, and surgical treatments such as the mid urethral sling and autologous fascial pubovaginal sling. CONCLUSIONS: Treatment of UI in women requires a graded approach that considers patient goals and symptom severity, beginning with lifestyle and behavioral modifications before progressing to more aggressive interventions.

Surgical management of vaginal prolapse: current surgical concepts.

INTRODUCTION Pelvic organ prolapse (POP) is a condition defined by a loss of structural integrity within the vagina and often results in symptoms which greatly interfere with quality of life in women. POP is expected to increase in prevalence over the coming years, and the number of patients undergoing surgery for POP is expected to increase by up to 13%. Two categories of surgery for POP include obliterative and reconstructive surgery. Patient health status, goals, and desired outcomes must be carefully considered when selecting a surgical approach, as obliterative surgeries result in an inability to have sexual intercourse postoperatively. MATERIALS AND METHODS: This review article covers the role of traditional native tissue repairs, surgical options and techniques for vaginal and abdominal reconstruction for POP and the associated complications, and considerations for prevention and management of post-cystectomy vaginal prolapse. RESULTS: Studies comparing native and augmented anterior repairs demonstrate better anatomic outcomes in patients with mesh at the cost of more surgical complications, while different procedures for posterior repair result in similar improvements in symptoms and quality of life. In the management of apical prolapse, vaginal obliterative repair, namely colpocleisis, results in very low risk of recurrence at the cost of the impossibility of having sexual intercourse postoperatively. Reconstructive procedures preserve vaginal length along with the ability to have intercourse, but show higher failure rates over time. They can be divided into vaginal approaches which include sacrospinous ligament fixation (SSLF) and uterosacral vaginal vault suspension (USVS), and the abdominal approach which primarily includes abdominal sacrocolpopexy (ASC). There is evidence that ASC confers a distinct advantage over vaginal approaches with respect to symptom recurrence, sexual function, and quality of life. Patients who have had radical cystectomy for bladder cancer are at an increased risk of POP, and may benefit from preventative measures and prophylactic repair during surgery. Importantly, the success rates of POP surgery vary depending on whether anatomic or clinical definitions of success are used, with success rates improving when metrics such as the presence of symptoms are incorporated. CONCLUSIONS: The surgical management of POP should greatly take into account the postoperative goals of every patient, as different approaches result in different sexual and quality of life outcomes. It is important to consider clinical metrics in the evaluation of success for POP surgery as opposed to using exclusively anatomic criteria. Preoperative counseling is critical in managing expectations and increasing patient satisfaction postoperatively.

Addressing the need for preclinical study of penile prosthesis infection: a new animal model and narrative review.

Background and Objective: Erectile dysfunction (ED) is a common condition in men, and many patients refractory to conservative treatment may undergo penile prostheses (PPs) placement. The primary concern following PP implantation is device infection. Although antibiotic and hydrophilic coatings have reduced the incidence of inflatable PP (IPP) infections, there remains room for improvement. Optimization of PP outcomes requires a practical in vivo model to better understand mechanisms of infection and to test new infection control strategies. We aimed to describe a new rabbit model which contains a functional IPP and review previously reported animal PP models. Methods: An IPP was placed into rabbit flanks and cycled for functionality testing. Rabbits were evaluated for signs of pain and distress over 14 days. Separately, narrative review methodology was utilized to search the PubMed and Scopus databases for all publications through March 21, 2023, which studied PP within an in vivo setting. Three independent reviewers ultimately selected 12 papers from 1992-2021 for inclusion. Key Content and Findings: Several animal studies highlighted the initial functionality or feasibility of devices for ED before their introduction in the clinical setting. There are several subsequent studies aimed at optimizing the type of antibiotic use or coating material using segments of PP material in an in vivo setting. However, the literature lacks a contemporary animal model containing a functional IPP. Our novel rabbit model offers a safe, practical way to implant a functioning IPP and investigate new perioperative infection prevention and treatment strategies before trials in the clinical setting. Conclusions: Animal models have played a key role in testing medical devices, including PPs, prior to their clinical introduction. Our review uncovered no modern animal studies involving placement of a functional PP. A new animal model can facilitate study of evolving microorganism profiles, novel methods to enhance antibiotic delivery, and proposed treatment options.

The Impact of COVID-19 on the Urology Residency Match and Geographic Proximity of Applicants.

OBJECTIVE: To determine the impacts of COVID-19 pandemic-related changes and program-specific characteristics on the geographic diversity of the 2021 and 2022 urology match classes. METHODS: We gathered publicly available information to compare match outcomes in 2021 and 2022 to the previous 5 application cycles (2016-2020). Variables included residency program class size, program and resident AUA section, and program and resident medical school. Univariate comparisons were made with Fisher's t-tests. Odds ratios were calculated following multivariable analysis. RESULTS: Comparing the previous 5 application cycles to the 2 pandemic years individually and together showed no significant changes in home or in-section matches. However, when comparisons were stratified by small (1-2 residents) vs large (3+ residents) programs, a significant increase in at-home and in-section matches was observed for small programs in 2021. Large programs did not experience significant changes in match patterns. Multivariate analysis showed that small programs had significantly lower odds of matching applicants from home institutions and within AUA sections. Additionally, certain AUA sections demonstrated significantly increased likelihood of accepting in-section applicants. CONCLUSION: The changes from in-person to virtual application cycles during the pandemic particularly affected small residency programs in 2021. With easing restrictions and logistical improvements in the 2022 cycle, locoregional match rates partially shifted back to prepandemic patterns, though not completely. Although the pandemic did not affect geographic diversity in urology as much as in other surgical subspecialties, these findings and further study should be considered to optimize upcoming cycles.

The use of individualized 3D-printed models on trainee and patient education, and surgical planning for robotic partial nephrectomies.

3D printing is a growing tool in surgical education to visualize and teach complex procedures. Previous studies demonstrating the usefulness of 3D models as teaching tools for partial nephrectomy used highly detailed models costing between $250 and 1000. We aimed to create thorough, inexpensive 3D models to accelerate learning for trainees and increase health literacy in patients. Patient-specific, cost-effective ($30-50) 3D models of the affected urologic structures were created using pre-operative imaging of 40 patients undergoing partial nephrectomy at Thomas Jefferson University Hospital (TJUH) between July 2020 and May 2021. Patients undergoing surgery filled out a survey before and after seeing the model to assess patient understanding of their kidney, pathophysiology, surgical procedure, and risks of surgery. Three urological residents, one fellow, and six attendings filled out separate surveys to assess their surgical plan and confidence before and after seeing the model. In a third survey, they ranked how much the model helped their comprehension and confidence during surgery. Patient understanding of all four subjects significantly improved after seeing the 3D model (P < 0.001). The urology residents (P < 0.001) and fellow (P < 0.001) reported significantly increased self-confidence after interacting with the model. Attending surgeon confidence increased significantly after seeing the 3D model (P < 0.01) as well. Cost-effective 3D models are effective learning tools and assist with the evaluation of patients presenting with renal masses, and increase patient, resident, and fellow understanding in partial nephrectomies. Further research should continue to explore the utility of inexpensive models in other urologic procedures.

Multiparametric MRI is not sufficient for prostate cancer staging: A single institutional experience validated by a multi-institutional regional collaborative.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) has been increasingly utilized in prostate cancer (CaP) diagnosis and staging. While Level 1 data supports MRI utility in CaP diagnosis, there is less data on staging utility. We sought to evaluate the real-world accuracy of mpMRI in staging localized CaP. MATERIALS AND METHODS: Men who underwent radical prostatectomy (RP) for CaP in 2021 at our institution were identified. Sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in predicting pT2N0 organ confined disease , extracapsular extension , seminal vesicle invasion , lymph node involvement, and bladder neck invasion were evaluated. Associations between MRI accuracy and AUA risk stratification (AUA RS), MRI institution (MRI-I), MRI strength (1.5 vs. 3T) (MRI-S), and MRI timing (MRI-T) were assessed. These analyses were repeated using Pennsylvania Urologic Regional Collaborative (PURC) data. RESULTS: Institutional and community mpMRI CaP staging data demonstrated poor sensitivity (2.9%-49.2%% vs. 16.8%-24.4%), positive predictive value (40%-100% vs. 35.8%-68.2%), and negative predictive value (56.3%-94.3% vs. 68.4%-96.2%) in predicting surgical pathologic features - in contrast, specificity (89.1%-100% vs. 93.9%-98.6%) was adequate. mpMRI accuracy for extracapsular extension, seminal vesicle invasion, and lymph node involvement was significantly (p < 0.001) associated with AUA RS. There was no association between mpMRI accuracy and MRI-I, MRI-S, and MRI-T. CONCLUSION: Despite enthusiasm for its use, in a real-world setting, mpMRI appears to be a poor staging study for localized CaP and is unreliable as the sole means of staging patients prior to prostatectomy. mpMRI should be used cautiously as a staging tool for CaP, and should be interpreted considering individual patient risk strata.

Recent advances in UroLift: A comprehensive overview.

OBJECTIVE: Recent years have seen a steep rise in minimally invasive surgical therapy (MIST) for benign prostate hyperplasia (BPH). Prostatic urethral lift (UroLift) is a mechanical intervention aimed at reducing lower urinary tract symptoms, which affect patients with BPH. MATERIAL AND METHODS: A narrative synthesis of all studies regarding UroLift is performed over the last decade, evaluating its impact on International Prostate Symptom Score (IPSS), quality of life (QoL), Qmax, Benign Prostate Hypertrophy Impact Index, and sexual health metrics. RESULTS: The studies included have demonstrated significant improvements in the objective parameters measured. UroLift has a low side-effect profile and is comparable to transurethral resection of the prostate in QoL changes and is superior with respect to recovery time and ejaculatory function. CONCLUSION: Our findings suggest that UroLift may be an appropriate treatment for individuals undergoing treatment for BPH who are concerned with sexual and ejaculatory functions. More studies are needed to determine who is eligible for UroLift, as well as the long-term impact of UroLift on individuals with BPH.