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Optimization of the initial phasing has been a decisive factor in the success of the subsequent electron-density modification, model building and structure determination of biological macromolecules using the single-wavelength anomalous dispersion (SAD) method. Two possible phase solutions (ϕ1 and ϕ2) generated from two symmetric phase triangles in the Harker construction for the SAD method cause the well known phase ambiguity. A novel direct phase-selection method utilizing the θDS list as a criterion to select optimized phases ϕam from ϕ1 or ϕ2 of a subset of reflections with a high percentage of correct phases to replace the corresponding initial SAD phases ϕSAD has been developed. Based on this work, reflections with an angle θDS in the range 35-145° are selected for an optimized improvement, where θDS is the angle between the initial phase ϕSAD and a preliminary density-modification (DM) phase ϕDMNHL. The results show that utilizing the additional direct phase-selection step prior to simple solvent flattening without phase combination using existing DM programs, such as RESOLVE or DM from CCP4, significantly improves the final phases in terms of increased correlation coefficients of electron-density maps and diminished mean phase errors. With the improved phases and density maps from the direct phase-selection method, the completeness of residues of protein molecules built with main chains and side chains is enhanced for efficient structure determination. [ABSTRACT FROM AUTHOR]

Branched-chain aminotransferases (BCAT), which utilize pyridoxal 5'-phosphate (PLP) as a cofactor, reversibly catalyze the transfer of the α-amino groups of three of the most hydrophobic branched-chain amino acids (BCAA), leucine, isoleucine, and valine, to α-ketoglutarate to form the respective branched-chain α-keto acids and glutamate. The BCAT from Deinococcus radiodurans (DrBCAT), an extremophile, was cloned and expressed in Escherichia coli for structure and functional studies. The crystal structures of the native DrBCAT with PLP and its complexes with L-glutamate and α-ketoisocaproate (KIC), respectively, have been determined. The DrBCAT monomer, comprising 358 amino acids, contains large and small domains connected with an interdomain loop. The cofactor PLP is located at the bottom of the active site pocket between two domains and near the dimer interface. The substrate (L-glutamate or KIC) is bound with key residues through interactions of the hydrogen bond and the salt bridge near PLP inside the active site pocket. Mutations of some interaction residues, such as Tyr71, Arg145, and Lys202, result in loss of the specific activity of the enzymes. In the interdomain loop, a dynamic loop (Gly173 to Gly179) clearly exhibits open and close conformations in structures of DrBCAT without and with substrates, respectively. DrBCAT shows the highest specific activity both in nature and under ionizing radiation, but with lower thermal stability above 60°C, than either BCAT from Escherichia coli (eBCAT) or from Thermus thermophilus (HB8BCAT). The dimeric molecular packing and the distribution of cysteine residues at the active site and the molecular surface might explain the resistance to radiation but small thermal stability of DrBCAT. [ABSTRACT FROM AUTHOR]

Objective: We evaluated 5-year safety, efficacy and prostate volume data from BPH patients treated with finasteride or dutasteride. Methods: A retrospective analysis of 378 consecutive men treated with 5[alpha]-reductase inhibitor monotherapy between January 2004 and September 2009 (197 on finasteride and 211 on dutasteride) in a single clinic was performed. Efficacy assessments included International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), postvoid residual urine volume (PVR), prostate-specific antigen (PSA) and prostate volume (PV). Safety assessments included International Index of Erectile Function (IIEF) and adverse events. Patients were evaluated at 3 months, 1 year and yearly thereafter. Results: Mean age of the group was 58.7 ± 6.7 years. Maintenance of therapy at 5 years was 57.4% and 42.5% for the finasteride and dutasteride groups respectively. Changes in IPSS, Qmax, PVR, PV and PSA were similar for both groups at 5 years. The incidence of erectile dysfunction, ejaculatory dysfunction and decreased libido resulting in discontinuation from therapy was significantly (p < 0.01) higher in the dutasteride (5.1%, 2.4%, 2.7% respectively) compared with the finasteride (2.1%, 1.8%, 1.4% respectively) group. In addition, the incidence of self-reported breast tenderness and/or enlargement was significantly (p < 0.01) greater in the dutasteride (3.5%) compared with the finasteride (1.2%) group. Conclusions: In this retrospective analysis of data from consecutive patients treated at a single clinic, both finasteride and dutasteride were effective therapies for the management of lower urinary tract symptoms. However, dutasteride resulted in significantly more sexual side effects and breast complications than finasteride. [ABSTRACT FROM AUTHOR]

Examines the role of hydrazine, 5-amino-2-methoxybenzoic acid and oxalic acid (Hao) in duplicating the hydrogen-bonding functionality of tripeptide beta-strand. Preparation of Hao derivatives; Synthetic and structural properties of Hao; Propensity of Hao-containing peptide to form a beta-sheetlike dimer.

Purpose: The purpose of this guideline is to provide evidence-based guidance to clinicians of all specialties on the evaluation, management, and treatment of idiopathic overactive bladder (OAB). The guideline informs the reader on valid diagnostic processes and provides an approach to selecting treatment options for patients with OAB through the shared decision-making process, which will maximize symptom control and quality of life, while minimizing adverse events and burden of disease., Methods: An electronic search employing OVID was used to systematically search the MEDLINE and EMBASE databases, as well as the Cochrane Library, for systematic reviews and primary studies evaluating diagnosis and treatment of OAB from January 2013 to November 2023. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. Following the study selection process, 159 studies were included and were used to inform evidence-based recommendation statements., Results: This guideline produced 33 statements that cover the evaluation and diagnosis of the patient with symptoms suggestive of OAB; the treatment options for patients with OAB, including Noninvasive therapies, pharmacotherapy, minimally invasive therapies, invasive therapies, and indwelling catheters; and the management of patients with BPH and OAB., Conclusion: Once the diagnosis of OAB is made, the clinician and the patient with OAB have a variety of treatment options to choose from and should, through shared decision-making, formulate a personalized treatment approach taking into account evidence-based recommendations as well as patient values and preferences., (© 2024 by American Urological Association Education and Research, Inc.)

Introduction: Most urologic surgeons will experience surgical complications during their career. These complications can traumatize the surgeon. A national survey of AUA members was conducted to better understand the impact of surgical complications on mental, emotional, and physical health., Methods: An anonymous survey was distributed to a random sample of 4528 AUA members (US urologists and trainees). Survey items were designed to identify the prevalence of surgical complications, and consequential mental, emotional, and physical impact on the surgeon. Also assessed was the support infrastructure available to urologists who experienced complications., Results: The survey was completed by 467 urologists (10.3% response rate), 432 (95%) of whom reported having experienced a serious complication. The most common mental/emotional experiences were anxiety (85%), guilt/shame (81%), and grief/sadness/depression (71%). The most common physical symptoms reported were insomnia (62%), loss of appetite (23%), and headache (13%). Approximately 94% of respondents reported that they did not receive any counseling, and 69% reported not receiving any emotional support following the incident. Urologists reported that shame, lack of administrative time, fear, stigma, and guilt were barriers to seeking support., Conclusions: The overwhelming majority of urologists experience significant complications. These complications are associated with a high incidence of physical and emotional distress, and there is poor access to support. There is an opportunity for the AUA and other agencies to address barriers to seeking and accessing care for urologists who experience mental, emotional, and physical distress after experiencing surgical complications.

The salt-inducible kinases (SIK) 1-3 are key regulators of pro- versus anti-inflammatory cytokine responses during innate immune activation. The lack of highly SIK-family or SIK isoform-selective inhibitors suitable for repeat, oral dosing has limited the study of the optimal SIK isoform selectivity profile for suppressing inflammation in vivo. To overcome this challenge, we devised a structure-based design strategy for developing potent SIK inhibitors that are highly selective against other kinases by engaging two differentiating features of the SIK catalytic site. This effort resulted in SIK1/2-selective probes that inhibit key intracellular proximal signaling events including reducing phosphorylation of the SIK substrate cAMP response element binding protein (CREB) regulated transcription coactivator 3 (CRTC3) as detected with an internally generated phospho-Ser329-CRTC3-specific antibody. These inhibitors also suppress production of pro-inflammatory cytokines while inducing anti-inflammatory interleukin-10 in activated human and murine myeloid cells and in mice following a lipopolysaccharide challenge. Oral dosing of these compounds ameliorates disease in a murine colitis model. These findings define an approach to generate highly selective SIK1/2 inhibitors and establish that targeting these isoforms may be a useful strategy to suppress pathological inflammation., Competing Interests: Competing interests statement:The authors’ employment information at the time of data generation are marked in the “Author affiliations” section. H.B., T.B.S., M.T., M.S., G.B., W.C., L.C, De M.C., K.C., B.C., M.F., A.G., P.A.M., A.M., E.V.M.-M., M.-L.R., M.R., P.L.S., R. Smith, J. Smith, R. Steele, H.S., J. Suarez, G.T., N.M., L.P.V., J.W., P.T.D., L.L.O., T.K., S.D.G., G.H., T.O., N.S., S.P., J.D.V., J.E.T. are current or former employees of Janssen Research & Development, LLC, and employees may own stock/stock options in Johnson & Johnson, of which Janssen Research & Development, LLC is a subsidiary. R.J.X. is co-founder of Jnana Therapeutics and Celsius Therapeutics, scientific advisory board member at Nestlé and Magnet BioMedicine, board director at MoonLake Immunotherapeutics; these organizations had no roles in this study. G.B., W.C., De M.C., S.D.G., G.H., V.K.K., E.V.M.-M., D.D.R., H.S., M.S., R. Smith, T.B.S., M.T., J.D.V., J.W., and R.J.X. are named as inventors on the PCT patent application “Small Molecule Inhibitors of Salt Inducible Kinases”, published as WO 2022/165529, and N.M., R.J.X., T.B.S., G.T., and H.B. are named inventors on the PCT patent application “Materials and Methods for Differentiating CREB Regulated Transcription Coactivator 3”, published as WO 2022/260995.

Objective: To understand the availability and content of patient support groups on social media platforms., Materials and Methods: Five prevalent benign, urologic conditions affecting adult women were selected for analysis. Facebook support groups for these conditions were identified. Groups specific to one urologic condition and with at least 400 members were included, and groups for pediatric and malignant conditions were excluded. Each support group was analyzed for member count, posts per month, and period of activity. The 100 most recent posts in the largest support groups were manually reviewed and further categorized into content subsections., Results: A total number of 56 Facebook support groups were identified that satisfied the inclusion/exclusion criteria. Interstitial cystitis (IC) had 25 groups (68 466 members; 4825 posts), pelvic organ prolapse (POP) had 14 groups (72 342; 3067), UTI had nine groups (36 414; 3204), overactive bladder and/or urinary incontinence (OAB/UI) had seven groups (8246; 306), urinary retention had one group (1168; 118). Across all groups, post content was predominantly informational support (77.6%). Remaining post content was both informational and emotional support (10.0%), emotional support only (7.6%), or unrelated to either informational or emotional support (4.8%)., Conclusion: Individuals with benign urologic conditions are utilizing social media support groups predominantly to seek and share informational support from patient peers. The number of existing groups as well as the level of activity and number of members within individual support groups varies significantly between different urologic conditions. This suggests that there is an unmet need for accessible informational content for patients who suffer with benign urological conditions., (© 2023 Wiley Periodicals LLC.)

Objective: The aim of the study was to compare 12-month subjective and objective outcomes between 3 approaches to apical pelvic organ prolapse (POP) surgery in patients presenting with uterovaginal or posthysterectomy vaginal prolapse enrolled in the Pelvic Floor Disorders Registry for Research., Study Design: This was an analysis of a multicenter, prospective registry that collected both patient- and physician-reported data for up to 3 years after conservative (pessary) and surgical treatment for POP. Twelve-month subjective and anatomic outcomes for patients who underwent surgical treatment were extracted from the registry for analysis. Pelvic organ prolapse recurrence was defined as a composite outcome and compared between the 3 apical surgery groups (native tissue repair, sacrocolpopexy, colpocleisis) as well as the 2 reconstructive surgery groups (native tissue repair and sacrocolpopexy)., Results: A total of 1,153 women were enrolled in the registry and 777 (67%) opted for surgical treatment, of whom 641 underwent apical repair and were included in this analysis (404 native tissue repair, 187 sacrocolpopexy, and 50 colpocleisis). The overall incidence of recurrence was as follows: subjective 6.5%, anatomic 4.7%, retreatment 7.2%, and composite 13.6%. The incidence of recurrence was not different between the 3 surgical groups. When baseline patient characteristics were controlled for, composite POP recurrence between the native tissue and sacrocolpopexy groups remained statistically nonsignificant. Concurrent perineorrhaphy with any type of apical POP surgery was associated with a lower risk of recurrence (adjusted odds ratio, 0.43; 95% confidence interval, 0.25-0.74; P = 0.002) and prior hysterectomy was associated with a higher risk (adjusted odds ratio, 1.77, 95% confidence interval, 1.04-3.03; P = 0.036)., Conclusion: Pelvic Floor Disorders Registry for Research participants undergoing native tissue apical POP repair, sacrocolpopexy, and colpocleisis surgery had similar rates of POP recurrence 12 months after surgery., Competing Interests: C.F. received royalties from UpToDate and Elsevier. C.B. received research grants from the National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases, travel support and textbook royalties from Elsevier, travel support and honorarium for FPMRS Division membership and oral board examiner work from the American Board of Obstetrics and Gynecology, and travel support for board of directors membership from the American Urogynecologic Society. R.G. is a consultant strategic advisory board member of Boston Scientific, UpToDate Royalties Urethral diverticulum section; expert witness slings of Johnson and Johnson. P.M. received NIH R012R01 HD083383-06, Mesh complications: The role of local mechanical stresses on tissue remodeling following mesh implantation; NIH R01 HD097187, Overcoming complications of polypropylene prolapse meshes: Development of novel elastomeric auxetic devices; and NIH UG3UG1HD06900-10S1, Pittsburgh Pelvic Floor Research Program; Pelvic Floor Disorders Network. J.A. received research grants from the Agency for Healthcare Research and Quality, Patient Centered Outcomes Research Institute. The other authors have declared they have no conflicts of interest., (Copyright © 2023 American Urogynecologic Society. All rights reserved.)

Introduction: Contemporary US resident exposure to Female Pelvic Medicine and Reconstructive Surgery (FPMRS) faculty during urology residency is unknown., Methods: Accredited US urology residencies were identified through the American Urological Association (AUA). Accredited, urology-based FPMRS fellowships were identified through the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction. The number of faculty and residency positions were obtained from program AUA profiles if they were last modified within the current application cycle; this information was obtained from program websites if AUA profiles were outdated. Data on faculty fellowship training was manually extracted from program websites. A quality control cross-check of program and faculty training characteristics was performed through direct communication with 5% of programs., Results: Of 139 accredited residency programs assessed, 10.8% were affiliated with an accredited, urology-based FPMRS fellowship. In total, 29.5% of residency programs, representing 25% of US urology residents, had neither a FPMRS fellowship nor any FPMRS certified faculty. The national FPMRS faculty-to-resident ratio was 1:10.8, and 7.4% of faculty at all residency programs were FPMRS certified. In comparison, faculty-to-resident ratios for other subspecialties were: 1:4.7 for pediatrics, 1:3.6 for oncology, 1:5.9 for minimally invasive surgery/endourology, 1:14.2 for trauma/reconstruction, and 1:11.8 for andrology or male sexual/reproductive health. The FPMRS faculty-to-resident ratio was 1:5.1 in programs with a urology-based FPMRS fellowship compared with 1:13.4 in programs without a FPMRS fellowship., Conclusions: 30% of US urology residency programs lack FPMRS trained faculty. Even when FPMRS faculty are on staff, the field is often underrepresented relative to other urologic subspecialties. Further studies are required to ascertain if inadequate exposure to FPMRS cases and mentors during training contribute to the shortage of urology residents who choose to specialize in FPMRS. This link has important implications for the current shortage of FPMRS providers., (© 2023 Wiley Periodicals LLC.)

Introduction: Nocturia negatively impacts the quality of life and is associated with poor general health, but our understanding of its etiologies is incomplete. Urodynamic studies (UDS) findings in patients with nocturia are not well described and may help guide management. Our objective was to compare UDS findings with age-matched patients with and without nocturia., Materials and Methods: We retrospectively reviewed UDS findings of 1124 patients (2010-2017). A total of 484 (43%) presented with nocturia and 821 (73%) were female. Female patients were separated into age-matched groups with and without nocturia. Urinary symptoms, past medical diagnoses, demographic information, and UDS findings were compared., Results: A total of 596 female patients were included, 298 (50%) with nocturia and 298 without. Past medical history, including diabetes mellitus and cardiovascular disease, did not differ between groups. Patients with nocturia were more likely to have pelvic pain (p = 0.0014) and other daytime symptoms (frequency, urgency, and urgency incontinence). On UDS, patients with nocturia were more likely to have bladder outlet obstruction (BOO) (p = 0.025) and dysfunctional voiding (DV) (p < 0.0001). There was no difference in the frequency of detrusor overactivity (DO). Bladder capacity and postvoid residual volumes were lower, though not significantly, in the nocturia group., Conclusions: When comparing UDS findings in contemporary, age-matched groups of female patients with and without nocturia, we found only BOO and DV to be associated with nocturia. While the treatment of nocturia is often aimed at managing DO, our data suggest that this may not be the primary urodynamic correlation with nocturia. Further studies are needed to assess whether successful treatment of BOO and DV can improve nocturia., (© 2022 Wiley Periodicals LLC.)

Aims: Discuss the efficacy, safety, and future directions of neuromodulation in special populations of patients with neurological conditions., Methods: A literature review was done to find meta-analyses, review articles, studies, and case reports of the use of neuromodulation, either sacral neuromodulation or percutaneous tibial nerve stimulation, in patients with various neurological conditions of interest., Results: Sacral neuromodulation (SNM) and posterior tibial nerve stimulation (PTNS) appear to be safe and effective in special neurological populations of patients with multiple sclerosis (MS), Parkinson's disease (PD), and spinal cord injury (SCI). The majority of publications are smaller retrospective case series. Outcomes appear similar to those seen in nonneurogenic patients but also partly depend on disability progression. Magnetic resonance imaging (MRI) compatibility has helped to improve eligibility for SNM in these special populations., Conclusions: In a small number of studies, SNM and PTNS appear to be safe and effective in special neurological populations of patients with MS, PD, and SCI. MRI compatibility has helped to improve eligibility for SNM in these special populations. Studies looking at SNM are limited by a small number of subjects, lack of prospective trials, and selection bias. Larger, randomized studies with long-term follow up are needed to better predict response to SNM and PTNS in these populations., (© 2022 Wiley Periodicals LLC.)

Background: The utility of prophylactic endovascular internal iliac balloon placement in the surgical management of placenta accreta spectrum is debated., Objective: In this study, we review outcomes of surgical management of placenta accreta spectrum with and without prophylactic endovascular internal iliac balloon catheter use at a single institution., Study Design: This is a retrospective cohort study of consecutive viable singleton pregnancies with a confirmed pathologic diagnosis of placenta accreta spectrum undergoing scheduled delivery from October 2018 through November 2020. In the T1 period (October 2018-August 2019), prophylactic endovascular internal iliac balloon catheters were placed in the operating room before the start of surgery. Balloons were inflated after neonatal delivery and deflated after hysterectomy completion. In the T2 period (September 2019-November 2020), endovascular catheters were not used. In both time periods, all surgeries were performed by a dedicated multidisciplinary team using a standardized surgical approach. The outcomes compared included the estimated blood loss, anesthesia duration, operating room time, surgical duration, and a composite of surgical complications. Comparisons were made using the Wilcoxon rank-sum test and the Fisher exact test., Results: A total of 30 patients were included in the study (T1=10; T2=20). The proportion of patients with placenta increta or percreta was 80% in both groups, as defined by surgical pathology. The median estimated blood loss was 875 mL in T1 and 1000 mL in T2 (P=.84). The proportion of patients requiring any packed red blood cell transfusion was 60% in T1 and 40% in T2 (P=.44). The proportion of patients requiring >4 units of packed red blood cells was 20% in T1 and 5% in T2 (P=.25). Surgical complications were observed in 1 patient in each group. Median operative anesthesia duration was 497 minutes in T1 and 296 minutes in T2 (P<.001). Median duration of operating room time was 498 minutes in T1 and 205 minutes in T2 (P<.001). Median surgical duration was 227 minutes in T1 and 182 minutes in T2 (P<.05). The median duration of time for prophylactic balloon catheter placement was 74 minutes (range, 46-109 minutes). The median postoperative length of stay was similar in both groups (6 days in T1 and 5.5 days in T2; P=.36)., Conclusion: The use of prophylactic endovascular internal iliac balloon catheters was not associated with decreased blood loss, packed red blood cell transfusion, or surgical complications. Catheter use was associated with increased duration of anesthesia, operating room time, and surgical time., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To compare the safety and effectiveness of transvaginal mesh repair and native tissue repair, in response to a U.S. Food and Drug Administration (FDA) 522 study order to assess co-primary endpoints of superiority and noninferiority., Methods: This was a prospective, nonrandomized, parallel cohort, multi-center trial comparing transvaginal mesh with native tissue repair for the treatment of pelvic organ prolapse. The primary endpoints were composite treatment success at 36 months comprised of anatomical success (defined as pelvic organ prolapse quantification [POP-Q] point Ba≤0 and/or C≤0), subjective success (vaginal bulging per the PFDI-20 [Pelvic Floor Distress Inventory]), and retreatment measures, as well as rates of serious device-related or serious procedure-related adverse events. Secondary endpoints included a composite outcome similar to the primary composite outcome but with anatomical success defined as POP-Q point Ba<0 and/or C<0, quality-of-life measures, mesh exposure and mesh- and procedure-related complications. Propensity score stratification was applied., Results: Primary endpoint composite success at 36 months was 89.3% (201/225) for transvaginal mesh and 80.2% (389/485) for native tissue repair, demonstrating noninferiority at the preset margin of 12% (propensity score-adjusted treatment difference 6.5%, 90% CI -0.2% to 13.2%). Using the primary composite endpoint, transvaginal mesh was not superior to native tissue repair (P=.056). Using the secondary composite endpoint, superiority of transvaginal mesh over native tissue repair was noted (P=.009), with a propensity score-adjusted difference of 10.6% (90% CI 3.3-17.9%) in favor of transvaginal mesh. Subjective success for both the primary and secondary endpoint was 92.4% for transvaginal mesh, 92.8% for native tissue repair, a propensity score-adjusted difference of -4.3% (CI -12.3% to 3.8%). For the primary safety endpoint, 3.1% (7/225) of patients in the transvaginal mesh (TVM) group and 2.7% (13/485) of patients in the native tissue repair (NTR) group developed serious adverse events, demonstrating that transvaginal mesh was noninferior to native tissue repair (-0.4%, 90% CI -2.7% to 1.9%). Overall device-related and/or procedure-related adverse event rates were 35.1% (79/225) in the TVM group and 46.4% (225/485) in the NTR group (-15.7%, 95% CI -24.0% to -7.5%)., Conclusion: Transvaginal mesh repair for the treatment of anterior and/or apical vaginal prolapse was not superior to native tissue repair at 36 months. Subjective success, an important consideration from the patient-experience perspective, was high and not statistically different between groups. Transvaginal mesh repair was as safe as native tissue repair with respect to serious device-related and/or serious procedure-related adverse events., Funding Source: This study was sponsored by Boston Scientific and developed in collaboration with FDA personnel from the Office of Surveillance and Biometrics, Division of Epidemiology., Clinical Trial Registration: ClinicalTrials.gov, NCT01917968., Competing Interests: Financial Disclosure Bruce S. Kahn disclosed receiving research support from Solaire, payments from AbbVie and Douchenay as a speaker, payments from Caldera and Cytuity (Boston Scientific) as a medical consultant, and payment from Johnson & Johnson as an expert witness. Lioudmila Lipetskaia disclosed that money was paid to their institution from Medtronic and Boston Scientific (both unrestricted educational grants for cadaveric lab). Karen Noblett is Chief Medical Officer at Axonics. Ayman Mahdy receives research funding from Axonics and is a consultant for Group Dynamics, Medpace and FirstThought. Ayman Mahdy was one of the PIs for the study few years ago and this entailed study support by the vendor. This support paid the study staff and patient recruitment process. Miles Murphy received research support and is a consultant for Boston Scientific, and is an expert witness for Johnson & Johnson. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Onabotulinumtoxin A (BTX-A) is an effective therapy for overactive bladder (OAB), however, adverse events may prevent patients from initiating therapy. The study objective was to report real-world rates of incomplete emptying and urinary tract infection (UTI) in men and women undergoing BTX-A for OAB., Methods: Eleven clinical sites performed a retrospective study of adults undergoing first-time BTX-A injection (100 units) for idiopathic OAB in 2016. Exclusions included: postvoid residual (PVR) > 150 ml, prior BTX-A, pelvic radiation, or need for preprocedure catheterization. Primary outcomes at 6 months were incomplete emptying (clean intermittent catheterization [CIC] or PVR ≥ 300 ml without the need for CIC); and UTI (symptoms with either positive culture or urinalysis or empiric treatment). We compared rates of incomplete emptying and UTI within and between sexes, using univariate and multivariable models., Results: 278 patients (48 men and 230 women) met inclusion criteria. Mean age was 65.5 years (range: 24-95). 35% of men and 17% of women had incomplete emptying. Men had 2.4 (95% CI: 1.04-5.49) higher odds of incomplete emptying than women. 17% of men and 23.5% of women had ≥1 UTI, the majority of which occurred within the first month following injection. The strongest predictor of UTI was a history of prior UTI (OR: 4.2 [95% CI: 1.7-10.3])., Conclusions: In this multicenter retrospective study, rates of incomplete emptying and UTI were higher than many previously published studies. Men were at particular risk for incomplete emptying. Prior UTI was the primary risk factor for postprocedure UTI., (© 2022 Wiley Periodicals LLC.)

Objectives: To assess the characteristics and quality of patient education content for overactive bladder (OAB) on YouTube., Methods: We searched YouTube on September 10, 2019 and reviewed the top 25 search results for "overactive bladder." For comparison, we reviewed 3 Urology Care Foundation (UCF) OAB education videos on YouTube. Videos were scored using the Agency for Healthcare Research and Quality's Patient Education Materials Assessment Tool (PEMAT) for Audiovisual materials, which is subdivided into understandability and actionability domains, each with a maximum score of 100%., Results: The mean length was 9.5 (0.9-34) minutes and the mean number of views was 151,382 (127-2,032,441). Of the top 25 search results, the mean PEMAT understandability score was 74% ± 16% (range 41%-100%). The mean PEMAT actionability score was 57% ± 39% (range 0%-100%). Seventy-two percent of the reviewed videos featured a physician. In comparison, the 3 UCF videos had an average of 5840 views, 3 minutes length, and PEMAT understandability and actionability scores of 93% and 100%. All UCF OAB videos featured urologists., Conclusion: The quality of OAB patient education materials on YouTube varies significantly in understandability and actionability. Although the UCF videos scored much higher on the PEMAT than our reviewed videos, they did not appear within the top 25 search results for OAB. There is great opportunity for the American Urological Association (AUA)/UCF and Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) to increase its outreach to patients on platforms like YouTube., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: Female urethral stricture disease is rare and has several surgical approaches including endoscopic dilations (ENDO), urethroplasty with local vaginal tissue flap (ULT) or urethroplasty with free graft (UFG). This study aims to describe the contemporary management of female urethral stricture disease and to evaluate the outcomes of these three surgical approaches., Methods: This is a multi-institutional, retrospective cohort study evaluating operative treatment for female urethral stricture. Surgeries were grouped into three categories: ENDO, ULT, and UFG. Time from surgery to stricture recurrence by surgery type was analyzed using a Kaplan-Meier time to event analysis. To adjust for confounders, a Cox proportional hazard model was fit for time to stricture recurrence., Results: Two-hundred and ten patients met the inclusion criteria across 23 sites. Overall, 64% (n = 115/180) of women remained recurrence free at median follow-up of 14.6 months (IQR, 3-37). In unadjusted analysis, recurrence-free rates differed between surgery categories with 68% ENDO, 77% UFG and 83% ULT patients being recurrence free at 12 months. In the Cox model, recurrence rates also differed between surgery categories; women undergoing ULT and UFG having had 66% and 49% less risk of recurrence, respectively, compared to those undergoing ENDO. When comparing ULT to UFG directly, there was no significant difference of recurrence., Conclusion: This retrospective multi-institutional study of female urethral stricture demonstrates that patients undergoing endoscopic management have a higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft., (© 2020 Wiley Periodicals LLC.)

Introduction: We aimed to assess safety and efficacy of incobotulinumtoxinA for the treatment of neurogenic detrusor overactivity (NDO)., Methods: We identified patients with NDO confirmed on urodynamics (UDS) and reported urgency incontinence (UI) in those who received intravesical incobotulinumtoxin A injection for neurogenic bladder between November 2013 and May 2017. Parameters studied were daytime frequency, daily incontinence episodes, daily pad use, clean intermittent catheterization (CIC) volumes, symptom scores (UDI6, IIQ7, PGII), and complications., Results: We examined 17 male patients who met inclusion criteria and underwent incobotulinumtoxinA injection. Mean age was 61.2±15.4 years. Fourteen patients (82%) were taking oral antimuscarinics prior to the incobotulinumtoxin A injection. There were improvements in the following parameters: average daily pads (4.5 to 3.3, p=0.465), daily urinary frequency (9.4 to 4.6, p=0.048), daily incontinent episodes (2.5 to 0.4, p=0.033), CIC volumes (400 to 550 mL, p=0.356), hours in between CIC (3.6 to 5.2, p=0.127), and the validated questionnaires UDI6 (30.6 to 7.4, p=0.543) and IIQ7 (52.4 to 6.8, p=0.029). There were no documented symptomatic urinary tract infections (UTIs) within 30 days of injection or reports of de novo urinary retention. Nine of 17 patients (53%) reported being dry at their first postoperative visit., Conclusions: In this preliminary pilot study of a small cohort of males with NDO and UI, significant improvements were seen following incobotulinumtoxinA injection in daily frequency, incontinence episodes, hours in between CIC, and quality of life. Larger-scale and long-term studies are required to confirm these results, but initial findings are promising for wider use of this formulation.

A strategy to conformationally restrain a series of GlyT1 inhibitors identified potent analogs that exhibited slowly interconverting rotational isomers. Further studies to address this concern led to a series of azetidine-based inhibitors. Compound 26 was able to elevate CSF glycine levels in vivo and demonstrated potency comparable to Bitopertin in an in vivo rat receptor occupancy study. Compound 26 was subsequently shown to enhance memory in a Novel Object Recognition (NOR) behavioral study after a single dose of 0.03 mg/kg, and in a contextual fear conditioning (cFC) study after four QD doses of 0.01-0.03 mg/kg., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: We hypothesized that instruments of pelvic floor dysfunction would yield similar responses on web-based and smartphone administration compared with paper., Methods: Subjects presenting with pelvic floor disorders were prospectively enrolled at 5 sites and invited to complete 4 validated pelvic floor disorder questionnaires (Pelvic Floor Distress Inventory 20, Pelvic Floor Impact Questionnaire 7, Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire 12, Bristol Stool Scale) on both paper and electronic formats, 2 weeks apart, with the order of administration being randomized. Participants completed the questionnaires electronically on the internet via REDCap or using the PelvicTrack App on a smartphone or tablet., Results: Two hundred thirty-four subjects were enrolled, and 132 subjects (56%) completed both sets of questionnaires with no intervening treatment. This group was 58 (±15) years old with body mass index 28 (±6) kg/m and parity 2 (1, 3) and was 77% white, 6% African American, 7% Asian, and 10% other. Presenting complaints were classified as 58% urinary, 37% prolapse, and 5% defecatory. There was no difference in overall demographic information between those who completed the second round of questionnaires and those who did not. There was no difference in age between those who chose to complete the questionnaires via REDcap and those who chose to complete the questionnaires via smartphone. Correlation coefficients between questionnaire administration range from 0.5 to 0.8. There was no significant difference in the responses for each total scale and individual scale between the first or second administration., Conclusions: We demonstrated moderate to strong reliability between scales of pelvic floor dysfunction administered electronically compared with paper version. Our results strongly suggest that it is feasible and reliable to administer pelvic floor questionnaires in an electronic format on REDCap and on smartphones.

Aims: The aim is to assess whether subjects with diabetes mellitus (DM) have greater urinary retention and increased post-void residual volume (PVR) following mid-urethral sling (MUS) surgery., Methods: This multi-center retrospective study included patients who underwent MUS (2012-2016). Baseline data included demographics, comorbidities, urinary symptoms, urodynamics data, PVR, and responses to validated questionnaires (UDI6 and IIQ7). Intraoperative data, postoperative voiding trial results, postop questionnaires, and complications were also noted. Patients with and without DM were compared. Significance was defined as P < .05., Results: A total of 605 MUS were included, 538(89%) without DM and 67(11%) with DM, of which 69% were transobturator and 31% retropubic. No differences were seen in urinary retention and passing void trial(79% DM vs 81% non-DM; P = .72). Mean PVR at discharge was similar between groups (136 mL DM vs 139 mL non-DM; P = .922). There were no differences between groups in UDI6 and IIQ7 sum scores at baseline and 1 month. DM subjects reported more bother at baseline on certain UDI-6 and IIQ-7 items including frequent urination, leakage related to urgency, and feeling frustrated. At 3 months postop, all subjects demonstrated improvement in scores. Interestingly, patients with DM reported worse quality of life on the IIQ7 sum., Conclusions: Among subjects with well-controlled diabetes and more comorbidities who underwent MUS there were few differences in postoperative voiding dysfunction or PVR compared to nondiabetic women. DM patients were more bothered at baseline by urge-related symptoms. Quality of life following sling surgery appears to be worse in patients with DM at 3 months based on IIQ7. This data suggests that diabetic women with lower HbA1C can be counseled similarly to these complication rates and voiding dysfunction after MUS., (© 2020 Wiley Periodicals, Inc.)

Objectives: Few contemporary studies exist regarding urodynamic (UDS) findings in patients with diabetes mellitus (DM), and data are conflicting. Our aim was to compare UDS findings in women with and without DM., Methods: Data from female patients in a prospectively maintained UDS database (2010-2014) were reviewed. Studies were performed according to International Continence Society standards. Clinical data, presenting symptoms, and UDS findings were compared in women with and without DM, controlling for demographic and pertinent variables., Results: There were 384 patients who met the inclusion criteria, of whom 88 (26%) had DM. Symptoms at presentation were not statistically different in women with and without DM. Women with DM had larger bladder capacity (mean, 493 mL vs 409 mL; P = 0.005) and had more detrusor underactivity (30% vs 18%, P = 0.042) when compared with nondiabetic women. Diabetic women were more frequently diagnosed as having impaired sensation, or lack of desire to void, at 75% of capacity (17% vs 5%, P = 0.001). In women with diabetes, a serum hemoglobin A1c level of at least 7.5% was associated with delayed first sensation and first urge. Diagnosis of DM of more than 10 years was associated with greater volume at first urge, and maximal capacity, lower detrusor pressures, and higher postvoid residual., Conclusions: In this contemporary series, women with DM demonstrated similar presenting complaints to women without DM but had significantly altered UDS findings. Among diabetic female patients, diabetes control and duration of diabetes seem to impact bladder sensation and contractility. Urodynamics may be helpful in diabetic female patients to diagnose underlying concealed bladder dysfunction before initiation of treatment.

Discussion and management of incontinence in a patient with spina bifida by four international experts followed by a literature review.

Objective: To examine the effects of trainee involvement on fundamental urology procedures., Methods: Current Procedural Terminology codes were used to identify patients within the National Surgical Quality Improvement Program database who underwent a selection of fundamental general urology procedures (2005-2013). Operative time and perioperative complications (30-day) were compared between cases with and without trainee involvement., Results: 29,488 patients had general urology procedures with information regarding trainee involvement, 13,251 (44.9%) with trainee involvement, and 16,237 (55.1%) without. Overall patients who underwent procedures with trainee involvement were younger and had fewer comorbidities (Table 1). Trainee involvement showed significant increase in operative time in all procedures included in the study (Table 2). On multivariate analysis trainee involvement increased the risk of complications (Odds Ratio (OR) 1.61, 95% CI 1.45-1.78, P < .001). Other factors that increased the risk of complications were: American Society of Anesthesiologists (ASA) class 3-4 (OR 2.01, 95% CI 1.46-2.77, P < .001), partially or totally dependent functional status (OR 2.22, 95% CI 1.68-2.94, P < .001), diabetes mellitus (OR 1.21, 95% CI 1.05-1.39, P = .008), heart disease (OR 1.19, 95% CI 1.02-1.38, P = .027), and respiratory disease (OR 1.33, 95% CI 1.09-1.63, P = .027)., Conclusion: While trainees are valuable members of the urology team at teaching hospitals and training is necessary, their involvement in urologic surgery appears to increase operative time for all procedures and complications in certain procedures. Further research needs to be done on how to mitigate these effects while preserving surgical education quality., (Copyright © 2018. Published by Elsevier Inc.)

Aims: To evaluate the utility of catheterized samples in reducing overdiagnosis of UTI based on voided specimens among patients presenting with a range of urinary symptoms. We also aimed to determine variables that may modify the predictive value of the voided midstream urine culture., Methods: Patient charts were reviewed to identify female patients referred to our voiding dysfunction clinic with a range of complaints warranting urine studies (5/2014-8/2016). Patients with a positive voided urine culture who also had a catheterized urine culture in our system were included. Multiple logistic regression analysis was performed to identify patient characteristics associated with a negative catheterized specimen despite a positive voided specimen., Results: One hundred and seven women were included in the study. Eighty percent of the cohort was post-menopausal. Although all patients had positive voided specimens, only 53 (49.5%) had positive catheterized specimens. On multivariate analysis negative nitrites on clean catch UA was a significant predictor of a negative catheterized sample (adjusted OR 8.9, 95%CI 2.2-43.7, P = 0.003). WBC/HPF <10 on clean catch UA trended towards significance (adjusted OR 4.72, 95%CI 1.1-26.1, P = 0.05)., Conclusions: Relying on clean catch urine samples may lead to significant over-diagnosis of UTIs. Our study suggests that in female patients who have vague symptoms of UTI, obtaining catheterized specimens may be beneficial in avoiding the overdiagnosis of UTIs and the overuse of antibiotics. Larger, prospective studies testing our hypothesis are necessary, and would greatly assist in establishing clinical practices that reduce the amount of antibiotics inappropriately prescribed., (© 2018 Wiley Periodicals, Inc.)