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OBJECTIVE: To evaluate the efficacy and tolerability of extended-release oxybutynin in combination with the alpha1-blocker tamsulosin in reducing lower urinary tract symptoms in men. PATIENTS AND METHODS: In this multicenter, double-blind trial performed between March 29, 2004, and June 22, 2005, 420 men aged 45 years or older with a total International Prostate Symptom Score (IPSS) of 13 or more and IPSS for storage of 8 or more were randomized to receive tamsulosin (0.4 mg/d) with either extended-release oxybutynin (10 mg/d) or placebo for 12 weeks. Eligibility requirements included a maximum flow rate of 8 mL/s or more with voided volume of 125 mL or more and a postvoid residual volume of 150 mL or less on 2 occasions. Postvoid residual volume and peak flow rates at weeks 4, 8, and 12 were measured. The primary end point was change from baseline in total IPSS after 12 weeks of treatment. Secondary outcomes included change in IPSSs for storage and quality of life. RESULTS: Tamsulosin combined with extended-release oxybutynin resulted in significantly greater improvement in total IPSS compared with tamsulosin and placebo after 8 (P=.03) and 12 (P=.006) weeks of treatment, and improved IPSS for storage and quality of life at all assessment points (P<.01). The incidence of postvoid residual volume higher than 300 mL was 2.9% (6/209) in patients receiving combination therapy compared with 0.5% (1/209) in patients receiving tamsulosin alone (P=.12). Occurrence of peak flow rates below 5 mL/s was 3.8% (8/209) for combination therapy and 5.7% (12/209) for tamsulosin alone (P=.49). CONCLUSION: In men with substantial storage symptoms, combination therapy with tamsulosin and extended-release oxybutynin demonstrated greater efficacy than and comparable safety and tolerability to tamsulosin monotherapy. [ABSTRACT FROM AUTHOR] more...

Frequency, urgency, and pain characterize interstitial cystitis/ painful bl a dder syndrome (IC/PBS). However, u n d i agnosed vulvar pain may be mistaken for bladder pain. This mailed surv ey study assessed the relationship of IC/PBS to vulvar pain symptoms in adolescence, adulthood, and the past year. [ABSTRACT FROM AUTHOR] more...

Objectives: This study aimed to evaluate the preliminary feasibility and safety of a new implantable tibial nerve stimulator device in patients with overactive bladder (OAB)., Materials and Methods: Ten patients with OAB in whom conservative treatments had failed participated in the study. All patients received daily stimulation therapy for two weeks and weekly stimulation therapy for 13 weeks, at the lowest electrical output amplitude at which paresthesia or motor response occurred. OAB symptoms (three-day bladder diary), quality-of-life scores (OAB-questionnaire Short Form), and patient global response (GRA) were assessed at each follow-up visit., Results: Among the patients enrolled (mean age 68 years), seven were OAB-wet and three OAB-dry. After 13 weeks of therapy delivery, a reduction in the number of daily voids during waking hours (8.5 ± 2.5 to 6.3 ± 1.9; p = 0.016), incontinence episodes (2.5 ± 1.8 to 0.3 ± 0.5; p < 0.001), and the daily voids associated with urgency (7.6 ± 3.1 to 3.0 ± 3.1; p < 0.001) was reported. Eight of the ten subjects were classified as responders for ≥one OAB component, with one patient reporting worsened symptoms of urgency (+6%). All ten patients reported global improvement in symptoms on the GRA with a median score of 6. Improvements in OAB severity and health-related quality-of-life scores were noted from pre- to posttreatment across participants (p < 0.001). No serious adverse effects were noted., Conclusion: This first-in-human pilot study allowed for capture of preliminary safety and effectiveness information on a new implantable tibial nerve stimulator device in the population of interest to adequately power a larger, pivotal randomized study., Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT04115228., Competing Interests: Conflict of Interest Parminder S. Sethi is a consultant for Coloplast and was previously a shareholder in Nine Continents Medical. Kenneth M. Peters is a consultant for Coloplast and Uromedical and equity owner of Uromedical., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) more...

Introduction and Objectives: Aquablation (Aqua) is a novel technique for treating benign prostatic hyperplasia and lower urinary tract symptoms. This study compares Aqua to simple prostatectomy (SP), analyzing functional urinary outcomes, adverse events (AE), and retreatment rates. Methods: A single-institution retrospective chart review was conducted for men undergoing open/robotic SP or Aqua from 2017 to 2023 for prostates >80 mL. Data collected included blood transfusions, AE, retreatment rates, postoperative medication use, and International Prostate Symptom Score (IPSS) with quality-of-life (QOL) indicator. To address differences in baseline characteristics, including prostate size, we applied inverse probability of treatment weighting (IPTW). Statistical analyses were performed using R 4.4.0. Results are presented as IPTW-adjusted comparing SP to Aqua using Fischer's exact test and analysis of variance reported as beta (B) for continuous variables and odds ratios (OR) for categorical variables with 95% confidence intervals (CI). Results: In total, 172 patients were studied: 111 Aqua and 61 SP. Groups were well-matched for body mass index (Aqua 28.77 vs SP 28). Aqua patients were older (73.04 vs 68.89), had smaller prostates (135.46 vs 186.53 mL), and lower preoperative urinary retention (21.8% vs 47.5%). Baseline characteristics between groups were adjusted using IPTW. SP outperformed Aqua in 1-year IPSS scores ( B = -3.4, CI: -5.7, -1.1, p = 0.005), whereas QOL was comparable ( B = -0.46, CI: -1.3, 0.33, p = 0.2). SP patients continued alpha-blockers less often postoperatively ( B = -0.27, CI: -0.39, -0.41, p = 0.001). SP showed higher blood transfusion rates (OR = 4.22, CI: 1.64, 13.2, p = 0.006), longer hospital stays ( B = 1.7, CI: 1.0, 2.4, p < 0.001), and longer operating times ( B = 119, CI: 101, 135, p < 0.001). SP had lower retreatment rates (OR = 0.46, CI: 0.23, 0.87, p = 0.019). AE were not significantly different ( p = 0.8). Conclusions: Aqua outperformed SP for blood transfusions, hospital stay, and operative time. SP outperformed Aqua for retreatment rates, IPSS scores at 1-year follow-up, and reliance on alpha-blockers. more...

Purpose: Retinoids for acne, finasteride/saw palmetto for hair loss/BPH, and selective Serotonin Reuptake inhibitors (SSRIs) for depression, have all been implicated in severe, persistent sexual dysfunction that occurs after stopping these medications. The underlying mechanism of this post-drug syndrome is unknown, nor is an effective treatment available. The purpose of this investigation is to use a retrospective chart review to characterize a cohort of patients who suffer from post-drug syndrome and to determine if improvement in symptoms is feasible when focusing treatment on the peripheral nerves of the genitalia., Methods: Three male patients seen in our urology clinic were sequentially treated with high frequency electrical stimulation and low intensity extracorporeal shock wave therapy for a total of 16 weeks. Symptom improvement was assessed using the International Index of Erection Function (IIEF), the Masturbation Erection Index (MEI), global response assessment scale, corneal confocal microscopy, the FirmTech® Ring to monitor nocturnal erections pre- and post-peripheral nerve treatment and von Frey filament testing., Result: Mild-moderate erectile function improvement, mild penile sensitivity improvement, and mild nocturnal erection improvement were seen across all three patients. Peripheral neuropathy was noted in two patients via corneal confocal microscopy, however central symptoms remain., Conclusion: The post-drug syndrome appears to consist of a peripheral component which may be treatable using our regimen, as we saw overall improvement in penile sensitivity and erections following treatments. However, patients were still profoundly affected by their symptoms post-treatment and thus there is an urgent need for additional research on this syndrome., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.) more...

Background: Surgical management options for lower urinary tract symptoms due to benign prostatic hypertension have remained limited in prostates of large volume. The advent of the Aquablation has created a potential minimally invasive option for treatment in prostates of all volumes. Thus, this study aims to evaluate outcomes and complications of Aquablation in clinical practice based on prostate volume., Methods: Collected variables included adverse events with Clavien-Dindo classifications, transfusion rates, surgical retreatment rates, continued medication use postoperatively, and International Prostate Symptom Score (IPSS) with Quality-of-Life indicator. Aquablations were stratified by preoperative prostate volume., Results: One hundred seventy-four men were included in the study. The average postop decrease in IPSS was 10.28, with a 2.02 point decrease in Quality-of-Life at 1 year. Postop increase in peak urinary flow rate was 7.65 mL/s for an average of 16.44 mL/s. Hemoglobin drop average was 1.78 g/dL, but only 2.3% of patients required a transfusion. 12.9% of patients required surgical retreatment. Six months after Aquablation, 22.9% and 12.9% of patients continued taking Alpha-blockers and Androgen receptor inhibitors, respectively. Adverse events occurred in 33 patients (19.0%). Eighteen patients were excluded from secondary analysis due to unrecorded prostate volume, leaving 123 with volumes <150 mL and 33 with volumes ≥150 mL. Groups were comparable with respect to length of stay, adverse events, blood transfusion, IPSS with Quality-of-Life indicator preoperative and postoperative, postop peak urinary flow, and postop alpha-blocker use. Larger prostates had a higher rate of adverse events, retreatment, postop hemoglobin drop, and postop use of finasteride., Conclusions: Aquablation is a viable treatment option for benign prostatic hyperplasia. Efficacy, safety, subjective outcomes, and adverse event rates were not impacted by prostate volume. However, size does matter as prostates ≥150 mL had higher surgical retreatment rates and postop finasteride use., (© 2024 Wiley Periodicals LLC.) more...

Purpose: To assess efficacy and safety of URO-902, an investigational gene therapy expressing the α subunit of the large-conductance Ca 2+ -activated K +erscript> channel, in a phase 2a placebo-controlled trial in women with overactive bladder (OAB)., Materials and Methods: Women, age 40 to 79 years, with OAB and urge urinary incontinence who were refractory to OAB medications were randomized to single-dose URO-902 24 and 48 mg or placebo administered by intradetrusor injection by cystoscopy under local anesthesia. Efficacy end points included change from baseline to week 12 in mean daily micturitions, urgency episodes, urge urinary incontinence episodes, and patient-reported outcomes. Safety assessments included adverse events and postvoid residual urine volume., Results: Of 80 patients randomized (URO-902 24 mg, n = 26; URO-902 48 mg, n = 27; placebo, n = 27), 74 received treatment and 67 reached week 24. At week 12, URO-902 24 and 48 mg were associated with significant improvement vs placebo in daily micturitions (least squares mean change from baseline, -2.3 and -2.4 vs -0.8; least squares mean difference [95% CI], ‒1.5 [‒2.7 to ‒0.3] and ‒1.6 [‒2.8 to ‒0.4], nominal P = .017 and P = .009, respectively). URO-902 48 mg was associated with significant improvements vs placebo in urgency episodes (‒3.4 vs ‒1.1; ‒2.2 [‒4.0 to ‒0.4]; nominal P = .016) and percentage of Patient Global Impression of Change responders (58% vs 31%; nominal P = .026). Among patients receiving URO-902 24 mg, 48 mg, and placebo, 46%, 54%, and 54%, respectively, experienced ≥ 1 treatment-emergent adverse events, most commonly UTI (0%, 15%, 4%) and hematuria (6%, 8%, 8%)., Conclusions: In this phase 2a trial, treatment with URO-902 was associated with improvements vs placebo in efficacy and patient-reported outcomes and was safe and well tolerated. more...

Introduction: Clitoral priapism is persistent clitoral engorgement without sexual stimulation. Presentation is sparse, and therefore limited treatment options have been investigated., Aim: We present a case report of a 34-year-old female presenting with persistent nonischemic clitoral priapism 5 years after aggressive clitoral stimulation., Methods: Patient underwent six weekly Li-ESWT sessions at frequency 4 Hz, energy 0.11 mJ for 2000 shocks per session. Assessment included physical examination of clitoral glans engorgement and retraction, global response assessment (GRA) score, need for topical phenylephrine, and ability to achieve orgasm., Results: At the end of the therapy, examination revealed complete resolution of priapism with a normal-appearing clitoris fully retracted behind the clitoral hood. The patient reported no longer requiring topical phenylephrine, a significant improvement in GRA, and the ability to achieve orgasm., Conclusion: We present a case of nonischemic clitoral priapism resolved with Li-ESWT. More investigation regarding the utilization of Li-ESWT in the treatment of clitoral priapism is highly encouraged., Competing Interests: Dr. Kenneth Peters is a consultant for Thermaquil Inc, Urovant, Collamedix, Iota Bioscience, and Uromedical and is an equity owner of UroMedical. Dr. Priya Padmanabhan is a PI for Medtronic, coinvestigator for Cook Medical and Urovant, and has received honoraria from Axonics. The remaining authors have no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine.) more...

Purpose: Neurogenic lower urinary tract dysfunction (NLUTD) is highly prevalent among patients with neurologic disorders. Some studies have demonstrated that implantable neuromodulation can improve symptoms of NLUTD. We seek to describe our experience with sacral and pudendal neuromodulation in patients with NLUTD., Methods: A retrospective chart review of patients with "neurogenic bladder" ICD-9/10 (International Classification of Diseases, Ninth Revision/10th Revision) code was performed at a single institution. This included patients from 2008 to 2020 who underwent stage 1 neuromodulation trial. Demographic and clinical information was collected, including neurologic diagnosis, the character of patients' voiding symptoms, the presence or absence of fecal incontinence, the need for intermittent catheterization, and whether patients had sufficient (>50%) improvement in their symptoms to undergo stage 2 implantable pulse generator (IPG) placement., Results: We identified 82 patients with neurologic diagnoses who underwent stage 1 neuromodulation. The most common diagnoses were diabetic cystopathy (17.07%), spinal surgery (17.07%), and spinal cord injury (12.20%). The most commonly reported symptoms were urinary urgency, and urge urinary incontinence. Overall, 59 patients (71.95%) advanced to stage 2 IPG placement including 72% of patients with sacral leads and 76% with pudendal leads., Conclusion: Neuromodulation is feasible and effective in the treatment of NLUTD. Further investigation into its utilization is warranted. more...

Aims: This study aimed to determine the efficacy and safety of iltamiocel investigational autologous muscle cell therapy in females with stress urinary incontinence (SUI)., Methods: Adult females were randomized 2:1 to iltamiocel (150 × 10 6  cells) or placebo and stratified by severity and prior SUI surgery. The primary objective was efficacy based on the frequency of stress incontinence episodes (SIE) recorded in a 3-day diary at 12 months posttreatment. After 12 months, placebo participants could elect to receive open-label iltamiocel. Efficacy and safety analyses were performed using all patients as treated populations., Results: The study enrolled 311 patients, 297 were randomized to either iltamiocel (n = 199) or placebo (n = 98). Of the 295 participants that completed 12 months blinded follow-up, the proportion achieving the primary endpoint of ≥ 50% SIE reduction was not statistically different between treatment groups (52% vs. 53.6%; p = 0.798). A significantly greater proportion of iltamiocel participants in the prior SUI surgery stratum group achieved ≥ 75% SIE reduction compared with placebo, (40% vs. 16%; p = 0.037). Treatment response was maintained at 24 months in 78.4% and 64.9% of iltamiocel participants who achieved ≥ 50% and ≥ 75% SIE reduction, respectively, at Month 12. Adverse events related to the treatment were reported in 19 (9.5%) iltamiocel participants and 6 (6.1%) placebo participants., Conclusion: The study did not meet its primary endpoint however, iltamiocel cell therapy is safe and may be ideally suited to female patients who have undergone prior surgery for SUI. Additional study in this group of patients with high unmet medical needs is warranted., Trial Registration: ClinicalTrials.gov identifier: NCT01893138; EudraCT number: 2014-002919-41., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.) more...

Background: Escherichia coli is the most common cause of human bloodstream infections and bacterial sepsis/septic shock. However, translation of preclinical septic shock resuscitative therapies remains limited mainly due to low-fidelity of available models in mimicking clinical illness. To overcome the translational barrier, we sought to replicate sepsis complexity by creating an acutely critically-ill preclinical bacterial septic shock model undergoing active 48-h intensive care management., Aim: To develop a clinically relevant large-animal (ovine) live-bacterial infusion model for septic shock., Methods: Septic shock was induced by intravenous infusion of the live antibiotic resistant extra-intestinal pathogenic E. coli sequence type 131 strain EC958 in eight anesthetised and mechanically ventilated sheep. A bacterial dose range of 2 × 10 5 -2 × 10 9  cfu/mL was used for the dose optimisation phase (n = 4) and upon dose confirmation the model was developed (n = 5). Post-shock the animals underwent an early-vasopressor and volume-restriction resuscitation strategy with active haemodynamic management and monitoring over 48 h. Serial blood samples were collected for testing of pro-inflammatory (IL-6, IL-8, VEGFA) and anti-inflammatory (IL-10) cytokines and hyaluronan assay to assess endothelial integrity. Tissue samples were collected for histopathology and transmission electron microscopy., Results: The 2 × 10 7  cfu/mL bacterial dose led to a reproducible distributive shock within a pre-determined 12-h period. Five sheep were used to demonstrate consistency of the model. Bacterial infusion led to development of septic shock in all animals. The baseline mean arterial blood pressure reduced from a median of 91 mmHg (71, 102) to 50 mmHg (48, 57) (p = 0.004) and lactate levels increased from a median of 0.5 mM (0.3, 0.8) to 2.1 mM (2.0, 2.3) (p = 0.02) post-shock. The baseline median hyaluronan levels increased significantly from 25 ng/mL (18, 86) to 168 ng/mL (86, 569), p = 0.05 but not the median vasopressor dependency index which increased within 1 h of resuscitation from zero to 0.39 mmHg -1 (0.06, 5.13), p = 0.065, and. Over the 48 h, there was a significant decrease in the systemic vascular resistance index (F = 7.46, p = 0.01) and increase in the pro-inflammatory cytokines [IL-6 (F = 8.90, p = 0.02), IL-8 (F = 5.28, p = 0.03), and VEGFA (F = 6.47, p = 0.02)]., Conclusions: This critically ill large-animal model was consistent in reproducing septic shock and will be applied in investigating advanced resuscitation and therapeutic interventions., (© 2024. The Author(s).) more...

Purpose: SARS-CoV-2 infection can result in genitourinary symptoms, such as frequency, urgency, nocturia, and pain/pressure. In this study, we followed the progression of overactive bladder (OAB) symptoms in patients that reported new or worsening OAB symptoms after coronavirus disease-19 (COVID-19) diagnosis., Materials and Methods: Individuals from a COVID-19 serology study were invited to participate in a follow-up study. Respondents were divided into three groups based on prior COVID-19 testing. Patients scored symptoms retrospectively before the pandemic, at study onset, and prospectively during 12-month follow-up. Genitourinary symptoms were assessed using international consultation on incontinence questionaire for OAB (ICIQ-OAB). Change in ICIQ-OAB scores from baseline were calculated. The minimal important difference of one on ICIQ-OAB is considered a significant change., Results: 26.0% of participants previously had positive COVID polymerase chain reaction (PCR) test (PCR+), 5.6% a positive serology test only (Ser+), and 65.5% were COVID naïve (COVID-). 23.8% of participants reported a significant increase in ICIQ-OAB score at study onset compared to prepandemic. ICIQ-OAB scores were similar at prepandemic but significantly higher at study start (p < 0.001) in PCR+ group. During follow-up, change in ICIQ-OAB scores from baseline remained unchanged for COVID- group, but gradually reduced for PCR+, reaching similar levels as COVID- group by 12 months. By 12 months, 71.4% of PCR+, 42.9% of Ser+, and 68.8% of COVID- participants still reported significant increase in ICIQ-OAB scores., Conclusions: Most COVID-19 patients experienced return of symptoms to baseline, indicative of the potential resolution of COVID-associated cystitis. A subset of cases did not, raising questions about the underlying factors contributing to this outcome. Additional research is needed to assess long COVID on urological health., (© 2024 Wiley Periodicals LLC.) more...

Objective: To improve diagnosis of interstitial cystitis (IC)/bladder pain syndrome(IC) we hereby developed an improved IC risk classification using machine learning algorithms., Methods: A national crowdsourcing resulted in 1264 urine samples consisting of 536 IC (513 female, 21 male, 2 unspecified), and 728 age-matched controls (318 female, 402 male, 8 unspecified) with corresponding patient-reported outcome (PRO) pain and symptom scores. In addition, 296 urine samples were collected at three academic centers: 78 IC (71 female, 7 male) and 218 controls (148 female, 68 male, 2 unspecified). Urinary cytokine biomarker levels were determined using Luminex assay. A machine learning predictive classification model, termed the Interstitial Cystitis Personalized Inflammation Symptom (IC-PIS) Score, that utilizes PRO and cytokine levels, was generated and compared to a challenger model., Results: The top-performing model using biomarker measurements and PROs (area under the curve [AUC]=0.87) was a support vector classifier, which scored better at predicting IC than PROs alone (AUC=0.83). While biomarkers alone (AUC=0.58) did not exhibit strong predictive performance, their combination with PROs produced an improved predictive effect., Conclusion: IC-PIS represents a novel classification model designed to enhance the diagnostic accuracy of IC/bladder pain syndrome by integrating PROs and urine biomarkers. The innovative approach to sample collection logistics, coupled with one of the largest crowdsourced biomarker development studies utilizing ambient shipping methods across the US, underscores the robustness and scalability of our findings., Competing Interests: Declaration of Competing Interest Laura E. Lamb – Has intellectual property associated with methods for diagnosing interstitial cystitis and is an employee/has stock options for Strata Oncology. Joseph J. Janicki – Has intellectual property associated with methods for diagnosing interstitial cystitis. Michael B. Chancellor – Has intellectual property associated with methods for diagnosing interstitial cystitis. The other authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) more...

The tibial nerve is an established target for neuromodulation in the management of overactive bladder (OAB) and its associated symptoms, including urge urinary incontinence (UUI). Technologies are currently available to deliver tibial nerve stimulation (TNS) through percutaneous devices or through implantable devices. The benefits and safety of percutaneous TNS have led to it as a guideline-recommended therapy. However, patient compliance is limited by the burden of weekly office visits and the need for maintenance treatments. Further, insurance often only covers a limited number of lifetime visits for percutaneous TNS. These factors and others have led to the development, study, and utilization of implantable TNS devices. Implantable TNS devices deliver the same therapeutic mechanism of action for nerve stimulation with a permanent implanted device that provides at-home stimulation rather than in-office therapy delivery. Additionally, there is an added potential for dynamic and patient-centered stimulation. There is a large body of high-quality evidence published for TNS, including numerous randomized controlled trials published on percutaneous TNS which have consistently demonstrated superior efficacy to sham and similar efficacy to that of anticholinergic medications. Percutaneous TNS also performs better than conservative therapy including pelvic floor muscle training. The percutaneous and implantable approaches deliver nerve stimulation to the same target nerve, using the same mechanism of action. Therefore, data from randomized trials of percutaneous TNS are informative for implantable TNS devices. At the time of this article's publication, at least two implantable TNS devices have received marketing authorization from the Food and Drug Administration (FDA). The objective of this review is to discuss the mechanism of action for TNS and summarize the published literature from clinical trials of percutaneous TNS as a foundation of high-quality evidence for implantable devices targeting the tibial nerve., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.) more...

Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection., Competing Interests: NN, MP, SH, KP, LA, BF, SA, TM, PH, SB, SS, HB, PT, AB, BW, AI, MS No competing interests declared, (© 2023, Nhu et al.) more...

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized in part by urinary urgency, frequency, and pain. There is a strong interest in gathering more data to compare and assess the differences in characteristics based on the presence of Hunner's lesions in patients with IC/BPS., Materials and Methods: Using a nationwide crowdsource effort, we collected surveys and urine samples from patients with a history of IC/BPS. Participants completed the Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), Overactive Bladder questionnaire (OABq SF), and pain scores. In addition, participants reported any co-morbidities and lifestyle modifications. Urinary cytokine levels were measured and compared to symptom severity., Results: 491 participants enrolled: 119 with history of ulcerative Hunner's lesions (UIC), 372 reported no lesions (NHIC), and 2 unknowns. 96.3% were female, and prevalence of UIC was equal for both genders. Average age was higher for UIC vs. NHIC group (P = 0.011), as was the duration since diagnosis (P < 0.001). Symptom scores were elevated in UIC patients (P < 0.001). Both groups widely implemented lifestyle modifications, with dietary changes being most prevalent (70.1%), followed by prescription medication usage (63.1%). More UIC compared to NHIC participants experienced co-morbidities (P = 0.010). Urine samples were analyzed for GRO, IL-6, IL-8, and MCP-1. MCP-1 levels were significantly higher in UIC patients (P = 0.044). Weak positive correlation was found between cytokines and symptom scores., Conclusions: Patients with UIC and NHIC from across the United States displayed distinct phenotypic and urine biological characteristics. These findings contribute to increased understanding of IC/BPS and may aid in improving our knowledge of the condition., Competing Interests: MBC has intellectual property associated with methods for diagnosing interstitial cystitis., (AJCEU Copyright © 2024.) more...

Urinary tract infections (UTIs) are one of the most common bacterial infections in humans, with ~400 million cases across the globe each year. Uropathogenic Escherichia coli (UPEC) is the major cause of UTI and increasingly associated with antibiotic resistance. This scenario has been worsened by the emergence and spread of pandemic UPEC sequence type 131 (ST131), a multidrug-resistant clone associated with extraordinarily high rates of infection. Here, we employed transposon-directed insertion site sequencing in combination with metabolomic profiling to identify genes and biochemical pathways required for growth and survival of the UPEC ST131 reference strain EC958 in human urine (HU). We identified 24 genes required for growth in HU, which mapped to diverse pathways involving small peptide, amino acid and nucleotide metabolism, the stringent response pathway, and lipopolysaccharide biosynthesis. We also discovered a role for UPEC resistance to fluoride during growth in HU, most likely associated with fluoridation of drinking water. Complementary nuclear magnetic resonance (NMR)-based metabolomics identified changes in a range of HU metabolites following UPEC growth, the most pronounced being L-lactate, which was utilized as a carbon source via the L-lactate dehydrogenase LldD. Using a mouse UTI model with mixed competitive infection experiments, we demonstrated a role for nucleotide metabolism and the stringent response in UPEC colonization of the mouse bladder. Together, our application of two omics technologies combined with different infection-relevant settings has uncovered new factors required for UPEC growth in HU, thus enhancing our understanding of this pivotal step in the UPEC infection pathway., Importance: Uropathogenic Escherichia coli (UPEC) cause ~80% of all urinary tract infections (UTIs), with increasing rates of antibiotic resistance presenting an urgent threat to effective treatment. To cause infection, UPEC must grow efficiently in human urine (HU), necessitating a need to understand mechanisms that promote its adaptation and survival in this nutrient-limited environment. Here, we used a combination of functional genomic and metabolomic techniques and identified roles for the metabolism of small peptides, amino acids, nucleotides, and L-lactate, as well as the stringent response pathway, lipopolysaccharide biosynthesis, and fluoride resistance, for UPEC growth in HU. We further demonstrated that pathways involving nucleotide metabolism and the stringent response are required for UPEC colonization of the mouse bladder. The UPEC genes and metabolic pathways identified in this study represent targets for the development of innovative therapeutics to prevent UPEC growth during human UTI, an urgent need given the rapidly rising rates of global antibiotic resistance., Competing Interests: The authors declare no conflict of interest. more...

Bacteria adapt to selective pressure in their immediate environment in multiple ways. One mechanism involves the acquisition of independent mutations that disable or modify a key pathway, providing a signature of adaptation via convergent evolution. Extra-intestinal pathogenic Escherichia coli (ExPEC) belonging to sequence type 95 (ST95) represent a global clone frequently associated with severe human infections including acute pyelonephritis, sepsis, and neonatal meningitis. Here, we analysed a publicly available dataset of 613 ST95 genomes and identified a series of loss-of-function mutations that disrupt cellulose production or its modification in 55.3% of strains. We show the inability to produce cellulose significantly enhances ST95 invasive infection in a rat model of neonatal meningitis, leading to the disruption of intestinal barrier integrity in newborn pups and enhanced dissemination to the liver, spleen and brain. Consistent with these observations, disruption of cellulose production in ST95 augmented innate immune signalling and tissue neutrophil infiltration in a mouse model of urinary tract infection. Mutations that disrupt cellulose production were also identified in other virulent ExPEC STs, Shigella and Salmonella, suggesting a correlative association with many Enterobacteriaceae that cause severe human infection. Together, our findings provide an explanation for the emergence of hypervirulent Enterobacteriaceae clones., (© 2024. The Author(s).) more...

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) manifests as urinary symptoms including urgency, frequency, and pain. The IP4IC Study aimed to establish a urine-based biomarker score for diagnosing IC/BPS. To accomplish this objective, we investigated the parallels and variances between patients enrolled via physician/hospital clinics and those recruited through online crowdsourcing., Methods: Through a nationwide crowdsource effort, we collected surveys from patients with history of IC/BPS. Study participants were asked to complete the validated instruments of Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), as well as provide demographic information. We then compared the survey responses of patients recruited through crowdsourcing with those recruited from three specialized tertiary care urology clinics engaged in clinical research., Results: Survey responses of 1300 participants were collected from all 50 states of the USA via crowdsourcing and 319 from a clinical setting. ICSI and ICPI were similar for IC/BPS patients diagnosed by the physicians in clinic and self-reported by subjects via crowdsourcing stating they have a history of previous physician diagnosis of IC/BPS. Surprisingly, ICSI and ICPI were significantly lower in crowdsourced control than in-clinic control subjects., Conclusion: The IP4IC Study provides valuable insights into the similarities and differences between patients recruited through clinics and those recruited through online crowdsourcing. There were no significant differences in disease symptoms among these groups. Individuals who express an interest in digital health research and self-identify as having been previously diagnosed by physicians with IC/BPS can be regarded as reliable candidates for crowdsourcing research., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.) more...

A 45-year-old male with diabetes, hypertension and hyperlipidemia was referred to urology due to persistent symptoms of urinary frequency, urgency, nocturia, erectile dysfunction, and constant pain localized to the bladder, pelvis, and perineal area, 3-4 months after SARS-CoV-2 infection. A bladder biopsy showed urothelial mucosa and submucosa with hemorrhage and fibrin microthrombi in blood vessels. Hydrodistention of the bladder and pelvic floor physical therapy resolved symptoms, though bladder and pain symptoms returned upon reinfection with SARS-CoV-2. Urinalysis revealed elevated urinary interleukin-8, which may indicate localized bladder inflammation., Competing Interests: The authors declare no financial competing interests with this study., (© 2023 The Authors.) more...

Objectives: Tibial nerve stimulation is an effective treatment for overactive bladder (OAB) and has been utilized as an in-person recurring session treatment option for many years. The primary objective of this study was to evaluate the safety and efficacy of a long-term implantable device and the method of utilizing a retrograde approach to place the device (a percutaneous implantable pulse generator [pIPG] with integrated quadripolar electrodes) at the tibial nerve (Protect PNS; Uro Medical Corp.)., Methods: A novel retrograde implant technique was developed through multiple cadaveric dissections to percutaneously implant a chronic, wireless, minimally invasive pIPG device with integrated quadripolar electrodes (now licensed to Uro Medical) at the tibial nerve. A proof-of-concept pIPG device approved as part of an FDA IDE was designed to gain early experience in subjects with refractory OAB. The pIPG was implanted in the office under local anesthesia using the novel retrograde approach, and stimulation was activated using an external wireless energy source called a transmitter. Initially, a pilot study was designed to compare outcomes in subjects randomized to either percutaneous tibial nerve stimulation (PTNS) or Protect PNS. However, due to the small sample sizes available at this time, it was not possible to compare the two groups. Thus, the purpose of this manuscript is to describe the outcome of subjects who underwent implantation of the Protect PNS system. Twelve-month safety and efficacy were evaluated., Results: Nine subjects were enrolled in the randomized pilot study; 5 to the pIPG group and 4 to PTNS, and all completed the 13-week primary endpoint. Subsequently, two subjects in the PTNS group chose to cross over and have the pIPG implanted after 13 weeks. Outcomes of the seven subjects who underwent implantation of the pIPG are described. No complications related to the office procedure were noted. Two of the older model pIPG devices became nonresponsive at 1 and 4 weeks and were replaced. Six minor adverse events were reported and resolved. Subjects reported improvement in urge urinary incontinence (UUI) episodes, OAB symptoms, and quality of life. Subjects impanted with a pIPG reported a 50% reduction in UUI as early as 1 week., Conclusions: Results of this pilot study suggest that retrograde percutaneous implantation of a pIPG is a safe, minimally invasive one-stage office procedure for treatment for urge incontinence related OAB symptoms, without significant complications after 12 months follow-up. Future studies will be required to compare outcomes among treatment modalities., (© 2022 Wiley Periodicals LLC.) more...

This is a report of a women who failed 2 surgical repairs of vesicovaginal fistula secondary to refractory bladder spasms. After each surgical procedure - the hysterectomy and subsequent fistula repairs - the patient reported severe bladder spasms refractory to medical management. Our treatment was intradetrusor onabotuliniumtoxinA injections 4 weeks prior to a planned surgical fistula repair. The patient had successful vaginal approach fistula repair and has not required any subsequent overactive bladder (OAB) treatment., (© 2022 The Authors. Published by Elsevier Inc.) more...

Background: Literature is sparse on COVID-19-associated cystitis (CAC), a novel condition comprising frequency, urgency, and nocturia after COVID-19 infection., Objective: To determine the incidence of CAC and correlation with SARS-CoV-2 antibody levels., Design Setting and Participants: This was a retrospective study in which urinary symptoms were scored using the International Consultation on Incontinence Questionnaire-overactive bladder (ICIQ-OAB) at three time points: before the pandemic (January 2020), 2 mo after COVID-19 infection (if applicable), and at the time of the study (May 2021). The setting was a regional health care system. The 18 785 healthcare employees who took part in the BLAST COVID study group were invited to participate, of whom 1895 responded., Outcome Measurements and Statistical Analysis: The outcome measured was the percentage of COVID-positive patients with a significant change on ICIQ-OAB over time. Pearson's χ 2 test was used for comparison of categorical data, and one-way analysis of variance for continuous data and multivariate analysis. A sample size of 618 was calculated for power of 80% and α = 0.05., Results and Limitations: Of the 1895 participants, 31.9% ( n  = 605) were positive for COVID-19 according to positive serology or a polymerase chain reaction (PCR) test. Of these, 492 were PCR-positive and had 2-mo postinfection data, with 36.4% (179/492) reporting an increase of ≥1 point on the ICIQ-OAB compared to baseline (before the pandemic), with de novo OAB in 22% of these cases (40/179). Comparison of symptoms between baseline and the study time revealed that 27.4% (31/113) of those with positive serology only (asymptomatic COVID) and 37.8% (186/492) of those with PCR positivity (symptomatic COVID) had an increase of ≥1 point on the ICIQ-OAB, compared to 15.8% ( n  = 204) of uninfected patients, with odds ratios of 2.013 (95% confidence interval [CI] 1.294-3.138; p  = 0.0015) and 3.236 (95% CI 2.548-4.080; p  < 0.0001), respectively. The retrospective nature of the study and the volunteer sample are limitations., Conclusions: COVID-19 infection increases the risk of developing new or worsening OAB symptoms., Patient Summary: We compared overactive bladder symptoms in a large group of participants between individuals with and without a previous COVID-19 infection. We found that symptomatic infection was associated with a three times greater risk of developing new or worsening overactive bladder symptoms among COVID-19 patients., (© 2022 The Author(s).) more...

Introduction: Clinical research can be expensive and time consuming due to high associated costs and/or duration of the study. We hypothesized that urine sample collection using online recruitment and engagement of research participants via social medial has the potential to reach a large population in a small timeframe, at a reasonable cost., Methods: We performed a retrospective cost analysis of a cohort study comparing cost per sample and time per sample for both online and clinically recruited participants for urine sample collection. During this time, cost data were collected based on study associated costs from invoices and budget spreadsheets. The data were subsequently analyzed using descriptive statistics., Results: Each sample collection kit contained 3 urine cups, 1 for the disease sample and 2 for control samples. Out of the 3,576 (1,192 disease + 2,384 control) total sample cups mailed, 1,254 (695 control) samples were returned. Comparatively, the 2 clinical sites collected 305 samples. Although the initial startup cost of online recruitment was higher, cost per sample for online recruited was found to be $81.45 compared to $398.14 for clinic sample., Conclusions: We conducted a nationwide, contactless, urine sample collection through online recruitment in the midst of the COVID-19 pandemic. Results were compared with the samples collected in the clinical setting. Online recruitment can be utilized to collect urine samples rapidly, efficiently, and at a cost per sample that was 20% of an in-person clinic, and without risk of COVID-19 exposure. more...

In 2021, a national network of multidisciplinary medical competence-centers has established itself in Germany that is committed to ensuring the care of people with thalidomide embryopathy. This article would like to draw attention to this competence network and give an overview of the most important medical care needs of aging people with thalidomide-induced body and sensory impairments. Here, the available scientific evidence and clinical peculiarities in medical care from a general medical-internal, orthopedic-paintherapeutic, sociomedical and psychosomatic-psychotherapeutic perspective will be presented and necessary tasks for the future will be discussed., Competing Interests: RB, KP und VS erhielten finanzielle Förderungen zum Aufbau Multidisziplinärer Medizinischer Kompetenzzentren von der Conterganstiftung für behinderte Menschen.JSH ist Mitglied der Medizinischen Kommission der Conterganstiftung. Darüber hinaus haben die Autoren keine Interessenkonflikte., (Thieme. All rights reserved.) more...

Post orgasmic illness syndrome (POIS) is increasingly being recognized as a debilitating cause of sexual dysfunction in males. It is often misdiagnosed due to its unfamiliarity to providers, resulting in numerous potentially unnecessary tests and treatments. Currently, there is no known single most effective treatment, but several case reports suggest desensitization, hormonal therapy, and other treatment modalities may be useful. However, these treatments are experimental in nature and have not been evaluated in placebo-controlled trials. We report on the use of a simple over-the-counter antihistamine in the management of POIS., Competing Interests: AS, JRS and CL have no conflicts of interest or disclosures. KMP is a co-founder of Micron Medical and serves as a consultant for Urogen and Urovant., (© 2022 The Authors.) more...

Background: As individuals with thalidomide embryopathy now reaching their 60's they undergo long-term sequelae of their prenatal damage and experience a wide range of secondary health problems, in particular chronic musculoskeletal pain, movement restrictions, and mental disorders. These health problems are having a negative impact on their life circumstances and their health-related quality of life (HRQOL)., Objective: The aim of this study was to determine the HRQOL in individuals with thalidomide embryopathy in comparison to individuals of the age-adjusted general population in Germany with and without chronic disease conditions (primary outcome). And, further explore the influence of impairment patterns, pain stage, and mental disorders on physical and mental dimensions of HRQOL (secondary outcome)., Methods: A cross-sectional survey of 202 individuals with thalidomide embryopathy from North Rhine-Westphalia/Germany was conducted, which gathered information about physical examinations including a standardized determination of the pain stage, a structured psychological interview, and the HRQOL. The final dataset was 186 cases for primary outcome., Results: Individuals with thalidomide embryopathy (50.6 years, 55.9% females) show a significantly reduced physical HRQOL comparison to the age-adjusted German population with chronic diseases (physical component score; pcs: 33.4 vs. 45.3, p < .001). In addition, male individuals with thalidomide embryopathy show a significantly reduced mental HRQOL to their male counterparts in this comparison (mental component score; mcs: 45.0 vs. 50.0, p = .005). The subgroup analyses show that individuals with thalidomide embryopathy with quadruple impairment have a significantly lower physical HRQOL than those with hearing loss (pcs: 25.0 vs. 38.5; ci's not overlapping). Second, individuals with thalidomide embryopathy with severe compared to mild stages of pain have significantly poorer levels of physical and mental HRQOL (pcs: 25.8 vs. 37.7, ci not overlapping; mcs: 40.4 vs. 51.8, ci's not overlapping). And, individuals with thalidomide embryopathy without a mental disorder show a high mental HRQOL (mcs: 53.2), while in comparison to the total sample those with somatoform and personality disorders have a significantly reduced physical HRQOL (pcs: 27.5 and 24.8; both ci's not overlapping), and those with depressive disorders have a significant reduced mental HRQOL (mcs: 38.0 vs. 45.8, ci's not overlapping)., Conclusions: A longitudinal decreasing HRQOL in individuals with thalidomide embryopathy is known, as well as high prevalence of mental disorders and chronic pain syndromes. This study shows a strong association between these two influencing factors and a poor HRQOL., (© 2022 The Authors. Birth Defects Research published by Wiley Periodicals LLC.) more...

Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut colonisation remain to be properly understood. Ucl fimbriae are attachment organelles that facilitate ExPEC adherence. Here, we investigated cellular receptors for Ucl fimbriae and Ucl expression to define molecular mechanisms of Ucl-mediated ExPEC colonisation of the gut. We demonstrate differential expression of Ucl fimbriae in ExPEC sequence types associated with disseminated infection. Genome editing of strains from two common sequence types, F11 (ST127) and UTI89 (ST95), identified a single nucleotide polymorphism in the ucl promoter that changes fimbriae expression via activation by the global stress-response regulator OxyR, leading to altered gut colonisation. Structure-function analysis of the Ucl fimbriae tip-adhesin (UclD) identified high-affinity glycan receptor targets, with highest affinity for sialyllacto-N-fucopentose VI, a structure likely to be expressed on the gut epithelium. Comparison of the UclD adhesin to the homologous UcaD tip-adhesin from Proteus mirabilis revealed that although they possess a similar tertiary structure, apart from lacto-N-fucopentose VI that bound to both adhesins at low-micromolar affinity, they recognize different fucose- and glucose-containing oligosaccharides. Competitive surface plasmon resonance analysis together with co-structural investigation of UcaD in complex with monosaccharides revealed a broad-specificity glycan binding pocket shared between UcaD and UclD that could accommodate these interactions. Overall, our study describes a mechanism of adaptation that augments establishment of an ExPEC gut reservoir to seed disseminated infections, providing a pathway for the development of targeted anti-adhesion therapeutics., Competing Interests: The authors have declared that no competing interests exist. more...

Eligible for 1 MOC SA CreditFrom the ABD This Photo Challenge in our print edition is eligible for 1 self-assessment credit for Maintenance of Certification from the American Board of Dermatology (ABD). After completing this activity, diplomates can visit the ABD website (http://www.abderm.org) to self-report the credits under the activity title "Cutis Photo Challenge." You may report the credit after each activity is completed or after accumulating multiple credits. more...

Background: Patients with intractable pain in the pudendal nerve distribution may benefit from pudendal neuromodulation; however, some may have previously undergone pudendal nerve entrapment surgery (PNES), potentially altering nerve anatomy and function., Aim: We examined pudendal neuromodulation outcomes in patients with prior PNES., Methods: Patients with a history of PNES and quadripolar, tined pudendal lead placement for urogenital pain were reviewed. Symptoms and outcomes were collected from existing medical records., Outcomes: Patients with pudendal neuromodulation and prior PNES were compared to patients with no prior PNES who had pudendal lead placement., Results: Fifteen patients with a history of 1, 2, or 3 prior PNES (n = 13, 1, and 1, respectively) were evaluated. Most (10; 67%) were female, with bilateral pain (9; 60%), and symptoms of 5-26 years. After trialing the lead, bladder symptoms and pain were improved in 8 of 12 and 9 of 14 patients, respectively, and 80% of patients (12/15) underwent permanent generator implantation. When prior PNES patients were compared to those with no prior PNES (n = 43), gender (67% vs 77% female; P = .50) and age (median 63 vs 58 years; P = .80), were similar; however, BMI differed (mean 24 vs 29; P = .008) and a lower proportion (12/15; 80% vs 42/43; 98%; P = .049) had generator implantation. Importantly, median lead implant time (48 vs 50 minutes; P = .65) did not differ between the 2 groups., Clinical Implications: Pudendal neuromodulation has the potential to provide pain relief for a very difficult-to-treat population; furthermore, it does not appear that prior PNES surgery made lead placement significantly more challenging., Strengths & Limitations: Study strengths include being a tertiary referral center for urogenital pain and having a single surgeon perform all procedures in a regimented way. Limitations include the retrospective study design, small sample size and various approaches to PN CONCLUSION: Chronic pudendal neuromodulation can be a viable option even after prior PNES. Kristen M. Meier, Patrick M. Vecellio, Kim A. Killinger, Judith A. Boura, Kenneth M. Peters. Pudendal Neuromodulation is Feasible and Effective After Pudendal Nerve Entrapment Surgery. J Sex Med 2022;19:995-1001., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.) more...

The formation of aggregates and biofilms enhances bacterial colonisation and infection progression by affording protection from antibiotics and host immune factors. Despite these advantages there is a trade-off, whereby bacterial dissemination is reduced. As such, biofilm development needs to be controlled to suit adaptation to different environments. Here we investigate members from one of largest groups of bacterial adhesins, the autotransporters, for their critical role in the assembly of bacterial aggregates and biofilms. We describe the structural and functional characterisation of autotransporter Ag43 variants from different Escherichia coli pathotypes. We show that specific interactions between amino acids on the contacting interfaces of adjacent Ag43 proteins drives a common mode of trans-association that leads to cell clumping. Furthermore, subtle variation of these interactions alters aggregation kinetics and the degree of compacting within cell clusters. Together, our structure-function investigation reveals an underlying molecular basis for variations in the density of bacterial communities., (© 2022. The Author(s).) more...

Many antibiotic resistant uropathogenic Escherichia coli (UPEC) strains belong to clones defined by their multilocus sequence type (ST), with ST131 being the most dominant. Although we have a good understanding of resistance development to fluoroquinolones and third-generation cephalosporins by ST131, our understanding of the virulence repertoire that has contributed to its global dissemination is limited. Here we show that the genes encoding Afa/Dr fimbriae, a group of adhesins strongly associated with UPEC that cause gestational pyelonephritis and recurrent cystitis, are found in approximately one third of all ST131 strains. Sequence comparison of the AfaE adhesin protein revealed a unique allelic variant carried by 82.9% of afa -positive ST131 strains. We identify the afa regulatory region as a hotspot for the integration of insertion sequence (IS) elements, all but one of which alter afa transcription. Close investigation demonstrated that the integration of an IS 1 element in the afa regulatory region leads to increased expression of Afa/Dr fimbriae, promoting enhanced adhesion to kidney epithelial cells and suggesting a mechanism for altered virulence. Finally, we provide evidence for a more widespread impact of IS 1 on ST131 genome evolution, suggesting that IS dynamics contribute to strain level microevolution that impacts ST131 fitness. IMPORTANCE E. coli ST131 is the most common antibiotic resistant UPEC clone associated with human urinary tract and bloodstream infections. Understanding the features of ST131 that have driven its global dissemination remains a critical priority if we are to counter its increasing antibiotic resistance. Here, we utilized a large collection of ST131 isolates to investigate the prevalence, regulation, and function of Afa/Dr fimbriae, a well-characterized UPEC colonization and virulence factor. We show that the afa genes are found frequently in ST131 and demonstrate how the integration of IS elements in the afa regulatory region modulates Afa expression, presenting an example of altered virulence capacity. We also exploit a curated set of ST131 genomes to map the integration of the antibiotic resistance-associated IS 1 element in the ST131 pangenome, providing evidence for its widespread impact on ST131 genome evolution. more...

Vulvodynia is a debilitating disorder which can prove extremely difficult to treat. Neuromodulation is increasingly becoming a frontline therapy in various chronic pain syndromes. We present a relatively simple surgical technique utilizing targeted neuromodulation leading to the successful treatment of vulvodynia. more...

Escherichia coli ST131 is a recently emerged antibiotic resistant clone responsible for high rates of urinary tract and bloodstream infections. Despite its global dominance, the precise mechanisms that have driven the rapid dissemination of ST131 remain unknown. Here, we show that the plasmid-associated resistance gene encoding the AAC(6')-Ib-cr enzyme that inactivates the fluoroquinolone (FQ) antibiotic ciprofloxacin is present in >70% of strains from the most rapidly expanding subgroup of multidrug resistant ST131. Using a series of genome-edited and plasmid-cured isogenic strains, we demonstrate that the aac(6')-Ib-cr gene confers a selective advantage on ST131 in the presence of ciprofloxacin, even in strains containing chromosomal GyrA and ParC FQ-resistance mutations. Further, we identify a pattern of emerging carbapenem resistance in other common E. coli clones carrying both aac(6')-Ib-cr and chromosomal FQ-resistance mutations, suggesting this dual resistance combination may also impart a selective advantage on these non-ST131 antibiotic resistant lineages. more...

Objective: The aim of the study was to show the frequency, localisation, intensity, quality and degree of chronic pain in people with thalidomide-induced congenital defects (thalidomide embryopathy) and to investigate the association with biopsychosocial factors more closely., Methods: A group of 202 people from North Rhine-Westphalia with thalidomide embryopathy were studied for the first time both physically for the pattern of the original damage and also psychiatrically in a structured diagnostic interview (SCID I & SCID II). The results were combined with a standardized pain interview (MPSS) and questionnaires on further pain-related (SF-36, painDETECT) and sociodemographic variables and analysed. In the analysis 167 completed datasets were included., Results: The prevalence of pain in the sample population was 94%. The majority (107, 54.0%) already showed an advanced stage of chronicity in the MPSS: 63 subjects with Stage II (37.7%) and 44 with Stage III (26.3%). In 74 subjects (44.3%) the PainDetect score showed a possible or neuropathic pain component. The factors that most reliably influenced the chronicity of pain proved to be hip pain (p<0.001) and also mental health disorders (p=0.001), above major depression (p<0.001) and also somatic symptom disorders and substance-related disorders (p=0.001 in each case). Social variables proved non-significant here (p=0.094 for living alone, p=0.122 for unemployment, p=0.167 for lack of college education), as did the care situation (p=0.191 for care dependency) and the underlying pattern of organ damage (p=0.229 for damage to hearing, p=0.764 for dysmelia)., Conclusions: People with thalidomide defects frequently suffer from a separate pain disorder which can be seen as secondary thalidomide-induced damage and which requires specialized and personalized multimodal pain management., Competing Interests: K. M. Peters hat Honorare für Referententätigkeit der Firmen Amgen und Kyowa Kirin erhalten. Die anderen Autorinnen/Autoren erklären, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.) more...

Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein ( Selenof ) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof 's potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing. more...

Neuromodulation has become a valid therapeutic option for patients with various lower urinary tract disorders. In clinical practice, the most used and recommended neuromodulation techniques are sacral neuromodulation (SNM), pudendal neuromodulation (PN), and percutaneous tibial nerve stimulation (PTNS). There are many theories concerning the mechanism of action of neuromodulation. Although SNM, PN, and PTNS show their activities through different nerve roots, all provide central and peripheral nervous system modulations. SNM has been approved for the treatment of overactive bladder (OAB), nonobstructive urinary retention, and fecal incontinence, while PTNS has been approved for OAB treatment. However, they are also used off-label in other urinary and nonurinary pelvic floor disorders, such as neurogenic lower urinary system disorder, interstitial cystitis, chronic pelvic pain, and sexual dysfunction. Minor and nonsurgical reversible complications are usually seen after neuromodulation techniques. In addition, in the last few years, there have been various developments in neuromodulation technology. Some of the examples of these developments are rechargeable batteries with wireless charging, improvements in programing, less invasive single-stage implantation in outpatient settings, and lower-cost new devices. We performed a literature search using Medline (PubMed), Cochrane Library, EMBASE, and Google scholar databases in the English language from January 2010 to February 2021. We included reviews, meta-analyses, randomized controlled trials, and prospective and retrospective studies to evaluate the activities and reliability of SNM, PN, and PTNS and the developments in this area in the last decade based on the current literature. more...

Aims: Two phase 2 studies were conducted to assess the efficacy and safety of lidocaine-releasing intravesical system (LiRIS) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with (Study 001; NCT02395042) or without, (Study 002; NCT02411110) Hunner lesions (HL)., Methods: Both were multicenter, randomized, double-blind, placebo-controlled, and enrolled women aged ≥18 years. In Study 001, patients were randomized 2:1:1 to LiRIS 400 mg/LiRIS 400 mg, placebo/LiRIS 400 mg, or placebo/placebo for a continuous 28 (2 × 14)-day period. In Study 002, patients were randomized 1:1 to LiRIS 400 mg or placebo for a continuous (single treatment) 14-day period., Results: In total, 59 and 131 patients received treatment in Studies 001 and 002, respectively. There was no statistically significant difference in the primary endpoint, the change from baseline to Week 4 of follow-up post-removal in mean daily average bladder numeric rating scale (NRS) pain score in either study (Study 001: placebo/placebo, -1.6; LiRIS/LiRIS, -2.7, p = 0.142; placebo/LiRIS, -2.5, p = 0.319; Study 002: LiRIS -1.2; placebo, -1.5, p = 0.505). There was no statistically significant difference between groups in daily worst NRS pain score, number of micturitions/day or urgency episodes/day. There was no clear trend for reduction in number of HL for LiRIS vs placebo. The frequency of treatment-emergent adverse events was similar between treatment groups in both studies; most were mild or moderate intensity., Conclusion: These studies did not demonstrate a treatment effect of LiRIS 400 mg compared with placebo, either in patients with IC/BPS with HL, or in those without HL., (© 2021 Wiley Periodicals LLC.) more...

Aims: In patients with pudendal neuralgia, prior studies have shown efficacy in chronic stimulation with Interstim® (Medtronic, Inc.). This feasibility study reports on the initial experience of using a wireless system to power an implanted lead at the pudendal nerve, StimWave®, to treat pudendal neuralgia., Methods: Retrospective chart review identified patients with a lead placed at the pudendal nerve for neuralgia and powered wirelessly. Clinical outcomes were assessed at Postoperative visits and phone calls. Administered non-validated follow-up questionnaire evaluated the Global Response Assessment, percentage of pain improvement, satisfaction with device, and initial and current settings of the device (h/day of stimulation)., Results: Thirteen patients had the StimWave® lead placed at the pudendal nerve, 12 (92%) female and 1 (7.6%) male. Mean age was 50 years (range: 20-58). Failed prior therapies include medical therapy (100%), pelvic floor physical therapy (92%), pudendal nerve blocks (85%), pelvic floor muscle trigger point injections (69%), neuromodulation (30.7%), or surgeries for urogenital pain (23.1%). After the trial period, 10/13 (76.9%) had >50% improvement in pain with 6/13 (46.1%) reporting 100% pain improvement. Nine underwent permanent lead placement. At last postoperative visit (range, 6-83 days), 5/9 patients reported >50% pain improvement. Seven patients reached for phone calls (22-759 days) reported symptoms to be "markedly improved" (n = 2), "moderately improved" (n = 4), or "slightly improved" (n = 1). At follow up, complications included lead migration (n = 2), broken wire (n = 1), or nonfunctioning antenna (n = 2)., Conclusion: Complex patients with pudendal neuralgia may benefit from pudendal nerve stimulation via StimWave®., (© 2021 Wiley Periodicals LLC.) more...