Citations

Abstract Introduction Significant clinical variations exist in the definitions of acute/active vs chronic/stable Peyronie’s Disease (PD). While the American Urological Association’s 2015 guidelines define the acute phase as involving symptoms that change and the presence of pain, they do not specify a timeframe. Historically, acute-phase features include penile pain and worsening curvature, with symptom duration ranging from less than 3 to 18 months. Although temporally categorizing PD may have academic value, it may unnecessarily limit or delay treatment. In the United States, collagenase clostridium histolyticum (CCH) is the only FDA-approved treatment for adult men with PD who have a palpable plaque and a curvature deformity of at least 30 degrees. Several real-world studies suggest CCH is safe and effective during the acute phase. Objective To evaluate differences in outcomes by penile pain and symptom duration and to determine whether these factors should inform timing of CCH treatment in men with Peyronie’s disease. Methods A post hoc analysis of pooled data from 2 phase 3 randomized double-blind trials of CCH in PD (IMPRESS I, NCT01221597; IMPRESS II, NCT01221623). Men treated with CCH were stratified by baseline penile pain (Any Pain vs No Pain), based on both investigator-assessed and patient-reported measures. A subgroup analysis further stratified men with Any Pain by disease duration. The primary efficacy endpoint in the phase 3 study was the percentage change in penile curvature from baseline to week 52. A 2-sample t test was used to compare group means for each pain-related measure. Results A total of 364 CCH-treated men were included. Mean penile curvature improvements at week 52 were similar across all 4 investigator-assessed and patient-reported penile pain measures (35.0%-36.7% improvement for the No Pain group vs 32.2%-33.9% improvement for the Any Pain group, P=0.14-0.65). Among those experiencing Any Pain, no statistical differences were observed in men with disease durations that were shorter (12-18 months; 21.8%-34.8% improvement) vs longer (greater than 18 months; 31.4%-36.8% improvement, P=0.20-0.95). Conclusions This study found similar curvature improvements among men treated with CCH regardless of baseline pain or disease duration. Results align with prior studies showing no outcome differences by pain status or disease phase. These findings suggest that pain and disease duration should not be viewed as contraindications to CCH or used to guide clinical decision-making. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc. Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

Abstract Introduction Introduction: Peyronie’s disease (PD) is a fibrosing condition of the tunica albuginea characterized by a palpable plaque with varying impacts on the patient’s erection: curvature, shortening, indentations, hinging, and narrowing. Stepwise intralesional injection of collagenase clostridium histolyticum (CCH) is the only FDA approved medical treatment for PD. We retrospectively reviewed Xiaflex® treated patients for satisfaction with therapy or pursuit of subsequent surgery. Objective Objective: To assess global satisfaction with intralesional Xiaflex based on whether patients subsequently elected surgery. Methods Methods: This is a retrospective review of patients presenting with PD to a single center and managed by a single provider from 2020-2024 with six-month follow-up post-treatment. Patient presentations were recorded in an Institutional Review Board approved database. Data storage and analytics were conducted using REDCap. Results Results: The cohort for this study was 159 men treated with intralesional Xiaflex. 18 of the 159 were excluded from analysis due to ongoing treatment. 48.9% of patients (69/141) were satisfied with CCH outcomes and sought no further therapy. 51.1% of patients (72/141) were not satisfied with their outcomes. Of the patients not satisfied with treatment, 48/72 (66.7%) elected subsequent surgical interventions: 18 penile plications, 8 incision and grafting and 22 inflatable penile prostheses. 51.7% (73/141) of patients completed (8) CCH treatments. Among the 73 men who had a complete set of CCH injections, 24.6% (18/73) elected subsequent surgery. Among the patients who had fewer than 8 treatments 46.9% (30/64) elected surgery following Xiaflex. Conclusions Conclusion: If successful medical management of Peyronie’s disease is defined by men who decline subsequent surgical interventions, Xiaflex® was highly successful 75% (55/73). Patients who have Peyronie’s disease are highly motivated and will pursue surgical interventions following a trial of CCH. Disclosure No

Abstract Introduction Oncologic testicular sperm extraction (oncoTESE) remains a poorly defined concept that is a heterogeneous and understudied fertility preservation option for cancer patients with male gonads. Given variation in practice patterns, reproductive insurance coverage, and provider availability, there is significant diversity among the accepted indications, desired evaluations, and surgical practices afforded to patients facing a cancer diagnosis. Objective This study aimed to characterize and help further define oncoTESE practice patterns across the United States. Methods A 34-item, anonymized survey assessed provider demographics and oncoTESE practice patterns, including indications, contraindications, workflows, and institutional barriers surrounding OncoTESE procedures. A survey was created and electronically distributed to reproductive urologists across the United States using email addresses obtained via society membership websites. Results Thirty-eight urologists (20%, 38/189) from 21 states responded to the survey. Most (95%, 36/38) were fellowship-trained reproductive urologists, and nearly all (87%, 33/38) reported offering oncoTESE to indicated patients. The most cited indications for oncoTESE were azoospermia (78%, 28/36), anejaculation (72%, 26/36), and severe oligozoospermia or cryptozoospermia on ejaculated specimen (53%, 19/36). Less commonly reported indications included prepubertal or peripubertal status (33%, 12/36) and elevated sperm DNA fragmentation (19%, 7/36). Relative contraindications included inability to consent (86%, 31/36), clinical instability (83%, 30/36), thrombocytopenia (61%, 22/36), and a history of remote chemotherapy (58%, 21/36). When asked how many semen analyses are obtained to confirm azoospermia before proceeding to oncoTESE in patients able to ejaculate, the majority reported two analyses (67%, 24/36), while 28% (10/36) reported one. There was stronger consensus that oncoTESE includes sperm retrieval during back-table orchiectomy (94%, 34/36) and ipsilateral microTESE during partial orchiectomy (86%, 31/36). Greater variability was noted regarding contralateral microTESE at the time of orchiectomy (64%, 23/36), procedures for non-genitourinary malignancies (61%, 22/36), and delayed procedures performed years after diagnosis (42%, 15/36). (Figure 1) Estimated patient costs for oncoTESE were most commonly reported as $2,000–$5,000 (39%, 14/36), followed by $500–$2,000 (22%, 8/36), $5,000–$10,000 (19%, 7/36), and over $10,000 (3%, 1/36); 14% (5/36) were unsure. On a 10-point Likert scale, the most significant barriers to performing oncoTESE were logistical challenges (mean 6.6, median 8), followed by patient cost (mean 5.4, median 5.5) and patient illness (mean 5.3, median 5.0). Conclusions This multi-institutional survey found strong agreement among reproductive urologists on core procedural elements, but substantial variation on oncoTESE definition, patient selection criteria, pre-procedural evaluation, and fertility preservation management. Similar institutional barriers across centers highlight opportunities to improve accessibility and standardize oncoTESE practices. Disclosure No

Abstract Introduction While most patients with Peyronie’s disease (PD) present with dorsal or lateral curvature, a significant number have ventral curvature (VC). These patients face limited treatment options, as they were excluded from initial clinical trials of collagenase clostridium histolyticum (CCH) due to safety concerns related to the proximity of the injection site to the urethra. However, urethral involvement is rare, as PD plaques develop in the tunica albuginea rather than the corpus spongiosum surrounding the urethra. Moreover, multiple prospective and retrospective studies have demonstrated favorable outcomes with CCH treatment in men with VC. Objective To evaluate the effectiveness and safety of CCH in men with PD and VC in a multicenter, real-world, retrospective study. Methods This is an ongoing phase 4, multicenter, retrospective review of medical records from 15 US physician sites. Eligible patients consisted of patients who are: age ≥18 years with a diagnosis of VC in PD with a palpable plaque that was treated with CCH from 2014 to the study start date at each site. Patients missing baseline (BL; pretreatment) or final (last measurement within 6 months of final CCH treatment) penile curvature measurements were excluded. Effectiveness endpoints included percentage change in VC from BL to last visit, mean change in VC (in degrees) from BL to last visit, and proportion of patients with ≥30% improvement in VC from BL to last visit. Safety was assessed as proportions of patients reporting treatment-related adverse events (TRAEs) throughout the study period. Results As of April 22, 2025, there were 116 patients with mean (SD) age of 58 (10.3) years who were eligible for analysis. Mean baseline VC decreased from 58 degrees to 37 degrees at last visit (37% improvement). An improvement in VC of ≥30% was seen in 73/116 (63%) of patients, with 81/116 (69.8%) experiencing ≥20% improvement. At least 1 TRAE was reported by 12 (10%) patients. TRAEs were mild-to-moderate in severity in 9 (75%) patients and unknown in 3 patients, with most events (14/17 [82%]) related to injection site reactions. As of the data cut, there were no treatment-related serious or treatment-related severe AEs, no reports of urethral involvement or injury, and no reports of corporal rupture. Conclusions Men with PD who present with ventral curvature represent an underserved patient population. Concerns about potential urethral injury pose a significant barrier to both minimally invasive and surgical treatments, thereby limiting available therapeutic options. These updated results from a multi-institutional real-world clinical cohort align with previous findings, and demonstrate that the clinical effectiveness and safety profile of CCH is consistent with the profile of CCH seen in other clinical presentations of PD. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

Abstract Introduction 0.05% Chlorhexidine Gluconate (CHG) has gained popularity as an irrigant and dip for inflatable penile prosthesis (IPP) surgery. Prior in vitro data is conflicting on the impact of CHG use with hydrophilic coated devices. Objective We sought to identify possible associations between CHG use and hydrophilic IPP infection rate. Methods We conducted a retrospective cohort study of 2,933 patients undergoing IPP implantation across 14 referral centers. Data collection spanned from January 1, 2017 to March 1, 2024. Each surgeon contributed patients who underwent IPP implantation with CHG used as an irrigant and/or dip as well as an equal number of consecutive control patients without CHG use. The primary outcome was IPP explant for postoperative infection. Univariable analysis was used to compare patient demographics, and logistic regression analysis was performed to assess factors associated with infection. Results Hydrophilic devices were implanted in 2,150 patients. Median follow-up for non-CHG patients was 13 months (IQR 18) and four months (IQR 9) for CHG patients. The incidence of infection with intraoperative CHG use was significantly higher compared to those without CHG use (4.6%, 46/1,001 vs. 2.1%, 24/1,148, p<0.001). On multivariable logistic regression analysis, intraoperative CHG use was associated with infection (OR 2.07, 95% CI 1.24-3.47, p=0.01). Additional variables associated with infection included immunosuppression, prior IPP infection, prior priapism, and revision surgery (p<0.01, Table). On subgroup analyses, the increased infection risk of CHG was most clear when CHG was used as both irrigation and dip (OR 2.03, 95% CI 1.19-3.46, p=0.01) and when CHG was used during revision surgery (OR 3.36, 95% CI 1.15-9.82, p=0.03). Conclusions In a large multi-institutional cohort, intraoperative CHG use was associated with an elevated incidence of hydrophilic IPP infection. Providers may take these findings into consideration when performing IPP surgery with hydrophilic devices, especially during revision surgery. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast Corporation and Boston Scientific

Abstract Rheumatoid arthritis (RA) is a chronic disease involving inflammation of the joints. While the etiology of RA remains unknown, evidence exists for a significant contribution of the major histocompatibility complex (MHC). Environmental factors are also indicated as playing an etiological role. Since it is impossible to define the mechanisms contributing to disease onset and progression in humans, mouse models have been used widely. While many animal models have been generated by immunization with self‐proteins to induce arthritis, type II collagen (CII)‐induced arthritis is one of the most commonly used models utilized to understand the immunopathology of RA. CII constitutes 80% to 90% of total collagen content of hyaline cartilage found in joints and is a genetically conserved sequestered protein. Immunization with heterologous CII with an adjuvant in mice leads to cellular and humoral responses to heterologous and autoreactive CII‐specific responses and collagen‐induced arthritis (CIA). Mice immunized with CII develop inflammatory arthritis that shares many similarities in clinical, serological, and radiological features with RA in humans. However, selecting an antigen for inducing arthritis and the mouse strain are important, as not all strains are susceptible to CIA. A critical difference between RA and CIA is that in mice that lack the expression of human MHC II, the development of CIA is linked to the H2A locus, which is the homologue of HLA‐DQ, while most human studies have linked RA susceptibility with HLA‐DR alleles. Mice expressing HLA‐DQ and HLA‐DR molecules have been used to understand the role of MHC genes in susceptibility to RA. The protocols for inducing CIA in the HLA expressing transgenic mice described in this article can be used to understand how the different HLA molecules confer susceptibility to RA. © 2025 Wiley Periodicals LLC. Basic Protocol 1 : Use of mouse strains and humanized mice for modeling rheumatoid arthritis Basic Protocol 2 : Use of humanized mice for therapeutic protocols

Objectives: In the United States, training for physicians who manage critically ill adult patients (intensivists) evolved through parallel subspecialty critical care medicine (CCM) pathways with significant commonality. The Society of Critical Care Medicine Adult Critical Care Physician Core Knowledge and Skills Task Force aimed to delineate the common core knowledge and skills required of all intensivists. Design: A master list of content areas and procedural skills was compiled from all CCM subspecialty program requirements and blueprints of the certification examinations. Using a modified Delphi approach, participants were asked to categorize the knowledge items as “advanced knowledge is essential,” “general, but not advanced, knowledge is essential,” or “knowledge is not essential.” Procedures were categorized as “intensivist performs routinely,” “intensivist only performs in an emergency,” or “intensivist knows” about the procedure. Setting: Representatives from CCM stakeholder organizations, including accreditation and certification organizations, critical care societies, and program directors’ societies, were invited to participate. SUBJECTS: Members of the Adult Critical Care Physician Core Knowledge and Skills Task Force of the Society of Critical Care Medicine. Interventions: For the first two rounds of the modified Delphi process, Research Electronic Data Capture was used. For the third and fourth rounds, the process was completed through online meetings with Zoom (Zoom Video Corporations, San Jose, CA) utilizing Zoom’s polling feature. Measurements and Main Results: A total of 541 items were determined to be essential, with 145 requiring advanced knowledge and 323 requiring general knowledge. For 73 items, consensus regarding advanced vs. general could not be achieved, but they remained essential. Only eight items were felt to be nonessential. Of the 16 procedures, most were categorized as “intensivist performs.” Conclusions: The large number of items included in the list of essential knowledge and skills demonstrates the complexity of modern CCM. Utilization of a common framework across the subspecialties of CCM could lead to greater harmonization among the fellowship program requirements and certification examinations.

Adoptive cell therapy (ACT) has shown remarkable success in the treatment of some malignancies, particularly leukemia. However, there are multiple factors that limit the durability of ACT in solid tumors, including dose-limiting toxicities, the immunosuppressive tumor microenvironment, and T-cell exhaustion. As the manufacture and preparation of adoptive T-cell therapies allows time and adequate conditions for ex vivo T-cell engineering, forward genetic screens can identify novel genetic targets that could improve their effectiveness. CRISPR is a commonly used functional genomics tool that has been successfully used to both enhance our understanding of mechanisms of resistance and to discover potential genetic edits to improve ACT. A complementary approach, Sleeping Beauty transposon mutagenesis provides additional opportunities to identify novel genetic edits without being constrained by the annotated human genome. Here, we summarize forward genetic screens and their tools to uncover strategies to enhance ACT. Complementary approaches can be combined and improved on to identify translatable genetic editing strategies through studies that accurately recapitulate disease-specific challenges.