Citations

Abstract Regulation of gene expression is central to the development of immune cells and their ability to respond to infection. As part of a clinical evaluation, we identified two sisters with recurrent infections, hypogammaglobulinemia, and memory B cell deficiency, diagnosed as common variable immunodeficiency. Whole exome sequencing identified a heterozygous variant (Leu50Ser, L50S) in a conserved region of EZH2, the catalytic subunit of the epigenetic gene repressor Polycomb Repressive Complex 2 (PRC2). EZH2-catalyzed histone H3 lysine 27 methylation (H3K27me) in bulk was not overall significantly disrupted by this variant, in patient samples or cell lines expressing EZH2-L50S. EZH2-L50S protein is expressed similar to wild-type and can form PRC2. However, we find that specific genomic regions that normally have high wild-type levels of H3K27me3 are deficient in the L50S context, particularly around gene promoters. EZH2-L50S is still recruited to these sites, but is not as active. Using recombinant purified PRC2, we determine that L50S affects methylation of nucleosomes and disrupts allosteric stimulation that normally amplifies H3K27me3, consistent with the location of L50 in the allosteric regulatory region of PRC2. Thus, variation of EZH2 L50, occurring at low frequency in the population may interfere with normal B cell gene expression patterns, contributing to immunodeficiency. This study has implications for genetic variation in PRC2 in the general population.

Abstract Introduction Infection following inflatable penile prosthesis (IPP) placement is an uncommon yet serious complication, and its management poses significant clinical challenges. IPP infection management strategies continue to evolve, however, multicenter and robust studies evaluating and describing current practice patterns are lacking. Objective Using a large cohort from tertiary IPP referral centers in the United States to evaluate current infection management practice patterns and to identify factors that could predict the approach to managing IPP infections. Methods We queried a retrospective 14-center multi-institutional database for patients with IPP infections between April 2017 and January 1/2025. Patients were categorized by infection management strategy, which included device explant, malleable salvage, and 3-piece IPP salvage. Patient characteristics were compared using chi-square and independent t-tests. Multinomial analysis was performed to investigate patient and perioperative factors associated with management strategy at the time of infection. Results Among 2,934 cases, 85 (2.9%) patients developed IPP infection at a median of 40 (22-78) days after IPP implantation. Infections occurred after primary IPP surgery in 59 (69%), revision in 25 (29%), and after infection salvaged with IPP in 1 (1%). Infections were managed with device explant in 32 (38%), malleable salvage in 43 (51%), and IPP salvage in 10 (12%). A significantly higher proportion of non-White patients underwent salvage (either with malleable or IPP) compared to White patients (p=0.01). Multinomial regression showed no association between patient and perioperative characteristics and infection management (p>0.05). Conclusions In this multi-institutional cohort of experienced implanters, infections were most commonly managed with malleable salvage. Patient and perioperative factors did not predict management approach, suggesting that the decision between explanation and salvage is primarily driven by individual surgeon preference. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston scientific

Abstract Introduction With the growing use of 0.05% Chlorhexidine Gluconate (CHG) as irrigation and dip for inflatable penile prosthesis (IPP) surgery, understanding the possible relationship between CHG use and non-infectious complications is imperative. Such information may guide provider decision-making during implant surgery. Objective We therefore sought to determine whether the use of 0.05% Chlorhexidine Gluconate (CHG) during inflatable penile prosthesis (IPP) surgery was associated with non-infectious wound complications. Methods We performed a multi-institutional retrospective cohort study of patients undergoing IPP surgery from January 2017 to March 2024. The primary outcome was wound complications (ex. rash, wound dehiscence, edema). Secondary outcomes included other non-infectious complications (Table 1). The primary exposure was whether patients received intraoperative CHG either as irrigation or dip. Descriptive comparisons were used to compare CHG and non-CHG cohorts. Univariable logistic regression was utilized to assess if CHG use was associated with any non-infectious complication. Multivariable logistic regression was subsequently performed to assess factors associated with certain non-infectious complications after IPP surgery – controlling for age, body mass index, race, diabetes, and hypertension as covariables. Results Across 2,933 patients, there were 1,573 non-CHG and 1,359 CHG patients. Non-infectious complications occurred in 83 (5%) non-CHG patients and in 65 (5%) CHG patients. Median follow-up was 22 months (IQR 7-59) for non-CHG patients and 8 months (IQR 3-16) for CHG patients. The incidence of wound complications was greater among CHG patients than non-CHG patients (1.0% vs. 0.1%, p<0.01). On univariable logistic regression, CHG use was associated with increased odds of wound complications (OR 7.34, 95% CI 1.65-32.71) but was not associated with any other non-infectious complication (Table 2). On multivariable logistic regression, CHG use remained associated with an increased odds of wound complications (OR 13.86, 95% CI 1.80-106.44). Conclusions Among patients experiencing non-infectious complications after IPP, CHG use during IPP surgery appears to be associated with an increased odds of wound complications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast Corporation and Boston Scientific

Abstract Introduction Penile implant (PI) surgery is a well-recognized strategy for erectile dysfunction (ED) with excellent functional/satisfaction outcomes. To date, little attention has been paid to the attitudes and satisfaction outcomes of female partners of such patients. Objective To qualitatively assess how female partners feel about PI surgery to inform the development of a female partner specific questionnaire. Methods Female partners of men who had undergone PI surgery (3-piece inflatable) underwent concept elicitation interviews. Prior to this, a panel of experts in female sexual health and PI surgery was convened to define potential domains of interest. Women were interviewed by one of two female sexual medicine clinicians to elicit concepts. As part of the spontaneous item generation phase, participants were asked about their attitudes, hopes and concerns prior to PI surgery, as well as changes in partner post-surgery. Participants were then asked whether they identified domains raised by the expert panel that were not mentioned during the spontaneous phase. Additional open-ended questions were asked about experiences before and after PI surgery. Interviews were transcribed verbatim for subsequent qualitative analysis by 2 trained members of the study team. Results 12 women have been interviewed. Mean partner age = 60 years, relationship duration = 20 years. Interviews were held <12 months post-PI for 17% of partners, 12-24 months for 25%, >24 months for 58%. Partner communication and involvement in decision to get the implant were uniquely raised as pre-surgical concerns, whereas PI attributes were uniquely mentioned as post-surgical concerns. How the PI has impacted the man’s self-esteem, whether impacts to self-esteem have affected the partner, and overall satisfaction with sex were most common concepts raised across pre- and post-surgery (See Table). Conclusions Using rigorous qualitative methodology, we have identified concepts that are unique to pre-surgery, post-surgery, and common across the surgical experience among partners of men who have undergone penile implant surgery. These data will facilitate development of a tool to assess female partner attitudes, beliefs and satisfaction prior to and after PI surgery. Disclosure No

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

OBJECTIVE Achieving submillimetric accuracy in stereotactic neurosurgery remains critical for safely targeting deep brain structures. Current workflows rely on intraoperative CT to register stereotactic frames to preoperative imaging, but this introduces additional radiation exposure, cost, and workflow complexity. Three-dimensional surface scanning (3DSS) potentially offers a fast radiation-free alternative capable of capturing detailed craniofacial anatomy and frame geometry. Therefore, the aim of this cadaveric study was to evaluate the feasibility, accuracy, and navigational compatibility of integrating 3DSS into stereotactic workflows as a potential replacement for intraoperative CT. METHODS A human cadaveric head was imaged with both thin-slice CT and structured-light 3DSS after mounting stereotactic frame components. CT, 3DSS, and computer-aided design (CAD) models were registered using a multistep point cloud alignment pipeline involving the fast point feature histogram, the random sample consensus method, and the iterative closest point algorithm. Accuracy was assessed using surface deviation error, root mean square error (RMSE), and fiducial registration error within a commercial neuronavigation platform. RESULTS Fusion of the 3D facial scan with CT provided a mean surface deviation error of approximately 0.4 mm. Registration of the 3DSS-derived N-bar localizer to its CAD reference model produced a frame alignment RMSE of 1.3 mm. Within the navigation system, the 3DSS-based workflow achieved a mean fiducial registration error of 0.14 mm (range 0.02–0.20 mm), outperforming the conventional CT-based method (mean error 0.20 mm, range 0.09–0.40 mm). CONCLUSIONS The 3DSS-based method enabled precise submillimetric stereotactic registration without the need for intraoperative CT, reducing radiation exposure and operative complexity. This workflow is fully compatible with existing navigation systems and could serve as a practical radiation-free alternative in stereotactic neurosurgery. Future work will focus on automating frame detection, incorporating artificial intelligence–driven fusion methods, and validating this approach in live surgical settings.

ABSTRACT Background Older adults are at high risk for severe injuries and death from falls. Physical therapist (PT) and occupational therapist (OT) evaluations have been introduced into Emergency Department (ED) care to assist with fall risk evaluation and fall prevention care. An evaluation of current evidence was undertaken to inform the Geriatric ED Guidelines 2.0. Methods Systematic review of physical and/or occupational therapy evaluation for fall prevention in the ED. The intervention was evaluation by a rehabilitation therapist (PT, OT, or both) for fall prevention, fall assessment, or mitigation of fall risk factors. Studies that did not perform the evaluation during the ED or ED Observation Unit visit were excluded, such as referrals for home consultation. The published literature was searched using strategies created by a medical librarian and was implemented in Embase and PubMed in March 2025. Covidence was used for article collation and review. Risk of bias was assessed using the Cochrane Risk of Bias v2 and the Ottawa–Newcastle scale. Results The search resulted in 387 articles with 52 duplicates, for 335 unique citations. Ten articles on 6 datasets were included (4 abstracts and 6 published manuscripts). One article was at high risk of bias as very few intervention patients received therapist evaluation. The remaining 5 datasets had varied co‐interventions in addition to PT and/or OT evaluations. PT or OT evaluation in the ED was associated with reduced ED revisits at 1, 2, and 6 months. Evaluations in the ED were not associated with increased hospital admission rates or ED length of stay. A meta‐analysis was infeasible due to varied outcome timeframes. Conclusions PT and/or OT evaluations for fall prevention were associated with reduced subsequent ED revisits for older adults. However, the impact of co‐interventions and heterogeneity limits strong conclusions.

BACKGROUND AND OBJECTIVES: Preventive treatment of unruptured intracranial aneurysms (UIAs) requires assessment of treatment risks vs expected benefit. Although established scores exist to estimate rupture and growth risk, currently, no externally validated tools exist to estimate the risks of microsurgical treatment of UIAs. Clinical prediction models based on machine learning enable generation of personalized risk estimates for each individual patient based on their specific patient and aneurysm characteristics. METHODS: Using data from 20 international centers from the prediction of adverse events after microsurgery for intracranial unruptured aneurysms study on patients treated microsurgically for UIAs, we developed and externally validated clinical prediction models for 3 outcomes measured at hospital discharge: poor neurological outcome (modified Rankin Score ≥3), new sensorimotor neurological deficits, and all-cause adverse events (Clavien-Dindo Grade ≥1). RESULTS: A total of 3705 patients were included. Data from 13 centers (2881, 78%) were used for model development. Fully trained models were evaluated on 824 patients (22%) from 7 additional centers. Average age was 56 ± 12 years, and 1049 (28%) were male. At discharge, poor neurological outcome was seen in 514 patients (14%). New sensorimotor deficits were observed in 534 patients (14%), and 894 patients (24%) experienced adverse events until discharge. At external validation, prediction of poor neurological outcome was achieved with good calibration and an area under the curve (AUC) = 0.70 (95% CI: 0.63-0.75). Similarly, new neurological deficits were predicted with good calibration and with an AUC = 0.69 (95% CI: 0.63-0.74). Prediction of all-cause adverse events only achieved an AUC = 0.59 (95% CI: 0.55-0.64) with fair calibration. The prediction model was integrated into a web application accessible at https://neurosurgery.shinyapps.io/PRAEMIUM/. CONCLUSION: The developed models for prediction of poor neurological outcome and new sensorimotor neurological deficits at discharge exhibit good calibration and fair discrimination based on a multinational external validation, indicating that the predicted probabilities correspond well to real-world risks and may thus be clinically useful in more objectively estimating the risk of microsurgical treatment.

Abstract Introduction Benign prostatic hyperplasia (BPH) is an age-related condition affecting many men. Emerging evidence highlights a strong relationship between BPH, lower urinary tract symptoms (LUTS) and sexual dysfunction, including erectile dysfunction (ED), reduced sexual desire, hormonal imbalances, and ejaculatory dysfunction, warranting a comprehensive approach to diagnosis and management. Objectives This report aims to provide recommendations for identifying and managing sexual dysfunction associated with BPH and LUTS. Methods Based on guidelines from the International Consultation on Sexual Medicine, a literature review was conducted. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation system. Results The association between BPH, LUTS, and sexual dysfunction is significant, with ED, ejaculatory dysfunction, and hypogonadism being common complications. Lifestyle modifications, medical therapies, minimally invasive surgical therapies, prostate artery embolization, and surgeries (eg, Transurethral resection of the prostate, HoLEP, Aquablation) are among the recommended treatments. Each intervention carries varying risks of sexual dysfunction, requiring specific tailored treatment plans. Conclusions BPH/LUTS significantly affect sexual health, emphasizing the need for a multidisciplinary approach to management. Future research should refine diagnostic criteria and develop treatments that minimize sexual side effects. Enhanced education for patients and their partners could improve quality of life and coping mechanisms.