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 Proximal perforation in complex penile prosthesis placement is well recognized. If recognized, suture sling repair amongst other techniques is our favored approach. Unrecognized proximal perforation often results in unilateral or bilateral perineal bruising, often with eventual proximal device migration and palpability of the proximal device in the buttock. Objective We present a series of 5 cases in which the suture sling technique was utilized for known proximal perforation, with subsequent need for immediate or delayed revision. Methods We assessed all cases performed at Mayo Clinic since 2018 that resulted in a known suture sling complication amongst 3 high volume implanters. We identified 5 cases in which the suture sling technique required revision surgery. All patients underwent cross sectional imaging for further evaluation. Results Patients were males aged 59 to 89 with erectile dysfunction. There were no consistent factors amongst the 5 cases that may have predicted suture sling complication. The majority of cases were inflatable penile prostheses (4/5), were prosthesis revision cases (3/5), utilized the penoscrotal approach (4/5), were Coloplast devices (4/5), utilized rear tip extenders (3/5), utilized Prolene suture sling (3/5), and returned to OR within 2 days for revision (3/5). The majority of the complications (4/5) involved excessive proximal cylinder length that were palpable on examination of the buttocks or near the rectum (one felt on rectal exam). One case demonstrated improper anchoring of the device not allowing proximal seating and thus S shaped deformity. We noted medial cylinder deviation on all imaging, as corporal perforation was always medial to the true corporal path. Conclusions When performing suture slings, surgeons should be very wary of oversizing. The medial cylinder path and prior surgical capsule may mislead surgeons when choosing appropriate cylinder length. If perforated, we advocate against rear tips and for under sizing in general, as proximal anchoring is reliant upon the suture, not a true corporal boundary. Similarly, the device should be fully inflated and proximally seated on palpation prior to tying down the sling to avoid S deformities. Disclosure No

Abstract Introduction Glans ischemia and subsequent necrosis is a rare but devastating complication of inflatable penile prosthesis (IPP) placement. Differentiating true glans ischemia from severe ecchymosis can be difficult but is critical, particularly in light of the adage, “when in doubt, take it out.” However, post-operative glans discoloration can be misleading and result in premature device explantation. Objective To present clinical cases and identify distinguishing features between true glans ischemia and pronounced post-operative ecchymosis, with emphasis on risk factors and evaluation techniques. Methods A retrospective case series was conducted on four IPP patients in 2025 who presented with significant glans discoloration concerning for ischemia. Key operative variables, physical exam findings, and postoperative images were reviewed. Additionally, a prospective database of 298 implants placed under local anesthesia since 2024 was analyzed for glans bruising severity on postoperative day (POD) 3, using a 0–4 scale. Results Common ischemia risk factors included tight circumferential wrap (e.g., Coban), vasculopathy (e.g., prior arterial bypass), prolonged catheterization, and concomitant procedures. Case 1: History of pelvic radiation with ecchymotic meatus and glans. Improved after wrap removal and better lighting. Case 2: Extensive ecchymosis and discoloration of glans and scrotum noted on POD1 after uneventful IPP under local. Case 3: Patchy glans discoloration after multiple Keith needle passes. Skin tone complicated assessment. Case 4: Severe glans bruising immediately post-op following multiple needle passes due to suture breakage. In all cases, the glans was warm, well-perfused, and not painful out of proportion to appearance. No patients required explantation. Glans bruising rates in 298 implants under local anesthesia were: 0 (3.7%), 1 (48.7%), 2 (25.5%), 3 (21.1%), 4 (0.3%), notably higher than with general anesthesia. Key Clinical Indicators: Favors Hematoma: • Vascular corpora • Small/no catheter • Bruising elsewhere • Wrap excluded glans • No blistering • No paresthesias • Glans warm to touch Favors Ischemia: • Avascular corpora • Large indwelling catheter • Minimal bruising elsewhere • Coban wrap on shaft • Blistering present • Pain or paresthesias • Glans cold to touch Conclusions Significant glans bruising can mimic ischemia, particularly in IPPs placed under local anesthesia. Factors such as multiple Keith needle passes, tight wrapping, and poor photographic lighting may contribute to this diagnostic confusion. Warm, non-painful glans with widespread ecchymosis are reassuring. Avoiding premature explantation requires thorough clinical assessment, device unwrapping, and close patient monitoring. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: UroFill, Coloplast, Boston Scientific, Rigicon

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.

Delirium is a serious neuropsychiatric condition marked by acute confusion and cognitive decline, commonly affecting postoperative and critically ill patients. It is especially prevalent in older adults and those requiring intensive care, including patients undergoing major surgery or receiving mechanical ventilation. For anesthesiologists, delirium is a critical and often underrecognized postoperative complication with complex perioperative contributors. Intensive care unit patients with delirium face increased mortality, cognitive impairment, and persistent symptoms beyond discharge. Despite its clinical significance, the pathophysiology of delirium remains poorly understood, with no standardized classification or targeted therapy. In light of emerging evidence connecting blood–brain barrier (BBB) permeability to the onset of delirium, we found that BBB dysfunction may represent a key mechanism underlying its pathophysiology. Through a thorough examination of predisposing and precipitating factors that impair both BBB integrity and cognitive function, we identified many points of connection between BBB dysfunction and delirium specifically. We include here a summary of our diagnostic approach with the aim of improving therapeutic strategies based on preserving BBB function to prevent or mitigate delirium.

ABSTRACT Purpose There is limited evidence regarding the optimal timing of urosymphyseal fistula (USF) repair. Our aim was to conduct a comparative analysis evaluating the postoperative complications and surgical outcomes among patients undergoing surgery for USF, comparing those treated in an early versus delayed fashion. Methods Fifty‐eight patients with diagnosis of USF and who underwent fistula decompression, pubic bone resection, and urinary tract reconstruction were included. Patients who underwent USF repair within 100 days of diagnosis were classified as having early repair, while those treated after 100 days were considered to have delayed repair. Results Thirty‐one underwent delayed USF repair (53.4%), while 27 underwent early repair (46.6%). Most patients were male (96.8%). The median age (72 years vs . 69 years, p = 0.13) and mean BMI (28.7 vs . 28.6, p = 0.97) were comparable between groups. The rate of overall 90‐day complications following USF repair was comparable between groups (77.4% vs . 63%, p = 0.228). We did not find a difference between the rates early complications among groups. The rates of long‐term recurrent pain (46.7% vs . 11.1%, p = 0.004), recurrent osteomyelitis (20% vs . 0%, p = 0.014), and fistula (23.3% vs . 3.7%, p = 0.033) were higher in the delayed USF repair group compared to the early USF repair group. The follow up time was similar between groups too (25.43‐months vs . 32.8‐months, p = 0.257). Conclusion While early USF repair might not affect the incidence of early complications within 90 days post‐surgery, it is associated with reduced rates of long‐term recurrent pain, recurrent osteomyelitis, and fistula recurrence compared to delayed USF repair.

We report that moderate hyperoxia during a critical window of mucociliary differentiation disrupts terminal maturation in neonatal airway epithelial cells cultured in a three-dimensional model. Hyperoxia induces mitochondrial bioenergetic dysfunction and metabolic reprogramming, with proteomic analysis identifying complex I disruption as a key driver of impaired differentiation. Overall, these findings reveal a previously underrecognized link between mitochondrial bioenergetics and airway epithelial development, positioning metabolic dysfunction as an early trigger of hyperoxia-induced neonatal airway injury.