Citations

Abstract Context Recent studies suggest glucagon-like peptide receptor-1 agonists (GLP-1RA) and glucose-dependent insulinotropic polypeptide (GIP) may contribute to altered calcium metabolism. Objective This study examines the association between GLP-1RA/GIP-RA use and risk of post-thyroidectomy hypocalcemia. Methods This propensity-matched cohort study utilized the TriNetX Platform to analyze adult patients who underwent total thyroidectomy (2010 to 2024). The intervention cohort included patients with a GLP-1RA or GIP-RA prescription 1 year before thyroidectomy; the control group had no GLP-1RA/GIP-RA history. Propensity score matching controlled for demographics and relevant clinical covariates. Primary outcomes included risk of hypocalcemia at 0-1 month, 1-6 months, and 6-12 months after surgery. Using Poisson regression, odds ratios were reported (alpha = 0.05). Results Among 70 665 patients, 1759 (2.59%) received a GLP-1RA or GIP-RA. Each matched cohort contained 1732 patients with similar preoperative parathyroid hormone or calcium levels. The GLP-1RA/GIP-RA cohort had a 12% lower risk of hypocalcemia from 0 to 1 month after surgery (relative risk [RR] 0.88; 95% CI: 0.81-0.97). In the sensitivity analysis considering postoperative calcitriol supplementation, recipients with GLP-1RA/GIP-RAs use were less likely to develop hypocalcemia in the month after surgery (RR 0.84; 0.74-0.96), as were those with GLP-1RA/GIP-RAs who never received calcitriol in the month after surgery (RR 0.81; 0.72-0.90). Under subgroup analysis, semaglutide was the sole agent associated with a reduced risk of hypocalcemia. Conclusion Patients with a history of GLP-1RA/GIP-RA use may experience a lower risk of short-term hypocalcemia after thyroidectomy, suggesting personalized supplementation strategies may be required for this population.

Background/Objectives: Overall survival in patients with amyotrophic lateral sclerosis (ALS) is linked to the rate of predicted respiratory vital capacity (PVC) loss. The objective of this study was to test whether changes in quantitative PVC measures over time linked to survival would define an immunopathogenic subset of ALS responsive to NP001, a regulator of innate immunity. Methods: In a retrospective study, data from intent-to-treat (ITT) population of two phase 2 trials of NP001 were evaluated for over time changes in PVC, time-to-event (TTE) loss of 15% PVC and PVC change from baseline, as linked to survival outcomes in patients treated with NP001 vs placebo. Results: Treatment with NP001 was associated with a significantly lower risk compared to placebo in the loss of 15% PVC over six months (p = 0.01; HR = 0.60, 95% CI: 0.39, 0.90). Data from the two trials were subsequently divided by a disease progression rate (DPR) value of 0.50 units of ALSFRS-R score lost per month for analysis of slow vs. rapid disease. In ALS patients with slowly progressive disease (DPR < 0.50), TTE PVC changes from baseline were slowed (p < 0.0005) and overall survival extended significantly (18.5 months) in NP001-treated vs. placebo groups. The rapidly progressive ALS patients (DPR ≥ 0.50) treated with NP001 showed no significant difference in PVC change or survival from the placebo group. Conclusions: These hypothesis-generating observations suggest that inflammation might play a significant role in the loss of respiratory function in a major subset of ALS patients.

Abstract The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient and disease characteristics. In the landmark analysis, rituximab maintenance was associated with improved event-free survival (EFS; median, 49.9 vs 29.7 months; P&lt; .001) as well as overall survival (OS; median, 109.5 vs 74.2 months; P&lt; .001). The EFS and OS benefits were observed across most of the subgroups. EFS and OS differences were statistically significant in those who achieved a complete response to 1L BR (n = 590; median EFS, 62.7 vs 31.1 months [P&lt; .001]; median OS, 136.1 vs 75.3 months [P&lt; .001]), but the analysis among those who achieved a partial response to 1L BR was limited by the small sample size. These results provide additional evidence for the survival benefit of rituximab maintenance after BR in MCL and support its use in clinical trial design and routine practice.

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.