Citations

Abstract Introduction Obesity, defined as an elevated Body Mass Index (BMI) >30, is a prevalent public health concern with far-reaching implications for various medical procedures and outcomes. In the context of inflatable penile prosthesis placement (IPP), where patient well-being and surgical success are of paramount importance, the impact of obesity on postoperative and intraoperative complications warrants thorough investigation. Objective We aimed to investigate the impact of BMI on both postoperative and intraoperative complications in an international, multi-institutional cohort of patients who underwent IPP placement. Methods We performed a retrospective chart review of 4,398 cases. These cases were divided into two distinct groups based on BMI: less than 30 (n = 2,260) and greater than or equal to 30 (n = 2,138). The study assessed various surgical factors as well as complications, including overall complications, corporal scarring, incontinence, intraoperative complications, proximal perforation, distal perforation, proximal crossover, distal crossover, and urethral injury. Results Our analysis revealed that there were no statistically significant differences in intraoperative or postoperative complications between the two BMI categories. Notably, proximal corporal measurement was significantly higher for >30 BMI group with 1858 (86.9%) compared to 1919 (84.9%) for <30 BMI group, (p = < 0.001). The incidence rates for overall complications (30.2% vs. 28.7%; p = 0.164), corporal scarring (18.2% vs. 16.7%; p = 0.36), incontinence (3.53% vs. 3.13%; p = 0.076), intraoperative complications (1.94% vs. 1.68%; p = 0.253), and specific complications all exhibited no significant differences. Similarly, post-operative complications, including both non-infectious (6.99% vs. 6.22%; p = 0.215) and infectious (2.61% vs. 1.87%; p = 0.165) complications, did not significantly vary between BMI categories. Conclusions Our findings indicate that BMI does not exert a statistically significant influence on postoperative and intraoperative complications in the context of high-volume prosthetic urology. In the absence of any other differences between patients of differing BMIs, the IPP industry may need to consider device specific alterations with pump tubing length in obese patients. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Clarus Therapeutics, Antares Pharma, Acerus.

Abstract Introduction Inflatable penile prosthesis (IPP) surgery is a well-established treatment for erectile dysfunction (ED). There is little information in the literature regarding the utilization of perioperative antimicrobial prophylaxis in primary and revision IPP surgeries. Objective We investigated the patterns of perioperative antimicrobial prophylaxis among a large multinational cohort of primary and revision IPP surgeries. Methods We conducted a retrospective analysis of 5,400 patients (4,187 primary IPP patients and 849 revision IPP patients) from our Prosthetic Urology Multi-Institutional Partnership (PUMP) institutions. Usage data for intravenous (IV), preoperative oral, and postoperative oral antimicrobials were analyzed. We specifically assessed patient profiles, antimicrobial selection, and antimicrobial duration. Multivariate statistical analyses were conducted to identify significant variations between primary and revision surgeries. Results For patients undergoing primary IPP placement, 81.9% received IV antibiotics for <24 hours whereas 18.1% received IV antibiotics for >24 hours. Preoperative oral antimicrobials were used in 59.4% of patients and 99.4% received postoperative oral antimicrobials. The overall infection rate for primary implants was 2%. Notably, quinolone administration shows a higher postoperative infection rate (11.4%) compared to gentamicin (1.9%), cephalosporin (0%), and vancomycin (1.0%). Multivariable regression analysis identifies factors such as a history of infection, diabetes, and priapism as predictors for postoperative infections. Furthermore, the study finds that perioperative antifungal use is associated with a decreased risk of infection. Conclusions This study provides valuable insights into the patterns of perioperative antimicrobial prophylaxis. Duration, type, and route of antibiotics given preoperatively or postoperatively do not affect postoperative infection rates among high volume prosthetic urologists. Giving IV antibiotics for more than 24 hours does not affect postoperative infection. Perioperative antifungals are a protective factor. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Clarus Therapeutics, Antares Pharma, Acerus.

Abstract Introduction The utilization of rear tip extenders (RTE) is often imperative during Inflatable Penile Prosthesis (IPP) placement. The impact of RTE on perioperative morbidity of IPP surgery is underexplored. Objective In this study, we assess intraoperative and postoperative outcomes among patients undergoing primary IPP implantation with or without RTE. Methods We performed a multicenter, retrospective analysis of men undergoing primary IPP placement between July 2016 and July 2021. A total of 4308 patients were identified, of which 2963 had no RTE and 1345 had RTE. After 1:1 propensity score matching for all confounding variables, 840 patients without RTE were compared to patients with RTE for intraoperative and postoperative outcomes. Chi-square and Mann–Whitney tests were used for statistical analysis for categorial and continuous variables respectively. For multivariable analysis, we used a forward stepwise model and included significant variables found on preoperative characteristics of patients. Kaplan–Meier time to event analysis were compared with Mantel-Cox log-rank test. Results Patients with RTE use had more postoperative complications (9.6% vs 5.2%, p < 0.001). More specifically, RTE patients had more episodes of postoperative hematoma and bleeding (2.0% vs 0.7%, p = 0.033), device malfunction (2.7% vs 1.8%, p = 0.006), and glans-related complications (0.8% vs 0, p = 0.015). On multivariable analysis, use of RTE (OR 1.58, 95% CI 1.07-2.34, p = 0.021), AMS 700 series device (OR 1.93, 95% CI 1.27-2.94, p = 0.002), penoscrotal approach (OR 2.60, 95% CI 1.61-4.18, p < 0.001), and older age (OR 1.02, 95% CI 1.00-1.04, p = 0.035) were associated with increased risk of postoperative complications. Patients with RTE use had increased rate of postoperative IPP revision (5.0% vs 2.1%, p = 0.002). The use of RTE (OR 1.71, 95% CI 1.00-2.90, p = 0.046), AMS 700 series device (OR 1.73, 95% CI 1.01-2.97, p = 0.048), penoscrotal approach (OR 3.16, 95% CI 1.63-6.17, p < 0.001), and history of Peyronie’s disease (OR 2.24, 95% CI 1.31-3.82, p = 0.003) were associated with increased risk of postoperative IPP revision or explantation. On Kaplan–Meier analysis, use of RTE was associated with increased risk of postoperative complications and IPP revision or explantation within 48 months (log rank p = 0.001 and p = 0.002 respectively). Conclusions In this large multi-institutional cohort, patients with RTE experienced more hematoma, device malfunctioning, and glans related post operative complications. The use of RTE is an independent predictor of post-operative complications and IPP revision or explanation. Disclosure No.

Objectives To evaluate the pre‐ and intraoperative variables that impact the integrity of the corporal bodies over time after inflatable penile prosthesis (IPP) placement, as predictors of intraoperative corporal perforation and delayed cylinder complications have not been well characterized. Patients and Methods We retrospectively reviewed a 16‐centre multi‐institutional database of IPP surgeries performed by experienced implanters from 2016 to 2021. Poor corporal integrity (PCI) was defined as intraoperative (iPCI) corporal complications or postoperative (pPCI) corporal complications. Multivariable analysis was performed to identify independent predictors of PCI, iPCI, and pPCI. Primary outcomes included intra‐ and postoperative corporal complications. Results We identified 5153 patients for analysis from 5406 IPP cases, finding 152 (2.95%) cases of PCI. On multivariable analysis, predictors of PCI included revision IPP surgery (odds ratio [OR] 8.16, 95% confidence interval [CI] 5.15–12.92; P < 0.001), sequential dilatation (OR 2.12, 95% CI 1.32–3.39; P = 0.002), coronary artery disease (CAD)/peripheral vascular disease (PVD) (OR 1.81, 95% CI 1.18–2.77; P = 0.006), older age (OR 1.02, 95% CI 1.01–1.04; P = 0.013), and corporal scarring (OR 1.58, 95% CI 1.0–2.5; P = 0.049). Predictors of iPCI included revision IPP surgery (OR 7.34, 95% CI 4.18–12.88; P < 0.001), corporal scarring (OR 2.77, 95% CI 1.64–4.69; P < 0.001), radiation therapy (OR 2.25, 95% CI 1.0–5.04; P = 0.049), and older age (OR 1.03, 95% CI 1.0–1.05; P = 0.025). Revision IPP surgery (OR 7.92, 95% CI 3.69–17.01; P < 0.001), sequential dilatation (OR 3.4, 95% CI 1.61–7.19; P = 0.001), CAD/PVD (OR 2.98, 95% CI 1.56–5.72; P = 0.001), and history of priapism (OR 3.59, 95% CI 1.08–11.99; P = 0.038) were predictive of pPCI. Conclusion Coronary artery disease/PVD, being of older age, having corporal scarring, undergoing IPP revision surgery and sequential dilatation were predictive risk factors for complications associated with PCI. Identifying patients who are at risk of having PCI may improve patient‐specific counselling, consideration of referral to more experienced implanters, and surgical planning to potentially promote longer‐term device viability.

Abstract Introduction Inflatable penile prosthesis (IPP) surgery is a well-established treatment for erectile dysfunction (ED). There is little information in the literature regarding the utilization of perioperative antimicrobial prophylaxis in primary and revision IPP surgeries. Objective We investigated the patterns of perioperative antimicrobial prophylaxis among a large multinational cohort of primary and revision IPP surgeries. Methods We conducted a retrospective analysis of 5400 patients (4187 primary IPP patients and 849 revision IPP patients) from our Prosthetic Urology Multi-Institutional Partnership (PUMP) institutions. Usage data for intravenous (IV), preoperative oral, and postoperative oral antimicrobials were analyzed. We specifically assessed patient profiles, antimicrobial selection, and antimicrobial duration. Multivariate statistical analyses were conducted to identify significant variations between primary and revision surgeries. Results For patients undergoing primary IPP placement, 81.9% received IV antibiotics for &lt;24 hours whereas 18.1% received IV antibiotics for &gt;24 hours. Preoperative oral antimicrobials were used in 59.4% of patients and 99.4% received postoperative oral antimicrobials. The overall infection rate for primary implants was 2%. Notably, quinolone administration shows a higher postoperative infection rate (11.4%) compared to gentamicin (1.9%), cephalosporin (0%), and vancomycin (1.0%). Multivariable regression analysis identifies factors such as a history of infection, diabetes, and priapism as predictors for postoperative infections. Furthermore, the study finds that perioperative antifungal use is associated with a decreased risk of infection. Conclusions This study provides valuable insights into the patterns of perioperative antimicrobial prophylaxis. Duration, type, and route of antibiotics given preoperatively or postoperatively do not affect postoperative infection rates among high volume prosthetic urologists. Giving IV antibiotics for more than 24 hours does not affect postoperative infection. Perioperative antifungals are a protective factor. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Clarus Therapeutics, Antares Pharma, Acerus.

Abstract Objectives Diagnostic reconciliation is the collaborative process between patients and clinicians to create and reconcile evidence-based, feasible, and desirable care plans. However, the specific components of this process remain unclear. The objective of this study was to develop the first comprehensive framework to elucidate the diagnostic reconciliation process. Methods We followed a multi-step and iterative approach to develop the framework, including a focused systematic review of diagnostic conversations, quantitative evaluation of recordings of real-life clinical visits recordings, and stakeholder engagement (e.g., patients, clinicians, researchers). Results We identified 17 potential components to the process of diagnostic reconciliation through literature review and stakeholder engagement. After review of 56 clinical visits and further stakeholder engagement, we developed a final framework including four categories: 1) understanding the need for a test/referral, 2) logistics of test/referral scheduling, 3) test/referral information, and 4) test/referral results. Conclusions The proposed framework lays the foundation for evaluation and improvement of diagnostic conversations in practice. Clinicians can enhance patient-centered diagnosis by co-creating diagnostic plans of care in practice and using the components described in the novel diagnostic reconciliation framework.

Introduction: Brexu-cel is an autologous anti-CD19 CAR T-cell therapy approved in the US and EU for treatment of adults with R/R MCL (after ≥2 prior therapies in EU) based on a high objective response rate (ORR; 93%; 67% complete response [CR] rate) in pts who received the pivotal dose (2×106 anti-CD19 CAR T cells/kg; Cohort 1; N=60) in ZUMA-2 (NCT02601313; Wang et al, N Engl J Med 2020). After ~4 years (y) of median follow-up, Brexu-cel demonstrated a median overall survival (OS) of 46.4 months (mo) in 68 pts with R/R MCL in Cohort 1 (Goy et al. ASH 2023). Cohort 2 was established to assess a lower dose (0.5 x 106 anti-CD19 CAR T cells/kg); however, the risk/benefit ratio of the Cohort 1 dose was deemed the optimal dose before Cohort 2 reached full enrollment. Here we report primary outcomes of Cohort 2 and 5-y outcomes of Cohorts 1 and 2. Methods: Pts with R/R MCL and ≤5 prior therapies including a BTKi received optional bridging therapy (protocol-defined), lymphodepleting chemotherapy, and 1 infusion of brexu-cel. The primary endpoint was ORR (CR + partial response [PR]) per Lugano classification (Cheson et al. J Clin Oncol. 2014) by independent radiology review committee (IRRC) assessment. Key secondary endpoints were duration of response (DOR), best objective response (BOR), progression-free survival (PFS), OS, and safety. After ≥24 mo of assessment, pts could transition to long-term follow-up (LTFU), NCT05041309, where they were monitored for late-onset targeted/serious adverse events (AEs) possibly related to brexu-cel, presence of replication-competent retrovirus (RCR), and/or insertional mutagenesis. Descriptive statistics are reported herein. Results: As of the primary analysis data cutoff date, July 24, 2019, 17 pts enrolled in Cohort 2, 14 (82%) of whom were treated with brexu-cel with median follow-up of 16.0 mo (range, 13.9-18.0). Pt characteristics for Cohort 2 (N=14) were similar to Cohort 1; median (range) age and number or prior therapies was 61.5 y (52-73) and 3 (2-5); 100% US-treated, 79% male, 71% extranodal disease, 50% intermediate or high s-MIPI scores, 50% refractory to last therapy, and 43% had prior autologous stem cell transplantation. ORR was 93% (95% CI, 66.1-99.8) per IRRC; 64% had a CR (95% CI, 35.1-87.2), 29% had a PR (95% CI, 8.4-58.1) and 1 pt was not assessed. All 14 pts had ≥1 AE of any grade (Gr), with Gr ≥3 AEs occurring in 93% of pts; the most common being hypotension (50%), white blood cell count decrease (50%), anemia (43%), and neutrophil count decrease (43%). Rates of Gr ≥3 cytokine release syndrome (CRS) and neurological events were 7% and 43%, respectively. As of April 1, 2024, median follow-up (range) for Cohort 1 and 2 was 67.8 mo (58.2-88.6; N=68) and 72.3 mo (70.1-74.3; N=14), respectively. In Cohort 1, 24 pts were still alive (35%; 2 withdrew consent and 1 lost to follow up) and 44 pts died (65%). In Cohort 2, 8 pts were still alive (57%; 2 withdrew consent and 1 lost to follow up) and 6 pts died (43%). A total of 27 pts (Cohort 1, n=23; Cohort 2, n=4) enrolled in the LTFU study by data cutoff with a median follow-up time of 70.2 mo (range, 58.2-88.6). Median (95% CI) investigator-assessed DOR and PFS were 36.5 mo (17.7-48.9; n=60; 17 patients in ongoing response, all CR) and 25.3 mo (12.7-46.6; N=68) in Cohort 1; and 57.5 mo (4.7-not estimable [NE]; n=12; 3 pts in ongoing response, all CR) and 29.5 mo (3.3-NE; N=14) in Cohort 2. Median OS (95% CI) and 60-mo OS rates (95% CI) were 46.5 mo (24.9- 60.2) and 38.5% (26.7-50.1) in Cohort 1; and not reached (9.4-NE) and 53.6% (23.8-76.2) in Cohort 2. One pt had 3 ongoing AEs on LTFU, hypogammaglobulinemia and 2 viral infections that arose prior to LTFU. Two pts died on LTFU, both due to progressive disease; no new secondary malignancies or RCR cases were reported. Conclusions: Consistent with Cohort 1, brexu-cel demonstrated a high ORR, durable responses, and an expected safety profile in pts with R/R MCL in Cohort 2 despite the lower dose. However, small sample size limits interpretation of these results. With &gt;5 y of median follow-up, pts in Cohort 1 and 2 continued to experience durable responses with high 60-mo OS rates. No new safety signals were detected and no secondary malignancies or RCR cases were reported in LTFU. Additionally, ZUMA-2 results are consistent with real-world outcomes of brexu-cel in the post BTKi R/R MCL setting (89% ORR and 81% CR rate; Wang Y, et al. J Clin Oncol. 2023). These results support the continued use of brexu-cel in R/R MCL.

Background: CLL is one of the most common types of leukemia in the United States, with an estimated 20,700 new cases in 2024. Although cBTKis have become the standard of care for CLL/SLL in treatment-naïve and relapsed/refractory patients, cardiovascular (CV) toxicity is a known side effect. Further, clinical outcomes often worsen as patients progress beyond 1st-line therapy (1L), and the frequency of CV adverse events (CVAEs) may increase with age and as patients progress to 2nd-line or later therapies (2L+). This research evaluated the real-world incidence of CVAEs and clinical outcomes in patients who initiated cBTKi between 2020 and 2023. Methods: Adult patients diagnosed with CLL/SLL who initiated cBTKi treatment (index date) between 2020-2023 in the United States were identified using claims data from Optum's de-identified Clinformatics® Data Mart Database and followed up to 36 months post-index. Cohorts were assessed as those initiating 1L or 2L+, reflecting treatment-naïve and relapsed/refractory patients. Results were presented for patients with an incident CVAE (not present pre-index) and those without. Demographics, incident CVAEs, overall survival (OS) and proportion of patients who discontinued index cBTKi therapy, initiated next treatment or experienced death (NT+D) were assessed. Time to CV event (TTCE) for ibrutinib and acalabrutinib were determined using a Kaplan-Meier (KM) model and Log rank test. Results: Overall, 2,163 eligible patients were identified with a mean ± SD age of 73.8 ± 9.2 years, and 40.6% were female. Of these, 1,958 (90.5%) were included in the 1L cohort and 205 (9.5%) in the 2L+ cohort; 619 (31.6%) and 63 (30.7%) patients had CVAEs, respectively. The mean ± SD [median] observation period was 1.6 ± 0.9 [2.0] years in 1L and 1.5 ± 1.0 [1.0] years in 2L+. The most common cBTKi (in 1L and 2L+) at index were ibrutinib (55.5% and 55.6%), followed by acalabrutinib (40.3% and 38.5%), and zanubrutinib (4.1% and 5.9%). At 12-months post-index, the proportion of 1L patients with and without CVAEs who discontinued treatment was 44.9% and 41.6%, rising to 65.6% and 59.0% by 36-months post-index, respectively. For those in 2L+, 50.8% and 40.8% of those with and without CVAEs discontinued treatment by 12-months; 68.3% and 55.6% discontinued by 36-months. Among those with and without CVAEs, NT+D in 1L patients was 35.9% and 22.5% within 12-months post-index and 56.9% and 32.8% by 36-months. In the 2L+ cohort, 46.0% and 31.7% experienced NT+D by 12-months, rising to 63.5% and 41.5% by 36-months. OS in 1L patients was 84.7% and 93.1% in those with and without CVAEs at 12-months and 69.1% and 88.0% at 36-months. For 2L+ patients, OS was 71.4% and 88.0% at 12-months and decreased to 54.0% and 80.3% at 36-months, among those with and without CVAEs, respectively. The most common incident CVAEs following cBTKi initiation in the 1L and 2L+ cohorts were hypertension (31.2% and 21.7%), heart failure (14.6% and 17.7%), atrial fibrillation (13.9% and 18.4%), atrial flutter (13.3% and 16.9%), and ventricular arrythmias (13.0% and 14.5%). The occurrence of incident CVAEs between 1L patients who received acalabrutinib and ibrutinib was 3.4% and 13.2% for atrial fibrillation, 2.7% and 12.7% for atrial flutter, 9.3% and 31.0% for hypertension, and 6.8% and 11.7% for ventricular arrythmias. For 2L+, the proportion experiencing CVAEs with index acalabrutinib or ibrutinib were 8.6% and 14.8% for atrial fibrillation, 7.6% and 14.8% for atrial flutter, 10.5% and 25.0% for hypertension, and 10.1% and 8.8% for ventricular arrythmias. Among acalabrutinib and ibrutinib patients, KM estimates (medians not reached) in 1L showed that 84% and 72% of patients would not experience a CVAE by 12 months, with 57% and 52% not experiencing a CVAE at 36-months (p&lt;0.001); 2L+ KM estimate rates were 77% and 73% at 12-months and 64% and 60% at 36-months (p=0.28). Mean TTCE for acalabrutinib and ibrutinib in 1L was 2.2 and 1.9 years with 1.6 and 1.2 years in 2L+. Summary/Conclusion: Utilizing real-world evidence from patients with CLL/SLL receiving cBTKIs, this study highlights the CV disease burden among patients who incur new CV events in 1L or later lines of therapy. This research underscores the need for innovative therapies with improved efficacy and CV safety profiles that delay progression to later lines of therapy, as well as careful CV monitoring to allow for early management and improved outcomes.