Citations

Abstract Background Eligibility criteria for clinical trials are crucial for maintaining safety and study integrity. However, overly restrictive criteria can result in unrepresentative trial populations, leading to gaps in understanding real‐world treatment efficacy. Addressing potentially modifiable exclusions (PMEs) could enhance trial accessibility and participation without compromising safety. Methods The authors retrospectively analyzed screen‐failed patients with biliary tract cancer or pancreatic cancer between August 2019 and November 2024 at The University of Texas MD Anderson Cancer Center. Screen‐failed patients were those who provided informed consent but did not participate for any reason. Clinical data were obtained from screening logs and electronic health records. PMEs were identified and validated by two independent medical oncologists. Results Of 585 screen‐failed patients from 18 trials, 509 were analyzed (367 with pancreatic cancer and 142 with biliary tract cancer) after excluding 76 because of incomplete data. Leading causes of screen failure were declined participation (19%), comorbidities (12%), suboptimal organ function (11%), absence of a biomarker (10%), and insufficient biospecimens (7%). Reasons for declining included preference for standard care (23%), travel (22%), and competing trials (5%). The authors identified 69 patients (13.6%) who had PMEs (primarily borderline laboratory abnormalities), including liver function (23%), kidney function (20%), platelet count (12%), hemoglobin (7%), and white blood cell count (6%) abnormalities. Other PMEs included previous or concurrent malignancies (9%) and viral hepatitis (4%). PMEs were evenly distributed across trials. Conclusions Rigid eligibility criteria exclude stable patients who might benefit from investigational treatments. Easing criteria related to incidental or asymptomatic laboratory abnormalities could broaden trial accessibility and improve enrollment in populations that are more representative of real‐world use.

Cervicofacial actinomycosis is a well-recognized infectious disease caused by Actinomyces, a Gram-positive filamentous bacterium. In contrast, Nocardia, a morphologically similar, hyphae-forming organism, is an exceedingly rare cause of cervicofacial abscesses, and even more uncommon associated osteomyelitis of mandible. We present such a case involving a kidney transplant recipient who presented with opioid-induced constipation, along with left jaw pain and swelling. CT scan of the soft tissue in the neck revealed a complex cervicofacial abscess with enhancement of underlying mandible. Culture growth and RNA sequencing of USG-guided aspirate identified a Nocardia species closely related to N. beijingensis/exalbida. The patient initially received broad-spectrum antibiotics, including ceftriaxone, imipenem, and trimethoprim-sulfamethoxazole (TMP-SMX). Imipenem was later discontinued in view of new-onset unexplained encephalopathy and replaced with linezolid, which was subsequently switched to minocycline following thrombocytopenia development. Minocycline therapy was intended for a total of 12 months. TMP-SMX was avoided long-term due to avoid nephrotoxicity risk in kidney transplant patients. On six-month follow-up, the patient showed clinical and radiological improvement; minocycline was discontinued after additional six months. This case highlights the importance of considering Nocardia as a differential diagnosis in immunosuppressed patients presenting with cervicofacial symptoms, especially following orofacial surgery or trauma. Early recognition, prompt diagnosis, and appropriate antibiotic therapy with adequate bone penetration seem crucial for optimal management and may help avoid the need for surgical intervention.

Abstract Introduction Down-sized inflatable penile prosthesis (IPP) cylinders are useful in cases with substantial penile fibrosis such as history of priapism or prior infection. Although down-sized IPP cylinders have a clear role in fibrotic corpora, their role in primary implant cases is unclear. Objective To identify factors associated with the use of down-sized cylinders in men undergoing primary IPP placement. Methods We conducted a retrospective analysis of 4,389 patients undergoing primary IPP placement from our multicenter database. Patients were categorized by down-sized (AMS 700 CXR, Coloplast NB) vs. standard sized cylinders (AMS 700 CX, AMS 700 LGX, Coloplast Titan). We collected demographic, intraoperative, and postoperative data. A multivariable analysis was performed to identify factors associated with use of down-sized cylinders Results A total of 4,389 men undergoing primary inflatable penile prosthesis (IPP) placement were included in the study, with a mean age of 62.3 ± 10.3 years. Among them, 1,485 (34%) had diabetes and 2,131 (49%) had hypertension. A total of 406 down-sized cylinders and 3,983 standard cylinders were implanted. Non-infectious complications occurred more frequently with the use of down-sized cylinders (odds ratio [OR] = 2.0, p < 0.001). Specifically, non-infectious complications were reported in 44 out of 185 men (23.8%) with down-sized cylinders, compared to 192 out of 2,727 men (10.9%) with standard cylinders. Cylinder complications constituted 13.9% and 13.0% of the non-infectious complications in the down-sized and standard cylinder groups, respectively. Conclusions The rate of cylinder-related complications were similar between the down-sized cylinder and standard cylinder groups. Urologists should be prepared to place down-sized cylinders during IPP placement in diabetic men and in men requiring serial dilation due to fibrosis. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Intuitive Surgical, Fidelis, Urofill, Boston Scientific, Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, Acerus Pharma; Endo Pharma.

Abstract Background Thrombotic Thrombocytopenic Purpura (TTP) is a rare, typically acquired disorder due to an immune-mediated deficiency of ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand Factor (vWF). In the absence of ADAMTS13 activity, ultra-large vWF multimers accumulate, promoting widespread platelet aggregation and microvascular thrombosis. This consumptive cascade leads to thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological symptoms, and rarely renal dysfunction. Although therapeutic plasma exchange (TPE) has long been the cornerstone of TTP treatment, the FDA approved Caplacizumab as a first-line treatment for TTP in 2019. This drug is a bivalent single-domain antibody that binds to the A1 domain of vWF and prevents its interaction with platelets, thus effectively interrupting the pathogenic cascade, which is associated with a risk of bleeding. Methods We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, comprising data from 152 healthcare organizations. Adults (≥18 years) with a diagnosis of TTP who received Caplacizumab plus TPE were compared to patients with TTP who received TPE alone. 1:1 propensity score matching (PSM) was performed to balance characteristics between cohorts. The primary outcomes assessed were all-cause mortality and major bleeding events over a period of 1 month. Results A total of 4084 patients with TTP were identified, of whom 356 received caplacizumab with TPE and 3728 received TPE. After PSM, 2 balanced cohorts were created: C+P (Caplacizumab + TPE), P only (TPE), each comprising 356 patients. The average age in C+P and P only, after PSM, was 50.4 +/- 16.2 and 50.8 +/- 16.2 years, respectively. Females formed 65.7% of both C+P and P only, and males accounted for 28.4% and 28.7% of C+P and P only, respectively. 2.8% patients in C+P and 7.06% patients in P only had all-cause mortality at the end of 1 month. One-month all-cause mortality was significantly lower in C+P (2.8%) compared to P only (7.06%), with an odds ratio (OR) of 0.385 (95% CI 0.182 to 0.814, p=0.010). Upon assessment of bleeding outcomes, no statistically significant risk difference was noted between the 2 groups, with the odds ratio being 0.974 (95% CI 0.399 to 2.379, p=0.954). Conclusion Our large database study suggests that the addition of caplacizumab to standard TPE therapy is associated with a reduction in one-month all-cause mortality in patients with TTP, without a corresponding increase in major bleeding. However, given the lack of granular clinical data, such as contraindications to caplacizumab use, it is possible that patients who received TPE alone were inherently at a higher risk. As such, while these findings support the potential benefit of early caplacizumab use, they should be interpreted with caution and warrant prospective validation to confirm causality and assess long-term outcomes.

Abstract Background: Leukemia, a type of cancer of the blood forming tissues, compromises the immune system putting the body at risk of aggressive infections like septicemia. This can not only progress to septic shock but also death. The occurrence of the two conditions makes it almost necessary to understand the epidemiological patterns to increase the rates of survival. This study assesses the trends in mortality in patients with leukemia and septicemia in the United States from 1999-2023. Methods : We analyzed death certificates of adults aged 5 to 84 years' from the CDC-WONDER database with Leukemia (ICD-10 codes: C91, C92) and Septicemia (ICD-10 codes: A40, A41) from 1999-2023. Age-adjusted mortality rates (AAMR) per 100,000 population were stratified by gender, race, census region, year and age. Join-Point analysis was performed to estimate annual percent change (APC) and average annual percent change (AAPC) in mortality trends, along with 95% confidence intervals (CIs). Results : Between 1999 and 2023, Leukemia and Septicemia caused 56,497 deaths in patients aged 5 to 84 years. The total AAMR decreased from 0.78 in 1999 to 0.66 in 2023. Demographically, AAMR among the men decreased significantly from 1.04 to 0.85 (AAPC: -0.65; 95% CI: -0.80 to -0.49). Females experienced a decline in mortality from 0.59 to 0.46(AAPC: -0.44; 95% CI: -0.71 to -0.17). In terms of race, a slight decrease in mortality was witnessed in the mortality of Non-Hispanic (NH) Black or African Americans from 0.91 to 0.7 (AAPC:-1.13 ; 95% CI: -1.43 to -0.82), moreover the AAMR in the Hispanics decreased from 0.8 to 0.63 (AAPC: -0.04; 95% CI: -0.04 to -0.58) while those among the white community decreased from 0.78 to 0.68 (AAPC: -0.39; 95% CI: -0.58 to -0.19). Moreover, the Asian community also experienced a declining death rate. Geographically, regions in the Midwest showed the highest overall AAMR (0.75), followed by the West,Northeast and areas in the South with an overall AAMR of 0.72 . Between the urban and rural areas, rural areas had a higher AAMR as compared to the urban areas with an overall AAMR of 0.17. When stratified according to states, AAMRs varied highly from the highest in Kentucky (0.89) to the lowest in Maine(0.26). Conclusion: The overall mortality rates for leukemia and septicemia decreased between the years 1999-2023. The greatest change was seen in males, regions in the Northeast, racially in NH Blacks and the rural areas.

Abstract Description Background Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease characterized by chronic inflammation and fibrosis of the bile ducts. The primary cells impacted in PSC are bile duct epithelial cells called cholangiocytes. Mucosal associated invariant T (MAIT) cells are enriched in human liver and associated with fibrosis. We hypothesize that cholangiocyte-activated MAIT cells drive fibrosis in PSC. Results Flow cytometry of PSC patient bile duct brushings show that 30% of T cells are MAIT cells, suggesting their co-existence with cholangiocytes within the peri-biliary environment. Re-analysis of single cell RNA sequencing data of PSC patient cholangiocyte organoids reveals upregulation of MR1 gene, indicating their enhanced ability to activate MAIT cells. Proteomics of human MAIT cells identify the expression of multiple profibrotic factors including secreted protein acidic and rich in cysteine (SPARC). Flow cytometry of TCR-activated MAIT cells show a significant and dose-dependent increase in a SPARClow MAIT population, indicating release of SPARC. Re-analysis of Olink proteomics on supernatant of PSC cholangiocyte organoids show IL-17C secretion. IL-17C treatment of TCR-activated MAIT cells result in significant upregulation of SPARC gene. Conclusion MAIT cells secrete profibrogenic mediators and MAIT cell profibrogenicity is enhanced by IL-17C, a novel cytokine released by cholangiocytes in PSC. Funding Sources C-SIG P30DK084567 Topic Categories Mucosal and Regional Immunology (MUC)

Background: Tricuspid regurgitation (TR) can lead to right ventricular failure (RVF) and poor clinical outcomes. The TriClip™ G4 transcatheter edge-to-edge repair (TEER) system has shown improved outcomes in TR patients and received FDA approval on April 2, 2024. The FDA’s Manufacturer and User Facility Device Experience (MAUDE) database collects mandatory manufacturer reports and voluntary provider reports on device-related complications. Methods: We retrieved all TriClip™-related adverse events from the MAUDE database post-FDA approval, excluding duplicate entries and literature reviews. After removing 47 literature reviews and 36 duplicate reports, 443 unique adverse event reports from 407 procedures (some with multiple events) were analyzed between April 2, 2024, and January 31, 2025. Results: SLDA (Single Leaflet Device Attachment) was the most frequent complication, occurring in 204 cases (Figure 1). Detached leaflets included septal (105 cases), anterior (46), posterior (27), lateral (3), multiple (2), and unreported. Contributing factors included poor imaging, tethered leaflet, clip-clip interaction, dense chordae, large right atrium (RA) or gap size, pacer lead, or prior valve intervention. Persistent TR was a common consequence. SLDA was addressed with additional clips in 77 cases (18 requiring multiple clips), no intervention in 55 cases (13 with significant residual TR), repeat TriClip procedures in 16 cases, and surgical repair in 4 cases. Other complications included partial SLDA (23 cases), clip deployment or gripper malfunctions (68), chordal entanglement (41), leaflet entanglement (3), and clip migration/embolization (6). Migrated clips were found in the RA, right atrial appendage, cardiac vein, or pulmonary artery; three required snare retrieval, and three were left in place. Triclip Steerable Guide Catheter (TSGC) malfunctions, such as leaks, loss of column support, and blockages, were reported in 29 cases, with 27 requiring replacement. Miscellaneous events included residual TR, leaflet grasping issues, F-knob malfunction, lock line jams, and TSGC entanglement. Clip opening during Establishing Final Arm Angle (EFAA) occurred in 25 cases, and leaflet puncture in 15 cases, with one requiring surgical intervention. Conclusion: SLDA was the most frequently reported complication following TriClip™ approval, with some cases leading to severe outcomes. Continued surveillance is crucial to assess long-term safety and optimize procedural strategies.

Background: Papillary Muscle (PM) related ventricular arrhythmia ablation is associated with lower acute success and suboptimal long-term outcomes due to complex anatomy, variable arrhythmogenic sites and dynamic exit points. Objective: To evaluate clinical and procedural outcomes of patients undergoing PM vs non-PM ablation. Methods: A retrospective analysis of adults (≥18 years) undergoing PVC ablation at Mayo Clinic (2019–2024) matched PM PVC ablations to controls (1:2) using propensity scoring based on age, sex, comorbidities and baseline LVEF. Chi-square and t-tests compared baseline and procedural characteristics. Logistic regression estimated odds ratios for immediate procedural success, PVC burden reduction and LVEF improvement at 3 months. Results: Of the 720 ablations, 392 cases were included after propensity matching: 132 PM and 260 non-PM. Patients in the PM group exhibited higher rates of complicated diabetes (9.8% vs 4.6%, p =0.045) and prior MI (18.2% vs 9.2%, p =0.011). Preprocedural ECG PVCs in the PM group showed a shorter intrinsicoid deflection (89.1 ± 35.0 msec vs 100.7 ± 24.3 msec, p <0.001) and longer coupling intervals (532.7 ± 100.3 vs 512.2 ± 81.4 msec, p =0.048).Moderate-to-severe MR was more prevalent in the PM group (17.4% vs 10.0%, p =0.036). Intraoperatively, the PM group had higher total energy delivery times (1939 ± 1336 sec vs 1227 ± 1033 sec, p <0.001) and more frequent cryoablation use (46.2% vs 7.3%, p <0.001). During post-ablation testing, non-clinical PVC was inducible in 39.5% of the cases in PM group compared to 25.7% in non-PM group ( p =0.005). More patients in the PM group were discharged on atleast one antiarrhythmic drug (AAD)(35.9% vs 18.5%, p <0.001) and AAD use persisted at 3 months (31.3% vs 18.4%, p =0.004). Outcomes were similar between groups, with no significant differences observed in immediate ablation success (aOR 0.64, p = 0.063, CI = 0.40-1.03), or >5% improvement in LVEF (aOR 0.76, p = 0.29) and PVC burden reduction (aOR 0.93, p = 0.81) at 3 months follow up. Conclusion: Patients undergoing PM ablation exhibited higher baseline rates of comorbidities. Intraoperatively they required greater energy delivery times, and an increased use of cryoablation. Postoperatively, a larger proportion of PM ablation patients required antiarrhythmic drug therapy. Despite these complexities, PM ablation showed no significant differences in PVC burden reduction, LVEF improvement, or procedural success compared to non-PM ablation.

Background: Catheter ablation of frequent premature ventricular complexes (PVCs) has been demonstrated to improve left ventricular ejection fraction (LVEF) in patients with PVC-induced cardiomyopathy. However, this improvement is not uniformly observed across all patients. Objective: To identify predictors of LVEF improvement following catheter ablation. Methods: This retrospective analysis included adult patients (≥18 years) who underwent PVC catheter ablation at Mayo Clinic, Rochester, between 2021 and 2024. Patients were grouped based on whether they experienced an LVEF improvement of ≥5%. Data on baseline comorbidities,, ECG characteristics, baseline transthoracic echocardiography (TTE), procedural details, and follow-up outcomes at 3-6 months (via Holter monitoring and TTE) were collected. Propensity matching (1:1) was performed using age(caliper=5), sex, and baseline LVEF(caliper=5). Comparative analyses used chi-square and t-tests. Variables with a p-value <0.1 were included in multivariate regression analysis. Results: After propensity matching, 98 patients with LVEF improvement and 98 controls were included. Table 1 summarizes baseline and procedural characteristics, and outcomes. Immediate PVC suppression was more common in the EF improvement group (74.2% vs. 60.4%, p=0.04), and fewer patients in this group were placed on long-term anti-arrhythmic medications (11.2% vs. 27.8%, p<0.01). Multivariate analysis showed that patients without PVC-related symptoms (OR=3.16, p=0.038) had higher odds of LVEF improvement, while those with CKD (OR=0.36, p=0.007) or a coupling interval ≥500 ms (OR=0.38, p=0.002) had lower odds of improvement.

Abstract Introduction Obesity, defined as an elevated Body Mass Index (BMI) &gt;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 Our study 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 4398 cases. These cases were divided into two distinct groups based on BMI: less than 30 (n = 2260) and greater than or equal to 30 (n = 2138). 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 &gt;30 BMI group (9.55 +/−2.18) compared to &lt;30 BMI group (9.14 +/−2.19), (p = &lt; 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, surgeons may need to be mindful of pump tubing length concerns 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.