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Abstract Funding Acknowledgements Type of funding sources: None. Background/introduction Morbidity and mortality associated with atherosclerotic cardiovascular diseases are prevalent in young patients. Meanwhile, traditional cardiovascular risk calculators underestimate disease risk in young adults. Purpose To characterize cardiometabolic risk factors and lipid levels in young adults with acute myocardial infarction. Setting: A multicenter, population-based analysis of patients diagnosed at our hospitals in Arizona, as well as our clinic health system spanning Minnesota and Wisconsin. Methods This is a retrospective cohort study including patients 18 to 50 years old diagnosed with acute myocardial infarction from October 1, 2015, to December 31, 2018. Parameters obtained included: Age, sex, ethnicity, body mass index, tobacco use, comorbid medical conditions, fasting blood glucose, hemoglobin A1c, lipid levels, and prescribed lipid-lowering therapy. Results Among 553 young patients diagnosed with acute myocardial infarction, the mean age at the time was 44.4 years, with men accounting for 69.1% of cases. The mean body mass index was 32.2 kg/m2. Hypertension, diabetes mellitus, and tobacco use were present in 64.7%, 25.9%, and 36.2% of patients. Insulin resistance, elevated triglycerides, and low HDL-C were present in 29.8%, 51.0%, and 62.8% of patients, respectively. Approximately 61.3% of patients within this cohort met World Health Organization criteria for diagnosis of metabolic syndrome. Mean LDL-C was 116 mg/dL and mean triglycerides were 190 mg/dL. Statin therapy was prescribed to 92 (16.6%) of patients prior to diagnosis of acute myocardial infarction, whereas 359 (67.3%) of patients met ACC/AHA criteria for lipid-lowering therapy. Within this subgroup receiving statin therapy, the mean serum LDL-C was 101 mg/dl, 26.1% had levels below 70 mg/dL, and 56.5% had LDL-C levels below 100 mg/dL. Thirty-four patients (6.1%) with LDL-C levels greater than 190 mg/dL, and 29 (85.3%) were not on lipid-lowering therapy. Conclusions and Relevance Multiple treatable risk factors were present in most young adults with acute myocardial infarction, including many with LDL-C levels below 100 mg/dL. Being overweight or obese was the most prevalent risk factor, while elevated non-HDL cholesterol was the most common lipid panel abnormality. In addition to known cardiometabolic risk factors, these findings build upon a growing body of evidence implicating triglyceride-rich lipoproteins in non-HDL and remnant cholesterol as an independent risk factor of ASCVD, which were common in this cohort of young patients presenting with myocardial infarction. In this cohort, lipid-lowering therapy was underutilized in young patients with known cardiometabolic risk factors, elevated estimated 10-year ASCVD risk, and individuals with phenotypic Familial Hypercholesterolemia.

After a virtual congress in 2021 and a previous absence in 2020 because of the coronavirus disease 2019 pandemic, the 27th Annual Congress of the International Liver Transplantation Society was held from May 4 to 7, 2022, in a hybrid format in Istanbul, with 1123 (58% on-site) liver transplant professionals from 61 countries attending the meeting. The hybrid format successfully achieved a balance of much yearned-for “in-person interaction” and global online participation. Almost 500 scientific abstracts were presented. In this report, the Vanguard Committee aims to present a summary of key invited lectures and selected abstracts for the liver transplant community.

Abstract Introduction Age is often correlated with various medical conditions, including bother with the condition itself. Peyronie’s disease (PD) is a condition which is most often associated with men in their 50-60’s, however, it does affect younger men as well. Anecdotally, younger men with PD appear to be more bothered by their condition compared to older men. We therefore sought to evaluate whether there is a difference among older vs younger men as to the degree of bother linked to PD. Objective To evaluate age as a potential predictor of bother associated with PD. Methods A prospective database has been maintained of men seeking treatment for PD. Beginning in Feb 2020, we began implementing men routinely completed standardized intake questionnaires relating to PD, including the Peyronie’s Disease Questionnaire (PDQ). The PDQ consists of 15 questions broken down into three key subdomains: psychological and physical, penile pain, and symptom bother. Men who had completed the PDQ questionnaire were evaluated to determine the correlation between various clinicopathologic variables and the PDQ-bother domain. Results A total of 645 men were seen for symptoms of PD and had PDQ questionnaire data available for review. Baseline demographics included a mean age was 51.8 years (SD 17.6), mean PD symptom duration 31.3 months (SD 65.3), estimated curve of 40.9 degrees (SD 26.8), and mean PDQ-Bother score 8.9 (SD 3.1 – Note: lower is better). Several clinicopathology variables were found to be associated with increased PDQ-bother scores, including age (younger = less bothered, parameter estimate -.0.03, p=0.03), the presence of indentation or hourglass (yes 9.4, no 8.4, p<0.05), pain (yes 9.3, no 8.5, p=0.16), PD preventing penetrative intercourse (yes 9.5, no 8.7, p=0.07), penile shortening (yes 9.3, no 8.7, p=0.10), subjective erectile dysfunction (yes 9.6, no 8.5, p<0.01), and subjective premature ejaculation (yes 9.8, no 8.4, p<0.01). Interestingly, several variables did not correlate, including the duration of relationship, frequency of intercourse, duration of symptoms, direction of curve, degree of curvature, partner pain with intercourse, or libido. Conclusions Several notable factors are associated with PD bother (as assessed by the PDQ-bother domain), and equally importantly, several factors are surprisingly not associated (e.g. curvature degree and direction). These factors provide useful information to the practicing clinician to help better identify men who may be at greater risk for bother associated with the condition. Disclosure No

Abstract Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH), few studies have been able to identify variables which predict curve improvements, with baseline extent of curvature most highly correlated. In addition to extent of baseline curvature, our team has previously identified curve direction and plaque calcification as additional predictive variables. We therefore sought to create an integrated predictive model which incorporated several factors to better estimate anticipated outcomes. Objective To report outcomes of a novel scoring system designed to better predict outcomes of men undergoing CCH injections for Peyronie’s disease (PD). Methods A prospective database has been maintained of men undergoing CCH injections for PD. Data were reviewed to identify variables predictive of curve improvements in men with isolated curvature as well as among those with key characteristics, including indentations, hourglass deformities, penile tapering, and calcification. A predictive model was subsequently developed to improve correlations between disease factors and subsequent CCH outcomes. The final model (CLINiC Score) assigned points as follows: +1 point for every 10 degrees of curvature (C for Curvature), +5 points for penile narrowing >25% (IN for INdent), +3 points for narrowing 0-25%, -4 points for pure lateral curvatures (L for Lateral), and -2 points for plaque calcification (C for Calcification). Patients were assigned scores based on the CLINiC model, and results were correlated with final curve outcomes. Results A total of 476 PD men were included in the current analysis. Baseline variables for the cohort included a mean age of 55.6 yrs (SD 10.9), PD duration 31.9 months (SD 61.4), composite curvature 64.6 degrees (SD 23.9), 47% with indentations, 42% with hourglass deformity, and 17% with calcification. The mean CLINiC score for the cohort was 6.9 (SD 3.4). For the overall cohort, the use of the CLINiC score increased the correlation coefficient from 0.35 to 0.46 (r-squared 0.13 vs 0.21), with a predictive linear formula of 2.1 - 3.2 * CLINiC score. The difference was more pronounced among a subset cohort of men who had pure lateral curvatures, plaque calcification, or narrowing deformity. In comparing the CLINiC predictive model to baseline curve alone, the correlation coefficient increased to 0.54 (r-squared 0.29, p<0.0001) compared to 0.38 (r-squared 0.15, p<0.001). The linear equation to predict curve improvement outcomes using the CLINiC score was 2.2 - 3.5 * total CLINiC score. Conclusions Use of a novel scoring system (CLINiC) improves upon baseline curvature alone to predict post-CCH curve improvements, with the difference more pronounced among men with pure lateral curvatures, plaque calcification, and/or narrowing deformities. External validation is warranted. Disclosure No

Abstract Introduction Limited data currently exist on the role and efficacy of additional series of collagenase clostridium histolyticum (CCH) injections among Peyronie’s disease (PD) men who have previously failed a first series of injections. We have previously reported outcomes of men undergoing a more aggressive protocol for CCH injections. We therefore sought to evaluate results of men who had previously failed CCH injections to determine if they would respond to a repeat course using a more aggressive protocol. Objective To evaluate outcomes of a novel, aggressive protocol for CCH injections among men who had previously failed 6-8 CCH injections using a traditional approach. Methods A randomized, controlled trial (NCT05108558) is ongoing. All participants had previously failed to achieve ≥20% curvature improvement with 6-8 prior CCH injections. Men are randomized 3:1 to receive either CCH + traction (RestoreX) + sildenafil (treatment) up front or initial observation followed by treatment (controls). Outcomes are subsequently compared between treatment and control groups. Key measures include objective curve improvements, and standardized / non-standardized questionnaires, with assessments obtained at baseline, 6-weeks after completion of CCH (treatment arm), after the no treatment period (controls), and at 1 year. Results A total of 11/40 men have been randomized to date, with one having completed four series of CCH injections, three completing one series, and three completing two series. The average age of the cohort is 64.4 years, with a mean PD duration of 28.1 months. Mean baseline curvature was 82.9 degrees (composite curve). The average estimated improvement with prior CCH injections (before enrollment in the current study) was 10%. Preliminary outcomes of men who had completed one series and had a follow-up curve assessment available (n=3) demonstrated an absolute improvement of 28.3 degrees (42%). Of the one patient who completed four full series, the absolute curve improvement was 55 degrees (65%). The overall range of improvement among the four men was 20 to 55 degrees or 31 to 65%, with no patients failing to experience improvements thus far. Conclusions Preliminary data suggests that a repeat course of CCH using a previously described more aggressive administration protocol is effective at improving penile curvature in the majority of men. It is unclear if the improvements are due to the difference in administration protocol, or due to the repeat course of CCH alone. Given the very preliminary nature of the current results, additional data, including external validation, are warranted. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceutical Clarification Industry funding only - investigator initiated and executed study

Abstract Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH) for the treatment of Peyronie’s Disease (PD), there has been significant debate as to its role and comparable efficacy in relation to surgical therapies. Specifically, investigators have compared relative utilization, costs, and outcomes with varying conclusions. Objective To compare various objective and subjective outcome measures between men undergoing CCH or surgery for PD. Methods A randomized, controlled trial (NCT04786106) is ongoing. Participants are randomized 1:1 to receive either CCH + traction (RestoreX) + sildenafil or penile surgery (plication and/or incision and grafting) + traction + sildenafil for PD. Objective, standardized (International Index of Erectile Function [IIEF] and Peyronie’s Disease Questionnaire [PDQ]), and non-standardized assessments are obtained at baseline, and post-treatment at 3, 6, 12, 24, 36, 48, and 60 months. Key outcomes include differences in standardized questionnaires, penile curvature, penile length, subsequent interventions, and non-standardized questionnaire responses. Curvature is measured in two planes and summed to provide a composite curvature. Penile length is measured from pubic symphysis to corona. All therapies were stopped prior to the 3-month time point (i.e. traction and sildenafil). Results A total of 40 men have been randomized, with 3-month data available on 27 men (CCH=14, surgery=13) and 12-month data on 15 men (CCH=5, surgery=10). Mean age at enrollment was 54.9 years, PD duration 36.6 months (mo), composite curvature 72.3 degrees (deg), and penile length 12.7 cm. All baseline variables were statistically similar between cohorts. Regarding the primary outcome, post-treatment, CCH men reported higher overall satisfaction (3-months: 100% vs 88% surgery, p=0.16; 12-months 80% vs 70%, p=0.52). For secondary outcomes at 3 months, the median differences between CCH and surgery respectively were: IIEF-EFD (+3.5 vs +7, p=0.64), PDQ-physical (-10 vs -7, p=0.47, note: lower is better for PDQ scales), PDQ-pain (-2 vs -0.5, p=0.21), PDQ-bother (-4.5 vs -8.5, p=0.60), length change (+1.0 vs -0.5 cm, p<0.01), curvature absolute change (-26 vs -65 degrees, p=0.01), and curvature percentage improvement (46% vs 84%, p<0.01). More CCH men felt that treatment improved sexual function (86% vs 79%, p=0.45), erectile function (64% vs 56%, p=0.04), penile length (36% vs 6%, p<0.0001), and had less impact on sensation (14% less sensation vs 56%, p<0.01), while surgery men were more likely to report satisfaction with curvature (75% vs 64%, p=0.52). 100% of men in both groups would recommend treatment to a friend at 3 months, whereas 100% of CCH vs 70% of surgery men would recommend their therapy at 12 months. When asked which treatment they would pick if they could start again, at 3 months 100% of CCH men reported CCH and/or traction, while 79% of surgery men indicated surgery. Conclusions Preliminary data suggests that, when compared to surgery, CCH results in higher overall satisfaction (not statistically significant), decreased curve improvement, improved penile length, and fewer impacts on erectile function and sensation. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceutical Clarification Industry funding only - investigator initiated and executed study

ImportanceThe BCG vaccine—used worldwide to prevent tuberculosis—confers multiple nonspecific beneficial effects, and intravesical BCG vaccine is currently the recommended treatment for non–muscle-invasive bladder cancer (NMIBC). Moreover, BCG vaccine has been hypothesized to reduce the risk of Alzheimer disease and related dementias (ADRD), but previous studies have been limited by sample size, study design, or analyses.ObjectiveTo evaluate whether intravesical BCG vaccine exposure is associated with a decreased incidence of ADRD in a cohort of patients with NMIBC while accounting for death as a competing event.Design, Setting, and ParticipantsThis cohort study was performed in patients aged 50 years or older initially diagnosed with NMIBC between May 28, 1987, and May 6, 2021, treated within the Mass General Brigham health care system. The study included a 15-year follow-up of individuals (BCG vaccine treated or controls) whose condition did not clinically progress to muscle-invasive cancer within 8 weeks and did not have an ADRD diagnosis within the first year after the NMIBC diagnosis. Data analysis was conducted from April 18, 2021, to March 28, 2023.Main Outcomes and MeasuresThe main outcome was time to ADRD onset identified using diagnosis codes and medications. Cause-specific hazard ratios (HRs) were estimated using Cox proportional hazards regression after adjusting for confounders (age, sex, and Charlson Comorbidity Index) using inverse probability scores weighting.ResultsIn this cohort study including 6467 individuals initially diagnosed with NMIBC between 1987 and 2021, 3388 patients underwent BCG vaccine treatment (mean [SD] age, 69.89 [9.28] years; 2605 [76.9%] men) and 3079 served as controls (mean [SD] age, 70.73 [10.00] years; 2176 [70.7%] men). Treatment with BCG vaccine was associated with a lower rate of ADRD (HR, 0.80; 95% CI, 0.69-0.99), with an even lower rate of ADRD in patients aged 70 years or older at the time of BCG vaccine treatment (HR, 0.74; 95% CI, 0.60-0.91). In competing risks analysis, BCG vaccine was associated with a lower risk of ADRD (5-year risk difference, −0.011; 95% CI, −0.019 to −0.003) and a decreased risk of death in patients without an earlier diagnosis of ADRD (5-year risk difference, −0.056; 95% CI, −0.075 to −0.037).Conclusions and RelevanceIn this study, BCG vaccine was associated with a significantly lower rate and risk of ADRD in a cohort of patients with bladder cancer when accounting for death as a competing event. However, the risk differences varied with time.

Accurate prediction of progression in subjects at risk of Alzheimer's disease is crucial for enrolling the right subjects in clinical trials. However, a prospective comparison of state-of-the-art algorithms for predicting disease onset and progression is currently lacking. We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of patient-specific biomarkers. On a limited, cross-sectional subset of the data emulating clinical trials, performance of the best algorithms at predicting clinical diagnosis decreased only slightly (2 percentage points) compared to the full longitudinal dataset. The submission system remains open via the website https://tadpole.grand-challenge.org, while TADPOLE SHARE (https://tadpole-share.github.io/) collates code for submissions. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

ObjectiveTo compare improvement in patient‐reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD).MethodologyProspective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10‐item Eating Assessment Tool (EAT‐10) pre‐ and post‐procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t‐test, Wilcoxon rank sum test or chi‐square test, as appropriate.ResultsOne hundred and forty‐seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT‐10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT‐10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow‐up was 86 and 97.5 days, respectively.ConclusionBoth endoscopic and open surgical management of ZD provide significant improvement in patient‐reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group.Level of Evidence3 Laryngoscope, 134:97–102, 2024

AbstractObjectiveAdrenal schwannomas and juxta‐adrenal schwannomas are rare tumours. We aimed to summarise their clinical, biochemical and imaging characteristics.DesignSingle‐centre retrospective study of eligible patients between 1995 and 2022.Patients and MeasurementsPatients with a histopathologic diagnosis of adrenal or juxta‐adrenal schwannoma.ResultsTwenty‐four patients were diagnosed with either primary adrenal schwannoma (8, 33%) or juxta‐adrenal schwannoma (16, 67%). Most tumours (21, 88%) were discovered incidentally on imaging. All tumours were unilateral, with 15 (62%) on the left and 9 (38%) on the right. At diagnosis, the median tumour size was 4 cm (range, 2–13 cm). Adrenal schwannomas were smaller when compared to juxta‐adrenal schwannomas (median of 3.1 cm [range, 2–9 cm] vs. 4.6 cm [range, 2.3–13.3 cm], p = .037). On imaging, the tumours were round or oval in shape in 16 (70%), lobulated in 7 (30%), solid in 15 (68%), solid‐cystic in 7 (32%), heterogeneous in 14 (61%) and homogeneous in 9 (39%). The median unenhanced computed tomography attenuation was 30 Hounsfield units (HU) (range, 12–38 HU). Of the 20 patients who underwent complete hormonal testing, all had nonfunctioning tumours. There was no recurrence or new tumour development in our cohort.ConclusionsAdrenal and juxta‐adrenal schwannomas are nonfunctioning benign tumours that present with indeterminate radiographic features, including large tumour size and increased unenhanced CT attenuation. We did not find an imaging phenotype that was diagnostic of schwannoma. The diagnosis of this rare tumour is based on biopsy or resection.