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Abstract Introduction Peyronie’s disease (PD) is traditionally categorized into 2 phases: acute (active) and chronic (stable) phase; however, clinical definitions and distinction between the phases vary in the literature and remain blurred.[1] The American Urological Association guidelines outline changing symptoms with the presence of pain as a defining symptom of acute disease, but provide little guidance about timeframe.[2] Historically, acute-phase characteristics include presence of penile pain and progressing deformity (eg, worsening penile curvature), with time from symptom onset to acute phase completion being <3–18 months.[1] While there may be academic utility in temporally categorizing PD, it may limit or postpone the treatment options for patients suffering from the condition. Collagenase clostridium histolyticum (CCH) is an approved nonsurgical PD treatment option and several studies suggest its safety and efficacy in acute phase PD.[3-6] In light of these studies and ambiguity in dichotomizing phases, previous clinical trial data were reanalyzed to investigate the potential for opening the gamut of treatment options at earlier timepoints in the disease process. Objective This analysis examines CCH treatment efficacy on improving penile curvature in participants presenting with/without penile pain at baseline and disease duration of 12–18 months or >18 months from the CCH clinical trial program. Methods Literature related to CCH treatment of acute phase PD was compiled and treatment outcomes assessed. Additionally, a post hoc analysis of pooled data from two phase 3 randomized, double-blind trials of CCH in PD (IMPRESS I, NCT01221597; IMPRESS II, NCT01221623) was conducted. CCH-treated participants were stratified by the reporting of moderate-severe pain or no pain at baseline based on the following study measures: penile pain on palpation, penile pain on erection, PD questionnaire (PDQ) combined questions 7–9, and PDQ question 10 only. Additional subgroup analyses stratified participants by presence of pain and disease duration (12–18 or >18 months). The primary efficacy endpoint was the percentage change in penile curvature at week 52 from baseline. Results The IMPRESS I/II data analysis found that participants who experienced moderate-severe pain at baseline had penile curvature improvements by week 52 similar to participants with no pain at baseline. Across all pain measures, the percentage decreases in mean penile curvature from baseline ranged from 29%–42% for moderate-severe pain groups and 35%–37% for no penile pain groups. There were no clear differences in mean penile curvature improvement between groups for any specific pain measure when stratified by disease duration of 12–18 months (moderate-severe pain, 32%–40% improvement; no pain, 23%–29% improvement) versus >18 months (moderate-severe pain, 24%–44% improvement; no pain, 37%–40% improvement). Outcomes from the IMPRESS trials were comparable in context with published literature. Conclusions Based on a subanalysis of IMPRESS data, there were no clear differences identified in CCH treatment outcomes between participants experiencing moderate-severe pain or no pain at baseline regardless of disease duration (12–18 versus >18 months). These analyses are consistent with other literature evaluating the efficacy of CCH in the acute phase of disease and suggest that ongoing pain is not a contraindication to CCH therapy. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals Inc. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals Inc; Boston Scientific Corporation; Antares Pharma, Inc; PathRight Medical.

Background: Following the adoption of new nomenclature for steatotic liver disease, we aimed to build consensus on the use of International Classification of Diseases codes and recommendations for future research and advocacy. Methods: Through a two-stage Delphi process, a core group (n = 20) reviewed draft statements and recommendations (n = 6), indicating levels of agreement. Following revisions, this process was repeated with a large expert panel (n = 243) from 73 countries. Results: Consensus ranged from 88.8% to 96.9% (mean = 92.3%). Conclusions: This global consensus statement provides guidance on harmonizing the International Classification of Diseases coding for steatotic liver disease and future directions to advance the field.

OBJECTIVE Poor pain control has a negative impact on postoperative recovery and patient satisfaction. However, overzealous pain management, particularly with opioids, can confound serial neurological assessments, increase morbidity, and predispose patients to long-term dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating postoperative pain and can limit opioid intake, but their use has been limited in patients undergoing craniotomy for brain tumor resection due to concerns of an increased hemorrhage risk. Herein, the authors aim to 1) address the safety of NSAID use in the immediate postoperative setting and 2) determine whether NSAID administration decreases opioid use following craniotomy for tumor resection in adult patients. METHODS The authors conducted a retrospective cohort study of patients 18 years and older with an estimated glomerular filtration rate ≥ 60 ml/min/body surface area who had undergone craniotomy for tumor resection at their institution between 2019 and 2021. NSAID use in the first 48 hours following surgery was recorded. Primary outcomes were postoperative hemorrhage requiring a return to the operating room before hospital discharge and within 30 days of surgery. Secondary outcomes were more-than-minimal hemorrhage that did not require reoperation, acute kidney injury, and total opioid use within 48 hours after craniotomy. RESULTS Among 1765 reviewed patient records, 1182 were eligible for inclusion in this analysis. Amid these records were 114 patients (9.6%) who had received at least one dose of an NSAID within 48 hours of their craniotomy. Four (0.3%) patients experienced bleeding requiring a return to operating room, one of whom was from the NSAID-treated group (RR 3.12, 95% CI 0.33–29.77, p = 0.30). No significant difference in nonoperative intracranial hemorrhage (RR 1.34, 95% CI 0.54–3.35, p = 0.53), postoperative acute kidney injury, or clinically significant extracranial bleeding was found between the NSAID and no-NSAID groups. Patients in the NSAID group had significantly higher oral morphine equivalent use (median 68 vs 30, p < 0.001). CONCLUSIONS Postoperative NSAID use following craniotomy for tumor resection was not associated with an increased risk of hemorrhage requiring a return to the operating room. The authors noted higher opioid use in the patients treated with NSAIDs, which may reflect underlying reasons for the decision to treat patients with NSAIDs in the immediate postoperative period. These data warrant further investigation of NSAIDs as a safe, opioid-sparing postoperative pain management strategy in patients with normal kidney function who are undergoing intracranial tumor resection.

Background: White matter hyperintensities (WMH) are associated with risk of dementia and stroke, so are an important therapeutic target for clinical trials. The cost of broad MRI screening to identify those individuals with significant WMH, however, limits the feasibility of designing clinical trials which target WMH presence and which test treatments that slow progression. Hypothesis: A low-cost retinal or clinical screening measure prior to an MRI screening stage reduces the cost of recruiting persons with significant WMH burden in a hypothetical clinical trial vs an MRI-only screening design. Method: Data were from participants in the Atherosclerosis Risk in Communities-Neurocognitive study with clinical, retinal and WMH measurements ( N = 1311) at ages 53-70 years. Significant WMH burden was defined as a Cardiovascular Health Study score >2. Three low-cost pre-screening measures were assessed: (1) retinal: a score incorporating multiple markers of abnormal retinal vasculature, (2) clinical: a score incorporating hypertension, diabetes, and age, (3) combined retinal-clinical: a score incorporating retinal and clinical factors. Given a prior published target sample for a WMH clinical trial (N= 646), we calculated a theoretical screening sample size based on the proportion of each pre-screening measure in the population multiplied by the proportion of significant WMH burden among those with a prevalent pre-screening feature. Total recruitment cost was calculated using standard retinal ($32.50) and MRI ($650) cost estimates. Results: Compared to the estimated cost of MRI-only screening (>$4.24M, requiring MRI screening 6,526 participants), pre-screening for a high clinical score reduced total cost to $2.47M, but increased the initial screening group to 52,778 participants, of whom 3,801 would be screened by MRI). A high retinal-clinical score cutoff reduced costs to $2.9M while only requiring 13,572 screened participants (of these only 3,801 would require MRI). Conclusion: A 2-stage recruitment design with a low-cost pre-screening retinal and clinical measure is a promising approach, resulting in a reduction of theoretical recruitment costs for recruiting persons with significant WMH burden compared to an MRI-only design.

Background: Endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) outcomes are unclear in patients with pre-stroke dementia or cognitive impairment. Although these individuals make up ~12% of acute stroke patients, they are often excluded from both stroke trials and routine care. This systematic review and meta-analysis explored reperfusion therapy outcomes in this population. Methods: Using the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, this systematic review investigated studies on acute ischemic stroke patients with dementia or cognitive impairment treated with either IVT or EVT. Primary outcome was defined as favorable 90-day outcome (modified Rankin Scale (mRS) score 0-2). Secondary outcomes included 90-day mortality, radiographic intracranial hemorrhage (ICH) and symptomatic ICH (SICH). Results: 9 articles were included from 825 screened. 5 observational studies of IVT use in patients with (n=1078) and without dementia (n=2805) were selected for a meta-analysis. There were no significant differences in favourable 90-day mRS (adjusted OR 0.61, 95% CI 0.24 to 1.59), 90-day mortality (unadjusted OR of 1.19, 95% CI 0.86 to 1.64), ICH (unadjusted OR 1.32, 95% CI 0.79 to 2.19) and SICH (unadjusted OR of 0.94, 95% CI 0.70 to 1.25). EVT in dementia patients in one study found only increased odds of ICH (adjusted OR 1.57 95%CI 1.03 to 2.40). For patients with cognitive impairment, no significant association was found with assessed outcomes in a pooled analysis of 3 IVT studies and one EVT study found poorer 90-day mRS outcomes. Conclusions: This systematic review and meta-analysis suggests no considerable safety concerns for IVT or EVT use in patients with pre-existing dementia or cognitive impairment, compared to those without. Uncertainty remains in the efficacy of these therapies for these individuals. Rigorous, patient-caregiver informed design, and a more nuanced outcome approach are warranted for future studies. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021240499.

SummaryObjectiveRising prevalence of obesity has led to increased rates of prediabetes and diabetes mellitus (DM) in children. This study compares rates of prediabetes and diabetes using two recommended screening tests (fasting plasma glucose [FPG] and haemoglobin A1c [HbA1c]).Study DesignData were collected prospectively from 37 multi‐component paediatric weight management programs in POWER (Paediatric Obesity Weight Evaluation Registry).ResultsFor this study, 3962 children with obesity without a known diagnosis of DM at presentation and for whom concurrent measurement of FPG and HbA1c were available were evaluated (median age 12.0 years [interquartile range, IQR 9.8, 14.6]; 48% males; median body mass index 95th percentile [%BMIp95] 134% [IQR 120, 151]). Notably, 10.7% had prediabetes based on FPG criteria (100–125 mg/dL), 18.6% had prediabetes based on HbA1c criteria (5.7%–6.4%), 0.9% had DM by FPG abnormality (≥126 mg/dL) and 1.1% had DM by HbA1c abnormality (≥6.5%). Discordance between the tests was observed for youth in both age groups (10–18 years [n = 2915] and age 2–9 years [n = 1047]).ConclusionThere is discordance between FPG and HbA1c for the diagnosis of prediabetes and DM in youth with obesity. Further studies are needed to understand the predictive capability of these tests for development of DM (in those diagnosed with prediabetes) and cardiometabolic risk.

SummaryThe thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild‐type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty‐two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9–5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9–16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.

314 Background: Prostate cancer patients (PC) face an elevated risk of both developing atherosclerotic cardiovascular disease (ASCVD). The American College of Cardiology Pooled Cohort Equations (PCE) for ASCVD predictions may lack accuracy. Methods: Males ≥18 years, diagnosed with PC between 2005-2012 at a hybrid academic-community practice were included. Using XGBoost algorithm we developed using a training subset of the cohort (50% train + 25% test), ranked 33 covariates (including demographic, treatment-related and social determinants of health (SDOH) information) for ASCVD prediction using SHAP (Shapley additive explanations) values. The top 10 predictors were transformed in a predictive equation using logistic regression models. This equation was tested in the cohort validation subset (25%), and subsequently compared to the PCE risk score. Results: We included 1,506 patients, with a median age of 67 (IQR 60-74) years, 13.8% had advanced stage disease (TNM III-IV), 1.5% had high risk PC (Gleason 8-10), and 20.5% received androgen deprivation therapy (ADT). Of those, 10.4% had a 10-year ASCVD risk. The PCE had an area under the curve (AUC)=0.61 and underestimated ASCVD in 0.9% (mean risk=20.1% [95% CI 17.2-23.0] vs. mean predicted risk=19.2% [95% CI 18.6-19.8]). The equation pooled from the top-10 predictors of the ML algorithm (C-index=0.78 [95% CI 0.75-0.81]) achieved an AUC=0.71 (Table). Conclusions: Conventional PCE tend to underestimate ASCVD risk in males with PC. A cancer-specific model inclusive of SDOH exhibits good performance for predicting ASCVD risk in this population. [Table: see text]