Citations

Purpose: This study aims to report the epidemiology of patellar sleeve injuries, describe diagnostic findings and treatment, and assess functional outcomes following different treatments. Methods: A medical database was queried from 1990 to 2016 to identify patients ≤18 years presenting to a single pediatric institution with a patellar sleeve injury. Patients with significant comorbidities or previously operatively treated for ipsilateral knee injuries were excluded. Standard demographic data, mechanism of injury, skeletal maturity, injury-related radiographic parameters, along with treatment paradigms, post-treatment clinical and radiographic findings, and patient-reported outcomes were collected. Results: A total of 90 patients, mean age of 10.7 years (range: 7–17) was included, of which 69 (77%) were male. Seventy-three percent of all injuries occurred while playing sports (particularly football/basketball/soccer), with “direct blow” or “landing” being the most prevalent mechanisms of injury. Twenty-six (29%) underwent operative treatment, with transosseous suture fixation being the most popular surgical technique (73%). Of the 64 (71%) non-operatively treated patients, 18 (39%) were placed in a hinged knee brace locked in extension with the remainder split between casting and standard knee immobilizer. Compared to the non-operative cohort, a higher percentage of the operative group had a pre-treatment extensor lag (p < 0.001) and greater fragment displacement (p < 0.001) with patella alta (p < 0.001) on imaging. There was no difference in outcome scores (Pedi-IKDC/Lysholm) or patella alta on radiographs between groups. Post-treatment surveys indicated no difference in residual pain or ability to return to sport. Conclusion: This large case series provides valuable epidemiologic, clinical, and radiographic data describing patellar sleeve fractures, along with outcomes following non-operative and operative treatments. Level of evidence: IV.

Abstract Introduction Radiation therapy (RT) can predispose the onset of corporal fibrosis and microvasculopathy. The impact of RT on intra-operative complications is not well described in the literature. Objective In this study, we assess intra-operative and post-operative outcomes among patients with or without prior history of RT following primary Inflatable Penile Prosthesis (IPP) implantation. Methods We performed a multicenter, retrospective analysis of men undergoing primary IPP placement between January 2015 and December 2022. A total of 3530 patients were identified, of which 3319 had no prior history of RT and 211 patients had history of RT. After 1:1 propensity score matching for all confounding variables, 211 patients with a history of RT were compared to 211 nonradiated patients for intra-operative and post-operative 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 pre-operative characteristics of patients. Kaplan-Meier time to event analysis were compared with Mantel-Cox log-rank test. Results Patients with history of RT encountered more intra-operative complications (4.3% vs 0.9%, p=0.032); specifically, these men experienced more distal crossover events (1.9% vs 0, p=0.044). On multivariable analysis, history of prior RT (OR 5.29, 95% CI 1.07-26.3, p=0.041) and diabetes mellitus (OR 10.5, 95% CI 2.58-43.5, p=0.01) were associated with increased risk of intra-operative complications. History of obesity (OR 0.11, 95% CI 0.01-0.91, p=0.040) reduced risk of intra-operative complications. There was no significant difference in early or late post-operative non-infectious complications between both groups and there was also no significant difference in risk of post-operative complications within 24 months on Kaplan Meier analysis (log rank p=0.9). Conclusions In this large multi-institutional cohort, history of RT is an independent predictor of intra-operative complications but not post-operative complications during primary IPP placement. These findings may help inform patient-specific counseling while guiding surgical planning to prevent untoward morbidity following surgery. Disclosure No.

Abstract Introduction Intracavernosal injection (ICI) therapy for erectile dysfunction (ED) carries a risk of corporal fibrosis, potentially making placement of an inflatable penile prosthesis more difficult. Prostate cancer treatment may also induce corporal fibrosis. Objective To assess whether a history of ICI or prostate cancer treatment is associated with complications following IPP placement. Methods A retrospective cohort study of primary IPP cases from 2016-2021 across 16 institutions. Patients were stratified by history of ICI and between-group differences in risk factors were assessed. Multivariable logistic regression was used to assess for predictors of intraoperative complications, postoperative non-infectious complications and postoperative infection. Results A total of 2540 patients met inclusion criteria of which 781 (30.8%) had a history of ICI. Patients with a history of ICI tended to be older (mean 63 vs 64 years, p=0.002) and were more likely to have history of radical prostatectomy (21.0% vs. 32.1%, p&lt;0.001) and/or radiation (5.51% vs 10.9%, p&lt;0.001). On multivariable regression, a history of ICI, prostatectomy, and radiation were all significant predictors of intraoperative complications (OR 2.11, p=0.03; OR 2.27, p=0.03; OR 2.40, p=0.04, respectively). A history of ICI and patient age were predictors of non-infectious postoperative complications (OR 1.44, p=0.02, OR 1.02, p=0.004 respectively)). None of the variables were significant predictors of infection. Conclusions In men undergoing IPP placement, a history of ICI is associated with an increased risk of both intraoperative and postoperative, non-infectious complications. Prostate cancer treatment with radiation or surgery is independently associated with increased risk of intraoperative complications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: D.O. has served as a consultant for Coloplast, Intuitive Surgical, and Fidelis. P.P. has served as a consultant for Coloplast, Boston Scientific, and Urofill. M.S. has served as a consultant for Boston Scientific and Coloplast. J.S. has served as a consultant for Boston Scientific and Coloplast. F.A.Y. has served as a consultant for Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, and Acerus Pharma. M.S.G. has served as a consultant for Coloplast. The other authors disclose no conflicts.

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.

Abstract The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis of age‐related muscle loss is crucial for developing strategies to combat this debilitating condition. Long noncoding RNAs (lncRNAs) are a largely uncharacterized class of biomolecules that have been implicated in cellular homeostasis and dysfunction across a many tissues and cell types. To identify lncRNAs that might contribute to skeletal muscle aging, we screened for lncRNAs whose expression was altered in vastus lateralis muscle from older compared to young adults. We identified FRAIL1 as an aging‐induced lncRNA with high abundance in human skeletal muscle. In healthy young and older adults, skeletal muscle FRAIL1 was increased with age in conjunction with lower muscle function. Forced expression of FRAIL1 in mouse tibialis anterior muscle elicits a dose‐dependent reduction in skeletal muscle fiber size that is independent of changes in muscle fiber type. Furthermore, this reduction in muscle size is dependent on an intact region of FRAIL1 that is highly conserved across non‐human primates. Unbiased transcriptional and proteomic profiling of the effects of FRAIL1 expression in mouse skeletal muscle revealed widespread changes in mRNA and protein abundance that recapitulate age‐related changes in pathways and processes that are known to be altered in aging skeletal muscle. Taken together, these findings shed light on the intricate molecular mechanisms underlying skeletal muscle aging and implicate FRAIL1 in age‐related skeletal muscle phenotypes.

529 Background: Radical cystectomy is recommended for patients with BCG-unresponsive (BU) non-muscle invasive bladder cancer (NMIBC) due to high risk of progression. Improved methods for assessing these risks would greatly facilitate the potential for bladder preservation. Here, we tested the capacity of the urinary comprehensive genomic profile (uCGP) to predict event-free survival (EFS) in patients with BU-NMIBC treated with atezolizumab in the single arm phase 2 trial SWOG S1605. Methods: Urine was collected from patients with BU NMIBC (CIS, Ta, T1) treated with at least one dose of intravenous atezolizumab at baseline and before the 5th cycle of therapy (3 months). The uCGP was assessed using UroAmp (Convergent Genomics). Risk scores for recurrence at baseline and at 3 months were calculated by a prespecified machine learning algorithm incorporating alterations in 60 genes and low pass whole genome sequencing, and categorized as high versus low. Molecular response was classified based on change in uCGP between the two time points. Risk scores and molecular response were submitted to SWOG for clinical correlation with EFS using a Cox model, adjusting for CIS status. Time to event was calculated from date of study entry (baseline risk) or from the 2nd collection time (3-month risk) to first high grade (HG) recurrence or persistent CIS at 3 months. Death unrelated to bladder cancer and patients last known to be alive without HG recurrence were censored at date of last visit. Results: Samples were provided at baseline in 89 patients and before the 5th cycle in 77; 68 had both samples available for paired analysis. The risk score at baseline was classified as high in 69% of samples (73% for CIS ±Ta/T1 and 62% for Ta/T1). At 12 and 18 months the EFS probabilities were 26% and 23% for high-risk and 67% and 51% for low-risk patients, respectively, with a HR of 2.82 (95% CI: 1.58, 5.03; p<0.001). The risk score at the 3-month timepoint was classified as high in 81% of samples, and the EFS probabilities at 12 and 18 months after urine collection were 26% and 22% for high-risk and 80% and 72% for low-risk patients, respectively, with a HR of 3.39 (95% CI: 1.41, 8.13; p<0.006). Molecular response to treatment was classified as complete (CR) in 8%, partial (PR) in 14%, stable (SD) in 25% and progression (PD) in 46%, with 7% having no detectable genomic abnormalities at both time points. Clinical recurrence was observed by 18 months in 0/6 patients with CR, 7/9 (78%) with PR, 11/14 (79%) with SD and 25/33 (76%) with PD by genomic profile. Conclusions: This study suggests that uCGP at baseline and after 4 cycles of treatment can identify genomic patterns associated with an increased risk of HG persistence, recurrence or progression in BU NMIBC treated with immune checkpoint inhibition. Future studies will determine if this can be used to guide early treatment intensification.

320 Background: sRT is used in men with prostate cancer (PC) recurrence following radical prostatectomy (RP) signaled by a persistent or delayed elevation in PSA. It was previously reported that the use of AAT with RT improved cancer control and overall survival (OS). Long-term follow-up (FU) results are presented here. Methods: From 1998to 2003, 760 eligible post-RP patients with Stage pT3N0 or with pT2N0 and positive margins and PSA from 0.2 to 4.0 ng/mL were randomly assigned on a double-blinded, placebo-controlled trial of RT + placebo vs. RT + anti-androgen therapy (AAT) (24 months of bicalutamide, 150mg daily) during and after RT (64.8 Gy in 36 fractions prostate bed). The primary endpoint was OS estimated using Kaplan-Meier method. Time to PC death and metastatic PC (competing risk of death without an event) was estimated using cumulative incidence. The hazard ratio (HR) was obtained using Cox models (OS) and subdistribution HRs (sHRs) used the Fine-Gray model (time to PC death and metastatic PC). All tests are one-sided based on study design. Results: Median FU for surviving patients was 19 years. OS at 18 years was 53% [95% confidence interval (CI): 47-58%] for RT + AAT and 43% [95% CI: 38-48%] for RT + placebo (adjusted HR 0.82 [95% CI: 0.67-1.00], p = 0.025). The 18-year incidence of centrally reviewed PC deaths were 18% [95% CI: 14-22%] RT + AAT and 28% [95% CI: 23-32%] RT + placebo (adjusted sHR = 0.57 [95% CI: 0.42-0.78], p<0.001). The 18-year incidence of metastatic PC was 22% [95% CI: 18-26%] and 31% [95% CI: 26-35%] for AAT and placebo arms respectively with adjusted sHR = 0.59 [95% CI: 0.44-0.80, p<0.001]. Subgroup analyses is shown in the Table. Conclusions: Long term results of 24-month duration AAT during and after sRT are consistent with the primary report with significantly improved long-term OS, reduced incidence of metastatic PC and PC death for RT+AAT. Statistically significant metastatic PC was noted for Gleason score 8-10, study entry PSA>1.5 and margin positive patients and borderline significance was observed in patients with study entry PSA 0.7-1.5. Clinical trial information: NCT00002874 . [Table: see text]

TPS587 Background: Biliary tract cancer (BTC) is characterized by generally poor prognoses with limited treatment options. Systemic chemotherapy usually begins with gemcitabine, platinum agents, and a checkpoint inhibitor followed by 5-FU and oxaliplatin, irinotecan or a taxane. Presently, there is no consensus second-line therapy for patients with BTC. The DLL/Notch signaling pathway has been described to be a major driver of cholangiocarcinogenesis and VEGF-A overexpression has been reported in BTC tumors, correlating with stage, metastasis, and prognosis of the disease. CTX-009 is a recombinant bispecific antibody that binds both delta-like ligand-4 (DLL4) and vascular endothelial growth factor A (VEGF-A). The antibody simultaneously inhibits the DLL4-Notch 1 and VEGF A-VEGF receptor signaling pathways. Methods: COMPANION-002 (CTX-009 -002) is an open-label, randomized, controlled study in patients in second line advanced or metastatic BTC. To be eligible, patients must have radiologically documented progression after a prior gemcitabine and platinum containing chemotherapy regimen as first line therapy for locally advanced unresectable or metastatic disease. 150 patients will be randomized in a 2:1 ratio to receive either CTX-009 plus paclitaxel or paclitaxel alone. The stratification factors to be used at randomization include stage (locally advanced vs. metastatic), anatomic subsite of primary tumor (intrahepatic cholangiocarcinoma vs. other, i.e. extrahepatic cholangiocarcinoma, gallbladder, or ampullary), and Eastern Cooperative Oncology Group (ECOG) Performance status (0 vs. 1). Patients will be treated in 28-day cycles, with CTX-009 administered at 10 mg/kg IV on Day 1 and 15, and paclitaxel administered at 80 mg/m2 on days 1, 8, and 15. The patients randomized to paclitaxel arm can crossover after disease progression if selection criteria continue to be met. The primary objective of the study is to assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone, as measured by Overall Response Rate (ORR) assessed by an Independent Central Radiology (ICR) review. Key secondary objectives include overall survival, progression-free survival, and duration of response. Clinical trial information: 251040.