Alexander T. Augusta Military Medical Center

Subcritical bone has been shown to result in a higher rate of recurrent instability and inferior outcomes after an arthroscopic soft tissue Bankart procedure alone. The ideal surgery for patients with subcritical bone loss remains controversial, with options including arthroscopic Bankart alone, Bankart plus Remplissage (BRR), open Bankart, or a bone transfer procedure. The purpose of this study is to compare the outcomes between the arthroscopic BRR with an open Latarjet for the treatment of anterior shoulder instability in patients with glenoid bone loss (GBL) from 13.5% to 24% in an active-duty military population. It was hypothesized that there will be no difference in recurrence rate or patient-reported outcomes between the 2 procedures. Cohort study; Level of evidence, 3. A retrospective matched-cohort comparison of patients who underwent anterior glenohumeral instability procedures with subcritical bone loss was performed. Inclusion criteria included symptomatic anterior shoulder instability, subcritical GBL (13.5% to 24%), recurrent instability with ≥2 instability episodes, surgical treatment with arthroscopic BRR or open Latarjet, and minimum follow-up of 2 years. Outcomes assessed included recurrent instability (defined as postoperative dislocation or subjective subluxation), military physical restrictions, Western Ontario Shoulder Instability Index (WOSI) score, and Single Assessment Numeric Evaluation (SANE) score. In total, 50 patients were included, 25 of whom underwent an arthroscopic BRR and 25 patients who were treated with an open Latarjet. Mean bone loss was 16.1% and 19.3%, respectively. Five patients experienced recurrent instability, 3 in the arthroscopic BRR group and 2 in the open Latarjet group (P = .64). Mean postoperative SANE score for the arthroscopic BRR group was 81.6% and open Latarjet group was 84.2% (P = .42). Mean postoperative WOSI score for the arthroscopic BRR group was 64.6% and open Latarjet group was 67.9% (P = .44). There was no difference in the number of patients placed on permanent military physical restriction in the arthroscopic BRR group (n = 2) compared with open Latarjet (n = 3) (P = .64). In our small cohort of active-duty military patients with subcritical GBL, there was no difference in recurrent instability between arthroscopic BRR compared with open Latarjet. Additionally, there was no significant difference in postoperative SANE or WOSI scores, complications, or the number of patients placed on permanent military restriction.

Abstract Background SARS-CoV-2 myocarditis is a rare but serious complication of COVID-19. The host response correlates of SARS-CoV-2 myocarditis remain unclear, thereby limiting therapeutic development. We therefore performed proteomic and transcriptomic phenotyping of SARS-CoV-2 myocarditis in Military Health System (MHS) beneficiaries. We included a bioenergetics focus given the emerging role of mitochondrial function in enteroviral myocarditis. Early (<30 days post infection) plasma proteomic biomarkers measured by the Ella 20-plex ELISA assay in cases (SARS-CoV-2 infections with myocarditis) versus controls (SARS-CoV-2 infections without myocarditis). Values are log10 transformed, and p-values are adjusted for multiple comparisons across the full twenty biomarkers (six shown here; * indicates a p-value < 0.05). CRP = C-Reactive Protein; IFNG = Interferon Gamma ; PCT= Procalcitonin; TNFR1 = Tumor necrosis factor receptor-1; DDIMER = D-dimer; and IL1RA = Interleukin-1 receptor antagonist. Methods We previously adjudicated five unvaccinated pre-Delta SARS-CoV-2 myocarditis cases among 5265 MHS beneficiaries who enrolled into the EPICC study with COVID-19; four of these cases had blood collected. We matched myocarditis cases 1:10 with sex, age, comorbidity, and blood sampling-time matched controls (SARS-CoV-2 infection with no myocarditis) from the EPICC study. Cases and controls underwent comparison of early (< 30 days post infection) plasma proteomic biomarkers measured by the Ella 20-plex ELISA assay (with multiplicity adjustment). We also performed early whole blood transcriptomic sequencing with DESeq2 and GSEA analysis of custom mitochondrial pathways, including mitochondrial (mtDNA) regulated innate immune pathways (with FDR for multiple comparisons). Gene set enrichment analysis of custom mitochondrial pathways in cases (SARS-CoV-2 infections with myocarditis) versus controls (SARS-CoV-2 infections without myocarditis). FDR = False Discovery Rate; NES = Normalized enrichment score. Results We detected higher post-infection Tumor Necrosis Factor Receptor-1 (TNFR1) and procalcitonin (PCT) plasma concentrations in myocarditis cases versus matched controls (TNFR1: 0.33 log10 pg/mL difference, p = 0.032; PCT: 0.59 log10 pg/mL difference, p = 0.02) (Fig 1). We noted no statistically significant difference in the 18 other proteomic markers tested. GSEA analysis noted upregulated mitochondrial central dogma and OXPHOS pathway genes, and downregulated mtDNA innate immune genes, in cases versus controls (FDR < 0.05) (Fig 2). Conclusion In this MHS study, SARS-CoV-2 myocarditis was associated with elevation of TNFR1 and PCT secretion, upregulated mitochondrial central dogma and OXPHOS gene expression, and downregulated mtDNA innate immunity. While constrained by small sample sizes of a rare complication, these biomarker associations prompt mechanistic studies which may direct development of therapies for myocarditis due to SARS-CoV-2 and perhaps other respiratory viral pathogens. Disclosures Simon Pollett, MBBS, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response David Tribble, MD, DrPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response Timothy Burgess, MD, MPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response

BackgroundPrimary prevention of atherosclerotic cardiovascular disease (ASCVD) is a vital component of care for people living with HIV (PLWH). Current guidelines recommend at least moderate intensity statin for low to moderate ASCVD risk and high intensity statin for high risk. Determining ASCVD risk in PLWH is difficult due to a paucity of precise risk calculators. We retrospectively compared available ASCVD risk calculators in a population who had known ASCVD events.MethodsWe included US Military HIV Natural History Study (NHS) participants between 2006-2019 who experienced a known ASCVD event as defined in Table 1. Participants missing data to perform all four calculators were excluded from the analysis. Four risk calculators: American College of Cardiology/American Heart Association Pooled Cohort Equation (PCE), Framingham Heart Study Risk Score (FRS), Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) model, and the newly published HIV-CARDIO-PREDICT (HCP) were applied for each participant at 10, 5, and 2 years prior to the ASCVD event. Proportion of participants categorized as high risk was determined for each calculator. Paired calculators were compared by Fisher’s exact or Chi-squared tests.ResultsA total of 134 participants met initial inclusion criteria (Table 2). Of these, 113, 75, and 42 were excluded from the 10, 5, and 2 year analyses respectively due to missing data. HCP had the highest percentage of high-risk participants at any given time interval (Table 3). PCE had the lowest percentage of high-risk participants across all intervals. Head-to head comparison of PCE versus HCP demonstrated a significant difference in proportion of participants classified as high risk at all time intervals (p < 0.0001).ConclusionIn this military study cohort of PLWH who had a known ASCVD event, HCP had the highest sensitivity in classifying participants as high risk at all intervals. PCE, which is guideline recommended for ASCVD risk analysis, had the worst sensitivity. Further understanding of these calculator scores including their driving components over time (especially for HCP), their correlations with outcomes when non-cases are included, and their predictive ability among younger participants are needed.DisclosuresAll Authors: No reported disclosures

Posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament injury and reconstruction (ACLR) is a prevalent cause of long-term disability. Few studies have compared the effect of ACLR timing on the development of PTOA. The purpose of this study was to compare the rate of PTOA at a long-term follow-up between patients who underwent early ACLR (<21 days after injury) versus delayed ACLR (>6 weeks after injury). The authors hypothesized that patients who underwent early ACLR would have lower rates of PTOA compared with the delayed ACLR cohort. Cohort study; Level of evidence, 2. The authors contacted patients from a previous prospective randomized controlled trial who were randomized to undergo either early (<21 days) or delayed (>6 weeks) ACLR with hamstring tendon autografts. Weightbearing radiographs were obtained at a minimum 15-year follow-up, and radiographic PTOA was evaluated using the Kellgren-Lawrence (K-L) classification system. The prevalence of pathologies was compared between the early and delayed groups using appropriate testing, and logistic regression was used to evaluate for associations with failure-a K-L grade of ≥2 or conversion to total knee arthroplasty (TKA). At a mean follow-up of 15.6 years, radiographs were obtained for 58 (28 early, 30 delayed) of the original 69 (84.1%) patients. High rates of PTOA (K-L grade ≥2) were observed in the early (82.1%) and delayed (86.7%) cohorts (P = .634). Two (7.1%) patients in the early cohort converted to TKA compared with 4 (13.3%) patients in the delayed cohort (P = .44). Surgical timing did not affect arthritis severity (P≥ .4), and no factors predicted developing radiographic PTOA in either cohort (P > .2). Increased time from injury decreased the odds of failure in the early ACLR cohort (odds ratio, 0.79; P = .041). In this study, >80% of patients who underwent ACLR with hamstring tendon autografts had radiographic evidence of PTOA at a mean 15.6-year follow-up, with no difference in the prevalence or severity of PTOA between the early and delayed groups. In addition, 11% of patients had converted to TKA by the time of the final follow-up, and the conversion rate did not differ according to the timing of ACLR.

2063 Background: Treatment options are limited for recurrent WHO Grade 3-4 glioma (HGG). Reirradiation (ReRT) is an option, but the ideal treatment regimen and the benefit of concurrent and adjuvant systemic therapy in the recurrent setting remains unclear. Methods: A retrospective review of patients with recurrent HGG treated with reRT was conducted at 12 institutions. Eligible patients were treated with two courses of fractionated RT (&gt;3 fractions) for glioma with the second course being for HGG. To estimate overall and progression free survival times, the Kaplan-Meier method was used. To assess the relationship between survival times and study variables, Cox proportional hazard regression models were used to calculate hazard ratios and the corresponding 95% confidence interval along with the p-value. SAS (version 9.4, Cary, NC, USA) was used for all analyses. P values &lt; 0.05 were assumed to be statistically significant. Results: 482 eligible patients were identified from 1997 to 2023. 235 (54%) had histologic confirmation of glioblastoma at reRT. The median age at reRT was 53.1 years and median KPS was 80. 196 patients (51%) were treated with reRT at their initial recurrence and 122 (30%) had an IDH mutation. The most common reRT dose and number of fractions were 35 Gy and 10 fractions. 192 patients (44%) and 95 (24%) received concurrent (conc) and adjuvant (adj) temozolomide (TMZ) respectively and 116 (27%) and 110 (28%) received conc and adj bevacizumab (BEV) respectively with reRT. Median OS and PFS were 9.8 and 5.3 months. OS (16.6 vs 7.8 months, HR 2.44 p &lt; 0.01) and PFS (8.6 vs 4.6 months, HR 1.85 p &lt; 0.01) were longer in patients with IDH mutations. Receipt of conc and adj TMZ with reRT was associated with improved OS (HR 0.67 p &lt; 0.01 and HR 0.49 p &lt; 0.01 respectively) and PFS (HR 0.66 p &lt;0.01 and HR 0.47 p &lt; 0.01 respectively). Receipt of concBEV with reRT was associated with worse OS (HR 1.66 p &lt; 0.01) but not PFS (HR 1.15 p = 0.28). AdjBEV was not associated with OS or PFS. Concurrent and adjTMZ were associated with improved OS ( p = 0.04 and &lt;0.01) and PFS ( p = 0.01 and &lt;0.01) for IDHwt tumors. In IDHmt tumors, concTMZ was associated with improved OS but not PFS ( p = 0.03 and 0.11), while adjTMZ was associated with improved OS and PFS ( p = 0.05 and &lt;0.01). Symptomatic adverse radiation effects and Grade 3 or greater neurologic toxicity were seen in 107 (25%) and 86 (20%) of patients respectively. Neither conc nor adjBEV nor TMZ were associated with symptomatic ARE. ConcBEV was associated with lower (13% vs 23%, p = 0.03) and concTMZ was associated with higher rates (25% vs 15%, p = 0.01) of Grade 3 or greater neurologic toxicity. Conclusions: The use of concurrent and adjuvant TMZ with reRT are associated with improved OS and PFS in recurrent HGG. OS and PFS are improved with conc and adjTMZ for IDHwt tumors, while there was no PFS benefit to concTMZ in IDHmt tumors. The rate of high grade neurologic toxicity was decreased with the use of concurrent BEV and increased with the use of concTMZ.

Neurofilament light chain (NfL) is a neuron-specific structural protein released into the extracellular space, including body fluids, upon neuroaxonal damage. Despite evidence of a link in neurological disorders, few studies have examined the association of serum NfL with mortality in population-based studies. Data from the National Health and Nutrition Survey were utilized including 2,071 Non-Hispanic White, Non-Hispanic Black and Hispanic adult participants and adult participants of other ethnic groups (20–85 years) with serum NfL measurements who were followed for ≤ 6 years till 2019. We tested the association of serum NfL with mortality in the overall population and stratified by sex with the addition of potential interactive and mediating effects of cardio-metabolic risk factors and nutritional biomarkers. Elevated serum NfL levels (above median group) were associated with mortality risk compared to the below median NfL group in the overall sample (P = 0.010), with trends observed within each sex group (P < 0.10). When examining Loge NfL as a continuum, one standard deviation of Loge NfL was associated with an increased mortality risk (HR = 1.88, 95% CI 1.60–2.20, P < 0.001) in the reduced model adjusted for age, sex, race, and poverty income ratio; a finding only slightly attenuated with the adjustment of lifestyle and health-related factors. Four-way decomposition indicated that there was, among others, mediated interaction between NfL and HbA1c and a pure inconsistent mediation with 25(OH)D3 in predicting all-cause mortality, in models adjusted for all other covariates. Furthermore, urinary albumin-to-creatinine ratio interacted synergistically with NfL in relation to mortality risk both on the additive and multiplicative scales. These data indicate that elevated serum NfL levels were associated with all-cause mortality in a nationally representative sample of US adults.