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Abstract Background Native joint septic arthritis (NJSA) is diagnosed by synovial fluid analysis to evaluate for evidence of infection but may be definitively established by a positive gram stain or culture. Antibiotics given prior to synovial fluid sampling have been described to alter cell count, gram stain, and culture results and are conventionally deferred until after arthrocentesis to optimize diagnostic yield. However, there is limited data on the impact of preoperative antibiotic therapy on operative culture yield in the diagnosis of NJSA. Methods Following IRB approval, we reviewed medical records of adults diagnosed with NJSA who underwent surgical intervention at Mayo Clinic facilities from January 2012 to December 2021. The effect of preoperative antibiotic therapy on operative culture yield was evaluated through a paired analysis of preoperative and operative cultures results utilizing logistic regression along with generalized estimating equations (GEE) to account for correlations of multiple measurements on the same subject. Results A total of 299 patients with NJSA of 321 joints with the accompanying characteristics who underwent surgery met study criteria (Table 1). Joint distribution, microbiology, and antibiotic administration are outlined in Table 2. Among those treated with preoperative antibiotics, there was a significant decrease in yield between preoperative and operative cultures (68.0% to 57.1%, p < .0001), whereas in patients without preoperative antibiotic exposure, there was an increase in yield (60.9% to 67.4%, p = 0.244; Figure 1). Logistic regression analysis revealed that preoperative antibiotic exposure was more likely to decrease operative culture yield as compared to non-exposure (change, -10.9% vs. +6.5%; p = .006). Secondary analyses restricted to individuals who received preoperative antibiotics revealed that an increasing number of doses and earlier administration of initial antibiotic therapy were associated with lower rates of operative culture yield (Figure 2). Joint distribution, diagnostic/microbiologic, and antibiotic administration characteristics of 321 joints in 299 patients with native joint septic arthritis Composite Image 1: Figure 1, 2a/2b Figure 1: Change in Preoperative and Operative Culture Yield with Antibiotic Exposure Figure 2: Effect of Antibiotic Doses and Timing of Therapy on Predicted Probability of Operative Culture Positivity Conclusion In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in which antibiotic therapy was held prior to obtaining operative cultures. Disclosures Brandon J. Yuan, M.D., American Association of Orthopaedic Surgeons: Board Member|DePuy, A Johnson & Johnson Company: Advisor/Consultant|Mid America Orthopaedic Association: Board Member|Stryker: Advisor/Consultant Gina A. Suh, M.D., Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: IP royalties|Phagelux: Grant/Research Support Aaron J. Tande, M.D., Musculoskeletal Infection Society: Board Member|Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing royalties, financial or material support

Abstract Background Non-diphtheriae Corynebacterium spp. are important human pathogens responsible for a broad spectrum of clinical syndromes. Data on species-specific susceptibility patterns is limited. In this study we aim to study these susceptibility patterns over time and summarize the species-specific resistance profile that could be used by clinicians to guide therapeutic decisions. Methods We conducted a retrospective review of all the Non-diphtheriae Corynebacterium isolates that were submitted for antimicrobial susceptibility testing (AST) between January-2012 and February of 2023 to our reference lab. Results A total of 1925 Corynebacterium isolates were submitted for susceptibility testing over the study period. The most commonly identified species was C. striatum (35.6%) followed by C. amycolatum (24.4%). Figure-1 outlines the species distribution. Temporal analysis showed decreasing susceptibility rates over the study period from 47.5% to 20.6% for penicillin & from 50% to 7.6% for clindamycin. Linezolid and vancomycin were universally active against all species (Table-1). Daptomycin non-susceptibility was reported in 25% of C. jeikeium isolates (MIC=2). High level resistance to daptomycin with MIC >256 were noted in seven C. striatum and single C. amycolatum isolate. Doxycycline has the highest susceptibility rates among the tested oral agents after linezolid for the non-striatum species. Significant variation in species-specific susceptibility pattern was noted and summarized in Table 1. C. striatum was associated with concerning resistance rates to beta-lactams, tetracyclines, trimethoprim-sulfamethoxazole & fluoroquinolones with limited reliable oral treatment options beside linezolid. C. kroppenstedtii (associated with granulomatous mastitis) showed high susceptibility rate to tetracyclines and trimethoprim-sulfamethoxazole despite prevalent penicillin resistance. Conclusion Non-diphtheriae Corynebacterium spp are commonly isolated from clinical specimens and are associated with various clinical syndromes. Significant variation in resistance profile exists between different species. Prevalent resistance among the most common species such as C. Striatum is associated with therapeutic challenges. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Audrey N. Schuetz, MD, Merck: Advisor/Consultant

Abstract Background Current approaches to diagnosing suspected native vertebral osteomyelitis (NVO) rely on imaging and microbiological workup, including blood and CT-guided biopsy cultures. These existing diagnostic methods often result in ambiguity, necessitating additional tests to distinguish NVO from its mimics. Our study aims to validate pilot findings demonstrating that an elevated neutrophil differential (PMN) in vertebral bone biopsy/ disc space fluid aspirate is associated with NVO. This may allow stratification of patients with suspected NVO into those who can be monitored closely versus those who may benefit from further invasive testing or empiric antibiotic therapy (Fig 1). Figure 1: Proposed workup of patients with suspected native vertebral osteomyelitis guided by disc space/ vertebral body neutrophil (PMN) differential. Methods This analysis examines a subset of patients from a prospective cohort study, enrolling adults referred to Mayo Clinic's neuroradiology department for spine biopsy. After collecting routine clinical specimens, the needle is rinsed with saline into an EDTA tube for automated cell count and differential analysis. To evaluate the predictive capacity of neutrophil (PMN) differential for NVO, logistic regression models were employed, and receiver operating characteristic (ROC) curve analyses were conducted for various PMN percentage cutoff points. Results In this preliminary analysis, 39 patients were included, comprising 7 patients with NVO and 32 patients with alternative diagnoses. Baseline characteristics are presented in Table 1. All NVO patients received antibiotics within two weeks of the spine biopsy. The median biopsy sample PMN percentage for NVO patients was 83.0 (77.5-88.0), compared to 65.0 (56.5-69.5) for those without NVO (p=0.005) (Fig 2A). The estimated relationship between the probability of NVO and each measure across the full range of percentages is illustrated in Fig 2B. The optimal ROC curve point corresponds to a PMN differential of 72.5% (sensitivity=0.86, specificity=0.81) (Fig 3).Table 1:Baseline Characteristics of Patients Included in the Preliminary AnalysisFigure 2:A) Distribution of spine biopsy neutrophil percent by native vertebral osteomyelitis (NVO) status, B) Loess nonparametric smoother showing the relationship between the probability of NVO and biopsy sample neutrophil percentage.Figure 3:ROC curve analysis of neutrophil percent and NVO Conclusion This preliminary analysis indicates that an elevated PMN differential in spine biopsy samples may serve as a valuable diagnostic tool for NVO, with results seemingly unaffected by recent antibiotic intake. The PMN differential cutoff of 72.5% exhibited notable sensitivity and specificity. Investigations are ongoing to further validate these findings Disclosures Brett Freedman, MD, Clear Choice Therapeutics: Stocks/Bonds|Medtronic: Grant/Research Support|Neuroinnovations: Stocks/Bonds Aaron J. Tande, M.D., Musculoskeletal Infection Society: Board Member|Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing royalties, financial or material support

Abstract Background Native joint septic arthritis (NJSA) of the wrist is a rare condition, with published literature suggesting an incidence of approximately 1.5% among patients presenting with acute painful and swollen wrist. The aim of this study was to investigate the characteristics, management, and outcomes of wrist NJSA at our institution. Methods We conducted a retrospective study of all adults diagnosed with wrist NJSA who underwent surgical intervention at Mayo Clinic facilities from January 2012 to December 2021. The diagnosis was confirmed based on clinical presentation, synovial fluid white blood cell count, and aspiration or operative cultures. Results A total of 557 patients developed NJSA during the study period, of whom 55 (9.9%) were diagnosed with wrist NJSA, median age was 63, with the associated demographics (Table 1). 12 (21.8%) had a history of antecedent trauma or procedure, 11 (20%) had synchronous joint infections, and 22 (40%) had positive blood cultures. The median synovial white blood cell count was 94,050/mm3 (IQR 51,920 – 139,941 /mm3). Crystals were detected in 5 patients (8.8%). Additional diagnostic data are available in Table 2. Open debridement was performed in 35 (61.4%) patients, and the rest underwent arthroscopy. Positive Gram stain results were detected in the preoperative synovial fluid of 12 (21.8%) cases. The most common pathogen isolated was Staphylococcus aureus in 13 (24%) of cases. The median duration of antimicrobial therapy was 31 days (IQR 26 – 45 days). There was no statistically significant difference in the incidence of complications between patients who underwent open debridement and those who underwent arthroscopy (Table 3). The most common complication of both groups was compromised range of motion of the wrist joint. Conclusion Native wrist septic arthritis comprised 9.9 % of all NJSA during the study period. Concomitant bacteremia and synchronous joint infections were common, highlighting the importance of obtaining blood cultures and comprehensive joint exam in this setting. Crystals and Gram stains were detected in 10 % and 22% of cases, respectively. These findings should not rule out NJSA. Decreased range of motion was common complication, affecting 21% of all cases. Disclosures Gina A. Suh, M.D., Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: IP royalties|Phagelux: Grant/Research Support Aaron J. Tande, M.D., Musculoskeletal Infection Society: Board Member|Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing royalties, financial or material support Brandon J. Yuan, M.D., American Association of Orthopaedic Surgeons: Board Member|DePuy, A Johnson & Johnson Company: Advisor/Consultant|Mid America Orthopaedic Association: Board Member|Stryker: Advisor/Consultant

Abstract Introduction Lipoprotein(a) [Lp(a)] is associated with an increased incidence of aortic stenosis. Bioprosthetic aortic valve degeneration and native aortic stenosis share similar pathological mechanisms. Evidence regarding the role of serum Lp(a) concentrations in bioprosthetic aortic valve degeneration is lacking. Purpose To evaluate the association between serum Lp(a) concentrations and bioprosthetic aortic valve degeneration. Methods In this retrospective multicenter study, consecutive patients who underwent a bioprosthetic aortic valve replacement between Jan-2010 and Dec-2020 and had a preoperatory serum Lp(a) measurement were included. A baseline transthoracic echocardiography (TTE) was performed following the aortic valve replacement and a follow-up TTE was performed at least 24 months after the baseline study to determine the presence of bioprosthetic valve degeneration. Significant degeneration was defined as: (a) an increase >10 mmHg in mean bioprosthetic aortic valve gradient from baseline status + a decrease in effective orifice area + a decrease in Doppler velocity index + exclusion of clinically thrombotic leaflet thickening, OR (b) new moderate or severe prosthetic aortic regurgitation (if the main component was periprosthetic, then it was not considered). Lp(a) concentrations were compared between patients with and without degeneration and regression analysis was conducted to investigate the association between bioprosthetic valve degeneration and Lp(a) levels. Results In total, 211 cases were included (mean age 74.1 ±9.4 years, 72.0% males, 29.9% transcatheter aortic valve replacements) (Figure 1). Median time between baseline and follow-up TTE was 5.0 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.6%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in the patients affected by degeneration versus non-affected cases (50.0 vs 15.7 mg/dl, p=0.003). In the regression analysis, high Lp(a) levels (≥30 mg/dl) were associated with degeneration both in a univariate analysis (OR 4.8, 95%CI 2.2-10.9, p<0.001) and multivariate analysis adjusted by other risk factors for bioprostheses degeneration (age, sex, hypertension, smoking, patient prosthesis mismatch, creatinine levels, and body surface area) (OR 5.2, 95%CI 2.1-12.8, p<0.001). Conclusion Serum Lp(a) concentrations seem to be a risk factor for bioprosthetic aortic valve degeneration (Figure 2). There is an increasing need to accurately predict bioprosthetic aortic valve degeneration and to develop novel methods and treatments to increase their durability. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) could slow bioprostheses degradation.Population characteristicsLp(a) and bioprostheses degeneration

Abstract Background Cardiac masses encompass a wide differential including primary and secondary malignancies and can present with a variety of symptoms, many of which are non-specific. Early identification and classification are important, particularly for cardiac malignancies such as sarcomas as these are aggressive tumours with exceptionally poor prognoses when metastases are present at diagnosis. Case summary We report two cases of patients who presented with dyspnoea and were diagnosed with cardiac sarcomas; the former a primary sarcoma (undifferentiated pleomorphic subtype) and the latter a secondary sarcoma (round cell myxoid liposarcoma) that serve as comparisons for presentation and management of different types of this disease. Computed Tomography (CT) and echocardiography imaging findings are demonstrated showing the typical location and morphology of each subtype. Discussion Cardiac sarcomas are the most common primary cardiac malignancy, of which undifferentiated pleomorphic sarcoma is a common subtype. Undifferentiated pleomorphic sarcomas are aggressive, have a tendency to arise in the left atrium, and can appear similar to benign cardiac masses. Round cell myxoid liposarcomas by contrast are rare causes of secondary cardiac malignancies, metastasizing to the heart from soft tissues. Both diagnoses carry poor prognoses and although rare, are important to recognize as timely intervention with surgery, radiotherapy, and consideration of chemotherapy is key to maximizing survival.

Background Acute pericarditis (AP) is considered a cardiovascular complication in patients with COVID‐19. We aimed to ass‐ess the incidence, associated complications, and clinical impact of AP on hospitalized patients with COVID‐19. Methods and Results In this retrospective cohort study, International Classification of Diseases, Tenthth Revision, Clinical Modification ( ICD‐10 ) codes were used to identify patients with COVID‐19 with or without AP in the National Inpatient Sample 2020 database. We compared outcomes between AP and non‐AP groups before and after propensity‐score matching for patient and hospital demographics and relevant comorbidities. A total of 211 619 patients with a primary diagnosis of COVID‐19 were identified, including 983 (0.46%) patients who had a secondary diagnosis of AP. Before matching, patients with COVID‐19 with AP were younger (59.93±19.24 years old versus 64.29±16.82 years old) and more likely to have anemia (40.5% versus 19.9%), cancer (6.7% versus 3.6%), and chronic kidney disease (29.3% versus 19.6%) (all P <0.05). After matching, patients with COVID‐19 with AP (n=980), when compared with the matched non‐AP group (n=2936), had higher rates of mortality (21.3% versus 11.1%, P <0.001), cardiac arrest (5.0% versus 2.6%, P <0.001), cardiogenic shock (4.2% versus 0.5%, P <0.001), ventricular arrhythmia (4.7% versus 1.9%, P <0.001), acute kidney injury (38.3% versus 28.9%, P <0.001), acute congestive heart failure (14.3% versus 4.8%, P <0.001), and longer length of stay (7.00±10.00 days versus 5.00±7.00 days, P <0.001) and higher total charges ($75066.5±$130831.3 versus $44824.0±$63660.5, P <0.001). Conclusions In hospitalized patients with COVID‐19, AP is a rare but severe in‐hospital complication and is associated with worse in‐hospital outcomes.

Abstract Background Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. Methods We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). Results Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, −14%; 95% CI, −19% to −8%; P &lt; .001; I 2 = 0%; relative risk, 0.58; 95% CI, .37–.92, P = .02, I 2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. Conclusions Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.

Objectives Lipoprotein(a) (Lp(a)) is associated with an increased incidence of native aortic stenosis, which shares similar pathological mechanisms with bioprosthetic aortic valve (bAV) degeneration. However, evidence regarding the role of Lp(a) concentrations in bAV degeneration is lacking. This study aims to evaluate the association between Lp(a) concentrations and bAV degeneration. Methods In this retrospective multicentre study, patients who underwent a bAV replacement between 1 January 2010 and 31 December 2020 and had a Lp(a) measurement were included. Echocardiography follow-up was performed to determine the presence of bioprosthetic valve degeneration, which was defined as an increase >10 mm Hg in mean gradient from baseline with concomitant decrease in effective orifice area and Doppler Velocity Index, or new moderate/severe prosthetic regurgitation. Levels of Lp(a) were compared between patients with and without degeneration and Cox regression analysis was performed to investigate the association between Lp(a) levels and bioprosthetic valve degeneration. Results In total, 210 cases were included (mean age 74.1±9.4 years, 72.4% males). Median time between baseline and follow-up echocardiography was 4.4 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.7%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in patients affected by degeneration versus non-affected cases: 50.0 (IQR 72.0) vs 15.6 (IQR 48.6) mg/dL, p=0.002. In the regression analysis, high Lp(a) levels (≥30 mg/dL) were associated with degeneration both in a univariable analysis (HR 3.6, 95% CI 1.7 to 7.6, p=0.001) and multivariable analysis adjusted by other risk factors for bioprostheses degeneration (HR 4.4, 95% CI 1.9 to 10.4, p=0.001). Conclusions High serum Lp(a) is associated with bAV degeneration. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) levels could slow bioprostheses degradation.