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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 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

A history of hypertensive disorders of pregnancy, including preeclampsia, place women at an elevated risk of developing hypertension and cognitive impairments as they age. The purpose of this study was to determine if aortic hemodynamics were related to cognition in postmenopausal women with a history of hypertensive disorders of pregnancy. We evaluated 33 postmenopausal women with a history of preeclampsia (PE: age = 59 ± 5 y; BMI = 29 ± 5 kg/m 2 ; years since last pregnancy = 35 ± 3 y) and 29 postmenopausal women with a history of normotensive pregnancy (NTP: age = 59 ± 5 y; BMI = 26 ± 5 kg/m 2 ; years since last pregnancy = 35 ± 3 y). Participants underwent a cognitive testing battery including letter‐number sequencing, trail making test B, letter fluency, and category fluency tests to evaluate executive functioning and working memory. Mean arterial pressure (MAP) was measured with a brachial blood pressure cuff. Applanation tonometry (SphygmoCor) was used to derive the aortic pressure waveform and calculate aortic systolic blood pressure (ASBP), aortic diastolic blood pressure (ADBP), augmentation index (AI), and augmented pressure (AP). There were no differences in cognitive scores between groups (p > 0.05). Brachial blood pressure (MAP: 103 ± 2 vs. 103 ± 3 mmHg) and aortic hemodynamic measures (ASBP: 123 ± 3 vs. 121 ± 3 mmHg; ADBP: 78 ± 2 vs. 77 ± 2 mmHg; AI: 31 ± 2 vs. 28 ± 1 %; AP: 17 ± 1 vs. 15 ± 1 mmHg) were also similar between PE women and NTP women, respectively (p > 0.05 for all). There were no associations between measures of aortic hemodynamics and cognitive scores in women independent of their pregnancy history (p > 0.05). When evaluating these relationships within each group, ADBP was significantly associated with worse scores for letter‐number sequencing and letter fluency in PE women (r = −0.433 and r = −0.441, respectively, p < 0.05). Taken together, our results indicate aortic hemodynamic measures are not associated with cognition in middle‐aged postmenopausal women with different pregnancy histories; however, future studies should address the influence of elevated aortic hemodynamic variables and the longitudinal change in cognitive function in postmenopausal women with different pregnancy histories. Support or Funding Information NIH AG44170, NIH 118154

Objective Preeclampsia (PE) is a hypertensive pregnancy disorder that represents a sex‐specific risk factor for future cardiovascular disease in affected women. This study evaluated the associations of a history of PE, conventional cardiovascular risk factors and vascular activation (defined by activation of blood elements and blood‐borne microvesicles (MV)) with carotid intima‐media thickness (CIMT) in menopausal women. Methods Caucasian women residents of Olmsted County, MN who delivered between 1976 and 1982 were identified from review of their medical records and matched for parity and age at index birth: 40 with a history of preeclampsia (PE) and 40 with a history of normotensive pregnancy (NP). Blood clinical chemistries and 38 measures of intravascular activation including differential cell counts, platelet aggregation and secretion, cell‐cell interactions, and blood‐borne MV were measured in venous blood. CIMT was measured by B‐mode ultrasound. The study was approved by the IRB at Mayo Clinic and all women gave written informed consent. Results Women averaged 60 years of age at the time of testing. CIMT was greater in the PE [0.80 mm (0.75, 0.85); median (25th, 75th percentile)] compared to the NP [0.73 mm (0.70, 0.78)] group (P=0.004). Body mass index, waist circumference, fasting insulin, high‐sensitive C‐reactive protein and present day hypertension were greater in the PE group. After adjusting for potential confounding factors, the odds of having a higher CIMT value was more than 3‐fold higher for women with a history of PE [OR 3.46 (1.38, 8.68); P=0.008]. Principal components (PC) analysis identified 7 components that accounted for 63% of the variability in measures of intravascular activation. The global test for association of intravascular activation with CIMT (P=0.009) was only significant among women with a history of NP. PC#4, which conveyed measures of whole blood platelet aggregation and platelet interactions with granulocytes and monocytes, positively associated with CIMT in the overall group after adjustment for PE status (partial ρ=0.290; P=0.009). PC#6, consisting of measures of platelet activation with platelet count and interactions between monocytes and the vascular endothelium, also showed a significant interaction with pregnancy history (P=0.014). Conclusion A history of preeclampsia accompanied by metabolic and pro‐coagulant/‐inflammatory intravascular cellular activation contributes to progression of CIMT in menopausal women. Support or Funding Information This work was funded by grants from the NIH AG44170, AG034676, UL1 TR000135 and the Mayo Foundation.

Objective Preeclampsia, a hypertensive pregnancy disorder, increases the risk for cardiovascular disease including coronary artery calcification (CAC) as women age. Controversy exists regarding the relationship between bone mineral density (BMD) and CAC in menopausal women. This study was designed to determine and compare the relationship between BMD and CAC in postmenopausal women with defined histories of either normotensive or preeclamptic pregnancies. Methods Women who gave birth in Olmsted County, MN between 1976 and 1982 were identified from their medical record as having a preeclamptic pregnancy (PE, n=40) and were age/parity‐matched with women having normotensive pregnancies (NP, n=40). The study was approved by the IRB at Mayo Clinic and all participants gave written informed consent. Quantitative Computed Tomography was used to assess vertebral (T7‐9) BMD and CAC. Statistical analyses included linear regression with general estimating equation (GEE) to correct for within‐subject correlations. Results Women averaged 35 years since the index pregnancy and were 60 years of age at the time of the study. CAC was significantly greater in women of the PE group (median (25 th , 75 th percentiles: 0 (0, 0.3) NP and 0 (0, 25) PE, P=0.026). There were no significant differences in cortical, trabecular or central BMD between PE and NP groups. However, there was a positive correlation between cortical BMD and CAC in the PE group (ρ=0.336, P=0.042) and a negative correlation between central BMD and CAC in the NP group (ρ=−0.392, P=0.017). Conclusions Although CAC was greater in women with a history PE, BMD did not differ from women with a history of NP. Associations between cortical and central BMD with CAC differed by pregnancy history suggesting that there may be underlying differences in calcium metabolism associated with PE. Support or Funding Information This work was funded by grants from the NIH AG44170, AG034676, UL1 TR000135 and the Mayo Foundation.

Abstract Background Limited research has focused on bloodstream infection (BSI) in patients with arterial grafts. This study aims to describe the incidence and outcomes of BSI after arterial aneurysm repair in a population-based cohort. Methods The expanded Rochester Epidemiology Project (e-REP) was used to analyze aneurysm repairs in adults (aged ≥18 years) residing in 8 counties in southern Minnesota from January 2010 to December 2020. Electronic records were reviewed for the first episode of BSI following aneurysm repair. BSI patients were assessed for vascular graft infection (VGI) and followed for all-cause mortality. Results During the study, 643 patients had 706 aneurysm repairs: 416 endovascular repairs (EVARs) and 290 open surgical repairs (OSRs). Forty-two patients developed BSI during follow-up. The 5-year cumulative incidence of BSI was 4.7% (95% confidence interval [CI], 3.0%–6.4%), with rates of 4.0% (95% CI, 1.8%–6.2%) in the EVAR group and 5.8% (95% CI, 2.9%–8.6%) in the OSR group (P = .052). Thirty-nine (92.9%) BSI cases were monomicrobial, 33 of which were evaluated for VGI. VGI was diagnosed in 30.3% (10/33), accounting for 50.0% (8/16) of gram-positive BSI cases compared to 11.8% (2/17) of gram-negative BSI cases (P = .017). The 1-, 3-, and 5-year cumulative post-BSI all-cause mortality rates were 22.2% (95% CI, 8.3%–34.0%), 55.8% (95% CI, 32.1%–71.2%), and 76.8% (95% CI, 44.3%–90.3%), respectively. Conclusions The incidence of BSI following aneurysm repair was overall low. VGI was more common with gram-positive compared to gram-negative BSI. All-cause mortality following BSI was high, which may be attributed to advanced age and significant comorbidities in our cohort.

Abstract Background The legality and use of marijuana is a controversial topic. With increased prevalence of usage, cannabis detection for legal, medical, and workforce drug testing is on the rise. LC-MS/MS quantification of delta 9-carboxy tetrahydrocannabinol (delta 9-THC-COOH) in urine is accepted as the standard to detect marijuana use. One challenge faced by testing laboratories has been identifying adulterated samples. Many products/reagents can be used to manipulate the urine to avoid positive drug testing results. In this study, we developed a dilute-and-shoot strategy to separate and quantify both the delta 8- and 9-THC-COOH in urine samples and tested the effects of adulteration using a combination of nitrite and/or acids which can be used to mask cannabinoid use. Methods Five authentic delta 8- and 9-THC-COOH positive specimens, and one spiked sample were treated with strong acids (1N HCL or 10% TCA), 500 µg/mL nitrite, or a combination. After hydrolysis with sodium hydroxide, the analytes were quantified using a 6495 Mass Spectrometer coupled to a StreamSelect LC system (Agilent). LC separation was performed with a CORTECS T3 column utilizing a shallow gradient. In addition, twelve urine specimens with varying concentrations of delta 8- and 9-THC-COOH were treated with nitrite and screened using a delta 9-THC-COOH immunoassay on the Roche Cobas C501 and analyzed by LC-MS/MS. Results Nitrite did not change the physical appearance or the pH of the urine samples. Strong acid treatment also did not alter the appearance but did drop the urine pH ≤2. Pre-treated specimens with 1N HCL, 10% TCA, or 500 µg/mL of nitrite did not affect the delta 8- and 9-THC-COOH concentrations up to 6 days (refrigerated); however, specimens treated with strong acid combined with 500 µg/mL of nitrite for 30 min made both analytes undetectable. Additional experiments confirmed that 0.5 and 1 mol/L of nitrite lowered the concentration of all analytes, including internal standard, to undetectable levels in 48 h. Twelve additional specimens were collected, 3 with delta 8-THC-COOH, 3 with delta 9-THC-COOH, and 6 with both. All 12 samples screened positive using the Roche immunoassay and were quantified using the LC-MS/MS method. After treatment with 0.5 mol/L of nitrite, 10 of the 12 samples were negative using the immunoassay, but 2 samples remained positive. However, all nitrite treated specimens were negative (&lt;LLOQ) using the LC-MS/MS method and the internal standard was eliminated. Later experiments confirmed that the delta 8- and 9-THC-COOH could be eliminated with as little as 0.1 mol/L nitrite for 30 min. Conclusion The unique dilute-and-shoot method can separate and quantify delta 8- and 9-THC-COOH. In addition, high concentrations of nitrite were shown to degrade both analytes along with the isotopically labeled internal standard. As a result, labs can distinguish true negative delta 8- and 9-THC-COOH (no analyte peaks) from nitrite adulterated specimens since the adulterated samples have no peaks for both the analytes and internal standard. A limitation of the study is that only sodium nitrite was tested. Other adulterants, such as potassium nitrite, pyridinium chlorochromate, peroxide etc. require further investigation.

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease (p = 0.002) and a foreign cardiovascular material (p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS (p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis, confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant.

Abstract Background Left ventricular assist devices (LVAD) have an associated infection rate of 13%–80% postimplant. An optimal strategy for surgical infection prophylaxis (SIP) at the time of implantation has not been well defined. We aimed to evaluate the different LVAD implantation antibiotic prophylaxis regimens as well as the incidence of LVAD infection at our institution. Methods We performed a single-center, retrospective study of patients who underwent LVAD implantation between February 2007 and June 2019. The primary outcome was the incidence of LVAD infection (LVADI), within 3 months and 1 year of placement, between patients who received expanded or narrow-spectrum regimens for SIP. We assessed outcomes using Kaplan-Meier, time-to-first event. We used a noninferiority analysis, which was established if the narrow-spectrum event rate was no more than 5% greater than the expanded-spectrum event rate. Results We included 399 patients, 305 (76.4%) patients received narrow-spectrum SIP, whereas the remaining 94 (23.6%) patients received the expanded-spectrum regimen. Statistical noninferiority of the narrow spectrum to the multiple drug regimen was demonstrated at both time points, and statistical superiority of the narrow-spectrum group across 12-month follow up was further evident (P = .037). Conclusions We report evidence supporting noninferiority, or even superiority, of the narrow-spectrum over expanded-spectrum antimicrobial prophylaxis strategy with respect to LVADI. These findings support data-driven antimicrobial prophylaxis strategies.

Abstract Background Cutibacterium acnes can cause spinal implant infections. However, little is known about the optimal medical management and outcomes of C. acnes spinal implant infections (CSII). Our study aims to describe the management of patients with CSII and evaluate the clinical outcomes. Methods We performed a retrospective cohort study of patients aged 18 years or older who underwent spinal fusion surgery with instrumentation between January 1, 2011, and December 31, 2020, and whose intraoperative cultures were positive for C. acnes. The primary outcome was treatment failure based on subsequent recurrence, infection with another organism, or unplanned surgery secondary to infection. Results There were 55 patients with a median follow-up (interquartile range) of 2 (1.2–2.0) years. Overall, there were 6 treatment failures over 85.8 total person-years, for an annual rate of 7.0% (95% CI, 2.6%–15.2%). Systemic antibiotic treatment was given to 74.5% (n = 41) of patients for a median duration of 352 days. In the subgroup treated with systemic antibiotics, there were 4 treatment failures (annual rate, 6.3%; 95% CI, 1.7%–16.2%), all of which occurred while on antibiotic therapy. Two failures occurred in the subgroup without antibiotic treatment (annual rate, 8.8%; 95% CI, 1.1%–31.8%). Conclusions Our study found that the estimated annual treatment failure rate was slightly higher among patients who did not receive antibiotics. Of the 6 failures observed, 4 had recurrence of C. acnes either on initial or subsequent treatment failures. More studies are warranted to determine the optimal duration of therapy for CSII.