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Abstract Background The opioid crisis and the increasing prevalence of multi-drug resistant organism (MDRO) infections pose a threat to public health. Opioid Use Disorder (OUD) patient are prone to MDRO colonization and infections, thus potentially leading to adverse outcomes during periods of critical illness. Understanding the prevalence and predictors of MDRO infections within this vulnerable population is critical to improving patient outcomes by optimizing interventions and treatment plans. Methods We conducted a retrospective, multicenter, cohort study to evaluate the prevalence of MDRO isolation among adults with OUD admitted to an intensive care unit (ICU) with an infection across four Mayo Clinic regions. Patients were classified to the MDRO cohort if an MDRO was isolated from standard cultures or rapid diagnostic testing within 48 hours of admission. We utilized descriptive statistics, univariate and multivariate least absolute shrinkage and selection operator (LASSO) regression analysis including random effect to account for site variability, to analyze demographic data, clinical characteristics, and outcomes. Results 790 critically ill adult OUD patients with infection-related admission were included in the study cohort. The prevalence of MDRO isolation was 22.5% (n=178), with MRSA being the predominant isolated MDRO. In LASSO regression analyses, we identified homelessness (OR: 1.79, p = 0.022), no Medications for OUD (MOUD) treatment (OR: 1.56, p=0.023), and positive Hepatitis C Virus (HCV) status (OR: 2.19, p = 0.012) as significant predictors for isolation of an MDRO. Intravenous (IV) antibiotic use in the preceding 90 days was also positively associated (OR: 1.04 per 24 hours, p = 0.007), alongside mental health disorders (OR: 2.03, p < 0.001) and diabetes (OR: 1.54, p = 0.023). Conclusion The high prevalence of MDRO isolation in critically ill OUD patients with infection is associated with complex social and clinical factors. Disclosures All Authors: No reported disclosures

Abstract Background Optimizing antimicrobial prescribing for urinary tract infections (UTI) represents an area of opportunity for ambulatory antimicrobial stewardship programs. A pre-populated, ambulatory antibiotic order panel for UTI was implemented in the Mayo Clinic Enterprise on 5/16/2022. The order panel provides antimicrobial regimens which align with both institutional and national treatment guidelines based on patient comorbidities, complicating factors, and beta-lactam allergy status. We aimed to assess the impact of panel use on antibiotic prescribing for complicated and uncomplicated cystitis in the ambulatory setting. Methods This retrospective review included ambulatory encounters from the Mayo Clinic Enterprise in 2022 and 2023. Eligible encounters were randomly selected and included those with a primary ICD-10 code of cystitis performed by primary care or urgent care clinicians. Encounters were excluded if patients had symptoms indicative of pyelonephritis, underwent urinary instrumentation within 30 days, or had a urinary pathogen isolated within 90 days. The primary outcome was concordance with institutional guidelines. Secondary outcomes included repeat healthcare contact and therapy duration. Outcomes were analyzed with Pearson's chi-squared and Wilcoxon rank sum tests (α level = 0.05). Results 793 encounters (397 panel vs. 396 non-panel) were included. Prescribing was guideline concordant in 79.3% and 64.9% (p< 0.001) of panel and non-panel encounters, respectively. Inappropriate duration was the most common reason for non-concordance in the panel use cohort. There was no difference between groups for repeat healthcare contact incidence. Antimicrobials prescribed differed between panel and no-panel groups (Table 1), with higher use of sulfamethoxazole/trimethoprim and lower use of cefdinir in the panel cohort. Numerically shorter durations were seen in the panel group, with more 3- and 5-day regimens than the no-panel group. Conclusion Use of a pre-populated antimicrobial order panel for outpatient cystitis encounters resulted in greater adherence to institutional guideline recommendations, particularly in terms of antimicrobial selection, without adversely impacting repeat healthcare contact. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|F2G: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support

Introduction Taxane medications, paclitaxel, and docetaxel, are chemotherapy agents that have a higher incidence of reported hypersensitivity and infusion reactions. To help classify these reactions, the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) is utilized. Prophylactic medications have been used to decrease the incidence and severity of these events. At our institution, medications that patients can receive prior to the initiation of a taxane infusion are a histamine 1 receptor antagonist (H1RA), histamine 2 receptor antagonist (H2RA), a steroid or a combination of these medications. The purpose of this retrospective review was to compare the rates and severity of infusion reactions based on the timing of prophylactic medication administration in the first and second doses of taxane infusions. Methods Patients who received paclitaxel or docetaxel from January 30 th , 2022, through January 30 th , 2023, were included in the analysis. To assist in the identification of a reaction, taxane administrations were flagged for review if a rescue medication was administered after the start of a paclitaxel or docetaxel infusion. The rates and severity of infusion reactions were analyzed based on the timing of prophylactic medication administration. A sub-group analysis comparing infusion reaction characteristics between taxanes given, was performed. Results Of the 1486 taxane infusions that were completed within the year, 249 infusion reactions were confirmed and graded utilizing the NCI CTCAE. When examining the first and second doses of a taxane (N = 536), we identified 222 infusions reactions. The odds of a patient having an infusion reaction, during the first and second doses, was found to be less likely for patients given a prophylactic medication 30 min prior to receiving a taxane compared to those who did not receive a pre-medication (p = 0.037). Conclusion This multisite retrospective study showed that administration of prophylactic medications 30 to 80 min prior to the first and second infusion of a taxane was the optimal timing to decrease the likelihood of patients having an infusion reaction. No difference in the severity of the reaction was seen. Most patients were able to complete the entire infusion, regardless of what rescue medications were used following the infusion reaction.

Background: The relative advantages and disadvantages of 2-stage versus 1-stage management of infection following total hip arthroplasty (THA) are the current subject of intense debate. To understand the merits of each approach, detailed information on the short and, importantly, longer-term outcomes of each must be known. The purpose of the present study was to assess the long-term results of 2-stage exchange arthroplasty following THA in one of the largest series to date. Methods: We identified 331 periprosthetic joint infections (PJIs) that had been treated with a 2-stage exchange arthroplasty between 1993 and 2021 at a single institution. Patients were excluded if they had had prior treatment for infection. The mean age at the time of reimplantation was 66 years, 38% of the patients were female, and the mean body mass index (BMI) was 30 kg/m 2 . The diagnosis of PJI was based on the 2011 Musculoskeletal Infection Society criteria. A competing-risk model accounting for death was utilized. The mean duration of follow-up was 8 years. Results: The cumulative incidence of reinfection was 7% at 1 year and 11% at 5 and 10 years. Factors predictive of reinfection included BMI ≥30 kg/m 2 (hazard ratio [HR] = 2; p = 0.049) and the need for a spacer exchange (HR = 3.2; p = 0.006). The cumulative incidence of any revision was 13% at 5 and 10 years. The cumulative incidence of aseptic revision was 3% at 1 year, 7% at 5 years, and 8% at 10 years. Dislocation occurred in 33 hips (11% at 10 years); 15 (45%) required revision. Factors predictive of dislocation were female sex (HR = 2; p = 0.047) and BMI <30 kg/m 2 (HR = 3; p = 0.02). The mean Harris hip score (HHS) improved from 54 to 75 at 10 years. Conclusions: In this series of 331 two-stage exchange arthroplasties that were performed for the treatment of infection, we found a low rate of aseptic revision (8%) and a low rate of reinfection (11%) at 10 years. These long-term mechanical and infection data must be kept in mind when considering a paradigm shift to 1-stage exchanges. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma and affects an estimated 1,500 people annually in the United States. DFSP frequently exhibits extensive local infiltration. Initial treatment is through surgical excision, and care should be taken to ensure that negative margins are achieved to minimize recurrence. Although DFSP has a reported high rate of recurrence, metastasis is more uncommon. Fibrosarcomatous DFSP is an aggressive variant with an increased risk for local recurrence and metastasis. If achieving negative margins or resection is not feasible, radiation therapy or systemic treatment are options that may be considered by a multidisciplinary team. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline recommended treatment options available for DFSP.

Abstract Background Clozapine is effective for treatment-resistant schizophrenia and bipolar disorder but is often discontinued due to adverse effects. This study compared early clozapine discontinuation rates and reasons in patients with mood and psychotic disorders. Methods Data from all individuals with mood or psychotic disorders who initiated clozapine for the first time at the inpatient psychiatric unit of Mayo Clinic, Rochester, Minnesota, between 2014 and 2022 were retrospectively analyzed. Early clozapine discontinuation, defined as discontinuation within 90 days of initiation, was the primary outcome. Cox proportional hazards regression was used to assess factors associated with discontinuation. Results Of 83 patients (mood group n = 37, psychosis group n = 46), those in the mood group were older (P = 0.022) and more likely to be nonsmokers (P = 0.034). The overall 90-day clozapine discontinuation rate was 45.7%. Early discontinuation was significantly higher in the mood group than in the psychosis group (hazard ratio = 2.41, 95% confidence interval = 1.26–4.64, P = 0.008). Other factors associated with early discontinuation were female sex (P = 0.033), older age (P = 0.026), and nonsmoking (P = 0.001). In multivariable analysis, smoking status was the only factor significantly inversely associated with early clozapine discontinuation (hazard ratio = 0.47, 95% confidence interval = 0.22–0.99, P = 0.048), while diagnostic group, sex, and age did not show significant associations (all P > 0.05). Discontinuations were primarily due to adverse drug reactions in both groups. Conclusions Nearly half of the patients discontinued clozapine early, with higher rates in the mood group. Studies should further explore potential pharmacodynamic and pharmacokinetic factors associated with discontinuation, including the influence of smoking. Careful monitoring and personalized management of side effects are crucial for optimizing clozapine therapy and improving treatment outcomes.

Importance There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN. Objective To present the long-term efficacy and safety of patisiran in adults with hATTR-PN. Design, Setting, and Participants This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE. Intervention Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years. Main Outcomes and Measures Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life–Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed. Results At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and –3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival. Conclusions and Relevance In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine. Trial Registration ClinicalTrials.gov Identifier: NCT02510261

AbstractBackgroundCerebral small vessel disease (SVD) related vascular contributions represent a major factor contributing to cognitive decline and dementia (VCID) in older adults. However, there has not been a validated biomarker for the diagnosis and treatment monitoring of this condition. Recently, the US National Institute on Neurological Disorders and Stroke (NINDS) funded the MarkVCID Consortium to identify and validate clinical‐trial‐ready biomarkers for VCID. Cerebrovascular reactivity (CVR) MRI is one of the selected biomarkers that underwent multi‐site testing in the Consortium. The present study aimed to report the relationship between CVR and cognitive function at independent sites, based on a pre‐specified hypothesis.MethodCVR, the ability of cerebral small vessels to dilate upon stimulus, is thought to directly reflect physiological function of the brain microvasculature. Based on previous single‐site findings, the pre‐defined hypothesis was that CVR will be associated with the global cognitive function measured by Montreal Cognitive Assessment (MoCA) after adjusting for age, sex, and education, and this association will be observed in data collected and analyzed at each individual site.A total of 264 older participants from three sites were included (Table 1). Each site performed an identical CVR MRI procedure using 5% CO2 inhalation, and a standardized clinical and cognitive evaluation. Multi‐linear regression analysis was conducted on a site‐by‐site basis to examine the pre‐defined hypothesis.ResultGray‐matter CVR showed a positive association with MoCA score after adjustment for age, sex, and education, in which participants with higher CVR had higher MoCA scores. This relationship was reproduced at each site (Figure 1, p<0.05 for each), confirming our pre‐specified hypothesis.In the secondary analysis of all data together, higher gray‐matter CVR was found to be significantly associated with better executive function measure of item response theory (IRT) score (β=2.87, p=0.003).ConclusionThe present study evaluated the relationship between CVR and cognition in a multi‐center setting. CVR was found to be positively associated with global cognitive function measured by the MoCA, which was shown to be reproducible across different sites with diverse cohorts. These findings support the utility of CVR as a biomarker in future clinical trials of SVD and VCID.

AimsThe purpose of this study was to directly compare the Modular Dual Mobility (MDM) Mobile Bearing Hip System (Stryker, USA) and large femoral heads (LFHs) in revision total hip arthroplasties (THAs) at mid-term follow-up, with specific emphasis on survival free of re-revision for dislocation, any re-revision, dislocation, and the risk of metal-related complications.MethodsWe identified 299 revision THAs performed at a single tertiary care academic institution from March 2011 to July 2014. Aseptic loosening of the acetabular component (n = 65), dislocation (n = 58), and reimplantation as part of a two-stage exchange protocol (n = 57) were the most common reasons for index revision. MDM constructs were used in 123 cases, and LFHs were used in 176 cases. Mean age was 66 years (28 to 93), mean BMI was 31 kg/m2 (18 to 55), and 45% (n = 136) were female. Mean follow-up was seven years (2 to 12).ResultsThe ten-year survival free of re-revision for dislocation was 99% (95% CI 95 to 100) in the MDM cohort and 91% (95% CI 84 to 96) in the LFH cohort, with a significantly increased risk of re-revision for dislocation in the LFH cohort (HR 7.1 (95% CI 1.3 to 40.8); p = 0.023). The ten-year survival free of any re-revision was 92% (95% CI 82 to 99%) in the MDM cohort and 84% (95% CI 74 to 90) in the LFH cohort with a significantly increased risk of any re-revision in the LFH cohort (HR 2.6 (95% CI 1.1 to 5.9); p = 0.024). The ten-year survival free of any dislocation was 95% (95% CI 85 to 99) in the MDM cohort and 87% (95% CI 78 to 92) in the LFH cohort with a significantly increased risk of any dislocation in the LFH cohort (HR 2.7 (95% CI 1.1 to 6.3); p = 0.028). There were no re-revisions or reoperations for metallosis or corrosion in the MDM cohort.ConclusionIn this head-to-head comparison, revision THAs with a MDM construct safely and effectively lowered the risk of re-revision for dislocation, any re-revision, and any dislocation compared to LFH at mid-term follow-up. There were no re-revisions or reoperations for metallosis or corrosion in the MDM cohort.Cite this article: Bone Joint J 2025;107-B(1):58–64.