Citations

ABSTRACT Chronic wound infections can be difficult to treat and may lead to impaired healing and worsened patient outcomes. Novel treatment strategies are needed. This study evaluated the effects of intermittently produced hydrogen peroxide (H 2 O 2 ) and hypochlorous acid (HOCl), generated via an electrochemical bandage (e-bandage), against methicillin-resistant Staphylococcus aureus biofilms in an agar membrane biofilm model. By changing the working electrode potential, the e-bandage generated either HOCl (1.5 V Ag/AgCl ) or H 2 O 2 (−0.6 V Ag/AgCl ). The degree of biocidal activity of intermittent treatment with HOCl and H 2 O 2 correlated with HOCl treatment time; HOCl treatment durations of 0, 1.5, 3, 4.5, and 6 hours (with the rest of the 6-hour total treatment time devoted to H 2 O 2 generation) resulted in mean biofilm reductions of 1.36 ± 0.2, 2.22 ± 0.16, 3.46 ± 0.38, 4.63 ± 0.74, and 7.66 ± 0.5 log CFU/cm 2 , respectively, vs. non-polarized controls, respectively. However, application of H 2 O 2 immediately after HOCl treatment was detrimental to biofilm removal. For example, 3 hours HOCl treatment followed by 3 hours H 2 O 2 resulted in a 1.90 ± 0.84 log CFU/cm 2 lower mean biofilm reduction than 3 hours HOCl treatment followed by 3 hours non-polarization. HOCl generated over 3 hours exhibited biocidal activity for at least 7.5 hours after e-bandage operation ceased; 3 hours of HOCl generation followed by 7.5 hours of non-polarization resulted in a biofilm cell reduction of 7.92 ± 0.12 log CFU/cm 2 vs. non-polarized controls. Finally, intermittent treatment with HOCl (i.e., interspersed with periods of e-bandage non-polarization) for various intervals showed similar effects (approximately 6 log CFU/cm 2 reduction vs. non-polarized control) to continuous treatment with HOCl for 3 hours, followed by 3 hours of non-polarization. These findings suggest that timing and sequencing of HOCl and H 2 O 2 treatments are crucial for maximizing biofilm control when using an e-bandage strategy.

Abstract Introduction Geriatric emergency department (ED) guidelines emphasize timely identification of delirium. This article updates previous diagnostic accuracy systematic reviews of history, physical examination, laboratory testing, and ED screening instruments for the diagnosis of delirium as well as test–treatment thresholds for ED delirium screening. Methods We conducted a systematic review to quantify the diagnostic accuracy of approaches to identify delirium. Studies were included if they described adults aged 60 or older evaluated in the ED setting with an index test for delirium compared with an acceptable criterion standard for delirium. Data were extracted and studies were reviewed for risk of bias. When appropriate, we conducted a meta‐analysis and estimated delirium screening thresholds. Results Full‐text review was performed on 55 studies and 27 were included in the current analysis. No studies were identified exploring the accuracy of findings on history or laboratory analysis. While two studies reported clinicians accurately rule in delirium, clinician gestalt is inadequate to rule out delirium. We report meta‐analysis on three studies that quantified the accuracy of the 4 A's Test (4AT) to rule in (pooled positive likelihood ratio [LR+] 7.5, 95% confidence interval [CI] 2.7–20.7) and rule out (pooled negative likelihood ratio [LR−] 0.18, 95% CI 0.09–0.34) delirium. We also conducted meta‐analysis of two studies that quantified the accuracy of the Abbreviated Mental Test‐4 (AMT‐4) and found that the pooled LR+ (4.3, 95% CI 2.4–7.8) was lower than that observed for the 4AT, but the pooled LR− (0.22, 95% CI 0.05–1) was similar. Based on one study the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU) is the superior instrument to rule in delirium. The calculated test threshold is 2% and the treatment threshold is 11%. Conclusions The quantitative accuracy of history and physical examination to identify ED delirium is virtually unexplored. The 4AT has the largest quantity of ED‐based research. Other screening instruments may more accurately rule in or rule out delirium. If the goal is to rule in delirium then the CAM‐ICU or brief CAM or modified CAM for the ED are superior instruments, although the accuracy of these screening tools are based on single‐center studies. To rule out delirium, the Delirium Triage Screen is superior based on one single‐center study.

AbstractBackgroundDespite the overall safety and efficacy of COVID‐19 vaccinations, rare cases of systemic autoimmune diseases (SAIDs) have been reported post‐vaccination. This study used a global survey to analyze SAIDs in susceptible individuals' post‐vaccination.MethodsA cross‐sectional study was conducted among participants with self‐reported new‐onset SAIDs using the COVID‐19 Vaccination in Autoimmune Diseases (COVAD) 2 study dataset—a validated, patient‐reported e‐survey—to analyze the long‐term safety of COVID‐19 vaccines. Baseline characteristics of patients with new‐onset SAIDs and vaccinated healthy controls (HCs) were compared after propensity score matching based on age and sex in a 1:4 ratio.ResultsOf 16 750 individuals, 74 (median age 52 years, 79.9% females, and 76.7% Caucasians) had new‐onset SAID post‐vaccination, mainly idiopathic inflammatory myopathies (IIMs) (n = 23, 31.51%), arthritis (n = 15; 20.53%), and polymyalgia rheumatica (PMR) (n = 12, 16.40%). Higher odds of new‐onset SAIDs were noted among Caucasians (OR = 5.3; 95% CI = 2.9–9.7; p < .001) and Moderna vaccine recipients (OR = 2.7; 95% CI = 1.3–5.3; p = .004). New‐onset SAIDs were associated with AID multimorbidity (OR = 1.4; 95% CI = 1.1–1.7; p < .001), mental health disorders (OR = 1.6; 95% CI = 1.3–1.9; p < .001), and mixed race (OR = 2.2; 95% CI = 1.2–4.2; p = .010), where those aged >60 years (OR = 0.6; 95% CI = 0.4–0.8; p = .007) and from high/medium human development index (HDI) countries (compared to very high HDI) reported fewer events than HCs.ConclusionThis study reports a low occurrence of new‐onset SAIDs following COVID‐19 vaccination, primarily IIMs, PMR, and inflammatory arthritis. Identified risk factors included pre‐existing AID multimorbidity, mental health diseases, and mixed race. Revaccination was well tolerated by most patients; therefore, we recommend continuing COVID‐19 vaccination in the general population. However, long‐term studies are needed to understand the autoimmune phenomena arising post‐vaccination.

Abstract Background: Breast Cancer (BC) incidence and the distribution of BC risk factors vary between racial and ethnic groups within the United States. It has been demonstrated that providing education on individualized breast cancer risk will improve patient uptake to recommended BC screening and prevention strategies. Most clinical risk assessment tools, including the validated IBIS model were derived from data using non-Hispanic white women. Consortia have also now identified over 300 common genetic susceptibility loci for BC, summarized by the polygenic risk score (PRS). When combined with clinical risk assessment tools, such as the IBIS or BCRAT models, the PRS can further refine risk estimation for patients. To date, most studies on the use of PRS have been done in non-Hispanic white women. While these PRS still perform well in racial minorities, there has been a recognized need to improve racial and ethnic diversity in genomic research cohorts. Herein, we aim to combine clinical risk assessment models that are already used in routine clinical practice with information derived from PRS testing in women of racial minorities to determine if this can improve risk estimation, patient understanding, and uptake to recommended breast cancer screening and prevention strategies. Design: This is a minimal risk prospective study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the information provided by the PRS influenced patient decisions regarding recommended BC screening and prevention. Patients will have IBIS and BCRAT risks calculated at baseline visit. A survey of patient perceptions/understanding of risk, intention to undergo screening, and use of preventive medicine is completed after baseline visit prior to receiving the PRS results. Blood sample is obtained at baseline and DNA samples are analyzed for approximately 300 SNPs on a custom-designed, targeted SNP panel from ThermoFisher Scientific by the Mayo Clinic Genomics Laboratory. This PRS result is then combined with the clinical risk assessments (IBIS and BCRAT scores) using the R package Individualized Coherent Absolute Risk Estimators (iCare) tool to provide a new estimate of breast cancer risk for 5year, 10year, and lifetime risk. Patients are seen for follow-up to review results and then complete a second survey to assess their understanding of the results, BC risk, and how the PRS impacted their decision to undergo screening/prevention strategies. Eligibility Criteria: Women who self-identify as African American/Black or Hispanic/Latinx between 30-75 years old with any of the following: 1.)IBIS score of ≥5% for the 10 year risk OR BCRAT score of ≥ 3 % for the 5 year risk. 2.) History of biopsy proven atypical hyperplasia 3.) History of biopsy proven lobular carcinoma in situ. Specific Aims: Aim 1: The primary aim of this study is to explore if the addition of PRS to the BCRAT and IBIS score will improve intentions to undergo recommended breast cancer screening strategies such as mammography, MRI, or molecular breast imaging in women of underserved racial minorities Aim 2: To explore if the addition of the PRS to the BCRAT and IBIS risk score will aid women of racial minorities in deciding whether to take preventative endocrine therapy. Aim 3: To understand how individualized risk assessment and information on PRS may alter perceived risk of breast cancer. Statistical Methods Analysis will be mostly descriptive. Continuous variables will be summarized as mean (standard deviation) or median (range) and categorical variables will be reported as frequency (percentage). Kaplan-Meier method will be used to estimate the long-term cumulative risk of cancer. Current Accrual: 3. Target Accrual: 50 Citation Format: Lauren Cornell, Sandhya Pruthi, Linda Hasadsri, Sarah McLaughlin. Genetic risk estimation in breast cancer and assessing health disparities [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-02.

Abstract Background: Patients with HER2+ early breast cancer (EBC) and invasive residual disease (RD) after neoadjuvant therapy (NAT) have a higher risk of relapse than patients who have a pathologic complete response (pCR). Escalation of therapy in patients with RD using post-neoadjuvant T-DM1 has become the new standard of care, leading to improved invasive disease-free survival (iDFS), but patients with estrogen receptor (ER)-negative or nodal RD have suboptimal outcomes, and central nervous system recurrences are a challenge. More effective treatment strategies are urgently needed. Alliance A011801 (CompassHER2 RD) is an escalation trial for patients with high-risk HER2+ RD after neoadjuvant systemic therapy, evaluating the addition of the HER2 selective tyrosine kinase inhibitor (TKI) tucatinib to post-neoadjuvant T-DM1. Methods: Eligibility and Intervention: Patients with high-risk HER2+ RD (i.e., ER-, node-positive, or both) after a predefined course of neoadjuvant HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 + placebo, vs. T-DM1 and tucatinib with adjuvant RT +/- ET. Eligibility criteria include completion of ≥ 6 cycles of NAT, including ≥ 9 weeks of paclitaxel and trastuzumab +/- pertuzumab. All chemotherapy (CT) must be completed preoperatively unless participating in EA1181 (~15-30% will be participants in the CompassHER2 pCR de-escalation companion trial [NCT04266249]; these patients must receive postoperative CT to complete ≥ 6 cycles prior to enrollment on A011801). Patients who received prior HER2-targeted TKIs or antibody-drug conjugates are ineligible. Objectives: The primary objective is to determine if iDFS is improved with addition of tucatinib to T-DM1 in patients with HER2+ EBC with RD after neoadjuvant systemic therapy; secondary endpoints include overall survival, breast cancer free survival, distant recurrence-free survival, brain metastases-free survival and disease-free survival. Correlative objectives include the association of i) tumor infiltrating lymphocyte (TILs) levels in the primary tumor and RD with iDFS, ii) TILs with tucatinib benefit, iii) iDFS and circulating tumor cells (CTC) at serial timepoints and iv) the magnitude of benefit of tucatinib (iDFS) in patients with/without detectable pretreatment CTCs. Quality of life and pharmacokinetic endpoints are also being evaluated. Statistics: A011801 is a prospective, double-blind, randomized, phase III superiority trial; stratified by i) receipt of postoperative CT (Y/N), ii) hormone receptor-status (+/-), and iii) pathologic lymph node status (+/-). The study targets an absolute difference of 5% in iDFS (control vs. experimental arm 82% & 87%, HR = 0.7), with a two-sided alpha of 0.05 and power of 80%. The sample size is 981; target accrual = 1031 patients; activation and estimated completion dates are 01/6/21 and ~ 01/2028. Accrual as of 7/10/2023: 438 patients. Support: U10CA180821, U10CA180882; Seagen Inc; https://acknowledgments.alliancefound.org. ClinicalTrials.gov Identifier: NCT04457596 Citation Format: Ciara O'Sullivan, Karla Ballman, Linda McCall, Tyler Zemla, Anna Weiss, Melissa Mitchell, Victoria Blinder, Nadine Tung, William Irvin, Myounghee Lee, Sailaja Kamaraju, Matthew Goetz, W. Fraser Symmans, Virginia Borges, Ian Krop, Ann Partridge, Lisa Carey. A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-11.

Background/Hypothesis: Women have higher morbidity and mortality associated with CABG procedures than men. The extent intra-operative red blood cell (RBC) transfusions contribute to gender differences in surgical outcomes is not established. We hypothesized that women are at increased risk for RBC transfusions due to lower pre-op hematocrit (Hct) and blood volume, but that other factors may also contribute. Methods: Consecutive, non-reoperative CABG procedures from 189 institutions (2012 -2015) were reviewed. Gender differences and odds ratios for intra-operative transfusion were evaluated with logistic regression models adjusting for age, blood volume (Nadler formula-to normalize for height and weight), procedure acuity, net extracorporeal circuit prime volume, use of retrograde autologous priming, first Hct in OR, nadir Hct on cardiopulmonary bypass (CPB), volume added on CPB, ultra-filtration volume, urine output on CPB, and procedure duration. Results: Among 54,122 patients (25.3% female), 21.9% (n=11,901) received a RBC transfusion. Compared to men, female patients were older (66 yrs vs. 64 yrs, p<.001), had lower blood volumes (4.3L vs. 5.6L, p<.001), and lower pre-op Hct (32.9% vs. 37.2%, p<.001). Transfusion rates were 3-fold higher in women vs. men (45.1% vs 13.7%, p<.001). Even after adjustment for independent predictors of intra-operative transfusion, women remained at increased risk vs men (OR = 1.3, 95% CI = 1.2 -1.4). No gender differences in transfusion rates were observed for Hct 21%-23% (Figure). Conclusions: Women have an increased risk of intra-operative RBC transfusion vs men. After adjusting for height and weight, much of this risk is due to gender differences in pre-op Hct and blood volume, however a residual significant risk remained after adjustment. Perfusion strategies aimed at gender differences may minimize unnecessary transfusions. Future study on the impact of gender on transfusion practice in cardiac surgery is warranted.