University Pathologists

Infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC) are associated with high mortality rates and limited treatment options. This study aims to evaluate the in vitro activity of clinically utilized antimicrobials against a contemporary collection of ABC isolates with a predominant carbapenem-resistant phenotype. Geographically dispersed US medical centers (n = 22) provided non-duplicate respiratory and bloodstream ABC isolates for surveillance testing. Antimicrobial susceptibility testing was conducted by broth microdilution and interpreted according to Clinical & Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) breakpoints. ABC isolates (n = 523) from respiratory tract (74.4%) and blood (25.6%) sources were recovered from patients (2023-2024). Forty percent were obtained from intensive care unit patients. Carbapenem non-susceptibility was observed in 76.9% of isolates and was more common among respiratory tract cultures. The addition of durlobactam to sulbactam decreased the MIC90 by three-doubling dilutions from 32 to 4 µg/mL, increasing the susceptibility rate to 96.9% from 33.8%. Genome sequencing of sulbactam-durlobactam non-susceptible isolates (16/523; n = 3.1%) revealed MBL and non-enzymatic resistance mechanisms. Cefiderocol inhibited 93.5% and 76.1% of isolates at CLSI and FDA susceptible breakpoints, respectively. Minocycline susceptibility was <50%, while tigecycline and eravacycline MIC50/90 were 1/2 and 0.5/1 µg/mL, respectively. Sulbactam-durlobactam displayed high activity against sulbactam (95.4%), carbapenem (96.3%), and cefiderocol (95.2%) non-susceptible isolates. Susceptibility rates of clinically utilized antimicrobials against a US collection of ABC isolates ranged from 23% to 97%, with meropenem displaying the lowest rate and sulbactam-durlobactam demonstrating the highest overall rate. Sulbactam-durlobactam activity was preserved against sulbactam, carbapenem, and cefiderocol non-susceptible isolates among respiratory tract and bloodstream isolates.

Our study addresses a significant issue in the medical and scientific community-the delayed administration of appropriate antimicrobial treatments due to the time-consuming process of phenotypic susceptibility data collection in gram-negative bloodstream infections. Our research indicates that a multiplex PCR rapid diagnostic test (RDT) significantly outperformed two clinical scoring tools in predicting ceftriaxone susceptibility. Multiplex PCR also led to reduced instances of undertreatment with ceftriaxone and minimized overtreatment with carbapenems. Furthermore, multiplex PCR demonstrated high sensitivity and specificity in predicting ceftriaxone susceptibility. The results of our study underscore the potential RDTs to reduce the time to appropriate antimicrobial therapy, leading to improved patient outcomes and reduced healthcare costs.

An intention-to-treat, double-blind, randomized, controlled, clinical trial comparing three treatment arms of ASA 81, 325, and 500 mg daily dosed for 14 days were evenly randomized across the dosing categories to measure the impact of dosing by body mass index (BMI) (20-24.9, 25-29.9, ≥30 kg/m2 ) on ASA anti-platelet effects. University Ambulatory Clinic. Healthy volunteers defined as individuals who were medication free without acute or chronic significant health problems. Change in ASA reactivity unit (ARU), salicylate levels, and thromboxane B2 (TxB2) levels were measured across BMI dosing categories and time. MAINRESULTS: Fifty-four participants with a mean (±SD) age of 34.4 ± 10.9 years (M:F; 23:31) completed the study. Baseline ARU and TxB2 levels were not significantly different between obese and non-obese individuals. BMI was not a predictor of platelet inhibition. There was no interaction between gender and platelet activation at baseline or following ASA treatment. ASA 81 mg was associated with a lower ARU response (approximate 50% lower response) than either the 325-mg or the 500-mg doses of ASA. TxB2 and salicylate levels exhibited lower trends at 81 mg compared with higher doses. In healthy male and female participants administered ASA for 14 days, obesity is not associated with increased basal platelet activation or ASA resistance. ASA 81 mg was significantly less effective in reducing platelet aggregation compared with ASA 325 and 500 mg, independent of BMI.

Congenital self-healing reticulohistiocytosis of Hashimoto and Pritzker (CSHR), a form of Langerhans Cell Histiocytosis (LCH), is a rare benign proliferative disorder that typically self-resolves at 6 months. We present an atypical case of CSHR with first onset at 10 months of age which showed histologic features of LCH.

254 Background: Quality improvement (QI) in cancer care delivery requires understanding the setting, clearly defining problem(s), and identifying targeted solutions. The Association of Community Cancer Centers (ACCC) conducted a national project to identify and provide guidance on key issues in care for patients with stage III/IV non-small cell lung cancer (NSCLC). We report the problems and solutions identified after a mixed-methods baseline data evaluation. Methods: The multi-phase ACCC QI initiative was guided by an expert steering committee. A request for applications was advertised to all ACCC programs, with committee members ranking each site in pre-specified categories (ex., replicability, practice champion engagement). After selection of sites, baseline data assessed programs’ patient populations, current care delivery practices, processes of care, and biomarker testing rates. A full-day workshop was conducted with multidisciplinary team members and expert faculty to review baseline data, refine problem statements, and identify site-specific QI solutions. Results: The 6 participating US sites were regionally diverse with a rural/urban mix. In baseline data, median patient ages were 65-72 years and patients treated were 50% stage III/50% stage IV. Biomarker testing practices, use of multidisciplinary tumor board, and clinical care pathways varied across sites. Five key QI areas were identified: 1.Management of immune related adverse events (irAE), 2.Biomarker testing, 3.Emergency visit management (EVM), 4.Access to clinical trials, and 5.Smoking cessation. Two sites identified problems with irAE management during immunotherapy (IT). The first identified needs for proactive symptom identification, assessment, and management. Solutions included: 1. a patient questionnaire to identify early signs of irAEs and 2. pilot testing a nurse-administered questionnaire. A second site identified that front-line clinicians may not be properly identifying possible irAEs. Solutions included: 1. form an IT toxicity working group and 2. educate front-line clinicians about irAEs. Two sites focused on biomarker testing. The first problem identified was inefficient tracking of testing results. Solutions were: 1. assign a nurse navigator to track, enter, and communicate test results and 2. proactively coordinate appointments for patients with positive test results. The second site identified delayed care when inadequate tissue was obtained. Solutions included: 1. pathology-driven reflex testing and 2. liquid biopsy order at diagnosis. Similar problems/solutions were developed for EVM, clinical trial access, and smoking cessation. Conclusions: Challenges in lung cancer care delivery can be identified and addressed using an intentional QI approach. Clearly defining the problem and identifying potential solution(s) are critical steps and should occur before implementation.

Skin cancer remains the most commonly diagnosed cancer in the USA with more than 1 million new cases each year. Melanomas account for about 1% of all skin cancers and most skin cancer deaths. Multiethnic individuals whose skin is pigmented underestimate their risk for skin cancers and melanomas and may delay seeking a diagnosis. The use of artificial intelligence may help improve the diagnostic precision of dermatologists/physicians to identify malignant lesions. To validate our artificial intelligence's efficiency in distinguishing between images, we utilized 50 images obtained from our International Skin Imaging Collaboration dataset (n = 25) and pathologically confirmed lesions (n = 25). We compared the ability of our artificial intelligence to visually diagnose these 50 skin cancer lesions with a panel of three dermatologists. The artificial intelligence model better differentiated between melanoma vs. nonmelanoma with an area under the curve of 0.948. The three-panel member dermatologists correctly diagnosed a similar number of images (n = 35) as the artificial intelligence program (n = 34). Fleiss' kappa (ĸ) score for the raters and artificial intelligence indicated fair (0.247) agreement. However, the combined result of the dermatologists panel with the artificial intelligence assessments correctly identified 100% of the images from the test data set. Our artificial intelligence platform was able to utilize visual images to discriminate melanoma from nonmelanoma, using de-identified images. The combined results of the artificial intelligence with those of the dermatologists support the use of artificial intelligence as an efficient lesion assessment strategy to reduce time and expense in diagnoses to reduce delays in treatment.