Citations

Accurate information regarding oxalate levels in foods is essential for managing patients with hyperoxaluria, oxalate nephropathy, or those susceptible to calcium oxalate stones. This study aimed to assess the reliability of chatbots in categorizing foods based on their oxalate content. We assessed the accuracy of ChatGPT-3.5, ChatGPT-4, Bard AI, and Bing Chat to classify dietary oxalate content per serving into low (<5 mg), moderate (5–8 mg), and high (>8 mg) oxalate content categories. A total of 539 food items were processed through each chatbot. The accuracy was compared between chatbots and stratified by dietary oxalate content categories. Bard AI had the highest accuracy of 84%, followed by Bing (60%), GPT-4 (52%), and GPT-3.5 (49%) (p < 0.001). There was a significant pairwise difference between chatbots, except between GPT-4 and GPT-3.5 (p = 0.30). The accuracy of all the chatbots decreased with a higher degree of dietary oxalate content categories but Bard remained having the highest accuracy, regardless of dietary oxalate content categories. There was considerable variation in the accuracy of AI chatbots for classifying dietary oxalate content. Bard AI consistently showed the highest accuracy, followed by Bing Chat, GPT-4, and GPT-3.5. These results underline the potential of AI in dietary management for at-risk patient groups and the need for enhancements in chatbot algorithms for clinical accuracy.

AbstractBackgroundPlasma biomarkers such as Aβ 42/40 have emerged as important tools to detect dementia risk, although whether plasma Aβ 42/40 levels and the associations with dementia risk differ by race is unclear. As part of the Health, Aging, and Body Composition study, we compared the plasma levels of Aβ 42/40 ratio and the associations with 15‐year dementia risk by race among community‐dwelling Black and White older adults.MethodsWe studied 997 dementia‐free participants (55% women, 54% Blacks) aged 70‐79 years (mean age 74.5±2.9) enrolled at baseline (1997‐98). We defined incidence dementia over 15 years based on hospital records, prescription for dementia medication, or a decline ≥1.5 standard deviations in the Modified Mini‐Mental State Examination score. Stored plasma obtained one year after baseline was used to measure Aβ with Innogenetics INNO‐BIA assays at Mayo Clinic, Jacksonville, FL. Plasma Aβ42/40 ratio was categorized into low, medium, and high tertiles. We used linear regression to estimate the difference in log‐transformed Aβ42/40 in Black and White participants and back‐transformed the effect estimates. We assess the association between Aβ42/40 (by tertiles) and dementia risk using Cox proportional hazards model stratified by race. All models were adjusted for age, sex, hypertension, diabetes, high cholesterol, and obesity, and we tested for interactions by race.ResultsBlack participants had significantly lower Aβ42/40 than White participants (‐4.4%, 95% CI ‐8.1% to ‐0.6%). In stratified analysis, lower Aβ42/40 was significantly associated with an increased risk of incident dementia among Black participants: 27.8% in medium (hazard ratio [HR] 1.69, 95% CI 1.07 to 2.68) and 33.5% in low (HR 2.07, 95% CI 1.32 to 3.24) compared with 17.3% in high Aβ42/40 tertile. The associations were somewhat weaker but showed the same trend among White participants: 20.3% in medium (HR 1.49, 95% CI 0.85 to 2.61) and 22.9% in low (HR 1.59, 95% CI 0.92 to 2.76) compared with 15% in high Aβ42/40 tertile. The interaction between Aβ42/40 and race was not statistically significant.ConclusionAmong community‐dwelling, non‐demented older adults, plasma Aβ42/40 differs by race, although the association with dementia risk does not differ by race.

Mucin-1 (MUC1) is a highly relevant antigen for cancer vaccination due to its overexpression and hypo-glycosylation in a high percentage of carcinomas. To enhance the immune response to MUC1, our group has developed C3-liposomes that encapsulate the MUC1 antigen along with immunostimulatory compounds for direct delivery to antigen-presenting cells (APCs). C3-liposomes bind complement C3, which interacts with C3-receptors on APCs, resulting in liposomal uptake and the delivery of tumor antigens to APCs in a manner that mimics pathogenic uptake. In this study, MUC1 and Toll-like receptor (TLR) agonists were encapsulated in C3-liposomes to provoke an immune response in transgenic mice tolerant to MUC1. The immune response to the C3-bound MUC1 liposomal vaccine was assessed by ELISA, ELISpot, and flow cytometry. Co-administering TLR 7/8 agonists with MUC1 encapsulated in C3-liposomes resulted in a significant antibody response compared to non-encapsulated MUC1. This antibody response was significantly higher in females than in males. The co-encapsulation of three TLR agonists with MUC1 in C3-liposomes significantly increased antibody responses and eliminated sex-based differences. Furthermore, this immunization strategy resulted in a significantly increased T cell-response compared to other treatment groups. In conclusion, the co-delivery of MUC1 and TLR agonists via C3-liposomes greatly enhances the immune response to MUC1, highlighting its potential for antigen-specific cancer immunotherapy.

AbstractRationaleExisting literature describing differences in survival following percutaneous coronary intervention (PCI) by patient sex, race‐ethnicity and the role of socioeconomic characteristics (SEC) is limited.Aims and ObjectivesEvaluate differences in 1‐year survival after PCI by sex and race‐ethnicity, and explore the contribution of SEC to observed differences.MethodsUsing a 20% sample of Medicare claims data for beneficiaries aged 65+, we identified fee‐for‐service patients who received PCI from 2007 to 2015. We performed logistic regression to assess how sex and race‐ethnicity relate to procedural indication, inpatient versus outpatient setting, and 1‐year mortality. We evaluated whether these relationships are moderated by sequentially controlling for factors including age, comorbidities, presence of acute myocardial infarction (AMI), county SEC, medical resource availability and inpatient versus outpatient procedural status.ResultsWe identified 300,491 PCI procedures, of which 94,863 (31.6%) were outpatient. There was a significant transition to outpatient PCI during the study period, especially for men compared with women and White patients compared with Black patients. Black patients were 3.50 percentage points (p < 0.001) and women were 3.41 percentage points (p < 0.001) more likely than White and male patients to undergo PCI at the time of AMI, which typically occurs in the inpatient setting. Controlling for age and calendar year, Black patients were 2.87 percentage points more likely than non‐Hispanic White patients to die within 1 year after PCI. After controlling for Black–White differences in comorbidities, the differences in 1‐year mortality decreased to 0.95 percentage points, which then became nonsignificant when further controlling for county resources and state of residence.ConclusionWomen were more likely to experience PCI in the setting of AMI and had less transition to outpatient care during the period. Black patients experienced higher 1‐year mortality following PCI, which is explained by differences in baseline comorbidities, county medical resources, and state of residence.

Introduction: Use of validated risk stratification tools for work up of suspected pulmonary embolism (PE) is an endorsed recommendation of the American Society of Hematology and the American College of Emergency Physicians. Due to variations in clinical practice, electronic health record (EHR) systems, and medical provider trainings, the use, documentation, and implementation of these tools vary widely. Current processes do not allow for electronic capture and quality reporting at most institutions. Methods: We sought to design and implement clinical pre-test probability (PTP) tools at three large healthcare institutions for use in emergency departments (ED). At each site, a hematologist partnered with ED physician leadership and local information technology experts to design and implement PTP tools in clinical workflows. Overall, 38 EDs (high volume tertiary EDs and smaller regional EDs) located in the United States along the East Coast and Midwest regions were involved. A major goal of implementation was integration into clinical workflow and automatic documentation. After design and implementation, awareness and education of the new EHR tool was distributed electronically to ED providers. After implementation, use of PTP tools was analyzed between September 12, 2022 and January 11, 2023. PTP use was examined as percent of visits for which patients underwent CT pulmonary angiography (CTPA). Results: Each institution chose the 3 tier Wells' Score for implementation while one site designed an integrated Wells'/PERC or YEARS score calculator. Two sites implemented the tool as an optional flowsheet and one site implemented the tool as mandatory parameters within the orders for PE imaging studies. The mandatory tool could be bypassed with prespecified selections or if a D-dimer existed within 48 hours . Complete details of the site-specific implementation are shown in Table 1. Over the 4-month evaluation timeframe, there was a total of 270,214 ED encounters. Uptake and utilization of the PTP tools are shown in Table 2. Use of PTP was highest at the site with forced PTP documentation which ranged from 49-53% of ordered CTPAs, compared to Site 2 where use was 2-3%, and Site 1 where use ranged from 1-3%. At Site 1, use of PTP increased slightly over the study period with signs that PE yield on imaging was increasing as well (3.4% to 5.9%). At Site 2, PE yield on imaging was overall high (9-10%), and remained similar with similar use of PTP tools over the study period. Use of PTP and PE yield (6-8%) on imaging also remained similar throughout the study at Site 3. Conclusion: Forced use of PTP within the orders for CTPA led to the highest use of PTP (Site 3) but this did not result in meaningfully higher PE yield on CTPA compared to the other sites. PE yield at each site was at or above the 5% yield for PE on CTPA which has been previously reported. Given that PTP uptake was relatively stable over the measurement period at Site 2 and 3, this indicates the process had mostly stabilized and that other strategies are needed to improve uptake of PTP, reduce utilization of CTPA, and further increase yield on CTPA. Increasing PTP use and rising PE yield at Site 1 demonstrated ongoing potential for improvements past this study timeframe.

While the cure rate of pediatric acute lymphoblastic leukemia (ALL) now exceeds ~90% with contemporary combination chemotherapy, the prognosis for adults with ALL remains significantly inferior with long-term overall survival ranging from 50% to 70%. Recent studies have uncovered marked differences in ALL genomics between children and adults, with some high-risk subtypes becoming more prevalent with age. However, the underlying biology of age-related disparities in ALL is not fully understood, especially with regard to differences in leukemia sensitivity to chemotherapy. To address this knowledge gap, we performed ex vivo drug sensitivity profiling (i.e., pharmacotyping) of 21 anti-leukemia agents on primary B-ALL diagnostic samples from 767 pediatric (age, 0-18 years) and 309 adult (19-84 years) patients. Drug sensitivity was measured as LC 50: the concentration of drug required to kill 50% of the leukemia cells (PMID: 36604538). A total of 7,975 unique LC 50 values were experimentally determined. RNA-seq was used for subtype classification and gene expression analysis. Among 21 drugs, seven showed significant differences in overall LC 50 between children and adults ( P&lt;0.05 after Bonferroni correction): children displayed higher sensitivity to asparaginase, prednisolone, mercaptopurine, daunorubicin, and inotuzumab, while adults showed higher sensitivity to dasatinib and nelarabine. In multivariate models adjusting for 23 ALL molecular subtypes, only mercaptopurine remained significantly associated with age ( P=1.5×10 -5), suggesting that age-related differences in drug sensitivity can be primarily attributed to the variation in ALL subtypes between children and adults. For mercaptopurine, within KMT2A, CRLF2, and DUX4 subtypes, pediatric samples consistently showed a lower LC 50 than adults carrying the same genomic abnormality ( P=0.032, 0.0045, and 0.02, respectively). To explore intra-subtype heterogeneity, we performed unsupervised clustering using gene expression data for each of these three subtypes. Remarkably, within each of these subtypes, we identified two clusters with distinct transcriptomic profiles that were also largely segregated by age group, i.e., an adult-dominated cluster (C-a) and a pediatric-dominated cluster (C-p). In the KMT2A subtype, cases in C-a exhibited an over-representation of the KMT2A:: AFF1 fusion, and resistance to mercaptopurine ( P=0.029), prednisolone ( P=0.0039), vincristine ( P=0.046) and cytarabine ( P=0.0037). Within CRLF2 ALL, cases in C-a were associated with the presence of BCR:: ABL1-like signature and IGH:: CRLF2 rearrangements, and were more resistant to mercaptopurine ( P=0.0073) and prednisolone ( P=0.00036) compared to those in C-p. For DUX4 ALL, C-a was characterized by an under-representation of ERG deletions and resistance to mercaptopurine ( P=0.0056) and prednisolone ( P=0.0031), compared to C-p within DUX4. To explore the clinical relevance of this heterogeneity, we analyzed the in vivo treatment response of KMT2A (N=35), CRLF2 (N=59) and DUX4 (N=118) B-ALL enrolled in six frontline ALL trials. Compared to cases in C-p (usually drug-sensitive), those in C-a (usually drug-resistant) consistently had significantly poorer initial treatment responses as measured by persistent end-of-induction minimal residual disease (≥0.01%) in KMT2A (58% vs 9%; P=0.0063), CRLF2 (74% vs 41%; P=0.030), and DUX4 (66% vs 40%; P=0.0058) ALL. In conclusion, these studies have revealed important new insights into the pharmacogenomic basis of age-related differences in B-ALL treatment response. These results indicate that both inter- and intra-subtype heterogeneity contribute to inferior prognosis in adults with ALL, but also point to therapeutic opportunities to improve their outcomes.

Introduction Pulmonary Embolism (PE) is a major cause of morbidity and mortality worldwide. Diagnosis is essential as untreated PE has a 30% mortality rate. Currently, computer tomography pulmonary angiogram (CTPA) is the standard of care to diagnose PE. However, this modality is expensive, exposes patients to radiation and increases risk of contrast induced nephropathy. Furthermore, only 5% of CTPAs performed are positive for PE signifying that many unnecessary tests are being performed. To address this gap, Pre-Test Probability (PTP) tools have been developed to safely exclude patients with low risk of PE and limit iatrogenic harm from over testing. Despite the tools being developed over 20 years ago, they are not widely available in electronic health record (EHR) systems and even when they are built in, uptake remains low. Methods Three large integrated health systems using Epic EHR systems across five states (MA, WI. MN, AZ, FL) built electronic PTP assessments into their EHR systems to safely exclude patients with low risk of PE and limit over testing. Two sites made the PTP optional, and one site made it a forced function (providers were forced to complete PTP prior to ordering CTPA unless a D-dimer result was present in the prior 48 hours). To assess the usability of these EHR tools, the team conducted a survey with ED clinicians across the three test sites. The survey was created to identify which PE risk stratification methods were employed by ED clinicians (EHR embedded PTP tool, apps on their phone, web applications like MDcalc, calculations from memory, or if they relied on clinical gestalt), and to identify barriers to using the EHR embedded PTP. Results Site 1 had 47 respondents, Site 2 had 94 respondents, and Site 3 had 16 respondents. Two key findings emerged from the survey (Figure 1). First, clinicians used a variety of risk stratification approaches and few of them documented their risk assessments in structured fields in the medical record. Second, clinical gestalt was the most used PE risk stratification approach, and this was true across all three test sites. In addition, the health system with a PTP prompt before clinicians could proceed with CTPA orders (Site 3) did not have a higher percentage of clinicians who reported using the EHR embedded tool than sites that did not prompt clinicians to fill in the PTP. Clinicians cited a variety of different barriers to using the EHR embedded PTP tool (Table 1). Conclusion While many clinicians indicated intermittent use of PTP criteria to aid in the diagnosis of PE, risk factors and scores from phone apps, web tools, and calculations from memory are unlikely to be documented in the patient's medical record, which means that they are not accessible to all members of the ED care team and cannot be used for electronic clinical quality measure. The biggest hurdles to increasing the use of structured PTP assessments in the ED setting to safely exclude PE and limit iatrogenic harm from over testing are (1) obtaining buy-in from ED clinicians that the PTP tools provide value over clinical gestalt, at least for a subset of patients who could most benefit, and (2) identifying best practices for incorporating PTP tools into EHR systems that make the tools easier to access and use 3) developing and implementing effective education and awareness programs around the PTP tools. This survey adds to the body of literature on PTP assessments in the ED setting and can help inform further research that is needed to continue to improve the diagnosis of PE. Funding: This project is funded in part by the Gordon and Betty Moore Foundation through Grant GBMF10778 to the American Society of Hematology.

Abstract Background Early diagnosis, prognostication, and treatment initiation are the cornerstones of sepsis management. There remains an immense interest in exploring the diagnostic and prognostic roles of neutrophil-lymphocyte ratio (NLR) in the sepsis population. Methods We performed a retrospective multi-center observational study including patients admitted to different Mayo Clinic sites with a diagnosis of sepsis between October 2018 and August 2022. Patients were excluded if they were aged &lt; 18 years, lacked research authorization, or had missing Neutrophil or Lymphocyte count at admission. Data were collected from an existing sepsis database and Mayo Data Explorer (MDE). Categorical variables were summarized as percentages and continuous variables were summarized as medians. Chi-square test for significance, independent sample t-test, and multivariate Cox Proportional Hazard models were performed on IBM SPSS Statistics v28.0. Results Our study cohort consisted of 13968 patients, of which the majority were males (55.9%), Caucasian (91.6%), and non-Hispanic or Latino (94.3%). The median age of the cohort was 71 (60, 80) years, and the median BMI was 27.7 (23.4, 33.3) kg/m2. Among all sepsis patients, 6.0% had a positive blood culture and the most common organisms were E. coli (26.5%), Klebsiella sp. (15.6%), Streptococcus sp. (12.8%) and Staphylococcus aureus (9.9%). 13131 patients (94.1%) survived the hospital stay and 837 (5.9%) did not. There was no difference in mortality based on blood culture positivity status (6.0% vs 6.6%, p=0.41). However, the median NLR was higher among patients with a positive blood culture (16.4 vs. 12.1, p&lt; 0.001) and among non-survivors (14.3 vs 12.2, p&lt; 0.001). NLR did not significantly vary based on the type of organism growing in the blood culture. A multivariate model revealed NLR as an independent predictor of mortality (HR 1.003, 95% CI: 1.000-1.006, p=0.029) after adjusting for comorbidities, baseline clinical and laboratory variables. (Tables 1 & 2) Conclusion Our retrospective multicentric study showed that the Neutrophil-Lymphocyte ratio at admission was higher among bacteremic sepsis patients and non-survivors. Further prospective studies are needed to explore its diagnostic and prognostic utility. Disclosures All Authors: No reported disclosures