Wilcoxon Rank Sum Test Research Articles

A Novel Pediatric Clinical Skills Curriculum to Prepare Medical Students for Pediatrics Clerkship

Abstract Introduction Medical students feel poorly prepared to examine pediatric patients during clerkship. Our institution’s introduction to clinical skills course lacked practice with pediatrics physical examination skills. We developed a novel clinical skills curriculum to increase students’ confidence in examining pediatric patients. Methods Ericsson’s deliberate practice conceptual framework guided curriculum design. We utilized a flipped-classroom model to teach the newborn examination. Students watched a video, then practiced with manikins and patients. For the child examination, students attended a lecture and practiced with hospitalized children and facilitators. Students then participated in a Home, Education, Eating/Exercise, Activities/Employment, Drugs, Suicidality, Sexuality, Safety (HEEADSSS) didactic and role play activity. Before and after participation, students completed REDCap surveys ranking confidence in performing pediatric examinations and identifying normal examination findings on a Likert scale (1 = “Not at all confident,” 4 = “Extremely confident”). We analyzed data using Wilcoxon rank sum tests. Results A total of 97 students participated in the curriculum. Respectively, 56 (58%) and 32 (30%) students completed pre- and post-participation surveys. Post-participation, students reported increased confidence in identifying normal infant (median [interquartile range]; (2 [2,2] vs 4 [3,4]; p < 0.001) and child (2 [2,2] vs 3 [3,4]; p < 0.001) examination findings as well as HEEADSSS assessment components (2 [1.5,2] vs 4 [3,4]; p < 0.001), and had significantly higher scores on confidence performing infant (2 [2,2.5] vs 4 [3,4]; p < 0.001), child (2 [2,2] vs 3 [3,4]; p < 0.001), and HEEADSSS assessment (2 [2,3] vs 4 [3,4]; p < 0.001). Discussion This multi-modal curriculum emphasizing pediatric examination skills improved students’ confidence in pediatric-specific knowledge and skills prior to clerkship.

Abstract B003: Dogs with cancer have higher plasma exosome concentrations compared with healthy dogs in the COED (canine osteosarcoma early detection) study

Abstract Background: Osteosarcoma a common cancer in dogs that can serve as a translational model for certain aspects of human osteosarcoma. We previously developed a serum exosome gene signature in dogs with osteosarcoma capable of detecting minimal residual disease and predicting prognosis after therapy. Our goal is to continue expanding our understanding of exosomes for liquid biopsy applications in dogs with cancer, and to leverage this information in the design of liquid biopsy tests to address risk, early detection, and management of human cancer patients. For this study, we hypothesized that dogs with cancer would have higher plasma exosome concentrations compared with healthy control dogs. Methods: Plasma exosomes were enriched from 29 dogs with cancer, including 8 dogs with osteosarcoma, and 26 healthy control dogs. Exosome size and concentration in the plasma samples were characterized with nanoparticle tracking analysis. Wilcoxon rank sum tests were performed to assess differences between groups. Results: Dogs with cancer had a higher mean exosome concentration at 1.4 x 1012 (+/- 1.1 x 1012) particles/ml, compared with 5.0 x 1011 (+/- 2.7 x 1011) particles/ml in healthy control dogs (p = 0.0046). There was no difference in exosome size between dogs with cancer (mean diameter = 99.9 nm) and healthy control dogs (107.8 nm; p = 0.16) when all cancer types were included. However, exosomes enriched from healthy control samples were found to be significantly larger when compared to the exosomes enriched from the subset of cancer dogs that had osteosarcoma (mean exosome diameter = 83.9 nm; p = 0.0065). Similarly, when comparing exosome size between dogs with osteosarcoma and dogs with other cancers, plasma exosomes were larger in the dogs with other cancers (107.4 nm; p = 0.023). Conclusions: In this population, dogs with cancer have higher plasma exosome concentrations compared with healthy control dogs. Interestingly, we also found that dogs with osteosarcoma had significantly smaller exosome size than dogs with other cancers and healthy control dogs. Though the size of exosomes from dogs with osteosarcoma was found to be smaller, it is possible that the larger exosome concentration in dogs with osteosarcoma results in a similar total exosomal mass. Ongoing work includes analysis of exosomal cargo to develop a liquid biopsy test capable of assessing risk of osteosarcoma development in dogs, and applying similar methodology to determine exosomal genes associated with prognosis in pediatric osteosarcoma. The higher exosome concentrations in dogs with cancer suggests that this feature, combined with analysis of exosomal cargo, may have utility in development of a liquid biopsy cancer test in dogs. Citation Format: Kelly M. Makielski, Jaron M. Magstadt, Courtney H. Labe, Ali Khammanivong, Meagan Wojtysiak, Kyle Duval, Mitzi Lewellen, Amber Winter, Kelly Reid, Andrea Chehadeh, Michelle Buettner, Caitlin Feiock, Aaron K. Rendahl, Gary R. Cutter, Logan G. Spector, Brenda J. Weigel, Jaime F. Modiano. Dogs with cancer have higher plasma exosome concentrations compared with healthy dogs in the COED (canine osteosarcoma early detection) study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B003.

Comprehensive analysis of molecular mechanisms underlying kidney stones: gene expression profiles and potential diagnostic markers

BackgroundThe study aimed to investigate the molecular mechanisms underlying kidney stones by analyzing gene expression profiles. They focused on identifying differentially expressed genes (DEGs), performing gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and screening optimal feature genes using various machine learning algorithms.MethodsData from the GSE73680 dataset, comprising normal renal papillary tissues and Randall’s Plaque (RP) tissues, were downloaded from the GEO database. DEGs were identified using the limma R package, followed by GSEA and WGCNA to explore functional modules. Functional enrichment analysis was conducted using KEGG and Disease Ontology. Various machine learning algorithms were used for screening the most suitable feature genes, which were then assessed for their expression and diagnostic significance through Wilcoxon rank-sum tests and ROC curves. GSEA and correlation analysis were performed on optimal feature genes, and immune cell infiltration was assessed using the CIBERSORT algorithm.Results412 DEGs were identified, with 194 downregulated and 218 upregulated genes in kidney stone samples. GSEA revealed enriched pathways related to metabolic processes, immune response, and disease states. WGCNA identified modules correlated with kidney stones, particularly the yellow module. Functional enrichment analysis highlighted pathways involved in metabolism, immune response, and disease pathology. Through machine learning algorithms, KLK1 and MMP10 were identified as optimal feature genes, significantly upregulated in kidney stone samples, with high diagnostic value. GSEA further elucidated their biological functions and pathway associations.ConclusionThe study comprehensively analyzed gene expression profiles to uncover molecular mechanisms underlying kidney stones. KLK1 and MMP10 were identified as potential diagnostic markers and key players in kidney stone progression. Functional enrichment analysis provided insights into their roles in metabolic processes, immune response, and disease pathology. These results contribute significantly to a better understanding of kidney stone pathogenesis and may inform future diagnostic and therapeutic strategies.

HPB SO10 - Evaluation of the impact of an Enhanced Recovery Pathway on clinical outcomes after Pancreaticoduodenectomy

Abstract Background Southampton General Hospital (SGH) is a high-volume HPB centre with a well-established Enhanced Recovery After Surgery pathway (ERAS). Despite the morbidity associated with pancreatic surgery, there is a large body of evidence supporting the use of a multi-modal approach to accelerate patient recovery. Within SGH, ERAS is utilised for all patients undergoing Pancreaticoduodenectomy (PD). Initial assessment of the pathway in SGH demonstrated a reduction in length of stay. Since its implementation, ERAS has been modified to optimise the pathway. The aim of this study was to assess whether the impact of ERAS had progressed over time. Method Single centre retrospective analysis of patients undergoing open PD from 2007-2023. Pancreatic reconstruction was with pancreaticojejunostomy. Pre and Post ERAS data were analysed. Post ERAS data was subdivided into Early, Middle and Late implementation time phases. Length of Stay, Complications (Clavien-Dindo Grade 3 and above), Readmissions and Mortality were all examined. Non-parametric data analysis was undertaken with Kruskal-Wallis, Spearman rank correlation and Wilcoxon rank-sum tests. Significance further assessed with Multi-variate regression (MVR). All Data were analysed using STATA. Results Overall, 861 patients underwent an open PD, the yearly volume increasing with time. Mean age was 66 years, which did not change with time. With ERAS implementation, Median Length of Stay (LOS) fell 13 to 9 days (p<0.01) and there was no statistically significant increase in Grade 3 complications or Readmissions (p=0.931, p=0.163). Grade 3 complications increased LOS (p<0.01). Increased age led to a small increase in LOS (p<0.01). Median LOS across Early, Middle and Late ERAS periods was 10, 9 and 9 respectively. LOS did not consistently demonstrate a statistically significant improvement across ERAS phases (MVR p=0.387, K-Wallis p<0.05). Conclusion The implementation of ERAS significantly reduced the median LOS for patients undergoing PD, without increasing their risk of complications or readmissions. This benefit has also been safely maintained across the period of its implementation.

Abstract A068: Evaluate the performance of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD), fibrosis, and cirrhosis are risk factors for hepatocellular carcinoma (HCC). Blood-based assays to date have limited accuracy for detecting MASLD and cirrhosis, and thus have not been widely adopted in the clinical setting. The identification and validation of a multiplex molecular signature associated with liver disease may address this unmet need. This prospective single-center US study evaluated the performance of the non-invasive Liver FibraChek Dx serum assay for detecting MASLD. The study algorithm analyzes weighted values of five serum biomarkers (AST, ALT, taurocholic acid, L-tyrosine, and platelet count) plus age to derive a risk score. Samples comprised 14 MASLD cases, 19 HCC cases, and 12 healthy controls. Liver status was confirmed by tissue biopsy. Wilcoxon rank sum tests determined the association between the risk score and confirmed liver histology. Diagnostic performance was assessed using ROC curves. The probability of identifying MASLD and/or HCC by Liver FibraChek Dx, in conjunction with other patient parameters, was demonstrated by an AUROC of 0.890 (95% CI: 0.776-1.000), with 93.9% sensitivity, 75.0% specificity, 91.1% positive predictive value, 81.8% negative predictive value, and 88.9% accuracy. Risk scores associated with the biomarker panel enabled accurate discrimination of liver disease from healthy controls. The non-invasive multiplex Liver FibraChek Dx test can effectively and accurately detect and classify hepatic fibrosis risk in peripheral blood samples and may have utility in diagnosing and monitoring liver pathogenesis. Citation Format: Fernando Siguencia, Michitaka Matsuda, Vijay Pandyarajan, Sunao Tanaka, Steven M Smith, Ekihiro Seki, Charles J Rosser, Hideki Furuya. Evaluate the performance of FibraChek™ for non-invasive detection of hepatic fibrosis and hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A068.

Abstract Su205: Using Emergency Medical Services Monitors for Cardiac Arrest Patients in the Emergency Department is Associated with Faster Initial Rhythm Analysis and Defibrillation

Introduction: The 2020 American Heart Association guidelines for Cardiopulmonary Resuscitation (CPR) emphasizes the importance of high-quality CPR and early defibrillation in improving cardiac arrest (CA) survival. Using our emergency department (ED) CA video review registry, we can capture metrics to reliably assess the effectiveness of different approaches to CA management. Goals/Hypothesis: We propose that emergency medical services (EMS) pads and defibrillators should be used to initially analyze cardiac rhythm in the ED. We hypothesize that this “EMS Equipment” approach is associated with shorter time to first ED rhythm detection and defibrillation, higher chest compression fraction (CCF), and improved return of spontaneous circulation (ROSC) rates. Methods: This is a single center, retrospective cohort study using our CA video review registry between 10/03/2018 – 2/20/2024. Atraumatic, out-of-hospital CA patients ≥18 years were included while patients arriving to the ED with ROSC were excluded. The “EMS Equipment” group utilized EMS pads and defibrillators while the “ED Equipment” group utilized ED pads and defibrillators for the first ED rhythm analysis. Wilcoxon rank sum tests were used to assess differences in time to first rhythm check and first defibrillation among the two groups. Chi-square tests were used to assess whether the proportions of patients achieving above median CCF, ROSC, survival to admission and discharge in the two groups were different. Results: A total of 247 patients were included in the analysis with 69 patients in the EMS Equipment group (27.9%) and 178 patients in the ED Equipment group (72.1%). The EMS Equipment group had a shorter median time to first ED rhythm detection (96 vs. 255 seconds, p <0.00001). Among the 63 patients defibrillated in the ED, the EMS Equipment group had a shorter median time to first ED defibrillation (103 vs. 413 seconds, p = 0.0024). There was no significant difference in CCF, ROSC rates, survival to admission or discharge. ROSC was achieved in 36% of cases. Conclusion: In conclusion, initial rhythm analysis with EMS pads and defibrillators was associated with shorter time to initial ED rhythm detection and defibrillation, but not improved CCF, ROSC rates, and survival. Larger studies are needed to verify these exploratory results in more diverse settings.

Abstract 4134900: Cellular Crosstalk in Endocardial Fibroelastosis: NRG Signaling Dysregulation Contributes to Fibrosis and Myocardial Dysfunction in Hypoplastic Left Heart Complex

Background: Endocardial fibroelastosis (EFE) is marked by a thickened fibro-elastic layer derived by endothelial-to-mesenchymal transition (EndMT), leading to restrictive myocardial function and poor cardiac growth, complicating biventricular repair in hypoplastic left heart complex (HLHC) patients. Neuregulin (NRG) signaling, crucial in EndMT and myocardial development, is implicated in various cardiomyopathies and heart failure, and its dysregulation may drive EFE pathogenesis. Hypothesis: NRG signaling dysregulation influences the cellular and molecular mechanisms of EFE. Methods: Single nucleus RNA sequencing (snRNA-seq) was conducted on human left ventricular (LV) tissue resected from 7 EFE patients (0.4-15 years) and 4 non-congenital heart disease (CHD) postmortem human controls (0.02-16 years). Differential gene expression was analyzed using the Wilcoxon Rank Sum test. We used CellChat, a computational tool for analyzing intercellular communication networks, to identify signaling changes via quantitative contrasts and joint manifold learning. Results: We identified 11 cell types in 64,963 nuclei. In EFE samples compared to non-CHD samples, NRG1-expressing fibroblasts increased from 3.4% to 21.2% (P<0.0001), and NRG2-expressing cardiomyocytes from 11.9% to 45.9% (P<0.001). CellChat analysis revealed a denser NRG signaling network in EFE, with enhanced interactions among cardiomyocytes, endocardial cells, fibroblasts, mast cells, and smooth muscle cells (Fig. 1A-B). Cardiomyocytes emerged as significant senders of NRG signaling in EFE, while endocardial cells, though still key senders, showed reduced influence. Fibroblasts became strong mediators, receivers, and influencers, smooth muscle cells emerged as prominent receivers, and mast cells gained roles as mediators and influencers (Fig. 1 C-D). These changes indicate a complex NRG signaling network in EFE, highlighting altered cellular interactions driving disease progression. Conclusion: Dysregulated NRG signaling in EFE contributes to pathological cellular crosstalk, fibrosis, and myocardial dysfunction, potentially hindering successful biventricular repair in HLHC patients. Targeting NRG pathways could represent a novel therapeutic approach. These findings offer promising implications for affected patients, potentially improving outcomes. Future research should explore additional molecular pathways involved in EFE and assess the therapeutic efficacy of targeting NRG signaling.

Abstract 4134560: Sex Differences in Repolarization Abnormalities Associated with Ventricular Arrhythmia in Mitral Valve Prolapse

Background: Compared to men, women with mitral valve prolapse (MVP) are more likely to present with sudden death, and most women who die suddenly are premenopausal. Repolarization abnormalities are common in patients with MVP-attributed sudden death. However, differences in repolarization between men and women with MVP are not known. Hypothesis: Repolarization abnormalities are associated with ventricular arrhythmia and are more common in women than men with MVP. Aims: To investigate associations of ECG repolarization abnormalities with sex and ventricular arrhythmia in MVP. Methods: We reviewed 12-lead ECGs from 272 adults with MVP for T-wave inversion, ST segment elevation, ST depression, QTc and QT dispersion. Patients were excluded if they had prior MI, coronary artery disease, mitral valve surgery, moderate or severe LVH, heart failure, reduced left ventricular ejection fraction, atrial fibrillation or QRS duration >120ms. Transthoracic echocardiograms were reviewed for mitral regurgitation, mitral annular disjunction, bi-leaflet or myxomatous MVP. Ambulatory ECGs (n=94) were assessed for NSVT or PVCs (> 1% burden) and ECGs for >1 PVC on any 10 second tracing. Associations were evaluated using Fisher’s exact test, Wilcoxon rank-sum test or multiple linear regression. Results: Among 272 patients, median (IQR) age was 58 (47-67) years, 162 (59.6%) were women, 46 (16.9%) were African American, and 34 (12.5%) had frequent ventricular ectopy. Women and men had similar rates of NSVT (15/66 [22.7%] vs 4/28 [14.3%], p=0.41) and frequent ventricular ectopy (25/162 [15.4%] vs 9/110 [8.1%], p=0.093). The QTc was longer in women (433 [417, 446] vs 423 [406, 442] ms, p=0.023) and in those with NSVT (437 [421, 444] vs 421 [405, 436] ms, p=0.028), but not in those with ventricular ectopy (437 [420, 445] vs 428 [410, 444] ms, p=0.15). There was a trend towards increased QTc in patients with mitral annular disjunction (433 [418, 454] vs 429 [408, 444] ms, p=0.054) and myxomatous MVP (434 [414, 450] vs 427 [408, 444] ms, p=0.076). Female sex was the only independent predictor of QTc (R 2 =0.14, p=0.0032). Conclusion: Among patients with mitral valve prolapse, women have longer QT interval than men, and longer QT interval is associated with nonsustained ventricular tachycardia. Subtle or dynamic delay in repolarization may promote malignant ventricular arrhythmias in women. Understanding these relationships may help identify patients at risk for sudden death.

Abstract 4135968: Radiomic features of skeletal muscle on prostate T1-Weighted MRI associated with MACE outcomes in prostate cancer patients undergoing hormonal therapy

Background: Patients with high-risk prostate cancer (PC) who undergo hormonal therapy(HT) frequently die of major adverse cardiovascular events (MACE). Skeletal muscle on abdominal T1-weighted MRI (T1W) has been shown to be associated with cardiovascular fitness. Aims: To quantify heterogeneity associated with skeletal muscle tissue composition on prostate MRI patients undergoing HT using computationally derived radiomic features and identify their association with MACE. Methods: Cohort of N=58 men diagnosed with PC who underwent a 3 Tesla pre-treatment multi-parametric MRI followed by HT and followed up for MACE events were identified. MACE is defined as a composite of cardiovascular death, atrial fibrillation, myocardial infarction, ischemic stroke, heart failure, coronary artery disease, and peripheral vascular disease. Regions of interest (ROI) of skeletal muscle, including the obturator externus, pectineus, and the adductor group of muscles, were delineated on axial T1W under the guidance of an experienced radiologist. A set of 120 radiomic features, including gray level statistics, co-occurrence, wavelet, and texture energy-based features, were extracted within the ROI which quantifies underlying subvisual texture-based heterogeneity. Radiomics associated with MACE events were identified using the Wilcoxon rank-sum test and univariate Cox-regression (p<0.05). Results: Of the N=58 patients included in this study, 18 experienced MACE. The most common MACE event was AF (8.6%). Median-time-to-MACE event was 7.3 years (6.2-8.2). 3 radiomic features (Table 1) quantifying the heterogeneity of skeletal muscle on prostate T1W were observed to be associated with MACE. Specifically, we observe that first order features have a lower response and wavelet features have a lower response in MACE patients which suggests a higher degree of local deformations and heterogeneity in skeletal tissue compared to non-MACE patients. Conclusions: Results from our study suggest that radiomics quantified texture characteristics of skeletal muscle tissue may indicate cardiovascular fitness, reflecting the likelihood of experiencing MACE following initiation of HT in PC men. Pre-treatment identification of PC patients at high risk of MACE may allow for alternative treatment options improving cardiovascular outcomes. Future studies will involve exploring larger, multi-site cohorts and machine learning modeling to determine cardiovascular risk.

Abstract 4136316: BMP10 as novel marker for right atrial dilatation and pressure in precapillary pulmonary hypertension

Introduction: Precapillary pulmonary hypertension (precPH) leads to increased right atrial (RA) stretch and pressure. The right atrium is the major source of bone morphogenetic protein 10 (BMP10) in adults. Aim: This study aims to investigate BMP10 in relation to RA dilatation and pressure overload. Methods: We studied BMP10 mRNA in fresh RA tissue of N=5 Chronic Thromboembolic Pulmonary Hypertension (CTEPH) patients and N=9 controls and protein expression in paraffin-embedded RA tissue of N=4 Pulmonary Arterial Hypertension (PAH) patients and N=6 controls. We prospectively included 48 precPH patients (N=22 idiopathic PAH, N=14 hereditary PAH and N=12 CTEPH, and N=16 controls. To study BMP10-induced transcriptional activity, we assayed serum samples in human microvascular endothelial cells (HMEC) with a BMP-responsive transcriptional luciferase assay. BMP10 activity was calculated by subtracting BMP activity after incubation with antibodies for Alk1Fc and bone morphogenetic protein 9 (BMP9). We assessed correlations between BMP10 activity and RA dilatation (RA max volume>79 ml/m 2 for male or >69 ml/m 2 for female) and right ventricular (RV) dilatation (RV end-diastolic volume>108 ml/m 2 for male and >96 ml/m 2 for female). In a cohort of CTEPH patients that underwent pulmonary endarterectomy (PEA) we assessed the effect of pressure unloading on BMP10 activity. Normality of data was checked and statistical differences between groups were tested using an independent sample t-test or Wilcoxon rank-sum test. Results: BMP10 mRNA, protein and downstream activity were higher in the precPH RA tissue (Figure 1A-F). High systemic BMP10 activity was associated with RA dilatation and high RA pressure, but not RV dilatation in precPH (Figure 2A-C). Finally, pressure unloading after PEA in CTEPH patients results in a reduction in BMP10 activity (figure 2D). Conclusions: Local RA BMP10 expression and activity is increased in precPH. Increased systemic BMP10 activity was related to RA dilatation and pressure. Pressure unloading of the right heart leads to a reduction of systemic BMP10 activity. Future studies are needed to determine whether increased BMP10 release is an adaptative mechanism or can be used as therapeutic target.

Abstract Su1206: Reduced Time to Goal Therapeutic Hypothermia With Implementation of a Post Cardiac Arrest Consult Service

Introduction: Critical care after advanced cardiac life support can be pivotal for survival and outcomes in patients with out-of-hospital cardiac arrest (OHCA). Prior studies have demonstrated improvements in survival after OHCA with shorter door-to-therapeutic hypothermia (TH) initiation times. Post-cardiac arrest consult teams (PCACT) can facilitate TH to goal 33°C and other aspects of post-arrest care. However, the effects of such a service on TH have not been consistently quantified. Hypothesis: More OHCA patients would undergo TH and reach goal temperature sooner following implementation of a PCACT. Aims: We aim to evaluate the effectiveness of a PCACT in optimizing TH in survivors of OHCA. Methods: We conducted a retrospective chart review of 305 patients admitted between January 1, 2021 and December 31, 2022. Implementation of a dedicated PCACT, comprised of a neurointensivist and an advanced practice provider or neurocritical care fellow, occurred on January 1, 2022. The PCACT was active on weekdays only. One year before and after this date were designated as “pre-PCACT” and “post-PCACT”, respectively. De-identified patient demographics, clinical features of cardiac arrest, and TH data were collected and compared using Wilcoxon rank-sum and Chi-squared tests for continuous and categorical variables, respectively. Results: Of the 305 patients admitted during the study period, 149 were in the pre-PCACT group and 156 were in the post-PCACT group. Baseline demographics between the two groups were similar except that the post-PCACT group had more patients with non-shockable rhythms (64% vs. 54%, p =0.001). Patients were not cooled to 33°C more frequently (50 vs. 52%) pre- or post-PCACT. TH to 33°C was performed in 156 (51%) patients, 78 patients (50%) pre- and post-PCACT implementation. There were no baseline demographic or temperature differences between the two groups amongst patients undergoing TH to 33°C. Post-PCACT patients were quicker to reach 33°C (1.6 vs. 3 hours, p =0.001). After PCACT implementation, this difference was noted during weekdays but not during weekends (1.3 vs. 2.7 hours, p =0.05).There were no differences in survival or neurologic outcomes pre- and post-PCACT introduction, nor between patients who were or were not cooled to 33C. Conclusion(s): Implementation of a PCACT may streamline care to reduce time to goal temperature during TH. However, further study is required to determine whether a PCACT can improve outcomes.

Abstract 4136498: Analysis of Cardiovascular Events in Cancer Survivors: A Comparative Study of Solid Tumors and Hematologic Malignancies at a Tertiary Cardiovascular Center

Background: Cardiovascular disease (CVD) and cancer represent the leading contributors of death worldwide. Although advancements in antineoplastic therapies have notably enhanced prognoses, CVD now emerges as the primary cause of mortality in this population. Ojective: To assess the occurrence of CVD in cancer survivors and investigate disparities based on their previous cancer diagnosis, categorized into solid tumors or hematological malignancies. Methods: A cross-sectional study was conducted, including adult oncology survivors who had previously undergone oncological treatment and were referred to our center between 2010 and 2023 due to the presentation of major adverse cardiovascular events (MACE). They were categorized into two groups: those with hematological cancer and those with solid tumors. We used Chi2 test to assess differences between categorical variables and the Wilcoxon rank-sum test to evaluate differences in continuous parameters. Statistical analysis was performed using R 4.0 and StataMP 14.1. Results: A total of 214 oncological patients were included (median age: 69 [IQR: 55-80], women: 53%), comprising 164 (76.6%) with solid tumors and 50 (23.4%) with hematological cancer. Baseline characteristics were mostly similar between the groups (Table 1), with diabetes being more prevalent in patients with solid tumors (26% vs 12%, p=0.036). The prevalence of heart failure was predominantly NYHA I and II in solid tumors and NYHA III in hematological cancer (p=0.002) (Table 2). The incidence of coronary artery disease (CAD) was the most common MACE in solid tumors (39% vs 34%), but this was not statistically significant (p=0.04). In hematological cancer, the most frequent MACE was myocardial dysfunction, showing a significant difference (46% vs 24%, p=0.002). Similarly, valvular heart disease (VHD) appeared more frequently in this group (38% vs 20%, p=0.01). The remaining MACEs did not show significant differences, nor did the count of MACEs upon hospital arrival. Conclusion: Myocardial dysfunction and VHD exhibited a higher incidence in hematological cancer compared to solid tumors. Conversely, the incidence of CAD was higher in the solid tumor group; however, similar to the occurrence of other MACEs, there was no significant difference between the two groups. These findings could emphasize the importance of closely monitoring specific cancer types to enhance prevention strategies but still need further analysis to also determine the exact etiologies.

Abstract Su202: Physiological response to vasopressor administration during hemodynamic-directed CPR

Background: The hemodynamic response to successive vasopressor doses during CPR and its association with survival is poorly defined. Understanding these relationships can facilitate identification of alternative vasopressor strategies. Hypothesis: Non-survival is associated with lower responsivity to successive vasopressors. Methods: We performed retrospective analysis of hemodynamic data acquired in pediatric swine models (sus scrofa, 9-12kg) of asphyxia-associated ventricular fibrillation cardiac arrest with use of hemodynamic-directed CPR (n=175). Starting 2m into CPR, if hemodynamic targets were not met, vasopressors were given in cycles comprising two doses of 0.02mg/kg epinephrine (Epi) followed by vasopressin (Vaso, 0.4U/kg), separated by a minimum of 1m. After a minimum of 2m, the cycle was repeated. Hemodynamic response was evaluated using the peak diastolic blood pressure (DBP) within 1m for Epi, 2m for Vaso administration and the difference between the initial and peak DBP (delta DBP). Subjects were classified as “responder” if either a delta DBP > 5 mmHg or a peak DBP > 25 mmHg was achieved, and a “non-responder” otherwise. Animals were deemed “survivors” if ROSC was achieved following initial defibrillation. The change in delta DBP for successive vasopressors was compared in survivors versus non-survivors using two-sided Wilcoxon rank-sum tests. Continuous variables are summarized using the median with interquartile ranges. The burden of “non-response” was used to a construct confusion matrix and calculate performance. Results: Non-survivors (n=30) had lower delta DBP than survivors (n=145) following successive vasopressor administration at the first cycle (first Epi dose: 7.8 [2.4, 14] vs 16 [7.5, 24], p< 0.01; second Epi: 2.0 [0, 4.7] vs 7.1 [2.0, 12], p< 0.01; Vaso : 1.1 [0, 2.3] vs 7.1 [2.0, 12], p< 0.01). Classification as a “non-responder” at the first cycle (Epi-Epi-Vaso) was significantly predictive of non-survival (Sensitivity 32%, Specificity 92%). Animals that failed to respond to all vasopressors at the first cycle had a significantly increased rate of mortality (86%; 6 non-survivors, 1 survivors) compared to animals that responded to all 3 vasopressors (13%; 16 non-survivors, 111 survivors). Conclusion: Mortality was significantly associated with lower DBP response to successive vasopressors during hemodynamic-directed CPR in pediatric swine models of cardiac arrest, which may suggest a critical timepoint to activate ECPR.

Machine fault detection model based on MWOA-BiLSTM algorithm

This paper proposes the Modulated Whale Optimization Algorithm(MWOA), an innovative metaheuristic algorithm derived from the classic WOA and tailored for bionics-inspired optimization. MWOA tackles common optimization problems like local optima and premature convergence using two key methods: shrinking encircling and spiral position updates. In essence, it prevents algorithms from settling for suboptimal solutions too soon, encouraging exploration of a broader solution space before converging, by incorporating cauchy variation and a perturbation term, MWOA achieve optimization over a wide search space. After that, comparisons were conducted between MWOA and seven recently proposed metaheuristics, utilizing the CEC2005 benchmark functions to assess MWOA’s optimization performance. Moreover, the Wilcoxon rank sum test is used to verify the effectiveness of the proposed algorithm. Eventually, MWOA was juxtaposed with the BiLSTM classifier and six other meta-heuristics combined with the BiLSTM classifier. The aim was to affirm that MWOA-BiLSTM outperforms its counterparts, showcasing superior performance across crucial metrics such as accuracy, precision, recall, and F1-Score. The study results unequivocally demonstrate that MWOA showcases exceptional optimization capabilities, adeptly striking a harmonious balance between exploration and exploitation.

Exaggerated T‐wave alternans in children with Angelman syndrome

AbstractObjectiveWe aimed to test whether T‐wave alternans (TWA), which is a marker of susceptibility to ventricular fibrillation, is abnormal in children with Angelman syndrome (AS) compared with typically developing children (TDC), and whether it can be used as a biomarker of AS.Materials and MethodsUsing surface electrocardiogram (ECG), we calculated TWA in AS and compared it between AS and TDC (Wilcoxon rank sum test). We then performed logistic regression to test TWA ability to distinguish AS from TDC.ResultsWe observed higher TWA in AS than TDC (44 vs. 33 uV, p = 0.009), while heart rate did not differ (p = 0.26), nor its variability (p = 0.72). TWA values enabled discrimination between AS and TDC (p = 0.0008) with accuracy of 81%, positive predictive value of 72%, and negative predictive value of 100%.InterpretationOur findings suggest that ECG in children with AS contains evidence of acquired cardiac abnormality via pathologically increased TWA.

NIMG-52. ARTIFICIAL INTELLIGENCE-BASED VOLUMETRIC KINETICS FOR EVALUATING TREATMENT RESPONSE IN IDH-MUTANT GLIOMA TREATED WITH IMMUNOTHERAPY

Abstract BACKGROUND Interpretating radiographic findings of glioma patients receiving immunotherapy is challenging. Repeated imaging is often required for clinical decisions, potentially delaying next line of treatment. Here we assess a glioma segmentation AI model to evaluate treatment response in IDH-mutant glioma patients receiving nivolumab. METHODS Clinical magnetic resonance imaging (MRI)s from twenty-nine patients enrolled in a clinical trial (NCT03718767) were retrospectively analyzed. All patients had at least two sequential MRIs, including baseline study. T2, T1 (pre/post-contrast), and T2 FLAIR MRI sequences were pre-processed using publicly available AI-based whole-brain segmentation models. Lesion contours were derived from a validated 4-class brain tumor segmentation AI model, distinguishing healthy brain parenchyma, peri-lesional edema, non-contrast enhancing volume (NEV), and contrast-enhancing volume (CEV). Total lesion burden volume (TLBV=NEV + CEV + Edema) was also calculated. Growth rates between responders (R) and non-responders (NR), defined as progression-free survival ≥ or < 6months, respectively, were compared using a Wilcoxon Rank Sum Test. RESULTS The R group displayed significantly lower median rates of change for CEV (R -35% vs. NR +142% p = 4.31e-04) and TLBV (R +6% vs NR +43% p = 1.55e-03), compared to NR from baseline to post-cycle 1-2. Additionally, similar trends persisted at post-cycle 3-4 for CEV (R -41% vs. NR +367% p = 3.03e-03) and TLBV (R +12% vs. NR +40% p = 7.74e-03). Although NR showed a higher average baseline TLBV, there was no discernible correlation detected between baseline TLBV and the rate of change during treatment. CONCLUSIONS AI-based volumetric analysis offers an objective response assessment, showing promise in tracking disease progression in IDH-mutant glioma patients on nivolumab, potentially enabling earlier identification of progressive disease and allowing for timely treatment adjustments. A larger prospective study is warranted to refine volumetric pattern analysis for early clinical decisions in immunotherapy.

NIMG-88. EVALUATION OF DIFFUSION AND PERFUSION MRI FEATURES FOR DIFFERENTIATING RECURRENT BRAIN METASTASES AND RADIATION NECROSIS

Abstract BACKGROUND Brain metastases (BM) are a frequent and serious complication of cancer. Differentiating between BM and radiation-induced necrosis (RN) after radiotherapy remains challenging. Diffusion-weighted imaging (DWI) derived apparent diffusion coefficient (ADC) maps and perfusion-weighted imaging (PWI) derived relative cerebral blood volume (rCBV) have the potential to distinguish between BM and RN. Despite the potential of these imaging modalities, previous studies have been limited by the absence of histopathological confirmation. In this study, we utilized a patient cohort that underwent stereotactic biopsy as part of their Laser Interstitial Thermal Therapy (LITT) following suspicious radiographic progression. This allowed us to evaluate the efficacy of ADC and rCBV imaging features with histopathological validation. METHODS In this study, 29 patients underwent MRI scans (3 with 1.5T, 26 with 3T) prior to LITT. Pathology confirmed 11 patients with BM and 18 with RN. Regions of interest (ROIs) in the contrast-enhanced lesion and T2 hyperintensity lesion were identified using post-contrast T1-weighted images and fluid-attenuated inversion recovery (FLAIR) images. Mean values and histogram-based features (standard deviation, 10%, 90%) of lesion volume, ADC, and rCBV within tumor ROIs were compared between the BM and RN using the Wilcoxon rank-sum test. RESULTS Our findings indicated that the mean values of ADC in the enhancing and non-enhancing lesion ROIs did not significantly differ between BM and RN patients. However, in the contrast-enhanced lesion regions, we observed a significant difference in the standard deviation of rCBV (p<0.05), and the 90th percentile value of rCBV also suggested potential differences between BM and RN (p=0.069). In the T2 hyperintensity lesion regions, lesion volume (p<0.05) and the mean of rCBV (p<0.05) show significant differences between BM and RN. CONCLUSION This study demonstrates the potential of using rCBV to aid in the clinical diagnosis of BM. Additionally, our findings indicate that T2 hyperintensity regions, beyond just contrast-enhancing lesions, may provide valuable information for differential diagnosis.

NIMG-87. MULTIREGIONAL, MRI-LOCALIZED SAMPLING OF HIGH GRADE GLIOMAS REVEAL SEX-DISTINCT PATTERNS OF 5-ALA FLUORESCENCE AND IMAGING FEATURES

Abstract High grade gliomas (HGGs) are aggressive brain tumors that are difficult to remove completely, leading to poor survival rates. Contrast enhancement on T1Gd magnetic resonance imaging (MRI) has traditionally been used to guide resection, however it often underestimates true tumor burden, adding a layer of uncertainty for surgeons during pre-operative planning. Fluorescence guided surgery using 5-aminolevulinic acid (5-ALA) has emerged as an intraoperative solution and understanding it in conjunction with MRI features can address the limitations of routine T1Gd imaging during surgical planning. Here we investigate sex-specific patterns in HGGs using 5-ALA fluorescence and imaging features. We analyzed a patient dataset of 202 multiregional MRI-localized biopsies from 42 HGG patients (20 male and 22 female). Data included patient demographics, 5-ALA status (positive or negative), MRI annotations (CE = contrast enhancement, NE = non-enhancement, BAT = brain around tumor non-enhancement), and survival outcomes. Statistical analyses included Wilcoxon rank-sum tests, Kruskal-Wallis tests, and chi-squared tests to assess differences in imaging annotations and 5-ALA positive vs negative status among sex cohorts. Among all samples, CE and BAT were associated with higher 5-ALA positivity, while NE was associated with higher 5-ALA negativity (p = 0.02119). Female patients were less likely to have detectable 5-ALA in their multiregional biopsy samples than males (p < 0.0001). CE at the biopsy location was more likely to be indicative of 5-ALA positivity in males than females (p = 0.001927); whereas NE was associated with higher 5-ALA negativity in females than males (p = 0.03426). BAT was associated with higher 5-ALA positivity in males than females (p = 0.03895). Our study reveals sex-specific patterns in 5-ALA fluorescence and image features among HGG patients. These unique features may serve as potential pre-surgical markers for tumor regions that are more likely to benefit from 5-ALA-guided resection.

Health Disparities in Hospitalized Pediatric Patients with Autism Spectrum Disorder and COVID-19

Background/Objectives: Pediatric patients with autism spectrum disorder (ASD) face unique challenges, especially amongst individuals from historically minoritized racial groups. ASD has also been associated with an increased mortality from COVID-19. This study aims to explore the differences in sociodemographic factors and health outcomes (as measured by length of stay) amongst hospitalized pediatric patients with COVID-19 infections and a diagnosis of ASD compared to individuals with a COVID-19 infection alone; Methods: We performed a retrospective cohort study examining pediatric patients (ages birth to 21) who were hospitalized with a diagnosis of ASD and COVID-19 compared to patients with a diagnosis of COVID-19 alone between January 2019 and June 2023 using Epic Systems Corporation’s Cosmos, a de-identified dataset aggregated from electronic health record data. We examined differences in demographic factors and length of stay (LOS) between groups by utilizing chi-square and Wilcoxon rank sum tests. Multiple logistic regression models were utilized to assess the association between length of stay and diagnosis; Results: A total of 21,708 distinct pediatric patients with a diagnosis of ASD and COVID-19 or COVID-19 alone were included in the analytical dataset. Patients with ASD and COVID-19, compared to patients with COVID-19 alone, had a higher proportion of individuals identifying as male and White. Patients with COVID-19 alone, compared to individuals with ASD and COVID-19, had higher proportions of individuals identifying as Black or African American. Higher proportions of individuals with ASD and COVID-19 had public insurance, compared to individuals with COVID-19 alone. Having a diagnosis of ASD and COVID, after controlling for covariates, was associated with higher odds of having a length of stay greater than the three days (cutoff value determined by the median LOS of three days) compared to having a diagnosis of COVID alone (aOR 1.19, 95% CI 1.04–1.35); Conclusions: Our study highlights the health disparities experienced during hospitalizations by pediatric patients with ASD and COVID-19. Further studies should address barriers and support health outcomes for pediatric patients with ASD.

Association between frailty status and risk of chronic lung disease: an analysis based on two national prospective cohorts

BackgroundThe association between the frailty index (FI) and the risk of chronic lung diseases (CLDs) remains unexplored, warranting further research.Methods and materialsThis study investigated the relationship between FI and CLD risk using data from the China Health and Retirement Longitudinal Study (CHARLS) and English Longitudinal Study of Ageing (ELSA), comprising a combined sample of 9642 individuals. Propensity score weighting was used to ensure similar distribution of covariates across FI groups. The Wilcoxon rank-sum test was used to analyze differences in FI scores between groups with and without CLD. Kaplan–Meier curves and Cox regression analysis were employed to explore the association between frailty status and CLD incidence, with sensitivity analyses conducted for validation.ResultsHigher FI scores were significantly associated with increased CLD risk in both cohorts (p < .05). Kaplan–Meier survival and Cox regression analyses indicated that frail individuals have a significantly elevated risk of CLD compared to robust individuals, particularly in certain subgroups (e.g., female) within the CHARLS cohort (p < .05). The ELSA cohort yielded similar results (p < .05), affirming FI as a strong predictor of CLD. Additional risk factors identified included age, smoking, and unmarried status (p < .05). Frail individuals consistently exhibited the highest risk in both cohorts (CHARLS HR = 1.54, p = .003; ELSA HR = 6.64, p < .001). The sensitivity analysis did not substantially alter the significant associations.ConclusionThese findings emphasize the critical role of frailty in the development of CLD, suggesting that targeted interventions could reduce CLD risk.