Citations

Abstract Aims The viability of cardiac resynchronization therapy (CRT) in inotrope-dependent heart failure (HF) has been a matter of debate. Methods and results We searched Medline, EMBASE, Scopus, and the Cochrane Library until 31 December 2022. Studies were included if (i) HF patients required inotropic support at CRT implantation; (ii) patients were ≥18 years old; and (iii) they provided a clear definition of ‘inotrope dependence’ or ‘inability to wean’. A meta-analysis was performed in R (Version 3.5.1). Nineteen studies comprising 386 inotrope-dependent HF patients who received CRT (mean age 64.4 years, 76.9% male) were included. A large majority survived until discharge at 91.1% [95% confidence interval (CI): 81.2% to 97.6%], 89.3% were weaned off inotropes (95% CI: 77.6% to 97.0%), and mean discharge time post-CRT was 7.8 days (95% CI: 3.9 to 11.7). After 1 year of follow-up, 69.7% survived (95% CI: 58.4% to 79.8%). During follow-up, the mean number of HF hospitalizations was reduced by 1.87 (95% CI: 1.04 to 2.70, P < 0.00001). Post-CRT mean QRS duration was reduced by 29.0 ms (95% CI: −41.3 to 16.7, P < 0.00001), and mean left ventricular ejection fraction increased by 4.8% (95% CI: 3.1% to 6.6%, P < 0.00001). The mean New York Heart Association (NYHA) class post-CRT was 2.7 (95% CI: 2.5 to 3.0), with a pronounced reduction of individuals in NYHA IV (risk ratio = 0.27, 95% CI: 0.18 to 0.41, P < 0.00001). On univariate analysis, there was a higher prevalence of males (85.7% vs. 40%), a history of left bundle branch block (71.4% vs. 30%), and more pronounced left ventricular end-diastolic dilation (274.3 ± 7.2 vs. 225.9 ± 6.1 mL). Conclusions CRT appears to be a viable option for inotrope-dependent HF, with some of these patients seeming more likely to respond.

Abstract Background Error analysis plays a crucial role in clinical concept extraction, a fundamental subtask within clinical natural language processing (NLP). The process typically involves a manual review of error types, such as contextual and linguistic factors contributing to their occurrence, and the identification of underlying causes to refine the NLP model and improve its performance. Conducting error analysis can be complex, requiring a combination of NLP expertise and domain-specific knowledge. Due to the high heterogeneity of electronic health record (EHR) settings across different institutions, challenges may arise when attempting to standardize and reproduce the error analysis process. Objectives This study aims to facilitate a collaborative effort to establish common definitions and taxonomies for capturing diverse error types, fostering community consensus on error analysis for clinical concept extraction tasks. Materials and Methods We iteratively developed and evaluated an error taxonomy based on existing literature, standards, real-world data, multisite case evaluations, and community feedback. The finalized taxonomy was released in both .dtd and .owl formats at the Open Health Natural Language Processing Consortium. The taxonomy is compatible with several different open-source annotation tools, including MAE, Brat, and MedTator. Results The resulting error taxonomy comprises 43 distinct error classes, organized into 6 error dimensions and 4 properties, including model type (symbolic and statistical machine learning), evaluation subject (model and human), evaluation level (patient, document, sentence, and concept), and annotation examples. Internal and external evaluations revealed strong variations in error types across methodological approaches, tasks, and EHR settings. Key points emerged from community feedback, including the need to enhancing clarity, generalizability, and usability of the taxonomy, along with dissemination strategies. Conclusion The proposed taxonomy can facilitate the acceleration and standardization of the error analysis process in multi-site settings, thus improving the provenance, interpretability, and portability of NLP models. Future researchers could explore the potential direction of developing automated or semi-automated methods to assist in the classification and standardization of error analysis.

Abstract Background: Nutritional and inflammatory factors collected in routine cancer labs, neutrophil percentage to albumin ratio (NPAR), neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR), have been shown feasible in identification of patients at risk of increased treatment complications, decreased cognition, anxiety and depression, and increased mortality. These have proven sensitive to multiple cancer types and stages, though little is known about causal pathways. The Vitamin/Mineral and Inflammatory Correlations To Understand Chronic Stress in the U.S. (The VICTUS Study) sought to elucidate a relationship between diet and food insecurity within these panels. Methods: Using NHANES 2017/2018 surveys, adults > 18 years without renal or hepatic disorders, pregnancy, alcohol, or supplement use were included. NPAR, NLR, MLR, and PLR were categorized as quartiles and compared to demographic, food security, plasma micronutrient statuses [vitamins A, B9, C, D, E, calcium (Ca), ferritin (Fe), phosphorus (P), potassium (K), sodium (Na)], and smoking, activity level, and sun exposure, using chi-square and ANOVA. ANOVA models compared food security and poverty to NPAR, NLR, MLR, and PLR means. Results: From 3,317 participants, 50.2% were male, 54.3% non-Hispanic White, 33.7%, food insecure, 51.1% food stamp recipients, 27.7% smokers, with a mean age of 42.5 (SD 0.44), poverty to income ratio 2.79 (SD 0.08), CRP 3.90 (SD 0.18), NPAR 14.1 (SD 0.14), NLR 2.07 (SD 0.04), MLR 0.28 (SD 0.003), and PLR 118.7 (SD 1.61). CRP was found to be statistically significantly associated with all biomarker ratios (p < 0.018). Significant micronutrient biomarker-inflammatory biomarker associations were identified in Fe [NPAR, MLR, PLR (p < 0.001)], P [NPAR, NLR, MLR, PLR (p < 0.033)], C [NPAR, NLR (p < 0.008)], E [MLR, PLR (p < 0.016)], K [NPAR, NLR, MLR, PLR (p < 0.015)], Ca [NPAR, PLR (p < 0.04)], A [NPAR (p < 0.023)] and D [NLR (p < 0.035)]. Significant micronutrient intake-inflammatory biomarker associations were detected in vitamin A [NPAR, PLR (p < 0.013)], lycopene [NLR, PLR (p < 0.035)], and B12 [NLR, PLR (p < 0.031)]. Age [NPAR, NLR, MLR, PLR (p < 0.001)], gender [NPAR, MLR, PLR (p < 0.001)], ethnicity [NPAR, NLR, MLR (p < 0.006)], and sedentariness [MLR, PLR (p < 0.039)] were also associated with inflammatory markers. Poverty was significantly associated with NPAR, NLR, MLR, and CRP (p < 0.018). Food insecurity was significantly associated with NPAR (p < 0.001) and CRP (p < 0.001). Discussion: Food insecurity and poverty were significantly associated with NPAR, a ratio implicated in overall poorer cancer health outcomes. Multiple inadequate micronutrient intakes and plasma biomarkers were associated with inflammatory panels, though neither nutritional biomarker nor food insecurity statuses and their contributions to inflammatory processes are routinely surveilled within cancer disease and treatment. Citation Format: Jennifer Crook, Eunkyung Lee, Rui Xie, Opeyemi Bolajoko, Victoria Loerzel. Nutritional mediators of inflammation: A cause for increased surveillance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2171.

Abstract Background: Though widely recognized in cancer pathogenesis, inflammatory pathways of allostatic load remain vaguely understood. A partial explanation may be found within the realm of food insecurity and micronutrient inadequacies, defined as nutrient intake less than the estimated average requirement. Many micronutrient deficiencies contribute to pro-inflammatory and immunocompromised milieus. Inadequacies, however, which may present without overt symptoms, are not currently well studied. The purpose of this study was to examine relationships between known inflammation-associated nutritional biomarkers of micronutrients and biomarker variables of allostatic load. Methods: Using NHANES 2017/2018 surveys, adults > 18 years without renal or hepatic disorders, pregnancy, alcohol, or supplement use were included. Plasma levels of vitamins A, B9, C, D, E, calcium (Ca), ferritin (Fe), phosphorus (P), potassium (K) and sodium (Na) were grouped into deficiency, inadequate and adequate groups based on clinically recognized standards. Micronutrient prevalence was assessed and variables of allostatic load [blood pressure, glucose, albumin, creatinine, red cell distribution width (RDW), high density lipoprotein (HDL), low density lipoprotein (LDL), cholesterol and triglycerides] were analyzed for mean differences among micronutrient groups, food security and poverty. Results: From 3,317 unique participants, inadequacy prevalence percentages were quantified as: vitamins A (0.4%), B9 (12.2%), C (58.3%), D (39.6%), E (21.0%), P (11.4%), K (3.4%), Na (24.2%), Ca (59.5%), and Fe (37.4%) [p < 0.001]. Statistically significant differences were identified in age [C, D, E, Ca, Fe, P, Na (p < 0.004)], race/ethnicity [B9, C, D (p < 0.006)], gender [C, E, Ca, Fe, P, K, Na (p < 0.018)], poverty [A, B9, C, D, E, Fe, K (p < 0.025)], and food security [B9, C, D, E, P (p < 0.032)]. Associations to allostatic load were discovered in: albumin [A, C, D, Ca, Fe, P, Na (p < 0.025)], glucose [C, E, Fe, P, Na (p < 0.009)], HDL [C, D, E, Fe, P, K (p<0.045)], LDL [E, Ca, Fe, Na (p<0.028)], creatinine [C, D, Ca, Fe (p<0.001)], triglycerides [B9, D, E, Fe (p<0.033)], cholesterol [C, D, E, Ca, Fe, Na (p<0.006)], B/P [C, E, Fe, P, Na (p < 0.035)], and RDW [C, D, Ca, Fe (p < 0.001)]. Poverty was significantly associated with all variables of allostatic load (F = 2.85, p = 0.002). Food security was significantly correlated with albumin (p < 0.001), glucose (p = 0.005) and HDL (p < 0.001). Conclusion: Allostatic load, poverty, and food security were significantly associated with subclinical micronutrient statuses, which may not present with signs of deficiency and are not currently well assessed. Similarly, poverty was significantly associated with all variables of allostatic load, though food security was only identified to be associated with albumin, glucose, and HDL, suggesting that food security may not be currently adequately defined for surveillance. Citation Format: Jennifer M. Crook, Eunkyung Lee, Opeyemi Bolajoko, Rui Xie. Poverty, food insecurity, and nutritional inflammatory mediators of allostatic load [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2198.

Background: Deeper depth of response (DpR) after induction therapy, especially gain of negative minimal residual disease (MRD), has been linked to prolonged survival in multiple myeloma (MM). However, flow-MRD examination focuses on the numbers but not on the biological characteristics of residual plasma cells (PCs). Objectives: To explore whether the genetic features of residual tumor cells affect the survival time of patients with MM. Design: A retrospective cohort study. Methods: We investigated the clonality of cytogenetic abnormalities (CAs) of the residual PCs using interphase fluorescence in situ hybridization (iFISH) in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Here, a longitudinal cohort of 269 patients with patient-paired diagnostic and post-induction iFISH results was analyzed. Results: Persistent CAs after induction therapy were detected in about half of the patients (118/269, 43%), and patients with undetectable CAs showed significantly improved survival compared with those with genetically detectable MRD [median progression-free survival (mPFS): 59.7 versus 35.7 months, p < 0.001; median overall survival (mOS): 97.1 versus 68.8 months, p = 0.011]. In addition, different patterns of therapy-induced clonal evolution were observed by comparing the clonal structure of residual PCs with paired baseline samples. Patients who maintained at a high risk during follow-up had the worst survival (mPFS: 30.5 months; mOS: 54.4 months), while those who returned to lower risk or had iFISH− at both time points had the best survival (mPFS: 62.0 months, mOS: not reached). Conclusion: These findings highlighted the prognostic value of genetic testing in residual tumor cells, which may provide a deep understanding of clonal evolution and guide clinical therapeutic strategies.

AbstractBackgroundLewy body dementia (LBD) is one of the most common causes of dementia and is characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of alpha‐synuclein in the form of Lewy bodies and neurites. Many of these individuals also have concomitant neuropathological changes such as vascular disease, tangles, and TDP‐43. Like in Alzheimer’s disease, APOE4 is the most significant genetic risk factor for the development of LBD. We sought to survey the landscape of transcriptional changes in the cingulate cortex from a large cohort of LBD cases (>400) compared to normal controls of both sexes.MethodWe performed bulk tissue RNAseq and aligned reads to a human reference genome that is informed on the sex chromosome complement of the sample. Differentially expressed genes were determined after genome‐wide correction.ResultWe found a core set of transcriptional changes that were shared between both sexes in pathways related to neuronal functions and inflammation. However, we also identified numerous changes in genetic female samples that were not significantly altered in genetic males, or that were significantly altered but in the opposite direction. Similar male‐specific changes were also found. These alterations were present for genes on both sex chromosomes as well as autosomes. Though cohort sizes were smaller, we also compared this dataset to Alzheimer’s disease and found shared but unique transcriptional alterations.ConclusionOverall, genetic males and females exhibit sex‐shared and sex‐specific gene expression patterns in dementia with Lewy bodies. We are currently assessing splice alterations, running causal gene network analysis, and performing histological validation.

AbstractBackgroundBrain glucose hypometabolism is among the earliest pathogenic changes in Alzheimer’s disease (AD). This metabolic dysfunction points to the personal bioenergetic capacity, defined as the ability to maintain energy homeostasis under all circumstances including deregulated glucose uptake, as a potential source of resilience to the disease. Fasting blood acylcarnitine profiles are a central readout for this capacity in the absence of dietary glucose and capture the activity and efficiency of glucose‐independent routes of mitochondrial energy metabolism.MethodWe used fasting serum acylcarnitine profiles of 1,531 participants (465 with normal cognition, 762 with mild cognitive impairment, and 304 with clinical AD) from the AD Neuroimaging Initiative to perform unsupervised subgroup identification using hierarchical clustering. Identified subgroups were investigated for differences in A/T/N biomarker profiles and cognitive status. The contributions of genetic and potentially modifiable factors defining the subgroups were quantified using analysis of explained variance. The influence of the strongest determining factors on longitudinal cognitive trajectories was estimated using linear mixed‐effects models and gene‐by‐environment interaction analysis.ResultWe found several bioenergetically distinct subgroups with significant differences in AD biomarker profiles and cognitive function. The strongest genetic contribution to this bioenergetic endophenotype seems to be specifically linked to succinylcarnitine metabolism and significantly modulates the rate of future cognitive decline. In contrast, potentially modifiable sustainment of beta‐oxidation efficiency seems to decelerate bioenergetic aging, thus creating a bioenergetic reserve that delays progression of cognitive decline. Using gene‐by‐environment interaction analysis, we demonstrate that this molecular framework identifies a subgroup of individuals that is likely to benefit significantly from personalized therapeutic, dietary or lifestyle interventions tailored to increase resilience against bioenergetic disturbances in AD.ConclusionOur study reports on a set of genetic and metabolic markers that define bioenergetically distinct subgroups with significant differences on the AD biomarker and cognitive level. Longitudinal data suggest that targeting the modifiable fraction of this endophenotype might be a promising strategy to slow down disease progression in individuals with specific allelic configurations.

Introduction: The impact of COVID-19 was felt across cardiology as resources were redirected to critical care, delaying elective cardiology procedures. Hypothesis: To evaluate differences in outcomes of cardiac implantable electronic device (CIED) procedures in 2020 (height of COVID) vs. 2016-2019 (pre-COVID). Methods: Adults >= 18 years undergoing CIED procedures were identified from National Inpatient Sample Databases (NIS) 2016-2020. Complications and mortality were assessed based on the type of device: Permanent Pacemaker (PPM); Implantable Cardioverter Defibrillator (ICD); Cardiac Resynchronization Therapy with Pacemaker (CRT-P) or defibrillator (CRT-D): Leadless PPM; Generator explant (GE), and Lead extraction (LE). Results: A 13.8% drop in CIED admissions was recorded between 2019 and 2020 (p<0.01). Fewer procedures involving PPM, ICD, CRT-P, CRT-D, LE, and GE were observed between 2019 and 2020. Leadless PPM utilization rose consistently between 2016-2020 (47.6% increase during 2020 vs 2019)(Figure). In 2020, a higher proportion of patients were classified with a Charlson Comorbidity Index score of ≥3 (severe) (47.4% in 2020 vs. 42.9% in 2016-2019, p<0.01). The table shows significantly higher complications during CIED implants with no changes in mortality related to procedures. Conclusions: Patients admitted for CIED implants in 2020 had more severe comorbidities and expressed considerable differences in complications than pre-COVID era (2016-2019), but mortality remained unchanged. Leadless PPM use increased during pandemic, as against a decrease in the use of other CIEDs.

Introduction: While Coronavirus disease 2019 (COVID-19) primarily affects the respiratory system but can impact the cardiovascular system can triggering various complications. Hypothesis: To investigate the trend in age-adjusted mortality rates (AAMRs) in patients with atrial fibrillation(AF) among COVID-19-positive patients (CPP) by race and sex. Methods: Trends in AAMRs (per 100,000) from all-cause in patients with AF between April to December 2016-2020 were evaluated via the National Inpatient Sample and the US Census Bureau. The AAMRs among CPP with AF in 2020 was also evaluated between racial and sex cohorts. Results: A gradual rise in AAMR(all causes) in patients with AF was observed between 2016-2019, with a 49.4% overall rise between 2019(271 per 100,000) and 2020(405 per 100,000) ( Table 1a and Figure ). Around 250475 COVID-19-positive patients had AF, and 24.2% of cases did not survive their hospitalization (vs. 10.9% in those without AF, p<0.01, aOR 1.457, 95% CI 1.438-1.477). Among CPP males and females with AF that died, White females and males were the oldest, while Black males and females reported the highest mean Charlson Comorbidity Index (CCI) score ( Table 1b ).Furthermore, among the CPP with AF in 2020, Hispanics reported a higher AAMR (119.6 per 100,000) than Whites(111.1 per 100,000) and Blacks(101.9 per 100,000). AAMRs in males were higher in Hispanic males (144.8 per 100,000), followed by White males (129.7 per 100,000), and Black males (110 per 100,000). However, the AAMRs in females were highest in Black females (91.3 per 100,000), followed by White females (88.3 per 100,000) and Hispanic females (87.0 per 100,000). ( Table 1c ) Conclusions: AAMRs in patients with AF are on the rise and a sharp growth was seen during the first year of the pandemic. AAMRs among CPP patients with AF were highest among Black females and Hispanic males, while White males and females were oldest and Black males and females reported the highest CCI scores.