tbuckley/cabot-search huggingface dataset:
Abstract 12008: Quantitative Pupillometry for Neuroprognostication in Post-Cardiac Arrest: A Prospective Validation Study
Authors: Benjamin C Nyholm, Laust Obling, Johannes Grand, Christian Hassager, Jacob Moller, Marwan Othman, Daniel Kondziella, Jesper Kjaergaard
Journal: Circulation (2021)

Background: Quantitative pupillometry is a new tool in multimodal neuroprognostication of comatose patients after out-of-hospital cardiac arrest, but the reliability and precision of quantitative pupillometry is not fully understood. Methods: We conducted a prospective blinded validation study with repeated patient assessment at our cardiac intensive care unit. To investigate intra- and interobserver variability of pupil size (mm), each assessment was performed on the same patient by two staff nurses within 2 minutes. The sequence consisted of a series of measurements with quantitative-, and manual pupillometry, performed subsequently to each other. Bland-Altman analysis with 95% limits of agreement (LoA) was used. Results: We included 14 sedated, comatose patients (6 females) with a mean age of 70 ± 12 years, resulting in 28 individual assessments. Quantitative pupillometry presented intraobserver variability with mean difference for maximum pupil size of 0.04 ± 0.13 with LoA of -0.21 to 0.28, and interobserver variability with mean difference of 0.03 ± 0.17 and of -0.31 to 0.36. For comparison, manual pupillometry revealed a mean difference of -0.02 ± 0.31 with LoA of -0.58 to 0.63, and -0.14 ± 0.44 with LoA of -1.00 to 0.71 for intra-, and interobserver variability, respectively. When comparing pupil size for left and right eyes, quantitative pupillometry resulted in LoA at -0.19, 0.25 (left) and -0.23, 0.32 (right), and LoA at -0.33, 0.39 (left) and -0.30, 0.34 (right) for intra-, and interobserver variability, respectively. Manual pupillometry presented LoA at -0.59, 0.63 (for both left and right), and LoA at -1.10, 0.79 (left) and -0.95, 0.83 (right) for intra-, and interobserver variability, respectively. Conclusion: Results from quantitative pupillometry are significantly more reproducible than manual measurements, suggesting it can be safely implemented in clinical practice for multimodal neuroprognostication of post-cardiac arrest patients.
Rates of Neutropenic Fever in Patients with Hematologic Malignant Diseases with Central Venous Access
Authors: Sujith Abbagoni, Sarah Malik, Ashley D Fox, Mohammad A. H. Mian, Tahsin Anwar, Danielle Bradshaw, Locke J. Bryan, Anand P Jillella, Ravindra Kolhe, Natasha M. Savage, Sandeep Padala, Vamsi Kota
Journal: Blood (2021)
Abstract 12363: Statin Use and Severity of First Manifestation of Coronary Heart Disease Across Age and Sex
Authors: Maria Bergami, Jinsung Yoon, Guiomar Mendieta, Sasko Kedev, Marija Zdravkovic, Zorana Vasiljevic, Davor Milicic, Olivia Manfrini, Mihaela van der Schaar, Chris P Gale, Lina Badimon, Edina Cenko, Raffaele Bugiardini
Journal: Circulation (2021)

Introduction: We investigate whether treatment recommendations for statins in primary prevention of cardiovascular disease (CVD) based on sex, age and risk factors translate to better CV outcomes in current routine clinical care. Methods: We studied a propensity match-weighted cohort of 14,542 Caucasian patients presenting with a first manifestation of CVD from the International Survey of Acute Coronary Syndromes (ISACS) Archives databank (NCT04008173) . Main outcome measures were the incidence of ST segment elevation myocardial infarction (STEMI) and acute heart failure (HF) on hospital admission. Results: Prior statin use was associated with a significantly decreased rate of STEMI (absolute difference 10.2%; RR ratio, 0.64; 95%CI 0.58 to 0.71) and acute HF (absolute difference 4.3%; RR ratio 0.72, 95% CI 0.62 to 0.83). Benefits were not attenuated when controlling for age 75 years and older (RR ratios 0.59, 95% CI 0.46 to 0.75 for STEMI and 0.66, 95% CI 0.50 to 0.87 for HF). Statin therapy had no effect in patients with 10-year ASCVD risk threshold less than 10% (RR ratios:0.85,95%CI:0.66- 1.08 for STEMI and 0.85,95%CI:0.60-1.20 for HF). Reductions in major CV events with statins diminished with female sex (interaction p=0.0200 for STEMI, and 0.2180 for HF). Moreover, statin use determined a lower risk of 30-day mortality in patients presenting with HF on admission (5.2 % absolute risk reduction and a 29% relative risk reduction). Conclusions: Prevention statin therapy reduces the risk of STEMI and acute HF with benefit in mortality from HF. The most gain is attained in male sex and in subjects with 10-year ASCVD risk ≥10%
Correction to: Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma
Authors: Aibin Liu, Jinrong Zhu, Geyan Wu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Lili Jiang, Jueheng Wu, Mengfeng Li, Libing Song, Jun Li
Journal: Molecular Cancer (2021)
Abstract 13633: Cardiac Arrhythmias in Hospitalized Patients With Hereditary Hemochromatosis
Authors: Krunalkumar Patel, Shivani Dalal, Muhammad Zubair Khan, Jay Shah, Daniel Tran, Umang Patel, Steven Kutalek
Journal: Circulation (2021)

Introduction: Cardiac iron overload in Hereditary Hemochromatosis (HH) can lead to conduction disturbances, arrhythmias, and rarely, cardiac arrest. There is a paucity of data on HH and the burden of cardiac arrhythmias and its repercussions. Hypothesis: To determine baseline characteristics of HH patients with and without arrhythmias, frequency of subtypes of arrhythmias, and related in-hospital outcomes such as mortality, length of stay (LOS), and total hospital costs. Methods: An HH-related adult hospitalizations with or without arrhythmias were analyzed using the National Inpatient Sample database from 2016 to 2018. We used propensity score matching to balance out the differences in baseline characteristics among the 2 groups. Results: Out of 10455 HH hospitalizations, 2525 (24.2 %) had concurrent arrhythmias. The arrhythmia cohort consisted of older patients (mean age, 68.9 vs 59.8 years), predominantly males (71.1% vs 61.5%), and Caucasians (92.5% vs 89.3%) compared to those without arrhythmia (p&lt;.001). HH patients with arrhythmias had an almost 3-fold higher prevalence of congestive heart failure (11.5% vs 3.7%) and coronary artery disease (33.3% vs 12.2%) (p&lt;.001). Atrial fibrillation (AF) (73.3%) was the most common arrhythmia followed by atrial flutter (8.3%), ventricular tachycardia (8.1%), and supraventricular tachycardia (7.7%). The arrhythmia cohort had higher mortality (6.7% vs. 2.3%) and mean hospital cost ($ 25,957 vs $16,742) as compared to the non-arrhythmia cohort ( P &lt; .001). Mean LOS (6.7 vs 5.7 days, p=0.007) was comparable between the groups. Conclusions: Our study suggests a high burden of arrhythmia in HH-hospitalizations with AF being the most common arrhythmia. The arrhythmia cohort had significantly higher in-hospital mortality, and hospitalization cost. This warrants further studies to better delineate pathogenesis and early diagnosis and treatment strategies specifically curated for HH-associated arrhythmias.
Abstract 9758: Estimating Cardiovascular and Limb Benefits of Combined Contemporary Risk Reduction Therapies in Patients with Symptomatic Peripheral Artery Disease: An Analysis of Randomized Controlled Trials
Authors: Mohamad A Hussain, Tanujit Dey, Stuart R Lipsitz, Deepak L Bhatt, Subodh Verma, John W Eikelboom, Marc P Bonaca, Michael Belkin, C Keith Ozaki, Mohammed Al-Omran
Journal: Circulation (2021)

Introduction: Individual randomized controlled trials (RCTs) have shown beneficial effects of low dose rivaroxaban and PCSK9 inhibition (PCSK9i) in addition to background aspirin and statin in patients with peripheral artery disease (PAD). However, the combined effect of these pharmacotherapies is not known. In this analysis of RCT data, we sought to estimate the combined effect of contemporary risk reduction therapies in patients with PAD. Methods: We used data from the COMPASS (n=4,129) and FOURIER (n=3,642) trials to estimate the combined effect of contemporary (aspirin, statin, low dose rivaroxaban and PCSK9i) versus standard therapy (aspirin and statin) in symptomatic PAD patients. The primary outcome was a composite of major adverse cardiovascular (MACE) or limb (MALE) events. Using the hazard rates for low dose rivaroxaban versus control and PCSK9i versus control from the two trials, we estimated the hazard rate for combined therapy by assuming that the treatment effects are approximately additive on the log hazard rate (no interaction between the two treatments). We then used an exponential model to simulate event-free survival and cumulative incidence functions, and hazard ratios (HRs) for the combined versus the standard therapy group. Results: Compared with standard therapy, combined contemporary pharmacotherapy estimated a 50% reduction in MACE or MALE (HR, 0.50; 95% confidence interval [CI], 0.36-0.70; P&lt;0.001). The 3-year cumulative incidence probability of MACE or MALE was 9.1% in the combined group and 15.4% in the standard therapy group ( Figure ). The hazards for MACE (HR, 0.52; 95% CI, 0.36-0.75; P=0.001) and MALE (HR, 0.35; 95% CI, 0.18-0.68; P=0.002) also favored combined contemporary therapy. Conclusions: Thoughtful incorporation of contemporary pharmacotherapies that include low dose rivaroxaban and PCSK9i in addition to aspirin and statin has the potential to substantially reduce cardiovascular and limb events in patients with PAD.
Dyrk1b promotes hepatic lipogenesis by bypassing canonical insulin signaling and directly activating mTORC2 in mice
Authors: Neha Bhat, Anand Narayanan, Mohsen Fathzadeh, Mario Kahn, Dongyan Zhang, Leigh Goedeke, Arpita Neogi, Rebecca L Cardone, Richard G Kibbey, Carlos Fernandez-Hernando, Henry N Ginsberg, Dhanpat Jain, Gerald I Shulman, Arya Mani
Journal: Journal of Clinical Investigation (2021)

Mutations in Dyrk1b are associated with metabolic syndrome and nonalcoholic fatty liver disease in humans. Our investigations showed that DYRK1B levels are increased in the liver of patients with nonalcoholic steatohepatitis (NASH) and in mice fed with a high-fat, high-sucrose diet. Increasing Dyrk1b levels in the mouse liver enhanced de novo lipogenesis (DNL), fatty acid uptake, and triacylglycerol secretion and caused NASH and hyperlipidemia. Conversely, knockdown of Dyrk1b was protective against high-calorie-induced hepatic steatosis and fibrosis and hyperlipidemia. Mechanistically, Dyrk1b increased DNL by activating mTORC2 in a kinase-independent fashion. Accordingly, the Dyrk1b-induced NASH was fully rescued when mTORC2 was genetically disrupted. The elevated DNL was associated with increased plasma membrane sn-1,2-diacylglyerol levels and increased PKCε-mediated IRKT1150 phosphorylation, which resulted in impaired activation of hepatic insulin signaling and reduced hepatic glycogen storage. These findings provide insights into the mechanisms that underlie Dyrk1b-induced hepatic lipogenesis and hepatic insulin resistance and identify Dyrk1b as a therapeutic target for NASH and insulin resistance in the liver.
The Lack of Helmets in Olympic Skateboarding—Skating Into Dangerous Territory
Authors: Mary O’Connor, Setu Mehta, Ruth Milanaik
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract P462: Bscl2/seipin Deficiency In Heart Causes Energy Deficit And Heart Failure Via Inducing Excessive Lipid Catabolism
Authors: Hongyi Zhou, Jie Li, Huabo Su, Ji Li, Todd A Lydic, Martin E Young, Weiqin Chen
Journal: Circulation Research (2021)

Heart failure (HF) is one of the leading causes of death world-wide and is associated with cardiac metabolic perturbations. Human Type 2 Berardinelli-Seip Congenital Lipodystrophy (BSCL2) disease is caused by mutations in the BSCL2 gene. Global lipodystrophic Bscl2 –/– mice exhibit hypertrophic cardiomyopathy. Whether BSCL2 plays a direct role in regulating cardiac substrate metabolism and/or contractile function remains unknown. Here we show that mice with cardiac-specific deletion of Bscl2 ( Bscl2 cKO ) developed dilated HF. Myocardial BSCL2 deletion led to elevated ATGL expression and FA oxidation (FAO) along with reduced cardiac lipid contents. Cardiac dysfunction in Bscl2 cKO mice was independent of mitochondrial dysfunction and oxidative stress, but associated with decreased metabolic reserve and ATP levels. Importantly, heart failure in Bscl2 cKO mice could be partially reversed by pharmacological inhibition of FAO, or prevented by high fat diet (HFD) feeding. Lipidomic analysis further identified markedly reduced glycerolipids, glycerophospholipids, NEFA and acylcarnitines in Bscl2 cKO hearts, which were partially normalized by FAO inhibition or HFD. Our study reveals a new form of HF with excessive lipid catabolism, and identifies a crucial cardiomyocyte-specific role of BSCL2 in controlling cardiac lipid catabolism, energy state and contractile function. It also provides novel insights into metabolically treating energy-starved HF using FAO inhibitor or HFD.
CTNI-07. ABTC-1701: PILOT SURGICAL PK STUDY OF BGB324 (BEMCENTINIB) IN RECURRENT GLIOBLASTOMA PATIENTS – RESULTS FROM INTERIM FUTILITY ANALYSIS
Authors: L Burt Nabors, Ichiro Nakano, Jeff Supko, Mina Lobbous, Stuart Grossman, Xiaobu Ye, Serena Desideri, Neeraja Danda, Joy Fisher, Roy Strowd, Tobias Walbert
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma often can relapse as mesenchymal (MES) tumors, indicating a phenotypic shift during clinical progression. Glioma spheres, when they gain MES phenotypes, develop dependence on AXL for their growth both in vitro and in vivo. The first-in-class orally bioavailable AXL kinase inhibitor bemcentinib has IC50 of 14 nM and is &amp;gt; 100-fold selective for AXL over other kinases. Bemcentinib is currently under evaluation as a monotherapy and in combination with other treatments across various PhII trials in several oncology indications. METHODS This is an open-label, multicenter, intratumoral pharmacokinetic study of bemcentinib in patients with recurrent glioblastoma for whom a surgical resection is medically indicated. All subjects must have had histological confirmation of glioblastoma by either biopsy or resection that is progressive or recurrent following radiation therapy ± chemotherapy. Intratumoral drug levels were analyzed by LC/MS. RESULTS A planned analysis after the first 5 patients were enrolled with glioblastoma (4 IDH WT and 1 IDH-mutant), (3m, 2f, median age 57, KPS 80). Bemcentinib concentration in contrast enhancing brain tissue ranged from 3.1 to 43.0 uM with a geometric mean concentration of 11.1 uM (% CV, 132.1). The drug concentration in contrast enhancing tumor tissue exceeded the 1.0 uM threshold in all 5 patients, satisfying the criteria of the protocol to enroll an additional 15 patients into the surgical study. Total drug levels were approximately 2-fold greater in contrast enhancing tissue as compared to tissue from a non-enhancing region of the tumor (geometric mean, 5.8 uM; % CV, 187.7). The mean ratio of the drug concentration in brain tissue to plasma was 25.9 (% CV, 92.7) for contrast enhancing tissue and 13.4 (% CV, 126.8) for non-enhancing tissue. CONCLUSIONS Bemcentinib readily distributes in brain tumor tissue following oral administration. The study continues to complete accrual for the remaining 15 patients.
Delineating the Role of Interplay between m6A Machinery Genes and IGF2BP Group of RNA-Binding Proteins in B-Cell Acute Lymphoblastic Leukemia (B-ALL)
Authors: Sumedha Saluja, Jay Singh, Ayushi Jain, Shilpi Chaudhary, Karthikeyan Pethusamy, Parthaprasad Chattopadhyay, Sameer Bakhshi, Anita Chopra, Archna Singh, Subhradip Karmakar, Jayanth Kumar Kumar Palanichamy
Journal: Blood (2021)
Disease-related income and economic productivity loss in New Zealand: A longitudinal analysis of linked individual-level data
Authors: Tony Blakely, Finn Sigglekow, Muhammad Irfan, Anja Mizdrak, Joseph Dieleman, Laxman Bablani, Philip Clarke, Nick Wilson
Journal: PLoS Medicine (2021)

Background Reducing disease can maintain personal individual income and improve societal economic productivity. However, estimates of income loss for multiple diseases simultaneously with thorough adjustment for confounding are lacking, to our knowledge. We estimate individual-level income loss for 40 conditions simultaneously by phase of diagnosis, and the total income loss at the population level (a function of how common the disease is and the individual-level income loss if one has the disease). Methods and findings We used linked health tax data for New Zealand as a high-income country case study, from 2006 to 2007 to 2015 to 2016 for 25- to 64-year-olds (22.5 million person-years). Fixed effects regression was used to estimate within-individual income loss by disease, and cause-deletion methods to estimate economic productivity loss at the population level. Income loss in the year of diagnosis was highest for dementia for both men (US$8,882; 95% CI $6,709 to $11,056) and women ($7,103; $5,499 to $8,707). Mental illness also had high income losses in the year of diagnosis (average of about $5,300 per year for males and $4,100 per year for females, for 4 subcategories of: depression and anxiety; alcohol related; schizophrenia; and other). Similar patterns were evident for prevalent years of diagnosis. For the last year of life, cancers tended to have the highest income losses, (e.g., colorectal cancer males: $17,786, 95% CI $15,555 to $20,018; females: $14,192, $12,357 to $16,026). The combined annual income loss from all diseases among 25- to 64-year-olds was US$2.72 billion or 4.3% of total income. Diseases contributing more than 4% of total disease-related income loss were mental illness (30.0%), cardiovascular disease (15.6%), musculoskeletal (13.7%), endocrine (8.9%), gastrointestinal (7.4%), neurological (6.5%), and cancer (4.5%). The limitations of this study include residual biases that may overestimate the effect of disease on income loss, such as unmeasured time-varying confounding (e.g., divorce leading to both depression and income loss) and reverse causation (e.g., income loss leading to depression). Conversely, there may also be offsetting underestimation biases, such as income loss in the prodromal phase before diagnosis that is misclassified to “healthy” person time. Conclusions In this longitudinal study, we found that income loss varies considerably by disease. Nevertheless, mental illness, cardiovascular, and musculoskeletal diseases stand out as likely major causes of economic productivity loss, suggesting that they should be prioritised in prevention programmes.
CTIM-21. AN AGE-SPECIFIC BIOMARKER IN NEWLY-DIAGNOSED GLIOBLASTOMA PATIENTS TREATED WITH RADIATION, NIVOLUMAB AND BMS-986205
Authors: Miri Kim, Erik Ladomersky, Lijie Zhai, Lakshmi Bollu, April Bell, Kristen Lauing, Erik Rabin, Craig Horbinski, Rimas Lukas, Derek Wainwright
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION We previously determined that advanced age plays a negative role in the survival outcome of human recurrent glioblastoma (GBM) patients treated with immune checkpoint blockade. Here we investigate the immunologic “signature” of younger patients who are &amp;lt; 65 years of age and older adult GBM patients who are ≥ 65 years of age that undergo simultaneous treatment with standard radiation, nivolumab (anti-PD-1 mAb), and BMS-986205 (a potent IDO enzyme inhibitor) and are newly diagnosed with O6-methylguanine-DNA methyl-transferase (MGMT) unmethylated GBM. Our objective was to identify age-dependent immunologic changes before and after treatment with immunotherapy. METHODS Patients ≥ 18 years old with newly diagnosed MGMT unmethylated GBM, KPS ≥ 70, and minimal steroid use were eligible for enrollment in this phase 1 trial. PBMCs and serum were drawn at baseline and routine post-treatment time points followed by mass spec analysis of kynurenine (Kyn) and tryptophan (Trp) metabolites, RNAseq, and 18-color flow cytometric analysis. RESULTS 8 younger adults with a median age of 50 years old and 4 older adults with a median age of 68.5 years old were studied. The median overall survival of younger and older adults was 368 and 108.5 days, respectively (p=0.032, HR 4.8 for age). BMS-986205 treatment decreased the Kyn/Trp ratio of all patients irrespective of age. RNAseq analysis found significant age-related changes using Gene Ontology pathway analysis of T cell related immunity, lymphocyte activation, and NK cell mediated immunity. Flow cytometric analysis is ongoing. CONCLUSIONS Similar to what was reported in older adult mice treated with simultaneous RT, anti-PD-1 mAb, and IDO enzyme inhibitor, advanced age negatively affected the survival in older adult human GBM patients treated with an analogous clinical approach. Future determination of whether the age-related biomarker profile can be used diagnostically and therapeutically is now under investigation.
Abstract 13256: Factors Determining Mitral Valve Dysfunction in Patients Who Underwent Surgical Mitral Valve Replacement With Bio-Prosthetic Valves
Authors: Seo-yeon Gwak
Journal: Circulation (2021)

Introduction: There is increasing interest in bio-prosthetic MVD as recent advances in transcatheter MV interventions, but there is limited data. We sought to identify the factors determining mitral valve (MV) dysfunction (MVD) in patients who underwent MV replacement with bio-prosthetic valves and sought to clinical outcomes in patients with bio-prosthetic MVD. Hypothesis: MVD was related to younger age, renal dysfunction, postoperative elevated mean diastolic pressure gradient across the bio-prosthetic MV and anemia. Methods: A total of 233 patients underwent surgical bio-prosthetic MV replacement between June 1996 and May 2015. Finally, 226 patients (mean age 66.9±11.5 years, 74.3% of women) were analyzed. MVD was defined as an increase in mean gradient ≥ 5 mmHg with leaflet motion limitation and/or newly developed MV regurgitation during follow-up. Clinical outcome was defined as a composite of CV death, redo MV surgery or intervention, and hospitalization for heart failure. Results: During a median of 102 months (IQR 72 to 132 months), 65 patients (28.8%) revealed MVD. Factors associated with bio-prosthetic MVD were young age at operation (HR 0.97, 95% CI 0.95-0.99, p=0.001), end-stage renal disease (HR 4.29, 95% CI 1.45-12.71, p=0.007), elevated MDPG &gt;5.5 mmHg early after operation (HR 1.86, 95% CI 0.97-3.74, p=0.063) and anemia after operation (HR 0.84, 95% CI 0.74-0.95, p=0.007). Kaplan-Meier curves revealed significant differences in event-free survivals for the occurrence of bio-prosthetic MVD according to each factor ( Figure 1 ). Patients with bio-prosthetic MVD showed significantly poor clinical outcomes compared with those without bio-prosthetic MVD (EFS 43.1% vs. 91.9%, log-rank p&lt;0.001) during the follow-up. Conclusions: Young age at operation, ESRD, elevated MDPG and anemia after operation were associated with bio-prosthetic MVD in patients who underwent bio-prosthetic MV replacement.