tbuckley/cabot-search huggingface dataset:
Abstract 9165: Relationship Between the Cholesterol and Triglyceride Content of Lipoprotein Subclasses and Carotid Imtima-Media Thickness: Results from the Kyushu and Okinawa Population Study
Authors: Hiroaki Ikezaki, Norihiro Furusyo, Masumi Ai, Mitsuyo Okazaki, JUN HAYASHI, Eliana J Polisecki
Journal: Circulation (2021)

Introduction: The association between 20 lipoprotein cholesterol and triglycerides subclasses and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. Objective: Our goal was to assess which lipoprotein subclasses were associated with max cIMT levels. Methods: Levels of cIMT and 20 lipoprotein cholesterol and triglycerides subclasses using gel permeation high-performance liquid chromatography (GP-HPLC) were analyzed in 864 men and women (mean age 57 years, free of chronic liver or kidney diseases and off cholesterol-lowering, hormone replacement, or adrenocorticosteroid medications). Univariate and multivariate regression analyses were performed to examine the relationships between lipoprotein subclasses and max cIMT levels. Results: Max cIMT levels were 0.90 mm in women and 0.97 mm in men. After adjustment for age, gender, systolic blood pressure, smoking habits, diabetes, and hypertension treatment, elevated low-density lipoprotein cholesterol-2 and -3 were associated with higher max cIMT levels in both women and men. Decreased high-density lipoprotein cholesterol-7 were associated with higher max cIMT levels only in women (all P for trend &lt; 0.05). However, no associations were found between any triglyceride subclasses and max cIMT levels. Conclusions: Our data indicate that elevated smaller LDL cholesterol levels separated by GP-HPLC were significantly associated with max cIMT in both men and women. Our results support the concept that small dense LDL cholesterol is the most atherogenic lipoprotein parameter.
Trials in Progress: A Two-Cohort, Open-Label, Single-Arm Study of Emapalumab, an Anti-Interferon Gamma (IFNγ) Monoclonal Antibody, in Patients with Macrophage Activation Syndrome (MAS) in Rheumatic Diseases
Authors: Alexei A Grom, Jeanette Bachir, Veronica Asnaghi, Fabrizio De Benedetti
Journal: Blood (2021)
Abstract 10031: Gaps in Medical Therapy for Patients with Heart Failure and Reduced Ejection Fraction (HFrEF) in a Large, Diverse, Electronically Identified Cohort
Authors: Amrita Mukhopadhyay, Harmony Reynolds, Lawrence M Phillips, Arielle Nagler, Leora Horwitz, Stuart D Katz, Saul Blecker
Journal: Circulation (2021)

Background: National registries reveal significant gaps in medical therapy for patients with heart failure and reduced ejection fraction (HFrEF), but may not completely capture the population eligible for therapy. We developed an electronic health record-based algorithm to identify eligible HFrEF patients, and used this to assess prescribing in a large, diverse, urban health system. Methods: In this cross-sectional study of NYU Langone Health outpatients (&gt;350 sites) with EF≤40% on echocardiogram and clinic visit from 3/1/2019-2/29/2020, we assessed contraindication to and prescription of the following: beta-blocker (BB), angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonist (MRA). Results: We electronically identified 2,732 patients for analysis. Among those eligible for each medication class, 84.8% and 79.7% were appropriately prescribed BB and ACE-I/ARB/ARNI, respectively, while only 23.9% and 22.7% were appropriately prescribed MRA and ARNI, respectively. In adjusted models (Table), younger age, cardiology visit, and lower EF were associated with increased prescribing. Medicaid insurance was associated with increased prescribing of ARNI and Black race with prescribing of MRA. Conclusions: We observed significant gaps in MRA and ARNI therapy for HFrEF patients. Medicaid insurance was associated with increased ARNI use, possibly due to lack of prior authorization requirements under New York State Medicaid policy. Our findings support system- and policy-level interventions to increase use of these life-saving therapies.
Selectively targeting myeloid-derived suppressor cells through TRAIL receptor 2 to enhance the efficacy of CAR T cell therapy for treatment of breast cancer
Authors: Saisha A Nalawade, Paul Shafer, Pradip Bajgain, Mary K McKenna, Arushana Ali, Lauren Kelly, Jarrett Joubert, Stephen Gottschalk, Norihiro Watanabe, Ann Leen, Robin Parihar, Juan Fernando Vera Valdes, Valentina Hoyos
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Successful targeting of solid tumors such as breast cancer (BC) using chimeric antigen receptor (CAR) T cells has proven challenging, largely attributed to the immunosuppressive tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs) inhibit CAR T cell function and persistence within the breast TME. To overcome this challenge, we have developed CAR T cells targeting tumor-associated mucin 1 (MUC1) with a novel chimeric costimulatory receptor that targets tumor necrosis factor–related apoptosis-inducing ligand receptor 2 (TR2) expressed on MDSCs. Methods The function of the TR2.41BB costimulatory receptor was assessed by exposing non-transduced (NT) and TR2.41BB transduced T cells to recombinant TR2, after which nuclear translocation of NFκB was measured by ELISA and western blot. The cytolytic activity of CAR.MUC1/TR2.41BB T cells was measured in a 5-hour cytotoxicity assay using MUC1+ tumor cells as targets in the presence or absence of MDSCs. In vivo antitumor activity was assessed using MDSC-enriched tumor-bearing mice treated with CAR T cells with or without TR2.41BB. Results Nuclear translocation of NFκB in response to recombinant TR2 was detected only in TR2.41BB T cells. The presence of MDSCs diminished the cytotoxic potential of CAR.MUC1 T cells against MUC1+ BC cell lines by 25%. However, TR2.41BB expression on CAR.MUC1 T cells induced MDSC apoptosis, thereby restoring the cytotoxic activity of CAR.MUC1 T cells against MUC1+ BC lines. The presence of MDSCs resulted in an approximately twofold increase in tumor growth due to enhanced angiogenesis and fibroblast accumulation compared with mice with tumor alone. Treatment of these MDSC-enriched tumors with CAR.MUC1.TR2.41BB T cells led to superior tumor cell killing and significant reduction in tumor growth (24.54±8.55 mm 3 ) compared with CAR.MUC1 (469.79±81.46 mm 3 ) or TR2.41BB (434.86±64.25 mm 3 ) T cells alone. CAR.MUC1.TR2.41BB T cells also demonstrated improved T cell proliferation and persistence at the tumor site, thereby preventing metastases. We observed similar results using CAR.HER2.TR2.41BB T cells in a HER2+ BC model. Conclusions Our findings demonstrate that CAR T cells that coexpress the TR2.4-1BB receptor exhibit superior antitumor potential against breast tumors containing immunosuppressive and tumor promoting MDSCs, resulting in TME remodeling and improved T cell proliferation at the tumor site.
Abstract 9588: Higher Survival With the Use of Extracorporeal Cardiopulmonary Resuscitation Compared With Conventional Cardiopulmonary Resuscitation in Children Undergoing Cardiac Surgery: Analysis of the Get With the Guidelines Registry©
Authors: Ryan L Kobayashi, Kimberlee Gauvreau, Peta Alexander, Sarah A Teele, Melania Bembea, Ravi R Thiagarajan
Journal: Circulation (2021)

Introduction: Extracorporeal cardiopulmonary resuscitation (E-CPR) has been increasingly utilized during in-hospital arrest in postoperative pediatric cardiac surgical patients. Despite this and the significant associated mortality, few pediatric multicenter analyses have evaluated if E-CPR increases survival for in-hospital cardiac arrest compared with conventional cardiopulmonary resuscitation (C-CPR). Methods: Children &lt;18 years in the Get with the Guidelines-Resuscitation Registry© suffering in-hospital cardiac arrest following cardiac surgery who received ≥10 minutes of CPR between January 2008 and December 2020 were included. We compared patient factors, pre-arrest comorbid conditions, and survival to hospital discharge for E-CPR and C-CPR groups. Results: Among 1219 patients from 56 institutions, 483 patients (39.6%) received E-CPR. Nearly 75% (910/1219) of patients were &lt;1 year of age with 39% (477/1219) under 1 month. Older patients were more likely to receive E-CPR (p=0.004). E-CPR utilization increased over the study period (p&lt;0.001). Non-Hispanic White patients accounted for almost half of the population (575/1219) and were also more likely to receive E-CPR (p=0.044) compared to other races/ethnicities. Patients with cyanotic cardiac malformations (p=0.005), congestive heart failure prior to admission (p=0.007), and hypotension prior to arrest (p=0.014) were also more likely to receive E-CPR. Unadjusted survival of the index CPR event (98% vs. 63%, p&lt;0.001) and to hospital discharge (47% vs 39%, p=0.007) were both higher in the E-CPR compared to C-CPR group. Conclusions: In a large, multicenter study of pediatric cardiac surgical patients suffering in-hospital arrest, we found that E-CPR is commonly used and had significantly higher survival to hospital discharge compared with C-CPR. E-CPR is an important rescue strategy for children with heart disease and centers performing cardiac surgery should develop E-CPR programs.
Abstract 12563: The Trajectory of Platelet Factor 4 in Acute Myocardial Infarction and the Impact of PCSK9-Inhibition
Authors: Efthymios Ziogos, Marlene S Williams, Michael Vavuranakis, Michael J Blaha, Steven R Jones, Steven P Schulman, Shenghan Lai, Gary Gerstenblith, Thorsten M Leucker
Journal: Circulation (2021)

Introduction: Increased platelet activity during the peri- and early post-infarction period may contribute to adverse outcomes during that time. Platelet factor 4 (PF4) promotes coagulation and inflammation. The trajectory of PF4 and the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on that trajectory are unknown. Hypothesis: Early administration of the PCSK9 inhibitor evulocumab, added to dual anti-platelet therapy, inhibits a rise in PF4 during the early post-infarction period. Methods: Participants from the Evolocumab in Acute Coronary Syndrome trials (EVACS; NCT03515304, NCT04082442), with a NSTEMI and a troponin-I of &gt; 5 ng/ml or a STEMI were randomized to placebo or to 420 mg SQ of evolocumab within 24 hours of hospitalization. We performed serial ex vivo serum PF4 levels obtained at baseline (prior to study drug administration), and at days 1 and 30 and PF4 values were normalized to total platelet count. Normally distributed data were summarized using means and standard deviations and non-normally distributed data using medians and interquartile ranges. Results: Twenty-three participants were randomized to placebo and 23 to evolocumab. Mean age was 60±13 years, 48% were women, 22% were African American and 96% were on dual anti platelet therapy. Baseline PF4 concentrations (expressed as ng/1k platelets) did not differ between the two groups (placebo: 9.3 [4-12] vs evolocumab 8.0 [4-12], p=0.8). There was no significant change in PF4 in the placebo group from baseline to day 1 but a significant increase to 13.0 [11-14], p&lt;0.01 (baseline vs 30 days) at 30 days (+32%). In contrast, there were no significant changes from baseline in the evolocumab group at either of the timepoints. At 30 days PF4 was higher in the placebo group 13.06 [11-14] than the evolocumab group 10.7 [6-13], p=0.04. Further analysis of results in the evolocumab group did not show any significant changes in PF4 based on the type of P2Y12 inhibitor used and no association with the change in LDL-cholesterol. Conclusion: A rise in PF4 levels was observed during the early post-infarction period in acute myocardial infarction patients. This rise was reversed by a single 420 mg SQ dose of evolocumab administered within 24 hours of hospital admission.
Abstract 10793: Duration of Rhythm Monitoring and Arrhythmia Recurrence After Pulmonary Vein Isolation for Atrial Fibrillation: A Systematic Review and Meta-Regression Study
Authors: Rudy R Unni, Roupen Odabashian, Ross Prager, Jimmy J Zhang, Nicholas Ng Fat Hing, Lebei Pi, Lily Chen, George Wells, Girish Nair
Journal: Circulation (2021)

Introduction: The effect of the rhythm monitoring strategy after catheter ablation for atrial fibrillation (AF) on reported atrial arrhythmia (AA) recurrence is not well characterized. We aimed to determine whether continuous rhythm monitoring after AF ablation detects more AA recurrence than intermittent rhythm monitoring, and whether the total duration of intermittent rhythm monitoring predicts reported AA recurrence. Methods: EMBASE, MEDLINE, and CENTRAL databases were systematically searched for randomized controlled trials (RCT) of adult patients undergoing first catheter ablation for AF from 2007 to 2019. Studies with a minimum of 12 months follow-up were included. We selected trial arms of patients undergoing first-time ablation for AF using pulmonary vein isolation alone, without additional left-sided ablation lesion sets. Studies of surgical and hybrid ablation, or those without full rhythm monitoring details were excluded. Duration of rhythm monitoring was extracted and summed in duplicate. Meta-regression with random effects and mixed-effects models was used to identify any association between duration of monitoring and single-procedure AA recurrence. Analyses were performed separately on arms of patients with paroxysmal AF, and persistent AF (PeAF) or combined PAF/PeAF. Results: The search strategy and study selection yielded 47 trial arms from 46 RCTs comprising 4236 patients: 30 arms of patients with PAF and 17 arms of patients with PeAF or both PAF/PeAF. There was less AA recurrence in arms undergoing intermittent monitoring than continuous monitoring in PAF arms (31.1% vs. 44.4%, p &amp;lt; 0.01), but not in PeAF/ PAF-PeAF combined arms (47.1% vs. 63.6%, p=0.22). There was no significant relationship between the duration of intermittent rhythm monitoring and AA recurrence in both PAF (p=0.87) and PeAF/ PAF-PeAF combined arms (p=0.14). Conclusions: In RCTs of catheter ablation for PAF, continuous rhythm monitoring detected higher AA recurrence rates than intermittent rhythm monitoring. The duration of intermittent rhythm monitoring did not influence reported AA recurrence. These findings have important implications to the care of patients with AF and to researchers studying AF ablation.
A Survey Conducted during COVID-19 Pandemic Among Brazilian Chronic Myeloid Leukemia and Philadelphia-Negative Myeloproliferative Neoplasms Patients
Authors: Leonardo Fechio, Ana Vitória Ferreira Mota, Jaisson Bortolini, Gislaine B O Duarte, Marcia Delamain, Samuel S Medina, Guilherme Brasil Duffles Amarante, Fernando Vieira Pericole, Hanalydia Machado, Marcelo Addas Carvalho, Katia B Pagnano
Journal: Blood (2021)
Abstract 14779: The Association of Disease Progression With Cardiovascular and Limb Outcomes in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial
Authors: Jennifer A Rymer, Hillary Mulder, Frank W Rockhold, William R Hiatt, Francis G Fowkes, Iris Baumgartner, Jeffrey S Berger, Brian Katona, Kenneth W Mahaffey, Lars Norgren, Juuso Blomster, William S Jones, Manesh R Patel
Journal: Circulation (2019)

Background: Patients with PAD have a high risk of future cardiovascular (CVD) events and mortality. Little is known about the changes in clinical disease stage over time in PAD patients, and the as...
Fractionated Inotuzumab Ozogamicin Combined with Low-Intensity Chemotherapy Provides Very Good Outcome in Older Patients with Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: First Results from the EWALL-INO Study
Authors: Patrice Chevallier, Thibault Leguay, Michael Doubek, Francoise Huguet, Cyril Salek, Aurélie Cabannes, Ulla Wartiovaara-Kautto, Colombe Saillard, Emmanuel Raffoux, Thomas Cluzeau, Stéphane Leprêtre, Marie Balsat, Anna Berceanu, Nicolas Boissel, Emmanuelle Clappier, Laure Morisset, Claude Gardin, Hervé Dombret, Philippe Rousselot
Journal: Blood (2021)
Association of a Healthy Lifestyle With All-Cause and Cause-Specific Mortality Among Individuals With Type 2 Diabetes: A Prospective Study in UK Biobank
Authors: Han Han, Yaying Cao, Chengwu Feng, Yan Zheng, Klodian Dhana, Shu Zhu, Cong Shang, Changzheng Yuan, Geng Zong
Journal: Diabetes Care (2021)

OBJECTIVE To evaluate the association of a healthy lifestyle, involving seven low-risk factors mentioned in diabetes management guidelines (no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, less sedentary behavior, adequate sleep duration, and appropriate social connection), with all-cause and cause-specific mortality among individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS This study included 13,366 participants with baseline type 2 diabetes from the UK Biobank free of cardiovascular disease (CVD) and cancer. Lifestyle information was collected through a baseline questionnaire. RESULTS During a median follow-up of 11.7 years, 1,561 deaths were documented, with 625 from cancer, 370 from CVD, 115 from respiratory disease, 81 from digestive disease, and 74 from neurodegenerative disease. In multivariate-adjusted model, each lifestyle factor was significantly associated with all-cause mortality, and hazard ratios associated with the lifestyle score (scoring 6–7 vs. 0–2 unless specified) were 0.42 (95% CI 0.34, 0.52) for all-cause mortality, 0.57 (0.41, 0.80) for cancer mortality, 0.35 (0.22, 0.56) for CVD mortality, 0.26 (0.10, 0.63) for respiratory mortality, and 0.28 (0.14, 0.53) for digestive mortality (scoring 5–7 vs. 0–2). In the population-attributable risk analysis, 29.4% (95% CI 17.9%, 40.9%) of deaths were attributable to a poor lifestyle (scoring 0–5). The association between a healthy lifestyle and all-cause mortality was consistent, irrespective of factors reflecting diabetes severity (diabetes duration, glycemic control, diabetes-related microvascular disease, and diabetes medication). CONCLUSIONS A healthy lifestyle was associated with a lower risk of all-cause mortality and mortality due to CVD, cancer, respiratory disease, and digestive disease among individuals with type 2 diabetes.
The Role of Lipoprotein(a) in Cardiovascular Diseases—Reply
Authors: Pradeep Natarajan, Hannah Miksenas, James L. Januzzi
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
EXTH-05. TUMOR TREATING FIELDS IN COMBINATION WITH THE TERT-INHIBITOR ERIBULIN HAVE SYNERGISTIC ANTIPROLIFERATIVE EFFECTS ON HUMAN GLIOBLASTOMA CELLS
Authors: Marco Stein, Piet Beusker, Hanna Goett, Malgorzata Kolodziej, Eberhard Uhl
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The optimal combination therapy for Tumor Treating Fields (TTFields) in glioblastoma (GBM) treatment is unknown. The aim of our study was to analyze, the effects of the TERT-inhibitor eribulin in combination with TTFields on human GBM cells. METHODS Human GBM cells of the established cell lines U87, A172 and U251, and two patient-derived cell lines, were treated with eribulin monotherapy, TTFields monotherapy, or both modalities together. After 72 hours of therapy, cell counts were measured and clonogenic assays were performed. Annexin staining and fluorescence-activated cell scanning (FACS) was used to analyze cell death. RESULTS Overall surviving fractions were 39.8±11.0% for eribulin monotherapy, 32.2±23.9% for TTFields monotherapy, and 10.9±9.9% for the combined treatment. Mean observed annexin positive fractions were 11.2±8.2% (control), 28.6±9.7% (eribulin), 34.8±8.1% (TTFields), and 78.1±13.5% (combination), respectively. The mean clonogenic fractions over all cell lines were 25.9±7.8% for eribulin and 46.4±12.9% for TTFields. For the combination therapy, a synergistic effect with a decreased mean of 3.6% clonogenic fractions was observed. CONCLUSION Eribulin increases cell death and reduces clonogenicity our experiments. Additionally, a synergistic effect of the combined treatment of TTFields and eribulin synergistic was observed. Eribulin in combination with TTFields could be a new effective therapy for GBM.
FOXQ1 is a novel p21 regulator in colorectal cancer cells.
Authors: Hiroyasu Kaneda, Tokuzo Arao, Kaoru Tanaka, Mari Maegawa, Kazuko Matsumoto, Kanae Kudo, Yoshihiko Fujita, Isamu Okamoto, Kazuhiko Nakagawa, Kazuto Nishio
Journal: Cancer Research (2008)

88  Forkhead box Q1 (FOXQ1) is known as a transcript factor and this gene has been proposed to participate in processes of hair follicle morphogenesis and DNA-dependent regulation of transcription. Microarray analysis (Affymetrix U133 ver 2) of 30 clinical specimen of colorectal cancer (CRC) revealed that FOXQ1 is overexpressed in CRC. To clarify the biological function of FOXQ1, we transfected the FOXQ1-targeting siRNA into the DLD-1 CRC cell line and analyzed the gene expression using the microarray. Knocked down of FOXQ1 decreased p21waf1/cip1 expression specifically. RT-PCR and western blotting confirmed this phenomenon. Conversely, retroviral transfection of FOXQ1 induced the expression of p21 waf1/cip1 mRNA and protein as compared with mock-transfected cells. Luciferase assay demonstrated that FOXQ1 enhanced transcriptional activity of cis-acting element of p21waf1/cip1 significantly. Direct binding of FOXQ1 by gel-shift assay in CRC will be presented. These results suggest that FOXQ1 regulates the p21 transcriptional levels specifically in CRC.
NHS charging system for migrants harmful, unjust, and not cost effective, report finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The NHS charging system forces migrants to pay 150% of the cost of their healthcare and is plagued with racial profiling and poor decision making, the charity Institute for Public Policy Research (IPPR) has found.1

The IPPR report warned that the system is a threat to public health and extremely costly to administer. It was found to have delayed people receiving treatment and dissuaded both people liable for charging and those who mistakenly feared they might be charged from seeking urgent medical attention.

The institute also highlighted evidence of racial profiling when identifying chargeable patients, as well as critical charging decisions—especially around the domestic violence exemption—being left to people without the necessary skills.

IPPR associate director Marley Morris …