tbuckley/cabot-search huggingface dataset:
Trends in HF Hospitalizations Among Young Adults in the United States From 2004 to 2018
Authors: Vardhman Jain, Abdul Mannan Khan Minhas, Safi U. Khan, Stephen J. Greene, Ambarish Pandey, Harriette G.C. Van Spall, Gregg C. Fonarow, Robert J. Mentz, Javed Butler, Muhammad Shahzeb Khan
Journal: JACC Heart Failure (2022)
Error in Tables
Authors: Andrew Chanen, Jennifer Betts, Henry Jackson
Journal: JAMA Psychiatry (2022)

Boris Birmaher, MD; Danella Hafeman, MD; John Merranko, MA; Alyson Zwicker, PhD; Benjamin Goldstein, MD, PhD; Tina Goldstein, PhD; David Axelson, MD; Kelly Monk, BSN, RN; Mary Beth Hickey, BA; Dara Sakolsky, MD; Satish Iyengar, PhD; Rasim Diler, MD; Vishwajit Nimgaonkar, MD; Rudolf Uher, MD
PD-L1 siRNA–hyaluronic acid conjugate for dual-targeted cancer immunotherapy
Authors: Suyeon Kim, Roun Heo, Seok Ho Song, Kwon-Ho Song, Jung Min Shin, Se Jin Oh, Hyo-Jung Lee, Jo Eun Chung, Jae Hyung Park, Tae Woo Kim
Journal: Journal of Controlled Release (2022)

"Foreignization" of tumor cells via delivery of a non-self foreign antigen (Ag) into tumors is an appealing strategy to initiate anti-tumor immunity that can facilitate tumor rejection by pre-existing foreign-Ag-reactive T cells. However, the immune-suppressive factors in the tumor microenvironment (TME) limit the durable and potent immune response of these cells against tumor antigens, stressing the need for improved tumor-foreignization strategies. Here, we demonstrate that blockade of programmed cell death ligand 1 (PD-L1) on both tumor cells and dendritic cells (DCs) can markedly potentiate the induction of tumor-reactive T cells, thereby strengthening the anti-tumor immunity ignited by tumor-foreignization. Specifically, we developed a polymeric nanoconjugate (PEG-HA-OVA/PPLs), consisting of siPD-L1-based polyplexes, PEGylated hyaluronic acid as the CD44-targeting moiety, and ovalbumin (OVA) as a model foreign antigen. Notably, PEG-HA-OVA/PPLs were simultaneously delivered into CD44high tumor cells and CD44high DCs, leading to efficient cross-presentation of OVA and downregulation of PD-L1 in both cell types. Importantly, the nanoconjugate not only allowed OVA-specific T cells to vigorously reject the foreignized tumor cells but also reprogrammed the TME to elicit robust T-cell responses specific to the endogenous tumor Ags, eventually generating long-lasting protective immunity. Thus, our combination strategy represents an innovative approach for the induction of potent tumor immunity via a two-step consecutive immune boost against exogenous and endogenous tumor Ags.
Association of Maryland Global Budget Revenue With Spending and Outcomes Related to Surgical Care for Medicare Beneficiaries With Cancer
Authors: Anaeze C. Offodile, Yu-Li Lin, Alexander Melamed, J. Alejandro Rauh-Hain, Donna Kinzer, Nancy L. Keating
Journal: JAMA Surgery (2022)

In 2014, Maryland initiated the global budget revenue (GBR) model, placing caps on total hospital expenditures across all care sites. The GBR program aims to reduce unnecessary utilization while maintaining or improving care quality. To date, there has been limited examination of program effects on cancer care.To compare changes in spending, clinical outcomes, and acute care utilization through 4 years of the GBR program among Medicare beneficiaries who undergo cancer-directed surgery in Maryland vs matched control states.Drawing from a matched pool of hospitals in Maryland (n = 35) and 24 control states with a similar timing of Medicaid expansion (n = 101), we identified Medicare beneficiaries from Maryland and control states who underwent any cancer-directed surgery from 2011 through 2018. Using difference-in-differences analysis, we compared changes in outcomes from before (2011-2013) to after (2015-2018) GBR implementation between patients treated in Maryland and control states. We also performed a subgroup analysis among patients who underwent major surgical procedures that are usually performed in the inpatient setting (cystectomy, esophagectomy, gastrectomy, colorectal resection, nephrectomy, pancreatectomy, and lung resection).Thirty-day episode spending, mortality, readmissions, and emergency department (ED) visits.Relative to Medicare beneficiaries undergoing cancer surgery in control states (n = 4737; 3323 [70.1%] female; 571 [12.1%] dual-eligible; mean [SD] age 74.9 [6.5] years), patients in Maryland (n = 20 320; 14 068 [69.2%] female; 1705 [8.4%] dual-eligible; mean [SD] age 74.9 [6.5] years) had a statistically significant reduction of 2.2 percentage points (95% CI, -4.3 to -0.1) in the 30-day readmission rate. We found no statistically significant changes in 30-day spending, mortality, or ED visits. We report no significant results in the subgroup analysis of patients undergoing major surgical procedures.Global budget revenue was not associated with changes in expenditures, ED utilization, or clinical outcomes after cancer-directed surgery through 4 years. There was a modest decline in 30-day readmissions. Specialty-specific definitions of care quality and better alignment across the entire care delivery value chain (ie, physician incentives) may be strategies that could improve delivery of high-value care for beneficiaries undergoing cancer surgery.
Estimated Health Outcomes and Costs Associated With Use of Monoclonal Antibodies for Prevention or Mitigation of SARS-CoV-2 Infections
Authors: Minah Park, Kelvin Bryan Tan, Shawn Vasoo, Borame L. Dickens, David Lye, Alex R. Cook
Journal: JAMA Network Open (2022)

This economic evaluation investigates the health outcomes and costs associated with use of monoclonal antibodies for treatment of SARS-CoV-2 in 14 scenarios stratified by age, vaccination status, and source of infection.
Mechanistic insight of SARS-CoV-2 infection using human hepatobiliary organoids
Authors: Yi Zhao, Xiaoxue Ren, Jing Lu, Minghui He, Zhe Liu, Lina Yi, Mingle Huang, Ming Kuang, Haipeng Xiao, Joseph JY Sung, Xiaoxing Li, Lixia Xu, Jun Yu
Journal: Gut (2022)
COVID-19 associated phrenic nerve mononeuritis: a case series
Authors: Sheonagh MacPhail Law, Kathryn Scott, Ahmed Alkarn, Aisha Mahjoub, Arup K Mallik, Giles Roditi, Brian Choo-Kang
Journal: Thorax (2022)

This study characterised the hemidiaphragm elevation on 3-month interval chest X-rays (CXRs) of patients post COVID-19 pneumonia. 467 CXRs were screened; 19 (4.1%) had an elevated hemidiaphragm. There were 15 (3.2%) patients of interest with new hemidiaphragm elevation, persisting on average 7 months post COVID-19 diagnosis. Symptomatic patients underwent diaphragm ultrasound (n=12), pulmonary function test (n=10), muscle function test (n=6) and neurophysiology (n=5), investigating phrenic nerve function. Ultrasound demonstrated reduced/paradoxical diaphragmatic movements in eight; four of eight had reduced thickening fraction. Neurophysiology peripheral limb studies did not support the differential diagnoses of critical illness neuropathy/myopathy. We propose that, in selected patients, COVID-19 may cause phrenic nerve mononeuritis.
TIGIT-CD226-PVR axis: advancing immune checkpoint blockade for cancer immunotherapy
Authors: Eugene Y Chiang, Ira Mellman
Journal: Journal for ImmunoTherapy of Cancer (2022)

Recent advances in understanding the roles of immune checkpoints in allowing tumors to circumvent the immune system have led to successful therapeutic strategies that have fundamentally changed oncology practice. Thus far, immunotherapies against only two checkpoint targets have been approved, CTLA-4 and PD-L1/PD-1. Antibody blockade of these targets enhances the function of antitumor T cells at least in part by relieving inhibition of the T cell costimulatory receptor CD28. These successes have stimulated considerable interest in identifying other pathways that may bte targeted alone or together with existing immunotherapies. One such immune checkpoint axis is comprised of members of the PVR/nectin family that includes the inhibitory receptor T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT). Interestingly, TIGIT acts to regulate the activity of a second costimulatory receptor CD226 that works in parallel to CD28. There are currently over two dozen TIGIT-directed blocking antibodies in various phases of clinical development, testament to the promise of modulating this pathway to enhance antitumor immune responses. In this review, we discuss the role of TIGIT as a checkpoint inhibitor, its interplay with the activating counter-receptor CD226, and its status as the next advance in cancer immunotherapy.
<i>TET2</i>-Driven Clonal Hematopoiesis and Response to Canakinumab
Authors: Eric C. Svensson, Aviv Madar, Catarina D. Campbell, Yunsheng He, Marc Sultan, Margaret L. Healey, Huilei Xu, Katie D’Aco, Anita Fernandez, Clarisse Wache-Mainier, Peter Libby, Paul M. Ridker, Michael T. Beste, Craig T. Basson
Journal: JAMA Cardiology (2022)

<h3>Importance</h3> Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of atherosclerotic cardiovascular disease, and mouse experiments suggest that CHIP related to<i>Tet2</i>loss of function in myeloid cells accelerates atherosclerosis via augmented interleukin (IL) 1β signaling. <h3>Objective</h3> To assess whether individuals with CHIP have greater cardiovascular event reduction in response to IL-1β neutralization in the Canankinumab Anti-inflammatory Thrombosis Outcomes Trial (CANTOS). <h3>Design, Setting, and Participants</h3> This randomized clinical trial took place from April 2011 to June 2017 at more than 1000 clinical sites in 39 countries. Targeted deep sequencing of genes previously associated with CHIP in a subset of trial participants using genomic DNA prepared from baseline peripheral blood samples were analyzed. All participants had prior myocardial infarction and elevated high-sensitivity C-reactive protein level above 0.20 mg/dL. Analysis took place between June 2017 and December 2021. <h3>Interventions</h3> Canakinumab, an anti–IL-1β antibody, given at doses of 50, 150, and 300 mg once every 3 months. <h3>Main Outcomes and Measures</h3> Major adverse cardiovascular events (MACE). <h3>Results</h3> A total of 338 patients (8.6%) were identified in this subset with evidence for clonal hematopoiesis. As expected, the incidence of CHIP increased with age; the mean (SD) age of patients with CHIP was 66.3 (9.2) years and 61.5 (9.6) years in patients without CHIP. Unlike other populations that were not preselected for elevated C-reactive protein, in the CANTOS population variants in<i>TET2</i>were more common than<i>DNMT3A</i>(119 variants in 103 patients vs 86 variants in 85 patients). Placebo-treated patients with CHIP showed a nonsignificant increase in the rate of MACE compared with patients without CHIP using a Cox proportional hazard model (hazard ratio, 1.32 [95% CI, 0.86-2.04];<i>P</i> = .21). Exploratory analyses of placebo-treated patients with a somatic variant in either<i>TET2</i>or<i>DNMT3A</i>(n = 58) showed an equivocal risk for MACE (hazard ratio, 1.65 [95% CI, 0.97-2.80];<i>P</i> = .06). Patients with CHIP due to somatic variants in<i>TET2</i>also had reduced risk for MACE while taking canakinumab (hazard ratio, 0.38 [95% CI, 0.15-0.96]) with equivocal difference compared with others (<i>P</i>for interaction = .14). <h3>Conclusions and Relevance</h3> These results are consistent with observations of increased risk for cardiovascular events in patients with CHIP and raise the possibility that those with<i>TET2</i>variants may respond better to canakinumab than those without CHIP. Future studies are required to further substantiate this hypothesis. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01327846
It is vital that we retain some reliable covid-19 surveillance tools
Authors: Sylvia Richardson
Journal: BMJ (2022)

It is vital that we retain some reliable covid-19 surveillance tools Sylvia Richardson presidentLike many others, I was alarmed by the news that the REACT programme was discontinued at the end of March.There also remains considerable uncertainty over whether other covid surveillance studies will stay in place and if they do whether they'll be reduced in size.
Clarification of Conflict of Interest Disclosure
Journal: JAMA Network Open (2022)

Beth D. Darnall, PhD; Anuradha Roy, MSc; Abby L. Chen, BS; Maisa S. Ziadni, PhD; Ryan T. Keane, MA; Dokyoung S. You, PhD; Kristen Slater, PsyD; Heather Poupore-King, PhD; Ian Mackey, BA; Ming-Chih Kao, PhD, MD; Karon F. Cook, PhD; Kate Lorig, DrPH; Dongxue Zhang, MS; Juliette Hong, MS, MEd; Lu Tian, PhD; Sean C. Mackey, MD, PhD
Five-Year Outcomes of a Melanoma Screening Initiative in a Large Health Care System
Authors: Martha Matsumoto, Sarah Wack, Martin A. Weinstock, Alan Geller, Hong Wang, Francis X. Solano, John M. Kirkwood, Laura K. Ferris
Journal: JAMA Dermatology (2022)

<h3>Importance</h3> Population-based skin cancer screening is currently not recommended owing to lack of data to quantify the balance of benefits and harms. <h3>Objective</h3> To compare thickness-specific incidence of melanoma in screened vs unscreened patients following the initiation of a primary care–based skin cancer screening initiative. <h3>Design, Setting, and Participants</h3> This observational study of a quality improvement initiative was conducted from January 1, 2014, through December 31, 2018, among patients 35 years and older presenting for a primary care visit at primary care practices within an academic and community-based health care system during the study period. Data analysis was performed January 2020 to January 2022. <h3>Interventions</h3> Primary care clinicians were offered training in melanoma identification through skin examination and encouraged to offer annual screening to patients 35 years and older. <h3>Main Outcomes and Measures</h3> Thickness of melanomas diagnosed in screened and unscreened patients. <h3>Results</h3> Among 595 799 analyzed screen-eligible patients, 144 851 (24.3%) were screened at least once. Screened patients were older (median [IQR] age, 59 [49-67] vs 55 [45-66] years) and more likely to be female (82 244 [56.8%] vs 250 806 [55.6%];<i>P</i> &lt; .001) and non-Hispanic White (124 747 [86.1%] vs 375 890 [83.4%];<i>P</i> &lt; .001) than unscreened patients. After adjusting for age, sex, and race, screened patients were more likely than unscreened patients to be diagnosed with in situ (incidence, 30.4 vs 14.4; hazard ratio [HR], 2.6; 95% CI, 2.1-3.1;<i>P</i> &lt; .001) or thin invasive (≤1 mm) melanoma (incidence, 24.5 vs 16.1; HR, 1.8; 95% CI, 1.5-2.2;<i>P</i> &lt; .001). Screened patients were also more likely than unscreened patients to be diagnosed with in situ (incidence, 26.7 vs 12.9; HR, 2.1; 95% CI, 1.7-2.6;<i>P</i> &lt; .001) or thin invasive (≤1 mm) interval melanomas (melanoma diagnosed at least 60 days after initial screening examination) (incidence, 18.5 vs 14.4; HR, 1.3; 95% CI, 1.0-1.7;<i>P</i> = .03). Incidence of melanoma thicker than 4 mm in unscreened and screened patients, respectively, was 3.3 and 2.7 (HR, 0.8; 95% CI, 0.4-1.4;<i>P</i> = .38) for all melanomas and 2.7 and 1.5 (HR, 0.6; 95% CI, 0.2-1.2;<i>P</i> = .15) for interval melanomas. <h3>Conclusions and Relevance</h3> In this quality improvement study, primary care–based melanoma screening was associated with increased detection of thin melanoma, raising concern about overdiagnosis. Further studies with longer follow-up are needed to determine the influence of screening on the incidence of thick melanoma and outcomes associated with high costs and poor outcomes, such as metastasis.
Unsupervised machine learning improves risk stratification in newly diagnosed multiple myeloma: an analysis of the Spanish Myeloma Group
Authors: Adrian Mosquera Orgueira, Marta Sonia González Pérez, Jose Diaz Arias, Laura Rosiñol, Albert Oriol, Ana Isabel Teruel, Joaquin Martinez Lopez, Luis Palomera, Miguel Granell, Maria Jesus Blanchard, Javier de la Rubia, Ana López de la Guia, Rafael Rios, Anna Sureda, Miguel Teodoro Hernandez, Enrique Bengoechea, María José Calasanz, Norma Gutierrez, Maria Luis Martin, Joan Blade, Juan-Jose Lahuerta, Jesús San Miguel, Maria Victoria Mateos, Adrian Mosquera Orgueira, Marta Sonia González Pérez, Jose Diaz Arias, Laura Rosiñol, Albert Oriol, Ana Isabel Teruel, Joaquin Martinez Lopez, Luis Palomera, Miguel Granell, Maria Jesus Blanchard, Javier de la Rubia, Ana López de la Guia, Rafael Rios, Anna Sureda, Miguel Teodoro Hernandez, Enrique Bengoechea, María José Calasanz, Norma Gutierrez, Maria Luis Martin, Joan Blade, Juan-Jose Lahuerta, Jesús San Miguel, Maria Victoria Mateos
Journal: Blood Cancer Journal (2022)

Abstract The International Staging System (ISS) and the Revised International Staging System (R-ISS) are commonly used prognostic scores in multiple myeloma (MM). These methods have significant gaps, particularly among intermediate-risk groups. The aim of this study was to improve risk stratification in newly diagnosed MM patients using data from three different trials developed by the Spanish Myeloma Group. For this, we applied an unsupervised machine learning clusterization technique on a set of clinical, biochemical and cytogenetic variables, and we identified two novel clusters of patients with significantly different survival. The prognostic precision of this clusterization was superior to those of ISS and R-ISS scores, and appeared to be particularly useful to improve risk stratification among R-ISS 2 patients. Additionally, patients assigned to the low-risk cluster in the GEM05 over 65 years trial had a significant survival benefit when treated with VMP as compared with VTD. In conclusion, we describe a simple prognostic model for newly diagnosed MM whose predictions are independent of the ISS and R-ISS scores. Notably, the model is particularly useful in order to re-classify R-ISS score 2 patients in 2 different prognostic subgroups. The combination of ISS, R-ISS and unsupervised machine learning clusterization brings a promising approximation to improve MM risk stratification.
Transient versus persistent improved ejection fraction in non‐ischaemic dilated cardiomyopathy
Authors: Paolo Manca, Davide Stolfo, Marco Merlo, Caterina Gregorio, Antonio Cannatà, Federica Ramani, Vincenzo Nuzzi, Lars H. Lund, Gianluigi Savarese, Gianfranco Sinagra
Journal: European Journal of Heart Failure (2022)
Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction
Authors: Prakriti Gaba, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, Jean-Claude Tardif, Robert P. Giugliano, Fabrice M.A.C. Martens, C. Michael Gibson, Christie M. Ballantyne
Journal: Journal of the American College of Cardiology (2022)

REDUCE-IT was a double-blind trial that randomized 8,179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in the primary endpoint, including death from cardiovascular (CV) causes. The specific impact of IPE among patients with prior myocardial infarction (MI) was unknown.Our goal was to examine the benefit of IPE on ischemic events among patients with prior MI in REDUCE-IT.We performed post hoc analyses of patients with prior MI. The primary endpoint was CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was CV death, MI, or stroke.A total of 3,693 patients had a history of prior MI. The primary endpoint was reduced from 26.1% to 20.2% with IPE vs placebo; HR: 0.74 (95% CI: 0.65-0.85; P = 0.00001). The key secondary endpoint was reduced from 18.0% to 13.3%; HR: 0.71 (95% CI: 0.61-0.84; P = 0.00006). There was also a significant 35% relative risk reduction in total ischemic events (P = 0.0000001), a 34% reduction in MI (P = 0.00009), a 30% reduction in CV death (P = 0.01), and a 20% lower rate of all-cause mortality (P = 0.054), although there was a slight increase in atrial fibrillation. Sudden cardiac death and cardiac arrest were also significantly reduced by 40% and 56%, respectively.Patients with a history of prior MI in REDUCE-IT treated with IPE demonstrated large and significant relative and absolute risk reductions in ischemic events, including CV death. (A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. [REDUCE-IT]; NCT01492361).
Psychometric parameters of food allergy quality of life during an allergen immunotherapy trial
Authors: Gabriel Lins de Holanda Coelho, Audrey DunnGalvin, Matthew Greenhawt, Jonathan O'B Hourihane, David M. Fleischer, Gang Chen, Marcus Shaker, Dianne E. Campbell, Todd D. Green, Philippe Bégin
Journal: Allergy (2022)

The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a commonly used patient-reported outcome measure in food allergy (FA) research. It was developed before FA treatment clinical trials were commonplace and is used as a secondary outcome measure in pivotal FA treatment trials. We examined the psychometric properties of the FAQLQ-PF and its relevance to children with peanut allergy engaged in an epicutaneous immunotherapy (EPIT) clinical trial.Analysis was performed on 26 universally answered items of the FAQLQ-PF, from assessments undertaken during the phase 3 PEPITES study (baseline, Month 12), which examined the safety and efficacy of EPIT for children with peanut allergy aged 4-11 years. Item response theory (IRT) was used to assess psychometric parameters of the FAQLQ-PF (i.e., discrimination, difficulty, and information). Confirmatory factor analysis was also employed; reliability was assessed using McDonald's omega (ω) and Cronbach's alpha (α).A total of 23 of 26 items presented very high discrimination levels (>1.7), and all 26 fell within the recommended difficulty threshold (between -1.5 and 1.5). The items contributed a reasonable information level for their respective factors/subdomains. The measure also presented a marginally acceptable model fit for the 3-factor structure (e.g., comparative fit index = 0.88, Tucker-Lewis index = 0.87) and good reliability levels across time points (ω and α > 0.90).Herein, we present a novel reanalysis of the FAQLQ-PF items using IRT. The longitudinal performance of individual items and subscales was corroborated, and items with the highest discrimination were identified, showing that the tool is suitable for longitudinal measurements in FA treatment trials.