tbuckley/cabot-search huggingface dataset:
Effect of glutamate infusion on NT-proBNP after coronary artery bypass grafting in high-risk patients (GLUTAMICS II): A randomized controlled trial
Authors: Jonas Holm, Gabriele Ferrari, Anders Holmgren, Farkas Vanky, Örjan Friberg, Mårten Vidlund, Rolf Svedjeholm
Journal: PLoS Medicine (2022)

Background Animal and human data suggest that glutamate can enhance recovery of myocardial metabolism and function after ischemia. N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction after coronary artery bypass surgery (CABG). We investigated whether glutamate infusion can reduce rises of NT-proBNP in moderate- to high-risk patients after CABG. Methods and findings A prospective, randomized, double-blind study enrolled patients from November 15, 2015 to September 30, 2020, with a 30-day follow-up at 4 academic cardiac surgery centers in Sweden. Patients underwent CABG ± valve procedure and had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h started 10 to 20 minutes before releasing the aortic cross-clamp, then continued for another 150 minutes. Patients, staff, and investigators were blinded to the treatment. The primary endpoint was the difference between preoperative and day-3 postoperative NT-proBNP levels. Analysis was intention to treat. We studied 303 patients (age 74 ± 7 years; females 26%, diabetes 47%), 148 receiving glutamate group and 155 controls. There was no significant difference in the primary endpoint associated with glutamate administration (5,390 ± 5,396 ng/L versus 6,452 ± 5,215 ng/L; p = 0.086). One patient died ≤30 days in the glutamate group compared to 6 controls (0.7% versus 3.9%; p = 0.12). No adverse events linked to glutamate were observed. A significant interaction between glutamate and diabetes was found ( p = 0.03). Among patients without diabetes the primary endpoint (mean 4,503 ± 4,846 ng/L versus 6,824 ± 5,671 ng/L; p = 0.007), and the incidence of acute kidney injury (11% versus 29%; p = 0.005) was reduced in the glutamate group. These associations remained significant after adjusting for differences in baseline data. The main limitations of the study are: (i) it relies on a surrogate marker for heart failure; and (ii) the proportion of patients with diabetes had almost doubled compared to the cohort used for the sample size estimation. Conclusions Infusion of glutamate did not significantly reduce postoperative rises of NT-proBNP. Diverging results in patients with and without diabetes agree with previous observations and suggest that the concept of enhancing postischemic myocardial recovery with glutamate merits further evaluation. Trial registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02592824 . European Union Drug Regulating Authorities Clinical Trials Database ( Eudra CT number 2011-006241-15 ).
Remote Monitoring and Behavioral Economics in Managing Heart Failure in Patients Discharged From the Hospital
Authors: David A. Asch, Andrea B. Troxel, Lee R. Goldberg, Monique S. Tanna, Shivan J. Mehta, Laurie A. Norton, Jingsan Zhu, Lauren G. Iannotte, Tamar Klaiman, Yuqing Lin, Louise B. Russell, Kevin G. Volpp
Journal: JAMA Internal Medicine (2022)

Close remote monitoring of patients following discharge for heart failure (HF) may reduce readmissions or death.To determine whether remote monitoring of diuretic adherence and weight changes with financial incentives reduces hospital readmissions or death following discharge with HF.The Electronic Monitoring of Patients Offers Ways to Enhance Recovery (EMPOWER) study, a 3-hospital pragmatic trial, randomized 552 adults recently discharged with HF to usual care (n = 280) or a compound intervention (n = 272) designed to inform clinicians of diuretic adherence and changes in patient weight. Patients were recruited from May 25, 2016, to April 8, 2019, and followed up for 12 months. Investigators were blinded to assignment but patients were not. Analysis was by intent to treat.Participants randomized to the intervention arm received digital scales, electronic pill bottles for diuretic medication, and regret lottery incentives conditional on the previous day's adherence to both medication and weight measurement, with $1.40 expected daily value. Participants' physicians were alerted if participants' weights increased 1.4 kg in 24 hours or 2.3 kg in 72 hours or if diuretic medications were missed for 5 days. Alerts and weights were integrated into the electronic health record. Participants randomized to the control arm received usual care and no further study contact.Time to death or readmission for any cause within 12 months.Of the 552 participants, 290 were men (52.5%); 291 patients (52.7%) were Black, 231 were White (41.8%), and 16 were Hispanic (2.9%); mean (SD) age was 64.5 (11.8) years. The mean (SD) ejection fraction was 43% (18.1%). Each month, approximately 75% of participants were 80% adherent to both medication and weight measurement. There were 423 readmissions and 26 deaths in the control group and 377 readmissions and 23 deaths in the intervention group. There was no significant difference between the 2 groups for the combined outcome of all-cause inpatient readmission or death (unadjusted hazard ratio, 0.91; 95% CI, 0.74-1.13; P = .40) and no significant differences in all-cause inpatient readmission or observation stay or death, all-cause cardiovascular readmission or death, time to first event, and total all-cause deaths. Participants in the intervention group were slightly more likely to spend fewer days in the hospital.In this randomized clinical trial, there was no reduction in the combined outcome of readmission or mortality in a year-long intensive remote monitoring program with incentives for patients previously hospitalized for HF.ClinicalTrials.gov Identifier: NCT02708654.
Improving health and social systems for all children in LMICs: structural innovations to deliver high-quality services
Authors: Margaret E Kruk, Todd P Lewis, Catherine Arsenault, Zulfiqar A Bhutta, Grace Irimu, Joshua Jeong, Zohra S Lassi, Susan M Sawyer, Tyler Vaivada, Peter Waiswa, Aisha K Yousafzai
Journal: The Lancet (2022)
Screening for Chronic Obstructive Pulmonary Disease
Authors: Carol M. Mangione, Michael J. Barry, Wanda K. Nicholson, Michael Cabana, Aaron B. Caughey, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Katrina E. Donahue, Carlos Roberto Jaén, Martha Kubik, Li Li, Gbenga Ogedegbe, Lori Pbert, John M. Ruiz, James Stevermer, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2022)

<h3>Importance</h3> Chronic obstructive pulmonary disease (COPD) is an irreversible reduction of airflow in the lungs. Progression to severe disease can prevent participation in normal activities because of deterioration of lung function. In 2020 it was estimated that approximately 6% of US adults had been diagnosed with COPD. Chronic lower respiratory disease, composed mainly of COPD, is the sixth leading cause of death in the US. <h3>Objective</h3> To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update that focused on targeted key questions for benefits and harms of screening for COPD in asymptomatic adults and treatment in screen-detected or screen-relevant adults. <h3>Population</h3> Asymptomatic adults who do not recognize or report respiratory symptoms. <h3>Evidence Assessment</h3> Using a reaffirmation process, the USPSTF concludes with moderate certainty that screening for COPD in asymptomatic adults has no net benefit. <h3>Recommendation</h3> The USPSTF recommends against screening for COPD in asymptomatic adults. (D recommendation)
Immunomodulatory impact of α-fetoprotein
Authors: Paul V. Munson, Juraj Adamik, Lisa H. Butterfield
Journal: Trends in Immunology (2022)

α-Fetoprotein (AFP) is a fetal glycoprotein produced by most human hepatocellular carcinoma tumors. Research has focused on its immunosuppressive properties in pregnancy, autoimmunity, and cancer, and human AFP directly limits the viability and functionality of human natural killer (NK) cells, monocytes, and dendritic cells (DCs). AFP-altered DCs can promote the differentiation of naïve T cells into regulatory T cells. These properties may work to shield tumors from the immune system. Recent efforts to define the molecular characteristics of AFP identified key structural immunoregulatory domains and bioactive roles of AFP-bound ligands in immunomodulation. We propose that a key mechanism of AFP immunomodulation skews DC function through cellular metabolism. Delineating differences between fetal 'normal' AFP (nAFP) and tumor-derived AFP (tAFP) has uncovered a novel role for tAFP in altering metabolism via lipid-binding partners.
Time to Clinical Benefit of Intensive Blood Pressure Lowering in Patients 60 Years and Older With Hypertension
Authors: Tao Chen, Fang Shao, Kangyu Chen, Yang Wang, Zhenqiang Wu, Yongjuan Wang, Yanpei Gao, Victoria Cornelius, Chao Li, Zhixin Jiang
Journal: JAMA Internal Medicine (2022)

Recent guidelines recommend a systolic blood pressure (BP) goal of less than 150 mm Hg or even 130 mm Hg for adults aged 60 years or older. However, harms from intensive BP treatments occur immediately (eg, syncope, fall), and benefits for cardiovascular event reduction emerge over time. Therefore, harms with low chance of benefit need to be clearer, particularly for those with limited life expectancy.
Heterogeneity in phenotype, disease progression and drug response in type 2 diabetes
Authors: Anand Thakarakkattil Narayanan Nair, Agata Wesolowska-Andersen, Caroline Brorsson, Aravind Lathika Rajendrakumar, Simona Hapca, Sushrima Gan, Adem Y. Dawed, Louise A. Donnelly, Rory McCrimmon, Alex S. F. Doney, Colin N. A. Palmer, Viswanathan Mohan, Ranjit M. Anjana, Andrew T. Hattersley, John M. Dennis, Ewan R. Pearson
Journal: Nature Medicine (2022)
Walking the talk?
Authors: None The Lancet Planetary Health
Journal: The Lancet Planetary Health (2022)

In the last few years, public awareness and concern about climate change has grown enormously. Movements like Fridays for Future and Extinction Rebellion have been far more successful in raising the profile of climate change and the need for a strong policy response than most commentators expected back in 2016 or 2017. Outright denial of the science of climate change has retreated to the fringes and in the latest set of IPCC Assessment Reports the language of unequivocality is remarkable. Net zero commitments abound at national, regional, and company levels.
Assessment of Neutralizing Antibody Response Against SARS-CoV-2 Variants After 2 to 3 Doses of the BNT162b2 mRNA COVID-19 Vaccine
Authors: Koichi Furukawa, Lidya Handayani Tjan, Yukiya Kurahashi, Silvia Sutandhio, Mitsuhiro Nishimura, Jun Arii, Yasuko Mori
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Although 2 and 3 doses of vaccine have been implemented against the SARS-CoV-2 pandemic, the level of immunity achieved by these additional vaccinations remains unclear. <h3>Objective</h3> To investigate the induction of neutralizing antibodies against the SARS-CoV-2 Omicron variant after 2 and 3 doses of the BNT162b2 messenger RNA (mRNA) vaccine among recipients of different ages. <h3>Design, Setting, and Participants</h3> A cohort study was conducted from June 1, 2021, to January 12, 2022, among 82 physicians at Kobe University Hospital who had received 2 doses of the BNT162b2 mRNA vaccine. <h3>Main Outcomes and Measures</h3> The rates of positive test results and the titers of neutralizing antibodies against the Omicron variant after 2 and 3 doses of the vaccine were compared with those against other variants and compared among 3 age groups (≤38 years [younger age group], 39-58 years [intermediate age group], and ≥59 years [older age group]). <h3>Results</h3> A total of 82 physicians (71 men [87%]; median age, 44 years [IQR, 33-58 years]) participated; 31 (38%) were in the younger age group, 32 (39%) were in the intermediate age group, and 19 (23%) were in the older age group. At 2 months after 2 doses of the vaccine, 23 participants (28%) had neutralizing antibodies against the Omicron variant, with a titer of 1.3 (95% CI, 1.2-1.4), which was 11.8-fold (95% CI, 9.9-13.9) lower than the titer against the D614G variant and the lowest among the variants tested. Although the titer of the neutralizing antibody against the Delta variant tended to be low among the older age group (2.9 [95% CI, 2.0-4.1]), the titers of the neutralizing antibody against the Omicron variant were low among all age groups (younger age group, 1.3 [95% CI, 1.1-1.6]; intermediate age group, 1.3 (95% CI, [95% CI, 1.1-1.5]; and older age group, 1.2 [95% CI, 1.0-1.4]). At 7 months after 2 doses of the vaccine, 5 participants (6%) had the neutralizing antibody against the Omicron variant, but after the booster (third dose) vaccination, all 72 participants who received the booster had the neutralizing antibody, and the titer was 41 (95% CI, 34-49), much higher than that at 7 months after 2 doses of the vaccine (1.0 [95% CI, 1.0-1.1]). This increase in titers was observed regardless of age groups; the titers were 44 (95% CI, 32-59) among the younger age group, 44 (95% CI, 32-59) among the intermediate age group, and 30 (95% CI, 22-41) among the older age group. <h3>Conclusions and Relevance</h3> In this cohort study of 82 Japanese participants, 2 doses of the BNT162b2 mRNA vaccine did not induce sufficient neutralizing antibody against the Omicron variant. However, booster vaccination was associated with induction of a high level of neutralizing antibodies against the Omicron variant, irrespective of the recipient's age.
Development of a core outcome set for basal cell carcinoma
Authors: Daniel I. Schlessinger, Kelly A. Reynolds, McKenzie A. Dirr, Sarah A. Ibrahim, Arianna F. Yanes, Jake M. Lazaroff, Victoria Godinez-Puig, Brian R. Chen, Anastasia O. Kurta, Jill K. Cotseones, Sarah G. Chiren, Karina C. Furlan, Sanjana Iyengar, Ramona Behshad, Danielle M. DeHoratius, Pablo Denes, Aaron M. Drucker, Leonard M. Dzubow, Jeremy R. Etzkorn, Catherine A. Harwood, John Y.S. Kim, Naomi Lawrence, Erica H. Lee, Gary S. Lissner, Ashfaq A. Marghoob, Rubeta N. Matin, Adam R. Mattox, Bharat B. Mittal, J. Regan Thomas, Xiaolong Alan Zhou, David Zloty, Jochen Schmitt, Jamie J. Kirkham, April W. Armstrong, Nicole Basset-Seguin, Elizabeth M. Billingsley, Jeremy S. Bordeaux, Jerry Brewer, Marc Brown, Mariah Brown, Scott A.B. Collins, Maria Concetta Fargnoli, Sergio Jobim De Azevedo, Reinhard Dummer, Alexander Eggermont, Glenn D. Goldman, Merete Haedersdal, Elizabeth K. Hale, Allison Hanlon, Kelly L. Harms, Conway C. Huang, Eva A. Hurst, Gino K. In, Nicole Kelleners-Smeets, Meenal Kheterpal, Barry Leshin, Michel Mcdonald, Stanley J. Miller, Alexander Miller, Eliot N. Mostow, Myrto Trakatelli, Kishwer S. Nehal, Desiree Ratner, Howard Rogers, Kavita Y. Sarin, Seaver L. Soon, Thomas Stasko, Paul A. Storrs, Luca Tagliaferri, Allison T. Vidimos, Sandra L. Wong, Siegrid S. Yu, Iris Zalaudek, Nathalie C. Zeitouni, John A. Zitelli, Emily Poon, Joseph F. Sobanko, Todd V. Cartee, Ian A. Maher, Murad Alam
Journal: Journal of the American Academy of Dermatology (2022)
Strengthening Causal Inference in Exposomics Research: Application of Genetic Data and Methods
Authors: Christy L. Avery, Annie Green Howard, Anna F. Ballou, Victoria L. Buchanan, Jason M. Collins, Carolina G. Downie, Stephanie M. Engel, Mariaelisa Graff, Heather M. Highland, Moa P. Lee, Adam G. Lilly, Kun Lu, Julia E. Rager, Brooke S. Staley, Kari E. North, Penny Gordon-Larsen
Journal: Environmental Health Perspectives (2022)

Summary: Advances in technologies to measure a broad set of exposures have led to a range of exposome research efforts. Yet, these efforts have insufficiently integrated methods that incorporate genetic data to strengthen causal inference, despite evidence that many exposome-associated phenotypes are heritable. Objective: We demonstrate how integration of methods and study designs that incorporate genetic data can strengthen causal inference in exposomics research by helping address six challenges: reverse causation and unmeasured confounding, comprehensive examination of phenotypic effects, low efficiency, replication, multilevel data integration, and characterization of tissue-specific effects. Examples are drawn from studies of biomarkers and health behaviors, exposure domains where the causal inference methods we describe are most often applied. Discussion: Technological, computational, and statistical advances in genotyping, imputation, and analysis, combined with broad data sharing and cross-study collaborations, offer multiple opportunities to strengthen causal inference in exposomics research. Full application of these opportunities will require an expanded understanding of genetic variants that predict exposome phenotypes as well as an appreciation that the utility of genetic variants for causal inference will vary by exposure and may depend on large sample sizes. However, several of these challenges can be addressed through international scientific collaborations that prioritize data sharing. Ultimately, we anticipate that efforts to better integrate methods that incorporate genetic data will extend the reach of exposomics research by helping address the challenges of comprehensively measuring the exposome and its health effects across studies, the life course, and in varied contexts and diverse populations. https://doi.org/10.1289/EHP9098
Omicron Variant in the Critical Care Units of the Paris Metropolitan Area: The Reality Research Group
Authors: Antoine Vieillard-Baron, Rémi Flicoteaux, Maud Salmona, Appoline Chariot, Bertrand De Maupeou D’Ableiges, Michael Darmon, Frédéric Batteux, Djillali Annane, Soufia Ayed, Elie Azoulay, Raphael Bellaiche, Sadek Beloucif, Enora Berti, Astrid Bertier, Sébastien Besset, Marlène Bret, Alain Cariou, Christophe Carpentier, Oussama Chaouch, Cyril Charron, Julien Charpentier, Cherifa Cheurfa, Bernard Cholley, Benjamin Chousterman, Sébastien Clerc, Yves Cohen, Alain Combes, Jean-Michel Constantin, Charles Damoisel, Vincent Degos, Sophie Demeret, Etienne De Montmollin, Alexandre Demoule, Francois Depret, Jean-Luc Diehl, Michel Djibré, Chung-Hi Do, Emmanuel Dudoignon, Jacques Duranteau, Muriel Fartoukh, Fabienne Fieux, Etienne Gayat, Mael Gennequin, Bertrand Guidet, Christophe Gutton, Sophie Hamada, Nicholas Heming, Romain Jouffroy, Hawa Keita-Meyer, Olivier Langeron, Brice Lortat-Jacob, Jonathan Marey, Alexandre Mebazaa, Bruno Megarbane, Armand Mekontso-Dessap, Jean-Paul Mira, Julie Molle, Nicolas Mongardon, Philippe Montravers, Capucine Morelot-Panzini, Safaa Nemlaghi, Bao-long Nguyen, Antoine Parrot, Romain Pasqualotto, Nicolas Peron, Lucile Picard, Marc Pineton de Chambrun, Benjamin Planquette, Benoit Plaud, Stéphanie Pons, Christophe Quesnel, Jean-Herlé Raphalen, Keyvan Razazi, Jean-Damien Ricard, Anne Roche, Benjamin Rohaut, Damien Roux, Laurent Savale, Jennifer Sobotka, Jean-Louis Teboul, Jean-François Timsit, Guillaume Voiriot, Emmanuel Weiss, Lucille Wildenberg, Elie Zogheib, Bruno Riou
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
In this Issue
Authors: Ruth Williams
Journal: Circulation Research (2022)

Arterial stiffness improves after COVID-19, but can linger for months, say Zanoli et al.Cardiovascular complications such as endothelial dysfunction, arterial stiffness, thrombosis and heart disease are common in COVID-19, but how quickly such issues resolve once the acute phase of the illness has passed remains unclear.To find out, Zanoli and colleagues examined aortic and brachial pulse wave velocity and other measures of arterial stiffness in 90 people who, several months earlier, had been hospitalized with COVID-19.These measurements were compared with those from 180 control individuals matched for age, sex, ethnicity and body mass index whose arterial stiffness had been assessed prior to the pandemic.41 of the COVID patients were also examined 27 weeks later to assess any change in arterial stiffness over time.Together the data showed arterial stiffness was higher in COVID patients than controls and, though it improved over time, it tended to remain higher than normal for almost a year after COVID.This finding could suggest residual structural damage to the arterial walls or, possibly, persistent low-grade inflammation in COVID patients.Either way, since arterial stiffness is a predictor of cardiovascular health, its potential long-term effects in COVID patients deserves further longitudinal studies, the authors say.
Understanding epilepsy in IDH-mutated gliomas: towards a targeted therapy
Authors: Frank Winkler
Journal: Neuro-Oncology (2022)

Journal Article Understanding epilepsy in IDH-mutated gliomas: towards a targeted therapy Get access Frank Winkler Frank Winkler Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, INF 400, 69120, Heidelberg, GermanyClinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Corresponding Author: Frank Winkler MD, PhD, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany (frank.winkler@med.uni-heidelberg.de) https://orcid.org/0000-0003-4892-6104 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 9, September 2022, Pages 1436–1437, https://doi.org/10.1093/neuonc/noac122 Published: 09 May 2022 Article history Published: 09 May 2022 Corrected and typeset: 31 May 2022
Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results
Authors: Changsong Qi, Jifang Gong, Jian Li, Dan Liu, Yanru Qin, Sai Ge, Miao Zhang, Zhi Peng, Jun Zhou, Yanshuo Cao, Xiaotian Zhang, Zhihao Lu, Ming Lu, Jiajia Yuan, Zhenghang Wang, Yakun Wang, Xiaohui Peng, Huiping Gao, Zhen Liu, Huamao Wang, Daijing Yuan, Jun Xiao, Hong Ma, Wei Wang, Zonghai Li, Lin Shen
Journal: Nature Medicine (2022)

Abstract Despite success in hematologic malignancies, the treatment landscape of chimeric antigen receptor (CAR) T cell therapy for solid tumors remains limited. Claudin18.2 (CLDN18.2)-redirected CAR T cells showed promising efficacy against gastric cancer (GC) in a preclinical study. Here we report the interim analysis results of an ongoing, open-label, single-arm, phase 1 clinical trial of CLDN18.2-targeted CAR T cells (CT041) in patients with previously treated, CLDN18.2-positive digestive system cancers ( NCT03874897 ). The primary objective was safety after CT041 infusion; secondary objectives included CT041 efficacy, pharmacokinetics and immunogenicity. We treated 37 patients with one of three CT041 doses: 2.5 × 10 8 , 3.75 × 10 8 or 5.0 × 10 8 cells. All patients experienced a grade 3 or higher hematologic toxicity. Grade 1 or 2 cytokine release syndrome (CRS) occurred in 94.6% of patients. No grade 3 or higher CRS or neurotoxicities, treatment-related deaths or dose-limiting toxicities were reported. The overall response rate (ORR) and disease control rate (DCR) reached 48.6% and 73.0%, respectively. The 6-month duration of response rate was 44.8%. In patients with GC, the ORR and DCR reached 57.1% and 75.0%, respectively, and the 6-month overall survival rate was 81.2%. These initial results suggest that CT041 has promising efficacy with an acceptable safety profile in patients with heavily pretreated, CLDN18.2-positive digestive system cancers, particularly in those with GC.