tbuckley/cabot-search huggingface dataset:
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update
Authors: Bryan J. Schneider, Jarushka Naidoo, Bianca D. Santomasso, Christina Lacchetti, Sherry Adkins, Milan Anadkat, Michael B. Atkins, Kelly J. Brassil, Jeffrey M. Caterino, Ian Chau, Marianne J. Davies, Marc S. Ernstoff, Leslie Fecher, Monalisa Ghosh, Ishmael Jaiyesimi, Jennifer S. Mammen, Aung Naing, Loretta J. Nastoupil, Tanyanika Phillips, Laura D. Porter, Cristina A. Reichner, Carole Seigel, Jung-Min Song, Alexander Spira, Maria Suarez-Almazor, Umang Swami, John A. Thompson, Praveen Vikas, Yinghong Wang, Jeffrey S. Weber, Pauline Funchain, Kathryn Bollin
Journal: Journal of Clinical Oncology (2021)

To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitor (ICPi) therapy.A multidisciplinary panel of medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to update the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 through 2021.A total of 175 studies met the eligibility criteria of the systematic review and were pertinent to the development of the recommendations. Because of the paucity of high-quality evidence, recommendations are based on expert consensus.Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to the organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, except for some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert ≤ grade 1. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids. Corticosteroids should be tapered over the course of at least 4-6 weeks. Some refractory cases may require other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, except for endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines.
Endocrine Treatment and Targeted Therapy for Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer: ASCO Guideline Update
Authors: Harold J. Burstein, Mark R. Somerfield, Debra L. Barton, Ali Dorris, Lesley J. Fallowfield, Dharamvir Jain, Stephen R. D. Johnston, Larissa A. Korde, Jennifer K. Litton, Erin R. Macrae, Lindsay L. Peterson, Praveen Vikas, Rachel L. Yung, Hope S. Rugo
Journal: Journal of Clinical Oncology (2021)

PURPOSE To update recommendations of the ASCO systemic therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC) guideline. METHODS An Expert Panel conducted a systematic review to identify new, potentially practice-changing data. RESULTS Fifty-one articles met eligibility criteria and form the evidentiary basis for the recommendations. RECOMMENDATIONS Alpelisib in combination with endocrine therapy (ET) should be offered to postmenopausal patients, and to male patients, with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, ABC, or MBC following prior endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. Clinicians should use next-generation sequencing in tumor tissue or cell-free DNA in plasma to detect PIK3CA mutations. If no mutation is found in cell-free DNA, testing in tumor tissue, if available, should be used as this will detect a small number of additional patients with PIK3CA mutations. There are insufficient data at present to recommend routine testing for ESR1 mutations to guide therapy for HR-positive, HER2-negative MBC. For BRCA1 or BRCA2 mutation carriers with metastatic HER2-negative breast cancer, olaparib or talazoparib should be offered in the 1st-line through 3rd-line setting. A nonsteroidal aromatase inhibitor (AI) and a CDK4/6 inhibitor should be offered to postmenopausal women with treatment-naïve HR-positive MBC. Fulvestrant and a CDK4/6 inhibitor should be offered to patients with progressive disease during treatment with AIs (or who develop a recurrence within 1 year of adjuvant AI therapy) with or without one line of prior chemotherapy for metastatic disease, or as first-line therapy. Treatment should be limited to those without prior exposure to CDK4/6 inhibitors in the metastatic setting. Additional information can be found at www.asco.org/breast-cancer-guidelines .
The importance of blood pressure thresholds versus predicted cardiovascular risk on subsequent rates of cardiovascular disease: a cohort study in English primary care
Authors: Emily Herrett, Helen Strongman, Sarah Gadd, Laurie Tomlinson, Dorothea Nitsch, Krishnan Bhaskaran, Elizabeth Williamson, Tjeerd van Staa, Reecha Sofat, Adam Timmis, Susan Wells, Liam Smeeth, Rod Jackson
Journal: The Lancet Healthy Longevity (2022)

For five decades, blood pressure lowering treatment has been recommended for patients with hypertension (currently defined as blood pressure of ≥140/90 mm Hg). In the past 20 years, guidelines for treatment began incorporating predicted absolute cardiovascular disease risk (predicted risk) and reducing blood pressure thresholds. The blood pressure threshold at which to start treatment has become a secondary consideration in some countries. We aimed to provide descriptive data to assess the relative importance of blood pressure thresholds versus predicted risk on the subsequent rate of cardiovascular disease to inform treatment decisions.
Encapsulation and subjectivity from the standpoint of viewpoint theory
Authors: Ezequiel Morsella, Anthony G. Velasquez, Jessica K. Yankulova, Yanming Li, Adam Gazzaley
Journal: Behavioral and Brain Sciences (2022)

Abstract The groundbreaking, viewpoint theory of Merker et al. explains several properties of the conscious field, including why the observer cannot directly apprehend itself. We propose that viewpoint theory might also provide a progressive, constitutive marker of consciousness and shed light on why most of the contents of consciousness are encapsulated.
Getting Through COVID-19: Keeping Clinicians in the Workforce
Authors: Marvin J. Bittner
Journal: Annals of Internal Medicine (2022)

LettersJanuary 2022Getting Through COVID-19: Keeping Clinicians in the WorkforceFREEMarvin J. Bittner, MDMarvin J. Bittner, MDCreighton University School of Medicine, Omaha, NebraskaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0688 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Barrett and colleagues' commentary (1) included a recommendation to reduce “lengthy online mandatory trainings that have not been shown to improve patient outcomes.” I have been told that many of these trainings are mandated by the Joint Commission. Is this accurate?If these trainings are mandated by the Joint Commission, is the American College of Physicians (ACP)—as a Joint Commission sponsor—willing to make hard decisions to insist that the Joint Commission expunge these trainings from its requirements? Is ACP willing to use its limited advocacy resources to insist that the National Institutes of Health fund studies on the value of mandatory trainings? To use its other limited resources to develop modules of training that are, indeed, of value and can be used by multiple hospitals (instead of, for example, requiring an internist with privileges at 3 hospitals to take 3 different versions of fire safety training)? To use its influence on the American Medical Association, Accreditation Council for Graduate Medical Education, and similar organizations to reduce these mandatory trainings? To stand up to purveyors of poorly designed training modules just as it has confronted third-party payers and pharmaceutical manufacturers who have engaged in undesirable practices?It's one thing to recognize how these trainings sap morale, but is ACP willing to act on these words?Reference1. Barrett E, Hingle ST, Smith CD, et al. Getting through COVID-19: keeping clinicians in the workforce [Editorial]. Ann Intern Med. 2021;174:1614-5. [PMID: 34570597] doi:10.7326/M21-3381 LinkGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Creighton University School of Medicine, Omaha, NebraskaDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L21-0688. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGetting Through COVID-19: Keeping Clinicians in the Workforce Eileen Barrett , Susan Thompson Hingle , Cynthia D. Smith , and Darilyn V. Moyer Getting Through COVID-19: Keeping Clinicians in the Workforce Cynthia D. Smith , Darilyn V. Moyer , Susan Thompson Hingle , and Eileen Barrett Metrics January 2022Volume 175, Issue 1Page: W2KeywordsCOVID-19Health care providersHealth promotionPersonal protective equipmentPsychiatry and mental healthSafety ePublished: 18 January 2022 Issue Published: January 2022 PDF downloadLoading ...
Abstract 10740: Improving Diabetes Care Through a Hospital Award Program: Implementation Challenges, Strategies, and Opportunities
Authors: Melody Halio, Heather Harpster, Susan Maynard, Renee M Sednew, Ray Niu, Katherine Overton, Liz Olson, Kathie Thomas, Michelle C Scharnott
Journal: Circulation (2021)

Background: Guideline recognition programs are known to drive hospital performance improvement, yet rapid translation of guidelines into practice continues to be a challenge. This analysis identifies guideline implementation challenges and strategies following the introduction of a new guideline recognition program for diabetes care of patients with heart failure and/or stroke. Methods: Hospitals participating in American Heart Association’s (AHA) Get With The Guidelines (GWTG)-Stroke and/or GWTG-Heart Failure modules are asked to document adherence to guidelines for diabetes care. Representatives from 21 GWTG-Stroke and GWTG-Heart Failure hospitals were invited to take part in virtual focus groups. Four focus groups with 21 participants were conducted in March 2021. Participants shared their attitudes, strategies, and challenges related to the diabetes recognition program. Transcripts were coded and analyzed for common themes with NVivo 12. Results: Participants consistently reported positive attitudes towards national recognition and guideline recognition programs. Improved team-based care, care coordination, and antihyperglycemic medication education were consistently reported as diabetes-guideline implementation opportunities. Standard protocols following diabetes diagnosis varied, as did hospital practices for ensuring adherence to treatment guidelines and complete data documentation. Conclusion: These findings demonstrated consistency in both positive attitudes towards recognition and opportunities for improved guideline-implementation. Variability in established diabetes-treatment protocols and strategies for ensuring guideline adherence suggests the need for increased best practice sharing and guideline-implementation support. These results may be used to inform successful implementation of future guideline-based award programs to improve the care of those with diabetes and CVD.
Vaccine-induced and naturally-acquired protection against Omicron and Delta symptomatic infection and severe COVID-19 outcomes, France, December 2021 to January 2022
Authors: Milena Suarez Castillo, Hamid Khaoua, Noémie Courtejoie
Journal: Eurosurveillance (2022)

We assessed the protection conferred by naturally-acquired, vaccine-induced and hybrid immunity during the concomitant Omicron and Delta epidemic waves in France on symptomatic infection and severe COVID-19. The greatest levels of protection against both variants were provided by hybrid immunity. Protection against Omicron symptomatic infections was systematically lower and waned at higher speed than against Delta in those vaccinated. In contrast, there were little differences in variant-specific protection against severe inpatient outcomes in symptomatic individuals.
Abstract EP45: Validation Of The Edinburgh Claudication Questionnaire For Identifying Peripheral Artery Diseasein Outpatient Cardiology Clinic: Single-center Experience
Authors: Justin Daneshrad, Hee D Jeon, Kevin B Lo, Matthew Gebre, Manolo R Garcia, Reza Amini
Journal: Circulation (2022)

Background: Peripheral artery disease (PAD) is prevalent in patients with chronic heart disease, and portends a worse cardiovascular outcome. Edinburgh Claudication Questionnaire (ECQ) is a commonly used screening tool aimed to identify PAD in general practice. Despite its common use, its accuracy had not been validated in a cardiac population in the USA. We aimed to evaluate the diagnostic accuracy of the ECQ as a means of identifying PAD in an outpatient cardiology clinic. Method: Subjects were recruited at outpatient cardiology clinic at Loma Linda University Medical Center between 2017 and 2019. Patients with previously diagnosed PAD were excluded. 119 patients completed ECQ during their routine clinic visit, and were subsequently referred for duplex ultrasound and Ankle-Brachial Index (ABI) measurement. ABI was used as a reference standard for the diagnosis of PAD. Result: rom a total of 119 patients, 53% were male with mean age was 68. Majority (87%) of patients had hypertension, and 16% were active smokers. There were 16% of patients who tested positive on the ECQ and 47% of them had positive ABI. In patients with a negative ECQ, 23% had a positive ABI result. Receiver operating characteristic curve analysis showed ECQ had sensitivity of 28% (95% CI 13.7-46.7), specificity of 89% (95% CI 79.8-94.3), PPV of 2.5% (95% CI 1.1-5.5) and NPV of 77.8% (0.7 to 1.0), which equates to a positive and negative likelihood ratio of 2.6 and 0.8 respectively. On subgroup analyses, the ECQ performed better among current smokers (AUC=0.64 95% CI 0.43 to 0.84) and among male patients (AUC=0.66 95% CI 0.53 to 0.78). In the subgroup of male patients who were currently smoking, the ECQ performed better with 50% sensitivity and 99% specificity (AUC=0.75 95% CI 0.56 to 0.94). Conclusion: The ECQ had good specificity but poor sensitivity in the cardiology outpatient setting making it a poor tool for screening on its own. Sensitivity was higher in male current smokers. Further study of its utilization in high-risk patients such as in male smokers may be of benefit.
Abstract P024: The Association Of Cardiac Valvular Abnormality With Prevalent And Incident Chronic Kidney Disease In Community-Dwelling Older Adults: The Atherosclerosis Risk In Communities Study
Authors: Vedika Karandikar, Yasuyuki Honda, Junichi Ishigami, Pamela L Lutsey, Michael E Hall, Scott Solomon, Josef Coresh, Amil M Shah, Kuni Matsushita
Journal: Circulation (2022)

Background: An improvement in kidney function has been reported after percutaneous valvular replacement therapies, implying pathophysiological contribution of valvular heart disease to chronic kidney disease (CKD). However, this association has not been investigated in community dwelling populations. Hypothesis: Valvular abnormality is associated with prevalent and incident CKD. Methods: We evaluated the association between valvular abnormality and prevalent CKD (primarily defined as estimated glomerular filtration rate [eGFR] &lt;60 mL/min/1.73m 2 ) in 5,216 participants (mean age 75.5 [SD 5.1] years) from the ARIC study (2011-2013) using logistic regression. Then, 3,752 participants without prevalent CKD were analyzed for incident CKD (progression to eGFR &lt;60 mL/min/1.73m 2 with ≥25% decline or hospitalization/deaths with CKD diagnosis) using Cox models. Valvular abnormality included echocardiography-based aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR). Results: There were 1.4% (n=74) with any AS, 10.6% (n=555) with any AR, and 43.1% (n=2,249) with any MR. The majority (57-96%) had mild or trace abnormality. After adjustment for potential confounders, any MR and moderate/severe AR showed significant associations with prevalent CKD (adjusted odds ratio 1.17 [95% CI 1.03-1.34] and 2.82 [1.12-7.10]), as did any AS in a sensitivity analysis with prevalent CKD defined including albuminuria ≥30 mg/g (1.83 [1.10-3.05]). Only any AS showed an independent association with incident CKD (adjusted hazard ratio: 2.12 [1.13-4.00]). The 5-year cumulative incidence of CKD was 17.3% in any AS and 7.4% in no AS (Figure). Conclusions: Different types of valvular abnormality were associated with prevalent CKD. Prospectively, only AS was associated with incident CKD. These findings suggest an etiological link between valvular abnormality and CKD and highlight the importance of clinical attention to kidney function in individuals with AS.
Case 3-2022: A 14-Year-Old Boy with Fever, Joint Pain, and Abdominal Cramping
Authors: Kerstin Zanger, Katherine Nimkin, Esther J. Israel, Angela R. Shih
Journal: New England Journal of Medicine (2022)

A 14-year-old boy was admitted with fatigue, fever, joint pain, abdominal cramping, and diarrhea. He had been well until 2 weeks earlier, when fatigue and fever developed on his final day of summer camp. On the day of admission, he had pain in his shoulders and knees and a temperature of 39.2°C. A diagnostic test was performed.
Methotrexate and TNF inhibitors affect long-term immunogenicity to COVID-19 vaccination in patients with immune-mediated inflammatory disease
Authors: Rebecca H Haberman, Seungha Um, Jordan E Axelrad, Rebecca B Blank, Zakwan Uddin, Sydney Catron, Andrea L Neimann, Mark J Mulligan, Ramin Sedaghat Herat, Simon J Hong, Shannon Chang, Arnold Myrtaj, Ghoncheh Ghiasian, Peter M Izmirly, Amit Saxena, Gary Solomon, Natalie Azar, Jonathan Samuels, Brian D Golden, Paula Rackoff, Samrachana Adhikari, David P Hudesman, Jose U Scher
Journal: The Lancet Rheumatology (2022)
Shh and Olig2 sequentially regulate oligodendrocyte differentiation from hiPSCs for the treatment of ischemic stroke
Authors: Jian Xu, Jingxin Zhao, Rui Wang, Yidi Zhang, Lan Shen, Qian Xiao, Yuan Xie, Jinjun Jiang, Yichu Nie, Wenbin Deng
Journal: Theranostics (2022)

Rationale: Demyelination is a major component of white matter injury, characterized by oligodendrocyte (OL) death and myelin sheath loss, which result in memory loss and cognitive impairment in the context of ischemic stroke.Accumulating evidence has shown that OLs can be generated by the direct activation of defined transcription factors (TFs) in human induced pluripotent stem cells (hiPSCs); however, the rapid acquisition of single TF-induced OL progenitor cells (OPCs) as cell therapy for ischemic stroke remains to be thoroughly explored.Methods: A stable, chemically defined protocol was used to generate a substantial number of transplantable and functional OLs through the partial inhibition of sonic hedgehog (Shh) activity by GANT61 during neural induction from hiPSCs and sequential induction of TF Olig2 overexpression.Transcriptome and metabolome analyses further revealed a novel molecular event in which Olig2 regulates OL differentiation from hiPSC-derived neural progenitor cells (NPCs).Olig2-induced NG2 + OPCs (Olig2-OPCs) were then evaluated for their therapeutic potential in cell-based therapy for ischemic stroke.Results: GANT61 treatment resulted in a motor neuron (MN)-OL fate switch during neural induction, and induced overexpression of Olig2 accelerated oligodendroglial lineage cell specification.Olig2-OPCs expressed typical oligodendroglial lineage marker genes, including NKX2.2, CSPG4, and ST8SIA1, and displayed superior ability to differentiate into mature OLs in vitro.Mechanistically, Olig2-OPCs showed increased gene expression of the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway, and activated CEPT1-mediated phospholipogenesis.Functionally, inhibiting PPARγ and knocking down CEPT1 further compromised the terminal differentiation of Olig2-OPCs.Most importantly, when transplanted into a rat model of transient middle cerebral artery occlusion (tMCAO), Olig2-OPCs efficiently promoted neurological functional recovery by reducing neuronal death, promoting remyelination, and rescuing spatial memory decline.Conclusions: We developed a stable, chemically defined protocol to generate OPCs/OLs with partial inhibition of Shh activity by GANT61 from hiPSCs and sequentially induced the expression of the single TF Olig2.Olig2-OPC transplantation may be an ideal alternative approach for ischemic stroke rehabilitation therapy.
Precision Dosing of Targeted Therapies Is Ready for Prime Time
Authors: Stefanie L. Groenland, Remy B. Verheijen, Markus Joerger, Ron H.J. Mathijssen, Alex Sparreboom, Jos H. Beijnen, Jan H. Beumer, Neeltje Steeghs, Alwin D.R. Huitema
Journal: Clinical Cancer Research (2021)

Fixed dosing of oral targeted therapies is inadequate in the era of precision medicine. Personalized dosing, based on pharmacokinetic (PK) exposure, known as therapeutic drug monitoring (TDM), is rational and supported by increasing evidence. The purpose of this perspective is to discuss whether randomized studies are needed to confirm the clinical value of precision dosing in oncology. PK-based dose adjustments are routinely made for many drugs and are recommended by health authorities, for example, for patients with renal impairment or for drug-drug interaction management strategies. Personalized dosing simply extrapolates this paradigm from selected patient populations to each individual patient with suboptimal exposure, irrespective of the underlying cause. If it has been demonstrated that exposure is related to a relevant clinical outcome, such as efficacy or toxicity, and that exposure can be optimized by PK-guided dosing, it could be logically assumed that PK-guided dosing would result in better treatment outcomes without the need for randomized confirmatory trials. We propose a path forward to demonstrate the clinical relevance of individualized dosing of molecularly-targeted anticancer drugs.
Responding to the opioid crisis in North America and beyond: recommendations of the Stanford–Lancet Commission
Authors: Keith Humphreys, Chelsea L Shover, Christina M Andrews, Amy S B Bohnert, Margaret L Brandeau, Jonathan P Caulkins, Jonathan H Chen, Mariano-Florentino Cuéllar, Yasmin L Hurd, David N Juurlink, Howard K Koh, Erin E Krebs, Anna Lembke, Sean C Mackey, Lisa Larrimore Ouellette, Brian Suffoletto, Christine Timko
Journal: The Lancet (2022)