tbuckley/cabot-search huggingface dataset:
FDA Approval Summary: Abemaciclib With Endocrine Therapy for High-Risk Early Breast Cancer
Authors: Melanie Royce, Christy Osgood, Flora Mulkey, Erik Bloomquist, William F. Pierce, Arpita Roy, Shyam Kalavar, Soma Ghosh, Reena Philip, Fatima Rizvi, Bronwyn D. Mixter, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Laleh Amiri-Kordestani
Journal: Journal of Clinical Oncology (2022)

The US Food and Drug Administration approved abemaciclib in combination with endocrine therapy (ET) for the adjuvant treatment of adult patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, early breast cancer (EBC) at high risk of recurrence and a Ki-67 score ≥ 20%.The approval was based on monarchE, a phase III, open-label, 2-cohort, multicenter trial of patients with EBC randomly assigned to receive abemaciclib plus ET (n = 2,808) or ET alone (n = 2,829). Abemaciclib was given at 150 mg orally twice daily for 2 years.Invasive disease-free survival (IDFS) in the intent-to-treat population was statistically significant at the second IDFS interim analysis (IA; March 2020; hazard ratio [HR; 95% CI], 0.747 [0.598 to 0.932]; P = .0096); however, only 12.5% of patients had completed adjuvant therapy, and the HR for overall survival (OS) was > 1. A prespecified, controlled analysis of IDFS in patients with Ki-67 ≥ 20% in cohort 1 was statistically significant at the final IDFS analysis (July 2020; HR [95% CI], 0.643 [0.475 to 0.872]; P = .0042). At the first OS IA (April 2021), the majority of patients had completed adjuvant therapy, IDFS remained consistent, and potential detriment in OS was not observed for this subgroup (HR [95% CI], 0.767 [0.511 to 1.152]). The HR for OS in the intent-to-treat population at OS IA remained > 1 (HR [95% CI], 1.091 [0.818 to 1.455]). More patients in the abemaciclib plus ET arm experienced treatment emergent adverse events (all grades 98.4% v 88.8%, grade 3 ≥ 49.7% v 16.3%).The approval of abemaciclib in adjuvant EBC was limited to patients with high risk of recurrence and Ki-67 ≥ 20%, given their favorable benefit:risk with a statistically significant IDFS advantage and no observed detriment on survival.
Abstract P001: Neck Circumference Is Not Associated With Health Outcomes In Older Athletes
Authors: Mayra dos Santos Silva, Guiomar Silva Lopes, Vagner Raso
Journal: Circulation (2022)

Purpose: This study was undertaken to understand the relationship of neck circumference with body mass index, waist circumference, disease, functional capacity, physical function, and sleep disorders in older athletes. Methods: This was a cross-sectional analysis of 212 older athletes competing at a local level in one of the largest populated cities in the world. Assessments included anthropometrics, disease history with drug treatments, functional capacity, physical function, and sleep disorders. Results: Most individuals with an increased neck circumference were overweight (N=69, 89%, p&lt;0.0001) and had a greater waist circumference (N=55, 71%, p&lt;0.0001). Neck circumference was associated with waist circumference (total sample, N=209: R=0.49, adjusted R 2 =0.24, p&lt;0001), but it was only related to BMI when individuals were analyzed by gender (female, N=127: R=0.49, adjusted R 2 =0.24, p&lt;0001; male, N=83: R=0.57, adjusted R 2 =0.31, p&lt;0001). Neck circumference was related neither to disease (p=0.98), drug use (p=0.65), functional capacity (p=0.46), physical function (p=0.15), nor sleep disorders (p=0.61). Metabolic equivalent per week and sleep disorders weakly related to disease (total sample, N=212: R=0.21, adjusted R 2 =0.03, p&lt;0.01) with borderline significance when the sample was subdivided by gender (female, N=129: R=0.22, adjusted R 2 =0.03, p=0.048; male, N=83: R=0.28, adjusted R 2 =0.06, p=0.035). Conclusion: Our study allows us to conclude that neck circumference may be associated with waist circumference and BMI. However, relationships with disease, functional capacity, physical function, and sleep disorders were not significant to suggest it as an indicator of health outcomes in older athletes.
Think Globally, Act Locally: Globalizing Precision Oncology
Authors: Justin T. Moyers, Vivek Subbiah
Journal: Cancer Discovery (2022)

Summary: Globalizing precision oncology should be a major priority for cancer care in the upcoming decades. In this issue, the K-MASTER study provides a framework for infrastructure building in East Asia illustrating the widening global potential of precision oncology. It is time to modify the precision oncology mantra: Give the right drug, to the right patient, at the right time in every country, to think globally and act locally. See related article by Park et al., p. 938 (3).
Secondary resistance to idelalisib is characterized by upregulation of IGF1R rather than by MAPK/ERK pathway mutations
Authors: Eugen Tausch, Viktor Ljungström, Andreas Agathangelidis, Marc Zapatka, Lydia Scarfò, Billy Michael Chelliah Jebaraj, Deyan Y. Yosifov, Annika Müller, Veerendra Munugalavadla, Jeremiah D. Degenhardt, Paolo Ghia, Richard Rosenquist, Stephan Stilgenbauer
Journal: Blood (2022)
Tepotinib Efficacy and Safety in Patients with <i>MET</i> Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice
Authors: Xiuning Le, Hiroshi Sakai, Enriqueta Felip, Remi Veillon, Marina Chiara Garassino, Jo Raskin, Alexis B. Cortot, Santiago Viteri, Julien Mazieres, Egbert F. Smit, Michael Thomas, Wade T. Iams, Byoung Chul Cho, Hye Ryun Kim, James Chih-Hsin Yang, Yuh-Min Chen, Jyoti D. Patel, Christine M. Bestvina, Keunchil Park, Frank Griesinger, Melissa Johnson, Maya Gottfried, Christian Britschgi, John Heymach, Elif Sikoglu, Karin Berghoff, Karl-Maria Schumacher, Rolf Bruns, Gordon Otto, Paul K. Paik
Journal: Clinical Cancer Research (2021)

Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups.This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity.152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7-53.0]. Patients aged <75 (n = 84) and ≥75 (n = 68) had ORRs of 48.8% (95% CI: 37.7-60.0) and 39.7% (95% CI: 28.0-52.3), respectively. Treatment-naïve (n = 69) versus previously treated (n = 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9-57.4) vs. 44.6% (33.7-55.9); median duration of response (95% CI): 10.8 (6.9-not estimable) vs. 11.1 (9.5-18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies.Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations. See related commentary by Rosner and Spira, p. 1055.
Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest
Authors: Barry J. Ruijter, Hanneke M. Keijzer, Marleen C. Tjepkema-Cloostermans, Michiel J. Blans, Albertus Beishuizen, Selma C. Tromp, Erik Scholten, Janneke Horn, Anne-Fleur van Rootselaar, Marjolein M. Admiraal, Walter M. van den Bergh, Jan-Willem J. Elting, Norbert A. Foudraine, Francois H.M. Kornips, Vivianne H.J.M. van Kranen-Mastenbroek, Rob P.W. Rouhl, Elsbeth C. Thomeer, Walid Moudrous, Frouke A.P. Nijhuis, Suzanne J. Booij, Cornelia W.E. Hoedemaekers, Jonne Doorduin, Fabio S. Taccone, Job van der Palen, Michel J.A.M. van Putten, Jeannette Hofmeijer
Journal: New England Journal of Medicine (2022)

Whether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain.We conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation.We enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, -7 to 11; P = 0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group.In comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.).
In long-term, higher-dose opioid use, dose tapering was linked to overdose and mental health crises
Authors: Peter MacDougall
Journal: Annals of Internal Medicine (2022)

ACP Journal ClubJanuary 2022In long-term, higher-dose opioid use, dose tapering was linked to overdose and mental health crisesPeter MacDougall, PhD, MDPeter MacDougall, PhD, MDDalhousie University, Halifax, Nova Scotia, Canada (P.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J21-0005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationAgnoli A, Xing G, Tancredi DJ, et al. Association of dose tapering with overdose or mental health crisis among patients prescribed long-term opioids. JAMA. 2021;326:411-9. https://pubmed.ncbi.nlm.nih.gov/34342618Clinical Impact RatingsGIM/FP/GP: References1. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain–United States, 2016. MMWR Recomm Rep. 2016;65:1-49. [PMID: 26987082] Google Scholar2. Busse JW, Craigie S, Juurlink DN, et al. Guideline for opioid therapy and chronic noncancer pain. CMAJ. 2017;189:E659-66. [PMID: 28483845] Google Scholar3. Ahonle ZJ, Jia H, Mudra SA, et al. Drug overdose and suicide among veteran enrollees in the VHA: comparison among local, regional, and national data. Fed Pract. 2020;37:420-5. [PMID: 33029067] Google Scholar Author, Article, and Disclosure InformationAffiliations: Dalhousie University, Halifax, Nova Scotia, Canada (P.M.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J21-0005.This article was published at Annals.org on 4 January 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics January 2022Volume 175, Issue 1Page: JC11KeywordsAddictionAnxietyBenzodiazepinesCohort studiesEmergency departmentOpioidsPalliative carePopulation statisticsPsychiatry and mental healthSuicide ePublished: 4 January 2022 Issue Published: January 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Electrocardiographic Manifestations of Immune Checkpoint Inhibitor Myocarditis
Authors: John R. Power, Joachim Alexandre, Arrush Choudhary, Benay Ozbay, Salim Hayek, Aarti Asnani, Yuichi Tamura, Mandar Aras, Jennifer Cautela, Franck Thuny, Lauren Gilstrap, Dimitri Arangalage, Steven Ewer, Shi Huang, Anita Deswal, Nicolas L. Palaskas, Daniel Finke, Lorenz Lehmann, Stephane Ederhy, Javid Moslehi, Joe-Elie Salem, Baptiste Abbar, Yves Allenbach, Tariq U. Azam, Alan Baik, Lauren A. Baldassarre, Barouyr Baroudjian, Pennelope Blakley, Sergey Brodsky, Johnny Chahine, Wei-Ting Chan, Amy Copeland, Shanthini M. Crusz, Grace Dy, Charlotte Fenioux, Kambiz Ghafourian, Arjun K. Ghosh, Valérie Gounant, Avirup Guha, Manhal Habib, Osnat Itzhaki Ben Zadok, Lily Koo Lin, Michal Laufer-Perl, Carrie Lenneman, Darryl Leong, Matthew Martini, Tyler Meheghan, Elvire Mervoyer, Cecilia Monge, Ryota Morimoto, Anna Narezkina, Martin Nicol, Joseph Nowatzke, Olusola Ayodeji Orimoloye, Milan Patel, Daniel Perry, Nicolas Piriou, Lawrence Piro, Tyler Moran, Ben Stringer, Kazuko Tajiri, Pankit Vachhani, Ellen Warner, Marie-Claire Zimmer
Journal: Circulation (2021)
Diagnosis and Management of Patients With Myocardial Injury After Noncardiac Surgery: A Scientific Statement From the American Heart Association
Authors: Kurt Ruetzler, Nathaniel R. Smilowitz, Jeffrey S. Berger, P.J. Devereaux, Bradley A. Maron, L. Kristin Newby, Vinicio de Jesus Perez, Daniel I. Sessler, Duminda N. Wijeysundera
Journal: Circulation (2021)

Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs. Myocardial injury after noncardiac surgery occurs in ≈20% of patients who have major inpatient surgery, and most are asymptomatic. Myocardial injury after noncardiac surgery is independently and strongly associated with both short-term and long-term mortality, even in the absence of clinical symptoms, electrocardiographic changes, or imaging evidence of myocardial ischemia consistent with myocardial infarction. Consequently, surveillance of myocardial injury after noncardiac surgery is warranted in patients at high risk for perioperative cardiovascular complications. This scientific statement provides diagnostic criteria and reviews the epidemiology, pathophysiology, and prognosis of myocardial injury after noncardiac surgery. This scientific statement also presents surveillance strategies and treatment approaches.
Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans
Authors: Young Jun Oh, Matthew W. Dent, Angela R. Freels, Qingwen Zhou, Carlito B. Lebrilla, Michael L. Merchant, Nobuyuki Matoba
Journal: Molecular Therapy (2022)

Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we showed that a lectibody consisting of the high-mannose glycan-binding lectin Avaren and human immunoglobulin G1 (IgG1) Fc (AvFc) selectively recognizes a range of cell lines derived from lung, breast, colon, and blood cancers at nanomolar concentrations. Binding of AvFc to the non-small cell lung cancer (NSCLC) cell lines A549 and H460 was characterized in detail. Co-immunoprecipitation proteomics analysis revealed that epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) are among the lectibody's common targets in these cells. AvFc blocked the activation of EGFR and IGF1R by their respective ligands in A549 cells and inhibited the migration of A549 and H460 cells upon stimulation with EGF and IGF1. Furthermore, AvFc induced potent Fc-mediated cytotoxic effects and significantly restricted A549 and H460 tumor growth in severe combined immunodeficiency (SCID) mice. Immunohistochemistry analysis of primary lung tissues from NSCLC patients demonstrated that AvFc preferentially binds to tumors over adjacent non-tumor tissues. Our findings provide evidence that increased abundance of high-mannose glycans in the glycocalyx of cancer cells can be a druggable target, and AvFc may provide a new tool to probe and target this tumor-associated glycobiomarker.
Sleep disturbances and sleep disorders as risk factors for chronic postsurgical pain: A systematic review and meta-analysis
Authors: Giorgia Varallo, Emanuele M. Giusti, Chiara Manna, Gianluca Castelnuovo, Fabio Pizza, Christian Franceschini, Giuseppe Plazzi
Journal: Sleep Medicine Reviews (2022)

This systematic review and meta-analysis aimed at evaluating the role of sleep disturbances and sleep disorders in influencing presence and intensity of chronic postsurgical pain (CPSP). We included cohort studies which enrolled adults, assessed sleep disturbances or disorders before surgery, measured pain intensity, presence of pain, or opioid use at least three months after surgery. Eighteen studies were included in a narrative synthesis and 12 in a meta-analysis. Sleep disturbances and disorders were significantly related to CPSP, with a small effect size, r = 0.13 (95% CI 0.06–0.20). The certainty of evidence was rated low due to risk of bias and heterogeneity. In subgroup analyses the above association was significant in studies that used pain intensity as the outcome, but not in those that used presence of pain; in studies on patients who underwent total knee arthroplasty or other surgeries, but not in those on patients who had breast cancer surgery or total hip arthroplasty; in the single study that assessed insomnia and in studies that assessed sleep disturbances as predictors. A meta-regression showed that the follow-up length was positively associated with the overall estimate. Our findings suggest that presurgical sleep disturbances and disorders should be evaluated to detect patients at risk for CPSP. Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=272654
Anti-SARS-CoV-2 IgA and IgG in human milk after vaccination is dependent on vaccine type and previous SARS-CoV-2 exposure: a longitudinal study
Authors: Marta Selma-Royo, Christine Bäuerl, Desirée Mena-Tudela, Laia Aguilar-Camprubí, Francisco J. Pérez-Cano, Anna Parra-Llorca, Carles Lerin, Cecilia Martínez-Costa, Maria Carmen Collado
Journal: Genome Medicine (2022)

Breast milk is a vehicle to transfer protective antibodies from the lactating mother to the neonate. After SARS-CoV-2 infection, virus-specific IgA and IgG have been identified in breast milk, however, there are limited data on the impact of different COVID-19 vaccine types in lactating women. This study is aimed to evaluate the time course of induction of SARS-CoV-2-specific IgA and IgG in breast milk after vaccination.
167P KRAS G12C lung adenocarcinoma represents a distinct group of patients with different response to immunotherapy
Authors: L. Masfarré, P. Rocha, S. Clavé, L. Moliner, N. Navarro-Gorro, A. Ríos-Hoyo, I. Sánchez, M. Giner, A. Corbera, A. Taus, B. Bellosillo, E. Arriola
Journal: Annals of Oncology (2022)
107P Application of contrast clearance analysis (CCA) to assess viable tumour in non-small cell lung cancer (NSCLC) brain metastases post-stereotactic radiosurgery (SRS)
Authors: S. Mohamedkhan, N. Williams, T. Millard, N. Rosenfelder, B. Sharma, A. Minchom
Journal: Annals of Oncology (2022)
Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of <i>Trypanosoma cruzi</i> –Seropositive Individuals
Authors: Maria Carmo P. Nunes, Lewis F. Buss, Jose Luiz P. Silva, Larissa Natany A. Martins, Claudia Di Lorenzo Oliveira, Clareci Silva Cardoso, Bruno Oliveira de Figueiredo Brito, Ariela Mota Ferreira, Lea Campos Oliveira, Ana Luiza Bierrenbach, Fabio Fernandes, Michael P. Busch, Viviane Tiemi Hotta, Luiz Mario Baptista Martinelli, Maria Carolina F. Almeida Soeiro, Adriana Brentegani, Vera M.C. Salemi, Marcia M. Menezes, Antonio Luiz P. Ribeiro, Ester Cerdeira Sabino
Journal: Circulation (2021)

There are few contemporary cohorts of Trypanosoma cruzi-seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with T. cruzi seropositivity.Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as T. cruzi-seropositive blood donors. T. cruzi-seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, ECG, and echocardiogram at enrollment (2008-2010) and at follow-up (2018-2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration ≥120 ms, or both. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection.We enrolled 499 T. cruzi-seropositive donors (age 48±10 years, 52% male), 488 T. cruzi-seronegative donors (age 49±10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48±8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000 py (17/114, 15%) in T. cruzi-seropositive donors with cardiomyopathy at baseline. Among T. cruzi-seropositive donors without cardiomyopathy at baseline, mortality was 3.7 events/1000 py (15/385, 4%), which was no different from T. cruzi-seronegative donors with 3.6 deaths/1000 py (17/488, 3%). The incidence of cardiomyopathy in T. cruzi-seropositive donors was 13.8 (95% CI, 9.5-19.6) events/1000 py (32/262, 12%) compared with 4.6 (95% CI, 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with T. cruzi seropositivity of 9.2 (95% CI, 3.6-15.0) events/1000 py. T. cruzi antibody level at baseline was associated with development of cardiomyopathy (adjusted odds ratio, 1.4 [95% CI, 1.1-1.8]).We present a comprehensive description of the natural history of T. cruzi seropositivity in a contemporary patient population. The results highlight the central importance of anti-T. cruzi antibody titer as a marker of Chagas disease activity and risk of progression.