tbuckley/cabot-search huggingface dataset:
Clonal Hematopoiesis–Associated Gene Mutations in a Clinical Cohort of 448 Patients With Ovarian Cancer
Authors: Konstantin Weber-Lassalle, Corinna Ernst, Alexander Reuss, Kathrin Möllenhoff, Klaus Baumann, Christian Jackisch, Jan Hauke, Dimo Dietrich, Julika Borde, Tjoung-Won Park-Simon, Lars Hanker, Katharina Prieske, Sandra Schmidt, Nana Weber-Lassalle, Esther Pohl-Rescigno, Stefan Kommoss, Frederik Marmé, Florian Heitz, Julia C Stingl, Rita K Schmutzler, Philipp Harter, Eric Hahnen
Journal: JNCI Journal of the National Cancer Institute (2021)

Cancer patients are at risk of secondary therapy-related myeloid neoplasms (t-MNs). Acquired blood-specific mutations in clonal hematopoiesis (CH)-associated genes are t-MN risk factors, and their occurrence associated with cancer therapy and age. Patients with ovarian cancer (OC) showed a particularly high prevalence of CH-associated gene mutations, which may additionally be explained by the high proportion of a hereditary disease cause in this cancer entity.We performed a retrospective analysis of 448 OC patients enrolled in the AGO-TR1 study; 249 were enrolled at primary diagnosis and 199 at platinum-sensitive recurrence. Analyses included the most frequently altered CH-associated genes (ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, TP53). Results were analyzed according to the BRCA1/2 germline (gBRCA1/2) mutation status. All statistical tests were 2-sided.Advanced age at blood draw and a high number of prior platinum-based chemotherapy lines were risk factors to acquire CH-associated gene mutations, with gene-specific effects observed. Binomial logistic regression suggested increased probabilities for gBRCA1/2 mutation carriers to acquire CH-associated PPM1D and TP53 gene mutations (PPM1D: odds ratio = 4.30, 95% confidence interval = 1.48 to 12.46, P = .007; TP53: odds ratio = 6.20, 95% confidence interval = 0.98 to 53.9, P = .06). This observation was due to a statistically significantly increased number of platinum-based chemotherapy lines in gBRCA1/2 mutation carriers vs noncarriers (PPM1D: mean [SD] = 2.04 [1.27] vs 1.04 [0.99], P < .001; TP53: mean [SD] = 2.83 [1.33] vs 1.07 [1.01], P < .001). No interaction between platinum-based chemotherapy and gBRCA1/2 mutation status with the occurrence of CH-associated gene mutations was observed.A positive gBRCA1/2 mutation status is not a risk factor to acquire CH-associated gene mutations. OC patients may benefit from monitoring CH-associated gene mutations, especially following carboplatin exposure. Future clinical studies are required to assess whether treatment regimen should be adapted according to individual t-MN risks.
79P Immune-related adverse events are correlated with significantly improved outcome in a phase I trial population exposed to combination immunotherapy
Authors: L. Mazzarella, F. Giugliano, E. Crimini, J. Uliano, C. Corti, P. D'Amico, P. Trillo Aliaga, C. Valenza, M. Repetto, E. Nicolo, G. Antonarelli, L. Ascione, G. Vivanet, P.P.M. Berton Giachetti, C. Belli, C. Criscitiello, A. Esposito, M.A. Locatelli, I. Minchella, G. Curigliano
Journal: Annals of Oncology (2021)
Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort
Authors: Celline C Almeida-Brasil, John G Hanly, Murray Urowitz, Ann Elaine Clarke, Guillermo Ruiz-Irastorza, Caroline Gordon, Rosalind Ramsey-Goldman, Michelle Petri, Ellen M Ginzler, D J Wallace, Sang-Cheol Bae, Juanita Romero-Diaz, Mary Anne Dooley, Christine Peschken, David Isenberg, Anisur Rahman, Susan Manzi, Søren Jacobsen, Sam Lim, Ronald F van Vollenhoven, Ola Nived, Andreas Jönsen, Diane L Kamen, Cynthia Aranow, Jorge Sanchez-Guerrero, Dafna D Gladman, Paul R Fortin, Graciela S Alarcón, Joan T Merrill, Kenneth Kalunian, Manuel Ramos-Casals, Kristján Steinsson, Asad Zoma, Anca Askanase, Munther A Khamashta, Ian N Bruce, Murat Inanc, Michal Abrahamowicz, Sasha Bernatsky
Journal: Annals of the Rheumatic Diseases (2021)

Objectives To evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance. Methods We analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999–2019). We evaluated person-time contributed while on the initial HCQ dose (‘maintenance’), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare. Results We studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts. Conclusions SLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (eg, seniors) may be helpful.
Abstract 17147: Multidisciplinary-team Management Of A Severely-ill Pregnant Covid-19 Patient With A Newly Diagnosed Severe Mitral Stenosis
Authors: Yazan Aljabery, Yosef Manla, Laszlo Gobolos, Gopal Bhatnagar, Mahmoud Traina
Journal: Circulation (2021)

A 30-year-old female who was 26 weeks pregnant, presented to an outside facility with acute hypoxic respiratory failure and was initially treated as an asthma exacerbation. Her chest X-ray and CT revealed extensive bilateral airspace disease of ground glass opacities (Figure 1A) and a main pulmonary artery diameter of 3.5 cm. Transesophageal echocardiogram revealed severe mitral stenosis (MS) with a high Wilkins-Abascal score of 11/16, a mean mitral gradient of 19 mmHg, and a right ventricular systolic pressure of 94 mmHg consistent with severe pulmonary hypertension (Figure 1B, 1C). Rapid COVID test was positive, patient clinically deteriorated and was emergently transferred to our facility. She rapidly required intubation and vasopressor support. Our multi-disciplinary team (MDT) decided to perform an emergent rescue percutaneous balloon mitral valvuloplasty, which led to an improvement of mitral stenosis, but with a resultant significant MR. Intraoperative decision was taken to proceed with an emergency cesarean section and a live male was delivered. Postoperatively, she was treated supportively for COVID pneumonia with rapid improvement in clinical status. She was extubated on the 3 rd postoperative day (POD), and was ambulating without any need for oxygen by the 7 th POD, and discharged home on the 11 th POD. Her infant continued to improve and was discharged 1 month later. Discussion: Rheumatic MS constitutes a major cause of acquired heart disease complicating pregnancy in the developing world. This case report features some of the challenges in the diagnosis and management of a complex condition in the pandemic environment and highlights the importance of MDT approach.
Macrophages acquire a TNF-dependent inflammatory memory in allergic asthma
Authors: Antonie Lechner, Fiona D.R. Henkel, Franziska Hartung, Sina Bohnacker, Francesca Alessandrini, Ekaterina O. Gubernatorova, Marina S. Drutskaya, Carlo Angioni, Yannick Schreiber, Pascal Haimerl, Yan Ge, Dominique Thomas, Agnieszka M. Kabat, Edward J. Pearce, Caspar Ohnmacht, Sergei A. Nedospasov, Peter J. Murray, Adam M. Chaker, Carsten B. Schmidt-Weber, Julia Esser-von Bieren
Journal: Journal of Allergy and Clinical Immunology (2021)
Private Equity and Health Care Delivery
Authors: Join Y. Luh, Eric R. Hansen, Sean Liston
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Evolving diagnostic techniques in mediastinal lymphadenopathy: is mediastinal cryobiopsy the new kid on the block?
Authors: Reinier R.L. Wener, Paul E. Van Schil
Journal: European Respiratory Journal (2021)

<b>Mediastinal cryobiopsy might have additional value in the diagnostic work up of hilar and mediastinal lymphadenopathy, especially in sarcoidosis and lymphoma. However, further research is necessary to estimate its true value.</b>https://bit.ly/3zreDSo
A strategy of vascular‐targeted therapy for liver fibrosis
Authors: Yuan Lin, Meng‐Qi Dong, Zhi‐Min Liu, Meng Xu, Zhi‐Hao Huang, Hong‐Juan Liu, Yi Gao, Wei‐Jie Zhou
Journal: Hepatology (2021)

Abstract Background and Aims No effective treatments are available for liver fibrosis. Angiogenesis is deeply involved in liver fibrogenesis. However, current controversial results suggest it is difficult to treat liver fibrosis through vascular targeting. There are three different microvessels in liver: portal vessels, liver sinusoids, and central vessels. The changes and roles for each of the three different vessels during liver fibrogenesis are unclear. We propose that they play different roles during liver fibrogenesis, and a single vascular endothelial cell (EC) regulator is not enough to fully regulate these three vessels to treat liver fibrosis. Therefore, a combined regulation of multiple different EC regulatory signaling pathway may provide new strategies for the liver fibrosis therapy. Herein, we present a proof‐of‐concept strategy by combining the regulation of leukocyte cell‐derived chemotaxin 2 (LECT2)/tyrosine kinase with immunoglobulin‐like and epidermal growth factor–like domains 1 signaling with that of vascular endothelial growth factor (VEGF)/recombinant VEGF (rVEGF) signaling. Approach and Results The CCl 4 ‐induced mouse liver fibrosis model and NASH model were both used. During fibrogenesis, vascular changes occurred at very early stage, and different liver vessels showed different changes and played different roles: decreased portal vessels, increased sinusoid capillarization and the increased central vessels the increase of portal vessels alleviates liver fibrosis, the increase of central vessels aggravates liver fibrosis, and the increase of sinusoid capillarization aggravates liver fibrosis. The combinational treatment of adeno‐associated viral vector serotype 9 (AAV9)–LECT2–short hairpin RNA (shRNA) and rVEGF showed improved therapeutic effects, but it led to serious side effects. The combination of AAV9‐LECT2‐shRNA and bevacizumab showed both improved therapeutic effects and decreased side effects. Conclusions Liver vascular changes occurred at very early stage of fibrogenesis. Different vessels play different roles in liver fibrosis. The combinational treatment of AAV9‐LECT2‐shRNA and bevacizumab could significantly improve the therapeutic effects on liver fibrosis.
Estimating the transmission advantage of the D614G mutant strain of SARS-CoV-2, December 2019 to June 2020
Authors: Kathy Leung, Yao Pei, Gabriel M Leung, Tommy TY Lam, Joseph T Wu
Journal: Eurosurveillance (2021)

Introduction The SARS-CoV-2 lineages carrying the amino acid change D614G have become the dominant variants in the global COVID-19 pandemic. By June 2021, all the emerging variants of concern carried the D614G mutation. The rapid spread of the G614 mutant suggests that it may have a transmission advantage over the D614 wildtype. Aim Our objective was to estimate the transmission advantage of D614G by integrating phylogenetic and epidemiological analysis. Methods We assume that the mutation D614G was the only site of interest which characterised the two cocirculating virus strains by June 2020, but their differential transmissibility might be attributable to a combination of D614G and other mutations. We define the fitness of G614 as the ratio of the basic reproduction number of the strain with G614 to the strain with D614 and applied an epidemiological framework for fitness inference to analyse SARS-CoV-2 surveillance and sequence data. Results Using this framework, we estimated that the G614 mutant is 31% (95% credible interval: 28–34) more transmissible than the D614 wildtype. Therefore, interventions that were previously effective in containing or mitigating the D614 wildtype (e.g. in China, Vietnam and Thailand) may be less effective against the G614 mutant. Conclusion Our framework can be readily integrated into current SARS-CoV-2 surveillance to monitor the emergence and fitness of mutant strains such that pandemic surveillance, disease control and development of treatment and vaccines can be adjusted dynamically.
A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus
Authors: William A. Fischer, Joseph J. Eron, Wayne Holman, Myron S. Cohen, Lei Fang, Laura J. Szewczyk, Timothy P. Sheahan, Ralph Baric, Katie R. Mollan, Cameron R. Wolfe, Elizabeth R. Duke, Masoud M. Azizad, Katyna Borroto-Esoda, David A. Wohl, Robert W. Coombs, Amy James Loftis, Paul Alabanza, Felicia Lipansky, Wendy P. Painter
Journal: Science Translational Medicine (2021)

There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration &lt;7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment ( P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients ( P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses.
Caustic Ingestion—The Haves and the Have Nots
Authors: Mark K. Ferguson
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Super-Enhancer-Driven PPP1R15B As an Oncogenic and Potential Therapeutic Target in Multiple Myeloma
Authors: Sinan Xiong, Jianbiao Zhou, Tze King Tan, Sabrina Hui-Min Toh, Kalpnaa Balan, Yunlu Jia, Tae-Hoon Chung, Takaomi Sanda, Wee Joo Chng
Journal: Blood (2021)
Telehealth Delivery of Tobacco Cessation Treatment in Cancer Care: An Ongoing Innovation Accelerated by the COVID-19 Pandemic
Authors: _ _
Journal: Journal of the National Comprehensive Cancer Network (2021)

The COVID-19 pandemic precipitated a rapid transformation in healthcare delivery. Ambulatory care abruptly shifted from in-person to telehealth visits with providers using digital video and audio tools to reach patients at home. Advantages to telehealth care include enhanced patient convenience and provider efficiencies, but financial, geographic, privacy, and access barriers to telehealth also exist. These are disproportionately greater for older adults and for those in rural areas, low-income communities, and communities of color, threatening to worsen preexisting disparities in tobacco use and health. Pandemic-associated regulatory changes regarding privacy and billing allowed many Cancer Center Cessation Initiative (C3I) programs in NCI-designated Cancer Centers to start or expand video-based telehealth care. Using 3 C3I programs as examples, we describe the methods used to shift to telehealth delivery. Although telephone-delivered treatment was already a core tobacco treatment modality with a robust evidence base, little research has yet compared the effectiveness of tobacco cessation treatment delivery by video versus phone or in-person modalities. Video-delivery has shown greater medication adherence, higher patient satisfaction, and better retention in care than phone-based delivery, and may improve cessation outcomes. We outline key questions for further investigation to advance telehealth for tobacco cessation treatment in cancer care.
Metformin—A Thought-provoking Addition to Anticancer Therapies—Reply
Authors: Theodoros Tsakiridis, Gregory R. Pond, James Wright
Journal: JAMA Oncology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
15P Serum immune checkpoint biomarkers as predictors of response to anti-PD-1/PD-L1 treatment in non-small cell lung cancer (NSCLC) patients
Authors: A. Raza, R. Mohsin, A. Kanbour, S. Vijayakar, A. Philip, M.A. Tauro, S. Sherif, M. Merhi, V. Inchakalody, A.R. Zar Gul, M.U. Al Homsi, S. Dermime
Journal: Annals of Oncology (2021)
136P Phase I dose escalation study of MCLA-145, a bispecific antibody targeting CD137 and PD-L1 in solid tumors
Authors: H. Prenen, C. Kyi, G. Van Lancker, S.P. Patel, D. Mittag, A. Weaver, K. Bol, V. Stalbovskaya, J. Pulini, G. Zhou, Z. Dong, E. Asatiani, F.S. Hodi
Journal: Annals of Oncology (2021)
Natural SARS-CoV-2 infection results in higher neutralization response against variants of concern compared with 2-dose BNT162b2 vaccination in kidney transplant recipients
Authors: Louise Benning, Christian Morath, Marie Bartenschlager, Marvin Reineke, Maximilian Töllner, Christian Nusshag, Florian Kälble, Paula Reichel, Matthias Schaier, Paul Schnitzler, Martin Zeier, Caner Süsal, Ralf Bartenschlager, Claudius Speer
Journal: Kidney International (2021)
Author Correction: The SEQC2 epigenomics quality control (EpiQC) study
Authors: Jonathan Foox, Jessica Nordlund, Claudia Lalancette, Ting Gong, Michelle Lacey, Samantha Lent, Bradley W. Langhorst, V. K. Chaithanya Ponnaluri, Louise Williams, Karthik Ramaswamy Padmanabhan, Raymond Cavalcante, Anders Lundmark, Daniel Butler, Christopher Mozsary, Justin Gurvitch, John M. Greally, Masako Suzuki, Mark Menor, Masaki Nasu, Alicia Alonso, Caroline Sheridan, Andreas Scherer, Stephen Bruinsma, Gosia Golda, Agata Muszynska, Paweł P. Łabaj, Matthew A. Campbell, Frank Wos, Amanda Raine, Ulrika Liljedahl, Tomas Axelsson, Charles Wang, Zhong Chen, Zhaowei Yang, Jing Li, Xiaopeng Yang, Hongwei Wang, Ari Melnick, Shang Guo, Alexander Blume, Vedran Franke, Inmaculada Ibanez de Caceres, Carlos Rodriguez-Antolin, Rocio Rosas, Justin Wade Davis, Jennifer Ishii, Dalila B. Megherbi, Wenming Xiao, Will Liao, Joshua Xu, Huixiao Hong, Baitang Ning, Weida Tong, Altuna Akalin, Yunliang Wang, Youping Deng, Christopher E. Mason
Journal: Genome biology (2021)