tbuckley/cabot-search huggingface dataset:
Comprehensive landscape of BRAF variant classes, clonalities, and comutations in metastatic colorectal cancer using ctDNA profiling.
Authors: Benny Johnson, Dong Yang, Hiba I. Dada, Leylah Drusbosky, Scott Kopetz
Journal: Journal of Clinical Oncology (2022)

152 Background: Although BRAF V600E accounts for the majority of the BRAF mutations in mCRC, non-V600 BRAF variants have been shown in recent years to represent a distinct molecular subtype of mCRC. This study provides a comprehensive profile of BRAF V600 and non-V600 variants, their clonalities and co-mutations in mCRC using a large genomic database of circulating tumor DNA (ctDNA). Methods: A systematic analysis of Guardant360 results was performed among ctDNA samples of mCRC patients from September 2014 to May 2021. A variant was defined as clonal if the mutant allele frequency (MAF) was greater than 50% of the highest somatic MAF in the sample; otherwise it was defined as subclonal. A previously validated anti-EGFR exposure score was applied to predict prior anti-EGFR therapies. Co-mutation analysis was conducted with BRAF, KRAS, NRAS, NF1, ERBB2, PIK3CA and SMAD4. Results: 1,733 out of 14,742 mCRC patients had at least one BRAF variant, including 6.5% of patients with BRAF V600 variants, 1.1% with class II variants, 1.9% with class III variants, and 3.2% with unclassified variants. 431 unique BRAF variants were identified in a total of 1,905 BRAF variants. 70.7% of BRAF V600 variants were clonal while most (56.0%-78.8%) class II, III and unclassified BRAF variants were subclonal (Table). Patients with non- BRAF V600 variants tend to be younger and male. The prevalence of BRAF class II and III variants were higher (2.1% and 3.7%) in patients with predicted prior anti-EGFR exposure compared with patients predicted to have no prior exposure (0.8% and 1.4%). BRAF variants of all classes are more likely to be subclonal in patients predicted to have anti-EGFR exposure than those predicted nonexposed ( p &lt;0.05 in all classes, Fisher’s exact test). Among patients with non- BRAF V600 variants, a greater fraction of co-occurring KRAS and NRAS mutations were detected in those predicted to have prior anti-EGFR exposure. In the patients without predicted EGFR exposure, BRAF class II and III variants showed a higher rate of co-occurring KRAS mutations (25.6% and 21.5%) and co-occurring NRAS mutations (5.8% and 2.7%) compared with BRAF V600 variants (2.4% for KRAS and 0.1% for NRAS); however, co-occurring KRAS G12C was only noted in one patient with a BRAF class II variant. The analysis of outcome data by variant class will be presented at the meeting. Conclusions: We noted significant differences between BRAF V600 and class II/III variants using a large genomic database. Within BRAF class II and III variants, the enrichment in patients with predicted anti-EGFR exposure and the high fraction of co-mutations in KRAS/ NRAS suggest a unique therapeutic need for these patients.[Table: see text]
Snake charmer needed to soothe this debate
Authors: P. Gunby
Journal: JAMA (1980)

More controversy than ever surrounds the already controversial use of snake venom for treatment of multiple sclerosis. The Food and Drug Administration and a Florida serpentarium are in federal court over manufacture and distribution of the venom product. The National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) has turned down a grant request from the National Multiple Sclerosis Society to study the venom. The National Center for Toxicological Research, located at the Army's Pine Bluff Arsenal, Jefferson, Ark, has begun animal tests with a small amount of the material, obtained from the FDA's Bureau of Biologics. The FDA initially asked the Florida serpentarium owner to stop selling the snake venom product to multiple sclerosis and arthritis patients for the time being. It then offered "to cooperate with anyone interested in testing the venom, marketed as PRO-ven." When the serpentarium owner apparently decided not to go along with the
Frequency, molecular characteristics, and therapeutic targeting of<i> ROS1</i> oncogenic fusions in colorectal cancer.
Authors: Saskia Hussung, Dilara Akhoundova, Smruthy Sivakumar, Abdullah Kahraman, Martin Zoche, Markus Rechsteiner, Florian Angst, Christian Britschgi, Antonia Töpfer, Holger Moch, Achim Weber, Ethan Sokol, Ralph M Fritsch
Journal: Journal of Clinical Oncology (2022)

160 Background: c-Ros oncogene 1, receptor tyrosine kinase ( ROS1) rearrangements have been reported in colorectal cancer (CRC), but little is known about the molecular and clinical features of ROS1-driven CRC and the response to ROS1-targeted treatment in CRC patients. Methods: We report disease course and treatment response of an index patient with chemotherapy-refractory right-sided metastatic CRC, harboring an activating ROS1 fusion ( GOPC-ROS1). Moreover, we examined 40,589 patients with CRC who underwent comprehensive genomic profiling as part of routine clinical care at Foundation Medicine (Cambridge, MA); all classes of alterations in at least 324 genes were assessed, including ROS1. Results: The index patient experienced a rapid and sustained partial response to molecularly targeted treatment with crizotinib. After 15 months on crizotinib, disseminated tumor progression occurred, with KRAS Q61H emerging in tumor tissue (53.7% variant allele frequency (VAF)) and liquid biopsy (13.5% VAF). Within the clinical cohort, ROS1 genomic rearrangements ( ROS1 RE (+)) were identified in 34 out of 40,589 (0.08%) CRC samples. GOPC-ROS1 was the most commonly identified ROS1 fusion (11/34 samples), followed by TTC28-ROS1 (3/34 samples). All ROS1-alterations were found in microsatellite-stable (MSS) CRCs, and ROS1 genomic alterations were significantly enriched in KRAS wild type tumors ( KRAS mutations in 23.5% of ROS1 RE(+) vs. 49.8% of ROS1 RE(-), p=0.003). Conclusions: ROS1 rearrangements represent rare but clinically actionable molecular driver alterations in MSS CRCs. The detection of ROS1 fusion oncogenes in CRC can pose diagnostic challenges since intrachromosomal ROS1 fusions including GOPC-ROS1 and non-canonical ROS1 fusions such as TTC28-ROS1 can remain negative on fluorescence in situ hybridization and immunohistochemistry assays, respectively. NGS-based comprehensive molecular profiling may be a useful tool to screen for rare fusion oncogenes.
Facebook versus the BMJ: when fact checking goes wrong
Authors: Rebecca Coombes, Madlen Davies
Journal: BMJ (2022)

<i>The BMJ</i> has locked horns with Facebook and the gatekeepers of international fact checking after one of its investigations was wrongly labelled with "missing context" and censored on the world's largest social network. <b>Rebecca Coombes</b> and <b>Madlen Davies</b> report
Chronic Obstructive Pulmonary Disease and Polycythemia
Authors: Jerry D. Reeves
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The editorial by William R. Barclay, MD (240:1520, 1978), regarding the report of Graham and Houston (240:1491, 1978) on the ability of persons with mild to moderate chronic obstructive pulmonary disease to tolerate short periods at high altitudes is worthy of note. Other factors also may warrant consideration, including the RBC mass. We recently observed a patient with previously undiagnosed chronic obstructive pulmonary disease who had polycythemia, gastrointestinal bleeding, and prolonged partial thromboplastin time (PTT), and who subsequently died of thrombotic complications. The case also illustrates the importance of ensuring that the required dilutional factors are met when determining the PTT. 10 20 30 40 50 60 70 Activated Partial Thromboplastin Time, s Variability of partial thromboplastin time with changes in ratio of sodium citrate to plasma volumes. Shaded area represents normal range (25 to 35 s) and demonstrates range of permissible sodium citrate dilution. <h3>Report of</h3>
Correction to Data in Trial of Convalescent Plasma Treatment for COVID-19
Authors: Zhong Liu
Journal: JAMA (2020)

Ling Li, MD, PhD; Wei Zhang, MD; Yu Hu, MD, PhD; Xunliang Tong, MD, PhD; Shangen Zheng, MD; Juntao Yang, PhD; Yujie Kong, MD; Lili Ren, PhD; Qing Wei, MD; Heng Mei, MD, PhD; Caiying Hu, MD; Cuihua Tao, MD; Ru Yang, MD; Jue Wang, MD; Yongpei Yu, PhD; Yong Guo, PhD; Xiaoxiong Wu, MD; Zhihua Xu, MD; Li Zeng, MD; Nian Xiong, MD, PhD; Lifeng Chen, MD; Juan Wang, MD; Ning Man, MD; Yu Liu, PhD; Haixia Xu, MD; E. Deng, MS; Xuejun Zhang, MS; Chenyue Li, MD; Conghui Wang, PhD; Shisheng Su, PhD; Linqi Zhang, PhD; Jianwei Wang, PhD; Yanyun Wu, MD, PhD; Zhong Liu, MD, PhD
American Journal of Pathology, New York
Journal: JAMA (1970)

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
Mortality among Care Home Residents in England during the first and second waves of the COVID-19 pandemic: an observational study of 4.3 million adults over the age of 65
Authors: Anna Schultze, Emily Nightingale, David Evans, William Hulme, Alicia Rosello, Chris Bates, Jonathan Cockburn, Brian MacKenna, Helen J Curtis, Caroline E Morton, Richard Croker, Seb Bacon, Helen I McDonald, Christopher T Rentsch, Krishnan Bhaskaran, Rohini Mathur, Laurie A Tomlinson, Elizabeth J Williamson, Harriet Forbes, John Tazare, Daniel Grint, Alex J Walker, Peter Inglesby, Nicholas J DeVito, Amir Mehrkar, George Hickman, Simon Davy, Tom Ward, Louis Fisher, Amelia CA Green, Kevin Wing, Angel YS Wong, Robert McManus, John Parry, Frank Hester, Sam Harper, Stephen JW Evans, Ian J Douglas, Liam Smeeth, Rosalind M Eggo, Ben Goldacre, David A Leon
Journal: The Lancet Regional Health - Europe (2022)

Residents in care homes have been severely impacted by COVID-19. We describe trends in the mortality risk among residents of care homes compared to private homes. On behalf of NHS England we used OpenSAFELY-TPP to calculate monthly age-standardised risks of death due to all causes and COVID-19 among adults aged >=65 years between 1/2/2019 and 31/03/2021. Care home residents were identified using linkage to Care and Quality Commission data. We included 4,340,648 people aged 65 years or older on the 1st of February 2019, 2.2% of whom were classified as residing in a care or nursing home. Age-standardised mortality risks were approximately 10 times higher among care home residents compared to those in private housing in February 2019: comparative mortality figure (CMF) = 10.59 (95%CI = 9.51, 11.81) among women, and 10.87 (9.93, 11.90) among men. By April 2020 these relative differences had increased to more than 17 times with CMFs of 17.57 (16.43, 18.79) among women and 18.17 (17.22, 19.17) among men. CMFs did not increase during the second wave, despite a rise in the absolute age-standardised COVID-19 mortality risks. COVID-19 has had a disproportionate impact on the mortality of care home residents in England compared to older residents of private homes, but only in the first wave. This may be explained by a degree of acquired immunity, improved protective measures or changes in the underlying frailty of the populations. The care home population should be prioritised for measures aimed at controlling COVID-19. Medical Research Council MR/V015737/1
A CASE OF ACROMEGALY.
Authors: D'ORSAY HECHT
Journal: JAMA (1905)

<h3>Patient.</h3> —The young woman whose case is herewith reported has been under the care of my colleague, Dr. Ludwing Simon, for several weeks, and I acknowledge my indebtedness to him for the privilege of citation. <h3>Family History.</h3> —The patient is of Scotch-English descent, was born in Cambridge, England, is 24 years old, single, and at the present time a governess by occupation. It is interesting to note that Prof. Clifford Albutt diagnosed a carcinoma of the bowel in the paternal grandfather of the patient; a carcinoma of the larynx in an aunt on the maternal side, and an uncle on the maternal side is now afflicted with carcinoma of the bladder. This familial tendency to malignant neoplasms made the patient feel that, perhaps, her headaches and general enlargement were due to a similar growth. Her father, mother, one brother and two sisters are all living and well, though none of
Long-Term Living Kidney Donor Risk: A Web-Based Calculator
Authors: Elise F. Palzer, Shruti Vempati, Erika S. Helgeson, Arthur J. Matas
Journal: Journal of the American Society of Nephrology (2020)

Living kidney donors are susceptible to the same diseases as the general population. Additionally, those with a family history of ESKD may be at increased risk for kidney disease. Long-term studies comparing donors with the general population have not found increased donor risks. However, two
Masthead
Authors: Willis Maddrey, Steven Schenker, Kunio Okuda, Serge Erlinger, Francis Simon, Jay Hoofnagle, Albert Jones, Neil Kaplowitz, Michael Gerber, Harold Conn, Irwin Arias, Little Roik, S Khan, Roger Lester, Little Rock, Michael Sorrell, Nebraska Secret Ary-, Anthony Tavill, Paul Berk, New York, Maryland Bethesda, Maryland Baltimore, Marcus Rothschild, York Ostrow, David Van Thiel, Hans Fromm, D Washington, R Bruce, St Bacon, Laurence Louis, Canada Ontario, Jorge Rakela, John Vierling, Russell Denver, Rochester Wiesner, Minnesota Chairman
Journal: Hepatology (1990)
Commentaire de travail de A. May et al., pp. 606
Journal: Endoscopy (2007)

See also:Prospective multicenter trial of capsule endoscopy in patients with chronic abdominal pain, diarrhea and other signs and symptoms (CEDAP-Plus Study)Endoscopy 2007; 39(07): 606-612DOI: 10.1055/s-2007-966640
From the Health Care Financing Administration
Authors: G. R. Wilensky
Journal: JAMA (1991)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Tranylcypromine
Journal: JAMA (1963)

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
A Monoclonal Antibody for Malaria Prevention
Authors: Martin R. Gaudinski, Nina M. Berkowitz, Azza H. Idris, Emily E. Coates, LaSonji A. Holman, Floreliz Mendoza, Ingelise J. Gordon, Sarah H. Plummer, Olga Trofymenko, Zonghui Hu, Andrezza Campos Chagas, Sarah O’Connell, Manjula Basappa, Naomi Douek, Sandeep R. Narpala, Christopher R. Barry, Alicia T. Widge, Renunda Hicks, Seemal F. Awan, Richard L. Wu, Somia Hickman, Diane Wycuff, Judy A. Stein, Christopher Case, Brian P. Evans, Kevin Carlton, Jason G. Gall, Sandra Vazquez, Britta Flach, Grace L. Chen, Joseph R. Francica, Barbara J. Flynn, Neville K. Kisalu, Edmund V. Capparelli, Adrian McDermott, John R. Mascola, Julie E. Ledgerwood, Robert A. Seder
Journal: New England Journal of Medicine (2021)

Additional interventions are needed to reduce the morbidity and mortality caused by malaria.
Errors in Text, Table, and Figure
Authors: Divya Gupta, J Lee, Alberty Lin, Nuh Rahbari, Emrullah Birgin, Jürgen Weitz
Journal: JAMA Surgery (2021)

Nuh N. Rahbari, MD; Emrullah Birgin, MD; Ulrich Bork, MD; Arianeb Mehrabi, MD; Christoph Reißfelder, MD; Jürgen Weitz, MD
Analysis of Health System Size and Variability in Diabetic Eye Disease Screening in Wisconsin
Authors: Loren J. Lock, Mark Banghart, Roomasa Channa, Maureen A. Smith, Meghan B. Brennan, Alejandra Torres Diaz, Yao Liu
Journal: JAMA Network Open (2022)

This cohort study uses statewide claims data to assess variability in diabetic eye disease screening across Wisconsin health systems and to examine the association between patient health system and screening receipt.
Detection of coronary steal phenomenon during pharmacological hyperemia by harmonic power doppler employing a simple pulsing sequence in patients with coronary stenosis Yuichiro Takagi, Koji Ohmori, Akira Oshita, Yu Yang, Yoshihiro Wada, Kazushi Yukiiri, Hiroto Takeuchi, Shiro Nozaki, Katsufumi Mizushige, Masakazu Kohno. Second Department of Internal Medicine Kagawa Medical University, Kagawa, Japan
Journal: Journal of the American College of Cardiology (2001)
Patterns of colorectal cancer (CRC) screening rates among the average risk U.S. population.
Authors: Deborah A Fisher, Nicole Engel-Nitz, Lesley-Ann Miller-Wilson, Lisa Le, Paul J. Limburg
Journal: Journal of Clinical Oncology (2022)

65 Background: There is consensus that the proportion of the average-risk US population up-to-date with CRC screening (58-65%) is insufficient. However, estimates of average risk CRC screening rates are inconsistent and impacted by inclusion of higher-risk individuals, and differing study designs. Accurate measurement of population screening rates is key to addressing gaps in care and assessing the impact of newer CRC screening tests. Methods: The study included individuals aged 50-75 years in a large de-identified claims database, with continuous enrollment during year of analysis, and a variable length baseline enrollment of 1-10 years. Average-risk designation excluded higher risk diagnoses (CRC familial syndromes, colorectal polyp or history of colorectal polyp, history of/current CRC, family history of gastrointestinal cancer, and inflammatory bowel disease). Up-to-date status was assessed within guideline-based time periods: colonoscopy (10 years); FIT or FOBT (annually); mt-sDNA (3 years); flexible sigmoidoscopy/CT colonography (5 years). Analyses assessed the proportion estimated as up-to-date and examined the sensitivity to: a) patient population (average-risk only vs. including higher-risk); b) study design (yearly cross-sectional vs. cohort of 50-year-old patients; c) methods (percent in patients with 10 years of enrollment vs. Kaplan Meier (KM) of censored variable pre-screening period). Results: The cross-sectional analysis average-risk population included 5.3 million individuals. Estimates of the proportion of those up-to-date with screening guidelines for average-risk patients varied by study design, population, and estimation method. KM estimates among the average-risk population (50-75) showed 49-50% were up-to-date in each calendar year. Including higher-risk patients in the KM analysis resulted in 70% up-to-date among the mixed average+higher-risk population. Using a cohort study design (average-risk patients aged 60 with 10 years of baseline data), 65% were up-to-date by age 60. Conclusions: In the base case analysis only half of average risk individuals were up-to-date with CRC screening, a rate lower than typically cited. Sensitivity analyses resulted in substantially different estimates and demonstrate the importance of clearly communicating the methodology used to define the study population. Higher rates quoted in the lay press and medical publications may be based on mixed populations of average+higher-risk individuals or on study designs that do not represent the full population at risk.
Research brief
Authors: Sharmila Devi
Journal: The Lancet Infectious Diseases (2020)

Researchers have discovered how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can block the production of cellular proteins and contributes to severe illness in its host. Previous studies had implicated a viral protein, nonstructural protein 1 or Nsp1, in the virus' ability to block cells' production of new proteins. The researchers were able to show that Nsp1 is one of SARS-CoV-2's most pathogenic viral proteins. In human lung cells, it can drastically alter host cell gene expression and essentially form a plug that prevents the ribosome from receiving genetic instructions for new proteins encoded in messenger RNA.
Last Rounds
Authors: Joseph T. Martorano
Journal: JAMA (1989)

I cradle my father carefully in my arms. His chin rests against my right shoulder as the physician slips the long thoracentesis needle into his back, searching for the cause of his inability to swallow food. The physician's eyes evade mine. We are both 50 years old and between us have practiced medicine for a collective half-century. My father is a 78-year-old general practitioner. Half a century earlier he caught his father's leg during an amputation for diabetes. Together the three of us complete a century of medicine. Finally the bitter answer comes. Ironically, my father, who has spent a lifetime railing against cigarette smoking, is to die of a rare lung cancer. We settle down. Even as we tell him the brutal diagnosis, I learn that a doctor dies differently. My father's initial response is muted anguish, but quickly his professional pride takes over. "I knew I was right."