tbuckley/cabot-search huggingface dataset:
Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: A retrospective real world study.
Authors: Yang Chen, Guanghai Dai
Journal: Journal of Clinical Oncology (2019)

113 Background: Although the clinical trial WJOG7112G was failed to prove weekly paclitaxel with trastuzumab in patients with HER2-positive gastric or gastro-esophageal junction (GEJ) cancer refractory to trastuzumab is better than paclitaxel alone, there are limited data concerning efficacy of continuing trastuzumab beyond first-line progression in the real world. Methods: This retrospective study included all consecutive patients with HER2-positive advanced gastric or GEJ adenocarcinoma who received a chemotherapy with trastuzumab in first-line, or second-line, or third-line therapy between 2010 and 2016 in Chinese People’s Liberation Army General Hospital. Progression-free survival (PFS) and overall survival (OS) were estimated from the initial chemotherapy. Results: A total of 67 patients (median age, 59 years; male, 71.6%) with HER-2 positive advanced gastric or GEJ adenocarcinoma treated with chemotherapy plus trastuzumab initially in first (n = 50), second (n = 13), or third (n = 4) line of therapy were included. The median OS of trastuzumab for initial first-line, second-line, or third-line treatment was 16.7 months, 14.2 months, and 13.2 months, respectively (P = 0.83). In patients initially using trastuzumab in first-line therapy, the continuation (n = 19) versus discontinuation (n = 31) of trastuzumab beyond first-line progression was significantly associated with an improvement of median PFS (3.4 versus 1.9 months; P = 0.02), but not OS (19.0 versus 16.4 months; P = 0.13). In the multivariate analysis including the ECOG PS, number of metastatic sites and chemotherapy regimen, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.77; 95% CI, 0.41-0.93; P = 0.04), but not OS (HR, 0.85; 95% CI, 0.56-1.22; P = 0.24). Conclusions: This study suggests that HER-2 positive advanced gastric or GEJ adenocarcinoma patients could benefit from trastuzumab no matter when they start receiving trastuzumab. The continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer for PFS, but not for OS. Large scale prospective randomized validation is warranted.
FLT3-ITD impedes retinoic acid, but not arsenic, responses in murine acute promyelocytic leukemias
Authors: Cécile Esnault, Ramy Rahmé, Kim L. Rice, Caroline Berthier, Coline Gaillard, Samuel Quentin, Anne-Lise Maubert, Scott Kogan, Hugues de Thé
Journal: Blood (2019)
Financial distress amongst older adults with gastrointestinal (GI) malignancies.
Authors: William Varnado, Kelly Kenzik, Andrew Michael McDonald, Mariel Parman, Ravi Kumar Paluri, Rudolph M. Navari, Crystal Young Smith, Matthew Robertson, Smita Bhatia, Grant Richard Williams
Journal: Journal of Clinical Oncology (2019)

517 Background: Many patients with cancer report financial distress (FD); however, the magnitude of FD in the growing number of older adults with cancer remains less clear, particularly in those with GI malignancies. The purpose of this study was to evaluate the proportion of older adults with GI malignancies reporting FD and to characterize geriatric assessment (GA) and cancer-related factors associated with FD. Methods: Older adults ( ≥ 60yrs) seen in the GI oncology clinic at the University of Alabama Birmingham (UAB) were asked to fill out a patient-reported GA, entitled the Cancer &amp; Aging Resilience Evaluation (CARE), at their visit. The CARE includes questions pertaining to patient’s independence in Activities of Daily Living (ADLs), Instrumental Activities of Daily Living (IADLs), falls, physical function, polypharmacy, and comorbidity. A single item question regarding FD from the patient satisfaction questionnaire (PSQ-18) was included. FD was defined as agreement with the phrase “Do you have to pay for more medical care than you can afford.” Demographic and GA characteristics were compared between those with and without FD using Chi-square and t-tests. Results: 233 patients completed the CARE a median of 71 days after diagnosis. Median age 68y (60-96); 54.5% male and 76.0% non-Hispanic white. Most common cancer types included colorectal (39.1%) and pancreatic cancers (20.6%). A total of 62 patients (26.6%) had FD. Patients with FD were more likely to be younger (68.1 vs. 70.1y, p = 0.04), of black race (37.1% vs. 15.8%, p = 0.007), have low education ( ≤ high school: 74.2% vs. 59.6%, p = 0.02), have one or more falls (31.5% vs. 19.9%, p = 0.077), to be limited a lot in walking 1 block (54.4% vs. 27.4%, p = 0.0003), take more than 4 medications (88.3% vs. 70.8%, p = 0.007), to have more than one comorbid condition (93.1% vs. 82.6%, p = 0.052), to report impaired IADLs (61.3% vs. 43.9%, p = 0.055), and impaired ADL (27.4% vs. 14.6%, p = 0.069). No associations were found with GI cancer type or stage, marital status, time from diagnosis, or hearing/vision impairments. Conclusions: Over a quarter of the older adult population with GI malignancies report FD. Several GA and demographic factors were associated with FD that may help identify older patients at risk for FD.
Abstract IA11: Epigenetic mechanisms in pathogenesis and targeted therapy for B-cell lymphomas
Authors: Ari Melnick
Journal: Clinical Cancer Research (2018)

Abstract Recent genome sequencing studies have revealed that somatic mutation of genes that control the epigenome are the most common class of genetic lesion in DLBCLs and FLs. The epigenome is composed of hundreds of distinct chemical modifications of DNA, histones, RNA, and other molecules. Collectively, the epigenome functions as cellular “software”: instructions that encode and determine the phenotype of every type of normal and malignant cell. The fact that mutations in epigenetic modifiers are so common in DLBCL and FL points to the significance of the epigenome in these tumors. The four most common mutations in epigenetic modifiers in DLBCL and FL affect the following genes: KMT2D (also called MLL2), CREBBP, EP300, and EZH2. Eighty percent of lymphoma patients have at least one of these four mutations and often have more than one. Moreover, these mutations usually occur very early during lymphomagenesis and so represent important “founder” events. One fascinating insight that has recently emerged is that these genes play critical roles in germinal center B cells, which are the cells from which DLBCL and FL arise. This is interesting because in many ways germinal center B cells already manifest tumor-like phenotypes. Indeed, it appears that much of the effect of mutations in KMT2D, CREBBP, EP300, and EZH2 is to “lock” B cells into the germinal center mode, which essentially means that it maintains B cells in a highly proliferative, mutagenic state that is hidden from immune surveillance. Fortunately, novel small-molecule inhibitors have been developed that can correct the abnormal epigenomic programs caused by these mutations, and some of these drugs are already showing efficacy in clinical trials. In addition to suppressing lymphoma cells, this kind of treatment may enhance antilymphoma response by restoring immune surveillance. In my talk I will explain how these mechanisms work, and how we can design and implement novel therapeutic regimens that can suppress lymphoma cells with minimal toxicity to other tissues. Citation Format: Ari Melnick. Epigenetic mechanisms in pathogenesis and targeted therapy for B-cell lymphomas [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr IA11.
Diffuse Bone Metastases in Pancreatic Neuroendocrine Tumor Shown on Octreoscan
Authors: Jake Adkins, Yang Lu
Journal: Clinical Nuclear Medicine (2019)

A 32-year-old man with a pancreatic neuroendocrine tumor and known liver metastasis presented with diffuse back pain. Workup octreoscan showed newly developed diffuse bone metastases, in addition to the persistent liver metastases. The bone metastases were later confirmed on MRI spine images.
Sanitary products should be freely available in all hospitals, say BMA
Authors: Abi Rimmer
Journal: BMJ (2019)

A significant number of UK hospital trusts and health boards provided little or no free sanitary products for patients, an investigation by the BMA has found.

The association is calling for sanitary products to be made freely available across all hospitals in the UK, as doctors say that it is essential to the health, dignity, and wellbeing of inpatients.

Of the 187 UK hospitals and health boards that responded to the BMA’s investigation, 25 (13%) said they did not supply patients with any sanitary products.1

A …
New Neuroscience of Homeostasis and Drives for Food, Water, and Salt
Authors: Bradford B Lowell
Journal: New England Journal of Medicine (2019)

Well-being requires the maintenance of energy stores, water, and sodium within permissive zones. The brain, as ringleader, orchestrates their homeostatic control. It senses disturbances, decides what needs to be done next, and then restores balance by altering physiological processes and ingestive drives (i.e., hunger, thirst, and salt appetite). But how the brain orchestrates this control has been unknown until recently — largely because we have lacked the ability to elucidate and then probe the underlying neuronal “wiring diagrams.” This has changed with the advent of new, transformative neuroscientific tools. When targeted to specific neurons, these tools make it possible to selectively map a neuron’s connections, measure its responses to various homeostatic challenges, and experimentally manipulate its activity. This review examines these approaches and then highlights how they are advancing, and in some cases profoundly changing, our understanding of energy, water, and salt homeostasis and the linked ingestive drives.
Abstract 20910: Alpha-Ketoglutarate Metabolism Regulates Oncometabolic Adaptation in the Heart
Authors: Anja Karlstaedt, Radhika Khanna, Daniel McNavish, Heinrich Taegtmeyer
Journal: Circulation (2017)

Introduction: The term “cancer and the heart” traditionally refers to the cardiotoxic effects of chemotherapeutic agents. However, independent of any cytostatic treatment cancer survivors have a five-fold higher risk for developing heart failure. Therefore, new therapeutic strategies must consider tumor biology when aiming at protecting the heart. In isocitrate dehydrogenase (IDH)1 and 2 mutant tumors, the elevated production of the oncometabolite D-2-hydroxyglutarate (D2-HG) is associated with systemic effects, including dilated cardiomyopathy. About 20% of acute myeloid leukemia cases harbor mutations of the IDH, which leads to reduced patient survival and causes metabolic dysfunction through production of the oncometabolite D2-HG. Recent findings have shown that D2-HG impairs oxidative decarboxylation of α-KG, which in turn increases ATP citrate lyase activity. Hypothesis: Based on these findings we are now proposing that modulation of ACL activity reverses D2-HG mediated metabolic changes. Methods: As models we used isolated working rat hearts; and combined C13-tracer studies with computational flux analysis. Results: Wild type rat hearts were perfused with the ACL inhibitor BMS303141 (0.5 μM; BMS) or D2-HG (1 mM). Cardiac power rapidly declined by 25% in the presence of BMS or D2-HG alone. Simultaneous perfusion with D2-HG and BMS, improved cardiac power, suggesting that modulation of ACL improves cardiac function only in presence of D2-HG. Further, α-KG dehydrogenase (α-KGDH) activity increased with ACL inhibition, reflecting an inverse relationship between these enzymes. Computational flux analysis using the metabolic genome-scale network CardioNet revealed that D2-HG-dependent inhibition by α-KGDH shifts cardiac metabolism towards increased reductive carboxylation of α-KG. Conclusions: Our findings suggest an “oncometabolic axis” in the heart and underscore the potential application of ACL inhibitors to protect the heart from failing in IDH-mutant tumors.
Reply
Authors: Maria Kalafateli, Emmanuel A. Tsochatzis
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. We thank Dr. Pedersen and colleagues for their interest in our work, and we welcome the external validation of the Royal Free Hospital Cirrhosis Glomerular Filtration Rate (GFR).1 As a general comment, the equation performs very well in this independent cohort and only slightly underestimates true GFR, unlike widely used formulas such as the Modification of Diet in Renal Disease. We would also like to discuss a few additional points. First, since the publication of our article, we have discovered an error in the originally reported formula and we have submitted an erratum, which is in press. The correct formula should read: GFR=45.9×(creatinine−0.836)×(urea−0.229)×(INR−0.113)×(age−0.129)×(sodium0.972)×1.236(if male)×0.92(if moderate/severe ascites).We presume that the GFR underestimation will be less pronounced should the authors use the corrected formula. Second, 51‐chromium‐ethylene diamine tetraacetic acid measurement in patients with ascites is more reliable when plasma samples are taken up to 24 hours postinjection rather than just 6 hours.2 This could have resulted in small inaccuracy of the "gold‐standard" measurement in the Danish cohort. Third, it would be of interest if the authors could show how the Royal Free Hospital cirrhosis GFR performs compared to other widely used GFR formulas in this independent data set. This would encourage a more widespread use of this equation. Ultimately, as we mentioned in our article, it would be valuable to explore whether the incorporation of this cirrhosis‐specific GFR equation instead of creatinine in prognostic scores such as Model for End‐Stage Liver Disease improves their performance; we are in the process of testing this using data from the NHS British Transplant database.
Comparison of Different Criteria for the Evaluation of Allergic Rhinitis Control in Adolescents
Authors: Laís Gomes Japiassú, Laís Japiassú, Pamela Pittelkow Silva, Pâmela Pittelkow, Patricia Guerzet Ayres Bastos, Patrícia Guerzet, Marina Medeiros Caputo, Marina Caputo, Gustavo F. Wandalsen, Gabriele F. Camilo, Dirceu Sole
Journal: Journal of Allergy and Clinical Immunology (2019)
Classification of global measles cases in 2013–17 as due to policy or vaccination failure: a retrospective review of global surveillance data
Authors: Minal K Patel, Walter A Orenstein
Journal: The Lancet Global Health (2019)

Despite improvements in reported coverage of measles-containing vaccine (MCV) and progress towards elimination of measles, 172 939 measles cases were reported worldwide in 2017. Questions have been raised about whether measles cases are due to failure of immunisation programmes or vaccine policy failure, which might require changes to vaccination schedules or number of doses.This retrospective review of global surveillance data analysed case-based data for cases of measles occurring during 2013-17 submitted to WHO by its member states. Cases were classified as programmatically preventable (ie, did not receive the age-appropriate number of doses for that country) or programmatically non-preventable (ie, appropriately vaccinated as per national programme) on the basis of age at onset, year of birth, vaccination status, and eligibility for MCV doses in the country reporting the case. We grouped reasons why cases were non-preventable into four categories as follows: (1) received at least two doses of MCV; (2) too young for first dose; (3) received one dose but was too young to receive the second; or (4) was only eligible for one dose according to the national schedule. We analysed numbers and proportions of preventable and non-preventable cases of measles by region and year, reasons for non-preventable cases by year, preventable cases by age group, and preventable and non-preventable cases, including reasons for non-preventable cases, by measles elimination status of countries.Between Jan 1, 2013, and Dec 31, 2017, 634 139 measles cases were reported; 7850 (1%) cases were excluded because they did not provide age at onset, so 626 289 were included in our analysis. 191 333 (31%) of these cases had unknown vaccination status. 275 754 (63%) of the 434 956 cases with available vaccination data were categorised as programmatically preventable, 213 461 (77%) of whom were aged 1 year to less than 15 years. 156 384 (36%) cases were categorised as non-preventable, of whom 38 677 (25%) were two-dose vaccine recipients, 74 438 (48%) were too young to receive their first MCV dose, 11 914 (8%) received their first dose and were too young to receive their second dose, and 31 355 (20%), mostly in the Africa region, were non-preventable because they were only eligible for one dose on the basis of the national immunisation programme.Most measles cases during 2013-17 were programmatically preventable, highlighting the need for improving the effectiveness of immunisation programmes that already exist. Individual countries should do similar analyses to establish the changes needed in their country to decrease numbers of measles cases.None.
Pregnancy Rates and Pregnancy Outcomes after Hematopoietic Stem Cell Transplantation in Childhood: a Cross-Sectional Survey of the EBMT Pediatric WP
Authors: Tamara Diesch, Gabor Szinnai, Alicia Rovo, Fabienne Gumy-Pause, Arnaud Dalissier, Adriana Balduzzi, Peter Bader
Journal: Blood (2018)
Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA
Authors: Jinglan Zhang, Jianli Li, Jennifer B. Saucier, Yanming Feng, Yanjun Jiang, Jefferson Sinson, Anne K. McCombs, Eric S. Schmitt, Sandra Peacock, Stella Chen, Hongzheng Dai, Xiaoyan Ge, Guoli Wang, Chad A. Shaw, Hui Mei, Amy Breman, Fan Xia, Yaping Yang, Anne Purgason, Alan Pourpak, Zhao Chen, Xia Wang, Yue Wang, Shashikant Kulkarni, Kwong Wai Choy, Ronald J. Wapner, Ignatia B. Van den Veyver, Arthur Beaudet, Sheetal Parmar, Lee-Jun Wong, Christine M. Eng
Journal: Nature Medicine (2019)
<b>Low-Carb Diets Help Maintain Weight Loss</b>
Authors: Anita Slomski
Journal: JAMA (2019)

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
Abstract 15293: Cardiorespiratory Fitness is Associated With Age-Related Carotid Enlargement: A 5-Year Longitudinal Study
Authors: Yuko Gando, Haruka Murakami, Ryoko Kawakami, Harumi Ohno, Kumpei Tanisawa, Kana Konishi, Susumu S Sawada, Nobuyuki Miyatake, Motohiko Miyachi
Journal: Circulation (2017)

Introduction: A high level of cardiorespiratory fitness is associated with a reduced risk of cardiovascular disease. Some studies reported that an increased carotid diameter (carotid enlargement) w...
Progressing Polygenic Medicine in Psychiatry Through Electronic Health Records
Authors: Cathryn M. Lewis, Saskia P. Hagenaars
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
Real-world safety of treatment with mepolizumab and reslizumab in patients with severe eosinophilic asthma
Authors: Karen A. Ordóñez Pinilla, Beatriz Moya Camacho, Consuelo Fernandez Rodríguez, Jesus F. Fernandez Crespo, Ismael García Moguel
Journal: Journal of Allergy and Clinical Immunology (2019)
Characterization of cell proliferation in idiopathic pulmonary fibrosis
Authors: Jutaro Fukumoto, Sahebgowda Patil, Sudarshan Krishnamurthy, Lakshmi Galam, Nirmal Sharma, Kapilkumar Patel, Robert Hooker, John Dunning, Richard F. Lockey, Narasaiah Kolliputi
Journal: Journal of Allergy and Clinical Immunology (2019)
BCL6 Evolved to Enable Stress Tolerance in Vertebrates and Is Broadly Required by Cancer Cells to Adapt to Stress
Authors: Tharu M. Fernando, Rossella Marullo, Benet Pera Gresely, Jude M. Phillip, Shao Ning Yang, Geoffrey Lundell-Smith, Ingrid Torregroza, Haelee Ahn, Todd Evans, Balázs Győrffy, Gilbert G. Privé, Masayuki Hirano, Ari M. Melnick, Leandro Cerchietti
Journal: Cancer Discovery (2019)

Abstract Several lines of evidence link the canonical oncogene BCL6 to stress response. Here we demonstrate that BCL6 evolved in vertebrates as a component of the HSF1-driven stress response, which has been co-opted by the immune system to support germinal center formation and may have been decisive in the convergent evolution of humoral immunity in jawless and jawed vertebrates. We find that the highly conserved BTB corepressor binding site of BCL6 mediates stress adaptation across vertebrates. We demonstrate that pan-cancer cells hijack this stress tolerance mechanism to aberrantly express BCL6. Targeting the BCL6 BTB domain in cancer cells induces apoptosis and increases susceptibility to repeated doses of cytotoxic therapy. The chemosensitization effect upon BCL6 BTB inhibition is dependent on the derepression of TOX, implicating modulation of DNA repair as a downstream mechanism. Collectively, these data suggest a form of adaptive nononcogene addiction rooted in the natural selection of BCL6 during vertebrate evolution. Significance: We demonstrate that HSF1 drives BCL6 expression to enable stress tolerance in vertebrates. We identify an HSF1–BCL6–TOX stress axis that is required by cancer cells to tolerate exposure to cytotoxic agents and points toward BCL6-targeted therapy as a way to more effectively kill a wide variety of solid tumors. This article is highlighted in the In This Issue feature, p. 565