tbuckley/cabot-search huggingface dataset:
Feasibility study of pemetrexed (PEM) plus bevacizumab (BV) as the first-line treatment for elderly advanced or recurrent non-squamous (non-Sq) non-small cell lung cancer (NSCLC): TORG1015.
Authors: Toshiyuki Kozuki, Naoyuki Nogami, Hiromoto Kitajima, Tetsu Shinkai, Fumiaki Kato, Emiko Sakaida, Yuichi Takiguchi, Satoshi Ikeda, Masahiro Yoshida, Yasunori Enomoto, Terufumi Kato, Takashi Ogura, Shingo Miyamoto, Satoshi Morita, Koshiro Watanabe
Journal: Journal of Clinical Oncology (2013)

e19054 Background: The addition of BV to cytotoxic agent(s) prolonged survival for non-Sq NSCLC patients (pts). However, there is no definitive evidence for the cytotoxic agent(s) plus BV is superior to the cytotoxic agent(s) alone for elderly non-Sq NSCLC. We conducted the feasibility study of PEM plus BV as the first-line treatment for elderly advanced or recurrent non-Sq NSCLC. Methods: Major eligibility and exclusion criteria were followings; chemotherapy-naïve; unfit for bolus combination chemotherapy; stage III/IV or relapsed non-Sq NSCLC; age≥70; PS 0-1; no evidence of brain metastasis; no history of hemoptysis and irradiation for thorax. PEM (500 mg/m 2 ) and BV (15 mg/kg) were administrated intravenously on day 1 every 3 weeks. The primary endpoint was toxicity and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the percentage of pts who completed more than 3 cycles. Results: From November 2010 to April 2012, total 12 pts were enrolled. Patients characteristics were following; male/female=6/6; Median age (range) 78 (72-81); histology was all adenocarcinoma; activating EGFR mutation no/yes/unknown=9/2/1; stage IIIB/IV/recurrence=2/8/2; ECOG PS 0/1=6/6; smoking history yes/no=6/6. Severe toxicities (Grade 3≥) were leukopenia (25%), neutropenia (25%), anemia (8%), thrombocytopenia (8%), febrile neutropenia (8%), anorexia (8%), hypertension (8%), fatigue (8%), nausea (8%), and perforation (colon) (8%). No dose-limiting toxicity and treatment-related death was occurred. Three patients achieved PR and the ORR was 25%. The median PFS and OS were 5.6 months (mo) (95% C.I. 1.1-7.9 mo) and 10.3 mo (95% C.I. 6.9-15.6 mo) in 11 evaluated pts, respectively. The 1-year survival rate was 49% (95% C.I. 12-79%). Seven of 12 pts (58%) received more than 3 cycles. Conclusions: PEM plus BV as first-line treatment for elderly non-Sq NSCLC was well tolerable and promising. Clinical trial information: UMIN000004263.
Lipotoxicity induces hepatic protein inclusions through TANK binding kinase 1–mediated p62/sequestosome 1 phosphorylation
Authors: Chun‐Seok Cho, Hwan‐Woo Park, Allison Ho, Ian A. Semple, Boyoung Kim, Insook Jang, Haeli Park, Shannon Reilly, Alan R. Saltiel, Jun Hee Lee
Journal: Hepatology (2017)

Obesity commonly leads to hepatic steatosis, which often provokes lipotoxic injuries to hepatocytes that cause nonalcoholic steatohepatitis (NASH). NASH, in turn, is associated with the accumulation of insoluble protein aggregates that are composed of ubiquitinated proteins and ubiquitin adaptor p62/sequestosome 1 (SQSTM1). Formation of p62 inclusions in hepatocytes is the critical marker that distinguishes simple fatty liver from NASH and predicts a poor prognostic outcome for subsequent liver carcinogenesis. However, the molecular mechanism by which lipotoxicity induces protein aggregation is currently unknown. Here, we show that, upon saturated fatty acid‐induced lipotoxicity, TANK binding kinase 1 (TBK1) is activated and phosphorylates p62. TBK1‐mediated p62 phosphorylation is important for lipotoxicity‐induced aggregation of ubiquitinated proteins and formation of large protein inclusions in hepatocytes. In addition, cyclic GMP‐AMP synthase (cGAS) and stimulator of interferon genes (STING), upstream regulators of TBK1, are involved in lipotoxic activation of TBK1 and subsequent p62 phosphorylation in hepatocytes. Furthermore, TBK1 inhibition prevented formation of ubiquitin‐p62 aggregates not only in cultured hepatocytes, but also in mouse models of obesity and NASH. Conclusion : These results suggest that lipotoxic activation of TBK1 and subsequent p62 phosphorylation are critical steps in the NASH pathology of protein inclusion accumulation in hepatocytes. This mechanism can provide an explanation for how hypernutrition and obesity promote the development of severe liver pathologies, such as steatohepatitis and liver cancer, by facilitating the formation of p62 inclusions. (H epatology 2018).
Effects of inspiratory muscle training on dyspnoea in severe COPD patients during pulmonary rehabilitation: controlled randomised trial
Authors: Marc Beaumont, Philippe Mialon, Catherine Le Ber, Patricia Le Mevel, Loïc Péran, Olivier Meurisse, Capucine Morelot-Panzini, Angelina Dion, Francis Couturaud
Journal: European Respiratory Journal (2018)

The benefit of inspiratory muscle training (IMT) combined with a pulmonary rehabilitation programme (PRP) is uncertain. We aimed to demonstrate that, in severe and very severe chronic obstructive pulmonary disease (COPD) patients, IMT performed during a PRP is associated with an improvement of dyspnoea. In a single-blind randomised controlled trial, 150 severe or very severe COPD patients were allocated to follow PRP+IMT versus PRP alone. The evaluations were performed at inclusion and after 4 weeks. The primary outcome was the change in dyspnoea using the Multidimensional Dyspnoea Profile questionnaire at the end of a 6-min walk test (6MWT) at 4 weeks. Secondary outcomes were changes in dyspnoea using the Borg (end of the 6MWT) and modified Medical Research Council scales and in functional parameters (maximal inspiratory pressure ( P Imax ), inspiratory capacity, 6MWT and quality of life). All analyses were performed on an intention-to-treat basis. Dyspnoea decreased significantly in both groups; however, the improvement of dyspnoea was not statistically different between the two groups. We only found a statistically significant greater increase of P Imax after IMT+PRP than after PRP alone. In this trial including severe or very severe COPD patients, we did not find a significant benefit of IMT during PRP+IMT as compared to PRP alone on dyspnoea, despite a significantly higher improvement of P Imax in the IMT group.
FDA Pursues Unproven Cancer Claims
Authors: Rebecca Voelker
Journal: JAMA (2017)

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
Specific Immune Responses for Leukemia-Associated Antigens Against Myeloid Leukemic Cells Are Increased By Immune Checkpoint Inhibition
Authors: Jochen Greiner, Marlies Götz, Vanessa Schneider, Hubert Schrezenmeier, Markus Wiesneth, Lars Bullinger, Hartmut Döhner, Susanne Hofmann
Journal: Blood (2016)
Orbital Metastasis
Authors: Tarun Kumar Jain, Ashwin Singh Parihar, Ashwani Sood, Rajender Kumar Basher, Neeraja Bollampally, Amit Singh Shekhawat, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2017)

Abstract Orbital metastases are known to arise from primary breast carcinoma followed by prostate, malignant melanoma, and lung carcinoma. We report a case of orbital metastasis as the initial presentation of an occult primary gall bladder carcinoma. The FDG PET/CT helped in localizing the occult distant primary site, which previously escaped detection, and also enabled the evaluation of orbital metastasis.
Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network
Authors: Heinz Ludwig, Michel Delforge, Thierry Facon, Hermann Einsele, Francesca Gay, Philippe Moreau, Hervé Avet-Loiseau, Mario Boccadoro, Roman Hajek, Mohamad Mohty, Michele Cavo, Meletios A Dimopoulos, Jesús F San-Miguel, Evangelos Terpos, Sonja Zweegman, Laurent Garderet, María-Victoria Mateos, Gordon Cook, Xavier Leleu, Hartmut Goldschmidt, Graham Jackson, Martin Kaiser, Katja Weisel, Niels W. C. J. van de Donk, Anders Waage, Meral Beksac, Ulf H. Mellqvist, Monika Engelhardt, Jo Caers, Christoph Driessen, Joan Bladé, Pieter Sonneveld
Journal: Leukemia (2018)

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.
ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis
Authors: Pierre Quartier, Amandine Baptiste, Véronique Despert, Emma Allain-Launay, Isabelle Koné-Paut, Alexandre Belot, Laurent Kodjikian, Dominique Monnet, Michel Weber, Caroline Elie, Bahram Bodaghi
Journal: Annals of the Rheumatic Diseases (2017)

To assess the efficacy and safety of adalimumab on uveitis in patients with early onset, chronic, juvenile idiopathic arthritis (JIA)-associated or idiopathic anterior uveitis and an inadequate response to topical steroids and methotrexate (MTX).Patients aged 4 years or more with ocular inflammation quantified by laser flare photometry (LFP) ≥30 photon units/ms were double-blindly randomised (1:1) to 2 groups, one treated with placebo and one with adalimumab subcutaneously at a dose of 24 mg/m2 in patients aged <13 years, 40 mg in the others, every other week. The primary outcome was response at month 2 (M2) defined as a 30% reduction of inflammation on LFP in the assessable eye with more severe baseline inflammation and no worsening on slit lamp examination. From M2 to M12, all patients received adalimumab.At M2, among 31 patients included in intention-to-treat analysis, there were 9/16 responders on adalimumab and 3/15 on placebo (P=0.038, Χ2 test; relative risk=2.81, 95% CI 0.94 to 8.45; risk difference: 36.3%, 95% CI 2.1 to 60.6); there was no significant difference using the Standardised Uveitis Nomenclature classification criteria of improvement. Thirty patients continued the trial after M2 and received adalimumab (open-label phase), 29 reached M12. There were seven serious adverse events none related to study treatment.This trial is in favour of using adalimumab in patients with early onset, chronic anterior uveitis, which is in most cases associated with JIA, in case of inadequate response to topical therapy and MTX. LFP could be a valuable tool to assess early treatment efficacy.NCT01385826.
A phase II clinical trial of capecitabine combined with recombinant human endostatin and stereotactic radiotherapy as firstâline treatment in patients with locally advanced pancreatic cancer.
Authors: Jinglu Shan, Yi Qing, Mengxia Li, Jiangdong Sui, Shiheng Zhang, Yan Feng, Dong Wang
Journal: Journal of Clinical Oncology (2015)

e15253 Background: The aim of this study was to investigate the efficacy and safety of capecitabine combined with recombinant human endostatin (endostar) and stereotactic radiotherapy to treat locally advanced pancreatic cancer. Methods: Patients aged 40 years or older with histologically diagnosed locally advanced pancreatic cancer recruited in Daping Hospital from October 2013 to October 2014 were eligible for enrollment in this single-arm phase 2 trial. Patients received capecitabine (1000 mg/m2 twice daily) concurrented with endostar (3ml concentrate to 500ml saline, uniform intravenous drip, drip time 3-4 hours) for 14 days and repeat every 21 days for 6 cycles. Stereotactic radiotherapy was applied to the local lesion of the pancreas with a total dose of 40 Gy in 10 fractions. The primary end point was progression-free survival (PFS), secondary end points included overall survival (OS), time to treatment failure (TTF) and safety, analysed by intention to treat including only those patients with valid CT assessments. This trial is registered with ChiCTR, number ChiCTR-ONC-13003720. Results: Thirteen patients were evaluable for responses. Median PFS was 10.0 months (95% CI 5.01-14.99), median OS was 20.0 months (95% CI 2.52-37.48) and median TTF was 10 months (95% CI 3.35-16.65). Grade 3/4 hematological and non-hematological toxicities were rare. All the side effects were tolerable and reversible. Conclusions: The combination of radio-chemotherapy and endostar has potential survival benefit in patients with locally advanced pancreatic cancer receiving capecitabine. Clinical trial information: ChiCTR-ONC-13003720.
Cognitive Functioning After Hematopoietic Cell Transplantation for Hematologic Malignancy: Results From a Prospective Longitudinal Study
Authors: Noha Sharafeldin, Alysia Bosworth, Sunita K. Patel, Yanjun Chen, Emily Morse, Molly Mather, Canlan Sun, Liton Francisco, Stephen J. Forman, F. Lennie Wong, Smita Bhatia
Journal: Journal of Clinical Oncology (2017)

Purpose Cognitive impairment is well-recognized after myeloablative allogeneic hematopoietic cell transplantation (HCT). However, cognitive functioning after reduced-intensity allogeneic or autologous HCT remains unclear. Methods A total of 477 HCT recipients (236 autologous, 128 reduced-intensity allogeneic, 113 myeloablative allogeneic) underwent standardized neuropsychologic testing before HCT and at 6 months and 1, 2, and 3 years after HCT. Ninety-nine frequency-matched healthy controls underwent testing at commensurate time points. Primary outcomes of the study were practice effect–adjusted domain-specific T scores and global deficit scores. Piecewise generalized estimating equation models were used to compare groups and to identify associated variables and post-HCT trends of cognitive impairment. Results Median age was 52 years (range, 18 to 74 years) for HCT recipients and 55 years (range, 19 to 73 years) for controls. Post-HCT scores were comparable between controls and autologous and reduced-intensity HCT recipients. Myeloablative HCT recipients had significantly lower ( P &lt; .001) post-HCT scores than controls for executive function, verbal speed, processing speed, auditory memory, and fine motor dexterity. Pre-HCT to 6 months post-HCT scores did not change after reduced-intensity HCT but declined significantly for fine motor dexterity ( P &lt; .001) after myeloablative HCT. However, pre-HCT to 3 years post-HCT scores declined significantly ( P &lt; .003) in reduced-intensity HCT recipients for executive function, verbal fluency, and working memory. Older age, male sex, and lower education, income, and cognitive reserve were associated with post-HCT cognitive impairment. At 3 years post-HCT, global cognitive impairment was present in 18.7% of autologous and 35.7% of allogeneic HCT recipients. Conclusion Myeloablative allogeneic HCT recipients showed significant cognitive decline compared with healthy controls. Reduced-intensity allogeneic HCT recipients showed evidence of delayed decline. Cognitive functioning in autologous HCT recipients generally was spared. The study identified vulnerable subpopulations that could benefit from targeted interventions.
Microglial Activation on 11C-CB184 PET in a Patient With Cerebellar Ataxia Associated With HIV Infection
Authors: Kenji Ishibashi, Yoshiharu Miura, Akifumi Imamura, Jun Toyohara, Kenji Ishii
Journal: Clinical Nuclear Medicine (2017)

A 63-year-old man complaining of prolonged imbalance underwent C-CB184 PET to assess microglial activation 3 years after being diagnosed with cerebellar ataxia associated with HIV infection. C-CB184 images revealed significant cerebellar uptake where MRI signal abnormalities were observed at disease onset, although these abnormalities had mostly disappeared at the time of C-CB184 PET. Microglia are believed to be a long-term reservoir for HIV infection, causing persistent immune activation (ie, chronic inflammation). Hence, in this case, increased C-CB184 binding may reflect persistent microglial activation along with HIV persistence in the cerebellum. However, further pathological investigations are desired to validate C-CB184 PET.
Стан моторно-евакуаторної функції шлунка за даними 13С-октаноєвого дихального тесту у хворих на гастроезофагеальну рефлюксну хворобу
Authors: V.G. Mishchuk, V.B. Boychuk, V.Yu. Vyshivanyuk
Journal: GASTROENTEROLOGY (2014)

Обстежено 58 хворих на ерозивну форму гастроезофагеальної рефлюксної хвороби та 10 здорових добровольців. Кожному пацієнту проведено фіброгастродуоденоскопію, добове моніторування рН нижньої третини стравоходу, 13С-октаноєвий дихальний тест, визначено концентрацію холецистокініну-панкреозиміну в сироватці крові. Встановлено, що у 44,83 % хворих на гастроезофагеальну рефлюксну хворобу мала місце сповільнена, у 36,21 % — прискорена та у 18,97 % — нормальна моторно-евакуаторна функція шлунка. У хворих із сповільненою моторикою шлунка відмічено переважання жовчних рефлюксів з рН у нижній третині стравоходу більше 6, що становили 42 % (р = 0,044), та підвищення концентрації у крові холецистокініну-панкреозиміну до (7,12 ± 0,21) нг/мл (p &lt; 0,05), у здорових — (5,91 ± 0,34) нг/мл. У пацієнтів з прискореною моторикою число рефлюксів менше 4 становило 45 %, а рівень холецистокініну-панкреозиміну — (4,4 ± 1,2) нг/мл. Отримані дані підтверджують думку інших авторів, що причинами печії як провідного симптому гастроезофагеальної рефлюксної хвороби можуть бути дуоденогастральний рефлюкс та вісцеральна гіпералгезія.
Development of the "treatment beliefs in knee and hip osteoarthritis (TOA)" questionnaire
Authors: E.M.H. Selten, J.E. Vriezekolk, H.J. Schers, M.W. Nijhof, W.H. Van der Laan, R.G. van der Meulen-Dilling, R. Geenen, C.H.M. van den Ende
Journal: Annals of the Rheumatic Diseases (2017)
OC-009 Progression of cirrhotic liver disease towards acute-on-chronic liver failure decompensation triggers changes in innate immune cell phenotype and their response to pro-inflammatory stimuli
Authors: AA Maini, L China, DW Gilroy, A O’Brien
Journal: Gut (2017)

Introduction  Bacterial infection is a major cause of hospital admission in liver cirrhosis and patients are highly prone to nosocomial infection. Innate immune dysfunction is implicated in these patients. As there are no current strategies to reverse immune dysfunction, antibiotics are liberally used to treat patients in an era of increasing anti-microbial resistance.  We aimed to determine whether progression to ACLF triggers a change in the receptor phenotype on innate immune cells reflecting impaired function. We also explored the response to inflammatory stimuli. Any changes in profile may reveal novel targets for immune therapy.  Method  Peripheral whole blood of healthy volunteers (HV), ambulant outpatients attending for drainage of ascites and acute decompensated (AD) cirrhotic patients was studied. Cells were analysed by flow cytometry for activation and cell type.  Whole blood was stimulated  ex vivo  with 1 ng/ml lipopolysaccharide for 4 hours. Supernatants were analysed for cytokines. Cells were analysed by flow cytometry.  Results  Neutrophils demonstrated a significant decrease in CD88 (p=0.0006) from HV to ACLF, with decreasing trends of CD11b, CD54, CD66b and significant increases in CD62L (p=0.0298) observed as disease severity increased. When stimulated with LPS, increases in CD11b (p  In mononuclear phagocytes HLA-DR was significantly reduced between HV and both ambulant (p=0.0019) and ACLF (p  TNF levels in the supernatants of the stimulated blood were reduced in both ambulant and AD patients compared to HV.  Conclusion  The phenotype of innate immune cells in ACLF was altered reflecting immune dysfunction and potentially explaining increased rates of bacterial infection. The response of innate cells to stimulation was also modified. These changes reflect a markedly reduced bactericidal and phagocytic potential of these cells. This is mirrored by the reduced production of TNF-a by whole blood stimulation. Overall, we see an immune-fatigued phenotype in innate immunity.  Disclosure of Interest  None Declared
The Regulatory Accountability Act of 2017 — Implications for FDA Regulation and Public Health
Authors: Jonathan J. Darrow, Erin C. Fuse Brown, Aaron S. Kesselheim
Journal: New England Journal of Medicine (2017)

The Regulatory Accountability Act has been described by its proponents as a way to reverse the increasing volume of regulatory requirements. But it could have potentially disastrous consequences for the FDA and other agencies that protect public health and safety.
Critical review of the diagnosis of columnar metaplasia in the esophagus and the esophagogastric junction: the Paris workshop
Authors: H. Barr, J. J. Bergman, M. I. Canto, T. Endo, R. Fujita, P. Hainaut, R. H. Hawes, Y. Hoshihara, H. Inoue, E. Jaramillo, M. Jung, T. Kouzu, R. Lambert, C. J. Lightdale, H. Makuuchi, H. Niwa, J. F. Rey, R. Riddell, R. E. Sampliner, P. Sharma, S. J. Spechler, K. Takubo, H. Tajiri, H. Watanabe
Journal: Endoscopy (2005)
Infarct Fibroblasts Do Not Derive From Bone Marrow Lineages
Authors: Thomas Moore-Morris, Paola Cattaneo, Nuno Guimarães-Camboa, Julius Bogomolovas, Marta Cedenilla, Indroneal Banerjee, Mercedes Ricote, Tatiana Kisseleva, Lunfeng Zhang, Yusu Gu, Nancy D. Dalton, Kirk L. Peterson, Ju Chen, Michel Pucéat, Sylvia M. Evans
Journal: Circulation Research (2017)

Rationale: Myocardial infarction is a major cause of adult mortality worldwide. The origin(s) of cardiac fibroblasts that constitute the postinfarct scar remain controversial, in particular the potential contribution of bone marrow lineages to activated fibroblasts within the scar. Objective: The aim of this study was to establish the origin(s) of infarct fibroblasts using lineage tracing and bone marrow transplants and a robust marker for cardiac fibroblasts, the Collagen1a1-green fluorescent protein reporter. Methods and Results: Using genetic lineage tracing or bone marrow transplant, we found no evidence for collagen-producing fibroblasts derived from hematopoietic or bone marrow lineages in hearts subjected to permanent left anterior descending coronary artery ligation. In fact, fibroblasts within the infarcted area were largely of epicardial origin. Intriguingly, collagen-producing fibrocytes from hematopoietic lineages were observed attached to the epicardial surface of infarcted and sham-operated hearts in which a suture was placed around the left anterior descending coronary artery. Conclusions: In this controversial field, our study demonstrated that the vast majority of infarct fibroblasts were of epicardial origin and not derived from bone marrow lineages, endothelial-to-mesenchymal transition, or blood. We also noted the presence of collagen-producing fibrocytes on the epicardial surface that resulted at least in part from the surgical procedure.
Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: Retrospective multicenter case-control study from France and Switzerland
Authors: Michael Benzaquen, Luca Borradori, Philippe Berbis, Simone Cazzaniga, René Valero, Marie-Aleth Richard, Laurence Feldmeyer
Journal: Journal of the American Academy of Dermatology (2017)