tbuckley/cabot-search huggingface dataset:
Updated analysis of phase II trial of irinotecan/s-1/cetuximab (IRIS/Cet) as second-line treatment in patients with <i>KRAS</i> exon2 wild type metastatic colorectal cancer (mCRC): HGCSG0902—Comparison of administration interval in cetuximab treatment.
Authors: Tomohiro Kondo, Satoshi Yuki, Yasuyuki Kawamoto, Yasushi Tsuji, Ayumu Hosokawa, Michio Nakamura, Osamu Muto, Takashi Kato, Ichiro Iwanaga, Atsushi Sato, Kazunori Eto, Kouichi Furukawa, Hideyuki Hayashi, Miki Tateyama, Yasuo Takahashi, Susumu Sogabe, Takuya Honda, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2016)

771 Background: HGCSG0902 is the multicenter phase II study to investigate the safety and efficacy of irinotecan, S-1 (IRIS) plus cetuximab as second line treatment in patients with KRAS exon2 wild type mCRC. Response rate (RR) was 33.3% (95%CI 20.8-45.9%), therefore primary endpoint was met (Muto O, et al. ESMO 2014). Here we report an exploratory analysis of outcomes based on administration interval of cetuximab (every week [EW] vs bi-weekly [BW]). Methods: Eligibility includes histologically confirmed mCRC, previously received oxaliplatin-contained chemotherapy, PS: 0-1, EGFR positive and KRAS exon2 wild type. Patients received S-1 80-120 mg/day p.o. on days 1-14 and irinotecan 100mg/m 2 on day 1 and 15 repeated every 28 days. Cetuximab was administrated 400mg/m 2 as loading dose and continued 250mg/m 2 every week or 500mg/m 2 bi-weekly. The primary endpoint was RR and the secondary endpoints were disease control rate, PFS, OS and safety. To compare with EW and BW, Fisher’s exact test was used in terms of patient characteristics, AE, RR, and Log-rank test was used in terms of PFS and OS. Results: Between Mar 2010 and Sep 2013, 58 pts were enrolled. One patient was not administered (57 pts were safety analysis set), and 3 pts were ineligible (54 pts were efficacy analysis set). Based on each physician’s choice, 34 patients of EW and 23 of BW were included in the full safety analysis set. RR was 34.4% in the EW and 31.8% in the BW (p = 1.000). Median PFS was 4.2 months in the EW and 6.1 months in the BW (HR 0.752, p = 0.350). Median OS was 8.9 months in the EW and 10.7 months in the BW (HR 0.902, p = 0.737). The most common non-hematological adverse events of grade 3 or higher were diarrhea (23.5% in the EW vs 52.2% in the BW: p = 0.005) and stomatitis (2.9% in the EW vs 30.4% in the BW group: p = 0.046), these were significantly more common in the BW. Conclusions: IRIS/Cet appeared to be highly effective with RR, PFS and OS in the both treatment schedule. Diarrhea and stomatitis were significantly more common in the BW. Therefore, in case of treatment with IRIS/Cet should be administered in the EW. Clinical trial information: UMIN000004882.
Gastric cancers in young and old patients have different genomic profiles
Authors: Tineke E. Buffart, Beatriz Carvalho, Erik Hopmans, Victor Brehm, Elma Klein Kranenbarg, Tieneke Visser, Cornelis J. H. Van de Velde, Gerrit A. Meijer
Journal: Cancer Research (2005)

3560   Introduction Gastric cancer in young patients has been associated with a more aggressive behavior and poorer prognosis, compared to older patients. We recently demonstrated that patterns of DNA copy number alterations in gastric cancer correlated with clinical outcome (Weiss et al., Oncogene 2003; 22:1872-1879). The present study aimed to compare such copy number alterations between gastric cancers of young ( 2  tumor to normal fluorescence ratios of all (but the sex chromosomes derived) clones using TMEV software (www.tigr.org/software). Cluster membership was correlated to age. Results K-means cluster analysis of the array-CGH results revealed two clusters with different genomic profiles that correlated significantly with age (p=0.003). Since gastric cancer cases from cluster one, with mainly young patients, showed a significantly higher incidence of lymph node metastasis compared to cluster two, with mainly elderly gastric cancer patients (P=0.04), a sub-group analysis was performed with lymph node positive cases only (young: n=12; elderly: n=20). Again, K-means cluster analysis yielded two clusters of tumors with different genomic profiles, where cluster membership correlated significantly with age (P=0.008). Conclusion Gastric cancers of young and old patients have different genomic profiles, and this is independent of lymph node status. This may well reflect different pathogenic mechanisms of the disease.
Patient-Reported Outcomes (PRO) in the Setting of Relapsed Myeloma: The Influence of Treatment Strategies and Genetic Variants Predict Quality of Life and Pain Experience
Authors: Sam H Ahmedzai, John A Snowden, Angela Cox, David A Cairns, Cathy D Williams, Anna Hockaday, Jamie Cavenagh, Christopher Parrish, Kwee L Yong, Jim Cavet, Hannah Hunter, Jennifer Bird, John Ashcroft, Julia Brown, Curly Morris, Gordon Cook
Journal: Blood (2015)
Cognitive trade-offs and the costs of resilience
Authors: Bernard J. Crespi
Journal: Behavioral and Brain Sciences (2015)

Abstract Genetic, endocrinological, and psychological evidence demonstrates that resilience commonly trades off with sensitivity. The existence of such trade-offs indicates that resilience bears costs as well as benefits, and that some disorders can best be conceptualized in terms of extremes of trade-offs rather than expression of deficits. Testing for cognitive trade-offs should be a priority for psychiatry, psychology, neuroscience, and genetics.
Newer tests for hepatitis C virus could transform screening
Authors: Jacqui Wise
Journal: BMJ (2016)

Several newer tests for hepatitis C virus are highly sensitive and specific and could transform the current two test screening process into a single test, a systematic review has concluded.1

The review, published in the Annals of Internal Medicine , will inform an upcoming World Health Organization guideline on hepatitis C screening. As many as 150 million people are infected with chronic hepatitis C virus, and around three quarters of these are in low and middle income countries.

Currently, diagnosing hepatitis C virus is a two step process that starts …
A Phase 1/2 Study of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients with Relapsed/Refractory Multiple Myeloma.
Authors: James R. Berenson, James D. Hilger, Leonard M. Klein, Shahrooz Eshaghian, Youram Nassir, Regina A. Swift, Robert Vescio
Journal: Blood (2012)
Tipifarnib Is Well Tolerated as Maintenance Therapy In Acute Myeloid Leukemia (AML). Significant, but Non-Fatal, Hematologic Toxicity Not Ameliorated by Dose Reduction. Preliminary Results of the Phase III Intergroup Trial E2902
Authors: Selina Luger, Xiaopan Yao, Elisabeth Paietta, Rhett Ketterling, Witold Rybka, Mark R. Litzow, Jacob M. Rowe, Richard Larson, Martin S. Tallman
Journal: Blood (2010)
Electromechanical cardioplasty using a wrapped elasto-conductive epicardial mesh
Authors: Jinkyung Park, Suji Choi, Ajit H. Janardhan, Se-Yeon Lee, Samarth Raut, Joao Soares, Kwangsoo Shin, Shixuan Yang, Chungkeun Lee, Ki-Woon Kang, Hye Rim Cho, Seok Joo Kim, Pilseon Seo, Wonji Hyun, Sungmook Jung, Hye-Jeong Lee, Nohyun Lee, Seung Hong Choi, Michael Sacks, Nanshu Lu, Mark E. Josephson, Taeghwan Hyeon, Dae-Hyeong Kim, Hye Jin Hwang
Journal: Science Translational Medicine (2016)

Heart failure remains a major public health concern with a 5-year mortality rate higher than that of most cancers. Myocardial disease in heart failure is frequently accompanied by impairment of the specialized electrical conduction system and myocardium. We introduce an epicardial mesh made of electrically conductive and mechanically elastic material, to resemble the innate cardiac tissue and confer cardiac conduction system function, to enable electromechanical cardioplasty. Our epicardium-like substrate mechanically integrated with the heart and acted as a structural element of cardiac chambers. The epicardial device was designed with elastic properties nearly identical to the epicardial tissue itself and was able to detect electrical signals reliably on the moving rat heart without impeding diastolic function 8 weeks after induced myocardial infarction. Synchronized electrical stimulation over the ventricles by the epicardial mesh with the high conductivity of 11,210 S/cm shortened total ventricular activation time, reduced inherent wall stress, and improved several measures of systolic function including increases of 51% in fractional shortening, ~90% in radial strain, and 42% in contractility. The epicardial mesh was also capable of delivering an electrical shock to terminate a ventricular tachyarrhythmia in rodents. Electromechanical cardioplasty using an epicardial mesh is a new pathway toward reconstruction of the cardiac tissue and its specialized functions.
Role of Second Stem Cell Transplantation in Relapsed Lymphoproliferative Diseases: Remission Status Is the Most Important Factor Predicting the Outcome
Authors: Lidia Gil, Jan Styczynski, Agnieszka Piekarska, Beata Jakubas, Katarzyna Drabko, Tomasz Wrobel, Anna Czyz, Anna Lojko-Dankowska, Dominik Dytfeld, Adam Nowicki, Patrycja Mensah-Glanowska, Wanda Knopinska-Posluszny, Maria Bieniaszewska, Mariusz Wysocki, Andrzej Hellmann, Aleksander Skotnicki, Jerzy Kowalczyk, Kazimierz Kuliczkowski, Mieczyslaw Komarnicki
Journal: Blood (2011)
Failure of Dual Antimicrobial Therapy in Treatment of Gonorrhea
Authors: Helen Fifer, Usha Natarajan, Lucy Jones, Sarah Alexander, Gwenda Hughes, Daniel Golparian, Magnus Unemo
Journal: New England Journal of Medicine (2016)

Increasing antibacterial resistance in Neisseria gonorrhoeae is threatening the success of routine treatment. This letter describes the clinical failure of ceftriaxone and azithromycin in a patient with gonorrhea.
PDL1 and PD1 expression by tumor infiltrating lymphocytes in primary breast cancer
Authors: C. Solinas, L. Buisseret, S. Garaud, A. Boisson, C. Naveaux, R. de Wind, G. Van den Eynden, D. Brown, D. Larsimont, C. Sotiriou, K. Willard-Gallo
Journal: Annals of Oncology (2015)
Accroître la valeur prédictive des prélèvements pharyngés dans la surveillance virologique de la grippe
Authors: K Leitmeyer, U Buchholz, M. Kramer, B Schweiger
Journal: Eurosurveillance (2002)

Selon une etude nationale allemande, la surveillance virologique de la grippe peut etre amelioree lorsque les medecins sentinelle n’effectuent des prelevements pharynges que sur les malades qui consultent tot apres le debut de la maladie (dans les 48 heures), et lorsqu’ils suivent la stricte definition de cas du syndrome grippal. La PCR est recommandee pour detecter les virus grippaux.
HGF/Met Signaling in Head and Neck Cancer: Impact on the Tumor Microenvironment
Authors: Stefan Hartmann, Neil E. Bhola, Jennifer R. Grandis
Journal: Clinical Cancer Research (2016)

Studies to date have revealed several major molecular alterations that contribute to head and neck squamous cell carcinoma (HNSCC) initiation, progression, metastatic spread, and therapeutic failure. The EGFR is the only FDA-approved therapeutic target, yet responses to cetuximab have been limited. Activation and cross-talk of cellular receptors and consequent activation of different signaling pathways contribute to limited activity of blockade of a single pathway. The hepatocyte growth factor (HGF) receptor, Met, has been implicated in HNSCC tumorigenesis and EGFR inhibitor resistance. HGF, the sole ligand of Met, is overexpressed in the tumor microenvironment. The role of HGF/Met signaling in proliferation, metastasis, and angiogenesis has been investigated in HNSCC, leading to clinical trials with various Met inhibitors and HGF antibodies. However, the role of the HGF/Met signaling axis in mediating the tumor microenvironment has been relatively understudied in HNSCC. In this review, we discuss the functional roles of Met and HGF in HNSCC with a focus on the tumor microenvironment and the immune system. Clin Cancer Res; 22(16); 4005-13. ©2016 AACR.
Platelet MAO inhibition, urinary MHPG, and leukocyte beta-adrenergic receptors in depressed patients treated with phenelzine
Authors: R P Sharma, P G Janicak, J I Javaid, G N Pandey, B Gierl, J M Davis
Journal: American Journal of Psychiatry (1990)

The authors investigated three biochemical indices of peripheral catecholamine activity in 36 depressed inpatients treated with the monoamine oxidase (MAO) inhibitor phenelzine. Platelet MAO activity, urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), and leukocyte beta-adrenergic receptor functions were measured before and during the 4th week of phenelzine treatment. There were significant reductions in platelet MAO activity, urinary MHPG excretion, and depressive symptoms in all of the patients. Responders had the same decrease in MHPG as nonresponders. There were no changes in leukocyte beta-receptor function in a small subgroup of the patients.
Guidance on acetylcysteine for paracetamol ingestion needs review
Authors: Simon H L Thomas, D Nicholas Bateman, James W Dear
Journal: BMJ (2016)

Buckley and colleagues highlight differences in international guidance for treating acute paracetamol poisoning.1 Following recommendations by the Commission on Human Medicines (CHM), the UK uses lower thresholds for acetylcysteine use than almost all other countries, treating many more patients at low risk of toxicity. Anaphylactoid reactions are further increased, as these are more common in patients with …
Relationship between age and tricyclic antidepressant plasma levels
Authors: A Nies, D S Robinson, M J Friedman, R Green, T B Cooper, C L Ravaris, J O Ives
Journal: American Journal of Psychiatry (1977)

Older depressed patients treated with imipramine or amitriptyline developed higher steady-state plasma levels of imipramine, desipramine, and amitriptyline. In imipramine-treated patients this finding was associated with a decreased rate of drug elimination from plasma. These findings provide at least a partial explanation for the increased susceptibility of the older patient to tricyclic antidepressant side effects and also provide a pharmacological rationale for use of lower dosages in this age group.
Quantification and molecular characterization of circulating epithelial tumor cells (CETC) for determination of their metastatic potential.
Authors: K. Pachmann, S. Carl, T. Kroll, A. Plaschke-Schluetter, U. A. Pachmann
Journal: Journal of Clinical Oncology (2011)

e13585 Background: In breast cancer predictive markers for therapy are derived from the primary tumor but systemic therapy aims at eliminating the remnant tumor cells which are left in the body after surgery, part of which are the cells circulating in peripheral blood. In the future, it will become mandatory for individualized therapy to better characterize this remnant disease for targeted therapeutic approaches. Methods: From peripheral blood from each of 50 newly diagnosed breast cancer patients after surgery up to 100 vital circulating epithelial-antigen positive cells were isolated using an automated capillary cell isolation system (MMI CellEctor) and deposited individually into wells of Ampli Grid slides (Advalytics-Beckman, Munich) under visual control. The mRNA was reverse transcribed and amplified using primers for 6-15 different tumor associated target genes among them EpCAM and HER2/neu. Results: Expression profiling could be successfully performed from more than 80% of all individually deposited isolated cells demonstrating the epithelial nature of these cells. Cells of individual patients showed heterogeneity with respect to different genes. Expression profiling of the population of individually deposited circulating epithelial cells from breast cancer patients can now be compared to the profile of the primary tumor and correlated to the clinical course of disease Conclusions: Further analysis by high through-put profiling of the remnant tumor burden in breast cancer patients after surgery comprising the cells circulating in peripheral blood may contribute to better characterize the targets of systemic therapy in order to individualize cancer therapy.
Examination about febrile neutropenia in patient performed FEC with breast cancer
Authors: Mariko Kikuchi, Mina Waraya, Naoko Minatani, Hiroshi Nishimiya, Hiroshi Katoh, Masayoshi Kosaka, Takumo Enomoto, Norihiko Senngoku, Hirokazu Tanino, Masahiko Watanabe
Journal: Annals of Oncology (2015)
The Histological Quantification of Alpha-Smooth Muscle Actin Predicts Future Graft Fibrosis in Pediatric Liver Transplant Recipients
Authors: S. Varma, X. Stephenne, M. Komuta, C. Bouzin, J. Ambroise, F. Smets, R. Reding, E. Sokal
Journal: Journal of Hepatology (2016)
Serum Level of the Soluble Form of the CD30 Molecule Identifies Patients With Hodgkin's Disease at High Risk of Unfavorable Outcome
Authors: Gianpaolo Nadali, Luisa Tavecchia, Elisabetta Zanolin, Valeria Bonfante, Simonetta Viviani, Edgarda Camerini, Pellegrino Musto, Nicola Di Renzo, Mario Carotenuto, Marco Chilosi, Mauro Krampera, Giovanni Pizzolo
Journal: Blood (1998)
1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase 3 ALSYMPCA study.
Authors: Sten Nilsson, Nicholas J. Vogelzang, A. Oliver Sartor, David Bottomley, Robert E. Coleman, Irene Skjorestad, Mona Wahba, Chris Parker
Journal: Journal of Clinical Oncology (2014)

9 Background: Ra-223 is a first-in-class alpha-emitting pharmaceutical recently Food and Drug Administration approved for treatment (tx) of patients (pts) with CRPC and symptomatic bone metastases (mets). In ALSYMPCA, Ra-223 significantly improved overall survival by 3.6 months versus placebo (pbo) (HR = 0.70; 95% CI, 0.58-0.83; P &lt; 0.001) and was well tolerated. Reported here are long-term safety data ~1.5 years after the last pt’s final injection (inj) from the entire ALSYMPCA safety population. Methods: Eligible pts had progressive CRPC with ≥ 2 symptomatic bone mets and no known visceral mets, were receiving best standard of care, and had received docetaxel or were unfit for or declined docetaxel. Pts were randomized 2:1 to 6 inj of Ra-223 (50 kBq/kg IV; q 4 wk) or matching pbo. Only adverse events (AEs) considered tx related by the investigator were reported during follow-up. Long-term safety data were assessed by specific diseases, including acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or primary cancer in other organs. Results: ALSYMPCA safety population included 901 pts (Ra-223, n = 600; pbo, n = 301). Overall, 25 (4%) Ra-223 and 8 (3%) pbo pts had ≥ 1 tx-related AE (Table). During follow-up, primary cancer in other organs was reported in 5 pts (Ra-223, n = 2; pbo, n = 3). Conclusions: Ra-223 is an effective and well-tolerated tx for CRPC with symptomatic bone mets. No major safety issues were identified within ~1.5 years after tx in the ALSYMPCA safety population. Clinical trial information: NCT00699751. [Table: see text]
Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings
Authors: Paul K. Crane, Laura E. Gibbons, Kristen Dams-O’Connor, Emily Trittschuh, James B. Leverenz, C. Dirk Keene, Joshua Sonnen, Thomas J. Montine, David A. Bennett, Sue Leurgans, Julie A. Schneider, Eric B. Larson
Journal: JAMA Neurology (2016)

The late effects of traumatic brain injury (TBI) are of great interest, but studies characterizing these effects are limited.
NHS leaders condemn racist abuse of staff
Authors: Anne Gulland
Journal: BMJ (2016)

Eight NHS leaders have condemned hate crime after reports that staff members have been racially abused.

In a joint statement the leaders of NHS bodies in the south of England, including Solent NHS Trust, Portsmouth Hospitals NHS Trust, University Hospital Southampton NHS Trust, Southampton City Clinical Commissioning Group, and West Hampshire Clinical Commissioning Group underlined their commitment to zero tolerance of abuse.

“We are disheartened to hear of the abuse some of our colleagues have been subjected to, either while executing their duties or away from work. We condemn this in the strongest possible terms. We have a …
The 6-Minute-Walk Distance Test as a Chronic Obstructive Pulmonary Disease Stratification Tool. Insights from the COPD Biomarker Qualification Consortium
Authors: Bartolome Celli, Kay Tetzlaff, Gerard Criner, Michael I. Polkey, Frank Sciurba, Richard Casaburi, Ruth Tal-Singer, Ariane Kawata, Debora Merrill, Stephen Rennard
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: The 6-minute-walk distance (6MWD) test predicts mortality in chronic obstructive pulmonary disease (COPD). Whether variability in study type (observational vs. interventional) or region performed limits use of the test as a stratification tool or outcome measure for therapeutic trials is unclear.Objectives: To analyze the original data from several large observational studies and from randomized clinical trials with bronchodilators to support the qualification of the 6MWD test as a drug development tool in COPD.Methods: Original data from 14,497 patients with COPD from six observational (n = 9,641) and five interventional (n = 4,856) studies larger than 100 patients and longer than 6 months in duration were included. The geographical, anthropometrics, FEV1, dyspnea, comorbidities, and health status scores were measured. Associations between 6MWD and mortality, hospitalizations, and exacerbations adjusted by study type, age, and sex were evaluated. Thresholds for outcome prediction were calculated using receiver operating curves. The change in 6MWD after inhaled bronchodilator treatment and surgical lung volume reduction were analyzed to evaluate the responsiveness of the test as an outcome measure.Measurements and Main Results: The 6MWD was significantly lower in nonsurvivors, those hospitalized, or who exacerbated compared with those without events at 6, 12, and greater than 12 months. At these time points, the 6MWD receiver operating characteristic curve–area under the curve to predict mortality was 0.71, 0.70, and 0.68 and for hospitalizations was 0.61, 0.60, and 0.59, respectively. After treatment, the 6MWD was not different between placebo and bronchodilators but increased after surgical lung volume reduction compared with medical therapy. Variation across study types (observational or therapeutic) or regions did not confound the ability of 6MWD to predict outcome.Conclusions: The 6MWD test can be used to stratify patients with COPD for clinical trials and interventions aimed at modifying exacerbations, hospitalizations, or death.
Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma
Authors: G McNee, K L Eales, W Wei, D S Williams, A Barkhuizen, D B Bartlett, S Essex, S Anandram, A Filer, P A H Moss, G Pratt, S Basu, C C Davies, D A Tennant
Journal: Leukemia (2016)

Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survive and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM-a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM. In this study, we describe a mechanism by which increased expression of peptidyl arginine deiminase 2 (PADI2) by BMMSCs in patients with MGUS and MM directly alters malignant plasma cell phenotype. We identify PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through its enzymatic deimination of histone H3 arginine 26, PADI2 activity directly induces the upregulation of interleukin-6 expression. This leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26.