tbuckley/cabot-search huggingface dataset:
FORWARD II: A phase Ib study to evaluate the safety, tolerability and pharmacokinetics of mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin or pegylated liposomal doxorubicin in adults with folate receptor alpha (FRα)-positive advanced epithelial ovarian cancer (EOC), primary peritoneal, fallopian tube, or endometrial cancer.
Authors: David M. O'Malley, Lainie P. Martin, Kathleen N. Moore, Dale L. Nepert, Rodrigo Ruiz-Soto, Ignace Vergote
Journal: Journal of Clinical Oncology (2016)

TPS5611 Background: Elevated FRα expression is characteristic of a number of solid tumors, including EOC and endometrial cancer, thereby providing an attractive candidate for targeted therapeutic strategies in these indications. Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC), comprising a FRα-binding antibody linked to the tubulin-disrupting maytansinoid DM4, that has shown single agent clinical activity and favorable safety in an ongoing phase 1 trial (NCT01609556). Methods: FORWARD II is an open-label, non-randomized phase 1b study of IMGN853 in combination with bevacizumab (BEV), carboplatin, or pegylated liposomal doxorubicin (PLD) in EOC and endometrial cancer patients with FRα-positive tumors (low, medium, or high expression; 25-49%, 50-74%, ≥ 75% of cells with at least moderate staining intensity by IHC). In the dose escalation phase, ascending doses of IMGN853 are being evaluated in order to identify the maximum tolerated dose (MTD) for each of three combination regimens: Regimen A (IMGN853 + BEV), Regimen B (IMGN853 + carboplatin), and Regimen C (IMGN853 + PLD). The starting dose of IMGN853 is 5.0 mg/kg (calculated using adjusted ideal body weight), administered in combination on Day 1 of a 21- or 28-day cycle (Regimens A and B, Regimen C, respectively), with all three regimens being independently evaluated in parallel. Following MTD determination, an expansion phase for Regimen A is planned, wherein patients are assigned to cohorts as follows: Cohort 1, BEV-naïve EOC; Cohort 2, BEV-pretreated EOC; and Cohort 3, endometrial cancer. The primary objectives of the expansion phase are to assess the antitumor activity, safety, and tolerability of IMGN853 when administered in combination with BEV. Secondary endpoints include pharmacokinetic parameters and immunogenicity. Patient enrollment commenced in December 2015. Clinical trial information: NCT02606305.
Point-of-Care Hemostatic Testing in Cardiac Surgery
Authors: Keyvan Karkouti, Jeannie Callum, Duminda N. Wijeysundera, Vivek Rao, Mark Crowther, Hilary P. Grocott, Ruxandra Pinto, Damon C. Scales, B. Achen, S. Brar, D. Morrison, D. Wong, J. S. Bussières, T. de Waal, C. Harle, E. de Médicis, †C. McAdams, S. Syed, D. Tran, T. Waters
Journal: Circulation (2016)

Cardiac surgery is frequently complicated by coagulopathic bleeding that is difficult to optimally manage using standard hemostatic testing. We hypothesized that point-of-care hemostatic testing within the context of an integrated transfusion algorithm would improve the management of coagulopathy in cardiac surgery and thereby reduce blood transfusions.We conducted a pragmatic multicenter stepped-wedge cluster randomized controlled trial of a point-of-care-based transfusion algorithm in consecutive patients undergoing cardiac surgery with cardiopulmonary bypass at 12 hospitals from October 6, 2014, to May 1, 2015. Following a 1-month data collection at all participating hospitals, a transfusion algorithm incorporating point-of-care hemostatic testing was sequentially implemented at 2 hospitals at a time in 1-month intervals, with the implementation order randomly assigned. No other aspects of care were modified. The primary outcome was red blood cell transfusion from surgery to postoperative day 7. Other outcomes included transfusion of other blood products, major bleeding, and major complications. The analysis adjusted for secular time trends, within-hospital clustering, and patient-level risk factors. All outcomes and analyses were prespecified before study initiation.Among the 7402 patients studied, 3555 underwent surgery during the control phase and 3847 during the intervention phase. Overall, 3329 (45.0%) received red blood cells, 1863 (25.2%) received platelets, 1645 (22.2%) received plasma, and 394 (5.3%) received cryoprecipitate. Major bleeding occurred in 1773 (24.1%) patients, and major complications occurred in 740 (10.2%) patients. The trial intervention reduced rates of red blood cell transfusion (adjusted relative risk, 0.91; 95% confidence interval, 0.85-0.98; P=0.02; number needed to treat, 24.7), platelet transfusion (relative risk, 0.77; 95% confidence interval, 0.68-0.87; P<0.001; number needed to treat, 16.7), and major bleeding (relative risk, 0.83; 95% confidence interval, 0.72-0.94; P=0.004; number needed to treat, 22.6), but had no effect on other blood product transfusions or major complications.Implementation of point-of-care hemostatic testing within the context of an integrated transfusion algorithm reduces red blood cell transfusions, platelet transfusions, and major bleeding following cardiac surgery. Our findings support the broader adoption of point-of-care hemostatic testing into clinical practice.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02200419.
Use of Valacyclovir for the Treatment of Cytomegalovirus Antigenemia after Hematopoietic Stem Cell Transplantation
Authors: Shin-Yeu Ong, Ha Thi Thu Truong, Aloysius Y Ho, Yeh Ching Linn, Yeow-Tee YT Goh, Colin Phipps Diong, Yvonne Loh, William YK Hwang
Journal: Blood (2014)
P0924 : Cyclooxygenase-2 regulates miRNA expression in liver cells through dead box helicase p68 (DDX5). Role in insulin signaling
Authors: O. Motiño, D.E. Francés, R. Mayoral, L. Castro-Sánchez, M. Fernández-Velasco, L. Boscá, C. García-Monzón, M. Casado, N. Agra, P. Martín-Sanz
Journal: Journal of Hepatology (2015)
Deliberation to Promote Shared Sovereignty in Health Research: Four Questions to Clarify Goals, Methods, and Scope
Authors: Jantina de Vries, Syntia Nchangwi Munung, Paulina Tindana
Journal: The American Journal of Bioethics (2016)

Pratt and Hyder (2016) explore how governance mechanisms can help global health research consortia attain their explicit or underlying equity objectives. One key feature of their model concerns sha...
The impact of the radiotherapy boost in ductal carcinoma in situ.
Authors: P. Wong, C. Lambert, R. V. Agnihotram, M. David, M. Duclos, C. Maietta, E. Pietracupa, C. R. Freeman
Journal: Journal of Clinical Oncology (2010)

613 Background: Local recurrence (LR) of ductal carcinoma in situ (DCIS) is reduced by whole breast irradiation following breast conservative surgery (BCS). The benefit and indication for adding a radiotherapy boost to the surgical cavity for DCIS is unclear. Methods: 220 consecutive cases of DCIS treated at the McGill University Health Centre (MUHC) with BCS and radiotherapy between January 2000 and December 2006 were reviewed to assess the impact of the radiotherapy boost on local control. All patients were CT-simulated and received whole breast irradiation ranging from 42.4-50.4 Gy in 16-28 fractions. 36% of the patients received a radiotherapy boost of a median dose of 10 Gy (range: 9-16 Gy) to the surgical cavity. Median follow-up was same for Boost and No-Boost groups (46 months). Descriptive statistics and time to event analyses was carried out using Kaplan-Meir survival analyses. Results: Compared with the No-Boost group, patients who received the boost had more positive (6% vs. 1%) and < 0.1 cm margins (51% vs. 8%) (p < 0.0001), and were in higher risk categories as defined by the Van Nuys Prognostic (VNP) index (p = 0.015). Despite being in higher risk for LR, none (0/79) of the patients who received a boost recurred locally while 8/141 patients who did not receive a boost suffered an in-breast LR (Log-rank p = 0.03). Univariate analysis of prognostic factors (age, tumor size, margin status, histological grade, necrosis, and VNP risk category) revealed only the presence of necrosis to significantly correlate with LR (Log-rank p = 0.003). All 8 LR occurred in DCIS with necrosis. No significant difference in LR rate was observed between whole breast irradiation dose and fractionation schedule. Conclusions: Our results suggest that use of a radiotherapy boost significantly impacts local control in DCIS. The use of a boost may outweigh the poor prognostic effect of necrosis. No significant financial relationships to disclose.
Analysis of the <i>EGFR</i> mutations in non-small cell lung cancer patients after EGFR-TKI treatment.
Authors: H. Yamaguchi, T. Ikeda, N. Tomonaga, H. Nakano, T. Kitazaki, S. Doi, K. Nakatomi, T. Iida, Y. Nakamura, S. Kohno
Journal: Journal of Clinical Oncology (2010)

e18065 Background: Gefitinib and erlotinib are the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) that have the dramatically effects in selective patients with non-small cell lung cancer (NSCLC). EGFR mutations predict response and survival in patients treated with TKIs. However, most patients have a relapse within 1 year after the initiation of therapy. The most important mechanism of resistance to TKIs is a secondary EGFR mutation, threonine to methionine at codon 790 in exon 20 (T790M). Therefore, we analyzed EGFR mutations after TKIs treatment in addition to before treatment. Methods: 99 patients were analyzed mutation status between July 2004 to December 2009 in our institution. 71 patients were treated with TKIs (gefitinib 67 cases, erlotinib 9 cases), and mutations were detected in 31 patients. When tumor was relapsed, we got written informed consent, and re-examination of mutations was performed. Mutations were examined by mutant-enriched polymerase chain reaction method and/or peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp method. Samples were biopsied tissues, surgically resected tissues, bronchial washing liquids, and pleural effusion, and we used relapsed tumor samples at secondary analysis. In addition, we evaluated the response to treatment and progression-free survival. Results: 31 patients with NSCLC harboring mutations treated with TKIs. Response rate was 74.2% (23/31). Within 1 year, most patients were relapse (83.9%, median 149 days). In 10 patients, we could analyze mutations after TKIs treatment. T790M was detected in 4 patients, and EGFR status was maintained in 6 patients. In 2 of 6 patients without T790M, readministration of gefitinib was effective, and 1 of 6 patients responded to erlotinib. Despite emergence of T790M, readministration of gefitinib and switch to erlotinib was effective in 1 patient. Conclusions: These results suggested that we cannot decide next treatment after relapse to TKIs by reason of only T790M. We must consider the mechanism of resistance to TKIs and the new therapeutic strategy. No significant financial relationships to disclose.
Neutrophil Gelatinase-Associated Lipocalin for Acute Kidney Injury During Acute Heart Failure Hospitalizations
Authors: Alan S. Maisel, Nicholas Wettersten, Dirk J. van Veldhuisen, Christian Mueller, Gerasimos Filippatos, Richard Nowak, Christopher Hogan, Michael C. Kontos, Chad M. Cannon, Gerhard A. Müller, Robert Birkhahn, Paul Clopton, Pam Taub, Gary M. Vilke, Kenneth McDonald, Niall Mahon, Julio Nuñez, Carlo Briguori, Claudio Passino, Patrick T. Murray
Journal: Journal of the American College of Cardiology (2016)
Viral Suppression is Not a risk Factor for CKD in Viral Cirrhosis (ANRS CO12 CirVir Prospective Cohort)
Authors: C.I. Bagnis, R. Layese, G. Divard, P. Cacoub, V. Bourcier, L. Corvi, V. Petro-Sanchez, P. Marcellin, D. Guyader, S. Pol, D. Larrey, V. De Ledingen, D. Ouzan, F. Zoulim, G. Deray, F. Roudot-Thoraval, P. Nahon
Journal: Journal of Hepatology (2016)
CD38 Expression in Chronic Lymphocytic Leukemia (CLL) Patients Is Associated with Family History of Hematological Neoplasms.
Authors: E. Domingo-Domenech, A. Domingo-Claros, E. Gonzalez-Barca, Y. Benavente, T. Alvaro, C. Bellas, R. Font, A. Fernandez de Sevilla, S. de Sanjose
Journal: Blood (2005)
Cardiac involvement in Churg-Strauss syndrome and granulomatosis with polyangiitis (Wegeners)
Authors: M. RMark Hazebroek, M. J Kemna, S Schalla, R Dennert, Tatiana Kuznetsova, Jan A Staessen, H. P. Brunner-La Rocca, P Van Paassen, J. W. Cohen Tervaert, Stephane Heymans
Journal: European Journal of Heart Failure (2014)
Dynamics of Serum Quantitative Hepatitis B Surface Antigen Testing in Assessing Nucleos/Tide Analog Treatment Response and Disease Phenotype in Chronic Hepatitis B Patients in Canada
Authors: C.R. O’Neil, S.E. Congly, S.S. Lee, M. Borman, C.L. Charlton, C. Osiowy, M.G. Swain, K.W. Burak, C.S. Coffin
Journal: Journal of Hepatology (2016)
The Protease-Inhibitor SERPINB3 Activates Canonical WNT Pathway in Monocytes
Authors: A. Cappon, S. Quarta, A. Biasiolo, C. Turato, G. Villano, M. Ruvoletto, S. Fasolato, G. Zanus, U. Cillo, P. Pontisso
Journal: Journal of Hepatology (2016)
Indolent B-Cell Lymphomas Treated Upfront with Antiviral Therapy: a Series of 13 Patients
Authors: Andrea Ferrario, Alessio Aghemo, Maria Cecilia Goldaniga, Michele Merli, Daniele Vincenti, Francesca Gaia Rossi, Elisabetta De Gasperi, Barbara Olivero, Lilla Cro, Sara Rattotti, Luca Arcaini, Francesco Onida, Luca Baldini
Journal: Blood (2010)
HBV-HDV Co-Infection Constrains HBV Genetic Evolution in HBsAg
Authors: L. Colagrossi, R. Scutari, A. Battisti, R. Salpini, M. Pollicita, A. Bertoli, C. Minichini, P. Trimoulet, H. Fleury, E. Nebuloso, R. Longo, G. Cappiello, A. Spanó, V. Malagnino, L. Sarmati, T. Mari, A. Barlattani, N. Iapadre, M. Lichtner, C. Mastroianni, I. Lenci, L. Baiocchi, C. Pasquazzi, G.M. De Sanctis, A.G. Lanza, M. Stanzione, G. Stornaiuolo, M. Marignani, M. Andreoni, M. Angelico, C.-F. Perno, N. Coppola, V. Svicher
Journal: Journal of Hepatology (2016)
Polymorphism -238 G/A in Promotor Region of Tumor Necrosis Factor alpha Gene Is a Risk Factor for Ischemic Cerebrovascular Disease in Spanish Population.
Authors: Jaime Fernandez De Velasco, Pilar Llamas, Raquel De Ona, Ana Belen Santos, Elena Meseguer, Arancha Garcia-Raso, Raquel Mata, Jose Francisco Tomas
Journal: Blood (2004)
Validation of a new multidimensional scale to evaluate itch in children aged 6-14 years: Leuven Itch Scale children's version (LIS-C) and parents's version (LIS-P)
Authors: Marie Morren, J Basstanie, S Peeters, Philip Moons, Nady Van Broeck, P Byttebier
Journal: British Journal of Dermatology (2014)
Utility of Interim and Post-Therapy PET/CT in T-Cell and NK-Cell Lymphoma: A Single Institutional Analysis over 9 Years
Authors: Kota Fukumoto, Manabu Fujisawa, Yasuhito Suehara, Yoshiaki Usui, Kentaro Narita, Masami Takeuchi, Kosei Matsue
Journal: Blood (2015)
Also elderly patients (75 years or older) with stage III non-small cell lung cancer (nsclc) have survival gains with radical treatment: a prospective population-based study
Authors: Jessie Steevens, Dirk De Ruysscher, Anita Botterweck, Bart Reymen, Angela Van Baardwijk, Rinus Wanders, Jacques Borger, Anne-Marie C Dingemans, Gerben Bootsma, Cordula Pitz, R Lunde, Wiel Geraedts, Philippe Lambin
Journal: Journal of Thoracic Oncology (2011)
Pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma: Results of the KEYNOTE-029 expansion cohort.
Authors: Georgina V. Long, Victoria Atkinson, Jonathan S. Cebon, Michael B. Jameson, Bernie M. Fitzharris, Catriona M. McNeil, Andrew Graham Hill, Antoni Ribas, Michael B. Atkins, John A. Thompson, Wen-Jen Hwu, F. Stephen Hodi, Alexander M. Menzies, Alexander David Guminski, Richard Kefford, Xinxin Shu, Scot Ebbinghaus, Nageatte Ibrahim, Matteo S. Carlino
Journal: Journal of Clinical Oncology (2016)

9506 Background: Pembro (MK-3475), an anti–PD-1 antibody that prevents PD-1 from binding to its ligands, PD-L1 and PD-L2, is approved in several countries for treating advanced melanoma. In KEYNOTE-006, pembro showed superior OS over the anti–CTLA-4 inhibitor ipi. In a phase 3 trial, combination therapy with reduced-dose nivolumab (anti–PD-1) and standard-dose ipi showed higher ORR and longer PFS than either checkpoint inhibitor alone but was associated with increased toxicity. Preliminary data from the phase 1 KEYNOTE-029 study (NCT02089685) suggested that standard-dose pembro + reduced-dose ipi was safe and provided robust antitumor activity. Here, we present data from a larger population of patients (pts) treated with pembro + ipi in the KEYNOTE-029 expansion cohort. Methods: Eligible pts had advanced melanoma, ECOG PS 0-1, no active brain metastases, and no prior immune checkpoint inhibitor therapy. Pts received pembro 2 mg/kg Q3W + ipi 1 mg/kg Q3W for 4 doses, then pembro 2 mg/kg Q3W until intolerable toxicity, progression, or 2 y. Response was assessed by RECIST v1.1 at wk 12, every 6 wk until wk 30, then every 12 wk thereafter. Results: Of 153 pts enrolled in the expansion, 107 had ≥18 wk of follow-up (median 6.4 mo, range 4.3-9.4) by the Oct 26, 2015, data cutoff and were eligible for analysis. 18% of pts had elevated LDH, 55% had stage M1c disease, 36% were BRAFV600mutant, 13% received ≥1 prior therapy, and 12% received a prior BRAF ± MEK inhibitor; 84% had PD-L1–positive tumors (ie, ≥1% staining in tumor and adjacent immune cells). 79 pts (74%) received all 4 ipi doses; 73 pts (68%) remained on pembro. 41 pts (38%) had ≥1 grade 3-4 drug-related AE (DRAE); 68% of these DRAEs resolved by data cutoff. DRAEs led to discontinuation of pembro and ipi in 9 pts (8%), ipi alone in 11 (10%), and pembro alone in 4 (4%); there were no treatment-related deaths. Immune-mediated AEs of any grade and grade 3-4 severity occurred in 57 (53%) and 21 (20%) pts. ORR by investigator review was 57%, with 5 (5%) CR and 56 (52%) PR; by central review, ORR was 51%, with 9% CR and 42% PR. Conclusions: Pembro 2 mg/kg in combination with 4 doses of ipi 1 mg/kg has a manageable toxicity profile and provides robust antitumor activity in pts with advanced melanoma. Clinical trial information: NCT02089685.
Predictors of Fast Response to Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir ± Ribavirin in Real Life Amber Study in Genotype 1 and 4 HCV Infected Patients as a Rationale for Shortening of Treatment
Authors: R. Flisiak, J. Jaroszewicz, E. Janczewska, M. Wawrzynowicz-Syczewska, K. Nazzal, B. Bolewska, J. Bialkowska, D. Zarebska-Michaluk, H. Berak, K. Fleischer-Stepniewska, M. Tudrujek, K. Karwowska, K. Rostkowska, A. Piekarska, O. Tronina, A. Grabinska, A. Garlicki, M. Lucejko, A. Pisula, E. Karpinska, A. Wiercinska-Drapalo, I. Mozer-Lisewska, M. Jablkowski, W. Kryczka, A. Horban, B. Knysz, K. Tomasiewicz, W. Halota
Journal: Journal of Hepatology (2016)
Prior Coronary Artery Bypass Graft Portends High Risk in STEMI Patients Treated With Primary Percutaneous Coronary Intervention
Authors: Robert C Welsh, Christopher B Granger, Cynthia M Westerhout, James C Blankenship, David R Holmes, William W O'Neill, Christian W Hamm, Frans Van de Werf, Paul W Armstrong
Journal: Journal of the American College of Cardiology (2009)
Modulation of Intestinal Microbiota and Gut-Liver Axis by Quercetin Improve HFD-Induced Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease in Mice
Authors: D. Porras-Sanabria, M.V. García-Mediavilla, S. Martínez-Flórez, E. Nistal, J.L. Olcoz, R. Jover, J. González-Gallego, S. Sánchez-Campos
Journal: Journal of Hepatology (2016)
Long-term adherence to topical psoriasis treatment can be abysmal: a 1-year randomized intervention study using objective electronic adherence monitoring
Authors: H. Alinia, S. Moradi Tuchayi, J.A. Smith, I.M. Richardson, N. Bahrami, S.C. Jaros, L.F. Sandoval, M.E. Farhangian, K.L. Anderson, K.E. Huang, S.R. Feldman
Journal: British Journal of Dermatology (2016)

Most people with psoriasis have limited disease that could be treated with topicals, but topical efficacy is limited by low short‐term adherence. Psoriasis is a chronic disease, and long‐term adherence is an even bigger problem. To determine how well medication is used in the long‐term topical treatment of psoriasis and to assess the potential of an internet‐based reporting intervention to improve treatment adherence and outcomes. An investigator‐blinded, prospective study evaluated topical fluocinonide adherence in 40 patients with mild‐to‐moderate psoriasis over 12 months. Subjects were randomized in a 1 : 1 ratio to standard‐of‐care or internet‐based reporting group. Adherence was objectively monitored with Medication Event Monitoring System® caps. Fifty per cent of subjects discontinued the treatment. Greater adherence was seen in the intervention group compared with the standard‐of‐care group (50% vs. 35%, P = 0·08). Psoriasis Area and Severity Index improved more in the intervention group at month 1 (1·61 vs. −0·12, P = 0·003), month 3 (2·50 vs. 0·79, P = 0·025) and month 12 (3·32 vs. 0·34, P = 0·038) than in the standard‐of‐care group. This study likely underestimates the challenge of long‐term adherence, as adherence tends to be better in research studies than in clinical practice. This study also did not fully account for primary nonadherence. Adherence to topical treatment is low in the short term and decreased further in the long term, a considerable challenge for dermatologists to address. A reporting intervention may be one of the ways we can improve our patients’ treatment outcomes.
Asking More of Our Metaphors: Narrative Strategies to End the “War on Alzheimer's” and Humanize Cognitive Aging
Authors: Daniel R. George, Erin R. Whitehouse, Peter J. Whitehouse
Journal: The American Journal of Bioethics (2016)

In all facets of our lives, humans construct meaning to understand their place in the world and their relationships to one another and to broader environments. Within this semantic web, words, stor...
Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo
Authors: Kevin J. Kauffman, Faryal F. Mir, Siddharth Jhunjhunwala, James C. Kaczmarek, Juan E. Hurtado, Jung H. Yang, Matthew J. Webber, Piotr S. Kowalski, Michael W. Heartlein, Frank DeRosa, Daniel G. Anderson
Journal: Biomaterials (2016)
Therapeutic Strategies in the Real Life in BCLC-C Hepatocellular Carcinoma in Italy: Assessment in the Italian Liver Cancer and Validation in the Italian Association of Hospital Gastroenterologists Database
Authors: V. Vanin, A. Imondi, C. Pozzan, F. Murer, A. Vitale, U. Cillo, E. Dionigi, M. Borzio, F. Trevisani, F. Farinati
Journal: Journal of Hepatology (2016)
Survival in Patients with Hepatcellular Carcinoma after Transarterial Chemoembolisation is Determined by Tumor Biology and Hepatic Function
Authors: M.M. Kirstein, N. Schweitzer, N. Ay, C. Boeck, J. Hinrichs, T. Voigtländer, M. Manns, T. Rodt, A. Vogel
Journal: Journal of Hepatology (2016)