tbuckley/cabot-search huggingface dataset:
Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study
Authors: Marc A Rodger, Gregoire Le Gal, David R Anderson, Jeannot Schmidt, Gilles Pernod, Susan R Kahn, Marc Righini, Patrick Mismetti, Clive Kearon, Guy Meyer, Antoine Elias, Tim Ramsay, Thomas L Ortel, Menno V Huisman, Michael J Kovacs,
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To prospectively validate the HERDOO2 rule (Hyperpigmentation, Edema, or Redness in either leg; D-dimer level ≥250 μg/L; Obesity with body mass index ≥30; or Older age, ≥65 years), which states that women with none or one of the criteria can safely discontinue anticoagulants after short term treatment. <b>Design</b>&nbsp;Prospective cohort management study. <b>Setting</b>&nbsp;44 secondary or tertiary care centres in seven countries. <b>Participants</b>&nbsp;Of 3155 consecutive eligible participants with a first unprovoked venous thromboembolism (VTE, proximal leg deep vein thrombosis or pulmonary embolism) who completed 5-12 months of short term anticoagulant treatment, 370 declined to participate, leaving 2785 enrolled participants. 2.3% were lost to follow-up. <b>Interventions</b>&nbsp;Women with none or one of the HERDOO2 criteria were classified as at low risk of recurrent VTE and discontinued anticoagulants (intervention arm), whereas anticoagulant management for high risk women (≥2 HERDOO2 criteria) and men was left to the discretion of the clinicians and patients (observation arm). <b>Main outcome measure</b>&nbsp;Recurrent symptomatic VTE (independently and blindly adjudicated) over one year of follow-up. <b>Results</b>&nbsp;Of 1213 women, 631 (51.3%) were classified as low risk and 591 discontinued oral anticoagulant treatment. In the primary analysis, 17 low risk women who discontinued anticoagulants developed recurrent VTE during 564 patient years of follow-up (3.0% per patient year, 95% confidence interval 1.8% to 4.8%). In 323 high risk women and men who discontinued anticoagulants, 25 had VTE during 309 patient years of follow-up (8.1%, 5.2% to 11.9%), whereas in 1802 high risk women and men who continued anticoagulants 28 had recurrent VTE during 1758 patient years of follow-up (1.6%, 1.1% to 2.3%). <b>Conclusions</b>&nbsp;Women with a first unprovoked VTE event and none or one of the HERDOO2 criteria have a low risk of recurrent VTE and can safely discontinue anticoagulants after completing short term treatment. <b>Trial registration</b>&nbsp;clinicaltrials.gov NCT00967304.
C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial Microvesicles
Authors: Maria Mossberg, Anne-lie Ståhl, Robin Kahn, Ann-Charlotte Kristoffersson, Ramesh Tati, Caroline Heijl, Mårten Segelmark, L.M. Fredrik Leeb-Lundberg, Diana Karpman
Journal: Journal of the American Society of Nephrology (2017)

The kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P<0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor-depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation.
The value of personalizing medicine: Medical oncologists’ and patients’ perspectives on genomic testing of breast tumors in chemotherapy treatment decisions.
Authors: Maureen E. Trudeau, Yvonne Bombard, Linda Rozmovits, Natasha B. Leighl, Ken Deal, Deborah Marshall
Journal: Journal of Clinical Oncology (2012)

e11000 Background: Benefits of adjuvant chemotherapy for early-stage breast cancer patients (pts) depend on baseline recurrence risks. Gene expression profiling (GEP) of tumours informs baseline risk prediction, potentially reducing unnecessary treatment and healthcare costs. Limited evidence exists on its clinical utility; we explored pts and medical oncologists (MO) perspectives on GEP in chemotherapy decisions. Methods: We used a qualitative design of individual interviews with MO (n=10), focus groups and individual interviews with pts (n=20) from Ontario. Pts who underwent genomic testing of their tumours (‘OncotypeDx’), were recruited through clinics from two academic hospitals in Toronto. MO were recruited through clinics, advertisements and referrals from the research team. Data were analyzed using interpretative qualitative methods, including content analysis, qualitative description and constant comparison techniques. Results: Pts and MO valued GEP as an additional decision-support tool, complementing existing clinical indicators. Its perceived utility varied between pts and MO. Pts valued the test highly, suggesting it was one of the primary determinants of their treatment decision. All pts followed the course of action their results suggested. Pts with intermediate scores often used the results to reinforce their pre-existing treatment preferences. MO were mixed about the test’s utility. Some considered it another tool supporting their approach to risk assessments, while others used it more definitively to resolve their uncertainty. MO explained the test’s contribution to decision-making but remained uncertain about pts understanding and expectations of the test. Some raised concerns about the variability of its use and interpretation within their medical community. Conclusions: Pts and MO valued the test, often using it as a primary determinant in their treatment decision, despite MO concerns about its technical limitations and pts limited understanding. Results identify a need for informational decision aids and practice guidelines to support pts understanding and standardized application of the test.
LONG-TERM CARDIOVASCULAR OUTCOMES IN PATIENTS WITH ANOMALOUS CORONARY ARTERIES WISUALIZED BY CORONARY CT ANGIOGRAPHY: THE CONFIRM (CORONARY CT ANGIOGRAPHY EVALUATION FOR CLINICAL OUTCOMES: AN INTERNATIONAL MULTICENTER) REGISTRY
Authors: Subhi Al'Aref, Khalil Anchouche, Ashley Beecy, Heidi Gransar, Briain O. Hartaigh, Mahn Won Park, Asim Rizvi, Ji Hyun Lee, Donghee Han, Hadi Mirhedayati Roudsari, Daniel Berman, Tracy Callister, Augustin DeLago, Martin Hadamitzky, Joerg Hausleiter, Mouaz Al-Mallah, Matthew Budoff, Philipp Kaufmann, Gilbert Raff, Kavitha Chinnaiyan, Filippo Cademartiri, Erica Maffei, Todd Villines, Yong-Jin Kim
Journal: Journal of the American College of Cardiology (2017)
EFFICACY OF CATHETER ABLATION OF ATRIAL FIBRILLATION IN THE SETTING OF SYSTOLIC DYSFUNCTION: A META-ANALYSIS OF RANDOMIZED CONTROL TRIALS
Authors: Mohammad-Ali Jazayeri, Venkat Lakshmi Kishan Vuddanda, Valay Parikh, Madhav Lavu, Mohit Turagam, M. Rizwan Afzal, Donita Atkins, Sudharani Bommana, Luigi Di Biase, Andrea Natale, Madhu Reddy, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2017)
A phase I dose-escalation study of TAS-102 in patients (pts) with refractory metastatic colorectal cancer (mCRC).
Authors: Manish R. Patel, Johanna C. Bendell, Robert J. Mayer, Fabio M. Benedetti, Lee S. Rosen
Journal: Journal of Clinical Oncology (2012)

3631 Background: TAS-102 is an oral combination of a novel antimetabolite 5-trifluorothymidine (FTD) and a thymidine phosphorylase inhibitor (TPI) that prevents degradation of FTD. In preclinical studies, TAS-102 is effective against human colorectal tumors with innate and acquired resistance to 5FU. A Japanese randomized phase 2 study demonstrated a significant survival improvement of TAS-102 over placebo in refractory mCRC (HR=0.56 p=0.0011, EMCC2011). The present study was conducted to determine the MTD of TAS-102 in Western pts with refractory mCRC. Methods: Pts with mCRC who had received at least 2 lines of chemotherapy including a fluoropyrimidine, irinotecan and oxaliplatin were enrolled at an initial dose level of 30 mg/m 2 BID days 1- 5 and days 8-12 every 4wks using a standard 3+3 design. A second dose level of 35 mg/m 2 , which was the MTD for Japanese pts, was the maximal targeted dose in this study. Results: 12 pts received TAS-102 (30/35 mg/m 2 =3/9, M/F=7/5, Age 44-75, PS0/1=8/4). Pts received a median of 3 prior regimens for metastatic disease. No DLT was observed in the initial dose level (0/3) and one DLT (grade 3 febrile neutropenia) was observed at 35mg/m 2 (1/9). Other drug-related ≥ grade 3 toxicities observed in cycle 1 included neutropenia at 58% (7/12). To date, a median number of treatment cycles at the MTD has not been reached as 5 pts are still receiving therapy (range 1-3+ cycles). Conclusions: Western patients with refractory mCRC showed the same MTD as Japanese pts (35 mg/m 2 BID, days 1- 5 and days 8-12 every 4wks) and the safety profile was consistent between the populations. The trial has entered an expansion phase to assess further safety and preliminary efficacy. A phase 3 trial is being planned.
Aggressive Non Hodgkin lymphoma'patients Treated by High Dose Chemotherapy and Immunotherapy Has a Lower Relapse Rate: Results of a Computer Science Analysis.
Authors: Matteo Pelosini, Flavio Baronti, Francesco Caracciolo, Sara Galimberti, Edoardo Benedetti, Federico Papineschi, Enrico Orciuolo, Gabriele Buda, Antonina Starita, Mario Petrini
Journal: Blood (2009)
Government should raise taxes to fund NHS and social care, say experts
Authors: Gareth Iacobucci
Journal: BMJ (2017)

A group of healthcare experts has urged the government to consider various options for raising taxes to provide extra funding for the NHS and social care in England.

In an interim report published on Thursday 16 March, the expert panel, assembled by the Liberal Democrats’ shadow health secretary, Norman Lamb, to suggest solutions for tackling the current funding crisis, said it was “unanimously of the opinion that it is necessary to raise additional revenue for health and care through taxation.”1

The 10 strong panel, which includes the former …
QUANTITATIVE MEASUREMENT OF CORONARY INTRA-PLAQUE NECROTIC CORE BY CORONARY CT ANGIOGRAPHY IN VICTIMS OF AUTOPSY-PROVEN SUDDEN CORONARY DEATH: A COMPARISON TO A HISTOLOGIC REFERENCE STANDARD
Authors: Donghee Han, Fay Lin, Ji Hyun Lee, Asim Rizvi, Mahn Won Park, Hadi Mirhedayati Roudsari, Lohendran Baskaran, Heidi Gransar, Ashley Beecy, Khalil Anchouche, Subhi Al'Aref, Kazuyuki Yahagi, Sho Torii, Briain O. Hartaigh, Hyung Bok Park, Sang-Eun Lee, Robert Kutys, David Fowler, James Earls, Jessica Pena, Hyuk-Jae Chang, James Min, Renu Virmani
Journal: Journal of the American College of Cardiology (2017)
ROLE OF ANTICOAGULATION THERAPY AFTER ANTERIOR WALL ST-ELEVATION MYOCARDIAL INFRACTION IN PREVENTING LV THROMBUS: A META-ANALYSIS AND META-REGRESSION
Authors: Mohammed Makkiya, Pedro Villablanca, Mohammed Algodi, David Briceno, Maday Gonzalez, Faraj Kargoli, Tanush Gupta, Sahil Agrawal, Arthur Omondi, Divyanshu Mohananey, Nirmanmoh Bhatia, Jose Wiley, Harish Ramakrishna, Mark Menegus, Anna Bortnick, Cynthia Taub, Mario Garcia
Journal: Journal of the American College of Cardiology (2017)
Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart
Authors: Derek J. Hausenloy, David Garcia-Dorado, Hans Erik Bøtker, Sean M. Davidson, James Downey, Felix B. Engel, Robert Jennings, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Michel Ovize, Cinzia Perrino, Fabrice Prunier, Rainer Schulz, Joost P.G. Sluijter, Linda W. Van Laake, Jakob Vinten-Johansen, Derek M. Yellon, Kirsti Ytrehus, Gerd Heusch, Péter Ferdinandy
Journal: Cardiovascular Research (2017)

Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic—however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial IRI.
Inmunohistochemical expression of thymidilate synthase, ERCC1, pKDR, and LDH5 as predcitive markers of efficacy in patients with advanced colon cancer treated with XELOX or FOLFOX with or without bevacizumab.
Authors: Javier Garde, Elena Evgenyeva, Gil raga Mireia, Laia Bernet, Asuncion Juarez, Juan Laforga, Juan Manuel Gassent, Martin Demarchi, Carlos Camps, Antonio Llombart
Journal: Journal of Clinical Oncology (2013)

e14671 Background: Low Thymidilate Synthase (TS) and ERCC1 expression have been related with efficacy of Fluoropirimidines and Platinum compounds respectively. High expression of angiogenic related proteins pKDR and LDH5 have been related with worse prognosis. The aim of our study is to analyze the inmunohistochemical expression of these proteins and their role as predictive markers of efficacy in advanced colorectal carcinoma. Methods: Retrospective study of patients with advanced colorectal cancer treated in first line with FOLFOX or XELOX +/- Bevacizumab between 2007 and 2011. Inmunoreactivity has been scored for staining intensity and proportion of positive cells. Staining was semiquantitative evaluated: intensity scored as none (0), to Strong (3), and percentage was categorized into five groups 0 = 0%, 1 (1-25%), 2 (26-50%), 3 (51-75%), 4 (76-100%). Staining and percentage scores were multiplied to obtain final T score (range 0-12), low expression was defined as T score &lt;7, and high expression as T score ≥ 7. Results: 112 patients met inclusion criteria. Median age 68 years, 66 male (58.9%), 87 ECOG 0-1 (77.7%) and 58 (51,7%) with primary tumor removed before chemotherapy treatment. Seventy-five patients received bevacizumab (66.9%). Overall response rate was 56,3%, disease control rate 76.8%, and 18.8% of patients underwent surgery after treatment. Median PFS was 12 months and median OS 23 months. Preliminary results of TS expression showed 33.3% of patients with high vs 66.7% with low expression. There were not differences in response rate (60.7 vs 57.6%, p= 0.49), PFS (12 vs 13 m, p=0.48) or OS (22 vs 20 m, p= 0.6) between patients with low and high TS expression. Inmunohistochemical expression of ERCC1, LDH5 and pKDR is currently ongoing. Conclusions: Low inmunohistochemical expression of Thymidilate Synthase is not associated in our study with better outcomes in patients with advanced colon cancer treated with XELOX/FOLFOX +/- bevacizumab. Predictive value of ERCC1, LDH5 and pKDR expression is been evaluated, pending final results.
SYSTEMIC PENTRAXIN 3 IS A POTENTIAL BIOMARKER TO DIFFERENTIATE PLAQUE EROSION FROM PLAQUE RUPTURE IN ACUTE CORONARY SYNDROME PATIENTS
Authors: Irina Mustafina, Sining Hu, Haibo Jia, Gonghui Zheng, Wei Liu, Lulu Li, Yinchun Zhu, Chao Wang, Abigail Afolabi, Chunyang Zhe, Yan Wang, Hui Dong, Xiling Zhang, Lin Lin, Yandong Fu, Shaotao Zhang, Yang Liu, Shaosong Zhang, Naufal Zagidullin, Ik-Kyung Jang, Bo Yu
Journal: Journal of the American College of Cardiology (2017)
Continuation of adjuvant temozolomide until tumor progression after upfront chemoradiation therapy produces promising survival in patients with GBM, especially with pseudoprogression.
Authors: Seymur Gahramanov, Rose Marie Tyson, Cynthia Lacy, Joao Prola Netto, Morad Nasseri, Rochelle Fu, Stephen Giles, Tricia White, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2013)

e13001 Background: Radiation therapy with concomitant temozolomide (TMZ) followed by 6 months of adjuvant TMZ is standard of care in newly diagnosed glioblastoma multiforme (GBM). The 6-month time frame for adjuvant TMZ was chosen arbitrarily and the optimal duration of TMZ chemotherapy remains undefined. In addition, the duration of TMZ chemotherapy and survival can be affected by uncertainty in differentiating pseudoprogression (Ps), indicating necrosis/inflammation, from true tumor progression. This IRB-approved retrospective study determined the survival of GBM patients treated with chemoradiotherapy (CRT) and adjuvant TMZ continued until tumor progression. Methods: Patients with biopsy-proven newly diagnosed GBM at Oregon Health and Science University from January 2006 to June 2012 were treated with upfront CRT followed by adjuvant TMZ without Pneumocystis jirovecii pneumonia prophylaxis until tumor progression. Diagnosis of Ps was made by relative cerebral blood volume (rCBV) estimation based on perfusion MRI with ferumoxytol or RANO criteria. Survival was determined using Kaplan-Meier product limit analysis. Results: A total of 67 patients were included. Overall median survival in the whole group was 21.3 months (95% CI 17.3, 26.3), significantly higher than the median survival in Stupp et al (2008) (14.6 months; 95% CI 13.2, 16.8). However 46 (69%) patients of our series received bevacizumab. Ps was diagnosed in 17 of 47 patients underwent ferumoxytol perfusion MRI based on rCBV measurement; 4 additional Ps cases were diagnosed based on RANO criteria. Median survival in the 21 patients with Ps was 49.1 months, though the estimate may be unstable due to the small sample size and 12 patients remain alive. Median TMZ cumulative dose for all patients was 5250 mg/m 2 (range 2250 to 64000). Conclusions: The increase in median survival compared to historical data supports the continuation of adjuvant TMZ treatment, especially in patients with Ps. Differentiation between true tumor progression and Ps is important for treatment (TMZ) decisions and may affect survival. Ferumoxytol perfusion MRI may help as diagnostic tool.
Evaluating the impact of a trial in breast cancer tumor markers: A value of research analysis.
Authors: Rahber Thariani, David K Blough, William Barlow, Norah Lynn Henry, Julie Gralow, Scott David Ramsey, David L Veenstra
Journal: Journal of Clinical Oncology (2012)

e16524 Background: Despite not being recommended by clinical guidelines, the tumor markers carcinoembryonic antigen (CEA), cancer antigen (CA)15-3, and CA 27.29 are used by some clinicians to screen for increased risk of breast cancer recurrence. Although additional research may be warranted to evaluate the benefits and risks of breast cancer tumor marker tests, clinical trials would likely need to involve thousands of women and would take many years to complete. We conducted an analysis to assess the societal value of a prospective randomized clinical trial (RCT) for breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors Methods: We used value of information techniques to assess the benefits of reducing uncertainty of using breast cancer tumor markers. We developed a decision-analytic model of biomarker testing in addition to standard surveillance at follow-up appointments every 3-6 months for five years. Expected value of sample information (EVSI) was assessed over a range of trial sizes and assumptions. Results: The overall value of research for an RCT involving 9,000 women was $166 million (EVSI). The value of improved information characterizing the survival impact of tumor markers was $81 million, quality-of-life $38 million, and test performance $95 million. Conclusions: Our analysis indicates that substantial societal value may be gained by conducting a clinical trial evaluating the use of breast cancer tumor markers. The most important aspects of the trial in our analysis were information gained on survival improvements as well as quality-of-life parameters associated with testing and test sensitivity and specificity. Our analysis indicates that smaller randomized trials, as well as adding quality of life instruments to existing trials, retrospective, and observational trials can also generate valuable and relevant information.
Clonal Expansion in Paroxysmal Nocturnal Hemoglobinuria (PNH): Expression of Mutant HMGA2 Suggests That PNH Is a Benign Tumor of the Bone Marrow.
Authors: Norimitsu Inoue, Tomohisa Izui, Yoshiko Murakmai, Yuichi Endo, Jun-ichi Nishimura, Yuzuru Kanakura, Gabrielle Meyers, Carl Wittwer, Zhong Chen, William Babcock, Debra Frei-Lahr, Charles Parker, Taroh Kinoshita
Journal: Blood (2005)
Antigen presenting cell (APC)-targeted hCGβ vaccine for cancer therapy
Authors: M. Morse, R. Chapman, T. Clay, T. Osada, A. Hobeika, J. Green, T. Davis, T. Keler
Journal: Journal of Clinical Oncology (2007)

3013 Background: CDX-1307 is a novel vaccine approach designed to target antigens directly into the endocytic compartments of dendritic cells (DCs) and other professional APCs. The β subunit of human chorionic gonadotropin (hCGβ) is selectively over-expressed by a number of epithelial tumors and has been reported to correlate with stage of disease and prognosis. We have coupled this tumor-associated antigen to a human monoclonal antibody (B11) that targets mannose receptors on human dendritic cells and macrophages, and have demonstrated the efficacy of this approach in preclinical models using hCGβ-expressing tumors and cell lines. Methods: In this phase I, dose-escalating study, sequential cohorts of 6 patients with relapsed epithelial tumors receive 4 biweekly intradermal injections of CDX-1307 at either 0.3, 1.0 or 2.5 mg, or 2.5 mg concurrent with GM-CSF. Objectives: safety and tolerability; DLT, humoral and cellular immune response, and clinical activity. Results: Enrollment in the first three cohorts (n=18) is complete with no DLTs. Common potential treatment-related toxicities were injection site reaction (n=5) and fatigue/malaise (n=4), and were generally mild to moderate in severity. One transient Grade 3 generalized allergic reaction in the 1.0 mg cohort was suspected possibly related to either a nut allergy or CDX-1307. One mixed response was seen, with variable effects on circulating hCGβ. CDX-1307 localized to dermal macrophages and DCs in post-treatment biopsies. Conclusions: Administration of CDX-1307 is well tolerated and results in antigen localization in APCs of the skin. Immune Response and tumor impact are under evaluation. Further development includes systemic delivery that may provide antigen targeting to a broad APC population, and combination with immunostimulants to generate optimal immune responses. No significant financial relationships to disclose.