tbuckley/cabot-search huggingface dataset:
OX40 expression in tumor-associated Tregs as a potential prognostic biomarker and immunotherapeutic target in ovarian cancer.
Authors: Massimo A. Di Nicola, Roberta Zappasodi, Alessia Burocchi, Giusi Ruggiero, Anna Rossini, Fabio Martinelli, Claudio Tripodo, Michele Magni, Domenica Lorusso, Filippo G. De Braud, Francesco Raspagliesi, Mario Paolo Colombo
Journal: Journal of Clinical Oncology (2015)

e16576 Background: Treatment of ovarian cancer (OC) remains very challenging, with 80-85% of the cases still dying after relapse to standard chemotherapy, and novel treatments are urgently needed. Expansion of regulatory T cells (Tregs) is considered the major factor limiting immune responses to OC. Agonist antibodies against the co-stimulatory receptor OX40 have recently demonstrated to abrogate Treg functions and are under clinical evaluation. We thus studied whether OX40 constituted a valid target of OC-associated Tregs. Methods: Treg immunophenotypic analyses were performed by flow cytometry in ascites and OC specimens and studied in association with patients’ outcome Results: CD4+CD25+Foxp3+ Treg% and OX40 expression were measured in 50 OC cases (36, high grade serous carcinomas; 14, other histotypes). Treg% was significantly higher in ovary (47 evaluable cases) relative to ascites (39 evaluable cases) (p < 0.0001). Treg% in ascites and peripheral blood from OC patients or healthy donors were not significantly different. The fraction of Tregs expressing OX40, instead, dramatically increased from peripheral blood to ascites (p < 0.01), and was even higher within the tumor (p < 0.001). In 24 patients (stage IIC-IV; 19, high grade serous carcinoma; 5, other histotypes) with ≥ 12-month follow-up after surgery and carboplatin-paclitaxel, we analyzed OX40 expression on intratumor Tregs in function of the outcome. Patients with Treg% or OX40 MFI above the mean had a significantly reduced OS (p = 0.004, p = 0.02). Interestingly, having both high Treg% and OX40 MFI trended toward the worst OS, followed by high Treg% or OX40 MFI alone, whereas the lack of these parameters was associated with a significantly improved survival (mean: 28, 36, 41 and 53 months). OX40+ Tregs in both ascites and OC tissue included CD45RA-, Foxp3hi, ICOS+ IFNγ- effector Tregs, thus indicating that OX40 may define a subset of highly suppressive Tregs in OC. Conclusions: Our study underscores a negative prognostic impact of OX40 expression on OC-infiltrating Tregs and indicates that OX40 may constitute a rational target to counteract effector Treg functions and unleash potentially effective immune responses against OC.
Incidence of and Risk Factors for Major Hemorrhage in Patients Treated with Ibrutinib: Results from an Integrated Analysis
Authors: Jennifer R. Brown, Javid Moslehi, Michael S. Ewer, Susan M. O'Brien, Paolo Ghia, Florence Cymbalista, Tait D. Shanafelt, Graeme Fraser, Simon Rule, Steven E. Coutre, Marie-Sarah Dilhuydy, Paula Cramer, Ulrich Jaeger, Martin Dreyling, John C. Byrd, Steven Treon, Emily Liu, Stephen Chang, Amulya Bista, Rama Vempati, Lisa Boornazian, Rudolph Valentino, Vijay Reddy, Michelle Mahler, Huiying Yang, Jan A. Burger
Journal: Blood (2017)
Immunoglobulin G fragment C receptor polymorphisms and response to trastuzumab-based treatment in patients with HER-2/neu-positive metastatic breast cancer
Authors: Antonino Musolino, Nadia Naldi, Beatrice Bortesi, Marzia Capelletti, Debora Pezzuolo, Maria Michiara, Gabriele Missale, Diletta Laccabue, Alessandro Zerbini, Roberta Camisa, Andrea Ardizzoni
Journal: Cancer Research (2007)

4188  Background: The humanized anti-HER-2/neu monoclonal antibody Trastuzumab has been shown to engage both activation (FcγRIIIa; FcγRIIa) and inhibitory (FcγRIIb) antibody receptors on myeloid cells and FcγRpolymorphisms have been identified that may affect the antibody-dependent cytotoxicity (ADCC) of natural killer cells and macrophages. In this study, we tested whether FcγR polymorphisms are associated with clinical outcome of breast cancer patients who received trastuzumab.  Patients and methods: Forty consecutive HER-2/neu-amplified metastatic breast cancer patients receiving trastuzumab plus taxane (paclitaxel or docetaxel) as first-line therapy were examined for the FcγRIIIa 158 valine (V)/phenylalanine (F), FcγRIIa 131 histidine (H)/arginine (R), and FcγRIIb 232 isoleucine (I)/threonine (T) polymorphisms. A PCR based single-base extension method (SNaPshotTM , Applied Byosistems) using genomic and complementary DNA was performed for FcγRIIa and FcγRIIIa genotyping, respectively.FcγRIIb analysis was performed on cDNA using PCR amplification followed by direct sequencing. Patients’ peripheral blood mononuclear cells were drawn before treatment initiation and their trastuzumab-mediated killing function was measured by 51Cr release using a HER-2/neu-expressing human breast cancer cell line as a target. Case-matched controls comprised patients treated with taxane-based therapy without trastuzumab (n = 20).  Results: The FcγRIIIa 158 V/V genotype was significantly correlated with the response rate (RR) and Progression Free Survival (PFS). Also, there was trend significance in RR and PFS when patients with FcγRIIa 131 H/H genotype were compared with patients with H/R or R/R genotype. A significant difference was found between the trastuzumab-mediated ADCC of patients’ immune effector cells with 158 V/V and/or 131 H/H versus those without either genotype.  Conclusions: These data support for the first time the hypothesis that ADCC plays an important role in the clinical effect of trastuzumab at the level of the effector cell. Results from the 232 I/T polymorphism analysis will be presented at the meeting.
Update of treatment algorithms for Clostridium difficile infection
Authors: R.E. Ooijevaar, Y.H. van Beurden, E.M. Terveer, A. Goorhuis, M.P. Bauer, J.J. Keller, C.J.J. Mulder, E.J. Kuijper
Journal: Clinical Microbiology and Infection (2018)
Safety of 300IR 5-Grass Tablet in Children with Grass Pollen-Induced Allergic Rhinoconjunctivitis: Results of an Observational, Post-Marketing Safety Study
Authors: Michael Gertslauer, Zsolt Szepfalusi, David B.K. Golden, Agnès Viatte, Michel Melac, Kathy Abiteboul, None Jacques de Blic
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 16122: Is Vitamin D Deficiency Really Associated With an Increased Incidence of Statin Intolerance?
Authors: Tami L Bair, Stacey Knight, Heidi T May, Benjamin D Horne, Jeffrey L Anderson, Donald L Lappé, Joseph B Muhlestein
Journal: Circulation (2015)

Introduction: Statin therapy is potentially the most important treatment presently available to prevent the progression of atherosclerosis. Unfortunately, a significant number of patients cannot tolerate statins due to muscle aches. Vitamin D deficiency, which is also associated with a variety of muscular symptoms, is commonly identified among patients with an indication for statin therapy. Several small studies have proposed that vitamin D deficiency may contribute to statin intolerance, but this has not been definitively demonstrated. Hypothesis: Vitamin D deficiency is associated with greater risk of statin intolerance. Methods: In the Intermountain Healthcare electronic health record, 12,066 patients had an initial 25(OH) vitamin D (VitD) level available and an indication for statin therapy with either a documented statin intolerance or evidence of active statin therapy. Patient baseline clinical characteristics were collected and multivariable logistic regression analysis was used to evaluate associations between VitD levels (stratified into four categories (ng/ml): &lt;12 [n=660(5.5%)], 12 to &lt;20 [2,057(17.0%)], 20 to &lt;50 [8,183(67.8%)], ≥50 [n=1,166(9.7%)]) and statin intolerance. Results: Overall, 12,066 subjects (statin intolerant n=928 [7.7%]; age = 56±6 yrs; males = 37.5%, prior atherosclerotic cardiovascular disease = 1856 [15.4%]) were enrolled. Multivariable effects of VitD and other predictors on risk of statin intolerance are shown in the Table. Conclusion: In this large cohort of patients with an indication for statin therapy, baseline VitD levels were not significantly associated with statin intolerance. Characteristics that were associated with statin intolerance included older age, female gender, Caucasian race, diabetes and a prior diagnosis of hyperlipidemia.
IKZF1/3 and CRL4CRBN E3 Ubiquitin Ligase Mutations Associate with IMiD Resistance in Relapsed Multiple Myeloma
Authors: Santiago Barrio Garcia, Matteo Da Via, Andoni Garitano-Trojaola, Yanira Ruiz-Heredia, Max Bittrich, ChangXin Shi, Yuan Zhu, Nicola Lehners, Elias K Mai, Marc S Raab, Pieter Sonneveld, Joaquín Martínez, Andreas Rosenwald, Esteban Braggio, Hermann Einsele, A. Keith Stewart, K. Martin Kortüm
Journal: Blood (2017)
Update on a Phase II Study of Ixazomib with Lenalidomide As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients with Multiple Myeloma
Authors: Krina K. Patel, Jatin J. Shah, Lei Feng, Hans C. Lee, Elisabet E. Manasanch, Sheeba K. Thomas, Donna M. Weber, Silvia C. Munoz, Ashley Morphey, Qaiser Bashir, Muzaffar H. Qazilbash, Robert Z. Orlowski
Journal: Blood (2017)
Efficient and cost-effective generation of hepatocyte-like cells through microparticle-mediated delivery of growth factors in a 3D culture of human pluripotent stem cells
Authors: Zeinab Heidariyan, Mohammad Hossein Ghanian, Mohsen Ashjari, Zahra Farzaneh, Mostafa Najarasl, Mehran Rezaei Larijani, Abbas Piryaei, Massoud Vosough, Hossein Baharvand
Journal: Biomaterials (2018)
Does Venous Thromboembolism Prophylaxis Policy Have Any Impact on Clot Risk Reduction in Hospitalized Solid Tumor Patients at Princess Margaret Cancer Centre: A Longitudinal Study?
Authors: Anna Xu, Tian Wang, Eshetu G Atenafu, Hassan Sibai, Arjun Datt Law, Kelsey Japs, Joseph Samuel, andreW. Stessman, Triyu Vather, Helen Vu, Jack Seki, Jennifer Carter
Journal: Blood (2017)
Abstract 17028: “Worsening Heart Failure” in Chronic Heart Failure With Reduced Ejection Fraction: Definition, Characteristics, and Effects of NT-proBNP Guided Therapy
Authors: Aditi Mallick, Parul U Gandhi, Hanna K Gaggin, James L Januzzi
Journal: Circulation (2015)

Introduction: Worsening heart failure (WHF) has been identified as a potentially relevant clinical event in patients with HF syndromes and increasingly used as an endpoint in clinical trials. No standardized definition of WHF exists, nor is it known how WHF relates to risk for other events or how HF therapies may impact it. Hypothesis: Using the definition of WHF in the ProBNP Outpatient Tailored Chronic HF (PROTECT) study, we sought to characterize WHF. Methods: PROTECT was a randomized trial of 151 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF), comparing standard of care HF management with or without a goal to lower amino-terminal pro-B type natriuretic peptide (NT-proBNP) concentrations &lt;1000 pg/mL. WHF was defined as 1) new or progressive symptoms/signs of decompensated HF, 2) resulting in unplanned intensification of diuretic therapy. Results: Over mean follow-up of 10 months, 45 subjects developed WHF, the majority of whom had one or two WHF episodes. At baseline, patients destined to develop WHF had higher EF (31% vs. 25%, p=0.03), were more likely to have jugular venous distension and edema (p&lt;0.02), were less likely to receive angiotensin converting enzyme inhibitors (ACEi), and more likely to receive lower ACEi doses (p&lt;0.04); patients destined for WHF also received higher baseline loop diuretic doses (p&lt;0.001) and had higher concentrations of several HF biomarkers including NT-proBNP, ST2, highly sensitive troponin, and galectin-3 (p &lt;0.001). While numerous baseline factors were univariate predictors of WHF, only ST2 concentrations (p&lt;0.001) and EF (p=0.03) at baseline were independently predictive of future WHF. Occurrence of WHF was strongly associated with subsequent HF hospitalization/CV death (56% vs 6%; p &lt;0.001). Relative to therapies, ACEi use and dose were inversely associated with WHF (p&lt;0.05), while loop diuretic dose was directly associated (P =0.006). Allocation to NT-proBNP-guided care independently predicted fewer WHF in adjusted analyses (HR=0.52, p=0.06) and improved time to first WHF event (log rank p=0.04). Conclusion: In chronic HFrEF, WHF is associated with substantial risk for morbidity and mortality. NT-proBNP guided care reduced risk for this important and deleterious outcome.
Clinical and Immunological Profiles of 14 Patients With Bullous Pemphigoid Without IgG Autoantibodies to the BP180 NC16A Domain
Authors: Kenta Nakama, Hiroshi Koga, Norito Ishii, Chika Ohata, Takashi Hashimoto, Takekuni Nakama
Journal: JAMA Dermatology (2018)

Enzyme-linked immunosorbent assay (ELISA) and/or chemiluminescent enzyme immunoassay (CLEIA) for BP180 noncollagenous 16A (NC16A) extracellular domain is a sensitive diagnostic tool for bullous pemphigoid (BP). However, some patients with BP have negative results for these assays.To elucidate the clinical and immunological features of patients with BP without antibodies that react to BP180 NC16A.This retrospective case series study included 152 patients who were diagnosed with BP and followed up at the Kurume University Hospital in Japan from 2007 to 2016. The diagnosis was made using clinical, histological, and immunological findings.Clinical and immunological features of patients with BP who had negative results for BP180 NC16A using ELISA and/or CLEIA.Of the 152 patients, 69 (45.4%) were men and 83 (54.6%) were women. The mean (SD) age of participants was 75.2 (14.4) years. Of the 152 patients with BP, 14 (9.2%) had negative results for BP180 NC16A on ELISA and/or CLEIA; most of these patients exhibited no erythema and had relatively mild phenotypes. Two (14%) of the 14 patients had positive results for intact BP180 in epidermal extracts, 10 (71%) had positive results for a 120-kD fragment of BP180 (LAD-1) and 3 (21%) had positive results for BP180 C-terminal domain. Seven (50%) patients tested positive in BP230 ELISA. Five (36%) patients did not require oral prednisolone treatment, whereas the others required a dose of prednisolone at less than 30 mg per day. Three (21%) patients were administered a dipeptidyl peptidase-4 inhibitor (DPP4i) before disease onset. This ratio was not significantly higher than that in patients with BP who tested positive for BP180 NC16A ELISA and/or CLEIA (19 [14%] of 138 patients). Our follow-up study (mean [SD], 31.9 [33.2] weeks; range, 0-108 weeks) revealed that patients with BP tested negative for BP180 NC16A ELISA and/or CLEIA during the later stages of the disease.This study indicates that patients with BP negative for BP180 NC16A ELISA and/or CLEIA had milder phenotypes, fewer erythemas, and required less extensive treatments.
C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy
Authors: Andrew S. Bomback, Dominick Santoriello, Rupali S. Avasare, Renu Regunathan-Shenk, Pietro A. Canetta, Wooin Ahn, Jai Radhakrishnan, Maddalena Marasa, Paul E. Rosenstiel, Leal C. Herlitz, Glen S. Markowitz, Vivette D. D’Agati, Gerald B. Appel
Journal: Kidney International (2018)
Observational, multicentre study on the epidemiology of haemoptysis
Authors: Michele Mondoni, Paolo Carlucci, Sara Job, Elena Maria Parazzini, Giuseppe Cipolla, Matteo Pagani, Francesco Tursi, Luigi Negri, Alessandro Fois, Sara Canu, Antonella Arcadu, Pietro Pirina, Martina Bonifazi, Stefano Gasparini, Silvia Marani, Andrea Claudio Comel, Franco Ravenna, Simone Dore, Fausta Alfano, Giuseppe Francesco Sferrazza Papa, Fabiano Di Marco, Stefano Centanni, Giovanni Sotgiu
Journal: European Respiratory Journal (2018)

Haemoptysis, which is a challenging symptom accounting for 10–15% of all pulmonology consultations, may be associated with life-threatening medical conditions such as lung cancer [1–7]. Malignancy is the main haemoptysis aetiology in our Italian cohort <http://ow.ly/goUb30gRT5b>
FDG PET and FES PET Predict PFS on Endocrine Therapy—Letter
Authors: Lemonitsa H. Mammatas, Erik J. van Helden, Henk M.W. Verheul, Catharina W. Menke-van der Houven van Oordt
Journal: Clinical Cancer Research (2018)

With great interest, we read the article by Kurland and colleagues ([1][1]) that investigates the value of 18F-fluoroestradiol (FES) and 18F-fluorodeoxyglucose (FDG) PET for the prediction of progression-free survival (PFS) in 84 patients with advanced, estrogen receptor (ER)–positive breast
Recurrence of Reflux After Laparoscopic Antireflux Surgery—Reply
Authors: John Maret-Ouda, Jesper Lagergren
Journal: JAMA (2018)

In Reply We do not believe that our view of the use of antireflux surgery is very different from that of Drs Patti and Schlottmann, but we would like to respond to the 4 potential limitations of the study that were brought to our attention.
A transatlantic perspective on the integration of immuno-oncology prognostic and predictive biomarkers in innovative clinical trial design
Authors: M. Morfouace, S.M. Hewitt, R. Salgado, K. Hartmann, S. Litiere, S. Tejpar, V. Golfinopoulos, T. Lively, M. Thurin, B. Conley, D. Lacombe
Journal: Seminars in Cancer Biology (2018)
What are your burning issues for 2018?
Authors: Fiona Godlee
Journal: BMJ (2018)

The new year is a chance to take stock, personally and professionally, privately and publicly, and to consider with fresh eyes the challenges and opportunities ahead. We’ve been doing this at The BMJ over recent weeks, taking to heart the words of Hugh Clegg, our editor in chief from 1947 to 1965, that “a subject that needs reform should be kept before the public until it demands reform.” There’s no shortage of such subjects. Our question for you is which ones should we focus …
Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis
Authors: Amir Ahmadi, Jonathon Leipsic, Kristian A Øvrehus, Sara Gaur, Emilia Bagiella, Brian Ko, Damini Dey, Gina LaRocca, Jesper M Jensen, Hans Erik Bøtker, Stephan Achenbach, Bernard De Bruyne, Bjarne L Nørgaard, Jagat Narula
Journal: JACC. Cardiovascular imaging (2018)
Safety and Activity of the Highly Specific BTK Inhibitor BGB-3111 in Combination with the PD-1 Inhibitor BGB-A317 in Patients with B-Cell Lymphoid Malignancies
Authors: Gavin Cull, Stephen Opat, Judith Trotman, James Hilger, Xiaoping Zhang, Shibao Feng, Sunhee Ro, Jane Huang, Constantine S. Tam
Journal: Blood (2017)
Your Genes: One Size Doesn't Fit All
Authors: Mary E. Freivogel, Stephanie A. Cohen
Journal: Journal of the National Comprehensive Cancer Network (2018)

Counselors and Senior Director of Clinical Operations at InvisionSally Jobe Breast Centers in the Denver area.In 2009, she was hired as the first genetic counselor at this organization, which now has a robust Genetic Services department with 3 genetic counselors, 1 nurse practitioner, and 1 medical assistant.Ms. Freivogel has led the implementation of processes that efficiently identify patients at high-risk for breast cancer and communicate this risk to these patients and their referring physicians.She has presented information at various professional meetings and published on this topic in national peer-reviewed journals.She is actively involved with the National Accreditation Program for Breast Centers and the National Consortium of Breast Centers, as well as the American Cancer Society, with regard to breast cancer risk assessment efforts.She is passionate about the genetic counseling profession and believes that genetic counselors have an infinite number of talents and unique contributions to provide to breast cancer risk assessment efforts and countless other areas.
Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease
Authors: Noha Abdel-Wahab, Mohsin Shah, Maria A. Lopez-Olivo, Maria E. Suarez-Almazor
Journal: Annals of Internal Medicine (2018)

Background: Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease. Purpose: To summarize the evidence on adverse events associated with CPIs in patients with cancer and preexisting autoimmune disease. Data Sources: MEDLINE, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through September 2017 with no language restrictions. Study Selection: Original case reports, case series, and observational studies describing patients with cancer and autoimmune disease who were receiving CPIs. Data Extraction: 2 reviewers independently extracted data and assessed the quality of reporting. Data Synthesis: 123 patients in 49 publications were identified; 92 (75%) had exacerbation of preexisting autoimmune disease, irAEs, or both. No differences in adverse events were observed in patients with active versus inactive disease. Patients receiving immunosuppressive therapy at initiation of CPI therapy seemed to have fewer adverse events than those not receiving treatment. Most flares and irAEs were managed with corticosteroids; 16% required other immunosuppressive therapies. Adverse events improved in more than half of patients without discontinuation of CPI therapy. Three patients died of adverse events. Limitations: The quality and quantity of data were limited. Case reports typically describe unique manifestations and are not generalizable to the population at large. Because there were no prospective observational studies, incidence could not be determined. Conclusion: Flares and irAEs in patients with autoimmune disease who are receiving CPIs can often be managed without discontinuing therapy, although some events may be severe and fatal. Prospective longitudinal studies are needed to establish incidence of adverse events and evaluate risk–benefit ratios and patient preferences in this population. Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Transcatheter Versus Surgical Aortic Valve Replacement
Authors: J. Matthew Brennan, Laine Thomas, David J. Cohen, David Shahian, Alice Wang, Michael J. Mack, David R. Holmes, Fred H. Edwards, Naftali Z. Frankel, Suzanne J. Baron, John Carroll, Vinod Thourani, E. Murat Tuzcu, Suzanne V. Arnold, Roberta Cohn, Todd Maser, Brenda Schawe, Susan Strong, Allen Stickfort, Elizabeth Patrick-Lake, Felicia L. Graham, Dadi Dai, Fan Li, Roland A. Matsouaka, Sean O’Brien, Fan Li, Michael J. Pencina, Eric D. Peterson
Journal: Journal of the American College of Cardiology (2017)
Multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): a pragmatic, randomised controlled, superiority trial
Authors: Peter Fonagy, Stephen Butler, David Cottrell, Stephen Scott, Stephen Pilling, Ivan Eisler, Peter Fuggle, Abdullah Kraam, Sarah Byford, James Wason, Rachel Ellison, Elizabeth Simes, Poushali Ganguli, Elizabeth Allison, Ian M Goodyer
Journal: The Lancet Psychiatry (2018)
Gold nanoparticle should understand protein corona for being a clinical nanomaterial
Authors: Fahimeh Charbgoo, Mojgan Nejabat, Khalil Abnous, Fatemeh Soltani, Seyed Mohammad Taghdisi, Mona Alibolandi, W. Thomas Shier, Terry W.J. Steele, Mohammad Ramezani
Journal: Journal of Controlled Release (2018)
Bortezomib, Liposome Doxorubicin and Dexamethasone (PDd) Is Superior in Safety and Not Inferior in Efficiency to Bortezomib, Doxorubicin and Dexamethasone (PAd) As Induction Therapy in New-Diagnosed Multiple Myeloma Patients: An Interim Report from China's Multicenter Study
Authors: Song Jin, Yun Xu, Jin Zhou, Jingjing Shang, Lingzhi Yan, Chengcheng Fu, Depei Wu
Journal: Blood (2017)