tbuckley/cabot-search huggingface dataset:
Clinical Outcomes of Chronic Lymphocytic Leukemia (CLL) Patients with Richter's Transformation (RT) to Aggressive Non-Hodgkin Lymphoma (aNHL): a Single-Institution Experience
Authors: Mazyar Shadman, Sirin Khajavian, Andrew J. Cowan, Andrei R. Shustov, Brian G Till, Ryan D. Cassaday, Mohamed L Sorror, Leona Holmberg, E Houston Warren, Lori Soma, Edward N. Libby, David G. Maloney, Ajay K. Gopal, Oliver W. Press, Stephen D. Smith
Journal: Blood (2017)
Consequences of the 340B Drug Pricing Program
Authors: Sunita Desai, J. Michael McWilliams
Journal: New England Journal of Medicine (2018)

The 340B Drug Pricing Program entitles qualifying hospitals to discounts on outpatient drugs, increasing the profitability of drug administration. By tying the program eligibility of hospitals to their Disproportionate Share Hospital (DSH) adjustment percentage, which reflects the proportion of hospitalized patients who are low-income, the program is intended to expand resources for underserved populations but provides no direct incentives for hospitals to use financial gains to enhance care for low-income patients.We used Medicare claims and a regression-discontinuity design, taking advantage of the threshold for program eligibility among general acute care hospitals (DSH percentage, >11.75%), to isolate the effects of the program on hospital-physician consolidation (i.e., acquisition of physician practices or employment of physicians by hospitals) and on the outpatient administration of parenteral drugs by hospital-owned facilities in three specialties in which parenteral drugs are frequently used. For low-income patients, we also assessed the effects of the program on the provision of care by hospitals and on mortality.Hospital eligibility for the 340B Program was associated with 2.3 more hematologist-oncologists practicing in facilities owned by the hospital, or 230% more hematologist-oncologists than expected in the absence of the program (P=0.02), and with 0.9 (or 900%) more ophthalmologists per hospital (P=0.08) and 0.1 (or 33%) more rheumatologists per hospital (P=0.84). Program eligibility was associated with significantly higher numbers of parenteral drug claims billed by hospitals for Medicare patients in hematology-oncology (90% higher, P=0.001) and ophthalmology (177% higher, P=0.03) but not rheumatology (77% higher, P=0.12). Program eligibility was associated with lower proportions of low-income patients in hematology-oncology and ophthalmology and with no significant differences in hospital provision of safety-net or inpatient care for low-income groups or in mortality among low-income residents of the hospitals' local service areas.The 340B Program has been associated with hospital-physician consolidation in hematology-oncology and with more hospital-based administration of parenteral drugs in hematology-oncology and ophthalmology. Financial gains for hospitals have not been associated with clear evidence of expanded care or lower mortality among low-income patients. (Funded by the Agency for Healthcare Research and Quality and others.).
The Zika Contraception Access Network: a feasibility programme to increase access to contraception in Puerto Rico during the 2016–17 Zika virus outbreak
Authors: Eva Lathrop, Lisa Romero, Stacey Hurst, Nabal Bracero, Lauren B Zapata, Meghan T Frey, Maria I Rivera, Erin N Berry-Bibee, Margaret A Honein, Judith Monroe, Denise J Jamieson
Journal: The Lancet Public Health (2018)

Prevention of unintended pregnancy is a primary strategy to reduce adverse pregnancy and birth outcomes related to Zika virus infection. The Zika Contraception Access Network (Z-CAN) aimed to build a network of health-care providers offering client-centred contraceptive counselling and the full range of reversible contraception at no cost to women in Puerto Rico who chose to prevent pregnancy during the 2016-17 Zika virus outbreak. Here, we describe the Z-CAN programme design, implementation activities, and baseline characteristics of the first 21 124 participants.
Phase Ib study combining ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with CD20-positive B-cell non-Hodgkin lymphoma (NHL).
Authors: Anas Younes, Ian Flinn, Jesus G. Berdeja, Jonathan W. Friedberg, Sara Alberti, Catherine Thieblemont, Franck Morschhauser, Peter Hellemans, Brett Hall, Johan Smit, Donna Skee, Ronald de Vries, Marija Todorovic, Imran Khan, Nele Fourneau, Yasuhiro Oki
Journal: Journal of Clinical Oncology (2013)

8502 Background: Ibrutinib, a first-in-class oral Bruton’s tyrosine kinase inhibitor, has demonstrated single-agent activity in a variety of relapsed or refractory B-cell malignancies with limited toxicity, making it an appropriate drug to combine with standard R-CHOP chemotherapy in patients with previously untreated NHL. Methods: Patients received oral daily dose of ibrutinib (280, 420, or 560 mg) in combination with standard doses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, and vincristine on day 1, and prednisone on days 1 through 5 of each 21-day cycle for up to 6 cycles). The primary objective was to determine the recommended phase 2 dose (RP2D) of ibrutinib in combination with standard R-CHOP (IR-CHOP). The secondary objectives were to assess safety, overall response rate, pharmacokinetics, and pharmacodynamic biomarkers. Results: Seventeen patients (7, 4, and 6 in increasing ibrutinib doses) were enrolled: 59% male, median age 65 (range 46-81) years, diffuse large B-cell lymphoma 47%, mantle cell lymphoma 29% and follicular lymphoma 24%. In the 280 mg cohort, 2 patients had dose-limiting toxicity (DLT): 1 with transient syncope and 1 with periorbital cellulitis; at 560 mg, 1 patient had gastritis (grade 2). The RP2D was established at 560 mg ibrutinib. The most common (≥ 20% of patients) adverse events (AEs) were neutropenia (77%), thrombocytopenia (65%), vomiting (59%), anemia (53%), nausea (47%), fatigue (35%), headache (29%), constipation (24%), diarrhea (24%), and dizziness (24%). To date, 6 patients completed 6 cycles of treatment, and 2 patients discontinued treatment (1 due to noncompliance with the study drug and 1 due to non-DLT AE). At the time of this analysis, of the 10 patients had at least one post baseline tumor, the overall response rate was 100% (7 complete and 3 partial responses). Conclusions: The combination of IR-CHOP has an acceptable safety profile. No new toxicities were noted with adding ibrutinib to R-CHOP. An expansion cohort 560 mg ibrutinib (RP2D) is being opened to further explore the safety and efficacy of IR-CHOP in patients with newly diagnosed diffuse large B-cell lymphomas. Clinical trial information: NCT01569750.
First Report of the Gimema LAL1811 Phase II Prospective Study of the Combination of Steroids with Ponatinib As Frontline Therapy of Elderly or Unfit Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Authors: Giovanni Martinelli, Alfonso Piciocchi, Cristina Papayannidis, Stefania Paolini, Valentina Robustelli, Simona Soverini, Carolina Terragna, Roberto M Lemoli, Fabio Guolo, Paolo Di Bartolomeo, Monia Lunghi, Paolo de Fabritiis, Anna Candoni, Carmine Selleri, Federico Simonetti, Monica Bocchia, Antonella Vitale, Luca Frison, Alessandra Tedeschi, Antonio Cuneo, Massimiliano Bonifacio, Brunangelo Falini, Stefano D'Ardia, Silvia Trappolini, Patrizia Tosi, Piero Galieni, Francesco Fabbiano, Maria Chiara Abbenante, Giovanni Marconi, Chiara Sartor, Michele Cavo, Robin Foà, Paola Fazi, Marco Vignetti, Michele Baccarani
Journal: Blood (2017)
OC-011 A novel population of immunosuppressive cd8 t cells is expanded in patients with decompensated liver disease
Authors: F Lebossé, A Singanayagam, R Nathwani, O Pop, N Kumar, S Mukherjee, Tz Hou, A Quaglia, F Zoulim, J Wendon, M Thursz, A Dhar, W Khamri, C Antoniades, C Gudd
Journal: Gut (2017)

Introduction  Cirrhosis associated immune dysfunction is central to immuneparesis, infection susceptibility and adverse outcome in patients with chronic liver disease (CLD). Whilst defects in innate immune responses are recognised, the role of adaptive immunity in CLD remains unexplored. Regulatory HLADR+ CD8+ T cells are recently shown to possess immunosuppressive properties. Our aims were to determine whether negative regulation of CD8+ T cell responses contribute to impaired antimicrobial responses in CLD.  Method  Circulating CD8 subsets from 33 CLD patients (with chronic cirrhosis, acute decompensation (AD) or acute on chronic liver failure (ACLF)) and 14 healthy controls (HC) were determined using flow cytometry and a panel of phenotypic markers to identify naive, memory (CD45RO, CD45RA, CCR7, CD62L) subsets as well as expression of activation (CD27, CD28), inhibition (CTLA4, PD1) and suppressive (HLADR, CD25, FOXP3) markers. Immunohistochemistry was performed on explant liver tissue (n=8). Functional analyses of CD8+ T cells were performed using anti-CD3 in the presence of allogeneic dendritic cells or CD3/CD28 beads. Suppressive assay were performed using HLA-DR- or + CD8+ T cells in co-culture with autologous CD3/CD28 stimulated PBMCs.  Results  Compared to HC, the proportion of circulating and intrahepatic immunosuppressive HLADR+CD8+ T cells were higher in CLD (mean of 20vs37%;p=0.0002). Immunophenotypic analyses of HLADR+CD8+ T cells identify that these cells are characterised by increased CTLA4 expression compared to HLADR-CD8+ (9.2 vs 0.1%;p in vitro  stimulation but a trend to a higher proliferation (76 vs 84%; p=0.053). Finally,  in vitro  assays show that, contrary to HLADR-CD8+ T cells, HLA-DR+CD8+ T cells could inhibit CD8+ T cells proliferation at different ratio.  Conclusion  Our novel data has identified expansion of a regulatory HLADR-expressing CD8 population in CLD patients. These cells are characterised by an elevated CTLA4 expression that is increased in AD patients, suppression of proliferation and may contribute to infection susceptibility in CLD.  Disclosure of Interest  None Declared
EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice
Authors: Christian Dejaco, Sofia Ramiro, Christina Duftner, Florent L Besson, Thorsten A Bley, Daniel Blockmans, Elisabeth Brouwer, Marco A Cimmino, Eric Clark, Bhaskar Dasgupta, Andreas P Diamantopoulos, Haner Direskeneli, Annamaria Iagnocco, Thorsten Klink, Lorna Neill, Cristina Ponte, Carlo Salvarani, Riemer H J A Slart, Madeline Whitlock, Wolfgang A Schmidt
Journal: Annals of the Rheumatic Diseases (2018)

To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [ 18 F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV.
C-Reactive Protein Promotes Bone Destruction in Human Myeloma By Stimulating Myeloma Cell Production of Osteolytic Cytokines Via the CD32/FcγRII-p38MAPK-Twist Axis
Authors: Jing Yang, Zhiqiang Liu, Huan Liu, Jin He, Jianling Yang, Pei Lin, Qiang Wang, Juan Du, Wencai Ma, Richard E Davis, Robert Z. Orlowski, Jian Hou, Qing Yi
Journal: Blood (2017)
Prevalence of Disclosed Conflicts of Interest in Biomedical Research and Associations With Journal Impact Factors and Altmetric Scores
Authors: Quinn Grundy, Adam G. Dunn, Florence T. Bourgeois, Enrico Coiera, Lisa Bero
Journal: JAMA (2018)

This study estimates the prevalence of conflict of interest disclosures in medical journal articles published in 2016 and associations between disclosures and median journal impact factor and article Altmetric scores.
OCT Biomarkers as Functional Outcome Predictors in Diabetic Macular Edema Treated with Dexamethasone Implant
Authors: Dinah Zur, Matias Iglicki, Catharina Busch, Alessandro Invernizzi, Miriana Mariussi, Anat Loewenstein, Catharina Busch, Zafer Cebeci, Jay Kumar Chhablani, Voraporn Chaikitmongkol, Aude Couturier, Samantha Fraser-Bell, Ermete Giancipoli, Matias Iglicki, Alessandro Invernizzi, Inês Laíns, Anat Loewenstein, Marco Lupidi, Matus Rehak, Patricio Rodriguez, Thais Sousa Mendes, Anna Sala-Puigdollers, Dinah Zur
Journal: Ophthalmology (2017)
Migrant Workers and Their Occupational Health and Safety
Authors: Sally C. Moyce, Marc Schenker
Journal: Annual Review of Public Health (2018)

In 2015, approximately 244 million people were transnational migrants, approximately half of whom were workers, often engaged in jobs that are hazardous to their health. They work for less pay, for longer hours, and in worse conditions than do nonmigrants and are often subject to human rights violations, abuse, human trafficking, and violence. Worldwide, immigrant workers have higher rates of adverse occupational exposures and working conditions, which lead to poor health outcomes, workplace injuries, and occupational fatalities. Health disparities of immigrant workers are related to environmental and occupational exposures and are a result of language/cultural barriers, access to health care, documentation status, and the political climate of the host country. Recommendations on global and local scales are offered as potential solutions to improving the health of immigrant workers.
Elephant in the room
Authors: Daniel M Hartung, Kirbee Johnston, David M Cohen, Thuan Nguyen, Atul A Deodhar, Dennis N Bourdette
Journal: Annals of the Rheumatic Diseases (2018)

We read with interest the article by Aggarwal et al on repository corticotropin injection (RCI) in the treatment of refractory polymyositis and dermatomyositis (PM and DM) published in the Annals of the Rheumatic Diseases .1

The authors, who are well-respected researchers in the field of myositis, have done a good job in conducting a small open-label trial of RCI in the treatment of PM/DM using validated disease activity measures and outcome measures. Whether these patients were truly ‘resistant’ is debatable, since only 3 of the 11 patients were treated with intravenous immunoglobulin (IVIG) …
Abstract #3070: Reduced PIAS3 levels in T47D breast cancer cells promotes epithelial-mesenchymal transition and generates stem-like cells
Authors: Terry Medler, Charles Clevenger
Journal: Cancer Research (2009)

PIAS3 is an E3-like SUMO ligase that alters activity of several transcription factors involved in breast cancer. Our lab has recently shown that PIAS3 is upregulated in primary tumors and may contribute to primary tumor growth in part to its effects on prolactin-mediated signaling. Specifically, overexpression of PIAS3 has been shown to enhance PRL-mediated effects on factors that contribute to proliferation (CyclinD1, CISH) and survival (Bcl-6) while decreasing markers of differentiation (\#946;-casein). In this current study, we show that stable knockdown of PIAS3 in the T47D breast cancer cell line induces epithelial-mesenchymal transition. T47D cells that have reduced PIAS3 levels lose their hallmark cobblestone appearance and become more spindle-shaped with filopodia. Additionally, these cells express low or undetectable levels of the epithelial marker E-cadherin, while expressing high levels of the mesenchymal markers fibronectin and vimentin. We also show that reduced PIAS3 levels generates cells that have properties of stem cells. Approximately 10% of these cells form mammospheres in anchorage-independent conditions, which arise from a single cell. There are an increased number of cells in these mammospheres that are positive for the stem cell marker ALDH1. Furthermore, proteins that have been demonstrated to be indispensible for stem cell maintenance (Oct4 and Sox2) are increased. Finally, a large subset of cells stain CD44+/highCD24-/low, further indicating that reduction of PIAS3 generates stem-like cells. Assays measuring proliferation, migration, and invasion have demonstrated that cells with reduced levels of PIAS3 proliferate, migrate, and invade at a higher rate than normal T47D cells. Analysis of a breast cancer progression microarray containing patient-matched specimens has not only confirmed that PIAS3 is significantly upregulated in primary breast cancer, but has also revealed that PIAS3 is down-regulated in its metastasis. Collectively, our studies point to a dual role of PIAS3 in human breast cancer. Overexpression of PIAS3 appears to have a tumor-promoting effect, in part by driving PRL-induced cellular proliferation and survival. However, subsequent reduction of PIAS3 levels drives EMT and generates stem-like cells, resulting in enhanced migration, invasion, and colonization of distant sites.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3070.
Chimeric Antigen Receptor (CAR) T Cells Specific for CD229: A Potentially Curative Approach for Multiple Myeloma
Authors: Sabarinath Venniyil Radhakrishnan, Tim Luetkens, Sara Yousef, Neelam Bhardwaj, Mary Nicole Steinbach, Janet Weidner, Christa Shorter, Douglas W. Sborov, Djordje Atanackovic
Journal: Blood (2017)
Immune gene expression profiling in children and adults with acute myeloid leukemia identifies distinct phenotypic patterns
Authors: Jayakumar Vadakekolathu, Tasleema Patel, Stephen Reeder, Heidi Schaarschmidt, Marc Schmitz, Martin Bornhäuser, Sarah E. Warren, Tressa Hood, Patrick Danaher, Alessandra Cesano, Joseph M. Beechem, A. Graham Pockley, Sarah K Tasian, Sergio Rutella
Journal: Blood (2017)
Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout
Authors: Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc P. Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard C. Rossier, Edith Hummler
Journal: Journal of the American Society of Nephrology (2018)

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the α ENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of α ENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa + )/low potassium (LK + ) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γ ENaC subunit in the PHA-I phenotype. Nephron-specific γ ENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking α ENaC or β ΕΝaC, an HNa + /LK + diet did not normalize plasma potassium (K + ) concentration or increase NCC activation. However, when K + was eliminated from the diet at the time that γ ENaC was deleted, plasma K + concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced β ENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K + concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na + balance in γ ENaC-deficient mice.
The use of the Vulnerable Elders Survey (VES-13) geriatric screening tool for selecting elderly patients for adjuvant chemotherapy.
Authors: satish kumar, Paul Lewis, Rachel Jones, Gianfillipo Bertelli, John Wagstaff, Robert Leonard
Journal: Cancer Research (2007)

4299   Background: An increasing number of elderly patients are becoming candidates for adjuvant chemotherapy (CT). These patients frequently have co-morbidity that can affect their ability to tolerate this treatment. Tools that are able to predict which patients are likely to experience increased morbidity and mortality would be useful by allowing such patients to be followed more intensively. In this study we have correlated results from the Vulnerable Elders Survey 13 (VES-13) geriatric screening tool with toxicity and mortality in patients > 65 years receiving adjuvant CT.  Methods: Prior to starting chemotherapy patients completed the VES-13 screening tool, the EORTC qlq c-30 v3 quality of life questionnaire (QOLQ). The WHO PS, any co-morbidity and concurrent medications were also recorded. During CT the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3 was used to record toxicity. The QOLQ was repeated half way through and at the end of CT. The data were categorised into VES-13 scores of   3. Differences between the groups were assessed using the Chi square test and correlation between VES-13 and tolerability/ QOLQ were done using Spearman’s coefficient.  Results: 54 patients have been recruited into the study and there have been 2 treatment related deaths. There was a significant correlation between VES-13 scores > 3 and treatment related death (p = 0.01), incidence of grade 3 toxicity (p = 0.047) & discontinuation of treatment (p = 0.001). There was a negative correlation between VES-13 > 3 and physical function domain of QOL throughout CT.  Conclusions: These data suggest that the VES-13 geriatric screening tool is an easy to use & sensitive means of determining which patients are likely to experience increased morbidity and mortality during adjuvant chemotherapy. This information will be useful when discussing risk/benefit ratios with individual patients. This tool will be of value when conducting phase III trials in elderly patients.
Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial
Authors: Elizabeth A Thiele, Eric D Marsh, Jacqueline A French, Maria Mazurkiewicz-Beldzinska, Selim R Benbadis, Charuta Joshi, Paul D Lyons, Adam Taylor, Claire Roberts, Kenneth Sommerville, Boudewjin Gunning, Jacek Gawlowicz, Pawel Lisewski, Maria Mazurkiewicz Beldzinska, Krystyna Mitosek Szewczyk, Barbara Steinborn, Marta Zolnowska, Elaine Hughes, Ailsa McLellan, Selim Benbadis, Michael Ciliberto, Gary Clark, Dennis Dlugos, Francis Filloux, Robert Flamini, Jacqueline French, Michael Frost, Sheryl Haut, Charuta Joshi, Siddarth Kapoor, Sudha Kessler, Linda Laux, Paul Lyons, Eric Marsh, David Moore, Richard Morse, Venkatesh Nagaraddi, William Rosenfeld, Laurie Seltzer, Renée Shellhaas, Joseph Sullivan, Elizabeth Thiele, Liu Lin Thio, David Wang, Angus Wilfong
Journal: The Lancet (2018)
Abstract 14400: Pre-Hospital Delays in Care for STEMI Patients in Mumbai: Challenges and Opportunities
Authors: Farah Noorani, Mason Runge, Sushil Tripathi, Devendra Patil, Charan Lanjewar, Kim Eagle, Prafulla Kerkar
Journal: Circulation (2016)

Introduction: Coronary heart disease is growing at an alarming rate in developing countries. In India, ST-segment elevation myocardial infarction (STEMI) is pervasive and accounts for over 60% of a...