tbuckley/cabot-search huggingface dataset:
Efficacy and Updated Safety Analysis of a Safety Run-in Cohort from Griffin, a Phase 2 Randomized Study of Daratumumab (Dara), Bortezomib (V), Lenalidomide (R), and Dexamethasone (D; Dara‐Vrd) Vs. Vrd in Patients (Pts) with Newly Diagnosed (ND) Multiple Myeloma (MM) Eligible for High‐Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT)
Authors: Peter M. Voorhees, Cesar Rodriguez, Brandi Reeves, Nitya Nathwani, Luciano J Costa, Yana Lutska, Daniela Hoehn, Huiling Pei, Jon Ukropec, Ming Qi, Thomas Lin, Paul Richardson
Journal: Blood (2018)
"Duration of Deep Molecular Response" Has Most Impact on the Success of Cessation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukemia - Results from the EURO-SKI Trial
Authors: Susanne Saussele, Johan Richter, Joelle Guilhot, Henrik Hjorth-Hansen, Antonio Medina de Almeida, Jeroen J. W. M. Janssen, Jiri Mayer, Perttu Koskenvesa, Panayiotis Panayiotidis, Ulla Olsson-Strömberg, Juan Luis Steegmann, Hanne Vestergaard, Hans Ehrencrona, Veli Kairisto, Kateřina Machová Poláková, Martin Müller, Satu Mustjoki, Marc G. Berger, Philippe Rousselot, Martine Escoffre-Barbe, Gabriel Etienne, Jolanta Dengler, Françoise Rigal-Huguet, Nikolas von Bubnoff, Hana Klamova, Edgar Faber, François Guilhot, Kourosh Lotfi, Delphine Rea, Tim H. Brümmendorf, Gorgine de Greef, Leif Stenke, Franck Emmanuel Nicolini, Laurence Legros, Andreas Burchert, Jaroslava Voglová, Aude Charbonnier, Emmanuel Gyan, Maria-Elisabeth Goebeler, Peter E. Westerweel, Andreas Hochhaus, Markus Pfirrmann, Francois-Xavier Mahon
Journal: Blood (2017)
The iR2 Regimen(Ibrutinib, Lenalidomide, and Rituximab) Is Active with a Manageable Safety Profile in Patients with Relapsed/Refractory Non-Germinal Center-like Diffuse Large B-Cell Lymphoma
Authors: Radhakrishnan Ramchandren, Peter Johnson, Nilanjan Ghosh, Jia Ruan, Kirit M. Ardeshna, Roderick Johnson, Gregor Verhoef, David Cunningham, Sven de Vos, Shireen Kassam, Luis Fayad, John Radford, Sarah Bailly, Fritz Offner, David Morgan, Javier Munoz, Jerry Ping, Melannie Co, Jutta K. Neuenburg, Andre Goy
Journal: Blood (2018)
Association Between Market Competition and Prices of Generic Topical Dermatology Drugs
Authors: David G. Li, Cara Joyce, Arash Mostaghimi
Journal: JAMA Dermatology (2018)

During the last decade, increases in drug prices for commonly prescribed dermatologic medications have outpaced the rate of inflation, national health care growth, and reimbursements. Among nondermatologic medications, studies have shown a role for robust generic market competition in reducing drug prices. The association between competition and the costs of topical dermatologic generic drugs has not been evaluated.To characterize the association between changes in drug price and the number of US Food and Drug Administration (FDA)-approved manufacturers among the most commonly used topical dermatologic generic products.This retrospective cost analysis of the most commonly prescribed topical dermatologic generic drugs used cumulative annual claims data from the Medicare Part D Prescriber Public User File to identify 597 dermatologist-prescribed drugs with more than 10 claims. The number of manufacturers and the price per unit were identified from the FDA Orange Book and the National Average Drug Acquisition Cost (NADAC) database, respectively, for 2013 through 2016. Drugs that were nondermatologic, were not topically administered, were missing NADAC data, were lacking a generic formulation, or had fewer than 400 claims were excluded.Primary outcomes included per-unit drug price and number of FDA-approved manufacturers. Pricing measures were adjusted for inflation and are reported in 2016 dollars.The present analysis included 116 topical dermatologic generic formulations, representing 70.5% of the total Medicare Part D dermatologist-coded claims from 2015. Drug formulations with 1 to 2 manufacturers during the study period sustained a median percentage increase in price of 12.7%, whereas those with more than 6 manufacturers had a median percentage decrease in price of 20.5%. Formulations with 1 to 2 manufacturers had a 20.6%, 19.5%, and 33.2% higher percentage increase in price than those with 3 to 4 manufacturers, 5 to 6 manufacturers, and more than 6 manufacturers, respectively. There was a statistically significant inverse association between the percentage change in drug price and median number of manufacturers (Spearman correlation coefficient, -0.26; P = .005).The negative association between the change in drug price and the median number of manufacturers of generic topical dermatologic drugs indicates a role for market competition in controlling the costs of generic drug prices within dermatology. These findings support policies that facilitate robust market competition among topical dermatologic generic drugs produced by a limited number of manufacturers.
Concurrent Genetic Alterations Predict the Progression to Target Therapy in EGFR-Mutated Advanced NSCLC
Authors: Youjin Kim, Boram Lee, Joon Ho Shim, Se-Hoon Lee, Woong-Yang Park, Yoon-La Choi, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park
Journal: Journal of Thoracic Oncology (2018)
Abstract 19325: Hemodynamic Effects of Guideline-compliant Asynchronous vs. Synchronous Ventilations During Cardiopulmonary Resuscitation in a Porcine Model
Authors: Christiane Skåre, Theresa Olasveengen, Jo Kramer-Johansen, Fredrik Nordum, Eriksen Morten, Per Andreas Norseng, Marianne Skjerven-Martinsen, Lars Wik
Journal: Circulation (2015)

Background: Current guidelines for cardiopulmonary resuscitation (CPR) emphasize reducing pauses in chest compressions, and suggest ventilating with 1 second inspiration time and with enough volume to produce normal chest rise 10 times per minute. No specific advice is provided on how ventilations should be timed with ongoing chest compressions. We have compared hemodynamic effects of ventilating synchronously vs. asynchronously during chest compressions in a porcine model. Methods: Twenty anaesthetized domestic pigs (approx. 30 kg) were randomized into two groups; synchronous vs. asynchronous ventilation. Ventricular fibrillation is induced electrically and left for 2 minutes before initiation of basic 30:2 CPR for 4 minutes. CPR with continuous mechanical chest compressions was continued for another 8 minutes with either synchronous or asynchronous ventilation before defibrillation was attempted. Aortic, right atrial and intracerebral pressures, carotid and cerebral blood flow and cardiac output (thermodilution) were measured. Airway monitoring included capnography and spirometry. Results: Hemodynamics, blood gas analysis and airway pressures were similar for both groups during baseline and 30:2 CPR periods. The asynchronous group had higher median peak inspiratory airway pressure (94 vs. 57 cm H 2 O, p&lt;0.001) and lower EtCO 2 (1.8 vs. 3.5 kPa, p=0.023) compared to synchronous group during the last 30 seconds of CPR (after 12 minutes). Asynchronous group also had higher pH (7.55 vs. 7.35, p&lt;0.001), lower pCO 2 (2.4 vs. 4.7, p&lt;0.001) and higher pO 2 (62.1 vs. 29.4, p&lt;0.001) compared to synchronous group. There were no significant differences in any of the measured hemodynamic variables between the two groups with similar coronary and cerebral perfusion pressures. ROSC was achieved in 5/10 vs. 3/10 animals in the synchronous and asynchronous groups, respectively. Conclusion: Synchronous and asynchronous ventilation during mechanical chest compressions provide similar hemodynamics, but guideline-compliant asynchronous ventilation yields significantly higher airway pressures and hyperventilation. Implications for lung injury need to be assessed.
Testing an adherence-improving app for patients with psoriasis
Authors: M.T. Svendsen, F. Andersen, K.H. Andersen, A. Pottegård, H. Johannessen, S. Möller, B. August, S.R. Feldman, K.E. Andersen
Journal: British Journal of Dermatology (2018)

Psoriasis is a common chronic inflammatory skin disease which causes red, scaly plaques (patches of skin), often on the knees, elbows, scalp and trunk. Psoriasis can have a negative impact on patients’ quality of life, and additionally creates a ‘socioeconomic burden’ due to healthcare costs, time off work, etc. Topical calcipotriol with corticosteroids are a recommended first treatment of mild‐to‐moderate psoriasis, but many patients ‐ for many different reasons ‐ do not apply the creams or ointments as prescribed. This study investigated if the use of a patient‐supporting applications for smartphones (apps) could improve patients' use of a topical (applied to the skin) drug (calcipotriol/betamethasone dipropionate combination in a cutaneous foam) and in addition reduce severity of psoriasis and improve quality of life short‐ and long‐term. Danish dermatologists conducted a trial at a dermatology clinic at Odense University Hospital in Denmark. 134 patients were included and allocated to either use the drug (66 patients) or to use the drug together with support from an app (68 patients) for a 4‐week period. The app provided once‐daily compulsory treatment reminders and was also able to monitor if patients were using their medication, through an electronic‐monitor chip mounted on top of the foam dispenser. The information was synchronized via Bluetooth® to the patient's smartphone. 91% of the patients returned for all follow‐up visits during a half‐year period. This controlled trial showed that patients using the app significantly improved use of the medication in the 4‐week period and had a short‐term reduction in severity of psoriasis. The authors concluded that apps have potential to improve psoriasis patients’ use of topical medications.
Understudied populations with hepatitis C
Authors: Doris B. Strader
Journal: Hepatology (2002)

Managing patients with hepatitis C virus (HCV) infection consists primarily of antiviral treatment, currently with peginterferon and ribavirin. Unfortunately, treatment recommendations derive largely from trials that have focused on highly selected patient populations. As a consequence of the strict inclusion and exclusion criteria in these studies, more than half of all HCV-infected patients would be ineligible for enrollment. Even among the selected patients enrolled into studies, only 50% achieve a sustained virological response (SVR). Patients not eligible for current therapies include those with mild disease and normal alanine aminotransferase (ALT) levels, patients with advanced and decompensated liver disease, children, the elderly, patients with ongoing or recent alcohol and substance abuse, renal disease, human immunodeficiency virus (HIV) infection, severe psychiatric or neurologic illness, autoimmune disorders, solid organ transplant, and other significant comorbid conditions. Because these patients have been excluded from most clinical trials, little is known about the safety or efficacy of therapy in these populations. The expense and side effects of therapy are also an impediment to treatment of patients who are on public assistance, in prisons, and in institutions. Clearly, new efforts and new approaches are needed to expand the eligibility for antiviral therapy of hepatitis C and make treatment more available for understudied populations with this disease.
THU0068 Identification and verification of biomarker candidates for monitoring rheumatoid arthritis activity by mass spectrometry
Authors: L. González-Rodríguez, V. Calamia, P. Fernández-Puente, C. Ruiz-Romero, L. Lourido, M. Camacho-Encina, A. Juliá, A. Fernández-Nebro, J. Tornero, S. Marsal, F.J. Blanco
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a long-lasting inflammatory autoimmune disorder that ultimately leads to the destruction of joint architecture. The activity of this disease is measured by the assessment of clinical symptoms. <h3>Objectives</h3> To apply a proteomic strategy to find serum biomarkers able to discriminate patients with different RA activities. <h3>Methods</h3> To facilitate the complex measurement of serum by proteomics, a simple, fast and reproducible albumin-specific depletion method using ethanol was optimised and applied to the samples employed in this study. 80 samples from the IMID consortium, classified according to the DAS28 score into low activity<sup>40</sup> and high activity<sup>40</sup> were analysed by mass spectrometry. Four independent pools of the high RA activity samples (10 samples per pool) and 4 pools of the low RA activity samples were firstly albumin-depleted, and then the remnant serum proteins were digested and differentially labelled with iTraq 8-plex reagents. Subsequently, the 8 labelled pools were combined and cleaned using StageTips-C18. Finally, the pool mixture was fractionated by HPLC (Zorbax-C18) and the resulting fractions were analysed by nanoLC-MS/MS using MALDI-TOF/TOF, TripleTOF and LTQ-Orbitrap. <h3>Results</h3> The mass spectrometry analysis led to the identification of 186 proteins. In this screening step, the abundance of 9 proteins was found to be significantly different between patients with high (H) and low (L) RA activity. Orthogonal experiments, using Western Blot, protein bead arrays and Multiple Reaction Monitoring (MRM) with synthetic heavy-labelled peptides, were conducted in order to verify some of these these biomarker candidates of RA activity. The results obtained from the verification phase, conducted by MRM on 50 samples from the same cohort, show a decrease of Apolipoprotein B (ratio H/L=0.84, p=0.00), Histidine Rich Glycoprotein (ratio H/L=0.86, p=0.01) and Plasma protease C1 inhibitor (ratio H/L=0.84, p=0.02). Furthermore, this verification phase shows also an increase of Haptoglobin (ratio H/L=1.34, p=0.01) and Serum Amyloid A1 (ratio H/L=1.64, p=0.05), in accordance with that observed in the screening. These proteins are related with the RA process and the effects caused by this type of disease (inflammation and immune disorder in joints). <h3>Conclusions</h3> In this proteomic study, 5 proteins were found to be quantitatively altered between patients with high and low RA activity using shotgun and targeted mass spectrometry. <h3>Disclosure of Interest</h3> None declared
Abstract 21073: Succinate Dehydrogenase Assembly Factor 1 Regulates Mitochondrial Reserve Respiratory Capacity
Authors: Yong Heui Jeon, Jessica Pfleger, Minzhen He, Maha Abdellatif
Journal: Circulation (2017)

Under normal conditions, the myocyte runs on a fraction of its mitochondrial bioenergetics’ capacity, where the difference between the maximum respiratory capacity and basal respiratory capacity constitutes the reserve respiratory capacity (RRC). We have shown that the RRC allows the cell to respond to an increase in energy demand by promptly increasing supply, avoiding an “ATP crisis”. Our objective is to understand the source and mechanism of regulation of the RRC, which would allow us to augment it during increases in energy demand. Our data show that activation of AMP-activated kinase (AMPK) by AICAR or adiponectin, increases RRC (1.34-fold to 1.9-fold) in a substrate and Sirt3-dependent fashion, whereas, the level of the RRC positively correlates with cell survival. We have identified complex II (cII, or succinate dehydrogenase complex) as the source of RRC, as its inhibition completely abrogates the reserve with no significant effect on basal oxygen consumption rates (OCR). In corroboration, disassembly of cII via knockdown of succinate dehydrogenase assembly factor 1 (Sdhaf1; mutated in infantile mitochondrial disease), also completely abrogates RRC, as higher doses induce cell death and reactive oxygen species (ROS) production. Conversely, over-expression of Sdhaf1 increases RRC (1.2-1.5-fold) during normoxia, and after non-lethal hypoxia (2 to 6-fold). Moreover, a unique acetylation-resistant Sdhaf1 mutant, has a more robust effect on RRC (4 to10-fold). We were further able to confirm that overexpression of Sdhaf1 or Sirt3 in cardiac myocytes reduced hypoxia-induced disassembly of cII. In summary, our data suggest that the RRC increases the survivability of myocytes after non-lethal periods of hypoxia, and can be manipulated by factors that regulate Sdhaf1 and assembly of cII.
Abstract 16262: Chronic Obstructive Pulmonary Disease Increases the Risk of New-Onset Atrial Fibrillation and Mortality of Patients With Atrial Fibrillation Especially Without Beta Blocker Use
Authors: Shinjeong Song, Pil-Sung Yang, Tae-Hoon Kim, Jae-Sun Uhm, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung
Journal: Circulation (2017)

Background: The relationship between the incidence of AF and comorbid chronic obstructive pulmonary disease (COPD) is unclear. And the risk of stroke or mortality associated with COPD in patients w...
<i>Notes from the Field:</i> Intestinal Colonization and Possible Iatrogenic Botulism in Mouse Bioassay–Negative Serum Specimens — Los Angeles County, California, November 2017
Authors: Umme-Aiman Halai, Dawn Terashita, Moon Kim, Nicole Green, Suzanne R. Kalb, Kevin Chatham-Stephens, Sharon Balter
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Mouse bioassay is the standard test for botulinum neurotoxin detection. However, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry testing can be 10–100 times more sensitive than MBA but is not yet widely available.
Abstract 14809: Impact of Tricuspid Regurgitation in Patients Undergoing TAVR for Low Flow Low Gradient Severe Aortic Stenosis
Authors: Mihir Barvalia, Rajiv Tayal, Lilia Uralsky, Marc Cohen, Mark Russo, Bruce Haik, Chunguang Chen
Journal: Circulation (2017)

Introduction: Tricuspid valve regurgitation (TR) is often not taken into consideration in pre procedural risk assessment of patients undergoing transcatheter aortic valve replacement (TAVR); thus i...
Maternal Gestational Diabetes Mellitus, Type 1 Diabetes, and Type 2 Diabetes During Pregnancy and Risk of ADHD in Offspring
Authors: Anny H. Xiang, Xinhui Wang, Mayra P. Martinez, Darios Getahun, Kathleen A. Page, Thomas A. Buchanan, Klara Feldman
Journal: Diabetes Care (2018)

To examine the relative importance of maternal preexisting type 1 diabetes (T1D), preexisting type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) on risk of attention deficit/hyperactivity disorder (ADHD) in offspring.This retrospective birth cohort study included 333,182 singletons born in 1995-2012 within Kaiser Permanente Southern California hospitals. Children were prospectively followed through electronic medical records from age 4 years. Relative risks of ADHD associated with diabetes exposures in utero were estimated by hazard ratios (HRs) using Cox regression with adjustment for potential confounders. For GDM, timing of exposure was evaluated by gestational age at diagnosis and severity was assessed by the need for antidiabetes medication treatment during pregnancy.A total of 37,878 (11.4%) children were exposed to diabetes (522 exposed to T1D, 7,822 T2D, and 29,534 GDM). During a median of 4.9 years (interquartile range 2.2, 9.6) of follow-up after age 4 years, 17,415 (5.2%) children were diagnosed with ADHD. ADHD risk was not associated with GDM taken as a whole (P = 0.50) or with gestational age at GDM diagnosis (P = 0.16). However, the risk was significantly greater for the GDM requiring versus not requiring antidiabetes medications (P < 0.001). Compared with children unexposed to diabetes, the adjusted HRs for ADHD in children were 1.57 (95% CI 1.09-2.25) for exposure to T1D, 1.43 (1.29-1.60) for T2D, 1.26 (1.14-1.41) for GDM requiring antidiabetes medications, and 0.93 (0.86-1.01) for GDM not requiring medications.The hierarchy of risks suggests that severity of maternal diabetes (T1D vs. T2D vs. GDM requiring antidiabetes medications) influences the risk of ADHD in offspring of mothers with diabetes.
Infographic. The Adductor Strengthening Programme prevents groin problems among male football players
Authors: Joar Harøy, David Pope, Benjamin Clarsen, Espen Guldahl Wiger, Mari Glomnes Øyen, Andreas Serner, Kristian Thorborg, Per Hölmich, Thor Einar Andersen, Roald Bahr
Journal: British Journal of Sports Medicine (2018)

Groin injuries represent a considerable problem in male football, accounting for 4% to 19% of all time-loss injuries.1 At the elite level, 14% to 17% of all players incur a groin injury causing time-loss each season.2 During a period with match congestion, 59% of men reported at least one episode with 37 …
Low Dose of Human scFv-Derived BCMA-Targeted CAR-T Cells Achieved Fast Response and High Complete Remission in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Songfu Jiang, Jie Jin, Siguo Hao, Min Yang, Linjun Chen, Huaying Ruan, Jun Xiao, Wei Wang, Zonghai Li, Kang Yu
Journal: Blood (2018)
First report of a novel HIV-1 recombinant form (CRF100_01C) comprising CRF01_AE and C among heterosexuals in Yunnan, China
Authors: Yue Feng, Chunyue Zhang, Mi Zhang, Li Gao, Jing Miao, Yuanyuan Jia, Xingqi Dong, Xueshan Xia
Journal: Journal of Infection (2018)
One-Year Update of a Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Patients (Pts) with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM): Alcyone
Authors: Meletios A Dimopoulos, Maria-Victoria Mateos, Michele Cavo, Kenshi Suzuki, Andrzej Jakubowiak, Stefan Knop, Chantal Doyen, Paulo Lucio, Zsolt Nagy, Polina Kaplan, Ludek Pour, Mark Cook, Sebastian Grosicki, Andre H Crepaldi, Anna Marina Liberati, Philip Campbell, Tatiana Shelekhova, Sung-Soo Yoon, Genadi Iosava, Tomoaki Fujisaki, Mamta Garg, Christopher Chiu, Jianping Wang, Anupa Kudva, Rachel Kobos, Susan Wroblewski, Ming Qi, Jesus F San-Miguel, Joan Bladé
Journal: Blood (2018)