tbuckley/cabot-search huggingface dataset:
Consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection: Public Health England HCV Resistance Group
Authors: Daniel Bradshaw, Jean L Mbisa, Anna Maria Geretti, Brendan J Healy, Graham S Cooke, Graham R Foster, Emma C Thomson, John McLauchlan, Kosh Agarwal, Caroline Sabin, David Mutimer, Peter Moss, William L Irving, Ellie Barnes
Journal: Journal of Infection (2019)
In Vitro Thrombogenicity Testing of Biomaterials
Authors: Steffen Braune, Robert A. Latour, Markus Reinthaler, Ulf Landmesser, Andreas Lendlein, Friedrich Jung
Journal: Advanced Healthcare Materials (2019)

The short- and long-term thrombogenicity of implant materials is still unpredictable, which is a significant challenge for the treatment of cardiovascular diseases. A knowledge-based approach for implementing biofunctions in materials requires a detailed understanding of the medical device in the biological system. In particular, the interplay between material and blood components/cells as well as standardized and commonly acknowledged in vitro test methods allowing a reproducible categorization of the material thrombogenicity requires further attention. Here, the status of in vitro thrombogenicity testing methods for biomaterials is reviewed, particularly taking in view the preparation of test materials and references, the selection and characterization of donors and blood samples, the prerequisites for reproducible approaches and applied test systems. Recent joint approaches in finding common standards for a reproducible testing are summarized and perspectives for a more disease oriented in vitro thrombogenicity testing are discussed.
A budget impact model for biosimilar myeloid growth factors (MGFs) within the Oncology Care Model (OCM): An oncology group practice perspective.
Authors: Ali McBride, Weijia Wang, Edward C. Li, Sanjeev Balu, Kim Campbell
Journal: Journal of Clinical Oncology (2019)

108 Background: Value-based programs, such as the OCM, provide incentives for healthcare providers to lower costs and improve patient outcomes. Use of biosimilar vs. reference MGFs for febrile neutropenia (FN) prophylaxis (Px) has been suggested as one strategy to help practices meet these goals. The purpose of this study is to quantify the potential impact of using biosimilar MGFs on OCM metrics from a US practice perspective. Methods: The budgetary impact of two scenarios of MGF Px for a hypothetical panel of 500 patients in 1 year receiving 6 cycles of FN-risk stratified chemotherapy (CT) was assessed; model inputs for the rates of MGF Px based on FN risk were estimated from the literature. The first scenario compares the projected 1-year total (i.e., drug and administration) costs of using LA-EP2006 (a proposed Sandoz pegfilgrastim biosimilar) vs. reference pegfilgrastim, assuming the same MGF utilization rate within the 500 patients. The second scenario evaluates the cost implications of expanding access to LA-EP2006 for 10% more patients receiving intermediate-FN risk CT and the subsequent impact on MGF costs and FN-related healthcare utilization costs (e.g., emergency visits, hospitalizations, outpatient management). MGF costs were derived from publically available data; healthcare resource utilization and costs were estimated from the literature. Results: For 500 patients receiving CT, 107 were estimated to receive MGF Px, resulting in total costs of $3.02 million (M) for reference pegfilgrastim and $2.42 M for LA-EP2006 with $1.05 M in FN-related healthcare utilization costs. If MGF access (using LA-EP2006) were expanded to 10% more patients receiving intermediate-FN risk CT, 129 patients would receive MGF Px at a cost of $2.91 M; FN-related healthcare costs would decrease by $27,155. Conclusions: Using biosimilar vs. reference pegfilgrastim can help OCM-participating practices reduce their drug costs. Potentially, a practice can address an existing gap in FN prevention by expanding biosimilar MGF access for patients receiving intermediate-FN risk CT, which may help to meet OCM metrics such as reducing hospitalizations and emergency visits.
Abstract 502: Reversible Cardiac Action Potential Recordings to Track Cellular Electrophysiology Over Days
Authors: Viviana Zlochiver, Stacie Edwards, Jonathan A Cook, Rosy Joshi-Mukherjee
Journal: Circulation Research (2019)

Long-term action potential (AP) studies from the same cell site over days in multicellular preparations are currently lacking, thus limiting our understanding of cardiac physiology in development and disease. We recently reported a novel high-throughput platform for label-free AP measurements using multielectrode array (MEA) technology to gain intracellular access by way of electroporation. We hypothesized that multiple reversible electroporations of the same cell site will allow high-resolution recordings of AP waveforms without detrimental effects to the cell membrane. A total of 19 hiPSC-CM constructs on multiwell MEAs were simultaneously electroporated by employing a train of low voltage pulses (1 V, 1 ms, 1 Hz) for 30 s to elicit a transient transformation of field potentials (FPs) to APs. Waveforms were recorded from 12 electrodes per construct for electrophysiological characterization of the network. Recurrent electroporations of the same cell site at 0, 24, 48, 72 and 96 h enabled tracking of the electrophysiological evolution of the AP waveforms (see figure). We analyzed millivolt AP signals 10 s following the end of electroporation before APs reverted to FP signals strongly suggesting cell membrane recovery and network integrity for subsequent recordings. This methodology allows for screening transmembrane APs from cardiomyocyte networks over days. Overall, we present a spatio-temporal model capable of tracking FPs and APs in a non-invasive approach for cardiomyocyte functional maturation, developmental and pharmacological studies.
Array-Based Comparative Genomic Hybridization for Genome-Wide Analysis of DNA Copy Number in Myelodysplastic Syndromes.
Authors: Masashi Sanada, Yasuhito Nanya, Akira Hangaishi, Noriko Hosoya, LiLi Wang, Mineo Kurokawa, Mitsuhiro Omine, Shigeru Chiba, Seishi Ogawa
Journal: Blood (2004)
Large granular lymphocytic leukemia coexists with myeloid clones and myelodysplastic syndrome
Authors: Jibran Durrani, Hassan Awada, Ashwin Kishtagari, Valeria Visconte, Cassandra Kerr, Vera Adema, Yasunobu Nagata, Teodora Kuzmanovic, Sanghee Hong, Bhumika Patel, Aziz Nazha, Alan Lichtin, Sudipto Mukherjee, Yogen Saunthararajah, Hetty Carraway, Mikkael Sekeres, Jaroslaw P. Maciejewski
Journal: Leukemia (2019)
Abstract 163: NFkB Promotes Oxidative Stress-induced Necrosis and Ischemia Reperfusion Injury Through NRF2-ARE Pathway
Authors: Xiaoyun Guo, Yi Chen, Rachel Steinmetz, Siqi Hong, Hui He, Yachang Zeng, Qinghang Liu
Journal: Circulation Research (2019)

Objective: Despite the well-studied pro-survival function of nuclear factor-κB (NFκB), recent studies suggest that NFκB may also play a pathogenic role in myocardial ischemia injury and adverse remodeling. This study aims to define a new pro-cell death role of NFκB in response to oxidative stress and the functional implications in ischemia reperfusion (I/R) injury. Methods and Results: We identified an unexpected pro-cell death role of NFκB in oxidative stress-induced necrosis, and provide new mechanistic evidence that NFκB, in cooperation with HDAC3, negatively regulates NRF2-ARE anti-oxidative signaling through transcriptional silencing. Genetic deletion of NFκB-p65 inhibits, whereas activation of NFκB promotes, oxidative stress-induced cell death and HMGB1 release, a biomarker of necrosis. Moreover, simulated ischemia reperfusion (sI/R) and doxorubicin (Dox) treatment both induce NFκB-luciferase activity in cardiomyocytes, and inhibition of NFκB diminishes sI/R- and Dox- induced necrosis. Importantly, NFκB negatively regulates NRF2-ARE activity and the expression of anti-oxidant proteins. Mechanistically, co-immunoprecipitation reveals that p65 is required for the association between NRF2 and HDAC3 and transcriptional silencing of NRF2-ARE activity. Further, the ability of HDAC3 to repress NRF2-ARE activity is lost in p65-/- cells. The HADC inhibitor TSA and NFκB inhibitor BMS-345541 both increase NRF2-ARE activity and promote cell survival following sI/R. In vivo , NFκB transcriptional activity in the heart is significantly elevated after I/R injury, which is abolished by cardiac-specific deletion of p65. Moreover, ablation of p65 using p65 fl/fl-Nkx-Cre mice reduces myocardial infarct size after acute I/R, and prevents chronic remodeling and contractile dysfunction after myocardial infarction. Conclusions: Our results identified NFκB as a key regulator of oxidative stress-induced necrosis by suppressing the NRF2-ARE anti-oxidant pathway through an HDAC3-dependent mechanism. Ablation of NFκB-p65 attenuates oxidative stress-induced necrosis and I/R injury, suggesting a new pathogenic role of the NFκB pathway, and thus a therapeutic target, in myocardial ischemic injury and remodeling.
Amplification of Drosophila Olfactory Responses by a DEG/ENaC Channel
Authors: Renny Ng, Secilia S. Salem, Shiuan-Tze Wu, Meilin Wu, Hui-Hao Lin, Andrew K. Shepherd, William J. Joiner, Jing W. Wang, Chih-Ying Su
Journal: Neuron (2019)
Improving patient access in radiation oncology from referral to consult.
Authors: Daphne Baracena, Jerry Jeff Jaboin, Michelle Bednar
Journal: Journal of Clinical Oncology (2019)

122 Background: To increase patient access, Oregon Health &amp; Science University set an institution-wide metric for ambulatory clinics to contact the patient within a specified time frame. For our study, we utilized targets of patient contact within three days from the date of referral and of scheduling and resolving referrals within six days. Since the reports for these metrics did not provide detailed reasons for the consult delays, we were unable to assess if these delays were due to pending patient action, provider recommendations, providers’ overbooked schedules, and/or an inefficient intake process. Methods: We targeted two providers’ schedules with the highest consult-to-treatment turnover and determined that 45% of consult delays were due to intake processing. The Department implemented two PDSA cycles: internal metrics were set for 97% of the patients to be contacted within three days and for 100% within six days; and a standardized workflow for the providers’ patient list was provided. Results: After the first PDSA cycle, patient contact within three days declined from 80% to 62% and within six days from 57% to 45%. However, the percent of patients scheduled within six days increased from 61% to 64%. After the second PDSA cycle, patient contact within three days increased to 70% and within six days to 68%. About 76% of referrals were scheduled within those six days. Conclusions: Although patient contact within three days declined from the baseline data for both PDSA cycles, we found that there was a gradual increase in patients being contacted and scheduled within six days, especially after the second PDSA cycle. Despite the progress observed, we did not hit our internal metrics and intend to launch an automated patient list to further improve intake processing.[Table: see text]
Bing Neel Syndrome: Retrospective Australasian Experience of a Rare Treatable Complication of Waldenström Macroglobulinaemia/ Lymphoplasmacytic Lymphoma
Authors: Dipti Talaulikar, Tara Cochrane, John Gibson, Nada Hamad, Phoebe Joy Ho, Samar Issa, Kwok Fiona, Jun Hee Lim, David Simpson, Constantine Tam, Jorge J. Castillo
Journal: Blood (2018)
Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors
Authors: Jawad Bilal, Adam Berlinberg, Irbaz Bin Riaz, Warda Faridi, Sandipan Bhattacharjee, Gilbert Ortega, Mohammad H. Murad, Zhen Wang, Larry J. Prokop, Abdullah A. Alhifany, C. Kent Kwoh
Journal: JAMA Network Open (2019)

The safety profile of interleukin (IL) inhibitors is not well established.To assess the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with IL inhibitors.Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations; Ovid MEDLINE Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus were searched (inception to November 30, 2018).Randomized, placebo-controlled trials that evaluated IL inhibitor therapies in rheumatic diseases and reported safety data were included in the analyses.This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two investigators independently extracted study data and assessed risk of bias and certainty in the evidence. Fixed-effects meta-analysis was conducted to pool odds ratios (ORs) for serious infections, opportunistic infections, and cancers for IL inhibitors vs placebo.The outcomes of interest were the number of serious infections, opportunistic infections, and cancers in individuals receiving IL inhibitor therapies compared with placebo.In this meta-analysis, 74 studies comprising 29 214 patients (24 236 patients for serious infections, 9998 for opportunistic infections, and 21 065 for cancer [number of patients overlaps for each outcome]) were included. Patients receiving IL inhibitors had a higher risk of serious infections (OR, 1.97; 95% CI, 1.58-2.44; P < .001, I2 = 0%; high certainty), opportunistic infections (OR, 2.35; 95% CI, 1.09-5.05; P = .03, I2 = 0%; moderate certainty), and cancer (OR, 1.52; 95% CI, 1.05-2.19; P = .03, I2 = 11%; moderate certainty).The risk of serious infections, opportunistic infections, and cancer appears to be increased in patients with rheumatologic diseases who are treated with IL inhibitors compared with placebo.
Annals for Hospitalist Inpatient Notes - Rethinking the Role of Functional Capacity in Preoperative Risk Stratification
Authors: Duminda N. Wijeysundera, Karim S. Ladha
Journal: Annals of Internal Medicine (2019)

Assessment of functional capacity is generally considered to be an integral part of preoperative risk stratification for major surgery. Here, the authors weigh the pros and cons of unstructured que...
Long-Term Use of Deferiprone Enhances Significantly the Left Ventricular Ejection Function in Thalassemia Major
Authors: Aurelio Maggio, Marcello Capra, Liana Cuccia, Francesco Gagliardotto, Paolo Rigano, Giusi Calvaruso, Lorella Pitrolo, Luciano Prossomariti, Aldo Filosa, Maria Antonietta Romeo, Vincenzo Caruso, Crocetta Argento, Calogera Gerardi, Saveria Campisi, Pietro Violi, Paolo Cianciulli, Michele Rizzo, Domenico Giuseppe D'Ascola, Ketty Perrotta, Carmelo Fidone, Gaetano Roccamo, Antonella Carollo, Luciana Rigoli, Francesca Valeria Commendatore, Roberto Giugno, Rossellina Rosso, Rocca Cingari, Maria Concetta Galati, Antonella Quarta, Angela Ciancio, Angela Vitrano
Journal: Blood (2011)
Association of Maternal Gastric Bypass Surgery With Offspring Birth Defects
Authors: Martin Neovius, Björn Pasternak, Ingmar Näslund, Jonas Söderling, Kari Johansson, Olof Stephansson
Journal: JAMA (2019)

Association of Maternal Gastric Bypass Surgery With Offspring Birth DefectsMaternal body mass index (BMI) and glucose control are associated with offspring birth defects. 1,2 Bariatric surgery results in weight loss and glucose normalization but is also associated with nutritional deficiencies and substance abuse, 3 which could cause birth defects as hypothesized based on case series. 4 It could be unethical to randomize pregnant women to bariatric surgery, and it is impossible to perform a randomized trial requiring pregnancy after alternative interventions.We conducted a nationwide matched cohort study to investigate major birth defect risk in infants born to women after gastric bypass surgery vs infants born to comparable women without bariatric surgery.Methods | We identified live-born singleton infants in the Swedish Medical Birth Register born in 2007 to 2014 to women Table.Maternal Characteristics for Singleton Infants Born to Women With Gastric Bypass Surgery and Matched Controls Characteristics a Women With Gastric Bypass Surgery (n = 2921) Matched Controls (n = 30 573) b Standardized Difference Maternal age, mean (SD), y 31 (5) 31 (6) 0.028 Maternal body mass index, No. (%) c 30-30.9 6 (0.2) 63 (0.2) 0.000 31-31.96 (0.2) 63 (0.2) 0.000 32-32.97 (0.2) 73 (0.2) 0.000 33-33.9 17 (0.6) 178 (0.6) 0.000 34-34.939 (1.3) 408 (1.3) 0.
Vascularized and Innervated Skeletal Muscle Tissue Engineering
Authors: Jordana Gilbert‐Honick, Warren Grayson
Journal: Advanced Healthcare Materials (2019)

Volumetric muscle loss (VML) is a devastating loss of muscle tissue that overwhelms the native regenerative properties of skeletal muscle and results in lifelong functional deficits. There are currently no treatments for VML that fully recover the lost muscle tissue and function. Tissue engineering presents a promising solution for VML treatment and significant research has been performed using tissue engineered muscle constructs in preclinical models of VML with a broad range of defect locations and sizes, tissue engineered construct characteristics, and outcome measures. Due to the complex vascular and neural anatomy within skeletal muscle, regeneration of functional vasculature and nerves is vital for muscle recovery following VML injuries. This review aims to summarize the current state of the field of skeletal muscle tissue engineering using 3D constructs for VML treatment with a focus on studies that have promoted vascular and neural regeneration within the muscle tissue post-VML.
Sequence Analysis of MPL Exon 10 of ET and MF JAK2 V617F Negative Patients Reveals a New Mutation
Authors: Celeste Bento, Marta Duarte, Helena Almeida, Cristina Menezes, Alexandra Estevinho, Margarida Coucelo, Jaspal Kaeda, Maria Leticia Ribeiro
Journal: Blood (2008)
Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL
Authors: Kevin J. Curran, Steven P. Margossian, Nancy A. Kernan, Lewis B. Silverman, David A. Williams, Neerav Shukla, Rachel Kobos, Christopher J. Forlenza, Peter Steinherz, Susan Prockop, Farid Boulad, Barbara Spitzer, Maria I. Cancio, Jaap Jan Boelens, Andrew L. Kung, Yasmin Khakoo, Victoria Szenes, Jae H. Park, Craig S. Sauter, Glenn Heller, Xiuyan Wang, Brigitte Senechal, Richard J. O’Reilly, Isabelle Riviere, Michel Sadelain, Renier J. Brentjens
Journal: Blood (2019)

Chimeric antigen receptor (CAR) T cells have demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We undertook a multicenter clinical trial to determine toxicity, feasibility, and response for this therapy. A total of 25 pediatric/young adult patients (age, 1-22.5 years) with R/R B-ALL were treated with 19-28z CAR T cells. Conditioning chemotherapy included high-dose (3 g/m2) cyclophosphamide (HD-Cy) for 17 patients and low-dose (≤1.5 g/m2) cyclophosphamide (LD-Cy) for 8 patients. Fifteen patients had pretreatment minimal residual disease (MRD; <5% blasts in bone marrow), and 10 patients had pretreatment morphologic evidence of disease (≥5% blasts in bone marrow). All toxicities were reversible, including severe cytokine release syndrome in 16% (4 of 25) and severe neurotoxicity in 28% (7 of 25) of patients. Treated patients were assessed for response, and, among the evaluable patients (n = 24), response and peak CAR T-cell expansion were superior in the HD-Cy/MRD cohorts, as compared with the LD-Cy/morphologic cohorts without an increase in toxicity. Our data support the safety of CD19-specific CAR T-cell therapy for R/R B-ALL. Our data also suggest that dose intensity of conditioning chemotherapy and minimal pretreatment disease burden have a positive impact on response without a negative effect on toxicity. This trial was registered at www.clinicaltrials.gov as #NCT01860937.
Patient and physician perceptions: Importance and documentation of patient priorities in treatment planning and decision-making.
Authors: Ellen Miller-Sonet, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2019)

224 Background: The National Academies of Medicine prioritizes patient’s needs, values, and preferences when patient’s and care teams make treatment decisions. However, the collection of this patient information is not part of the formal clinical intake process, nor are pertinent questions included in EHR templates. Methods: Surveys were conducted of cancer patients and cancer physicians to understand perceptions on whether patients’ quality of life priorities (e.g work, hobbies, key events, household responsibilities) are discussed, documented and reflected in treatment plans. Physicians were recruited via a market research panel. Patients were recruited from the Cancer Care data base via an email request to complete an online survey. Results: From February to October, 2018, 310 cancer patients and 109 cancer physicians completed surveys. Cancer patients were mostly female, 91% had been diagnosed in the last year, 61% had breast cancer, and 55% were stage 1 or 2. Among physicians, 88% self-identified as trained in oncology, 33% practice at academic centers, 51% in community practices, 34% from the Northeast, 21% the Southeast, and 25% the Midwest. Most patients (62%) said it was very/extremely important their doctor know their priorities. Most physicians (66%) report they most of the time/always know patients’ personal quality of life priorities before finalizing treatment plans, and 62% say this information has a large/major impact on recommendations. However, only 40% of patients report having this conversation before treatment started. Although 76% of doctors said they discussed what is important to patients most of the time or always, only 60% report it is documented, usually in the social history or notes fields. Only 36% of patients are sure this information is entered into their medical record. Conclusions: Cancer patients want their doctors to know what is important to them, and physicians agree. However, documentation is often relegated to narrative notes fields in the EHR. Considering the key role patients’ priorities should play in treatment planning, there need to be standardized collection tools so this information can be timely collected and shared.