tbuckley/cabot-search huggingface dataset:
Applying Academic Detailing and Process Change to Promote Choosing Wisely—Reply
Authors: Anna L. Parks, Patrick G. O'Malley
Journal: JAMA Internal Medicine (2017)

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Dose-Dense Induction Followed by Autologous Stem Cell Transplant (ASCT) as 1st Line Treatment in Peripheral T-Cell Lymphomas (PTCL) - A Phase II Study of the Nordic Lymphoma Group (NLG).
Authors: Francesco d’Amore, Thomas Relander, Grete Lauritzsen, Esa Jantunen, Hans Hagberg, Harald Anderson, Eva Cavallin-Ståhl, Harald Holte, Anders Østerborg, Mats Merup, Mads Hansen, Ragnar Telhaug, Martin Erlanson, Outi Kuittinen, Ole Gadeberg, Jan Delabie, Christer Sundström, Elisabeth Ralfkiær, Martine Vornanen, Charlotte B. Jensen
Journal: Blood (2006)
The effect of carfilzomib (CFZ) in patients (Pts) with bortezomib (BTZ)-naive relapsed or refractory multiple myeloma (MM): Updated results from the PX-171-004 study.
Authors: A. K. Stewart, J. L. Kaufman, A. J. Jakubowiak, S. Jagannath, V. Kukreti, K. T. McDonagh, M. Alsina, N. J. Bahlis, A. Belch, N. Y. Gabrail, F. J. Reu, J. Matous, D. H. Vesole, R. Z. Orlowski, L. A. Kunkel, M. Le, P. Lee, M. Sebag, M. Wang, R. Vij
Journal: Journal of Clinical Oncology (2011)

8026 Background: CFZ, a selective epoxyketone proteasome inhibitor, has potent, sustained action and lacks many BTZ-associated off-target activities. Durable activity has been observed in pts with advanced relapsed/refractory (R/R) MM, including those whose disease progressed on a BTZ-containing regimen. PX-171-004 is an ongoing phase (ph) II study of single-agent CFZ in pts with relapsed MM following 1–3 prior regimens. Here we present updated response, toxicity, and duration of response (DOR) data on BTZ-naive pts treated on this study. Methods: Pts in 2 sequential cohorts (Cohort 1 and Cohort 2) received IV CFZ on Days 1, 2, 8, 9, 15, 16 of every 28-day cycle (C), for up to 12 C. Both cohorts received 20 mg/m2 in C1; Cohort 2 dose escalated to 27 mg/m2 for C2–12. Primary endpoint was overall response rate (ORR) per IMWG criteria. Secondary endpoints were clinical benefit response (CBR), progression-free survival (PFS), DOR, overall survival (OS), time to progression (TTP), and safety. Results: 123 BTZ-naive pts were response-evaluable. Prior therapies included thalidomide (58%), lenalidomide (59%), alkylating agents (82%), and stem cell transplant (73%). 44 patients had disease refractory to the last prior therapy. Median TTP of 8.3 mo and median DOR of 13.1 mo were observed for Cohort 1; median TTP and DOR for Cohort 2 have not been reached. The most common grade (G) 3/4 AEs (all cause) were anemia (13%), lymphopenia (13%), pneumonia (13%), neutropenia (12%), and thrombocytopenia (11%). Treatment-emergent peripheral neuropathy (PN) was infrequent (18%) and mild. Only 1 case of G3 PN was observed. Overall, 49 pts (~40%) completed 12 C (~1 yr) and 27 pts continued CFZ therapy on an extension protocol. Conclusions: At the recommended phase III dose of CFZ, the 53% ORR is noteworthy for a single-agent regimen. Moreover, prolonged CFZ treatment is well-tolerated, with ~ 40% of pts completing 12 C and ~22% continuing treatment beyond 1 yr. Best response Cohort 1 N=59 20 mg/m2 n (%) Cohort 2 N=64 20/27 mg/m2 n (%) CR 2 (3) 1 (2) VGPR 8 (14) 17 (27) PR 15 (25) 16 (25) MR 10 (17) 6 (9) SD 13 (22) 12 (19) ORR (CR + VGPR + PR) 25 (42) 34 (53) CBR (ORR + MR) 35 (59) 40 (63)
Long-Term Outcome of Anemic Non Del 5q Lower-Risk MDS Refractory to or Relapsing After Erythropoiesis Stimulating Agents (ESAs)
Authors: Charikleia Kelaidi, Sophie Park, Rosa Sapena, Odile Beyne-Rauzy, Valérie Coiteux, Norbert Vey, Aspasia Stamatoullas, Bachra Choufi, Jacques Delaunay, Marie-Pierre Gourin, Stéphane Cheze, Christophe Ravoet, Augustin Ferrant, Martine Escoffre-Barbe, Linda Aljassem, Emmanuel Raffoux, Raphael Itzykson, Lionel Ades, Francois Dreyfus, Pierre Fenaux
Journal: Blood (2010)
Ultra-sensitive mass spectrometry allows 33% increased detection of somatic EGFR T790M mutation in plasma cfDNA samples
Authors: R. Saffroy, V. Suybeng, N. Bosselut, J. Hamelin, M. Becker, P. Pham, C. Khoja, J.-F. Morère, A. Lemoine
Journal: Annals of Oncology (2016)
A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma
Authors: Stanley J. Szefler, Kevin Murphy, Thomas Harper, Attilio Boner, István Laki, Michael Engel, Georges El Azzi, Petra Moroni-Zentgraf, Helen Finnigan, Eckard Hamelmann
Journal: Journal of Allergy and Clinical Immunology (2017)

Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma.We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma.In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy.Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV1 within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P < .001]; 2.5 μg, 35 mL [95% CI, -28 to 99; P = .27]), and the key secondary end point, trough FEV1 (5 μg, 87 mL [95% CI, 19-154; P = .01]; 2.5 μg, 18 mL [95% CI, -48 to 85; P = .59]). The safety and tolerability of tiotropium were comparable with those of placebo.Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.
Gene Expression Profiling (GEP) of CD38-Expressing/Unmutated B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells by Using a Statistical Approach Suitable for Analysis of Unbalanced Datasets.
Authors: Valter Gattei, Dania Benedetti, Daniela Marconi, Antonella Zucchetto, Michele Dal, Pietro Bulian, Giovanni Del Poeta, Giuseppe Palermo, Agostino Steffan, Massimo Degan, Renato Campanini, Riccardo Bomben
Journal: Blood (2006)
Prospective study of insomnia and incident asthma in adults: the HUNT study
Authors: Ben Brumpton, Xiao-Mei Mai, Arnulf Langhammer, Lars Erik Laugsand, Imre Janszky, Linn Beate Strand
Journal: European Respiratory Journal (2017)

Insomnia is highly prevalent among asthmatics; however, few studies have investigated insomnia symptoms and asthma development. We aimed to investigate the association between insomnia and the risk of incident asthma in a population-based cohort. Among 17 927 participants free from asthma at baseline we calculated odds ratios and 95% confidence intervals for the risk of incident asthma among those with insomnia compared to those without. Participants reported sleep initiation problems, sleep maintenance problems and nonrestorative sleep. Chronic insomnia was defined as those reporting one or more insomnia symptom at baseline and 10 years earlier. Incident asthma was defined by questions on asthma at baseline and follow-up (average 11 years). The prevalence of sleep initiation problems, sleep maintenance problems and nonrestorative sleep were 1%, 1% and 5%, respectively. The multi-adjusted odds ratios were 1.18 (95% CI 0.97–1.44), 1.30 (95% CI 1.03–1.64) and 1.70 (95% CI 1.37–2.11) for people with one, two and three insomnia symptoms, respectively, compared with people without symptoms (p&lt;0.01 for trend). The risk of developing asthma in those with chronic insomnia was three times higher (adjusted OR 3.16, 95% CI 1.37–6.40) than those without. Insomnia symptoms were associated with increased risk of incident asthma in this study.
Disorders of the JAK/STAT Pathway in T Cell Lymphoma Pathogenesis: Implications for Immunotherapy
Authors: Thomas A. Waldmann, Jing Chen
Journal: Annual Review of Immunology (2017)

Common gamma receptor-dependent cytokines and their JAK/STAT pathways play pivotal roles in T cell immunity. Abnormal activation of this system was pervasive in diverse T cell malignancies assessed by pSTAT3/pSTAT5 phosphorylation. Activating mutations were described in some but not all cases. JAK1 and STAT3 were required for proliferation and survival of these T cell lines whether or not JAKs or STATs were mutated. Activating JAK and STAT mutations were not sufficient to initiate leukemic cell proliferation but rather only augmented signals from upstream in the cytokine pathway. Activation required the full pathway, including cytokine receptors acting as scaffolds and docking sites for required downstream JAK/STAT proteins. JAK kinase inhibitors have depressed leukemic T cell line proliferation. The insight that JAK/STAT system activation is pervasive in T cell malignancies suggests novel therapeutic approaches that include antibodies to common gamma cytokines, inhibitors of cytokine-receptor interactions, and JAK kinase inhibitors that may revolutionize therapy for T cell malignancies.
Best Possible Treatment for All Patients with Primary Immune Deficiency (PID) in Sweden Regardless of Social Factors, Sex, Age or Residence
Authors: Janne F. Bjorkander, Nicholas Brodszki, Åsa Carlsson, Anders Fasth, Susanne Hansen, Ann-Sofie Isaksson-Nordmark, Susanne Larsson, Åsa Nilsdotter, Mats Nilsson, Lena Nordfält, Sólveig Oskarsdóttir, Annika Wallin, Per Wågström
Journal: Journal of Allergy and Clinical Immunology (2017)
Improving quality of care and reducing costs with angiogenesis-specific imaging tests in metastatic breast cancer.
Authors: Carolyn Bodnar, L. Clark Paramore, Kevin B. Knopf
Journal: Journal of Clinical Oncology (2012)

150 Background: Anti-angiogenesis (AA) drugs (e.g., bevacizumab) are expensive and their clinical benefit in metastatic breast cancer (MBC) has been challenged. Healthcare reform and financial pressures prioritize programs which improve patient quality of care and reduce costs of unnecessary care. Angiogenesis-specific imaging tests (A-IT) under development have potential to offer earlier, accurate determination of response. For A-IT-identified responders, AA treatment would be continued. For patients identified as non-responders, futile AA treatment and associated toxicities can be avoided and alternative therapies initiated. Methods: A decision-tree model was developed to estimate the impact of A-IT from determination of AA therapy eligibility through to disease progression. Key decision nodes were presence/absence of A-IT (assessing change in biomarker expression across 2 PET/CT scans: at AA eligibility, then after one cycle of AA), A-IT sensitivity/specificity (SE/SP) and clinician adherence to test results (tied to belief that results are valid enough to stop AA therapy). Key model inputs (and base case values): 1) median time to progression (TTP) for current MBC patients on AA therapies (9.5 months); 2) median TTP for A-IT identified responders (13 months); 3) costs of bevacizumab, one cycle ($5,200); 4) percentage of AA patients with hemorrhage (4%); 5) costs of hemorrhaging, per event ($14,694); 6) per patient costs for A-IT ($6,000); 7) estimated SE/SP of A-IT – 95%/75%; and 8) clinician adherence to test results (75%). Results: Based on a cohort of 100 MBC patients, use of A-IT results in 29 patients avoiding futile AA therapy with a saving of $460,000, versus a scenario where A-IT was not used. One-way threshold sensitivity analysis shows A-IT is cost-saving if SP &gt;62% or when clinician adherence is ≥63%; results are not sensitive to AA hemorrhage rate. Conclusions: Use of A-IT could improve quality of care by optimizing AA therapy, i.e., by identifying responders who will experience survival benefit and non-responders who can avoid futile therapy and toxicity risks. Significant cost savings may be possible as a result of early determination of response to AA drugs.
Microbial Respiration and Formate Oxidation as Metabolic Signatures of Inflammation-Associated Dysbiosis
Authors: Elizabeth R. Hughes, Maria G. Winter, Breck A. Duerkop, Luisella Spiga, Tatiane Furtado de Carvalho, Wenhan Zhu, Caroline C. Gillis, Lisa Büttner, Madeline P. Smoot, Cassie L. Behrendt, Sara Cherry, Renato L. Santos, Lora V. Hooper, Sebastian E. Winter
Journal: Cell Host & Microbe (2017)
Effect of a TNFα Blocker and Peginfa on Polycythemia Vera Clonal Hematopoiesis and Suppressed Normal Dormant Hematopoiesis
Authors: Sabina Swierczek, Soo Jin Kim, Mohamed E Salama, William L. Heaton, Michael W. Deininger, Josef T. Prchal
Journal: Blood (2014)
Investigating easy bruising in an adult
Authors: Laura B Harrison, Michael J Nash, David Fitzmaurice, Jecko Thachil
Journal: BMJ (2017)

#### What you need to know A 78 year old woman presents with a three month history of easy bruising. She also feels tired and has lost her appetite. She has hypertension and a history of myocardial infarction, and has been taking amlodipine and aspirin for the last five years. Clinical examination reveals bruising to the arms, legs, and abdomen, and poor oral health. ### How should I assess the patient? ### History Discuss the bruises . Ask questions such as: Bruising limited to the limbs suggests trauma, and that on the trunk and other areas is more suggestive of an underlying bleeding disorder.1 Bruises are considered to represent a bleeding disorder when five or more (greater than 1 cm in size) occur simultaneously in exposed areas. Petechiae, and haematomas, when occurring without trauma, are suggestive of a bleeding disorder2(Box 1). #### Box 1: Causes of easy bruising in adults ##### Common ##### Rare
Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials
Authors: Alexandra J. Lansky, Steven R. Messé, Adam M. Brickman, Michael Dwyer, H. Bart van der Worp, Ronald M. Lazar, Cody G. Pietras, Kevin J. Abrams, Eugene McFadden, Nils H. Petersen, Jeffrey Browndyke, Bernard Prendergast, Vivian G. Ng, Donald E. Cutlip, Samir Kapadia, Mitchell W. Krucoff, Axel Linke, Claudia Scala Moy, Joachim Schofer, Gerrit-Anne van Es, Renu Virmani, Jeffrey Popma, Michael K. Parides, Susheel Kodali, Michel Bilello, Robert Zivadinov, Joseph Akar, Karen L. Furie, Daryl Gress, Szilard Voros, Jeffrey Moses, David Greer, John K. Forrest, David Holmes, Arie P. Kappetein, Michael Mack, Andreas Baumbach
Journal: Journal of the American College of Cardiology (2017)
Prognostic Significance of Promoter Methylation of Multiple Genes in Germinal Center Hyperplasia (GCH) and Lymphomas of Germinal Center Origin.
Authors: Jose M Paz-Carreira, Arantxa Garcia-Rivero, Raquel Losada, Jose C Mendez, Manuel Albors, Fatima Miras, Augusto Alvarez, Fernando Bal, Jesus Alba, Guillermo Deben
Journal: Blood (2009)
Combined SNP Microarray Based Genomic Mapping and Next Generation Transcriptome Sequencing Confirms the Presence of Somatic STAT3 Mutations and Identifies Novel Chromosomal Imbalances and Candidate Genes in T Large Granular Lymphocytic Leukemia (T-LGL)
Authors: Patricia Johansson, Ludger Klein-Hitpass, René Scholtysik, Marc Seifert, Ulrich Jäger, Gertraud Tschurtschenthaler, Ulrich Dührsen, Ralf Küppers, Jan Dürig
Journal: Blood (2012)
Loss of ARID1A expression is associated with poor prognosis in patients with stage I/II clear cell carcinoma of the ovary
Authors: S. Sato, H. Itamochi, N. Oumi, T. Oishi, T. Shoji, H. Fujiwara, M. Suzuki, J. Kigawa, T. Harada, T. Sugiyama
Journal: Annals of Oncology (2016)
Hypersensitivity reactions to Enzyme Replacement Therapy for Lysosomal Diseases in Brazil: Outcomes and safety in 1140 rapid desensitizations
Authors: Carolina S. Aranda, Luis Felipe Ensina, Marcia C. Mallozi, Ines Camelo Nunes, Ekaterine S. Goudouris, Sueli Canossa, Ana Maria Martins, Dirceu Solé
Journal: Journal of Allergy and Clinical Immunology (2017)
Multiple Myeloma (MM) Is Characterized by Genomic Instability Regardless of Ploidy Categories and Degree of Karyotypic Complexity Is an Important Prognostic Factor.
Authors: Wee J. Chng, Jonathan J. Keats, Esteben Braggio, Angela Baker, P. Leif Bergsagel, John Carpten, Rafael Fonseca
Journal: Blood (2007)
Vacuum-assisted decellularization: an accelerated protocol to generate tissue-engineered human tracheal scaffolds
Authors: Colin R. Butler, Robert E. Hynds, Claire Crowley, Kate H.C. Gowers, Leanne Partington, Nicholas J. Hamilton, Carla Carvalho, Manuela Platé, Edward R. Samuel, Alan J. Burns, Luca Urbani, Martin A. Birchall, Mark W. Lowdell, Paolo De Coppi, Sam M. Janes
Journal: Biomaterials (2017)

Patients with large tracheal lesions unsuitable for conventional endoscopic or open operations may require a tracheal replacement but there is no present consensus of how this may be achieved. Tissue engineering using decellularized or synthetic tracheal scaffolds offers a new avenue for airway reconstruction. Decellularized human donor tracheal scaffolds have been applied in compassionate-use clinical cases but naturally derived extracellular matrix (ECM) scaffolds demand lengthy preparation times. Here, we compare a clinically applied detergent-enzymatic method (DEM) with an accelerated vacuum-assisted decellularization (VAD) protocol. We examined the histological appearance, DNA content and extracellular matrix composition of human donor tracheae decellularized using these techniques. Further, we performed scanning electron microscopy (SEM) and biomechanical testing to analyze decellularization performance. To assess the biocompatibility of scaffolds generated using VAD, we seeded scaffolds with primary human airway epithelial cells in vitro and performed in vivo chick chorioallantoic membrane (CAM) and subcutaneous implantation assays. Both DEM and VAD protocols produced well-decellularized tracheal scaffolds with no adverse mechanical effects and scaffolds retained the capacity for in vitro and in vivo cellular integration. We conclude that the substantial reduction in time required to produce scaffolds using VAD compared to DEM (approximately 9 days vs. 3–8 weeks) does not compromise the quality of human tracheal scaffold generated. These findings might inform clinical decellularization techniques as VAD offers accelerated scaffold production and reduces the associated costs.
573P The incidence of post-transplant malignancies in kidney transplantation recipients in King Chulalongkorn Memorial Hospital: A single institute with 44 year's experience in Thailand
Authors: S. Uttamapinan, P. Puapatanakul, T. Rattananupong, V. Sriuranpong, N. Townamchai, N. Parinyanitikul
Journal: Annals of Oncology (2016)
Development of second primary cancers in breast cancer survivors.
Authors: Hong Kyu Jung, Jihyoun Lee, Zisun Kim, Min Hyuk Lee, Ilkyun Lee
Journal: Journal of Clinical Oncology (2016)

257 Background: Breast cancer survivors have slightly increased risk of second primary cancers. Importance of screening for second cancers has been raised due to increased survival in those populations. Not only having genetic risk such as BRCA mutation, but also treatment-related risk presents. The most common second primary cancer is breast cancer. Colon cancer, uterine cancer, and ovarian cancer showed increased cumulative incidence. In this study, we assessed development second primary cancers in breast cancer survivors. Methods: Medical record of breast cancer patients was reviewed retrospectively in three tertiary medical institutions. Available data of ICD-9 record after breast cancer diagnosis was evaluated. Diagnosis of second primary breast cancer was excluded in evaluation. Results: Since Jan 1989 to Jan 2014, available medical records were reviewed in breast cancer patients(N = 5880) in three institutions(one urban and the other two rural institutions). Cumulative incidence of overall second primary cancers was 4.57%. Among 269 second primary cancers, thyroid cancer(44.2%) was most common second primary cancer, followed by gastric cancer(10.0%). Gastric cancers were more common in rural institution than urban area(14.2 % vs 5.5%), while incidence of thyroid cancer is elevated in urban institution(57.8% vs 31.9%). Among 9 patients who has been diagnosed endometrial cancer, 7 patients had history of selective estrogen receptor modulator(tamoxifen or toremifen) treatment. Development of lung cancer was not related to breast cancer radiation treatment(4 of 15 patients). Leukemia after breast cancer treatment was diagnosed in 5 patients (8.5% of second primary cancers), three of them were adult T cell leukemia and two of them were acute myeloid leukemia. Conclusions: Incidence of cancer in general population was reflected to development of second primary cancer in breast cancer survivors. Endocrine treatment was related increased incidence of endometrial cancer, respectively. Application of personalized cancer screening plan would be important in this patient group.
Clinical Characterization of a Large Population of Subjects with Respiratory Vs Cutaneous Non-Steroidal Anti-Inflammatory Drugs (NSAID) Hypersensitivity Reactions
Authors: Jesus Verge, Inmaculada DoÑa, Ibon Eguiluz Gracia, Ana Prieto del Prado, Luisa Galindo, Francisca Gomez, Jose Antonio Cornejo, Carmen Rondon Segovia, Paloma Campo
Journal: Journal of Allergy and Clinical Immunology (2017)
Graft-Versus-Host Disease Alters Intestinal Microbial Ecology by Inhibiting Production of Enteric Defensins
Authors: Yoshihiro Eriguchi, Shuichiro Takashima, Noriko Miyake, Yoji Nagasaki, Nobuyuki Shimono, Koichi Akashi, Takanori Teshima
Journal: Blood (2010)
Low Incidence and severity of Graft-Versus-host disease after outpatient allogeneic Peripheral Blood Stem Cell Transplantation employing a Reduced-Intensity Conditioning
Authors: Olga Cantú-Rodríguez, Juan A. Flores-Jiménez, Cesar H Gutiérrez-Aguirre, Guillermo J. Ruiz-Arguelles, A López-Otero, Consuelo Mancías-Guerra, Oscar Gonzalez-Llano, Oscar Treviño-Montemayor, Jose C. Jaime-Pérez, Silvia Martínez-Cabriales, David Gomez-Almaguer
Journal: Blood (2011)
Analysis of a p67phoxΔ401 Mutant Identified in Chronic Granulomatous Disease: Deletion of C-Terminal SH3 Binding Site for p47phox Still Supports NADPH Oxidase Activity in Cosphox Cells.
Authors: A. A. Arias, J. D. Matute, P. J. Patino, M. C. Dinauer
Journal: Blood (2004)
Coagulation Factors, Postmenopausal Hormone Replacement Therapy and the Risk of Venous Thrombosis: The WHI Clinical Trials of Postmenopausal Hormone Therapy.
Authors: Mary Cushman, Joseph Larson, Frits R. Rosendaal, Lawrence S. Phillips, Barbara V. Howard, J. David Curb, Jennifer Hays-Grudo, Alison Baird, Charles B. Eaton, Susan R. Heckbert, Randall S. Stafford
Journal: Blood (2007)