tbuckley/cabot-search huggingface dataset:
Association between sample characteristics and tumor mutational burden estimated by next-generation sequencing-based multiplex gene panel assay.
Authors: Quy Pham Nguyen, Masashi Kanai, Tadayuki Kou, Tomohiro Kondo, Yoshihiro Yamamoto, Junichi Matsubara, Akinori Hiroshima, Hiroaki Mochizuki, Tomohiro Sakuma, Keita Fukuyama, Shigemi Matsumoto, Manabu Muto
Journal: Journal of Clinical Oncology (2019)

148 Background: Tumor mutational burden (TMB) measured via next-generation sequencing (NGS)-based gene panel testing is a promising biomarker for response to immune checkpoint inhibitors (ICIs) in solid tumors. However, little is known about the characteristics of tissue sample that can affect the TMB score. Methods: Data of 199 patients with solid tumors who underwent NGS-based gene panel assay were reviewed. Associations between the TMB score and sample characteristics, including sample DNA quality, sample type, sampling site, and storage period, were analyzed. Clinical outcomes of patients with a high TMB score (≥10 mutations/megabase) who received anti-PD-1 antibodies (n = 22) were also analyzed. Results: TMB score was significantly higher in samples that yielded a DNA library concentration of &lt; 5 nM and in samples obtained from formalin-fixed paraffin-embedded tissue (FFPE) compared to fresh frozen tissue. The sample storage period was also positively correlated with TMB score. Of the 22 patients with a high TMB score, partial response and stable disease were observed in two (9.1%) and five (22.7%) cases, respectively. Among 15 non-responders, 11 (73.3%) had a low DNA library concentration, thereby indicating that a high TMB score might be attributable to false positive mutation calls. Conclusions: Our results suggest that the TMB score estimated via NGS-based gene panel assay could be affected by the DNA library concentration, sample type and storage period.
Inferior Caval Valve Implantation Versus Optimal Medical Therapy for Severe Tricuspid Regurgitation
Authors: Michael Laule, Isabel Mattig, Christoph Schöbel, Fabian Knebel, Alexander Lauten, Alexander Lembcke, Martin Thoenes, Herko Grubitzsch, Karl Stangl, Henryk Dreger
Journal: Journal of the American College of Cardiology (2019)
Effect of iFISH defined 1q21 amplification/gain in multiple myeloma patients treated on total therapy protocols.
Authors: Maurizio Zangari, Meera Mohan, Niels Weinhold, Leo Rasche, Jeffrey Sawyer, Frits Van Rhee, Sharmilan Thanendrarajan, Carolina D. Schinke, Faith Davies, Erming Tian
Journal: Journal of Clinical Oncology (2019)

8023 Background: The amplification of the proximal 1q21 region has been reported by interphase FISH (iFISH) in about 40% of newly diagnosed patients, and in 70% of MM patients at relapse. We hereby report the prognostic value of 1q21 amplification/gain by iFISH at enrollment in subjects treated on total therapy (TT) 4, 5 and 6 protocols. Methods: TT4 protocol enrolled newly diagnosed patients with LR disease as defined GEP 70 model ≤ 0.66. TT5 was designed for newly diagnosed patients with HR MM.TT6 enrolled previously treated patients with both HR and LR disease. iFISH was performed on bone marrow samples obtained at the time of study enrollment. FISH probes were generated from specific BAC DNA clone for CKS1B gene locus (1q21) gene locus. MM cells were identified post hybridization using isotype specific antibody conjugated with 7-amino-4-methylcoumarin-3-acetic acid (AMCA) to stain Ig-Kappa or Ig-Lambda light chain in cytoplasm (cIg) of MM cells. The iFISH signals in 100 of MM cells were recorded. A 20% cutoff point was used for detection of significant abnormalities i.e. gain of 1q21 (≥ 3 copies). Results: 607 patients were included in this analysis. With a median age of 61 years, 39% had high risk and 88% low risk disease. 1q21 abnormalities were present in 55% of patients at enrollment. 591 patients (97%) received at least one HDT ASCT. The analysis included 382 TT4 patients with a median PFS of 7.2 years and OS not yet reached. 75 patients enrolled on TT5 protocol experienced median PFS of 2.2 years and median OS of 5.6 years.150 TT6 enrolled patients experienced median PFS of 4.1 years and median OS of 7.5 years. Statistically significant difference in PFS (p &lt; 0.0001) and OS (p &lt; 0.0001) was observed between 1q21 defined groups (figure 1). No differences in survival were observed based on the 1q21 copy number &gt; 3. Conclusions: This retrospective analysis clearly showed that 1q21 amplification/gain detected by interphase iFISH in different stages of disease can identify patients with significant shorter progressive free and overall survival even if exposed to total therapy regimens. Clinical trial information: NCT00734877, NCT00869232.
A phase II study of cpi-0610, a bromodomain and extraterminal protein inhibitor (BETi) alone or with ruxolitinib (RUX), in patients with myelofibrosis (MF).
Authors: Marina Kremyanskaya, Ronald Hoffman, John Mascarenhas, Prithviraj Bose, Vikas Gupta, Gary J. Schiller, Elena Liew, Claudia Lebedinsky, Adrian Mario Senderowicz, Jennifer Mertz, Patrick Trojer, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2019)

7056 Background: BETi have been shown to regulate NF-κB, MYC, BCL2, and TGF-β signaling, important drivers of marrow fibrosis. Preclinical studies have suggested that combined BETi and JAK2 inhibition synergistically reduce MF-related splenomegaly, bone marrow fibrosis and the malignant allele burden (Kleppe, 2018). CPI-0610 is a selective and potent oral BETi, being evaluated in the first study of a BETi in MF. Methods: Phase 2 trial with 3 arms: CPI-0610 monotherapy (Arm 1) or RUX + CPI-0610 “add-on” (Arm 2) in pts who have progressed/ had an inadequate response to RUX, or CPI-0610 + RUX in JAK inhibitor-naïve pts with anemia (Arm 3). Arms 1 and 2 are stratified: transfusion dependence (TD) yes: A/no: B. The primary objectives are to evaluate the effect of CPI-0610 on transfusion dependence (TD, 1A and 2A) and spleen volume (1B, 2B and 3). A Simon two-stage design: if 2 responses are seen will advance to the 2nd stage. Results: 4 pts enrolled in Arm 1, 14 pts in Arm 2, no pts accrued to Arm 3 yet. Median age: 69 years (46-83), gender: 9 male pts; 11 pts received ≥1 prior therapy besides RUX. JAK2/MPL/CALR mutations: 17/18 pts, ≥3 mutations: 10 pts, ASXL1 mutations: 11 (61%) pts. Hemoglobin &lt;10 g/dL at baseline: 11 (61%) pts. 6 pts received ≥ 24 weeks of CPI-0610 treatment at this analysis. 2 TD pts in Arm 2 became transfusion independent, both remain on treatment free of transfusions. Hgb increase of ≥1.5 g/dL from baseline was observed with successive cycles of therapy in anemic pts: 2/2 pts in Arm 1 (100%) and 3/9 pts in Arm 2, (33%). Spleen volume reduction, by MRI (6-44%) was observed in all 10 evaluable pts irrespective of their driver mutation. Symptom improvement and reductions of cytokine levels were observed. In Arm 1: 2/2 evaluable pts had marrow fibrosis improvement with Hgb increase; additionally, thrombocytosis resolved in 2/2 pts (baseline ≥791 10 3 /uL). Most common adverse events were mild diarrhea, nausea/vomiting; and reversible and non-cumulative thrombocytopenia. Conclusions: CPI-0610 is a well-tolerated, and an effective therapeutic agent for the treatment of MF. Collectively, these data indicate that CPI-0610 +/- RUX might have disease modifying effects. Updated data will be provided. Clinical trial information: NCT02158858.
Dose-Ranging and Cohort-Expansion Study of Monalizumab (IPH2201) in Patients with Advanced Gynecologic Malignancies: A Trial of the Canadian Cancer Trials Group (CCTG): IND221
Authors: Anna V. Tinker, Holger W. Hirte, Diane Provencher, Marcus Butler, Heather Ritter, Dongsheng Tu, Hatem A. Azim, Paulo Paralejas, Nathalie Grenier, Shirley-Ann Hahn, Janelle Ramsahai, Lesley Seymour
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Monalizumab binds CD94/NKG2A, preventing HLA-E inhibition of tumor lymphocytes. A dose-ranging/cohort expansion trial of monalizumab for recurrent gynecologic malignancies was conducted to determine the recommended phase II dose (RP2D) and to explore clinical activity, pharmacokinetics, pharmacodynamics, safety, and immunogenicity. Patients and Methods: Participants (and part 2 expansion cohorts) included (i) platinum-sensitive ovarian, (ii) platinum-resistant ovarian, (iii) squamous cervical (CX), and (iv) epithelial endometrial (END) carcinomas. Part 1 assessed monalizumab at 1, 4, or 10 mg/kg every 2 weeks. In part 2, ≥4 patients/cohort underwent pre- and on-treatment tumor biopsies. Preset criteria determined cohort expansion. Results: A total of 58 participants were evaluable. The RP2D was 10 mg/kg i.v. every 2 weeks. Dose proportionality and 100% NKG2A saturation were observed. Related adverse events were mild: headache, abdominal pain, fatigue, nausea, and vomiting. Grade 3 related adverse events were nausea (1), vomiting (1), dehydration (1), fatigue (2), anorexia (1), dyspnea (1), and proctitis (1). Dose-limiting toxicities were not observed. Hematologic and biochemical changes were mild and not dose related. Best response was SD: part 1, 7 of 18 (39%) [3.4 months (1.4–5.5)], and part 2, 7 of 39 (18%) [1.7 months (CX) to 14.8 months (END)]. Neither a predictive biomarker for SD nor evidence of pharmacodynamic effects was identified. There was a trend to significance between a reduction in lymphocyte HLA-E total score and pharmacodynamics. Conclusions: Monalizumab 10 mg/kg i.v. every 2 week is well tolerated in patients with pretreated gynecologic cancers. Short-term disease stabilization was observed. Future studies should assess combinations with other agents, including immunotherapeutics.
Low specificity but high sensitivity of inflammatory back pain criteria in rheumatology settings in Europe: confirmation of findings from a German cohort study
Authors: Manouk de Hooge, Floris A van Gaalen, Thomas Renson, Ann-Sophie De Craemer, Marleen G van de Sande, Roberta Ramonda, Karen Minde Fagerli, Lennart T H Jacobsson, Désirée van der Heijde, Dirk Elewaut, Filip Van den Bosch
Journal: Annals of the Rheumatic Diseases (2019)

Inflammatory back pain (IBP) is considered so essential in the axial spondyloarthritis (axSpA) diagnostic process that it is recommended as referral parameter in primary care.1–3 However, axSpA patients without IBP do exist as well as patients with IBP that do not have an axSpA diagnosis, leaving IBP to be a strong and useful feature for recognising axSpA but not pathognomonic.4 5 A recent study in German chronic back pain patients with a suspicion of axSpA report on the performance of, among others, the Assessment of Spondyloarthritis international Society (ASAS) IBP criteria and individual IBP parameters. Data showed high sensitivity of the criteria and individual IBP parameters, however specificity was low.6 Important findings like low specificity indicate that in the German rheumatology setting diagnostic utility of IBP criteria was lower than expected. In addition, they commonly find IBP in patients in routine rheumatology care, suggesting that IBP is used as …
Ensuring the Best Use of Data
Authors: Wilson M. Compton, Gayathri J. Dowling, Hugh Garavan
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Dysregulation of the Reward and Learning Systems in Tourette Syndrome
Authors: Jens Kuhn, Juan Carlos Baldermann, Daniel Huys
Journal: JAMA Neurology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia
Authors: Valerie M. Vaughn, Scott A. Flanders, Ashley Snyder, Anna Conlon, Mary A.M. Rogers, Anurag N. Malani, Elizabeth McLaughlin, Sarah Bloemers, Arjun Srinivasan, Jerod Nagel, Scott Kaatz, Danielle Osterholzer, Rama Thyagarajan, Lama Hsaiky, Vineet Chopra, Tejal N. Gandhi
Journal: Annals of Internal Medicine (2019)

Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration.To examine predictors and outcomes associated with excess duration of antibiotic treatment.Retrospective cohort study.43 hospitals in the Michigan Hospital Medicine Safety Consortium.6481 general care medical patients with pneumonia.The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment.Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge.Retrospective design; not all patients could be contacted to report 30-day outcomes.Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes.Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program.
Medical oncology trainees’ perceptions of their education and preparedness for independent practice.
Authors: Geordie Linford, Nazik Hammad, Nancy Dalgarno, Nicholas Cofie, Ravi Ramjeesingh, Anna T. Tomiak
Journal: Journal of Clinical Oncology (2019)

10536 Background: This original research assesses Canadian Medical Oncology (MO) residents’ perceptions and satisfaction with their education and preparedness for practice prior to initiation of Competency Based Medical Education (CBME). Methods: Digital surveys were sent to MO residents in Canadian training institutions yearly from 2014–2017. Because of lower than expected response rates, invitations were subsequently extended to recent graduates completing training between 2009–2014. Ethics and funding were granted by Queen’s University. Results: A total of 71 surveys were received with representation from 11 training programs. Preparedness for Practice: Current trainees and recent graduates ranked preparedness for practice similarly in all assessment domains except Medical Expert (trainee mean 3.50, graduate mean 4.45, p=0.004; 1=not prepared, 5=well prepared). Means for the combined cohort shown in table. Usefulness of teaching modalities: Participants ranked learning in a clinical setting as most useful (6.53/8, 1=least useful, 8=most useful) and educational sessions by residents (4.24/8) and Journal Club (3.74/8) as least useful. Most participants felt their training was a shared learner-teacher responsibility (56.1%) or was learner-centered (22.5%). Quality of teaching: Participants reported similar levels of satisfaction with teaching across domains except for Manager which scored lowest (3.46/5, 1=poor, 5=excellent). Self-assessment of skills: Participants were most satisfied by their ability to assess their own performance and competence at the end of training (7.16/10, 1=not satisfied, 10= very satisfied). The degree to which their programs set expectations about required knowledge, skills, or attitudes at various points in training (6.63/10) and participants abilities to self-assess these skills during their training (6.64/10) scored lower. Conclusions: Participants reported low satisfaction with their ability to self-assess during their training and their training programs’ ability to communicate expectations. Transition to CBME training may address these issues, and follow-up is required.[Table: see text]
MPs vote to liberalise abortion rights in Northern Ireland
Authors: Clare Dyer
Journal: BMJ (2019)

MPs in the UK parliament have voted overwhelmingly to liberalise abortion laws in Northern Ireland and bring them into line with those in the rest of the UK.

The move happened after Labour MP Stella Creasy put down an amendment to the Northern Ireland Executive (Formation) Bill, a technical government bill connected to budgets and elections for the devolved Northern Ireland assembly.

Abortion is an area which is devolved to the assembly at Stormont and the government had argued that it was for the assembly …
Correction: Vertebrate genome evolution and the zebrafish gene map
Authors: John Postlethwait, Yi-Lin Yan, Michael Gates, Sally Horne, Angel Amores, Alison Brownlie, Adriana Donovan, Elizabeth Egan, Allan Force, Zhiyuan Gong, Carole Goutel, Andreas Fritz, Robert Kelsh, Ela Knapik, Eric Liao, Barry Paw, David Ransom, Amy Singer, Margaret Thomson, Tariq Abduljabbar, Pam Yelick, Dave Beier, None Joly, Dan Larhammar, Frederic Rosa, Monte Westerfield, Leonard Zon, Steve Johnson, William Talbot
Journal: Nature Genetics (1998)
Impact of age and gender on safety and efficacy of first-line FOLFOXIRI/bevacizumab in mCRC: a pooled analysis of TRIBE and TRIBE2 studies
Authors: G. Zucchelli, F. Marmorino, D. Rossini, G. Aprile, M. Casagrande, S. Lonardi, S. Murgioni, E. Dell’Aquila, G. Tomasello, R. Moretto, C. Antoniotti, B. Borelli, F. Urbano, M. Ronzoni, A. Zaniboni, S. Manglaviti, A. Buonadonna, G. Ritorto, G. Masi, G. Allegrini, A. Falcone, C. Cremolini
Journal: Annals of Oncology (2019)
Liposome-induced hypersensitivity reactions: Risk reduction by design of safe infusion protocols in pigs
Authors: Tamás Fülöp, Gergely T. Kozma, Ildikó Vashegyi, Tamás Mészáros, László Rosivall, Rudolf Urbanics, Gert Storm, Josbert M. Metselaar, János Szebeni
Journal: Journal of Controlled Release (2019)

Intravenous administration of liposomal drugs can entail infusion reactions, also known as hypersensitivity reactions (HSRs), that can be severe and sometimes life-threatening in a small portion of patients. One empirical approach to prevent these reactions consists of lowering the infusion speed and extending the infusion time of the drug. However, different liposomal drugs have different levels of reactogenicity, which means that the optimal protocol for each liposomal drug may differ and should be identified and evaluated to make the treatment as safe and convenient as possible. The goal of the present study was to explore the use of pigs for the above purpose, using PEGylated liposomal prednisolone (PLP) as a model drug. We compared the reactogenicities of bolus versus infusion protocols involving 2-, 3- and 4-step dose escalations for a clinically relevant total dose, also varying the duration of infusions. The strength of HSRs was measured via continuous recording of hemodynamic parameters and blood thromboxane B2 levels. We showed that bolus administration or rapid infusion of PLP caused transient changes in systemic and pulmonary blood pressure and heart rate, most notably pulmonary hypertension with paralleling rises in plasma thromboxane B2. These adverse responses could be significantly reduced or eliminated by slow infusion of PLP, with the 3-h 3-step dose escalation protocol being the least reactogenic. These data suggest that the pig model enables the development of safe infusion protocols for reactogenic nanomedicines.
The Use of Checkpoint Inhibitors before and after Allogeneic Stem Cell Transplantion: A Double-Edged Sword
Authors: Ali Younas Khan, Awais Ijaz, Muhammad Usman, Muhammad Junaid Tariq, Muhammad Asad Fraz, Muhammad Jahanzeb Khalil, Ceren Durer, Seren Durer, Fnu Sagar, Malik Qistas Ahmad, Chaudhry Saad Sohail, Zunairah Shah, Shehroz Aslam, Faiz Anwer
Journal: Blood (2018)
Abstract 17019: Pregnancy-associated Hypertensive Disorders and Risk of Subsequent Hypertension: Women's Ischemic Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) Cohort
Authors: Odayme Quesada, Ki Park, Janet Wei, Margo Minnissian, Galen Cook-Wiens, Eileen Handberg, Carl J Pepine, Noel C Bairey-Merz
Journal: Circulation (2017)

Introduction: Pregnancy-associated hypertensive disorders are prevalent in 5-10% of pregnancies in the United States (US) and accounted for 7.4% of pregnancy related deaths 2011-2013. Although preg...
Prevalence and Preliminary Validation of Screening Criteria to Identify Carriers of Germline BAP1 Mutations
Authors: Marjorie G. Zauderer, Gowtham Jayakumaran, Mariel DuBoff, Liying Zhang, Jasmine H. Francis, David H. Abramson, Andrea Cercek, Garrett M. Nash, Alexander Shoushtari, Paul Chapman, Sandra D’Angelo, Angela G. Arnold, Beth Siegel, Megan Harlan Fleischut, Andy Ni, Andreas Rimner, Valerie W. Rusch, Prasad S. Adusumilli, William Travis, Jennifer L. Sauter, Ahmet Zehir, Diana Mandelker, Marc Ladanyi, Mark Robson
Journal: Journal of Thoracic Oncology (2019)
Assessment of Macular Microvasculature in Healthy Eyes of Infants and Children Using OCT Angiography
Authors: S. Tammy Hsu, Hoan T. Ngo, Sandra S. Stinnett, Nathan L. Cheung, Robert J. House, Michael P. Kelly, Xi Chen, Laura B. Enyedi, S. Grace Prakalapakorn, Miguel A. Materin, Mays A. El-Dairi, Glenn J. Jaffe, Sharon F. Freedman, Cynthia A. Toth, Lejla Vajzovic
Journal: Ophthalmology (2019)