tbuckley/cabot-search huggingface dataset:
Polycythemia vera treatment algorithm 2018
Authors: Ayalew Tefferi, Alessandro M. Vannucchi, Tiziano Barbui
Journal: Blood Cancer Journal (2018)

Abstract Recently reported mature survival data have confirmed the favorable prognosis in polycythemia vera (PV), with an estimated median survival of 24 years, in patients younger than age 60 years old. Currently available drugs for PV have not been shown to prolong survival or alter the natural history of the disease and are instead indicated primarily for prevention of thrombosis. Unfortunately, study endpoints that are being utilized in currently ongoing clinical trials in PV do not necessarily target clinically or biologically relevant outcomes, such as thrombosis, survival, or morphologic remission, and are instead focused on components of disease palliation. Even more discouraging has been the lack of critical appraisal from “opinion leaders”, on the added value of newly approved drugs. Keeping these issues in mind, at present, we continue to advocate conservative management in low-risk PV (phlebotomy combined with once- or twice-daily aspirin therapy) and include cytoreductive therapy in “high-risk” patients; in the latter regard, our first, second, and third line drugs of choice are hydroxyurea, pegylated interferon-α and busulfan, respectively. In addition, it is reasonable to consider JAK2 inhibitor therapy, in the presence of protracted pruritus or markedly enlarged splenomegaly shown to be refractory to the aforementioned drugs.
Donor Lymphocyte Infusions for Haematological Malignancy Relapse
Authors: Guillermo Orti, Irene García-Cadenas, Isabel Sánchez-Ortega, Mª Jose Jimenez, Laura Alonso, Carmen Azqueta, Cristina Diaz de Heredia, Cristelle Ferra, Rocio Parody, Jorge Sierra, Sergio Querol, David Valcarcel
Journal: Blood (2016)
Fitness or Fatness
Authors: Ann Blair Kennedy, Carl J. Lavie, Steven N. Blair
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Spatial Variation of Endotoxin Concentrations Measured in Ambient PM10 in a Livestock-Dense Area: Implementation of a Land-Use Regression Approach
Authors: Myrna M.T. de Rooij, Dick J.J. Heederik, Erik J.H.M. van Nunen, Isabella J. van Schothorst, Catharina B.M. Maassen, Gerard Hoek, Inge M. Wouters
Journal: Environmental Health Perspectives (2018)

Background: Results from studies on residential health effects of livestock farming are inconsistent, potentially due to simple exposure proxies used (e.g., livestock density). Accuracy of these proxies compared with measured exposure concentrations is unknown. Objectives: We aimed to assess spatial variation of endotoxin in PM10 (particulate matter ≤10μm) at residential level in a livestock-dense area, compare simple livestock exposure proxies to measured endotoxin concentrations, and evaluate whether land-use regression (LUR) can be used to explain spatial variation of endotoxin. Methods: The study area (3,000 km2) was located in Netherlands. Ambient PM10 was collected at 61 residential sites representing a variety of surrounding livestock-related characteristics. Three to four 2-wk averaged samples were collected at each site. A local reference site was used for temporal variation adjustment. Samples were analyzed for PM10 mass by weighing and for endotoxin by using the limulus amebocyte lysate assay. Three LUR models were developed, first a model based on general livestock-related GIS predictors only, followed by models that also considered species-specific predictors and farm type–specific predictors. Results: Variation in concentrations measured between sites was substantial for endotoxin and more limited for PM10 (coefficient of variation: 43%, 8%, respectively); spatial patterns differed considerably. Simple exposure proxies were associated with endotoxin concentrations although spatial variation explained was modest (R2&lt;26%). LUR models using a combination of animal-specific livestock-related characteristics performed markedly better, with up to 64% explained spatial variation. Conclusion: The considerable spatial variation of ambient endotoxin concentrations measured in a livestock-dense area can largely be explained by LUR modeling based on livestock-related characteristics. Application of endotoxin LUR models seems promising for residential exposure estimation within health studies. https://doi.org/10.1289/EHP2252
No biased unmutaed VH1-69 gene usage in patients with chronic lymphocytic leukemia in Japan
Authors: A. Yamane, H. Koiso, T. Mitsui, Y. Hashimoto, I. Maekawa, A. Yokohama, M. Takafumi, N. Tsukamoto, H. Murakami, Y. Nojima, M. Karasawa
Journal: Blood (2003)
Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial
Authors: Ronald F van Vollenhoven, Edward Clark Keystone, Vibeke Strand, Cesar Pacheco-Tena, Jiří Vencovský, Frank Behrens, Arthur Racewicz, Daniela Zipp, Faiza Rharbaoui, Ralf Wolter, Luise Knierim, Rainer Schmeidl, Xuefei Zhou, Silke Aigner, Benjamin Dälken, Andrea Wartenberg-Demand
Journal: Annals of the Rheumatic Diseases (2018)

Objective To evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Methods 321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment. After 24 weeks, patients could continue treatment with tregalizumab for 24 weeks (extension phase). The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Safety and biological activity were monitored through week 48. Results At week 12, ACR20 response rates were not statistically significantly different between placebo and any of the tregalizumab doses. Tregalizumab injections were well tolerated; most adverse events were mild to moderate and comparable among treatment and placebo groups. Biological activity was shown by dose-dependent CD4 downmodulation. Conclusion Treatment with tregalizumab did not show significant clinical efficacy in patients with active RA compared with placebo but resulted in the expected biological effect on CD4 modulation. Tregalizumab was generally well tolerated, and no new safety findings were identified. Trial registration number NCT01999192 ; Results.
Clinical Ethics Consultation and Research Ethics Consultation: A Call for Italy
Authors: Ludovica De Panfilis, Domenico Franco Merlo, Roberto Satolli, Teresa Coppola, Luca Ghirotto, Massimo Costantini
Journal: The American Journal of Bioethics (2018)

"Clinical Ethics Consultation and Research Ethics Consultation: A Call for Italy." The American Journal of Bioethics, 18(1), pp. 63–64
Immune Responses in the Liver
Authors: Paul Kubes, Craig Jenne
Journal: Annual Review of Immunology (2018)

The liver is a key, frontline immune tissue. Ideally positioned to detect pathogens entering the body via the gut, the liver appears designed to detect, capture, and clear bacteria, viruses, and macromolecules. Containing the largest collection of phagocytic cells in the body, this organ is an important barrier between us and the outside world. Importantly, as portal blood also transports a large number of foreign but harmless molecules (e.g., food antigens), the liver's default immune status is anti-inflammatory or immunotolerant; however, under appropriate conditions, the liver is able to mount a rapid and robust immune response. This balance between immunity and tolerance is essential to liver function. Excessive inflammation in the absence of infection leads to sterile liver injury, tissue damage, and remodeling; insufficient immunity allows for chronic infection and cancer. Dynamic interactions between the numerous populations of immune cells in the liver are key to maintaining this balance and overall tissue health.
Comparison of surgical resection versus transarterial chemoembolization with additional radiation therapy in patients with hepatocellular carcinoma with portal vein invasion
Authors: Danbi Lee, Han Chu Lee, Jihyun An, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Young-Hwa Chung, Yung Sang Lee
Journal: Clinical and Molecular Hepatology (2018)

Portal vein invasion (PVI) is a poor prognostic factor in patients with hepatocellular carcinoma (HCC). We intended to compare the effects of surgical resection and transarterial chemoembolization (TACE) with additional radiation therapy (RT) in HCC patients with PVI.The subjects comprised 43 patients who underwent surgical resection for HCC with PVI without previous treatment and another 43 patients who received TACE followed by RT (TACE+RT) as initial treatment who were matched for Child-Pugh class, tumor size, and extent of PVI. Disease progression and death after the treatment were examined, and progression-free survival (PFS) and overall survival (OS) were compared between groups. Predisposing factors affecting OS were analyzed using univariate and multivariate analyses in HCC patients with PVI.The subjects (Age [51, 24-74; median, range], Sex [81/13; male/female], Etiology [78/1/15; hepatitis B virus {HBV}/ hepatitis C virus {HCV}/non-HBV and non-HCV]) were followed for a median of 17 (2-68) months. There were no differences in clinical or tumor characteristics between the resection and TACE+RT groups. The cumulative PFS was not significantly different between groups. The median PFS was 5.6 and 4.0 months in the resection and TACE+RT groups, respectively. However, the cumulative OS was significantly longer in patients treated with resection than in those treated with TACE+RT (P=0.04). The median OS was 26.9 and 14.2 months in the resection and TACE+RT groups, respectively. Univariate and multivariate analyses revealed that surgical resection was an independent predictive factor for better survival outcome.Surgical resection might be an effective treatment in HCC patients with PVI.
Abstract 11638: Angiographic Efficacy of the Atriclip Left Atrial Appendage (LAA) Exclusion Device Placed by Minimally Invasive Thoracoscopic Approach
Authors: Neel J Patel, Sam Aznaurov, Stephen K Ball, Steven J Hoff, Keith Adkins, Amanda Carroll, Jennifer R Williams, John J Carr, Kim L Sandler, Christopher R Ellis
Journal: Circulation (2016)

Introduction: Closure of the LAA with an endocardial device is associated with a low risk for AF related embolic stroke. The Atriclip exclusion device (Atricure, Inc., West Chester, OH, USA) allows epicardial closure of the LAA, avoiding the need for oral anticoagulation (OAC) post procedure. We sought to assess long-term LAA closure efficacy of the Atriclip applied via totally thoracoscopic (TT) approach. Hypothesis: LAA closure efficacy will be high. Methods: We performed a prospective CT angiography (CTA) study of all TT placed Atriclips at Vanderbilt Medical Center implanted June 13, 2011 to October 6, 2015. All subjects provided informed consent under Vanderbilt IRB approved protocol. Intra-op TEE was performed in all cases to confirm procedural success. At a minimum of 90 days postimplant, 3-D volumetric two phase CTA was performed to assess the presence of contrast leak, exposed trabeculations, residual stump and clip position. All CTA interpretation and data was obtained by chest radiologists. Results: As of June 1, 2016, 63 patients completed CTA. The mean age was 64.8 ± 8.87 years and 77.8% were male. The majority of patients had persistent AF (82.5%). Mean CHADS2VASC score was 2.43 ± 1.44 and HASBLED was score 2.21 ± 1.23. Adequate LAA closure was defined as complete exclusion of the trabeculated LAA, which was confirmed in 59 subjects (93.6%). Cases without complete closure (n=4) include: 2 malpositioned clip not addressing a secondary LAA lobe, and 2 clips placed too distal leaving a stump with exposed trabeculae. Of the patients with complete closure, 30 (50.8%) had a smooth proximal stump. There were no major complications associated with TT placed Atriclips. Prospective follow-up over 143 observed patient-years reveals 1 stroke in a patient with documented complete LAA closure and no thrombus (hypertensive CVA). Conclusions: Angiographic LAA closure efficacy with a TT placed Atriclip is high (93.6%). The clinical significance of a remnant stump is unknown.
Clinical Advances in Human Gene Therapies
Authors: Jennifer Abbasi
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The Combination of 41BB and CD28 Costimulatory Signals Endows Lower Affinity CAR T Cells with the Most Optimal Properties for Selective Targeting of the Tumor Associated Antigen CD38
Authors: Esther Drent, Renee Poels, Niels W. C. J. Van de Donk, Sonja Zweegman, Henk M. Lokhorst, Richard W. J. Groen, Tuna Mutis, Maria Themeli
Journal: Blood (2017)
Abstract 14800: Heterozygous Ablation of RORγt Gene Deteriorates Adverse Cardiac Remodeling After Myocardial Infarction
Authors: Daichi Enomoto, Masanori Obana, Kotaro Matsumoto, Yasushi Sakata, Makiko Maeda, Hiroyuki Nakayama, Yasushi Fujio
Journal: Circulation (2016)

Background: Inflammatory response is associated with progression of heart failure. Recent studies have revealed that retinoic acid receptor-related orphan nuclear receptor (RORγt) is a critical reg...
Genetic risk factors in non-BRCA breast/ovarian cancer families.
Authors: Nancy Uhrhammer, Antoine Tesniere, Laetitia Delort, Laurence Zitvogel, Marie-Laure Vuillaume, Yves-Jean Bignon
Journal: Cancer Research (2008)

1918   Mutations in the BRCA genes account for less than 30 % of hereditary breast/ovarian cancer families. It is therefore imperative to identify the other genetic factors contributing to familial breast cancer, to better ascertain risk to individuals in these families and decide on appropriate preventive and/or early detection measures. Deleterious mutations or polymorphisms of many genes have been described as associated with breast cancer risk. The association of cancer risk with DNA repair genes is well known. Mutations of many repair genes cause rare hereditary syndromes when homozygous (e.g. ATM, FANC genes, BLM, etc), often with moderately elevated cancer risk to heterozygotes. Variants of genes involved in other cellular processes may also contribute to HBOC, for example factors influencing proliferation, cell death, adhesion, and immune surveillance. Genes influencing hormone metabolism may be specifically involved in breast and ovarian cancer risk due to the hormone-responsive nature of these tissues.  Many candidate genes have been studied in different populations ; the systematic analysis of many genes in a single population should permit the development of a multiparametric model of genetic risk.  Six hundred cases from non-BRCA1/2 HBOC families and 400 women with no personal or familial breast/ovarian cancer history were identified at the Centre Jean Perrin, France. Written informed consent was obtained for genetic analysis, and DNA purified from peripheral blood. Four DNA repair-related genes were analysed by direct sequencing (Chek2, XRCC2, Mre11 and Rad50). SNPs or microsatellites in cancer-associated genes representing other pathways were also analysed (IGF-1, IGFBP3, EGFR, TLR4, LEP, LEPR).  Deleterious mutations and missense variants of Chek2 were significantly more frequent in cases than controls (OR 2.40, p = 0.05), and were observed in Mre11 and Rad50, though their rarity suggested minimal contribution to HBOC. While no deleterious XRCC2 mutations were observed, the variant allele His188 was non-significantly associated with cases (OR 1.76, p = 0.10). Polymorphisms affecting expression of IGF-1 were significantly different between cases and controls (OR 1.66, p
Abstract 15677: An Ascending Ramp First Phase Biphasic Shock Defibrillates With Lower Energy and Causes Markedly Less Damage
Authors: Jian Huang, Gregory P Walcott, Silvio H Litovsky, Scott J Bohanan, Richard B Ruse, Dawei Gong, Paul DeGroot, Raymond E Ideker
Journal: Circulation (2016)

Introduction:  ICD shocks damage the heart and may increase mortality.   Hypothesis:  We tested the hypothesis that a biphasic shock with an ascending ramp as first phase (RAMP, Fig A) causes less damage than a standard biphasic truncated exponential shock (BTE, Fig B).   Methods:  Either a 20J RAMP or a 25J BTE was delivered through right ventricular (RV) and SVC electrodes in pigs. To be considered a successful experiment, the waveform had to defibrillate 2 VF episodes 5 min apart. Six successes were required for each waveform. A bipolar recording between a tip lead electrode and the RV coil was made for STT changes. Blood samples were drawn before the first shock and hourly for 6 hours after the second shock for troponin I levels. Histologic sections were taken near the RV coil.   Results:  RAMP shocks succeeded in 6 successive pigs, while BTE shocks failed in 8 pigs before 6 successes were achieved (Fig C). Troponin I after 6 hours was ~4 times greater with BTE than with RAMP shocks (Fig 4, P   Conclusions:  Thus, RAMP shocks defibrillate more reliably at a lower energy and cause markedly less damage as indicated by troponin I, ST elevation, and histopathology.
Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction
Authors: James T. Thackeray, Henri C. Hupe, Yong Wang, Jens P. Bankstahl, Georg Berding, Tobias L. Ross, Johann Bauersachs, Kai C. Wollert, Frank M. Bengel
Journal: Journal of the American College of Cardiology (2018)
Clinical and inflammatory phenotyping by breathomics in chronic airway diseases irrespective of the diagnostic label
Authors: Rianne de Vries, Yennece W.F. Dagelet, Pien Spoor, Erik Snoey, Patrick M.C. Jak, Paul Brinkman, Erica Dijkers, Simon K. Bootsma, Fred Elskamp, Frans H.C. de Jongh, Eric G. Haarman, Johannes C.C.M in ‘t Veen, Anke-Hilse Maitland-van der Zee, Peter J. Sterk
Journal: European Respiratory Journal (2018)

Asthma and chronic obstructive pulmonary disease (COPD) are complex and overlapping diseases that include inflammatory phenotypes. Novel anti-eosinophilic/anti-neutrophilic strategies demand rapid inflammatory phenotyping, which might be accessible from exhaled breath. Our objective was to capture clinical/inflammatory phenotypes in patients with chronic airway disease using an electronic nose (eNose) in a training and validation set. This was a multicentre cross-sectional study in which exhaled breath from asthma and COPD patients (n=435; training n=321 and validation n=114) was analysed using eNose technology. Data analysis involved signal processing and statistics based on principal component analysis followed by unsupervised cluster analysis and supervised linear regression. Clustering based on eNose resulted in five significant combined asthma and COPD clusters that differed regarding ethnicity (p=0.01), systemic eosinophilia (p=0.02) and neutrophilia (p=0.03), body mass index (p=0.04), exhaled nitric oxide fraction (p&lt;0.01), atopy (p&lt;0.01) and exacerbation rate (p&lt;0.01). Significant regression models were found for the prediction of eosinophilic (R 2 =0.581) and neutrophilic (R 2 =0.409) blood counts based on eNose. Similar clusters and regression results were obtained in the validation set. Phenotyping a combined sample of asthma and COPD patients using eNose provides validated clusters that are not determined by diagnosis, but rather by clinical/inflammatory characteristics. eNose identified systemic neutrophilia and/or eosinophilia in a dose-dependent manner.
T Cells Expressing Anti-B-Cell Maturation Antigen (BCMA) Chimeric Antigen Receptors with Antigen Recognition Domains Made up of Only Single Human Heavy Chain Variable Domains Specifically Recognize Bcma and Eradicate Tumors in Mice
Authors: Norris Lam, Leah Alabanza, Nathan Trinklein, Ben Buelow, James N. Kochenderfer
Journal: Blood (2017)
Interim Results from a Phase 1 Study of ADCT-301 (Camidanlumab Tesirine) Show Promising Activity of a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate in Relapsed/Refractory Hodgkin/Non-Hodgkin Lymphoma
Authors: Steven M. Horwitz, Mehdi Hamadani, Michelle A. Fanale, Jay Feingold, Alexander I Spira, Paul A Fields, Tobias Menne, Anand Karnad, Alison J. Moskowitz, Catherine Hildyard, Shui He, Joseph Boni, Graham Collins
Journal: Blood (2017)
Using Chaplains to Facilitate Advance Care Planning in Medical Practice
Authors: Aoife C. Lee, Catherine E. McGinness, Stacie Levine, Sean O’Mahony, George Fitchett
Journal: JAMA Internal Medicine (2018)

This quality improvement study examines the effectiveness of having a board-certified chaplain conduct advance care planning conversations and end of life preferences with patients at the time of a routine office visit with a physician.