tbuckley/cabot-search huggingface dataset:
Indatuximab ravtansine (BT062) combination treatment in multiple myeloma: pre-clinical studies
Authors: Kurt Schönfeld, Chantal Zuber, Jan Pinkas, Thomas Häder, Katrin Bernöster, Christoph Uherek
Journal: Journal of Hematology & Oncology (2017)

Indatuximab ravtansine is a monoclonal antibody-linked cytotoxic agent that specifically targets CD138-expressing cells. Monotherapy has been shown to significantly inhibit multiple myeloma tumour growth in vivo and improve host survival. Here, we show that in most cell lines tested, indatuximab ravtansine acts additively or even synergistically with clinically approved therapies for treatment of multiple myeloma. In addition, in vivo mouse xenograft models confirmed the activity of indatuximab ravtansine in combination with lenalidamide and lenalidomide/dexamethasone. Indatuximab ravtansine may therefore be a suitable combination partner for multiple myeloma, and a clinical study is ongoing.
Surviving childhood cancer—What next? Challenges in developing countries.
Authors: P. Kurkure, V. Dhamankar, S. Goswami, N. Dalvi, E. Rawat-Pawar
Journal: Journal of Clinical Oncology (2011)

9571 Background: Advances in treatment of childhood cancer have increased survival, frequently accomplished at cost of late effects. Curing more children without sequelae is a moving goalpost. Management of childhood cancers is difficult and is often guided by socioeconomic constraints in developing countries. Morbidity of late effects adds to burden of therapy. A need to address these issues was felt. Methods: Drawing inspiration from efforts at St. Jude Children's Research Hospital long-term follow-up clinic for survivors of childhood cancer, appropriately named, After Completion of Therapy (ACT) Clinic to emphasize that ACTs are needed beyond therapy to achieve CURE, was initiated at Tata Memorial Hospital in February 1991. Aims of clinic are to monitor growth, development, sexual maturation and somatic late effects of therapy and to apply corrective measures. Results: From Feb 1991 to Feb 2011, 1,190 survivors (off therapy and disease free for >2 years) have been enrolled in ACT clinic. Highlights of observations are 1) striking male preponderance (3:1) suggestive of preferential treatment to male child in our society. 2) Less frequent (9%) grade III sequel in survivors of hematolymphoid malignancies vis-à-vis. Solid tumours( 29%) highlighting need for organ preservation protocols. 3) Increased risk of death attributed to late recurrence and SMN emphasizing need for life long follow up. Conclusions: Our ACT model has attained 3 milestones: 1) Providing longitudinal care at a tertiary care center. 2) Ongoing communication with primary care provider ensuring continuity of follow-up. 3) Education and empowerment of survivors through voluntary support group, UGAM, sensitizing them towards need for continued surveillance, healthy lifestyle and becoming ambassador of the message “Childhood Cancer is Curable” in society. Clinical characteristic of 1,190 survivors. Median age at diagnosis 6 yrs. (0-19 yrs) Median time since diagnosis 9 yrs. (2-37 yrs) Median time since cessation of therapy 8 yrs. (2-35 yrs) Median duration of follow-up 4 yrs. (0-19 yrs) Grading of late effects: Normal 0 559 (46%) Abnormal lab report—no intervention I 227 (19) Simple intervention II 110 (90%) Complex intervention III 241 (20%) Life-threatening complications IV 63 (5%)
Fatty Acids and NLRP3 Inflammasome–Mediated Inflammation in Metabolic Tissues
Authors: Jessica C. Ralston, Claire L. Lyons, Elaine B. Kennedy, Anna M. Kirwan, Helen M. Roche
Journal: Annual Review of Nutrition (2017)

Worldwide obesity rates have reached epidemic proportions and significantly contribute to the growing prevalence of metabolic diseases. Chronic low-grade inflammation, a hallmark of obesity, involves immune cell infiltration into expanding adipose tissue. In turn, obesity-associated inflammation can lead to complications in other metabolic tissues (e.g., liver, skeletal muscle, pancreas) through lipotoxicity and inflammatory signaling networks. Importantly, although numerous signaling pathways are known to integrate metabolic and inflammatory processes, the nucleotide-binding and oligomerization domain–like receptor, leucine-rich repeat and pyrin domain–containing 3 (NLRP3) inflammasome is now noted to be a key regulator of metabolic inflammation. The NLRP3 inflammasome can be influenced by various metabolites, including fatty acids. Specifically, although saturated fatty acids may promote NLRP3 inflammasome activation, monounsaturated fatty acids and polyunsaturated fatty acids have recently been shown to impede NLRP3 activity. Therefore, the NLRP3 inflammasome and associated metabolic inflammation have key roles in the relationships among fatty acids, metabolites, and metabolic disease. This review focuses on the ability of fatty acids to influence inflammation and the NLRP3 inflammasome across numerous metabolic tissues in the body. In addition, we explore some perspectives for the future, wherein recent work in the immunology field clearly demonstrates that metabolic reprogramming defines immune cell functionality. Although there is a paucity of information about how diet and fatty acids modulate this process, it is possible that this will open up a new avenue of research relating to nutrient-sensitive metabolic inflammation.
Predictive Factors for Rapid Engraftment of Neutrophil and Platelet After Allogenic Peripheral Blood Stem Cell Transplantation in Patients with Hematologic Malignancies
Authors: Ho Sup Lee, Lee Chun Park, Eun Mi Lee, Byeong Jin Ye, Joon Ho Moon, Won Sik Lee, Ho-Jin Shin, Jooseop Chung, Yang Soo Kim
Journal: Blood (2012)
Management of drug budgets
Authors: J. P Ballantyne, P. O Behan, I. Bone, W. F Durward, D. Grosset, P. G E Kennedy, R. A Metcalfe, C. P O'Leary, R. H K Petty, M. Thomas, H. J Willison, R. Duncan, A. G Wade
Journal: BMJ (1999)

Editor—As the local neurologists implementing the introduction of new drugs into neurological practice we take issue with the process described in Beard et al’s article about systems and strategies for managing the drugs budget in Glasgow.1 We recognise the importance of pragmatism and sound economic analysis in meeting the challenge of increasing drug costs to the NHS. However, we have no confidence in the methods currently implemented by the Glasgow area drugs and therapeutics committee in the assessment of new drugs.

It was made clear to us that if we did not participate in “pragmatic outcome studies” our patients would not have access to new treatments. For this reason we reluctantly agreed to provide limited reports to the drugs and therapeutics committee. These studies have been open label, uncontrolled, and of small numbers of patients. The criteria for assessing sufficient cost effectiveness, which the committee requires to justify subsequent funding, were not defined or explained to us at any stage. At best these studies might produce grade 4 data (as defined by United States Agency for Health Care Policy and Research2).

We regard it as crucial that the responsibility for funding decisions is seen to lie where it does, in fact, lie. The current strategy whereby “if hospital specialists cannot show that a treatment provides measurable and worthwhile benefit it will not be purchased” has the effect of shifting perceived responsibility for funding decisions away from the purchaser towards the clinician. We do not disagree with the concept of cost benefit or cost utility analysis (in distinction to cost effectiveness analysis) in evaluating new drugs, and would take part in such studies if they were adequately resourced and constructed in a manner that would produce new and useful data.

We cannot endorse Beard et al’s view that other health boards should follow the example of Glasgow—an example that the authors themselves recognise may lead to “postcode prescribing.” Beard et al’s paper shows the urgent need to advance national policies for introducing new drugs into clinical practice. We trust that such policies will begin to emerge with leadership from the Department of Health, the royal colleges, specialist societies, and the National Institute for Clinical Excellence. Such guidance should promote equity of access to treatment, appropriate use of drugs, and scientifically sound economic analysis of benefit.
Expressing N-RasG12D from the Endogenous Promoter Induces Myeloproliferative Disease (MPD) and Cooperates with Retroviral Insertional Mutagenesis (RIM) To Generate Acute Myeloid Leukemia (AML).
Authors: Qing Li, Kevin Haigis, Andrew McDaniel, Benjamin Huang, Michelle Miller, Angell Shieh, Scott Kogan, Lynda Wolff, Tyler Jacks, Kevin Shannon
Journal: Blood (2007)
Therapeutic Phlebotomy in Children with Sickle Cell Anemia, Stroke, and Iron Overload: The SWiTCH Experience
Authors: Banu Aygun, Nicole A Mortier, Karen Kesler, Willliam H Schultz, Ofelia A. Alvarez, Zora R. Rogers, Janet L. Kwiatkowski, Scott T Miller, Pamela Sylvestre, Alan R. Cohen, Russell E. Ware
Journal: Blood (2011)
Evaluation of Mechanisms of Resistance to Arsenic Trioxide In Patients with Acute Promyelocytic Leukemia
Authors: Ezhilarasi Chendamarai, Ansu Abu Alex, Saravanan Ganesh, Kavitha M Lakshmi, Sachin Jadhav, Biju George, Aby Abraham, Poonkuzhali Balasubramanian, Shaji Ramachandran, Alok Srivastava, Vikram Mathews
Journal: Blood (2010)
The evolution of clinical guidelines for dermatologists: <scp>GRADE</scp> , <scp>AGREE</scp> and occasionally consensus by experts
Authors: J.R. Ingram, A. Anstey
Journal: British Journal of Dermatology (2017)

E‐mail: IngramJR@cardiff.ac.uk J.R.I. http://orcid.org/0000-0002-5257-1142A.A. http://orcid.org/0000-0002-6345-4144 Guidelines abound in dermatology clinical practice covering all aspects of patient care. Their importance to busy clinicians was recognized more than 20 years ago as clinical practice became increasingly complex, risky and litigious. Many professional organizations across the international world of dermatology have created infrastructure to produce clinical guidelines to meet this demand. A range of guideline styles has emerged, from initial 'expert consensus reports', to more rigorous examples that incorporate the principles of evidence‐based medicine. But what evidence is there on how clinical guidelines are actually used by dermatologists? Do clinicians use the highest‐quality guidelines in their daily clinical practice, in spite of the documents being time consuming to digest, or do they prefer more concise expert consensus guidelines? Perhaps they use both? There is clearly a need for research into this topic to help guide the creation of guidelines. Guideline production by the British Association of Dermatologists (BAD) has achieved a new level of rigour and sophistication with the use of Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and broad stakeholder involvement. The updated methodology presented in this issue1 of the BJD is based on criteria set out in the Appraisal of Guidelines REsearch and Evaluation (AGREE II) instrument,2 to ensure that BAD guidelines continue to be accredited by the U.K. National Institute for Health and Care Excellence (NICE). Involvement of patient groups and patient representatives is emphasized, enabling the ultimate consumers of healthcare guidance to be involved in shaping the guidance from the very beginning.
Origin and evolution of the sponge aggregation factor gene family
Authors: Laura F. Grice, Marie E. A. Gauthier, Kathrein E. Roper, Xavier Fernàndez-Busquets, Sandie M. Degnan, Bernard M. Degnan
Journal: Molecular Biology and Evolution (2017)

Although discriminating self from nonself is a cardinal animal trait, metazoan allorecognition genes do not appear to be homologous. Here, we characterize the Aggregation Factor (AF) gene family, which encodes putative allorecognition factors in the demosponge Amphimedon queenslandica, and trace its evolution across 24 sponge (Porifera) species. The AF locus in Amphimedon is comprised of a cluster of five similar genes that encode Calx-beta and Von Willebrand domains and a newly defined Wreath domain, and are highly polymorphic. Further AF variance appears to be generated through individualistic patterns of RNA editing. The AF gene family varies between poriferans, with protein sequences and domains diagnostic of the AF family being present in Amphimedon and other demosponges, but absent from other sponge classes. Within the demosponges, AFs vary widely with no two species having the same AF repertoire or domain organization. The evolution of AFs suggests that their diversification occurs via high allelism, and the continual and rapid gain, loss and shuffling of domains over evolutionary time. Given the marked differences in metazoan allorecognition genes, we propose the rapid evolution of AFs in sponges provides a model for understanding the extensive diversification of self–nonself recognition systems in the animal kingdom.
HFE C282Y Mutation as a Genetic Modifier Influencing Disease Susceptibility for JAK2 V617F Positive Chronic Myeloproliferative Disease.
Authors: Hajnalka Andrikovics, Nora Meggyesi, Aniko Szilvasi, Julia Tamaska, Gabriella Halm, Sandor Lueff, Sarolta Nahajevszky, Miklos Egyed, Judit Varkonyi, Gabor Mikala, Andrea Sipos, Attila Tordai, Tamas Masszi
Journal: Blood (2006)
Symptomatic and Indolent Waldenström’s Macroglobulinemia Display Different Biological and Cytogenetic but Not Immunophenotypic Characteristics.
Authors: Enrique M. Ocio, Gema Mateo, Belen Vidriales, Consuelo Lopez-Berges, Norma C. Gutierrez, Jesus M. Hernandez, Fermin M. Sanchez-Guijo, Maria J. Moro, Jose Hernandez, Javier Fernandez-Calvo, Javier Garcia-Frade, Alberto Orfao, J.F. San Miguel
Journal: Blood (2004)
Mutation-Enrichment Next-Generation Sequencing for Quantitative Detection of <i>KRAS</i> Mutations in Urine Cell-Free DNA from Patients with Advanced Cancers
Authors: Takeo Fujii, Afsaneh Barzi, Andrea Sartore-Bianchi, Andrea Cassingena, Giulia Siravegna, Daniel D. Karp, Sarina A. Piha-Paul, Vivek Subbiah, Apostolia M. Tsimberidou, Helen J. Huang, Silvio Veronese, Federica Di Nicolantonio, Sandeep Pingle, Cecile Rose T. Vibat, Saege Hancock, David Berz, Vladislava O. Melnikova, Mark G. Erlander, Rajyalakshmi Luthra, E. Scott Kopetz, Funda Meric-Bernstam, Salvatore Siena, Heinz-Josef Lenz, Alberto Bardelli, Filip Janku
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Tumor-derived cell-free DNA (cfDNA) from urine of patients with cancer offers noninvasive biological material for detection of cancer-related molecular abnormalities such as mutations in Exon 2 of KRAS. Experimental Design: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA was developed, and results were compared with clinical testing of archival tumor tissue and plasma cfDNA from patients with advanced cancer. Results: With 90 to 110 mL of urine, the KRASG12/G13 cfDNA test had an analytical sensitivity of 0.002% to 0.006% mutant copies in wild-type background. In 71 patients, the concordance between urine cfDNA and tumor was 73% (sensitivity, 63%; specificity, 96%) for all patients and 89% (sensitivity, 80%; specificity, 100%) for patients with urine samples of 90 to 110 mL. Patients had significantly fewer KRASG12/G13 copies in urine cfDNA during systemic therapy than at baseline or disease progression (P = 0.002). Compared with no changes or increases in urine cfDNA KRASG12/G13 copies during therapy, decreases in these measures were associated with longer median time to treatment failure (P = 0.03). Conclusions: A quantitative, mutation-enrichment next-generation sequencing test for detecting KRASG12/G13 mutations in urine cfDNA had good concordance with testing of archival tumor tissue. Changes in mutated urine cfDNA were associated with time to treatment failure. Clin Cancer Res; 23(14); 3657–66. ©2017 AACR.
Evaluation of Azacitidine in Transfusion-Dependent, Epo-Refractory Patients with Lower-Risk Myelodysplastic Syndrome,
Authors: Magnus Tobiasson, Lena Brandefors, Ingunn Dybedal, Hege Garelius, Michael Grövdal, Inge Hoegh Dufva, Lars Kjeldsen, Lars Nilsson, Astrid Olsnes Kittang, Anna Porwit, Leonie Saft, Mette Skov Holm, Lars Möllgård, Eva Hellström-Lindberg
Journal: Blood (2011)
Clinical Patho-physiological Study on Effects of Pulmonary Arterial Pressure Decrease upon Ejection Time and Mechanical Effects of the Right Ventricle : Part I. Right Ventricular Ejection Time
Authors: Kenji Nariyama
Journal: Circulation (1965)

With an increasing interest in cor pulmonale, several factors influencing pulmonary hemodynamics have been investigated by many authors. Most of these authors have estimated the ventricular mechanical effect from minute mean value of both systolic and diastolic phases of the cardiac cycle. however, considering the fact that the maximum ventricular mechanical effect is performed at the ejection period during the systole and more particularly during the period when the semilunar valvular open, the measurement of the accurate ventricular mechanical effect should be obtained during the ejection period rather than during both systolic and diastolic phases as in previous works. In the present study, the author used three different vasopresser agents and analyzed various phases of pulmonary circulation. From these results, ejection time of the right ventricle, mean pulmonary pressure per ejection phase and the mechanical effects of the ejection were obtained and were compared with the results of previously described methods. Material and Method A total of 24 cases was used in this study including 3 cases of normal individuals, 16 cases of cardiacs, 4 with pulmonary diseases and one with hepatic disorder. A routine right heart catheterization was carried out with a double lumen catheter. The pressures of the right ventricle and pulmonar artery were measured with simultaneous recordings of both electrocardiogram and phonocardiogram. The subjects were divided into 2 groups according to their resting mean pulmonary arterial pressure. The group I of 11 cases showed their mean pressure not exceeding 11 mmHg, the group II, consists of 13 cases with mean pressure exceeding 18 mmHg. The blood gas analysis was carried out by the method of VAN SLYKE-NEIL and expired air was analyzed with SCHOLANDER'S gas analyzer. Cardiac output was measured by FICK'S method. The control pressure as first measured during room air breathing without drugs and the second measurement was carried out 15 to 20 minutes namely, 7-chlor-ethyl-theophylline (Cl. E. T.) intravenously (200 mg), 1.4 : 3.6-dianhy-drosorbitol-2.5-dinitrate (I. S. D. N.) sublingual (10 mg) and inhalation of 50 per cent O2, and following measurements were made.
Comparative in Vitro Cellular Data Alone Is Insufficient to Predict Clinical Responses and Guide Choice of BCR-ABL Inhibitor to Treat Imatinib-Resistant Chronic Myeloid Leukemia.
Authors: Pierre Laneuville, Clifford DiLea, Jürgen Mestan, Ophelia Yin, Richard C. Woodman, Paul Manley
Journal: Blood (2009)
Shigatoxin Triggers Thrombotic Thrombocytopenic Purpura in Genetically Susceptible ADAMTS13-Deficient Mice.
Authors: David G. Motto, Anil K. Chauhan, Guojing Zhu, Jonathon Homeister, Colin B. Lamb, Karl C. Desch, Han-Mou Tsai, Denisa D. Wagner, David Ginsburg
Journal: Blood (2005)
Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: A systematic review and meta-analysis
Authors: Woo-Jung Song, Hyun Jung Kim, Ji-Su Shim, Ha-Kyeong Won, Sung-Yoon Kang, Kyoung-Hee Sohn, Byung-Keun Kim, Eun-Jung Jo, Min-Hye Kim, Sang-Heon Kim, Heung-Woo Park, Sun-Sin Kim, Yoon-Seok Chang, Alyn H. Morice, Byung-Jae Lee, Sang-Heon Cho
Journal: Journal of Allergy and Clinical Immunology (2017)
Cleveland Clinic to re-evaluate its Wellness Institute after director questions vaccines
Authors: Owen Dyer
Journal: BMJ (2017)

The renowned US hospital the Cleveland Clinic is to re-examine the provision of alternative medicine services at its Wellness Institute after the institute’s medical director suggested a link between vaccines and autism in a blog published by local news sites.

Homeopathic products will no longer be sold at the site, and other services will be re-evaluated to determine whether they meet the clinic’s goal of providing evidence based medicine, a spokeswoman for the hospital said.

The Wellness Institute’s medical director and chief operating officer, Daniel Neides, a family doctor, sparked an online uproar when he wrote in a regular blog last week, “What I will stand up and scream is that newborns without intact immune systems and …
Determination of the Maximum Tolerated Dose of Panobinostat in Combination with a 5-Day Schedule of Azacitidine in High-Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia: Planned Interim Analysis of a Phase Ib/II Study
Authors: Peter T. Tan, Kate Reed, Patricia A. Walker, Sharon Avery, Sushrut S. Patil, Andrew Grigg, Peter Mollee, Othon L Gervasio, Ivo J. Winiger, Dirk Hönemann, Andrew H Wei, Andrew Spencer
Journal: Blood (2011)
Ongoing Activation of the BCR, NFκB, and Proliferation Pathways in Mantle Cell Lymphoma: Direct in Vivo Evidence for the Role of the Lymph Node Microenvironnment
Authors: Nakhle Saba, Delong Liu, Sarah E. M. Herman, Cliona Grant, Kieron Dunleavy, Stefania Pittaluga, Wyndham Wilson, Adrian Wiestner
Journal: Blood (2014)
Allogeneic Stem Cell Transplantation Is Associated with Prolonged Disease Control in Chemosensitive Aggressive Histology Lymphoma Patients When Done Early
Authors: Auro Viswabandya, Tony Panzarella, Dennis Dong Hwan Kim, Vikas Gupta, Jeffrey H. Lipton, Hans A. Messner, John Kuruvilla
Journal: Blood (2011)
Outcomes of Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Salvage Chemotherapy and Intention to Transplant in the Rituximab Era
Authors: Santosha A. Vardhana, Craig H. Moskowitz, Craig S. Sauter, Matthew J Matasar, Natasha Galasso, Kaitlin M Woo, Zhigang Zhang
Journal: Blood (2015)
GP workload is unsustainable, say researchers
Authors: Jacqui Wise
Journal: BMJ (2017)

The current GP workload is unsustainable and potentially affects patient safety and GPs’ wellbeing, researchers have concluded in the British Journal of General Practice .1

Caroline Croxson and colleagues, from the University of Oxford, said that their qualitative interview study shows that general practice may be at a crossroads regarding a sustainable model of care. They highlighted an urgent need to tackle the lack of investment and clinical capacity in general practice and said that managing patient expectations of what primary care can deliver and reducing bureaucracy …
Long-Term Responders after Brentuximab Vedotin: Experience on 57 Patients with Relapsed and Refractory Hodgkin and Anaplastic Large Cell Lymphoma
Authors: Pier Luigi Zinzani, Letizia Gandolfi, Beatrice Casadei, Cinzia Pellegrini, Alessandro Broccoli, Enrico Derenzini, Federica Quirini, Lorenzo Tonialini, Michele Cavo, Lisa Argnani, Vittorio Stefoni
Journal: Blood (2015)