tbuckley/cabot-search huggingface dataset:
Tipifarnib in Relapsed or Refractory Angioimmunoblastic T-Cell Lymphoma (AITL) and CXCL12+ Peripheral T-Cell Lymphoma (PTCL): Preliminary Results from an Open-Label, Phase 2 Study
Authors: Thomas E. Witzig, Lubomir Sokol, Eric D Jacobsen, Won-Seog Kim, Francine M. Foss, Ranjana H. Advani, Jose Maria Roncero Vidal, Ana Marin Niebla, Antonia Rodriguez Izquierdo, Raquel De Ona Navarrete, Fátima de la Cruz Vicente, Dolores Caballero, Rufino Mondejar, Miguel A. Piris, Robert Curry, Catherine Scholz, Antonio Gualberto
Journal: Blood (2018)
Prognostic value of serum TIE-2 and vascular endothelial growth factor levels in gastric cancer patients.
Authors: Mehmet Metin Seker, Enver Sancakdar, Ayse Seker, Aykut Bahceci, Turgut Kacan, Nalan Babacan
Journal: Journal of Clinical Oncology (2014)

e15085 Background: Angiogenesis is an essential process both for tumor growth and for metastasis. tyrosine kinase receptor-2 (TIE-2) and vascular endothelial growth factor (VEGF) are two important mediators of angiogenesis. Anti-VEGF therapies are being used in many solid tumors and there are many ongoing clinical trials with agents acting via TIE-2 pathway. In this trial we aimed to analyze the role of these mediators on chemotherapy response and survival. Methods: Forty cancer patients and 20 healthy controls were included in the study. All patients had treated with cytotoxic chemotherapy. Baseline serum samples were obtained from all participants and post-chemotherapy serum samples were obtained from patients. Serum vascular endothelial growth factor and TIE-2 levels were measured with quantitative enzyme-linked immunosorbent assay techniques. Results: The baseline serum vascular endothelial growth factor level was 189.85 pg/ml and 120.20 pg/ml, in cancer patients and the control group (p=0.004). The baseline serum TIE-2 level was 587.13 pg/ml and 233.0 pg/ml, in the patients and control group (p<0.001). There was a significant difference between patients’ baseline and post-chemotherapy VEGF levels (111.1 pg/ml; p<0.001) and patients’ baseline and post-chemotherapy TIE-2 levels (338.62 pg/ml; p<0.001). The median follow up period was 28 (12-88) months. The overall survival (OS) was 28 months and 3 year OS was 69.0% in patients whose VEGF level had decreased with chemotherapy or not (p=0.008). The overall survival (OS) was 28 months and 3 year OS was 82.4% in patients whose TIE-2 level had decreased with chemotherapy or not (p=0.001). Conclusions: Higher baseline TIE-2 and VEGF levels are related and worsen survival. Decreasing levels of VEGF and TIE-2 with chemotherapy, may be predictive for survival. Also, this trial showed that cytotoxic chemotherapy can influence angiogenesis as well as anti-VEGF therapies.
Clare Gerada: We need a complaints code of conduct
Authors: Clare Gerada
Journal: BMJ (2019)

The number of complaints against NHS staff is rising, possibly resulting (rightly) from better systems and general encouragement to complain if patients have concerns about their care. Complaints increased by 5% between 2016 and 2017.1 I have received my fair share of complaints, and all have affected me personally.

Patients must be able to complain when things have not gone as they should. But a complaint, no matter how trivial, is a powerful trigger for mental illness. A survey of nearly 8000 doctors found that 77% who had received a complaint were more likely to suffer moderate to severe depression and had twice the risk of moderate to severe anxiety compared to those with no history of a complaint.2 …
GATA1 in patients with essential thrombocythemia and anagrelide treatment.
Authors: Ciro Roberto Rinaldi, Ciaren Graham, Lillia BROWN
Journal: Journal of Clinical Oncology (2014)

7109 Background: GATA1 is the founding member of the GATA transcription factor family and is essential for cell maturation and differentiation within the erythroid and megakaryocytic lineages. Disturbance of its functions causes severe hematopoietic dysfunction and can result in blood disorders, such as thrombocytopenia, anaemia and even leukaemia. Several studies, have suggested a connection between GATA1 and myeloproliferative neoplasia (MPN). We previously reported, high GATA1 transcript levels are found in the bone marrow of patients with ET and PV, independent of the JAK2 V617F mutation, but not in other MPN. Anagrelide (ANA) has been proven to be an effective drug in reducing platelet count in ET. However, the mechanisms by which this drug induces this effect is still unclear. Recently Erusalimsky has reported that ANA results in down-modulation of GATA1 and its co-factor FOG1 in MK during in vitro differentiation. Methods: In this study, we analysed by Real Time PCR the expression of GATA1 in peripheral blood (PB) samples from 30 patients with ET and compared the levels of expression before and after treatment with common cytoreductive agents such as hydroxyurea (HU) and ANA. Results: We confirmed the data obtained in BM, with a significant up-regulation of GATA1 in ET compared to controls. When we measured the expression of GATA1 before and during treatment with ANA, there was a significant reduction of the GATA1 expression at 3 and 6 months of therapy, concomitantly with a reduction in platelets (PLT) counts. Interestingly, this was not equally observed in patients treated with HU, where despite reduction in PLT counts, the GATA1 levels rose. Furthermore, when we analysed patients on combination treatment ANA + HU, GATA1 expression reduced only when patients were taking ANA. When ANA treatment was stopped and the patient continued only on HU, GATA1 levels rose again. This data suggests a direct effect of ANA on GATA1 expression. Conclusions: GATA1 may represent a generic molecular marker in ET and a possible additional diagnostic criteria in thrombocytosis. GATA1 overexpression is independent from JAK2 mutations, and responds specifically to ANA therapy suggesting a role in monitoring therapy response.
iPSC-Derived NK Cells and Anti-PD-1 Antibody Synergize to Enhance T Cell Cytokine and Cytolytic Responses Against Multiple Tumors
Authors: Frank Cichocki, Ryan Bjordahl, Svetlana Gaidarova, Sajid Mahmood, Paul Rogers, Moyar Q. Ge, Dan S Kaufman, Sarah Cooley, Bahram Valamehr, Jeffrey S. Miller
Journal: Blood (2018)
Effect of exemestane plus everolimus on CTC counts and Ki-67 expression on CTCs in patients with advanced hormone receptor-positive, HER2-negative breast cancer.
Authors: Sofia Agelaki, Maria Spiliotaki, Christos Nikolaou, Eleni Politaki, Stella Apostolaki, Athanasios Kotsakis, Dimitrios Mavroudis, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (2014)

11042 Background: The utility of CTCs in predicting patient (pt) outcome has been demonstrated in metastatic breast cancer treated with chemotherapy or endocrine therapy. In this trial we evaluated the prognostic impact of CTC assessment in pts treated with exemestane plus the targeted therapy everolimus. Methods: Forty pts with HER2-negative metastatic breast cancer received exemestane plus everolimus. Blood was drawn for CTC assessment by CellSearch System and immunofluorescence (IF) analysis (7.5 and 10 ml, respectively) on day 1 of cycles 1 (n=40), 2 (n=39), 4 (n=28), on each disease evaluation and on relapse, whichever occurred first. Cytospins (106cells) of peripheral blood mononuclear cells (PBMCs) from 31 of 40 pts were double stained with pancytokeratin (CK) along with Ki-67 antibodies. Results: Using CellSearch 25 (62.5%) pts had detectable CTCs (cut-off ≥ 1 CTC) at baseline, 12 (30.8%) post-1st and 9 (32.1%), post-third cycle. In 9 pts no CTCs were observed at any time point. CTCs ≥5 were identified in 10 (25%), 6 (15.4%) and 3 (10.7%) pts at baseline, post-firstand post-third cycles, respectively. Four (40%) pts with baseline counts of CTCs ≥5 turned to <5 post-first ycle. Total CTC counts declined from 332 at baseline (mean number/pt 8.3, range 0-103) to 90 (mean 2.3, range 0-34) and 46 (mean 1.64, range 0 - 16) post-first and -third cycles, respectively. Using IF, 7 (22.5%) pts had detectable CK(+) CTCs (cutoff ≥ 1 CTC) at baseline; 8 (25.8%) of 31 and 7 (28%) of 25 were CTC(+) post -first and -third cycles, respectively. Total CTC numbers were 197 at baseline (mean, 16.42, range, 0-192) and 58 (mean 1.87, range 0-34) and 336 (mean 13.44, range 0 - 290) post-first and -third cycle, respectively; the ratio of Ki-67(+)/CK(+) CTCs declined from 32% to 13.8% and 13.4%, post-first and -third cycle, respectively. Conclusions: Exemestane plus everolimus effectively decreases CTC counts and the population of Ki-67(+) CTCs in HER2-negative metastatic breast cancer. Correlations with patient characteristics and outcome will be presented.
Catching the falling star: points to consider when using propensity scores
Authors: Fengchen Ouyang
Journal: Annals of the Rheumatic Diseases (2018)

Bergstra et al conducted a sophisticated study of a pertinent clinical question, ‘How to treat patients with rheumatoid arthritis when methotrexate has failed?’1 In particular, I welcome the introduction of the ‘multiple’ propensity score (PS) (better known by its more established name: generalised propensity score2 3) to observational studies in rheumatology. The authors provided a clear step-by-step tutorial which I am sure will be frequently used and cited. Since their article also aimed to teach, I would like to highlight some important points to readers who consider replicating these methods.

Use of PS methods has grown exponentially in clinical research. Suboptimal practice has unfortunately led to a level of scepticism for these versatile techniques.4 The theory and assumptions are often more involved, but some points can be easily conceptualised using …
New roads should prioritise cyclists to encourage physical activity, NICE recommends
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Local authorities should prioritise cyclists, pedestrians, and those who use public transport when building or upgrading new roads in order to encourage greater levels of physical activity, the National Institute for Health and Care Excellence (NICE) has advised.

In a draft quality standard1 for encouraging physical activity within the general population, NICE says that local planners should develop policies and schemes that prioritise safe, convenient, and inclusive access for pedestrians, cyclists, and people over motorised transports.

This should include providing tactile paving and even surfaces for people with limited mobility, and non-reflective, anti-glare paving surfaces for people …
Detection of BRAF mutations in the plasma of melanoma patients as an early marker of treatment efficiency.
Authors: Marc G. Denis, Amir Khammari, Audrey Vallee, Jean-Michel NGuyen, Anne-Chantal Knol, Melanie Saint-Jean, Lucie Peuvrel, Anabelle Brocard, Gaelle Quereux, Brigitte Dreno
Journal: Journal of Clinical Oncology (2014)

9069 Background: Mutant BRAF DNA can be detected in plasma of melanoma patients bearing a mutation in their tumor. Detection of these genetic alterations in circulating DNA has potential clinical applications. We investigated the relationship between mutant BRAF in plasma DNA and treatment response. Methods: DNA was extracted from plasma using the iPrep PureLink Virus Kit on an iPrep purification system (Invitrogen). BRAF mutations were detected using the Therascreen BRAF RGQ kit (Qiagen). Results: Seventeen patients (1 stage IIIC and 16 stage IV) with a mutated BRAF melanoma (V600E in all cases) were included. Pretreatment plasma samples were available in 10 of them, and the BRAF mutation was detected in 8 samples (80% sensitivity). Twelve patients were treated with a BRAF inhibitor, 4 with a combination of a BRAF inhibitor and a MEK inhibitor, and one patient was treated with chemotherapy (DTIC). After 3 months of melanoma treatment, the BRAF V600 mutation was detected in the plasma of 9 patients (9/17; 53,9%). The presence of mutant BRAF in plasma DNA was compared to the clinical response of patients. The BRAF mutation was present in the plasma of 6 out of the 7 patients who did not respond to treatment. In contrast, mutant BRAF DNA was absent from plasma in 7 out of the 10 patients with partial response to treatment (Fisher’s exact test : p = 0.04977). Mutant BRAF in circulating DNA was not associated with the number of metastatic sites at the same time (mean 2.625 in patients with mutant BRAF, and 2.22 in patients without mutant BRAF; p = 0.4266, Wilcoxon’s test). Conclusions: The sensitive detection of mutant BRAF in plasma would be useful for predicting treatment response to targeted therapy. Supported in part by a grant from Roche.
Association of <i>JAK2</i>-V617F Mutations Detected by Solid Tumor Sequencing With Coexistent Myeloproliferative Neoplasms
Authors: Gregory Riedlinger, Mohammad Hadigol, Hossein Khiabanian, Shridar Ganesan
Journal: JAMA Oncology (2019)

This study uses clinical sequencing data to examine the association between JAK2-V617F detected by solid tumor sequencing and mutations in the tumor, clonal hematopoiesis of indeterminate potential, or myeloproliferative neoplasms.
Factors associated with falls in older patients with cancer: A cross-sectional study of Medicare beneficiaries.
Authors: Allison Magnuson, Chintan Pandya, Supriya Gupta Mohile
Journal: Journal of Clinical Oncology (2014)

e20514 Background: Falls cause injuries, functional impairment and death. The aim of this study is to compare the prevalence of falls in older patients with and without cancer and to identify factors associated with falls. Methods: 2006-2007 SEER–Medicare Health Outcomes Survey linkage population-based database was used for this cross-sectional study. Falls in beneficiaries aged > 65 with breast, prostate, colon and lung cancer over the prior 12 months were compared to those without cancer. Logistic regression analysis was performed to evaluate factors associated with falls in a nationally representative population of older patients with and without cancer. Separate logistic regression analysis was performed with each cancer patient population separately (i.e., breast, prostate, colon, lung) to investigate the effect of cancer type, stage, treatment (radiation and/or surgery) and time since diagnosis on falls, after controlling for covariates. Results: The study population included 75,506 non-cancer and 1,736 beneficiaries with cancer. The prevalence of falls in cancer patients was 24.37% compared to 20.78% in non-cancer patients (p<0.001). Factors associated with falls included cancer (OR=1.17, p=0.001), female sex (OR=1.19), Caucasian (OR=1.23), older age (OR=1.84), single/divorced/widowed (OR=1.08), higher education (OR=1.21), higher household income (OR=1.16), ADL deficit (OR=1.23), multiple comorbid conditions (OR=1.57), depression (OR=1.50), poor vision (OR=1.32), less bodily pain (OR=1.02) and problem with balance/walking in past 12 months (OR=4.40). Unless noted, p<0.001. After controlling for covariates, breast cancer diagnosis was associated with falls (OR 1.36, p=0.003). Other cancer types, stage, treatment history, and time from diagnosis were not significantly associated with falls. Conclusions: Cancer is independently associated with falls in a nationally representative population of Medicare beneficiaries. Many factors associated with falls are modifiable and may be amenable to interventions. Comprehensive assessment and multifactorial intervention programs should be developed for this vulnerable population.
Boosting of cellular and humoral immune responses to HPV16/18 antigens by VGX-3100: A follow-on phase I trial.
Authors: Matthew P Morrow, Kimberly Kraynyak, Xuefei Shen, Christine Knott, Jian Yan, Kate Broderick, Amir Khan, Mary Giffear, Jessica Lee, Jean Boyer, David Weiner, Niranjan Sardesai, Mark Bagarazzi
Journal: Journal of Clinical Oncology (2014)

3101 Background: Despite the development of highly effective prophylactic vaccines against human papillomavirus (HPV) types 16 and 18, prevention of cervical dysplasia and cancer in women infected with high-risk HPV types remains an unmet medical need. We have previously reported data from a phase 1 dose escalation study for a therapeutic HPV16/18 vaccine, VGX-3100, delivered by in vivo electroporation (EP). Immunization in that study drove seroconversion as gauged by ELISA to at least one vaccine antigen in 100% of patients while 78% mounted an Interferon Gamma (IFNg)ELISpot response to the vaccine antigens.. Methods: Of the 18 patients enrolled in that trial, 13 were rolled into a second phase 1 immunogenicity trial entailing a single 6.0mg boost of VGX-3100 administered using EP. Results: Increases in immune reactivity following the boost were noted, as eleven patients showed boost-driven increases in ELISA titers and the mean ELISpot magnitude increased by at least 2-fold in seven patients irrespective of the dose of VGX-3100 they received in the first clinical trial. Additional Flow Cytometric analyses of cellular responses revealed increased HPV specific IFNg and TNFa production as compared to prior to the boost (0.34% to 0.57% and 0.27% to 0.60%, respectively) with contribution from both the CD4+ and CD8+ T cell compartments. Additionally, HPV specific CD8+ T cells expressing Fas Ligand concomitantly with either cytokine or the degranulation marker CD107a increased from 0.19% to 0.28% following the boost. Employment of staining for the activation marker CD137 (41BB) showed that patient CD8+ T cells continued to activate efficiently in response to HPV antigens following the boost, including a statistically significant increase in co-expression of Granzyme B and Perforin within the activated T cell subset (p=0.026). Conclusions: Taken together these data suggest that immunization with VGX-3100 drives immune responses that have the ability to be further boosted by additional administrations. Current studies are underway in an untreated HPV 16/18 associated CIN2/3 setting to assess whether these significant immune responses can translate into clinically effective treatment options to surgery. Clinical trial information: NCT01188850.
Does the presence of hepatitis B and/or C viruses affect the evolution of diffuse large B-cell lymphoma?
Authors: Judit Rubio, Fernando Franco, Magda Palka, David Perez, Elena Almagro, Miriam Mendez, Virginia Calvo, Isabel Millan, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2014)

e19526 Background: The aim of the study was to evaluate the clinical characteristics and survival of patients diagnosed with diffuse large-B-cell lymphoma (DLBCL) with positive hepatitis B and/or C virus (HBV-C). Methods: We reviewed 224 patients diagnosed with DLBCL in our hospital between October 1982 and September 2013. Clinical, treatment and following items were obtained. Results: We found 21 positive HBV and/or HCV (9.3%) [4 of them (1.78%) were both positive], and 203 (90.7%) negative virus (NV), without significant differences with respect to age, gender, histological grade, IPI, extranodal involvement, bone marrow disease or Bulky disease in both groups. 14 patients (67%) with HBV-C were diagnosed in stages III and IV, while 78 (40.1%) of NV were diagnosed in advanced stages. It exists significant differences in the median of nodal regions affected [HBV-C 4 (0-8) and NV 2 (0-14), p=0.05] and a worse liver function in patients with HBV-C (28.6% vs 10%, p=0.028). There were no differences in treatment modality, number of cycles, dose intensity nor response. No differences in the number of relapses were found either. All previous tumors, second tumors or simultaneous tumors appeared in the NV group. There were no differences in the study of the causes of death either (DLBCL, second tumor or other causes). No significant differences in the relative risk of death associated with virus (HR 0.87 (CI 95% 0.40-1.89, p=0.73) and the relative risk of events associated with virus (HR 0.96 (CI 95% 0.48-1.90, p=0.91) were found. The median DFS was 22.6 months (0.1-262) in NV group and 18.5 months (0.2-166) in HBV-C group. No significant differences in the median of probability of OS and DFS in both groups were found. Conclusions: Despite the differences in terms of stage, number of affected nodal regions and a worse liver function, patients with DLBCL and HBV-C were treated, responded and evolved in the same way that the NV patients.
Phase I-II Study of Crenolanib Combined with Standard Salvage Chemotherapy and Crenolanib Combined with 5-Azacitidine in Acute Myeloid Leukemia Patients with FLT3 Activating Mutations
Authors: Iman Aboudalle, Hagop M. Kantarjian, Maro N. Ohanian, Yesid Alvarado, Elias J. Jabbour, Guillermo Garcia-Manero, Kiran Naqvi, William G. Wierda, Naval G. Daver, Jan A. Burger, Marina Y. Konopleva, Koichi Takahashi, Michael Andreeff, Naveen Pemmaraju, Alessandra Ferrajoli, Gautam Borthakur, Tapan M. Kadia, Farhad Ravandi, Jorge E. Cortes
Journal: Blood (2018)
Abstract 19008: Reduction in Right Ventricular Myocyte Contractility in a Plakophilin-2 Mouse Model of Arrhythmogenic Cardiomyopathy
Authors: Emmanuel M Camors, Ryan D Sullivan, Enkhsaikhan Purevjav, Jeffrey A Towbin
Journal: Circulation (2017)

Background: Arrhythmogenic cardiomyopathies (ACM) are inherited genetic disorders characterized by a high risk of life-threatening arrhythmias. ACMs originate from mutations in desmosomal genes that prevent normal myocyte-myocyte adhesion and cause the loss of cardiac function, classically in the right ventricle (RV), due to progressive replacement of the cells by fibrofatty infiltration. Hypothesis: Our aim was to define the outcome of plakophilin-2 gene mutations on myocyte contractility. Methods: We created a knock-in mouse model based on a single thymidine insertion in the coding sequence of the plakophilin-2 (PKP2) gene, which resulted in the expression of a truncated PKP2-L404/X5 protein. Results: Serial echocardiography revealed that RV contractility in 18-week-old PKP2 heterozygous mice (PKP2+/-) was significantly reduced compared to WT and continued to deteriorate with aging (n= 5-7 hearts/group, P<0.05). Meanwhile, the LV of PKP2+/- hearts remained normal. Fibrosis was undetectable in RV and LV ...