tbuckley/cabot-search huggingface dataset:
Toxicity and Efficacy Probability Interval Design for Phase I Adoptive Cell Therapy Dose-Finding Clinical Trials
Authors: Daniel H. Li, James B. Whitmore, Wentian Guo, Yuan Ji
Journal: Clinical Cancer Research (2016)

Recent trials of adoptive cell therapy (ACT), such as the chimeric antigen receptor (CAR) T-cell therapy, have demonstrated promising therapeutic effects for cancer patients. A main issue in the product development is to determine the appropriate dose of ACT. Traditional phase I trial designs for cytotoxic agents explicitly assume that toxicity increases monotonically with dose levels and implicitly assume the same for efficacy to justify dose escalation. ACT usually induces rapid responses, and the monotonic dose-response assumption is unlikely to hold due to its immunobiologic activities. We propose a toxicity and efficacy probability interval (TEPI) design for dose finding in ACT trials. This approach incorporates efficacy outcomes to inform dosing decisions to optimize efficacy and safety simultaneously. Rather than finding the maximum tolerated dose (MTD), the TEPI design is aimed at finding the dose with the most desirable outcome for safety and efficacy. The key features of TEPI are its simplicity, flexibility, and transparency, because all decision rules can be prespecified prior to trial initiation. We conduct simulation studies to investigate the operating characteristics of the TEPI design and compare it to existing methods. In summary, the TEPI design is a novel method for ACT dose finding, which possesses superior performance and is easy to use, simple, and transparent. Clin Cancer Res; 23(1); 13-20. ©2016 AACR.
Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition
Authors: Jatinder K. Juss, David House, Augustin Amour, Malcolm Begg, Jurgen Herre, Daniel M. L. Storisteanu, Kim Hoenderdos, Glyn Bradley, Mark Lennon, Charlotte Summers, Edith M. Hessel, Alison Condliffe, Edwin R. Chilvers
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Acute respiratory distress syndrome is refractory to pharmacological intervention. Inappropriate activation of alveolar neutrophils is believed to underpin this disease’s complex pathophysiology, yet these cells have been little studied.Objectives: To examine the functional and transcriptional profiles of patient blood and alveolar neutrophils compared with healthy volunteer cells, and to define their sensitivity to phosphoinositide 3-kinase inhibition.Methods: Twenty-three ventilated patients underwent bronchoalveolar lavage. Alveolar and blood neutrophil apoptosis, phagocytosis, and adhesion molecules were quantified by flow cytometry, and oxidase responses were quantified by chemiluminescence. Cytokine and transcriptional profiling were used in multiplex and GeneChip arrays.Measurements and Main Results: Patient blood and alveolar neutrophils were distinct from healthy circulating cells, with increased CD11b and reduced CD62L expression, delayed constitutive apoptosis, and primed oxidase responses. Incubating control cells with disease bronchoalveolar lavage recapitulated the aberrant functional phenotype, and this could be reversed by phosphoinositide 3-kinase inhibitors. In contrast, the prosurvival phenotype of patient cells was resistant to phosphoinositide 3-kinase inhibition. RNA transcriptomic analysis revealed modified immune, cytoskeletal, and cell death pathways in patient cells, aligning closely to sepsis and burns datasets but not to phosphoinositide 3-kinase signatures.Conclusions: Acute respiratory distress syndrome blood and alveolar neutrophils display a distinct primed prosurvival profile and transcriptional signature. The enhanced respiratory burst was phosphoinositide 3-kinase–dependent but delayed apoptosis and the altered transcriptional profile were not. These unexpected findings cast doubt over the utility of phosphoinositide 3-kinase inhibition in acute respiratory distress syndrome and highlight the importance of evaluating novel therapeutic strategies in patient-derived cells.
Identification of Candidate Oncogenes in Acute Megakaryoblastic Leukemias with Gain of Chromosome 19.
Authors: Sara Alvarez, Cristina Largo, David Blesa, Alfonso Gomez-Pineda, M. Carmen Martin, Donal MacGrogan, Jose F. Garcia, Giovanna Roncador, Javier Benitez, Stephen D. Nimer, Juan C. Cigudosa
Journal: Blood (2004)
TCT-534 A Novel Magnesium Bioresorbable Stent Allows Coronary Vascular Restoration and Positive Remodeling in a Large Animal Model: A Sequential Optical Coherence Tomography Study
Authors: Celso K. Takimura, Rafael R. Cavalcanti, Micheli Z. Galon, Raul Arrieta, Armando Tellez, Carlos M. Campos, Luciano Curado, Clemens Meyer-Kobbe, Jose E. Krieger, Pedro A. Lemos
Journal: Journal of the American College of Cardiology (2015)
Expression of Apoptosis Repressor with Caspase Recruitment Domain (ARC), An Antiapoptotic Protein, Is Strongly Prognostic in Acute Myeloid Leukemia (AML).
Authors: Bing Z. Carter, Nianxiang Zhang, Kevin R. Coombes, Duncan H. Mak, YiHua Qiu, Deborah A. Thomas, Farhad Ravandi, Hagop Kantarjian, Michael Andreeff, Steven M. Kornblau
Journal: Blood (2009)
A Phase 1 Study of Sequential Idarubicin + Cytarabine, Followed by Lenalidomide, in Patients with Previously Untreated Acute Myeloid Leukemia (AML)
Authors: Jeffrey E. Lancet, Rami S. Komrokji, Daohai Yu, Anjali S. Advani, Tammy Searles, Mikkael A. Sekeres, Alan F. List
Journal: Blood (2011)
A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Philippe Jolliet, Lamia Ouanes-Besbes, Fekri Abroug, Jalila Ben Khelil, Mohamed Besbes, Aude Garnero, Jean-Michel Arnal, Fabrice Daviaud, Jean-Daniel Chiche, Benoît Lortat-Jacob, Jean-Luc Diehl, Nicolas Lerolle, Alain Mercat, Keyvan Razazi, Christian Brun-Buisson, Isabelle Durand-Zaleski, Joëlle Texereau, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O2, but its impact on clinical outcomes remains unknown.Objectives: To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O2 in reducing NIV failure (25–15%) in severe hypercapnic COPD exacerbations.Methods: This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries. Inclusion criteria were COPD exacerbations with PaCO2 ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, PaO2 ≤ 50 mm Hg, and oxygen saturation (arterial [SaO2] or measured by pulse oximetry [SpO2]) ≤ 90%. A 6-month follow-up was performed.Measurements and Main Results: The primary endpoint was NIV failure (intubation or death without intubation in the ICU). The secondary endpoints were physiological parameters, duration of ventilation, duration of ICU and hospital stay, 6-month recurrence, and rehospitalization rates. The trial was stopped prematurely (445 randomized patients) because of a low global failure rate (NIV failure: air/O2 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O2 group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, PaCO2, and encephalopathy score improved significantly faster with heliox. ICU stay was comparable between the groups. In patients intubated after NIV failed, patients on heliox had a shorter ventilation duration (7.4 ± 7.6 d vs. 13.6 ± 12.6 d; P = 0.02) and a shorter ICU stay (15.8 ± 10.9 d vs. 26.7 ± 21.0 d; P = 0.01). No difference was observed in ICU and 6-month mortality.Conclusions: Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O2 but does not prevent NIV failure. Overall, the rate of NIV failure was low.Clinical trial registered with www.clinicaltrials.gov (NCT 01155310).
Plasma Copeptin, Kidney Outcomes, Ischemic Heart Disease, and All-Cause Mortality in People With Long-standing Type 1 Diabetes
Authors: Gilberto Velho, Ray El Boustany, Guillaume Lefèvre, Kamel Mohammedi, Frédéric Fumeron, Louis Potier, Lise Bankir, Nadine Bouby, Samy Hadjadj, Michel Marre, Ronan Roussel
Journal: Diabetes Care (2016)

Plasma copeptin, a surrogate for vasopressin, has been associated with a decline in renal function and albuminuria in population-based studies as well as with progression of diabetic nephropathy in people with type 2 diabetes. We assessed the risk of kidney and coronary events and all-cause mortality associated with plasma copeptin in people with type 1 diabetes.Plasma copeptin was measured in baseline samples of the GENEDIAB (n = 398; 56% male; mean ± SD age 45 ± 12 years and diabetes duration 28 ± 10 years) and GENESIS (n = 588; 52% male; age 42 ± 11 years; diabetes duration 27 ± 9 years) cohorts. Follow-up data were available for 218 GENEDIAB and 518 GENESIS participants. Median duration of follow-up was 10.2 and 5.0 years, respectively.Upper sex-specific tertiles of copeptin were associated with a higher incidence of end-stage renal disease (ESRD) during follow-up (hazard ratio [HR] for third vs. first tertile 26.5 [95% CI 8.0-163.3; P < 0.0001]; analysis in pooled cohorts adjusted for age, sex, duration of diabetes, and cohort membership). The highest tertile of copeptin was also associated with incidence of myocardial infarction or coronary revascularization (HR 2.2 [95% CI 1.2-4.0]; P = 0.01) and all-cause mortality (HR 3.3 [95% CI 1.8-6.5]; P < 0.0001) during follow-up.Plasma copeptin is a predictor for the risk of ESRD, coronary heart disease, and all-cause mortality in people with type 1 diabetes. Results are consistent with data from experimental and epidemiological studies, suggesting that high circulating levels of vasopressin are deleterious to renal function.
TCT-228 A Simple Admission Risk Model for STEMI Treated with Primary PCI: Development and Comparative Validation
Authors: Istvan Hizoh, Dominika Domokos, Zalan Gulyas, Gyongyver Banhegyi, Zsuzsanna Majoros, Laszlo Major, Timea Ratkai, Robert Gabor Kiss
Journal: Journal of the American College of Cardiology (2015)
Specific Tumor Targeting and Potent Bystander Killing with SGN-35, an Anti-CD30 Antibody Drug Conjugate.
Authors: Nicole M. Okeley, Stephen C. Alley, Charles G. Cerveny, Jamie Andreyka, Russell J. Sanderson, Martha Anderson, Dennis R. Benjamin, Che-Leung Law, Eric Sievers, Nathan C. Ihle
Journal: Blood (2006)
Comparison of inflammatory breast cancer and T4 non-IBC breast cancer patients at a remote tertiary cancer center.
Authors: Daniel Adam Breadner, Andrew George Robinson
Journal: Journal of Clinical Oncology (2015)

e17581 Background: Inflammatory breast cancer (IBC) is a rare, more aggressive form of primary breast cancer comprising approximately 1-2% of all breast cancers. A multidisciplinary approach to the treatment of IBC has drastically changed the prognosis. Current therapy guidelines indicate systemic chemotherapy, followed by surgery, and then radiation therapy. The centralization of specialized medical services poses distinct barriers to some living in rural and remote areas. Specialists in rural hospitals have a larger breadth of practice, and thus see fewer IBC patients, so it is important to ensure all IBC patients’ care meets guidelines. The purpose of this study is to evaluate the timelines of care and outcomes in a rural setting, and to examine differences in the clinical features and care of patients with IBC (T4d) and T4 non-IBC (T4a,b,c). Methods: 89 consecutive T4 breast cancer patients referred to a tertiary cancer center in Northern Ontario between 2006 and 2012 where entered into a database to assess standard of practice, epidemiological, and pathological factors. IBC was diagnosed clinically using the AJCC 6thedition guidelines. Results: Patients with IBC presented were of a lower median age, 52 compared to 70.5 for non-IBC T4, were more likely to have attended screening. 61% vs. 27% of patients respectively, and more likely to be triple negative, 29.3% compared to 4.2% for non-IBC T4. 17.1% of IBC patients had complete pathological response at surgery compared to 2.1% of T4 non-IBC patients. Five year overall survival was 38% for IBC patients, and 44% for T4 non-IBC . Conclusions: T4 IBC and T4 non-IBC are distinct diseases affecting distinct populations, but with similar survival. T4 non-IBC is a disease of the elderly, underserviced, and unscreened. A multidisciplinary approach to the treatment of IBC using tri-modality therapy has improved 5 year survival to 40% in some recent analyses, which is consistent with our findings. Patients receiving treatment for IBC in Northeastern Ontario are largely (72%) following the guidelines of therapy despite geographic, health services, and economic barriers, although room for improvement exists.
A Holistic, Person-Centred Care Model for Victims of Sexual Violence in Democratic Republic of Congo: The Panzi Hospital One-Stop Centre Model of Care
Authors: Denis Mukwege, Marie Berg
Journal: PLoS Medicine (2016)

Denis Mukwege and Marie Berg describe the One Stop Centre at Panzi Hospital in Eastern Democratic Republic of Congo that provides care for girls and women who have been raped in combination with extreme bodily harm.
Possible Eradication of Minimal Residual Disease in Acute Leukemia.
Authors: Yasuki Hijikata, Yasuhiro Maeda, Terufumi Yamaguchi, Miyako Tanaka, Chikara Hirase, Takai Shunsuke, Yasuyoshi Morita, Mitsuhiro Matsuda, Akihisa Kanamaru
Journal: Blood (2005)
Acute Myeloid Leukemia (AML): Prospective Comparison of Different Treatments with a Common Standard Treatment - A Study by the German AML Intergroup
Authors: Thomas Buchner, Richard F. Schlenk, Markus Schaich, Konstanze Döhner, Rainer Krahl, J\)rgen Krauter, Maria Cristina Sauerland, Daniela Späth, Michael Kramer, Arnold Ganser, Dietger W Niederwieser, Gerhard Ehninger, Wolfgang E. Berdel, Wolfgang Hiddemann, Hartmut Dohner, Dieter Hoelzer, R\)diger Hehlmann, Verena Hoffmann, Markus Pfirrmann
Journal: Blood (2010)
Experimental Study on Prevention of GVHD by Selective Elimination of Alloreactive Donor Lymphocytes Prior to Stem Cell Transplantation.
Authors: Bao-An Chen, Wei-Min Dong, Jia-Hua Ding, Xiao-Jing Deng, Gang Zhao, Chong Gao, Yun-Yu Sun, Jun Wang, Jian Cheng, Ning-Na Chen, Fei Fei
Journal: Blood (2006)
TCT-692 The effect of balloon predilatation in TAVI on long-term mortality
Authors: Konstantinos Stathogiannis, Konstantinos Toutouzas, Maria Drakopoulou, George Latsios, Andreas Synetos, Constantina Aggeli, Odysseas Kaitozis, Georgios Trantalis, Antonios Mastrokostopoulos, Ulrich J. Gerckens, Eberhard Grube, Dimitrios Tousoulis
Journal: Journal of the American College of Cardiology (2015)
Highly Sensitive Droplet Digital PCR for MYD88L265P Mutation Detection and Minimal Residual Disease Monitoring in Waldenström Macroglobulinemia
Authors: Daniela Drandi, Elisa Genuardi, Paola Ghione, Daniele Grimaldi, Barbara Mantoan, Marina Ruggeri, Daniela Barbero, Luigia Monitillo, Marika Vasta, Eleonora Marzanati, Giulia Verardo, Paola Omedè, Federica Cavallo, Mario Boccadoro, Marco Ladetto, Simone Ferrero
Journal: Blood (2015)
Whole Exome Sequencing Of Multiple Myeloma Reveals An Heterogeneous Clonal Architecture and Genomic Evolution
Authors: Niccolo Bolli, Herve Avet-Loiseau, David Wedge, Peter Van Loo, Ludmil Alexandrov, Inigo Martincorena, Kevin Dawson, Francesco Iorio, Serena Nik-Zainal, Graham R Bignell, Jonathan Hinton, Jose Tubio, Stuart McLaren, O'Meara Sarah, Adam Butler, Teague Jon, Laura J Mudie, Yu-Tzu Tai, Masood Shammas, Adam Sperling, Mariateresa Fulciniti, Paul G. Richardson, Florence Magrangeas, Stephane Minvielle, Philippe Moreau, Michel Attal, Andy Futreal, Thierry Facon, Kenneth C. Anderson, Peter J. Campbell, Nikhil Munshi
Journal: Blood (2013)
Phase II study of combination carboplatin and erlotinib in patients with recurrent glioblastoma multiforme
Authors: J. F. De Groot, M. R. Gilbert, K. R. Hess, T. Hanna, M. Groves, C. Conrad, K. Aldape, H. Colman, V. Puduvalli, W. A. Yung
Journal: Journal of Clinical Oncology (2007)

2024 Background: Targeting the epidermal growth factor receptor (EGFR) in glioblastoma is effective in a subset of patients whose tumors express the phosphatase and tensin homolog (PTEN) tumor suppressor gene and overexpress the EGF variant vIII receptor. Therefore, this study was designed to assess the clinical activity of the EGFR inhibitor erlotinib when combined with carboplatin and to determine molecular predictors of response. The primary endpoint is progression-free survival (PFS). To be eligible for the study, patients had to have recurrent, histologically confirmed glioblastoma or gliosarcoma, no more than two prior relapses, a KPS = 60, and no enzyme-inducing anticonvulsants. Methods: In this ongoing phase II study, patients are given carboplatin intravenously on day 1 of every 28-day cycle to achieve a target AUC of 6 (mg x ml/min) based on creatinine clearance. Erlotinib is administered orally once daily throughout the 28-day cycle at 150 mg/day with dose escalation to 200 mg/day, as tolerated. Patients undergo clinical and MRI assessment every 4 weeks. The primary endpoint is median PFS using a Bayesian time-to-event design. To determine histologic correlates of response, tumor tissue is undergoing immunohistochemical evaluation for known markers of response to EGFR inhibitors, including PI3K/AKT and PTEN status. Results: Of the first 20 patients enrolled, 17 were evaluable and all had failed temozolomide-based therapy. The median age is 56 years, and the median KPS is 80. The median time to progression is 15.2 weeks with a 95% credible interval of 8.0 to 28.4 weeks. These results compare favorably with historical data (median of 9.0 weeks, 95% CI of 8.1 to 10.1 weeks). Bayesian analysis using computer-based simulations indicate a high probability (69%) that the median PFS in our study is at least 3 weeks longer than the historical median PFS. Grade 3 and 4 toxicities included fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. Conclusions: The results from this ongoing study suggest that the combination of carboplatin and erlotinib has promising activity in patients with recurrent glioblastoma who have failed temozolomide-based therapy. Tumor tissue is being analyzed to determine molecular markers of response. [Table: see text]
Study on the Burden of Abnormal Hematopoietic Clone of the Patients with Myelodysplastic Syndromes.
Authors: Zonghong Shao, Huaquan Wang, Jun Shi, Yanran Cao, Hong Liu, Jie Bai, Meifeng Tu, Liming Xing, Shihe Liu, Juan Sun, Hairong Jia
Journal: Blood (2005)
Prospective Longitudinal Quality of Life Assessment in Patients With Neuroendocrine Tumor Liver Metastases Treated With 90Y Radioembolization
Authors: Brandon Cramer, Minzhi Xing, Hyun S. Kim
Journal: Clinical Nuclear Medicine (2016)

To determine the effect of Y radioembolization therapy on health-related quality of life (HRQOL) in patients with neuroendocrine tumor liver metastases (NETLM) in a prospective longitudinal study.Baseline Short-Form 36 HRQOL scores were evaluated for significant change (P < 0.05) within the total patient population at 1, 3, 6, 12, and 24 months following Y using paired t-test. Overall survival (OS) times were calculated from first Y using the Kaplan-Meier method and analyzed using the log-rank test.Thirty patients were enrolled. There were no significant differences in any of the eight HRQOL domains when comparing baseline scores to 1, 3, or 24-month follow-up scores. At 6- and 12-month follow-up, mean mental health and social functioning domain scores were significantly higher than baseline, respectively (P = 0.007; P = 0.019). The remainder of domains showed no significant difference at 6 or 12 months. Patients with baseline Mental Component Summary (MCS) over 50.0 had significantly longer mean survival than those under 50.0 (37.50 vs. 18.19 months, P = 0.0263). Patients with baseline Physical Component Summary (PCS) over 50.0 had no significant difference in survival compared to those under 50.0 (38.09 vs. 30.69 months, P = 0.783).Patients with NETLM treated with Y have sustained HRQOL for up to 24 months following treatment. Temporary increases in mental health and social functioning at medium-term follow-up were observed. Patients with baseline MCS scores above the normalized U.S. population had longer overall survival compared to patients with baseline scores below the normalized U.S.
Outcome of 1,229 Adult Philadelphia Chromosome Negative B Acute Lymphoblastic Leukemia (B-ALL) Patients (pts) From the International UKALLXII/E2993 Trial: No Difference In Results Between B Cell Immunophenotypic Subgroups
Authors: Mark R. Litzow, Georgina Buck, Gordon Dewald, Adele Fielding, Rhett Ketterling, Hillard M. Lazarus, Selina Luger, David I. Marks, Andrew McMillan, Anthony V. Moorman, Elisabeth Paietta, Susan M Richards, Jacob M. Rowe, Martin S. Tallman, Anthony H. Goldstone
Journal: Blood (2010)
Molecular Basis of Biomechanics of Hemostasis and Thrombosis: Structural Molecular Transitions Underlying Deformation of Fibrin Clots and Thrombi.
Authors: Rustem I. Litvinov, Dzhigangir A. Faizullin, Yuriy F. Zuev, Artyom Zhmurov, Olga Kononova, Valeri Barsegov, John W. Weisel
Journal: Blood (2012)
Pre-B Cell Receptor Signaling Distinguishes E2A-PBX1 From Other Subtypes of Acute Lymphoblastic Leukemia
Authors: Rahul Nahar, Daniel Trageser, Lars Klemm, Cihangir Duy, Wolf-Karsten Hofmann, Eugene Park, Yong-mi Kim, Nora Heisterkamp, Hassan Jumaa, Markus Muschen
Journal: Blood (2010)
GW27-e0936 Assessment of the CHADS2 and CHA2DS2-VASc score in predicting thromboembolism in Chinese patients with nonvalvular atrial fibrillation: a real-world analysis
Authors: Yang Guo, Dong Zhao, Jiayi Sun, Miao Wang, Wuxiang Xie, Jing Liu
Journal: Journal of the American College of Cardiology (2016)