tbuckley/cabot-search huggingface dataset:
Abstract 19639: Infective Endocarditis Following Transcatheter Valve Implantation: A Systematic Review
Authors: Ignacio J Amat-Santos, Henrique B Ribeiro, Marina Urena, Ricardo Allende, Cristine Houde, Elisabeth Bedard, Robert DeLarrochellière, Jean-Michel Paradis, Eric Dumont, Daniel Doyle, Siamak Mohammadi, Mélanie Côté, Josep Rodés-Cabau
Journal: Circulation (2014)

Objectives: To describe the incidence, features, predisposing factors and outcomes of infective endocarditis (IE) following transcatheter valve implantation (TVI). Background: Very few data exist on IE following TVI. Methods: Studies published between 2000 and 2013 regarding IE in patients with aortic (TAVI) or pulmonary (TPVI) transcatheter valves were identified through systematic electronic search. Result: A total of 28 publications describing 60 patients (32 TAVI, 28 TPVI) were identified. Most TAVI patients (66% males, 80±7 years) had a very high-risk profile (LogEuroSCORE: 30.4±14.0%, p&lt;0.001 compared to previous TAVI registries). In TPVI patients (90% males, 19±6 years), IE was more frequent in stenotic conduit/valve (61%) (p &lt;0.001 vs. previous TPVI series). Median time between TVI and IE was 5.5 (2-12) months. Typical microorganisms were mostly found with a higher incidence of enterococci after TAVI (34.4% vs. 0%, p =0.009), and S.aureus after TPVI (29.4% vs. 6.2%, p =0.041). Up to 60% of the TAVI-IE patients were managed medically despite related complications such as local extension, embolism and/or heart failure in &gt;50% of patients. Valve explantation rate was 57% and 23% in balloon- and self-expandable valves, respectively (p=0.07). In-hospital mortality for TAVI-IE was 34.4%. Most TPVI-IE patients (75%) were managed surgically, and in-hospital mortality was 7.1%. Conclusions: Most cases of IE post-TVI were males, with a very high-risk profile (TAVI) or underlying stenotic conduit/valve (TPVI). Typical -but different- microorganisms of IE were involved in half of the TAVI and TPVI cases. Most TPVI-IE patients were managed surgically as opposed to TAVI patients, and mortality rate was high in both cohorts.
Objectively Measuring the Ghost in the Machine
Authors: Guglielmo M. Trovato, Marco Sperandeo
Journal: JACC. Cardiovascular imaging (2015)

Raso et al. [(1)][1] describe a software claimed as “a robust approach for developing a portable device for the individualized and automatic detection of pulmonary interstitial edema or fibrosis,” designed to detect B-lines. We are concerned that these are merely artifacts without anatomic
Abstract 344: Naturally Derived Cardiac Extracellular Matrix for Cardiac Progenitor Cell Therapy
Authors: Kristin M French, Archana V Boopathy, Jessica A DeQuach, Loice Chingozha, Karen L Christman, Hang Lu, Michael E Davis
Journal: Circulation Research (2012)

Cardiovascular disease is the leading cause of death in the United States. Following acute myocardial infarction, there is dramatic myocyte loss, and the cells are replaced with a collagen scar. Cell therapy directed toward regenerating infarcted myocardium suffers from poor retention of cells, possibly because the conditions are not ideal to support injected cells. Many studies show the local microenvironment is a potent regulator of cell fate. Therefore, we hypothesize that culturing cardiac progenitor cells (CPCs) on a naturally derived, cardiac extracellular matrix (cECM) will increase their function. CPCs were isolated from rat cardiac tissue-homogenate with magnetic beads conjugated with c-kit antibodies. Porcine, cardiac extracellular matrix (cECM) was decellularized, digested, and lyophillized to be used as a coating material. CPCs were cultured on cECM and examined for cardiogenic lineage markers, survival, proliferation and adherence. Our results show that CPCs cultured on cECM proliferate better (2.9-fold) as compared to COL (2.3-fold; p&lt;0.05). Additionally, CPCs demonstrate improved resistance to serum-starvation-induced apoptosis when cultured on cECM (40% ± 14%) as compared to COL (53% ± 14%; p&lt;0.001). Furthermore, CPCs adhered more strongly to cECM than COL as measured using microfluidics. CPCs showed enhanced progression toward the cardiomyoctye lineage when cultured on cECM (nkx2.5: 2.3 ± 0.4-fold; α-myosin heavy chain: 14.6 ± 4.4-fold; troponinC: 2.4 ± 0.2-fold; p-values &lt;0.05) as compared to COL. This was confirmed at the protein level with Gata-4 (1.8 ± 0.1-fold; p&lt;0.001) and Nkx2.5 (1.6 ± 0.2-fold; p&lt;0.05). A reduction in fibroblast specific protein-1 (0.5 ± 0.1-fold) was also seen on cECM as compared to COL and suggests the CPCs are less likely to contribute to scar formation. While these conditioned cells have not yet been examined in an in vivo setting, our comparison to COL mimics both the naked injection of these cells into an infarct zone, and comparison to a commonly used cell delivery vehicle. Our data suggest that CPCs delivered with cECM are more likely to survive and differentiate in the infarct zone than cells delivered by themselves or in collagen.
Improved overall survival for patients with advanced ovarian, tubal, and primary peritoneal carcinoma as a result of a change in surgical approach: A follow-up study
Authors: D. S. Chi, E. L. Eisenhauer, Y. Sonoda, N. R. Abu-Rustum, M. L. Gemignani, D. A. Levine, M. L. Hensley, P. Sabbatini, C. L. Brown, R. R. Barakat
Journal: Journal of Clinical Oncology (2007)

5530 Background: In January 2001, we initiated a programatic change in our primary surgical approach to advanced ovarian carcinoma utilizing extensive upper abdominal procedures as needed to achieve maximal cytoreduction. The objective of this study was to determine the impact of incorporating these procedures on overall survival in advanced ovarian, fallopian tube, and primary peritoneal carcinomas. Methods: Two groups of patients (pts) with stage IIIC and IV ovarian, tubal, and primary peritoneal carcinoma were identified for comparison. Group 1, the control group, consisted of all 168 pts who underwent primary cytoreduction between 1/96 and 12/99. Group 2, the study group, was composed of all 209 pts who underwent primary surgery between 1/01 and 12/04, during which time a more comprehensive debulking of upper abdominal disease was used, including diaphragm peritonectomy/resection, splenectomy, distal pancreatectomy, liver resection, resection of porta hepatis tumor, and cholecystectomy. Results: Comparison between the 2 groups revealed no significant difference in age, BMI, performance status, stage, tumor grade, proportion with primary ovarian cancer, preoperative CA-125 levels, preoperative platelet counts, percentage with ascites, or type of postoperative primary chemotherapy. The only 2 variables that differed significantly between the 2 groups were percentage of pts who had extensive upper abdominal surgery and percentage of pts cytoreduced to ≤1 cm residual disease (RD). Patients in Group 2 were more likely to have undergone extensive upper abdominal procedure(s) (37% vs. 1%; P &lt;0.001). Cytoreduction to RD ≤1 cm was achieved in 50% of Group 1 pts compared to 80% of Group 2 pts (P &lt;0.01). Overall median survival was significantly improved in Group 2 versus Group 1 pts (58 vs. 43 mos, [P=0.042], respectively). Conclusions: The recent incorporation of extensive upper abdominal surgical procedures to increase the rate of primary cytoreduction to residual disease ≤1 cm resulted in significantly improved overall survival. A paradigm shift toward more complete primary cytoreduction can improve survival for pts with advanced ovarian, fallopian tube, and primary peritoneal carcinomas. No significant financial relationships to disclose.
Combined Arsenic and Retinoic Acid Treatment Enhances Differentiation and Apoptosis in Arsenic-Resistant NB4 Cells
Authors: Maurizio Giannı̀, Marcel H.M. Koken, Mounira K. Chelbi-Alix, Gérard Benoit, Michel Lanotte, Zhu Chen, Hugues de Thé
Journal: Blood (1998)
Evaluating the Financial Impact of Clinical Trials in Oncology: Results From a Pilot Study From the Association of American Cancer Institutes/Northwestern University Clinical Trials Costs and Charges Project
Authors: Charles L. Bennett, Tammy J. Stinson, Victor Vogel, Lyn Robertson, Donald Leedy, Patrick O’Brien, Jane Hobbs, Tamara Sutton, John C. Ruckdeschel, Thomas N. Chirikos, Roy S. Weiner, Marguerite M. Ramsey, Max S. Wicha
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Medical care for clinical trials is often not reimbursed by insurers, primarily because of concern that medical care as part of clinical trials is expensive and not part of standard medical practice. In June 2000, President Clinton ordered Medicare to reimburse for medical care expenses incurred as part of cancer clinical trials, although many private insurers are concerned about the expense of this effort. To inform this policy debate, the costs and charges of care for patients on clinical trials are being evaluated. In this Association of American Cancer Institutes (AACI) Clinical Trials Costs and Charges pilot study, we describe the results and operational considerations of one of the first completed multisite economic analyses of clinical trials. METHODS: Our pilot effort included assessment of total direct medical charges for 6 months of care for 35 case patients who received care on phase II clinical trials and for 35 matched controls (based on age, sex, disease, stage, and treatment period) at five AACI member cancer centers. Charge data were obtained for hospital and ancillary services from automated claims files at individual study institutions. The analyses were based on the perspective of a third-party payer. RESULTS: The mean age of the phase II clinical trial patients was 58.3 years versus 57.3 years for control patients. The study population included persons with cancer of the breast (n = 24), lung (n = 18), colon (n = 16), prostate (n = 4), and lymphoma (n = 8). The ratio of male-to-female patients was 3:4, with greater than 75% of patients having stage III to IV disease. Total mean charges for treatment from the time of study enrollment through 6 months were similar: $57,542 for clinical trial patients and $63,721 for control patients (1998 US$; P = .4) CONCLUSION: Multisite economic analyses of oncology clinical trials are in progress. Strategies that are not likely to overburden data managers and clinicians are possible to devise. However, these studies require careful planning and coordination among cancer center directors, finance department personnel, economists, and health services researchers.
The Carboxyl-Terminal Region of Protein C Is Essential for Its Secretion
Authors: Akira Katsumi, Tetsuhito Kojima, Takao Senda, Tomio Yamazaki, Hiroaki Tsukamoto, Isamu Sugiura, Shigeru Kobayashi, Toshiyuki Miyata, Hideaki Umeyama, Hidehiko Saito
Journal: Blood (1998)
A phase II study of topotecan and bevacizumab in advanced refractory non-small cell lung cancer: Interim analysis.
Authors: A. Beitinjaneh, R. Bliss, P. Kumar, J. W. Leach, R. A. Kratzke, A. Dudek
Journal: Journal of Clinical Oncology (2010)

e18040 Background: Previous studies have suggested improved outcomes with a single topoisomerase I inhibitor for chemotherapy naïve advanced non-squamous non-small cell lung (NSCLC). Bevacizumab is approved for NSCLC in combination in first-line therapy. The objective of this study was to evaluate the effectiveness and toxicities of the combination of IV topotecan and bevacizumab in patients with stage IIIB/IV NSCLC who have failed prior systemic chemotherapy. Methods: 37 patients were enrolled between 10/2006-10/2009. Patients received topotecan 4.0 mg/m2 IV per day on days 1, day 8 and day 15 and bevacizumab 10 mg/kg IV was given day 1 and 15. Treatment was repeated every 28 days in the absence of disease progression or unacceptable toxicity. Response assessment (using RECIST) was done every two cycles. Statistical design; primary endpoint: median time to progression > 56 days with an 80% power and one-sided significance level of 0.05 using a one-sided one-sample test on exponential means. Results: Median age was 62 years old and 49% were male. There were 7/37 (19%) partial responses and 21/37 (57%) stable diseases with an overall response rate of 76%. Median progression-free survival was 137 days (95% CI; 68,188) and among responders (PR+SD) PFS was 171 days (95% CI; 124-270). Kaplan–Meier estimated median overall survival of 713 days (95% CI; 237, Inf). The most common nonhematologic toxicities were fatigue, headache, nausea and hypertension and most of those were mild (< grade 3). Hematological toxicities were manageable with G 3 neutropenia in 4 (11%), G 3 thrombocytopenia in 6 (16%), and G 3 anemia in 2 (1%). The treatment combination was well tolerated even in patients with history of brain metastatic disease (22%) and in patients 65 yrs or older (43%). Conclusions: The combination of topotecan and bevacizumab appears to be effective and safe for patients with metastatic non-squamous non small cell lung carcinoma. Further accrual to this study will be continued. No significant financial relationships to disclose.
Abstract 14182: Impact of Aortic Stiffness on Exercise Blood Pressure Response and Aerobic Fitness
Authors: Satyam Sarma, Graeme Carrick-Ranson, Shigeki Shibata, Naoki Fujimoto, Paul S Bhella, Jeffrey L Hastings, Kara Boyd, Dean Palmer, Benjamin Levine
Journal: Circulation (2013)

Introduction: Exercise induced hypertension (EiH) defined as exercise SBP >210 mmHg, is associated with increased risk for cardiovascular morbidity even in normotensive individuals. The physiologic...
Abstract 9385: Percutaneous Carbon Dioxide Treatment Using a Gas Mist Generator Accelerates Angiogenesis in the Ischemic Hindlimb
Authors: Yasukatsu Izumi, Takanori Yamazaki, Yasuhiro Nakamura, Takehiro Yamaguchi, Akihisa Hanatani, Kenei Shimada, Minoru Yoshiyama, Hiroshi Iwao
Journal: Circulation (2012)

Background: Although highly-concentrated carbon dioxide (CO 2 ) is thought to be useful for ischemic diseases, devising an artificial CO 2 -rich bath is difficult. Hypothesis: We hypothesized that the treatment with a few micrometers of CO 2 particles atomized by double-fluid nozzles (CO 2 mist) would exert an angiogenic effect in the ischemic hindlimb. Methods and Results: (1) Lower bodies of rats with unilateral hindlimb ischemia were wrapped in a polyethylene bag filled with CO 2 gas alone or CO 2 mist by a gas mist generator (Advance Biotron). Near-infrared spectroscopy revealed that CO 2 mist-treatment increased oxygenated hemoglobin and decreased deoxygenated hemoglobin in the ischemic leg of rats. However, CO 2 gas-treatment did not change these parameters. (2) Mice with unilateral hindlimb ischemia were divided into the untreated (UT) group and CO 2 mist-treated (CM) group. CO 2 mist was treated to mice in the same way as rats for 10 minutes a day. By a laser Doppler analysis, ischemic hindlimb blood flow in the CM group was higher persistently after 7th days of induction of ischemia than that in the UT group. Furthermore, capillary density by immunostaining with anti-CD31 was also significantly increased in the CM group at day 28, compared with the UT group. These effects were abolished by administration of Nω-Nitro-L-arginine, an inhibitor of nitric oxide synthase. Vascular endothelial growth factor mRNA expression at days 4 and 7 was increased in the CM group but not in the UT group. (3) At 4 days after ischemia, digested proteins of muscles from the nonischemic, UT or CM group were labeled with isobaric tag for relative and absolute quantitation (iTRAQ) reagents, and proteomic analysis was performed by liquid chromatography - tandem Mass spectrometry (LC/MS/MS). Sixty-eight and 62 of identified 195 proteins were increased and decreased by ischemia, respectively. The treatment of CO 2 mist downregulated some of the 68 increased proteins, which were mainly signal transduction-related proteins. On the other hand, CO 2 mist-treatment upregulated some of the 62 decreased proteins, which were mainly metabolic enzyme-related proteins. Conclusion: Percutaneous CO 2 mist therapy may be a potentially useful for ischemia-induced angiogenesis.
Metrics for ocular adverse events: Deciphering CTC AE v3.0
Authors: S. K. Kim, A. S. Garden
Journal: Journal of Clinical Oncology (2004)

6101 Background: Recommendations for updating adverse events for Common Toxicity Criteria v3.0 (CTCAE v3.0) were made via the Late Effects Workshop (LENT IV), in efforts to streamline toxicity reporting across multidiscipline. Here, we describe the rational for the expansion of ocular adverse events described in CTCAE v3.0 and the most effective ways to utilize these metrics in a clinical trial. Methods: New ocular adverse events in CTCAE v3.0 are catalogued and explanations of the present grading system are given. The consensus meeting of Late Effects Workshop (LENT IV) is detailed, and tables of how to capture ocular toxicity in real time is described. The known ocular toxicity metrics are reviewed. Briefly, known ocular toxicities of current cancer treatment and radiation ocular toxicity are reviewed. Clinically relevant tools for evaluation of various ocular toxicities and their treatment modalities are summarized. Results: The ocular adverse events in CTCAE v3.0 are designed to capture toxicity in real time, from anterior to posterior of the eye anatomically, which is the classic manner in which the eye findings are described in ocular literatures. 8 new ocular adverse events are catelogued and 11 are revised in the CTCAE v3.0. Subjective component can be graded by a clinician or research nurse during a clinical trial but other adverse events require ophthalmologic evaluation. Cancer treatment-related ocular and visual toxicities are observed with radiotherapy as well as with Gleevec, Taxotere, Iressa, Interferon, Tacrolimus, among others. These results are summarized in various figures. Conclusions: Reorganization of the ocular adverse events anatomically rather than alphabetically as listed in CTCAE v3.0 is the optimal metric to capture ocular acute and late toxicities. Understanding the rational and the strategies with which to grade ocular toxicity with CTCAE v3.0 may yield a more accurate measure of ocular adverse events in future clinical trials. No significant financial relationships to disclose.
The distinctive micromegakaryocytes of transformed chronic myeloid leukemia
Authors: Nicholas J. Fordham, Simon Stern, John Swansbury, Barbara J. Bain
Journal: American Journal of Hematology (2016)

A bone marrow aspirate showed active granulopoiesis. There were 34% blast cells, which were cytologically similar to those in the peripheral blood. Micromegakaryocytes constituted 24% of nucleated cells. Many of these were very distinctive, being lymphocyte-sized with condensed chromatin and with cytoplasm fragmenting into platelets (right). Cytogenetic analysis showed 46,XX,t(9;22)(q34;q11.2)[3]/46,XX,add(7)(p15), t(9;22)(q34;q11.2)[18]/46,XX[1], confirming the diagnosis of transformed chronic myeloid leukemia with clonal evolution. Fluorescence in situ hybridization (FISH) using a Vysis (Abbott) dual fusion probe found 100% of the cells scored to have BCR-ABL1 and ABL1-BCR fusions, with 20% having duplicated fusion signals. Immunophenotyping showed the blast cells to be negative for myeloperoxidase. In the chronic phase of chronic myeloid leukemia, megakaryocytes are smaller than normal but micromegakaryocytes are not a feature. However when megakaryoblastic/megakaryocytic transformation occurs, micromegakaryocytes are often numerous and lymphocyte-sized micromegakaryocytes with active platelet production are particularly characteristic.
Influence of Adult Thymectomy on Growth of Transplanted Tumors in Mice
Authors: Mariana Linker-Israeli, Nathan Trainin
Journal: JNCI Journal of the National Cancer Institute (1968)

Thymectomy of AKR and C3HeB mice at 4–8 weeks of age lowered their normal resistance to implanted tumors of foreign origin of the same or different H-2 transplantation locus. Five weeks after tumor implantation, the level of peripheral blood lymphocytes of thymectomized animals that had rejected the tumor was significantly lower than that of their intact controls. When SBL-H, a tumor conditioned to the C3HeB strain, was used, the neoplastic implant grew in both thymectomized and intact recipients. However, tumor grafts growing in thymectomized animals lacked the usual lymphocytic infiltration found at the periphery of the tumors growing in the intact controls. Apparently the thymus still plays a significant and specific role in adult mice in relation to their homograft response to foreign tumors.
A phase I study evaluating the pharmacokinetics (PK) and pharmacodynamics (PD) of the oral pan-phosphoinositide-3 kinase (PI3K) inhibitor GDC-0941
Authors: D. Sarker, R. Kristeleit, K. E. Mazina, J. A. Ware, Y. Yan, M. Dresser, M. K. Derynck, J. De-Bono
Journal: Journal of Clinical Oncology (2009)

3538 Background: The PI3K-PTEN-AKT signaling pathway is deregulated in a wide variety of cancers. GDC-0941 is a potent and selective oral inhibitor of class I PI3K and demonstrates activity in a broad range of preclinical models (breast, ovarian, lung, and prostate). Methods: Patients (pts) with histologically confirmed advanced solid tumors and ECOG PS 0–1 were treated with GDC-0941 using a 3+3 escalation design at a single institution. Treatment was a single dose with 1wk washout, followed by GDC-0941 qd on a 3wk on, 1wk off schedule. Objectives were to determine MTD and DLT, evaluate PD endpoints in surrogate (pAKT in platelet rich plasma) and tumor (pAKT and pS6 in paired tumor biopsies and FDG uptake via PET imaging) tissues, and describe anti-tumor activity. Results: Thirteen patients have been enrolled in 4 successive cohorts (15–60 mg qd). GDC-0941 was generally well-tolerated with no drug related Grade 3 or 4 AEs or DLTs to date. Grade 1 diarrhea, nausea, dysgeusia, peripheral sensory neuropathy, dry mouth, thrombocytopenia, and increased aspartate aminotransferase have been observed. Preliminary PK data suggest dose-proportional increases in fasting mean Cmax and AUC. Preliminary PD data show decreased levels of pAKT in platelet rich plasma correlated with GDC-0941 plasma concentrations. GDC-0941 effects on FDG-PET imaging is being assessed, with 1 patient with HER2+ metastatic breast cancer showing a reduction in FDG uptake and improvement of a chest wall lesion (dose level 60 mg qd). Evaluation of PI3K pathway modulation from paired tumor biopsies is underway. Conclusions: GDC-0941 is generally well tolerated when administered qd at doses associated with inhibition of pAKT in surrogate tissues. Evidence of PD activity in tumor tissue has also been observed. Dose-escalation continues and updated PK/PD data will be presented. [Table: see text]