tbuckley/cabot-search huggingface dataset:
Surgical Management of Infective Endocarditis Complicated by Embolic Stroke
Authors: Bobby Yanagawa, Gosta B. Pettersson, Gilbert Habib, Marc Ruel, Gustavo Saposnik, David A. Latter, Subodh Verma
Journal: Circulation (2016)

There has been an overall improvement in surgical mortality for patients with infective endocarditis (IE), presumably because of improved diagnosis and management, centered around a more aggressive early surgical approach. Surgery is currently performed in approximately half of all cases of IE. Improved survival in surgery-treated patients is correlated with a reduction in heart failure and the prevention of embolic sequelae. It is reported that between 20% and 40% of patients with IE present with stroke or other neurological conditions. It is for these IE patients that the timing of surgical intervention remains a point of considerable discussion and debate. Despite evidence of improved survival in IE patients with earlier surgical treatment, a significant proportion of patients with IE and preexisting neurological complications either undergo delayed surgery or do not have surgery at all, even when surgery is indicated and guideline endorsed. Physicians and surgeons are caught in a common conundrum where the urgency of the heart operation must be balanced against the real or perceived risks of neurological exacerbation. Recent data suggest that the risk of neurological exacerbation may be lower than previously believed. Current guidelines reflect a shift toward early surgery for such patients, but there continue to be important areas of clinical equipoise. Individualized clinical assessment is of major importance for decision making, and, as such, we emphasize the need for the functioning of an endocarditis team, including cardiac surgeons, cardiologists, infectious diseases specialists, neurologists, neurosurgeons, and interventional neuroradiologists. Here, we present 2 illustrative cases, critically review contemporary data, and offer conceptual and practical suggestions for clinicians to address this important, common, and often fatal cardiac condition.
Combined therapy for rectal cancer in the elderly
Authors: G. C. Bohac, K. Hartshorn, D. Cheng
Journal: Journal of Clinical Oncology (2007)

14504 Background: Neoadjuvant or Adjuvant Chemoradiotherapy (CRT) plus surgery is the standard of care for treatment of Stage II/Stage III rectal cancer. Previous studies of practice patterns have evaluated SEER data using single dose chemotherapy as a surrogate for having ever been treated. No study to date has evaluated the use of CRT along with surgery to determine the ability of elderly patients with rectal cancer to complete prescribed therapy. Methods: A retrospective study of all patients treated for Stage II/III rectal cancer identified by Tumor Registrar from January 1, 1987 to June 1, 2006 at the Boston VAMC and Boston Medical Center were analyzed. Data was extracted from computerized records and paper charts. Statistical analysis was performed with SAS software. The primary endpoint was to determine if younger (&lt;70 yr) and older (&gt;=70yr) patients were equally likely to complete CRT and surgery without having a dose of chemotherapy or radiation reduced, held, or delayed. Secondary endpoints were to determine if older and younger age groups were equally likely to receive CRT and a multivariate analysis of factors (age, having received neoadjuvant therapy, number of comorbidities, stage of tumor) had an effect on these outcomes. Results: A total of 266 patients were identified and included in the study. The likelihood of completing CRT and surgery without a dose being held, delayed or reduced was statistically similar among patients age 70 and older (16.1%) as among younger patients (23.9%) (Chi-square 2.16 p=0.1414). However, older patients were far less likely (58.24%) than younger patients (76%) to receive CRT (Chi-square 8.79 p=0.003). A multivariate analysis of factors associated with completion of CRT without a dose being held, delayed or reduced identified only the number of comorbidities (one or more) OR=0.383 (95% CI 0.186–0.790) as statistically significant. In addition, multivariate analysis of factors associated with receiving CRT identified having received neoadjuvant therapy OR=5.397 (95% CI 2.303–12.60) and age &gt;=70 OR=0.424 ( 95% CI 0.201–0.898) as statistically signficant. Conclusion: Elderly patients with rectal cancer are less likely to be prescribed CRT than younger patients. However, elderly patients who are prescribed to receive CRT appear to be able to tolerate the therapy as well as younger patients. No significant financial relationships to disclose.
Plasma concentration of amrubicinol in gamma phase in patients treated for 3 days with amrubicin and hematological toxicities
Authors: T. Kimura, S. Kudoh, S. Mitsuoka, H. Tanaka, S. Kyoh, T. Suzumura, N. Yoshimura, K. Asai, Y. Tochino, K. Hirata
Journal: Journal of Clinical Oncology (2009)

e14606 Background: Amrubicinol (AMR-OH) is an active metabolite of amrubicin (AMR), a novel synthetic 9-amino-anthracycline derivative. The time-concentration profile of AMR-OH exhibits a continuous long plateau slope in terminal phase. To determine the relationships between the steady-state plasma concentration of AMR-OH and treatment effects and toxicities associated with AMR therapy, we performed a PK/PD study of AMR in patients with lung cancer treated with AMR alone or the combination of AMR + cisplatin (CDDP). Methods: AMR was given at a dose of 30 or 40 mg/m 2 on days 1 to 3. Plasma samples were collected at pretreatment, 24 hours after the 1 st injection (day 2), and 24 hours after the 3 rd injection (day 4). Plasma concentrations of AMR, AMR-OH, and CDDP were determined by HPLC and AAS. Percent change in neutrophil count (dANC) and the plasma concentration of AMR-OH were evaluated using a sigmoid E max model. Results: A total of 35 patients with a median age of 65 years (range 40–78), including 10 with small cell lung cancer (SCLC), 23 with non-small cell lung cancer (NSCLC), 1 with thymic cancer, and 1 with neuroblastoma were enrolled. A total of 107 plasma samples were available for study. Mean concentrations of AMR on day 2, AMR on day 4, AMR-OH on day 2, and AMR-OH on day 4 were 8.52ng/mL+4.63, 16.55ng/mL+11.92, 7.28 ng/mL+3.56 SD, and 13.35ng/mL+5.56 (mean ± SD), with significant increase from day 2 to day 4 for both AMR (p&lt;0.0001) and AMR-OH (p&lt;0.0001). Significant relationships were observed between AMR-OH on day 4 and the toxicity grades of leukopenia, neutropenia, and anemia (p=.018, p=.012, and p=.025). Thrombocytopenia grade exhibited a tendency toward relationship with AMR-OH on day 4 (p = .081). No relationships were observed between drug concentrations and responses. The plasma concentration of AMR-OH on day 4 was positively correlated with dANC in the group of all patients, as well as in patients treated with AMR alone and in patients with co-administration with CDDP using a sigmoid E max model. Conclusions: The plasma concentration of AMR-OH on day 4 was correlated with hematological toxicities in patients treated with AMR. Assessment of plasma concentration of AMR-OH at one time point might enable prediction of hematological toxicities. No significant financial relationships to disclose.
Approved and Experimental Small‐Molecule Oncology Kinase Inhibitor Drugs: A Mid‐2016 Overview
Authors: Peter M. Fischer
Journal: Medicinal Research Reviews (2016)

Abstract Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small‐molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult—even for those working in the field—easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation. The purpose of this review is thus to provide an overview of the biomedical rationales for the kinases being targeted on the one hand, and the design principles, as well as chemical, pharmacological, pharmaceutical, and toxicological kinase inhibitor properties, on the other hand. Two issues that are especially important in kinase inhibitor research, target selectivity and drug resistance, as well as the underlying structural concepts, are discussed in general terms and in the context of relevant kinases and their inhibitors.
Transient transcriptional response to low-dose ionizing radiation in humans undergoing IMRT
Authors: Z. Goldberg, S. R. Berglund, J. Dai, A. Santana, D. M. Rocke
Journal: Journal of Clinical Oncology (2006)

20018 Background: As intensity modulated radiation therapy techniques are increasingly utilized to treat cancer, the area of normal tissue exposed to ionizing radiation is increasing. The biologic risks associated with this normal tissue low dose exposure (LDIR) are fundamentally unknown and of concern to cancer survivors following therapy. Current modeling for health regulations presupposes a linear, no-threshold model of radiation effects, which estimates the effect and risk at low dose by extrapolation from measured effects at high doses. Cell culture models of ionizing radiation (RT) exposure show variable effects, not consistent with a linear dose-response relationship. We therefore undertook the first study to our knowledge of transcriptional effects of LDIR over time in vivo in solid tissue in humans. Methods: Tissue was collected at pre-RT, 3, 8, and 24 hours post-IR at sites receiving 10cGy. Transcriptional response at 3 and 8 hours were compared to the 0 and 24 hour time points. If transcripts are up regulated or down regulated at 3 and 8 hours compared with 0 and 24 hours, we have detected a transient response. The method of Rocke (2005), which was designed to detect differentially expressed gene groups using the responses of multiple probe sets corresponding to gene groups, was used to allow us to test whether there is differential expression for each patient separately, as well as for all the patients together. Results: Significant (p &lt; 0.05) transient up regulation was shown in zinc finger proteins, keratins, BMP receptors, BAG, cyclins and BCL 6. Down regulation was detected in TNF, protein disulfide isomerase, interleukins, heat shock proteins, and S100. Nine gene groups did not show significant change; however, the number of significant gene groups (11) far exceeds the number expected by chance (2). In most cases in which a gene group was shown to be transiently altered, the tests of individual patients showed that most or all of the individuals also had differential expression of the same type. Conclusions: We have shown that it is possible to detect transient responses to LDIR in vivo in humans, and have identified eleven gene groups that demonstrate transient changes, as measured by a statistically principled analysis method. No significant financial relationships to disclose.
TCT-721 Reverse Causality and Effect of Body Mass Index on Clinical Outcomes and all-Cause Mortality after Transcatheter Aortic Valve Replacement
Authors: Masieh Abawi, Rik Rozemeijer, Pierfrancesco Agostoni, Michiel Voskuil, Pieter Doevendans, Pieter Stella
Journal: Journal of the American College of Cardiology (2016)
TCT-29 Performance and healing patterns after implantation of a novel sirolimus eluting bioresorbable scaffold. Six-month follow-up by optical coherence tomography in the FANTOM II study
Authors: Jo Simonsen, Emil Holck, Didier Carrié, Norbert Frey, Matthias Lutz, Joachim Weber-Albers, Dariusz Dudek, Bernard Chevalier, Jouke Dijkstra, Jens Flensted Lassen, Jeffrey Anderson, Evald Christiansen, Alexandre Abizaid, Niels Holm
Journal: Journal of the American College of Cardiology (2016)
TCT-70 Final 5 year results from the COMPARE II trial: comparison between the durable polymer coated everolimus-eluting Xience/Promus stent and the biodegradable polymer coated biolimus-eluting Nobori stent in all comer population
Authors: Pieter Smits, Sjoerd H. Hofma, Mario Togni, Peter den Heijer, Antonio Serra, Ton Slagboom, Ramiro Trillo, Mariano Valdes, Jose Vazquez, Vassilis Voudris
Journal: Journal of the American College of Cardiology (2016)
Case 42-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, William G. Couser, Robert B. Colvin
Journal: New England Journal of Medicine (1980)

Presentation of CaseA 71-year-old man was admitted to the hospital because of the nephrotic syndrome.He was in vigorous health until five weeks earlier, when watery diarrhea and peripheral edema developed. The diarrhea worsened, and during the three weeks before admission he experienced anorexia and polydipsia, with loss of 4.5 kg in weight. Two weeks before admission he entered another hospital. The urine gave a ++++ test for protein; the sediment contained 2 red cells, 4 white cells, and numerous hyaline and granular casts per high-power field. The hematocrit was 37 per cent. The urea nitrogen was 25 mg . . .
TCT-829 Biomechanical Behavior and Healing Response of a Novel Thin Strut Sirolimus Eluting Bioresorbable Scaffold Overexpanded up to 0.75 mm Beyond Nominal Compliance Chart Diameters in Porcine Coronary Artery Model
Authors: Pawel Gasior, Yanping Cheng, Jinggang Xia, Andres Valencia, Alex Estrada, Jenn McGregor, Kamal Ramzipoor, Chang Lee, Gerard Conditt, Juan Granada, Greg Kaluza
Journal: Journal of the American College of Cardiology (2016)
TCT-119 A New Risk Score to Predict Long-Term Cardiac Mortality in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock and Treated with Primary Percutaneous Intervention
Authors: Ruben Vergara, Renato Valenti, Angela Migliorini, Guido Parodl, Maria Grazia De gregorio, Maria Raffaella Aicale, Elena De Vito, Eleonora Gabrielli, David Antoniucci
Journal: Journal of the American College of Cardiology (2016)
TCT-740 Comparison of Procedural, Clinical and Functional Outcome after either Balloon- or Mechanical-expanding Transcatheter Heart Valve Implantation
Authors: Niklas Schofer, Florian Deuschl, Moritz Seiffert, Matthias Linder, Anna Fink, Isamu Mizote, Edith Lubos, Patrick Diemert, Johannes Schirmer, Hendrik Treede, Karsten Sydow, Hermann Reichenspurner, Stephan Blankenberg, Lenard Conradi, Ulrich Schaefer
Journal: Journal of the American College of Cardiology (2016)
TCT-151 Ventricular Septal Rupture Complicating ST-Elevation Myocardical Infarctions: A Nationwide Analysis
Authors: Vikas Singh, Alexis Rodriguez, Parth Bhatt, Badal Thakkar, Nileshkumar Patel, Mauricio Cohen, Igor Palacios, Ignacio Inglessis, Sammy Elmariah, William O'Neill
Journal: Journal of the American College of Cardiology (2016)
TCT-192 Combined Use of Neutrophil to Lymphocyte Ratio and C-Reactive Protein to predict Clinical Outcomes in Acute Myocardial Infarction Patients undergoing Percutaneous Coronary Intervention
Authors: Hocheol Shin, Jae-Sik Jang, Han-Young Jin, Jeong-sook Seo, Tae-Hyun Yang, Dae-Kyeong Kim, Dong-Soo Kim, Yun Seok Song, Pil Sang Song, Dong-Kie Kim, Doo-Il Kim
Journal: Journal of the American College of Cardiology (2016)
TCT-661 The Clinical Impact of Diabetes Mellitus on Outcomes After Transcatheter Aortic Valve Replacement: Insights from the PARTNER II SAPIEN 3 Cohort
Authors: Yigal Abramowitz, Brian Lindman, Tarun Chakravarty, Hasanian Jilaihawi, Samir Kapadia, Wilson Szeto, Philippe Pibarot, Vasilis Babaliaros, Howard Herrmann, Richard Smalling, Lars Svensson, Torsten Vahl, Vinod Thourani, Susheel Kodali, Craig Smith, Yiran Zhang, Maria Alu, Michael Mack, Martin Leon, Raj Makkar
Journal: Journal of the American College of Cardiology (2016)
TCT-358 Bleeding and vascular complication rates before and after implementation of a radial coronary catheterization programme – an observational study in 12 745 patients
Authors: Daniel Kiblboeck, Andreas Winter, Eduard Zeindlhofer, Kurt Hoellinger, Martin Schmid, Antonia Gierlinger, Goenuel Bozkaya, Wolfgang Lang, Alexandra Schiller, Lorenz Pilgerstorfer, Daniela Szuecs, Marlene Reiter, Alexander Kypta, Clemens Steinwender, Johann Reisinger, Peter Siostrzonek
Journal: Journal of the American College of Cardiology (2016)
Transgenic Targeting of Human FVIII Expression to Endothelial Cells Corrects the Murine Hemophilia A Phenotype and Re-Establishes a Releasable Pool of FVIII Together with VWF.
Authors: Qizhen Shi, Hartmut Weiler, Sandra L. Haberichter, Brian C. Cooley, Scot A. Fahs, Drashti Desai, Nancy J. Wandersee, Mary A. Jozwiak, Robert R. Montgomery
Journal: Blood (2005)
Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality
Authors: Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Stefano Volinia, James S. Blachly, Deedra Nicolet, Christopher Oakes, Karl Kroll, Shelley Orwick, Andrew J. Carroll, Richard M. Stone, John C. Byrd, Albert de la Chapelle, Clara D. Bloomfield
Journal: Cancer Research (2016)

Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML), which may give insights into the basis for its poor prognosis, have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and miRNA expression profiles were also determined using paired RNA and small RNA sequencing data. Notably, gene mutations were detected in all the major AML-associated functional groups, which include activated signaling, chromatin remodeling, cohesin complex, methylation, NPM1, spliceosome, transcription factors, and tumor suppressors. Gene mutations in the chromatin remodeling groups were relatively more frequent in patients <60 years of age, who also had less mutations in the methylation and spliceosome groups compared with patients ≥60 years of age. Novel recurrent mutational events in AML were identified in the SMARCA2 gene. In patients ≥60 years of age, the presence of spliceosome mutations associated with a lower complete remission rate (P = 0.03). RNA sequencing revealed distinct gene and miRNA expression patterns between the sole -7 and non -7 AML cases, with reduced expression, as expected, of many genes and miRNAs mapped to chromosome 7, and overexpression of ID1, MECOM, and PTPRM, among others. Overall, our findings illuminate a number of molecular features of the underlying aggressive pathobiology in -7 AML patients. Cancer Res; 77(1); 207-18. ©2016 AACR.
EPID-26EVALUATION OF METABOLIC ENZYME EXPRESSION AS PREDICTORS OF SURVIVAL IN AGGRESSIVE GLIOMAS
Authors: Mohammed Shaik, Howard Chang, Kenneth Schwartz, Karl Olsen, Mary Noel
Journal: Neuro-Oncology (2015)

INTRODUCTION: Aggressive primary brain cancers like glioblastoma multiforme (GBM) are metabolically active tumors with a poor prognosis. We hypothesize that expression of metabolic enzymes may be reflective of the tumors increased metabolism and might be useful in predicting survival. METHODS: Immunohistochemistry (IHC) reactions using formalin fixed paraffin embedded sections from brains, were performed with antibodies raised against the glycolytic enzyme Hexokinase-II (HK2) and several ketolytic enzymes [Succinyl CoA: 3-oxoacid CoA transferase 1 (OXCT1) cytosolic type 2 (R)-hydroxybutyrate dehydrogenase (BDH2) and Acetyl-CoA acetyltransferase (ACAT1)] on 23 patients, 18 with GBM and 5 with anaplastic gliomas. The immunoreactivities were graded by comparing the IHC staining observed in normal brain cells present in the periphery of the tissue with tumor cells using a semi-quantitative scale based on the percentage of positive cells: Positive (≥20%), Negative (< 20%). The survival of patients was evaluated using Kaplan Meier and an age adjusted hazard ratio (aHR) for death was obtained using cox proportional analysis for enzyme expression. RESULTS: Out of 23 patients 6 were female and 17 males, median age was 55 years with the median survival for all the patients of 11.3 months. Univariate analysis for survival using HK2 showed increased survival with decreased IHC expression with a aHR of 0.3 p = 0.02. Patients with increased expression of the ketolytic enzymes had increased survival: BDH2 with an aHR of 7.6 p = 0.008; ACAT1 aHR 0.2, p = 0.02; OXCT1 aH1.6, p = 0.08. In a multivariate analysis HK2 was the only enzyme that was statistically significant; median survival in 17 negative patients was 13.5 months and 3.8 months in 6 positive patients, aHR 0.3, p = 0.02. CONCLUSION: IHC analysis of metabolic enzymes may help to predict survival in patients with aggressive primary brain cancers, but this requires confirmation using a larger number of subjects.
Pattern of extramedullary relapse in latin patients with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and chemotherapy
Authors: L. A. Casanova, S. M. Quintana, S. P. Neciosup, C. A. Samanez
Journal: Journal of Clinical Oncology (2007)

17520 Background: Extramedullary relapse (EMR) is a rare event in APL and reports have suggested a possible rol of ATRA in its pathogenesis. Our study intent to determine the pattern of EMR in Latin patients treated whit trans-retinoic acid (ATRA) and chemotherapy (CT). Methods: We evaluated 87 patients diagnosed of APL from January 2001 to December 2005. They were treated with ATRA and chemotherapy. Results: 74/87 received ATRA plus chemotherapy. Median age was 28 (5–68). 39/74 (53%) patients were female. Subtype M3v constituted 21/74 (28%). 76% presented disseminated intravascular coagulation (DIC). Extramedullary deposit was observed in 7 cases, more frequent was central nervous system (CNS). According the Sanz Index, 32/74 (32%) were High Risk, 40/74 (54%) Intermediate Risk, 2 Low Risk. 31/55 (56%) presented t(15,17). 52/74 (70%) patients had complete response. EMR was documented in 8 (15%) (CNS: 5, External Auditory Foramen: 3), 4 were High Risk. Median time to EMR was 11.5 months (7.03–27.3). 55% are alive at date. The following median was 36 months, 41 months of Disease Free Survival (DFS), rate was 62 % to 3 years. Overall survival was 44 months; rate was 83% to 3 years. Conclusions: EMR incidence was 8%, higher report that other series, this event was presented in CNS and external auditory foramen. It suggest to establish EMR risk factors and to include CNS prophylactic treatment. No significant financial relationships to disclose.
Prognostic Role of Minimal Residual Disease before and after Hematopoietic Stem Cell Transplantation in Childhood Acute Lymphoblastic Leukemia
Authors: Bartolomeo Rossi, Mimma Campeggio, Elisa Magrin, Marco Zecca, Laura Rubert, Franca Fagioli, Paola Quarello, Federica Lovisa, Giuseppe Basso
Journal: Blood (2015)
­Resource Utilization and Cost Analysis By Treatment Arm on the Children’s Oncology Group AALL0232 Phase 3 High-Risk B-Precursor Acute Lymphoblastic Leukemia Trial: A Report from the Children’s Oncology Group
Authors: Amanda M. DiNofia, Alix E. Seif, Meenakshi Devidas, Yimei Li, Matthew Hall, Yuan-Shung Vera Huang, Rochelle Bagatell, William L. Carroll, Naomi J. Winick, Stephen P. Hunger, Brian T. Fisher, Eric C. Larsen, Richard Aplenc
Journal: Blood (2014)
Patient–Ventilator Asynchrony due to Reverse Triggering Occurring in Brain-Dead Patients: Clinical Implications and Physiological Meaning
Authors: Stéphane Delisle, Emmanuel Charbonney, Martin Albert, Paul Ouellet, Pierre Marsolais, Marceau Rigollot, Dominique Savary, Jean-Christophe M. Richard, Karim Serri
Journal: American Journal of Respiratory and Critical Care Medicine (2016)