tbuckley/cabot-search huggingface dataset:
Authors’ reply: Two severe human cases due to swine influenza A (H1N1)v in October 2016 in Europe were chronologic coincident yet distinct events
Authors: Francesca Rovida, Antonio Piralla, Federico Capra Marzani, Ana Moreno, Giulia Campanini, Francesco Mojoli, Marco Pozzi, Alessia Girello, Chiara Chiapponi, Fausto Vezzoli, Paola Prati, Elena Percivalle, Anna Pavan, Maria Gramegna, Giorgio Antonio Iotti, Fausto Baldanti
Journal: Eurosurveillance (2017)

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Recommended phase (Ph) II dose (RP2D) selection for investigational Aurora A kinase (AAK) inhibitor MLN8237 (Alisertib; A) combined with paclitaxel (P): Clinical pharmacokinetics (PK), drug-drug interaction (DDI) assessment, and translational exposure-efficacy modeling.
Authors: Karthik Venkatakrishnan, Xiaofei Zhou, Jeffrey Ecsedy, Jerome Mettetal, Ely Benaim, Hua Liu, Gerald Steven Falchook, Howard Fingert, Wen Chyi Shyu, Robert Kleinfield, Ashley Milton
Journal: Journal of Clinical Oncology (2013)

2598 Background: Two maximum tolerated doses (MTDs) were reported for P/A combination in Ph 1 of NCT01091428 (Falchook, ASCO 2012). Here we report clinical PK/DDI results in the context of preclinical exposure-efficacy relationship for P/A to select RP2D. Methods: Pts with advanced ovarian/breast cancer received A (oral BID D1–3, 8–10, 15–17) with 60 or 80 mg/m 2 P on D1, 8, 15 in 28-D cycles, with 3+3 dose escalation of A. PK of P was assessed on cycle 1 D1 (P+A); during cycle 2, A doses were withheld on D1–3 allowing for PK of P to be determined in the absence of A on D1. Isobolographic analysis of the response surface relating area under the plasma concentration-time curve (AUC) of A and P to tumor growth inhibition in mice bearing MDA-MB-231 xenografts incorporated mouse-human ratios of plasma free fraction and maximum tolerated exposures, allowing rank ordering of predicted antitumor activity for combined P and A. Results: MTDs were 80 mg/m 2 P + 10 mg BID A (80P/10A) and 60 mg/m 2 P + 40 mg BID A (60P/40A), as grade 3/4 toxicities (diarrhea, stomatitis, neutropenia, febrile neutropenia) precluded further escalation. Co-administration with A resulted in a small increase in AUC of P (20–25% at 80P/10A; 10–19% at 60P/40A; Table). AUC of P at 60P/40A was below 80P alone. GeoMean D3 concentrations of A at 80P/10A (340 nM) and 60P/40A (1490 nM) were respectively below and within the reported range (590–6580 nM) for tumor AAK inhibition by A (Cervantes, CCR 2012) for 60P/40A. Exposures of A dosed with P were as expected from previous single agent population PK (Venkatakrishnan, ASCO 2012). Exposure-efficacy modeling and isobolographic analysis predicted a rank-order of efficacy at clinical exposures of P/A: 60P/40A &gt; 80P/10A&gt;80P=60P. Conclusions: Safety, PK, and modeling results support 60P/40A as RP2D, currently employed in Ph 2 of NCT01091428, which is enrolling pts with advanced ovarian cancer. Clinical trial information: NCT01091428. [Table: see text]
USE OF INTERACTING DRUGS DID NOT MODIFY TREATMENT EFFECTS OF APIXABAN VERSUS WARFARIN FOR ATRIAL FIBRILLATION: RESULTS FROM THE ARISTOTLE TRIAL
Authors: Jeffrey B. Washam, Stefan Hohnloser, Daniel Wojdyla, Dragos Vinereanu, John Alexander, Renato Lopes, Bernard Gersh, Michael Hanna, John Horowitz, Elaine M. Hylek, Steen Husted, Denis Xavier, Freek W.A. Verheugt, Lars Wallentin, Christopher Granger
Journal: Journal of the American College of Cardiology (2017)
VENTRICULAR TACHYCARDIA IN A PATIENT WITH COEXISTING BRUGADA SYNDROME AND CORONARY VASOSPASM
Authors: Kunal M. Patel, Rahul Vasudev, Upamanyu Rampal, Hiten Patel, Hartaj Virk, Fayez Shamoon, Satish Tiyyagura
Journal: Journal of the American College of Cardiology (2017)
ECHO MILESTONES: A NOVEL SIMULATION-BASED ECHOCARDIOGRAPHY COMPETENCE TOOL FOR FORMATIVE ASSESSMENT IN CARDIOLOGY TRAINING
Authors: Sherryn Rambihar, Matthew Lineberry, Gillian Nesbitt, Jeremy Edwards, Gera Kisselman, Yoon Soo Park, Ara Tekian, Ryan Brydges
Journal: Journal of the American College of Cardiology (2017)
Physiological Effects of Ac4ManNAz and Optimization of Metabolic Labeling for Cell Tracking
Authors: Sang-Soo Han, Dong-Eun Lee, Hye-Eun Shim, Sangmin Lee, Taekhee Jung, Jung-Hwa Oh, Hyang-Ae Lee, Sung-Hwan Moon, Jongho Jeon, Seokjoo Yoon, Kwangmeyung Kim, Sun-Woong Kang
Journal: Theranostics (2017)

Metabolic labeling techniques are powerful tools for cell labeling, tracking and proteomic analysis.However, at present, the effects of the metabolic labeling agents on cell metabolism and physiology are not known.To address this question, in this study, we analyzed the effects of cells treated with Ac4ManNAz through microarray analysis and analyses of membrane channel activity, individual bio-physiological properties, and glycolytic flux.According to the results, treatment with 50 μM Ac4ManNAz led to the reduction of major cellular functions, including energy generation capacity, cellular infiltration ability and channel activity.Interestingly, 10 μM Ac4ManNAz showed the least effect on cellular systems and had a sufficient labeling efficiency for cell labeling, tracking and proteomic analysis.Based on our results, we suggest 10 μM as the optimum concentration of Ac4ManNAz for in vivo cell labeling and tracking.Additionally, we expect that our approach could be used for cell-based therapy for monitoring the efficacy of molecule delivery and the fate of recipient cells.
SUPRAVALVULAR AORTIC STENOSIS: A RARE COMPLICATION OF FAMILIAL HYPERCHOLESTEROLEMIA PRESENTING AS CARDIOGENIC SHOCK
Authors: Rani Upadhyay, Erika Jones, Meena Zareh, Donna Kang, Hartaj Girn, Anilkumar Mehra
Journal: Journal of the American College of Cardiology (2017)
A prospective evaluation of pulmonary, cardiac, and hepatic function (fn) in ‘<i>tAnGo’:</i> A randomized phase III trial of gemcitabine (G) in paclitaxel (T)-containing, epirubicin/cyclophosphamide (EC)-based, adjuvant chemotherapy (CT) for early stage breast cancer
Authors: C. J. Poole, H. C. Howard, L. Hiller, J. A. Dunn, A. M. Wardley, A. Bowman, R. E. Coleman, I. N. Fernando, D. M. Ritchie, H. M. Earl
Journal: Journal of Clinical Oncology (2004)

821 Background: tAnGo is an ongoing 3000-patient (pt) randomized trial evaluating for the first time the role of G in adjuvant CT for breast cancer. We present the results of a preliminary prospective safety study designed to assess the incidence of any treatment (trt)-related clinical or sub-clinical disturbances of pulmonary, cardiac, or hepatic fn in the first 135 pts randomised. Methods: Pulmonary (Hb-adjusted TLCO, FEV1, FVC, CXR), cardiac (LVEF, ECG), and hepatic (AST/ALT) fn tests were conducted in 135 pts (66 EC+T, 69 EC+GT) at baseline, mid-CT, post-CT/pre-RT, and 6 months post-CT. Results: Pulmonary fn tests: majority normal at all time points, with no differences between trts or changes over time in FEV1 (p>0.3 and 0.9 resp) or FVC (p=0.95 and 0.5 resp). TLCO dropped marginally during trt (p<0.001), slightly lower for EC+GT pts (p=0.03). 94% of all CXRs normal with no differences between trts (p>0.25) and no changes over time (p=0.14). Cardiac fn tests: 95% of all Echo/MUGA scans and 90% of all ECGs normal, with no differences between trts (p>0.35 and >0.25 resp) and no changes in Echo/MUGAs over time (p=0.4); only a slight time effect in ECGs (p=0.03). Hepatic fn tests: 92% of all AST levels and 82% of all ALT levels normal (majority of abnormal results graded 1/2): EC+T pts show a modest increase in transaminases at mid-CT but this resolves by post-CT (AST p=0.08 and ALT p=0.38 for change over time); transaminase increases in EC+GT pts persist post-CT but resolve by 6 months (AST p=0.004 and ALT p=0.001 resp for change over time). Acute skin toxicity during RT: 87% of reports graded this as Nil/Mild; only 1% as severe; no difference between trts (p>0.1), although severity increased over time (p<0.0001). There were no trt related deaths. Conclusions: These data suggest that clinically relevant trt effects on pulmonary or cardiac fn will be rare over the course of the entire study. Reported transaminase increases are both modest and reversible. Long term follow-up tests will be performed at 5 and 10 yrs. No significant financial relationships to disclose.
CLINICAL AND PATHOLOGIC FINDINGS OF AORTIC DISSECTION AT AUTOPSY: REVIEW OF 338 CASES OVER 6 DECADES
Authors: Nick Huynh, Sarah Thordsen, Shannon Mackey-Bojack, Taylor Thomas, Emily Duncanson, Darlington Nwaudo, Ross Garberich, Kevin Harris
Journal: Journal of the American College of Cardiology (2017)
Epsilon Aminocaproic Acid (EACA) Reduces Transfusion Requirements in Patients with Thrombocytopenic Hemorrhage.
Authors: Sujith Rao Kalmadi, Ramon Tiu, Christopher Lowe, Ronald Sobecks, Brian Bolwell, Alan Lichtin, Mohammad Hussein, Jarek Maciejewski, Anjali Advani, Mikkael Sekeres, Steven Andresen, Pohlman Brad, Paul Elson, Matt Kalaycio
Journal: Blood (2004)
SURROGATE ENDPOINTS AND THE DIFFERENTIAL RESPONSE TO ASV FOR SLEEP APNEA IN HFREF VERSUS HFPEF IN THE CAT-HF TRIAL
Authors: Adam Benjafield, JoAnn Lindenfeld, Olaf Oldenburg, David Whellan, Mona Fiuzat, Naresh Punjabi, Kevin Anstrom, Amy Blase, Holger Woehrle
Journal: Journal of the American College of Cardiology (2017)
Patient satisfaction with participation in phase II/III NCCTG clinical trials: Was it worth it? (N0392).
Authors: Cynthia Chauhan, Pamela J. Atherton, Daniel Satele, Amylou C. Dueck, Gamini S. Soori, David B. Johnson, Sumithra J. Mandrekar, Jan C. Buckner, Jeff A. Sloan
Journal: Journal of Clinical Oncology (2012)

6133 Background: Patient (pt) trial experience may give insight to quality of life (QOL) factors affecting accrual, retention and outcome. While pts are vital to clinical trial success, we know little about their post-trial opinions. This trial examined pt opinion of their trial and treatment decision making (TDM). Methods: Pts enrolled on designated North Central Cancer Treatment Group (NCCTG) phase II or III treatment trials completed the TDM Control Preferences Scale at baseline and the Was It Worth It (WIWI) satisfaction assessment at the ends of cycle 1 and active protocol treatment. The primary endpoint was the proportion of pts reporting worthwhile participation. Fisher Exact tests compared pt opinion across subgroups. Results: As of 01/15/2012, 264 pts were enrolled on 25 protocols and treated at 79 sites. 86% of pts were in phase II studies and 89% had stage IV disease. At the end of cycle 1, pts felt the trial was worthwhile (74%), would do it again (85%), and would recommend it to others (82%). 85% of pts reported undiminished QOL and only 7% rated the trial worse than expected. End of treatment responses were similar. Satisfaction rates varied by tumor site (p=0.04). 11% of pts having tumor response rated the trial as not worthwhile, and 66% of pts with progressive disease rated it worthwhile (see table). Pts with concordant preferred and actual TDM roles rated participation higher than pts with discordant TDM roles (see table). Conclusions: Most pts endorsed their clinical trial experience. Contrary to popular beliefs, treatment outcome did not have an overwhelming impact on pt satisfaction, and was just one of many factors such as TDM role discordance. Assessing pt satisfaction will inform future study design that can potentially improve pt accrual and retention. [Table: see text]
Determining issues of importance for patients with breast cancer: Results of a web-based study in 1,072 patients to enhance the content validity for the development of a new health-related quality of life (QL) instrument, the Breast Cancer Symptom Scale (BCSS)
Authors: J. L. Horigan, R. J. Gralla, B. J. Davis, P. J. Hollen, J. A. Petersen, K. Burg, A. Belland, J. Carleton
Journal: Journal of Clinical Oncology (2009)

e20615 Background: Identifying key issues for patients with malignancy is central to assessing QL and patient reported outcomes during all points of the illness trajectory. The involvement of patients in establishing content validity is crucial for instrument development. The conceptual model for the BCSS focuses on areas of importance for patients (Hollen, Supp Care Ca 1994). Methods: We used the established patient base of the web-based NexCura information resource to survey registered patients with breast cancer. Demographic stratifications included disease stage, age, menopausal status, time since diagnosis, prior/current treatment with surgery, RT, chemotherapy, hormonal, targeted, and CAM approaches. 1072 patients (median age 53, 65% stage I, 43% &gt; 2 years since diagnosis) completed the anonymous web-conducted survey. Patients ranked 21 issues on a 5-point scale, assessing the importance of each item. Issues included general, physical, functional, psychosocial and summative items. Results: The 9 highest ranked items are seen below. Results are described by the percent of patients choosing the top category (very important) and the top 2 importance categories. The five lowest ranked items dealt with appetite, breast-specific issues, hot flashes and sexuality. Ratings by breast cancer subsets (newly diagnosed, on treatment, NED, hormonal or non-hormonal treatment, metastatic disease, survivors) showed some differences compared with the whole group. Conclusions: These results represent one of the largest surveys of concerns expressed by patients with breast cancer and support using computer-assisted technology to assess such information for rapid input of large patient samples. This study gives strong support for content validity for the BCSS and provides data on which to base separate QL instruments for specific breast cancer settings. [Table: see text] [Table: see text]
CARDIAC ARREST AND NON-FATAL MYOCARDIAL INJURY AMONG MARATHON RUNNERS: 15 YEARS’ EXPERIENCE OF THE HONG KONG STANDARD CHARTERED MARATHON
Authors: Kit Chan, Kuang An Wan, Sai Chau Leung, Jessica Wai Ling Poon, Natalie Leung, Ngai Shing Mok, Yuk Kong Lau
Journal: Journal of the American College of Cardiology (2017)
Analysis of disease activity categories in chronic spontaneous/idiopathic urticaria
Authors: D. Stull, D. McBride, H. Tian, A. Gimenez Arnau, M. Maurer, A. Marsland, M.-M. Balp, S. Khalil, C. Grattan
Journal: British Journal of Dermatology (2017)

Measurement of disease activity guides treatment of chronic spontaneous urticaria (CSU). A weekly Urticaria Activity Score - here, the average of twice-daily patient assessment of itch and hives scores summed over 1 week (UAS7TD ) - measures severity from 0 to 42. Insufficient evidence exists on whether disease activity states, defined by categorical UAS7TD scores, correlate with other patient-reported outcomes and treatment response.To evaluate and compare categorical UAS7TD scores with selected measures of disease-related quality of life and impact.Data from three randomized clinical trials of omalizumab in CSU were pooled. Continuous UAS7TD scores were categorized into five disease activity states: urticaria-free, well-controlled, mild, moderate and severe urticaria. Total scores from the Dermatology Life Quality Index; the Chronic Urticaria Quality of Life questionnaire; and questions on sleep and daily activity interference, presence of angioedema and diphenhydramine use were compared within categorized UAS7TD disease-state scores, using anova for analysis at different time points and mixed-effects regressions for analysis of all data pooled.Pooled analyses showed that categorical UAS7TD disease states accurately predicted differences among treated patients with CSU with different levels of disease activity. A consistent pattern existed between categories, with higher-activity disease states associated with significantly higher impact and an increase in angioedema frequency. Results at different treatment time points were consistent.Categorical UAS7TD disease states can discriminate between measures when considering the impact of urticaria activity. Using five categorical disease states could simplify clinical assessment and monitoring of treatment efficacy.
ASSOCIATION OF OBJECTIVELY MEASURED SEDENTARY TIME, PHYSICAL ACTIVITY AND CARDIORESPIRATORY FITNESS LEVELS WITH CARDIOMETABOLIC RISK FACTORS AND CARDIAC STRUCTURE AND FUNCTION: FINDINGS FROM THE DALLAS HEART STUDY
Authors: Brad Peden, Ambarish Pandey, Colby Ayers, Jarett Berry
Journal: Journal of the American College of Cardiology (2017)
Residual tumor resections (RTR) in patients with germ cell tumors (GCT) after salvage chemotherapy.
Authors: Christian Winter, Cigdem Bingoel, Ralf Witthuhn, Patrick De Geeter, Peter Albers
Journal: Journal of Clinical Oncology (2012)

4601 Background: Residual tumor resections (RTR) after salvage chemotherapy are of utmost importance due to a much higher rate of vital carcinoma in the residual tumor. A complete RTR may lead to an improved long term survival of such patients (pts). Methods: A retrospective analysis was performed in 197 pts who underwent 209 RTRs in 2 referral centers (2003-2011) with identical surgical technique (2 surgeons). The RTR database was queried for pts who received salvage chemotherapy (conventional salvage chemotherapy (CCT) or high-dose salvage chemotherapy (HDCT)) and a subsequent RTR. Results: Sixty (29%) of all RTRs were performed after salvage chemotherapy. In 31 pts (52%) and 29 pts (48%) a CCT and HDCT was used as salvage regimen, respectively.Vital cancer was found in 48% and 45% of pts with CCT and HDCT. Respectively, vital cancer consisted of germ cell cancer and malignant transformed teratoma in 61% and 39% of the cases. In contrast, the percentage of vital cancer in pts after 1st-line treatment was 30% (p= 0.0365).This comparatively high rate is due to a 55% rate of intermediate/poor prognosis pts in the whole group of 209 RTRs. To date we have evaluated the oncological outcome in 171 of 197 pts with a median follow-up of 23 months (1-227). In 142 pts no relapse was observed, whereas in 29 pts a GCT relapse occured (17%), 7 (4.6%) of all evaluated pts had an “in-field”-relapse. 7 pts died due to tumor progression. The relapse rate in pts with RTR after salvage regime was significantly higher compared to RTR pts after primary chemotherapy (37% vs. 13%, p= 0.0008). The „in-field“-relapse rate in pts with RTR after salvage was only in 3.9%, 2 pts died due to tumor progression. Conclusions: Every second pts with RTR after salvage chemotherapy showed vital cancer in the residual tumor. The relapse rate in pts with RTR after salvage chemotherapy was significantly higher compared to RTR pts after first-line chemotherapy (p=0.0008) but the “infield” relapse rate was similar. A complete resection of all residual lesions after salvage chemotherapy is necessary to potentially improve the long-term disease-free survival. This is especially true for pts with malignant transformed teratoma and restricted options for repeated salvage chemotherapy.
TRANSCATHETER AORTIC VALVE REPLACEMENT PATIENTS WITH ATRIAL FIBRILLATION ARE AT HIGH RISK FOR STROKE AND BLEEDING: A RATIONALE FOR CONSIDERATION OF TRANSCATHETER AORTIC VALVE REPLACEMENT AND LEFT ATRIAL APPENDAGE CLOSURE AS COMPLEMENTARY THERAPIES
Authors: Kishore J. Harjai, Eugenia Hopkins, Vernon Mascarenhas, Samuel Crockett, Deepak Singh, Russell Stahl, Thomas J. Bules, Lori Scalzo, Pugazhendhi Vijayaraman
Journal: Journal of the American College of Cardiology (2017)
EFFECT OF DIABETES MELLITUS ON PULSATILE ARTERIAL LOAD AND HEMODYNAMICS IN HFPEF
Authors: Julio A. Chirinos, Payman Zamani, Zeba Hashmath, Maheshwara Reddy Koppula, Amer Ahmed Syed, Priyanka Bhattacharya, Jugal Chahwala, Harry G. Oldland, Rachana Miller, Uzma Kewan, Swapna Varakantam, Ali Tariq, Timothy S. Phan, Scott Akers
Journal: Journal of the American College of Cardiology (2017)
GENDER DIFFERENCES IN RATES OF HOSPITALIZATIONS FOR DECOMPENSATED HEART FAILURE AMONG ADULTS WITH CONGENITAL HEART DISEASES IN THE UNITED STATES: A 15 YEAR EXPERIENCE
Authors: Ghanshyam Palamaner Subash Shantha, Anita Kumar, Kongkiat Chaikriangkrai, Chakradhari Inampudi, Gardar Sigurdsson, Michael Giudici
Journal: Journal of the American College of Cardiology (2017)
Dosing of troxacitabine (Troxatyl [T], SGX-145) based on renal function
Authors: M. J. Kelner, F. J. Giles, E. J. Feldman, G. J. Roboz, D. J. Deangelo, S. K. Burley
Journal: Journal of Clinical Oncology (2006)

2025 Background: Troxacitabine (Troxatyl [T], SGX-145) is a novel L-configuration nucleoside analog anti-cancer agent with unique mechanistic/cytotoxic properties. T is clinically active against acute myelogenous leukemia (AML), chronic myeloid leukemia, myelodysplastic syndromes (MDS), renal cell carcinoma, and pancreatic cancer. A multi-center Phase 2/3 clinical trial is currently underway to evaluate the safety and efficacy of continuous IV infusion T treatment in second salvage AML. The major route of elimination of troxacitabine is renal excretion as unchanged drug (∼70%) and there is minimal protein binding. These results suggest that renal function may have a significant effect on steady-state troxacitabine plasma concentrations (Css). Methods: Pharmacokinetic and toxicity data from four AML clinical trials (&gt;200 patients) are being analyzed to (1) Identify a minimum Css for therapeutic efficacy; (2) Define an upper limit of Css for adverse risk; and (3) Develop a mechanism to prospectively modify the troxacitabine dose based on renal function, which would avoid excessive toxicity while maintaining therapeutic blood levels. Results: Initial results from 41 patients indicate that to induce remission in AML patients, troxacitabine steady-state plasma concentrations (Css) must be ≥ 80 ng/mL. However, higher Css values correlate with increased toxicity and, thereby, increase the risks of the treatment for an individual patient, although an upper limit for adverse risk has not yet been defined. For patients with normal renal function (creatinine clearance ≥ 50 but ≤ 125 mL/min), a Calvert style formula, based on a patient’s estimated creatinine clearance, has been developed to define the dose required to achieve a therapeutic Css ≥ 80 ng/mL. Both linear and non-linear nomogram models are also being developed to adjust troxacitabine dosage for patients with moderate renal impairment (30 mL/min &lt; creatinine clearance &lt; 50 mL/min) or for patients with high GFR (creatinine clearance &gt; 125 mL/min). Conclusion: A firm relationship exists between renal function, troxacitabine clearance, and Css values. This result indicates that a dosing strategy based on renal function may be warranted to obtain optimal troxacitabine Css values. [Table: see text]
ELECTROMECHANICAL ACTIVATION TIME VIA HEMOTAG AND 2D ECHOCARDIOGRAPHY: CORRELATION WITH TRICUSPID REGURGITATION PEAK VELOCITY AND IMPLICATIONS FOR DIAGNOSIS AND CLINICAL PRACTICE
Authors: Stephanie Hakimian, Mahdi Esfahanian, Kale Kaustubh, Elie Donath, Steven Borzak, Robert Chait
Journal: Journal of the American College of Cardiology (2017)
Erratum to: A multifunctional therapeutic approach to disease modification in multiple familial mouse models and a novel sporadic model of Alzheimer’s disease
Authors: Jia Luo, Sue H. Lee, Lawren VandeVrede, Zhihui Qin, Manel Ben Aissa, John Larson, Andrew F. Teich, Ottavio Arancio, Yohan D’Souza, Ahmed Elharram, Kevin Koster, Leon M. Tai, Mary Jo LaDu, Brian M. Bennett, Gregory R. J. Thatcher
Journal: Molecular Neurodegeneration (2016)