tbuckley/cabot-search huggingface dataset:
Evaluation of transcatheter arterial chemoembolization (TACE) plus sorafenib in Chinese patients with unresectable hepatocellular carcinoma: A subgroup analysis of START trial.
Authors: Guohong Han, Jijin Yang, Guoliang Shao, Gaojun Teng, Maoqiang Wang, Jianyong Yang, Zhaoyu Liu, Gansheng Feng, Renjie Yang, Ligong Lu, Yee Chao, Jianhua Wang
Journal: Journal of Clinical Oncology (2012)

e14605 Background: The therapeutic effect of TACE plus Sorafenib (Sor) for unresectable hepatocellular carcinoma (uHCC) was evaluated in the START (Study in Asia of the Combination of TACE with Sor in Patients with Hepatocellular Carcinoma) trial. The preliminary results presented at ILCA 2011 showed encouraging safety and efficacy profiles of TACE plus Sor in HCC, with a median time to progression (TTP) of 9.3 months and median overall survival (OS) not reached. Here we present results of a subgroup analysis of Chinese patients with more updated data. Methods: Patients with uHCC and candidates for TACE were enrolled. TACE with lipiodol and doxorubicin (30-60 mg) was performed every 6 to 8 weeks. Sor (400mg bid) was administrated 4 days after first TACE, and then continuously with interruption 3 days before and after the TACE procedure. Tumors were assessed 4 weeks after every TACE, and every 3 months thereafter if no TACE was indicated. Patients who do not require TACE due to complete response or intolerability continued to receive Sor until disease progression (PD) or unacceptable toxicity. This analysis was conducted to evaluate the efficacy of TACE plus Sor on TTP based on modified RECIST criteria, OS and response rate (RR) in Chinese patients with uHCC. Cut-off date for the efficacy analysis is Sep 30 th , 2011. Because no new or unexpected side effects were noted during this study period, safety data were not collected in this subgroup analysis. Results: A total of 64 patients enrolled from Sep. 2009 to Apr. 2010, were evaluated. The median age was 62 yr (range, 31-75) and all patients were ECOG Performance Status 0-1. The main etiology for HCC was hepatitis B in 94.9% of patients. The mean dose of Sor in this group of patients is 787.63mg.The median treatment duration was 6.4 months. The median TTP was 10.6 months, and the median OS was 16.5 months. The objective RR was 44.3%, and 11.5% of patients had PD. Conclusions: This subgroup analysis suggests that Chinese patients with uHCC may benefit from TACE and Sor combination therapy, with better improvement of TTP, compared to the interim analysis results of the overall population from the START trial.
Abstract 41: Cell Cycle Activation of Cardiomyocytes Derived From Induced Pluripotent Stem Cells for Cardiac Regeneration
Authors: Wuqiang Zhu, Meng Zhao, Saidulu Mattapally, Ling Gao, Jianyi Zhang
Journal: Circulation Research (2016)

Transplantation of cardiomyocytes derived from induced pluripotent stem cells (iPSCs) improves cardiac function in animal models with myocardial infarction. However, the poor number of survived cells and the low proliferation capability of cardiomyocyte derived from iPSCs are bottlenecks in myocardial repair with cell therapy. We hypothesize that increasing the number of surviving iPSC-CMs in the engraftment via cell cycle induction may lead to a transmural replacement of scar tissue and a lasting restoration of cardiac function. Cyclin D2 is a protein that regulates cell cycle transition from G1 to S phase. We transfected MHC-cyclin D2 (designated as MHC-cycD2) cDNA into the iPSCs, and differentiated the iPSCs into cardiomyocytes. Comparing to non-expressing cells, MHC-cycD2-expressing cardiomyocytes displayed increased Brdu incorporation activity, suggesting the enhanced cell cycle in MHC-cycD2-expressing cardiomyocytes. Cell cycle activity was confirmed by increased number of Ki-67 and PCNA positive immunostaining cardiomyocytes and more contractile embryonic body cell mass in MHC-cycD2-expressing culture compared to non-expressing culture. Data from Q-PCR and histology suggested that expression of MHC-cycD2 didn’t alter the pluripotency or cardiomyogenic potential of iPSCs. Thus, we have successfully induced cell cycle in iPSC-derived cardiomyocytes via expression of cyclin D2. We are currently studying if MHC-cycD2-expressing iPSC-cardiomyocytes exhibit superior regenerative potential compared to their non-expressing counterparts following transplantation into chronically infarcted hearts.
A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)
Authors: J. Mateo, D. Chakravarty, R. Dienstmann, S. Jezdic, A. Gonzalez-Perez, N. Lopez-Bigas, C.K.Y. Ng, P.L. Bedard, G. Tortora, J.-Y. Douillard, E.M. Van Allen, N. Schultz, C. Swanton, F. André, L. Pusztai
Journal: Annals of Oncology (2018)

In order to facilitate implementation of precision medicine in clinical management of cancer, there is a need to harmonise and standardise the reporting and interpretation of clinically relevant genomics data.
Abstract 11562: Computational Fluid Dynamics in Type B Aortic Dissection: A Systematic Review
Authors: Zhonghua Sun
Journal: Circulation (2015)

Introduction: Computational fluid dynamics (CFD) has been increasingly used to analyse cardiovascular hemodynamics through simulations to predict the behaviour of blood flow in the cardiovascular system. Hypothesis: It is hypothesized that CFD modelling assists in clinical decision-making by providing detailed analysis of flow patterns in patients with aortic dissection. Methods: A search of biomedical database for English literature was performed to identify studies investigating the CFD applications in type B aortic dissection. Only studies dealing with patient’s data were included, while reports based on phantom studies were excluded from the analysis. Results: Twelve studies were found to meet selection criteria and were included in the analysis. CFD simulations were based on a selected CT or MRI imaging data in 8 studies, while in the remaining four studies, CFD simulations were derived from 3 cases in two studies, and 4 and 8 cases in one study, respectively. CFD models and simulations were found to successfully capture the complex regions of hemodynamic flow by demonstrating low velocities in the false lumen and high velocities in the true lumen. In the true lumen, high time-averaged wall shear stress (TAWSS) was seen in the regions around the tear, while in the false lumen, TAWSS was less uniform due to recirculating flow in the dilated region (Figure). Presence of an additional re-entry tear was shown to provide an extra return path for blood back to the true lumen during systole, and an extra flow path into the false lumen during diastole. Following endovascular stent grafting, large WSS magnitudes were eliminated in the true lumen, while in the false lumen, the maximum WSS was reported to be reduced by more than a factor of 2. Conclusions: CFD offers insight into the hemodynamic factors such as velocity field and wall shear stress, and CFD models and simulations improve understanding of hemodynamics in type B aortic dissection.
Abstract 14616: Optimizing Guideline-Directed Medical Therapy Reduce Mortality but Not Heart Failure Readmission in Patients With Hospitalized Heart Failure - A Competing Risk Analysis
Authors: Tetsuo Yamaguchi, Yuya Matsue, Junji Yamaguchi, Takamichi Miyamoto, Tshihiro Nozato
Journal: Circulation (2017)

Introduction: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF; LVEF ≤40%) is recommended. However, prognostic impact of medication optimization bef...
Air Pollution Linked to Infant Deaths
Authors: M.J. Friedrich
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 16056: Ezetimibe Increases Reverse Cholesterol Transport in Humans
Authors: Xiaobo Lin, Susan B Racette, Lina Ma, Michael Wallendorf, Richard E Ostlund
Journal: Circulation (2016)

Introduction: Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. Although ezetimibe reduces LDL, it also lowers intestinal cholesterol absorption but the exact effec...
Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy
Authors: Mathew S. Maurer, Jeffrey H. Schwartz, Balarama Gundapaneni, Perry M. Elliott, Giampaolo Merlini, Marcia Waddington-Cruz, Arnt V. Kristen, Martha Grogan, Ronald Witteles, Thibaud Damy, Brian M. Drachman, Sanjiv J. Shah, Mazen Hanna, Daniel P. Judge, Alexandra I. Barsdorf, Peter Huber, Terrell A. Patterson, Steven Riley, Jennifer Schumacher, Michelle Stewart, Marla B. Sultan, Claudio Rapezzi
Journal: New England Journal of Medicine (2018)

Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis.In a multicenter, international, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive 80 mg of tafamidis, 20 mg of tafamidis, or placebo for 30 months. In the primary analysis, we hierarchically assessed all-cause mortality, followed by frequency of cardiovascular-related hospitalizations according to the Finkelstein-Schoenfeld method. Key secondary end points were the change from baseline to month 30 for the 6-minute walk test and the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS), in which higher scores indicate better health status.In the primary analysis, all-cause mortality and rates of cardiovascular-related hospitalizations were lower among the 264 patients who received tafamidis than among the 177 patients who received placebo (P<0.001). Tafamidis was associated with lower all-cause mortality than placebo (78 of 264 [29.5%] vs. 76 of 177 [42.9%]; hazard ratio, 0.70; 95% confidence interval [CI], 0.51 to 0.96) and a lower rate of cardiovascular-related hospitalizations, with a relative risk ratio of 0.68 (0.48 per year vs. 0.70 per year; 95% CI, 0.56 to 0.81). At month 30, tafamidis was also associated with a lower rate of decline in distance for the 6-minute walk test (P<0.001) and a lower rate of decline in KCCQ-OS score (P<0.001). The incidence and types of adverse events were similar in the two groups.In patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo. (Funded by Pfizer; ATTR-ACT ClinicalTrials.gov number, NCT01994889 .).
Google searches do not correlate with melanoma incidence in majority English speaking countries
Authors: Laura McDonald, Alex Simpson, Sophie Graham, Anna Schultze, Beth Nordstrom, Piyush Durani, Faisal Mehmud, Sreeram V. Ramagopalan
Journal: npj Digital Medicine (2018)

Recent reports have suggested that internet search behaviour may be a valuable tool to estimate melanoma incidence and mortality. Previous studies have used incorrect statistical methods, were focussed on the United States and/or did not use non-cancer control search terms to provide a context for interpreting the effects seen with the cancer-related terms. Using more robust statistical methods we found that no cancer search terms were significantly, or strongly correlated with melanoma incidence in 6 countries.
Letter to the editor: Measles cases among fully vaccinated persons
Authors: Yuzo Arima, Kazunori Oishi
Journal: Eurosurveillance (2018)

Preview this article: Letter to the editor: Measles cases among fully vaccinated persons, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/23/34/eurosurv-23-34-3-1.gif
Effect of Physical Activity on Frailty
Authors: Alan R. Ertle
Journal: Annals of Internal Medicine (2018)

Letters21 August 2018Effect of Physical Activity on FrailtyAlan R. Ertle, MD, MPH, MBAAlan R. Ertle, MD, MPH, MBAMercy Medical Group, Sacramento, California (A.R.E.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0242 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Trombetti and colleagues' article (1) with interest. My parents were born in the 1920s in Oregon. Into adulthood, I never saw them exercise for the sake of exercise. Being active was all that was required. However, ideas about exercise were changing. Jack LaLanne was on television, then came the publication of Dr. Kenneth Cooper's book Aerobics in 1968; the Presidential Physical Fitness Award, which heralded a new emphasis on physical fitness and testing, was initiated the same year. My parents were not interested.My father required aortic valve replacement in 1982 for a degenerating bicuspid ...Reference1. Trombetti A, Hars M, Hsu FC, Reid KF, Church TS, Gill TM, et al; LIFE Study Investigators. Effect of physical activity on frailty: secondary analysis of a randomized controlled trial. Ann Intern Med. 2018;168:309-16. [PMID: 29310138]. doi:10.7326/M16-2011 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Mercy Medical Group, Sacramento, California (A.R.E.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0242. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffect of Physical Activity on Frailty Andrea Trombetti , Mélany Hars , Fang-Chi Hsu , Kieran F. Reid , Timothy S. Church , Thomas M. Gill , Abby C. King , Christine K. Liu , Todd M. Manini , Mary M. McDermott , Anne B. Newman , W. Jack Rejeski , Jack M. Guralnik , Marco Pahor , Roger A. Fielding , and Effect of Physical Activity on Frailty Andrea Trombetti , Mélany Hars , Marco Pahor , Mary M. McDermott , and Roger A. Fielding Metrics 21 August 2018Volume 169, Issue 4Page: 266KeywordsDisclosureElderlyExerciseFrailtyHealth careHealth care providersHeart diseasesPatient advocacyPhysical fitnessStent implantation ePublished: 21 August 2018 Issue Published: 21 August 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 18708: Vascular Dysfunction in Hyperhomocysteinemia: In vitro Evidence for Endoplasmic Reticulum Stress-mediated Calcium-activated Potassium Channel Dysfunction
Authors: Wen-Tao Sun, Xiang-Chong Wang, Cheuk-Man Yu, Shun-Hay Pun, Qin Yang
Journal: Circulation (2015)

Objectives: KCa channels play an important role in the control of vascular tone. Opening of IKCa and SKCa in endothelial cells underlies the classic EDHF pathway and promotes NO production. Smooth muscle BKCa provides a negative feedback mechanism opposing vasoconstriction and is an effector of NO and EDHF. Previous studies demonstrated homocysteine (Hcy), a risk factor for atherosclerosis, compromises NO and EDHF function, however, whether KCa is involved is poorly studied and the underlying mechanisms remain unknown. We studied the effect of Hcy on vascular KCa with the role of endoplasmic reticulum (ER) stress explored. Methods: In vitro studies were performed in porcine coronary arteries and primary cultured porcine coronary endothelial (PCECs) and smooth muscle cells (PCSMCs). IKCa and SKCa-, and BKCa-mediated relaxations were studied in endothelium-intact and -denuded arteries in a myograph. IKCa and SKCa currents in PCECs and BKCa current in PCSMCs were analyzed by whole-cell patch clamp and channel expressions were examined by western blot. Results: Hcy impairs the role of IKCa and SKCa, and BKCa in vasorelaxation. Relaxant responses to channel activators NS309 and NS1619 were attenuated and EDHF-type response was inhibited. Hcy suppressed IKCa and SKCa currents in PCECs and BKCa currents in PCSMCs. Inhibition of ER stress enhanced KCa currents and improved EDHF-type and channel activators-induced responses. Whole-cell protein levels of IKCa and SKCa remained unchanged in Hcy-exposed PCECs whereas IKCa and SKCa at cell surface were significantly decreased. Hcy lowered protein of β1 but not α subunit of BKCa in PCSMCs. The decrease in cell surface IKCa and SKCa and reduction of BKCa β1 were restored by ER stress inhibition. Further, inhibition of PERK increased BKCa β1 protein and enhanced BKCa current. Conclusion: ER stress mediates Hcy-induced vascular dysfunction through inhibition of KCa. Suppression of cell surface expression underlies ER stress-mediated IKCa and SKCa inhibition. Downregulation of BKCa β1 by PERK-ER stress pathway plays a key role in the loss of BKCa function. This study provides new mechanistic insights into the role of ER stress in vascular dysfunction. Supported by RGC GRF CUHK4774/12M &amp; CUHK14118414, and NSFC 81200123.
The age of enlightenment in melanoma immunotherapy
Authors: Mark R. Albertini
Journal: Journal for ImmunoTherapy of Cancer (2018)

An updated survival analysis by Callahan et al. published in the February 1, 2018 issue of the <i>Journal of Clinical Oncology</i> reported a 3-year overall survival (OS) rate of 63% for 94 patients with previously treated or untreated advanced melanoma who received ipilimumab and nivolumab as concurrent therapy in a phase 1 dose escalation study CA209–004 (<i>n</i>&nbsp;= 53) or in an expansion cohort with the dose and schedule of concurrent ipilimumab and nivolumab now approved for patients with unresectable or metastatic melanoma (<i>n</i>&nbsp;= 41). While this 3-year OS rate of 63% in patients with measurable, unresectable stage III or IV melanoma is an impressive accomplishment that compares very favorably with historical metastatic melanoma survival rates, findings from larger phase 3 studies are needed to determine whether combination immunotherapy significantly improves survival more than single agent immunotherapy with PD-1 blockade. This Commentary discusses the transition from the dark ages to the age of enlightenment in melanoma immunotherapy and provides a roadmap for a better tomorrow for patients with metastatic melanoma.
Abstract 16768: Common Autosomal Variants Modify the Penetrance of Left-sided Cardiac Lesions in Turner Syndrome
Authors: Siddharth Prakash, Angela Lin, Laura Perrone, Giuseppe Limongelli, Hector Michelena, Scott Lemaire, Simon Body, Dianna Milewicz
Journal: Circulation (2016)

Background: Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Left-sided congenital cardiac lesions (LSL), primarily bicuspid aortic valve (...
Abstract 16098: Mechanism of Branch Pulmonary Artery Stenosis After the Arterial Switch Operation
Authors: Conall T Morgan, Luc Mertens, Heynric Grotenhuis, Shi-Joon Yoo, Mike Seed, Lars Grosse-Wortmann
Journal: Circulation (2015)

Background: Branch pulmonary artery (PA) stenosis, most commonly on the left, is a recognized postoperative complication of the arterial switch operation (ASO) for transposition of the great arteries. We hypothesized that greater rightward rotation of the neopulmonary root and dilation of the ascending aorta are associated with stenosis of the left PA (LPA). Methods: This study represents a retrospective analysis of cardiac magnetic resonance imaging (CMR) studies performed in patients after ASO. Neo-pulmonary root position in relation to the aorta was expressed as an angle, with a negative angle implying a rightward neo-pulmonary root. For the purpose of this study, perfusion imbalance was defined as &lt;40% of pulmonary blood flow to the affected lung. The offset between the LPA and right PA (RPA) as a result of cranial displacement of the LPA by asymmetric aortic root dilation was measured in the coronal plane. Results: 74 patients / studies were included for analysis. 73% had no branch PA stenosis, 24% had LPA stenosis and 3% had RPA stenosis. LPA area indexed to BSA was smaller than RPA area (287 ± 185mm2 vs 151 ± 114mm2, p=0.001). Smaller LPA area correlated with reduced LPA flow (r=0.213, p=0.0001) and a greater rightward positioning of the neopulmonary to aortic root (r=0.361, p=0.002). There was no correlation between LPA size or flow and offset of the LPA take-off due to an enlarged aortic root. Patients with reduced relative LPA flow were more likely to have required pulmonary arterioplasty with the primary repair (17% vs 2%, p=0.04), had a smaller LPA area [102±102mm2 vs 160±108mm2, p=0.04) and a smaller anterior-posterior thoracic diameter (101±53mm vs 131±55mm, p=0.04). There was no significant difference in patient demographics, cardiac diagnosis, age at operation, aortic root dimension, ventricular volumetrics or ventricular function between patients with normal LPA flow vs. reduced LPA flow. Patients with reduced LPA flow did not have greater peak gradients on echo. Conclusions: Greater rightward rotation of the neopulmonary root is associated with reduced LPA size and likely contributes to the development of LPA stenosis after ASO.
Syncope With Bifascicular Block Due to Infra-Hisian Wenckebach Conduction Abnormality
Authors: Tai H. Pham, Ezra Amsterdam, Matthew S. Glassy
Journal: JAMA Internal Medicine (2018)

This case report presents the electrocardiographic findings of a man in his 70s with a history of type 2 diabetes and hypertension who presented with syncope; there was no seizure activity or preceding chest pain, palpitations, or shortness of breath.