tbuckley/cabot-search huggingface dataset:
TCT-423 Is there a difference in cerebral infarcts in patients who undergo TAVR for calcified aortic valve stenosis compared to pure aortic regurgitation?
Authors: Ermela Yzeiraj, Timo Haselbach, Julian Witt, Klaudija Bijuklic, Lorenz Hansen, Friedrich-Christian Rieß, Joachim Schofer
Journal: Journal of the American College of Cardiology (2017)
TCT-474 Ultra-Low Contrast Coronary Angiography in Patients with Advanced Chronic Kidney Disease - Feasibility and Outcomes Compared to Standard Angiography
Authors: Navdeep Bhatti, Nisha Jhalani, Keyvan Karimi Galougahi, Yasir Parviz, Bharath Rathakrishnan, Tamim Nazif, Jeffrey W. Moses, Susheel Kodali, Dimitri Karmpaliotis, Gary Mintz, Akiko Maehara, Ajay Jayant Kirtane, Ali Akhund, Ori Ben-Yehuda, Gregg Stone, Russell Crew, Geoffery Dube, Mark Hardy, Sumit Mohan, Jai Radhakrishnan, David Cohen, Lloyd Ratner, Martin Leon, Ziad Ali
Journal: Journal of the American College of Cardiology (2017)
TCT-140 Long-term Sustained Reduction of Heart Failure Symptoms through Less-Invasive Ventricular Reshaping
Authors: Christoph Schmitz, Mauro Biffi, Davide Pacini, Roberto Di Bartolomeo, Petr Neuzil, Ivo Skalsky, Louis Labrousse, Horst Sievert, Christian Frerker, Tobias Schmidt, Karl-Heinz Kuck, Giedrius Davidavicius, Gintaras Kalinauskas, Kestutis Rucinskas, Lon Annest
Journal: Journal of the American College of Cardiology (2017)
Fibroblast bioenergetics to classify amyotrophic lateral sclerosis patients
Authors: Csaba Konrad, Hibiki Kawamata, Kirsten G. Bredvik, Andrea J. Arreguin, Steven A. Cajamarca, Jonathan C. Hupf, John M. Ravits, Timothy M. Miller, Nicholas J. Maragakis, Chadwick M. Hales, Jonathan D. Glass, Steven Gross, Hiroshi Mitsumoto, Giovanni Manfredi
Journal: Molecular Neurodegeneration (2017)

The objective of this study was to investigate cellular bioenergetics in primary skin fibroblasts derived from patients with amyotrophic lateral sclerosis (ALS) and to determine if they can be used as classifiers for patient stratification. We assembled a collection of unprecedented size of fibroblasts from patients with sporadic ALS (sALS, n = 171), primary lateral sclerosis (PLS, n = 34), ALS/PLS with C9orf72 mutations (n = 13), and healthy controls (n = 91). In search for novel ALS classifiers, we performed extensive studies of fibroblast bioenergetics, including mitochondrial membrane potential, respiration, glycolysis, and ATP content. Next, we developed a machine learning approach to determine whether fibroblast bioenergetic features could be used to stratify patients. Compared to controls, sALS and PLS fibroblasts had higher average mitochondrial membrane potential, respiration, and glycolysis, suggesting that they were in a hypermetabolic state. Only membrane potential was elevated in C9Orf72 lines. ATP steady state levels did not correlate with respiration and glycolysis in sALS and PLS lines. Based on bioenergetic profiles, a support vector machine (SVM) was trained to classify sALS and PLS with 99% specificity and 70% sensitivity. sALS, PLS, and C9Orf72 fibroblasts share hypermetabolic features, while presenting differences of bioenergetics. The absence of correlation between energy metabolism activation and ATP levels in sALS and PLS fibroblasts suggests that in these cells hypermetabolism is a mechanism to adapt to energy dissipation. Results from SVM support the use of metabolic characteristics of ALS fibroblasts and multivariate analysis to develop classifiers for patient stratification.
Disability Trajectories Before and After Stroke and Myocardial Infarction
Authors: Mandip S. Dhamoon, W. T. Longstreth, Traci M. Bartz, Robert C. Kaplan, Mitchell S. V. Elkind
Journal: JAMA Neurology (2017)

Ischemic strokes may accelerate long-term functional decline apart from their acute effects on neurologic function.To test whether the increase in long-term disability is steeper after than before the event for ischemic stroke but not myocardial infarction (MI).In the population-based, prospective cohort Cardiovascular Health Study (1989-2013), longitudinal follow-up was conducted for a mean (SD) of 13 (6.2) years. Follow-up data were used until September 1, 2013; data analysis was performed from August 1, 2013, to June 1, 2016. Models based on generalized estimating equations adjusted for baseline covariates and included a test for different slopes of disability before and after the event. Participants included 5888 Medicare-eligible individuals 65 years or older who were not institutionalized, expected to reside in the area for 3 or more years, and able to provide informed consent. Exclusions were needing a wheelchair, receiving hospice care, and undergoing radiotherapy or chemotherapy.Ischemic stroke and MI.Annual assessments with a disability scale (measuring activities of daily living [ADLs] and instrumental ADLs). The number of ADLs and instrumental ADLs (range, 0-12) that the participant could not perform was analyzed continuously.The mean (SD) age of the entire cohort (n = 5888) was 72.8 (5.6) years; 2495 (42.4%) were male. During follow-up, 382 (6.5%) participants had ischemic stroke and 395 (6.7%) had MI with 1 or more disability assessment after the event. There was a mean of 3.7 (2.4) visits before stroke and 3.7 (2.3) visits after stroke; there was a mean of 3.8 (2.5) visits before MI and 3.8 (2.4) visits after MI. The increase in disability near the time of the event was greater for stroke (0.88 points on the disability scale; 95% CI, 0.57 to 1.20; P < .001) than MI (0.20 points on the disability scale; 95% CI, 0.06 to 0.35; P = .006). The annual increase in disability before stroke (0.06 points per year; 95% CI, 0.002 to 0.12; P = .04) more than tripled after stroke (0.15 additional points per year; 95% CI, 0.004 to 0.30; P = .04). The annual increase in disability before MI (0.04 points per year; 95% CI, 0.004 to 0.08; P = .03) did not change significantly after MI (0.02 additional points per year; 95% CI, -0.07 to 0.11; P = .69).In this large, population-based study, a trajectory of increasing disability became significantly steeper after stroke but not after MI. Thus, in addition to the acute brain injury and consequent impairment, ischemic stroke may also be associated with potentially treatable long-term adverse effects on the brain that lead to accelerated functional decline.
Efficacy and safety of ixazomib plus lenalidomide-dexamethasone (IRd) vs placebo-rd in patients (pts) with relapsed/refractory multiple myeloma (RRMM) by cytogenetic risk status in the global phase III Tourmaline-MM1 study.
Authors: Paul G. Richardson, Hervé Avet-Loiseau, Antonio Palumbo, Luisa Viterbo, Arnon Nagler, Peter Ganly, Dina Ben Yehuda, Jesus San Miguel, S.Vincent Rajkumar, Ludek Pour, Christian Langer, Nizar J. Bahlis, Andrzej Pluta, Tamas Masszi, Deborah Berg, Jianchang Lin, Helgi Van De Velde, Dixie-Lee Esseltine, Alessandra di Bacco, Philippe Moreau
Journal: Journal of Clinical Oncology (2016)

8018 Background: TOURMALINE-MM1 (NCT01564537) showed a significant 35% improvement in progression-free survival (PFS) with IRd vs placebo-Rd (hazard ratio [HR] 0.742, p = 0.012) in pts with RRMM (Moreau et al, ASH 2015). Here we present an analysis of the efficacy and safety of IRd vs placebo-Rd by cytogenetic status. Methods: Pts with RRMM were randomized 1:1 to receive IRd or placebo-Rd. High-risk cytogenetic abnormalities were assessed at a central laboratory; cut-off values were based on false-positive rates of the FISH probes, and were 5%, 3%, and 3% for del(17p), t(4;14), and t(14;16), respectively. Post-hoc analyses were performed using different cut-offs for del(17p) and t(4;14). Results: Of 722 pts enrolled, 552 (76%) had cytogenetic results (97% central laboratory-confirmed), of whom 137 had high-risk abnormalities (75 IRd, 62 placebo-Rd). PFS was improved with IRd vs placebo-Rd in high- and standard-risk pts (Table); in high-risk pts, median PFS with IRd was similar to that in all pts and in standard-risk pts. PFS benefit with IRd vs placebo-Rd was consistent using different positivity cut-offs of 20% del(17p) (n = 59; median 21.4 vs 6.7 mos, HR 0.611), 60% del(17p) (n = 33; median 15.7 vs 5.1 mos, HR 0.49), and 10% t(4;14) alone (n = 59; median 18.5 vs 12.0 mos, HR 0.444). Median TTP with IRd vs placebo-Rd was 21.4 vs 12.0 mos and 20.6 vs 15.9 mos in high- and standard-risk pts. Overall response rate (CR+VGPR rate) with IRd vs placebo-Rd was 79% vs 60% (45% vs 21%) and 80% vs 73% (51% vs 44%) in high- and standard-risk pts. Rates of grade ≥ 3 AEs with IRd vs placebo-Rd were 66% vs 73% in high- and 75% vs 65% in standard-risk pts; rates of serious AEs were 42% vs 52% and 45% vs 47%, respectively. Conclusions: IRd showed substantial benefit vs placebo-Rd in RRMM pts with high-risk cytogenetic abnormalities, irrespective of the cut-offs used, with limited additional toxicity. Clinical trial information: NCT01564537.Pts Median PFS, mos HR IRd Placebo-Rd All (N = 722) 20.6 14.7 0.742 Standard-risk (n = 415) 20.6 15.6 0.640 High-risk (n = 137) 21.4 9.7 0.543 del(17p)* (n = 69) 21.4 9.7 0.596 t(4;14) alone (n = 61) 18.5 12.0 0.645 *Alone or with t(4;14) and/or t(14;16)
In severe asthma, benralizumab reduced daily oral glucocorticoid dose and asthma exacerbations at 6 months
Authors: Diego J. Maselli, Jay I. Peters
Journal: Annals of Internal Medicine (2017)

ACP Journal Club17 October 2017In severe asthma, benralizumab reduced daily oral glucocorticoid dose and asthma exacerbations at 6 monthsDiego J. Maselli, MD, Jay I. Peters, MDDiego J. Maselli, MDUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, USA (D.J.M., J.I.P.)Search for more papers by this author, Jay I. Peters, MDUniversity of Texas Health Science Center at San Antonio, San Antonio, Texas, USA (D.J.M., J.I.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-167-8-043 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationNair P, Wenzel S, Rabe KF, et al; ZONDA Trial Investigators. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-58. https://pubmed.ncbi.nlm.nih.gov/28530840Clinical Impact RatingsGIM/FP/GP: Allerg & Immunol: Pulmonology: References1 Bel EH, Wenzel SE, Thompson PJ, et al; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189-97. [PMID: 25199060] Google Scholar2 Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015;3:355-66. [PMID: 25736990] Google Scholar3 Bleecker ER, FitzGerald JM, Chanez P, et al; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115-27. [PMID: 27609408] Google Scholar4 FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388:2128-41. [PMID: 27609406] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA (D.J.M., J.I.P.)This article was published at Annals.org on 3 October 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Tempest: Difficult to Control Asthma in Adolescence 17 October 2017Volume 167, Issue 8Page: JC43KeywordsAsthmaEosinophilsForced expiratory volume in the first second of expirationGlucocorticoid therapyMonoclonal antibodiesQuality of lifeQuestionnairesRoutes of administrationSafetySafety studies ePublished: 17 October 2017 Issue Published: 17 October 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The effect of treatment with mifepristone on the length and quality of life of mice with a strong predisposition for prostate cancer
Authors: Ebony Dix, Jerome Check, Lynn SanSoucie, Diane Check, Chi Amadi
Journal: Cancer Research (2008)

2155   The purpose of the study was to determine if treatment of mice with a strong predisposition to developing prostate cancer with the progesterone (P) receptor antagonist mifepristone could improve length and quality of survival. Twenty-eight C57BL/6 mice were randomly assigned at 8 weeks of age to be gavaged three times per week with either mifepristone 3mg in olive oil vs. olive oil alone (controls). Survival was defined as mice that were still alive at the end of the year of treatment. Quality of life was measured by the number of days they are sick (body conditioning score (BCS)  1cm and bleeding from the penis). The survival analysis considered death as either expired or euthanized. The time until death was deferred as the number of days from the first treatment until the mouse was euthanized or expired naturally. Mice alive at the end of the study were considered right censored. Kaplan-Meier estimates of survival at the end of the year were computed. Log rank tests were used to compare the survival rates by treatment at the end of the study. 40.0% (6/15) of the mice given mifepristone were still alive vs. only 16.7% (2/12) of the controls. The Kaplan Weier estimate of survival rate following one year of treatment was not statistically significant (log rank test, p=0.620). The mean number of days sick (BCS  1cm) vs. 9 of 12 (75%) of the controls (8 with tumors >1cm and 1 with bleeding from the penis) (p=.021). The intention was to evaluate a larger group of mice but this was hampered by a lack of mice bred with predisposition for prostate cancer. Despite the small numbers the same trend for improved length of survival was found with mifeprsitone therapy compared to controls similar to the experience with other spontaneous murine cancers, e.g., leukemia/lymphoma, breast, lung, and testicular cancers. Although in the case of prostate cancer there was no improvement in the BCS relative to the controls there were significantly less larger tumors and less total adverse effects in the mifepristone treated mice. Though it has been suggested that some prostate cancers may have progesterone receptors, the reasons for using mifepristone for other murine cancers was not based on the likelihood of the premise of the tumors having progesterone receptors but rather the inhibition of the secretion of a progesterone induced immunomodulatory protein, known as the progesterone induced blocking factor, that normally suppresses natural killer cell activity in the tumor microenvironment. A larger series is needed to make more definitive conclusions.
Dual mTOR Kinase Inhibitor MLN0128 Sensitizes HR+/HER2+ Breast Cancer Patient-Derived Xenografts to Trastuzumab or Fulvestrant
Authors: Pei-Yin Hsu, Victoria Shang Wu, Noriko Kanaya, Karineh Petrossian, Hang-Kai Hsu, Duc Nguyen, Daniel Schmolze, Masaya Kai, Chun-Yu Liu, Hannah Lu, Peiguo Chu, Courtney A. Vito, Laura Kruper, Joanne Mortimer, Shiuan Chen
Journal: Clinical Cancer Research (2017)

Purpose: Therapeutic strategies against hormonal receptor-positive (HR+)/HER2+ breast cancers with poor response to trastuzumab need to be optimized.Experimental Design: Two HR+/HER2+ patient-derived xenograft (PDX) models named as COH-SC1 and COH-SC31 were established to explore targeted therapies for HER2+ breast cancers. RNA sequencing and RPPA (reverse phase protein array) analyses were conducted to decipher molecular features of the two PDXs and define the therapeutic strategy of interest, validated by in vivo drug efficacy examination and in vitro cell proliferation analysis.Results: Estrogen acted as a growth driver of trastuzumab-resistant COH-SC31 tumors but an accelerator in the trastuzumab-sensitive COH-SC1 model. In vivo trastuzumab efficacy examination further confirmed the consistent responses between PDXs and the corresponding tumors. Integrative omics analysis revealed that mammalian target of rapamycin (mTOR) and ERα signaling predominantly regulate tumor growth of the two HR+/HER2+ PDXs. Combination of the dual mTOR complex inhibitor MLN0128 and anti-HER2 trastuzumab strongly suppressed tumor growth of COH-SC1 PDX accompanied by increasing ER-positive cell population in vivo Instead, MLN0128 in combination with antiestrogen fulvestrant significantly halted the growth of HR+/HER2+ cancer cells in vitro and trastuzumab-resistant COH-SC31 as well as trastuzumab-sensitive COH-SC1 tumors in vivoConclusions: Compared with the standard trastuzumab treatment, this study demonstrates alternative therapeutic strategies against HR+/HER2+ tumors through establishment of two PDXs coupled with integrative omics analyses and in vivo drug efficacy examination. This work presents a prototype of future "co-clinical" trials to tailor personalized medicine in clinical practice. Clin Cancer Res; 24(2); 395-406. ©2017 AACR.
Response to: ‘Metabolic and cardiovascular benefits of hydroxychloroquine: exploration in a wider population at high CV risk’ by Pareek <i>et al</i>
Authors: Charlotte Hua, Claire Rempenault, Bernard Combe
Journal: Annals of the Rheumatic Diseases (2017)

Response to: 'Metabolic and cardiovascular benefits of hydroxychloroquine: exploration in a wider population at high CV risk' by Pareek et al In their letter to the editor, Pareek et al raised some issues regarding our recent paper. 1 2 We appreciate their interest in our study and their positive comments.Pareek et al highlight the fact that several studies addressing the metabolic effect of hydroxychloroquine (HCQ) have not been included in our meta-analysis due to our stringent inclusion criteria (HCQ users vs non-users in patients with rheumatoid arthritis (RA)).We acknowledge this point.However, we believe that to establish and to follow such strict inclusion criteria is important in a meta-analysis in order to reduce to a minimum heterogeneity of the pooled results.Indeed, there was no significant heterogeneity among studies that were included in our work. 2wo studies mentioned by Pareek et al regarding reduced diabetes incidence with HCQ were not included in our meta-analysis.This was due to heterogeneous study population for the paper by Solomon et al 3 and to a publication date posterior to the end of our meta-analysis timeline for the paper by Ozen et al. 4 Anyway, the data are consistent with our results and strengthen our conclusions.Focusing only on RA was a willingness, because by contrast to other diseases such as lupus, HCQ is not clearly recommended in RA due to its rather low efficacy on arthritis. 5etting proofs that it could have interesting benefit for patients with RA through its metabolic effect could have an effective impact in practice.Anyway, as indicated by Pareek et al, the beneficial effect of HCQ on cardiovascular risk factors that we found in our meta-analysis has also been noted in chronic inflammatory conditions other than RA, notably lupus.Thus, even if for methodological reasons we did not present in our article all the studies exploring the metabolic effect of HCQ, it appears that, as stated by Pareek et al, evidence supporting the metabolic and cardiovascular benefits of HCQ in inflammatory rheumatic diseases, including RA, begin to be quite strong in the literature.
Genomic Hallmarks of Thyroid Neoplasia
Authors: Thomas J. Giordano
Journal: Annual Review of Pathology Mechanisms of Disease (2017)

The genomic landscape of thyroid cancers that are derived from follicular cells has been substantially elucidated through the coordinated application of high-throughput genomic technologies. Here, I review the common genetic alterations across the spectrum of thyroid neoplasia and present the resulting model of thyroid cancer initiation and progression. This model illustrates the striking correlation between tumor differentiation and overall somatic mutational burden, which also likely explains the highly variable clinical behavior and outcome of patients with thyroid cancers. These advances are yielding critical insights into thyroid cancer pathogenesis, which are being leveraged for the development of new diagnostic tools, prognostic and predictive biomarkers, and novel therapeutic approaches.
Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases
Authors: Emilie Cornec-Le Gall, Vicente E. Torres, Peter C. Harris
Journal: Journal of the American Society of Nephrology (2017)

Data indicate significant phenotypic and genotypic overlap, plus a common pathogenesis, between two groups of inherited disorders, autosomal dominant polycystic kidney diseases (ADPKD), a significant cause of ESRD, and autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD. Eight genes have been associated with ADPKD (PKD1 and PKD2), ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B), or both (GANAB). Although genetics is only infrequently used for diagnosing these diseases and prognosing the associated outcomes, its value is beginning to be appreciated, and the genomics revolution promises more reliable and less expensive molecular diagnostic tools for these diseases. We therefore propose categorization of patients with a phenotypic and genotypic descriptor that will clarify etiology, provide prognostic information, and better describe atypical cases. In genetically defined cases, the designation would include the disease and gene names, with allelic (truncating/nontruncating) information included for PKD1 Recent data have shown that biallelic disease including at least one weak ADPKD allele is a significant cause of symptomatic, very early onset ADPKD. Including a genic (and allelic) descriptor with the disease name will provide outcome clues, guide treatment, and aid prevalence estimates.
Highlights of the 55th Annual Scientific Session of the American College of Cardiology—March 11–14, 2006
Authors: Robert A. Harrington, Christopher M. O’Connor, James H. Stein, Matthew R. Wolff, Rhondalyn C. McLean, Emile R. Mohler, Roger S. Blumenthal, William D. Knopf, John A. Ambrose, Lynne E. Wagoner, Randall C. Starling, Raymond J. Kim, Steven M. Markowitz, Michael J. Landzberg, Ross Ungerleider, Shahbudin H. Rahimtoola, Fredric S. Resnic, JoAnne Foody
Journal: Journal of the American College of Cardiology (2006)
Evolución del asma en Suiza: Red Suiza de Vigilancia Centinela, 1988-1996
Authors: U Bollag, J Cloetta, J Oberreich, W J Paget
Journal: Eurosurveillance (1999)

El asma es un problema sanitario importante en ninos y adultos de todo el mundo. Estudios poblacionales realizados sugieren que la prevalencia tanto de disneas espiratorias como de asma diagnosticada aumenta con el tiempo (1). Parte de este aumento aparente puede ser el resultado de un mayor conocimiento del asma por parte del publico, lo que llevaria a los padres a consultar a un medico para un tratamiento de asma por enfermedades de respiracion sibilante detectadas en sus hijos. La tos, sintoma principal de enfermedades respiratorias virales, puede atribuirse al asma cuando en realidad forma parte de un proceso infeccioso y corresponde a una constriccion no especifica del arbol bronquial (2).
IL-1/inhibitory κB kinase ε–induced glycolysis augment epithelial effector function and promote allergic airways disease
Authors: Xi Qian, Reem Aboushousha, Cheryl van de Wetering, Shi B. Chia, Eyal Amiel, Robert W. Schneider, Jos L.J. van der Velden, Karolyn G. Lahue, Daisy A. Hoagland, Dylan T. Casey, Nirav Daphtary, Jennifer L. Ather, Matthew J. Randall, Minara Aliyeva, Kendall E. Black, David G. Chapman, Lennart K.A. Lundblad, David H. McMillan, Anne E. Dixon, Vikas Anathy, Charles G. Irvin, Matthew E. Poynter, Emiel F.M. Wouters, Pamela M. Vacek, Monique Henket, Florence Schleich, Renaud Louis, Albert van der Vliet, Yvonne M.W. Janssen-Heininger
Journal: Journal of Allergy and Clinical Immunology (2017)