tbuckley/cabot-search huggingface dataset:
Abstract 16557: Revascularization versus Optimal Medical Therapy for Patients With Prior Coronary Artery Bypass Surgery: An Analysis From the Duke Databank for Cardiovascular Disease
Authors: Ralf E Harskamp, Karen Chiswell, Sharif Halim, Jennifer Rymer, Linda Shaw, L Kristin Newby
Journal: Circulation (2015)

Objectives: To describe treatment strategies of patients with prior coronary artery bypass grafting (CABG) who underwent subsequent coronary angiography and to compare clinical outcomes among patients who underwent coronary revascularization (CR) versus optimal medical therapy (OMT). Methods: From patients with prior CABG who underwent subsequent non-emergent coronary angiography at Duke University Hospital between January 2003 and October 2012, we identified those with documented stenosis of at least one vessel (native or bypass graft). All patients were followed for subsequent death, MI, or stroke through December 2013. Logistic and Cox-proportional hazards regression models were used for 30-day and 5-year outcomes, respectively. Results: A total of 3838 patients were included, of whom 1,672 (43.6%) were treated with CR within 30 days of index catheterization (1615 with PCI and 57 with CABG) and 2,166 (56.4%) received OMT. Median age was 66 (IQR 58-74) years; 26.5% were women. Heart failure was more common in the OMT group (NYHA&gt;II, 11.6% vs. 19.7%); ACS was more common in the CR group (44.7% vs. 36.6%). Rates of death, MI, or stroke were 2.4% in both groups at 30 days and 41.2% and 40.6% for CR and OMT, respectively, at 5-years (Figure 1). Adjusted death, MI or stroke rates were similar between groups at 30 days (OR: 1.05, 95% confidence interval (CI): 0.66-1.65, p=0.85) and 5 years (OR: 1.08, 95%-CI: 0.97-1.20, p=0.18). Five-year death or MI (OR: 1.04, 95% CI: 0.93-1.17, p=0.46) and all-cause mortality (OR: 0.93, 95% CI: 0.82-1.06, p=0.26) were also similar. Conclusion: Among patients with prior CABG who undergo subsequent coronary angiography, long-term outcomes are poor. In a non-randomized comparison, clinical outcomes with CR are similar to those for OMT.
Efficacy of sorafenib in patients with desmoid-type fibromatosis.
Authors: Rodrigo Ramella Munhoz, Robert A Lefkowitz, Deborah Kuk, Mark Andrew Dickson, Sandra P. D'Angelo, Mary Louise Keohan, Ping Chi, Aimee Marie Crago, Robert G. Maki, Gary K. Schwartz, Li-Xuan Qin, William D. Tap, Mrinal M. Gounder
Journal: Journal of Clinical Oncology (2016)

11065 Background: Desmoid tumors (DT) are rare fibroblastic neoplasms with a variable course. Observation, surgery, radiation and systemic agents are known therapies with variable outcomes. We previously reported on the efficacy of sorafenib (SO). Here we review a larger cohort with long-term follow up (FU). Methods: Patients (pts) with DT treated with SO were retrospectively identified. Baseline/treatment characteristics were analyzed using descriptive statistics. Response rates (RR) were calculated according to RECIST 1.1 and WHO criteria. Kaplan-Meier curves were estimated for survival and variables correlated with treatment outcomes were investigated. Results: We treated 79 pts with progressive or symptomatic DT with SO; median age was 37 years (range 17-81), 67% were female. Primary sites included extremities (n = 22; 28%), abdomen (n = 19; 24%), chest wall (n = 15; 19%), abdominal wall (n = 13; 16%) and other (n = 10; 13%). SO was the first systemic treatment in 49 pts (62%), most frequently at 400mg QD (n = 59; 75%). The median treatment duration was 13.6 months (mo). Reasons for treatment discontinuation included maximum benefit (n = 30; 38%), toxicity (n = 16; 20%) and disease progression (n = 10; 13%). Dose modifications were required in 47 cases (59%). After a median FU of 31.2 mo, 2 deaths occurred. The estimated median progression-free survival (mPFS) was 48.2 mo. Among 51 pts who discontinued SO for reasons other than progressive disease, 25/51 pts (49%) had durable disease control (median FU: 29.1 mo). Sixty-two pts were assessable for response; objective RR were 17.7% (RECIST) and 25.8% (WHO criteria). We identified a new cut-off of -5% (RECIST) that correlated with PFS (mPFS of 37.1 mo for pts with ≤ -5% reduction versus 18.7 mo for pts with variations ≥ -5%). PFS was not affected by site (p = 0.79), age (p = 0.72) or association with Familial Adenomatous Polyposis syndrome (p = 0.51). Conclusions: SO resulted in tumor reductions in pts with DT and a median PFS of 48.2 mo. Sustained stabilization was seen even after treatment interruption. Responses and drug activity were better characterized using WHO criteria. We found a -5% cut-off that was associated with prolonged disease control. Novel imaging criteria in DT are being evaluated.
Lenalidomide and Dexamethasone Therapy in Elderly Patients with Newly Diagnosed Multiple Myeloma to Determine Optimal Plasma Concentration of Lenalidomide
Authors: Takahiro Kobayashi, Masatomo Miura, Takenori Niioka, Yuki Fujioka, Maiko Abumiya, Tomoko Yoshioka, Yoshihiro Kameoka, Hiroyoshi Nishikawa, Naoto Takahashi
Journal: Blood (2017)
Abstract 17340: Stem Cell Source of Exosomes Determines Their Cardioprotective Effect
Authors: Yuping Duan, Bin Yu, Min Gong, Yi-Gang Wang, Muhammad Ashraf, Meifeng Xu
Journal: Circulation (2016)

Exosomes (Exo) released from stem cells play a critical role in alleviating ischemic myocardial injury. They are long-lived in body fluids with longer circulating half-life and cellular effects. To better understand Exo mediated therapy for ischemic myocardium, we used mesenchymal stem cells (MSCs) from adipose tissue (AD-MSC) and bone marrow (BM-MSC), and compared the effects of Exo derived separately from them on the cardiomyocyte (CM) protection against ischemic injury. MSCs were isolated from adipose tissue and bone marrow of 6-8 week-old mice. Exo were collected from conditioned medium using ExoQuick-TC Exosome Precipitation Solution. CMs were obtained from ventricles of 2-day-old rats, and were exposed to hypoxic culture (1% O 2 , 5%CO 2 , and 94% N 2 ) for 72 hrs. There was no difference on surface markers expression (Fig. A), although the proliferation speed was faster (Fig. B) in AD-MSCs compared to that in BM-MSCs. The amount of Exo secreted from AD-MSCs (Exo-AD) was more than that from BM-MSCs (Exo-BM) (Fig. C). Exo significantly protected CMs against the injury induced by exposure to hypoxia for 72 hrs (Fig. D). The survival rate was significantly higher in the group treated with Exo-AD derived from same number of MSCs than those from Exo-BM (Fig. E). However, the cell survival was better in CMs treated with Exo-BM compared to that that treated with Exo-AD when same amount of Exo were used (Fig. F). AD-MSCs proliferated faster and secreted more Exo compared to BM-MSCs. It is concluded that source of Exo may be important in designing their therapeutic effects.
Abstract P153: Association of Habitual Milk Intake with Cognitive Decline From Mid-life to Late-life: The Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study (NCS)
Authors: Natalia Petruski-Ivleva, Anna Kucharska-Newton, Priya Palta, David Couper, Lyn Steffen, Richey A Sharrett, Gerardo Heiss
Journal: Circulation (2016)

Background: Animal models and large population studies have related habitual milk intake to impaired cognitive performance via oxidative stress, but results are inconclusive. We report on the association of milk intake at midlife with 20-year cognitive decline in ARIC-NCS cohort. Methods: Average daily milk intake was assessed in 15,766 ARIC study participants with a standardized FFQ administered at cohort inception in 1987-1989. Reported milk intake was categorized as almost never, &lt;1glass/day, 1 glass/day, &gt;1 glass/day. Domain-specific and global cognitive decline was assessed on three occasions from 1990 through 2013, testing Delayed Word Recall (memory), Digit Symbol Substitution (executive function), and Word Fluency (language). A mixed effects model adjusted for age, race, sex, education, smoking, physical activity and ApoE4 was used to evaluate the association of milk intake with change in cognitive performance over 20 years. The MICE method was used to account for attrition. Results: Among 13,821 participants in the analytic set, the distribution of milk intake across the above four categories was 18.7%, 35.8%, 27.3%, and 18.1%, respectively. In race-combined fully adjusted models greater milk intake was associated with greater cognitive decline (Figure) as indicated by a significant trend (p=0.018). The average difference in the 20-year rate of change in global z between those who reported almost never drinking milk and those who consumed &gt;1glass/day was -0.053 [95%CI: -0.092, -0.014], approximately equivalent to 1 year of additional cognitive aging. The trend met nominal statistical significance in Whites, but not African Americans. Conclusions: Results of this study add to reports indicating that greater milk intake may be associated with greater rate of cognitive decline. Replication of these results and insights into interactions with the intestinal microbiota and other putative modifying factors of the reported association is warranted considering the widely prevalent intake of milk in US adults.
Identification of polymorphism associated with treatment response to anti-TNF in Danish RA patients by genome-wide association scan
Authors: Sophine Boysen Krintel, G. Palermo, Julia Sidenius Johansen, S. Germer, L. Essioux, R. Benayed, Merete Lund Hetland
Journal: Annals of the Rheumatic Diseases (2010)
Hypoxia induces CXCR4 overexpression in pancreatic cancer cells
Authors: Quyen Chu, Jesse Tubbs, Taylor Robertson, Carol Meschonat, Steve Alexander, James Mathis, Benjamin Li
Journal: Cancer Research (2008)

4472  Aims: Recent experimental evidence suggests that hypoxia plays a key role in cancer progression by altering the pattern of gene expression, one of which is upregulating proteins believed to be involved in the metastatic process. CXCR4 is a chemokine receptor that has recently been implicated to play a pivotal role in cancer growth and metastasis. For a variety of solid tumors, it is believed that hypoxia induces the overexpression of CXCR4, which may account for the aggressive behavior observed in these tumors. However, whether hypoxia induces CXCR4 overexpression in pancreatic cancer cells is not known.  Methods: The MDA-MB-231 (positive control), and two human pancreatic cancer cell lines (CRL 1469 and CRL 1918) were cultured. These cell lines were then subjected to hypoxia for 2, 4, 6, 12 or 24 hours. Protein was extracted for western blots. CXCR4 was detected and quantified by normalizing it against actin.  Results: Hypoxia, as expected, optimally stimulated CXCR4 expression in MDA-MB-231 at 24 hours. CXCR4 over-expression for both CRL 1918 and CRL 1469 pancreatic cancer cell lines were observed when exposed to the hypoxic environment. At 6 hours of hypoxia, there was a 2.5 fold and a 2.7 fold increase in CXCR4 expressions for CRL 1469 and CRL 1918 pancreatic cancer cells, respectively.  Conclusion: Hypoxia stimulates CXCR4 expression in two human pancreatic cancer cell lines, the CRL 1469 and CRL 1918, which may explain the aggressive behavior observed for pancreatic cancer. These findings may facilitate the development of novel therapeutic target in pancreatic cancer treatment.
Endoscopic submucosal tunnel dissection for early squamous cell carcinoma of the esophagus
Authors: Iman Andalib, Enad Dawod, Monica Saumoy, Melanie Johncilla, Amy Tyberg, Michel Kahaleh
Journal: Endoscopy (2018)

We report the case of an 83-year-old man with past medical history of hypertension who was initially referred for the evaluation of newly diagnosed squamous cell cancer (SCC) of the esophagus. An endoscopic ultrasound was performed and showed a medium-sized flat lesion in the mid-esophagus, which appeared to be invading the muscularis mucosa (T1a). During a multidisciplinary meeting, it was decided that the patient would benefit from an endoscopic submucosal dissection of the lesion.
Abstract 10306: Identification and Characterization of Orally Bioavailable Small Molecule Protease Proprotein Convertase Subtilisin-like Kexin Type 9 Inhibitors <i>(Best of Basic Science Abstract)</i>
Authors: Nabil A Elshourbagy, Harold V Meyers, Shaker A Mousa, Sherin S Abdel-Meguid
Journal: Circulation (2015)

Intervention with drugs to reduce low density lipoprotein-cholesterol (LDL-C) has proven to decrease mortality and morbidity. Here, we report the development of small molecules that lower LDL-C by targeting the LDL-receptor (LDLR) degradation pathway, which is modulated by the protease proprotein convertase subtilisin-like kexin type 9 (PCSK9). PCSK9 is synthesized as a 72-kDa zymogen that undergoes autocatalytic processing between the prodomain and catalytic domain, an important step that is absolutely required for secretion of PCSK9 and its function. Secreted PCSK9 binds to the LDLR and enhances its degradation. We have identified inhibitors of the autocatalytic processing by virtual docking of millions of commercial compounds into the atomic structure of the PCSK9 active site. Top scoring compounds that showed the best fit in the active site were selected for screening. These compounds were tested for their ability to inhibit the autocatalytic processing/secretion of PCSK9. The most potent compounds exhibited a concentration-dependent inhibition of the PCSK9 processing/secretion with IC50’s in the nanomolar range. These compounds were tested for selectivity against other PCSK’s. The data demonstrated that these compounds were selective in that they inhibit PCSK9 processing/secretion without affecting the secretion of other related PCSK’s. Furthermore, these compounds exhibited a 5- to 10-fold LDLR upregulation at 1.6 μM in two recombinant cell-based assays as well as exhibited an increase in the fluorescently labeled DiI-LDL uptake in situ in the nanomolar range. In animal studies, intraperitoneal (IP) injection of these compounds administered alone resulted in more than 20% reduction in LDL-C in mice fed a high fat/high cholesterol diet and over 40% reduction in LDL-C if administered in combination with atorvastatin. In vivo pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of these compounds demonstrated that they are orally efficacious, with one compound exhibiting 43% oral bioavailability. Thus, identifying small molecule, orally active PCSK9 modulators represents a significant advance and opportunityfor drug development.
Cerebral tryptophan metabolism and outcome of tuberculous meningitis: an observational cohort study
Authors: Arjan van Laarhoven, Sofiati Dian, Raúl Aguirre-Gamboa, Julian Avila-Pacheco, Isis Ricaño-Ponce, Carolien Ruesen, Jessi Annisa, Valerie A C M Koeken, Lidya Chaidir, Yang Li, Tri Hanggono Achmad, Leo A B Joosten, Richard A Notebaart, Rovina Ruslami, Mihai G Netea, Marcel M Verbeek, Bachti Alisjahbana, Vinod Kumar, Clary B Clish, A Rizal Ganiem, Reinout van Crevel
Journal: The Lancet Infectious Diseases (2018)
What About Alcohol? An Illustrated Outline of Scientific Facts About Alcohol and Alcohol Drinking
Journal: JAMA (1935)

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 Journals 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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
Efficacy and Safety of Imetelstat in RBC Transfusion-Dependent (TD) IPSS Low/Int-1 MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agents (ESA) (IMerge)
Authors: Pierre Fenaux, Azra Raza, Edo Vellenga, Uwe Platzbecker, Valeria Santini, Irina Samarina, Koen Van Eygen, Maria Díez-Campelo, Mrinal M. Patnaik, Laurie Sherman, Libo Sun, Helen Varsos, Esther Rose, Aleksandra Rizo, David P. Steensma
Journal: Blood (2017)
Interim Analysis of a Single Arm Phase II Study of Cpi-613 in Combination with High Dose Cytarabine and Mitoxantrone for Patients with Relapsed or Refractory AML
Authors: Timothy S Pardee, Scott Isom, Leslie Renee Ellis, Dianna S. Howard, Rupali Bhave, Megan Manuel, Sarah Dralle, Susan Lyerly, Bayard L. Powell
Journal: Blood (2017)
Dimethyl fumarate potentiates oncolytic virotherapy through NF-κB inhibition
Authors: Mohammed Selman, Paula Ou, Christopher Rousso, Anabel Bergeron, Ramya Krishnan, Larissa Pikor, Andrew Chen, Brian A. Keller, Carolina Ilkow, John C. Bell, Jean-Simon Diallo
Journal: Science Translational Medicine (2018)

Resistance to oncolytic virotherapy is frequently associated with failure of tumor cells to get infected by the virus. Dimethyl fumarate (DMF), a common treatment for psoriasis and multiple sclerosis, also has anticancer properties. We show that DMF and various fumaric and maleic acid esters (FMAEs) enhance viral infection of cancer cell lines as well as human tumor biopsies with several oncolytic viruses (OVs), improving therapeutic outcomes in resistant syngeneic and xenograft tumor models. This results in durable responses, even in models otherwise refractory to OV and drug monotherapies. The ability of DMF to enhance viral spread results from its ability to inhibit type I interferon (IFN) production and response, which is associated with its blockade of nuclear translocation of the transcription factor nuclear factor κB (NF-κB). This study demonstrates that unconventional application of U.S. Food and Drug Administration-approved drugs and biological agents can result in improved anticancer therapeutic outcomes.
Basophils from allergic patients are neither hyperresponsive to activation signals nor hyporesponsive to inhibition signals
Authors: Lydie Cassard, Katia Sperber, Tan-Phuc Buivan, Aurélie Cotillard, Raphaëlle Bourdet-Sicard, Matthew L. Albert, Estelle Mottez, Jérôme Laurent, Marie-Thérèse Guinnepain, Marc Daëron
Journal: Journal of Allergy and Clinical Immunology (2018)
Epistemic authority, episodic memory, and the sense of self
Authors: Jennifer Nagel
Journal: Behavioral and Brain Sciences (2018)

Abstract The distinctive feature of episodic memory is autonoesis, the feeling that one's awareness of particular past events is grounded in firsthand experience. Autonoesis guides us in sharing our experiences of past events, not by telling us when our credibility is at stake, but by telling us what others will find informative; it also supports the sense of an enduring self.
Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines
Authors: Kathleen L. Dooling, Angela Guo, Manisha Patel, Grace M. Lee, Kelly Moore, Edward A. Belongia, Rafael Harpaz
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

On October 20, 2017, Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline, [GSK] Research Triangle Park, North Carolina), a 2-dose, subunit vaccine containing recombinant glycoprotein E in combination with a novel adjuvant (AS01
Association of T-cell infiltration assessed in pretherapeutic biopsies (PTB) of patients with locally advanced rectal adenocarcinoma (LARC) with tumor response and relapse after chemoradiotherapy (CRT) and rectal surgery.
Authors: Marc Van Den Eynde, Carine El Sissy, Amos Kirilovsky, Florence Marliot, Nacilla Haicheur, Cristina Anca Dragean, Etienne Danse, Marie-Armelle Denis, Alex Kartheuser, Christophe Remue, Daniel Leonard, Radu Bachman, Pamela Baldin, Astrid Decuyper, Yves Humblet, Pierre Scalliet, Anne Jouret-Mourin, Jerome Galon, Franck Pages
Journal: Journal of Clinical Oncology (2017)

3599 Background: Pre-operative CRT followed by total mesorectal excision (TME) is nowadays the standard of care for patient with LARC (cT3-T4N0 or cTxN+). Currently, pathologic complete response occurs in +/- 15% after CRT. Colorectal cancer T-cell infiltration is a strong prognostic factor for survival after primary tumor resection. Our aim was to determine whether T-cell infiltration in PTB could be predictive of tumor response and relapse after CRT + TME. Methods: Between 1999 and 2012, patients with LARC who underwent CRT + TME and with available clinical follow-up and PTB (with sufficient tumor cells density) were identified at the Cliniques universitaires St-Luc. The density of CD3 (T cells) and CD8 (cytotoxic) was quantified on immunostained PTB slides and analyzed with a dedicated image analysis software on whole-slide imaging. Comparisons were made using the Wilcoxon-Mann-Whitney test. Cumulative disease-free survival (DFS) was performed using the Kaplan-Meier estimator and compared by log-rank tests. Cox regression we used for uni- and multi-variate analysis. P value of less than 0.05 was considered statistically significant. Results: 154 patients (sex ratio M/F 1.8; mean age 65 years-old; upper (20%), mid (29%) and low rectum (51%), synchronous metastases (11%)) were analyzed. High CD3 and CD8 PTB densities were significantly associated with a higher pathological response (Dworak 3-4) and lower ypTNM stage after CRT +TME (p &lt; 0,05). Higher CD3 and CD8 PTB densities were associated with higher patient DFS (CD3: HR = 2,30 (CI95%:1,15-4,59) p = 0,02; CD8: HR = 1,95 (CI95%: 1,01-3,75) p = 0,04). These results were confirmed in uni and multivariate analysis. CD3 and CD8 PTB densities added to pathological response (ypTNM/Dworak) but also clinical response (ycTNM) after CRT + TME increases significantly the accuracy prediction of tumor relapse. Conclusions: Pretherapeutic T-cell infiltration of LARC is predictive of tumor response and relapse after CRT +TME. This biomarker could be helpful for patient treatment decision. It must be validated in larger patient cohorts.
Abstract 20688: Potassium-Facilitated Defibrillation in Patients With Prolonged Refractory Ventricular Fibrillation Cardiac Arrest
Authors: Jason A Bartos, Emily Caldwell, Demetris Yannopoulos
Journal: Circulation (2016)

Introduction: Potassium-based cardioplegia is used in the operating theater to induce asystole. This effect is rapidly reversed with wash-out of the potassium resulting in resumption of electrical ...