tbuckley/cabot-search huggingface dataset:
Abstract 4469: Reversal of No-Reflow/Slow-Flow during Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction–A Prospective Randomized Study Comparing Intracoronary Infusion of Diltiazem, Verapamil and Nitroglycerin
Authors: Dong Huang, Feng Zhang, Juying Qian, Xiangfei Wang, Junbo Ge
Journal: Circulation (2008)

No-reflow/slow-flow is a frequent observation during direct PCI for AMI and associated with a poor clinical outcome. The present pharmacological management involves the use of different vasodilators including nitrates, verapamil, adenosine and nicorandil. But no randomized trial has been conducted to assess any of these agents, or to determine the appropriate dosage. In a consecutive series of 236 direct PCI for AMI, no-reflow/slow-flow phenomenon [TIMI flow grade (TFG) &lt;3] was observed in 30 patients (12.7%). All lesions in the infarction-related-coronary (IRC) were treated by stents. The 30 patients were randomised to one of three groups: intracoronary infusion of diltiazem (n=10), verapamil (n=10) and nitroglycerin (n=10). All the drugs were given via an infusion catheter distal to the angioplasty site. Pre-PCI, post-PCI and after drugs were given, IRC flow was assessed using TFG and TIMI frame count (TFC) by blinded angiographic readers. LVEF through echocardiography and NT-proBNP levels were measured at days 1 and 30 post-PCI. Patient, procedural characteristics and the baseline IRC flow post-PCI in the three groups were similar. The average intracoronary infusion drug dose was diltiazem 0.8mg, verapamil 0.4mg and nitroglycerin 0.4mg. All the three drugs could improve the IRC flow measured by TFG and TFC significantly (p&lt;0.05). Compared with nitroglycerin, diltiazem and verapamil could improve the IRC flow more significantly (p&lt;0.05). The improvements in TFG and TFC did not differ significantly between the diltiazem and verapamil groups (p&gt;0.05). Five patients in the verapamil group developed transient heart block, not seen with diltiazem (p&lt;0.01). During 30 days follow-up, the LVEF improved insignificantly in the three groups. The NT-proBNP levels in the diltiazem and verapamil groups were lower than nitroglycerin group (p&lt;0.05). There is no significant difference in the NT-proBNP levels between the diltiazem and verapamil groups. The intracoronary infusion of diltiazem or verapamil can reverse no-reflow/slow flow phenomenon more effectively than infusion of nitroglycerin during direct PCI for AMI. The efficacy of diltiazem and verapamil is similar but diltiazem seems safer.
Distinct Induced Pluripotent Stem Cell Clones with Somatic Mutations Prepared From PV Patients
Authors: Zhaohui Ye, Lucie Piterkova, Cyndi F Liu, Sarah N Dowey, Bin-Kuan Chou, Xiaosong Huang, Jerry L. Spivak, Sabina Swierczek, Alison R. Moliterno, Josef T. Prchal, Linzhao Cheng
Journal: Blood (2011)
Moderate LDL cholesterol reduction with statins shows similar benefit to aggressive lipid lowering in ischaemic heart disease
Authors: Susan Mayor
Journal: BMJ (2016)

Moderate reduction of low density lipoprotein (LDL) cholesterol with statins achieved similar reductions in adverse cardiac outcomes in patients with ischaemic heart disease to aggressive lipid lowering, shows a retrospective cohort study.1

The study, reported in JAMA Internal Medicine , compared the risk for major cardiac events in patients with ischaemic heart disease treated with statins and achieving a low LDL cholesterol level of ≤70 mg/dL with patients achieving moderate levels (70.1 to 100 mg/dL) or high levels (100.1 to 130 mg/dL) …
Maximising HIV prevention by balancing the opportunities of today with the promises of tomorrow: a modelling study
Authors: Jennifer A Smith, Sarah-Jane Anderson, Kate L Harris, Jessica B McGillen, Edward Lee, Geoff P Garnett, Timothy B Hallett
Journal: The Lancet HIV (2016)

Many ways of preventing HIV infection have been proposed and more are being developed. We sought to construct a strategic approach to HIV prevention that would use limited resources to achieve the greatest possible prevention impact through the use of interventions available today and in the coming years.
Glucose Metabolism of Tumors Induced by Rous Sarcoma Virus. I. Comparison of Chorioallantoic Membrane With Tumor of the Chorioallantois Induced by Rous Sarcoma Virus&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Alvin S. Levine, Richard Uhl, James Ashmore
Journal: JNCI Journal of the National Cancer Institute (1961)

Essentially linear rates of glucose utilization were observed over various concentrations: (a) Tumor of the chorio-allantois induced by Rous sarcoma virus (RSV tumor) had a maximal rate of glucose utilization 6 times that of chorio-allantoic membrane (CAM). (b) Half maximal velocity was achieved with 5 mmoles per liter glucose by RSV tumor and 1.3 mmoles per liter glucose by CAM. Glycolytic activity was markedly greater with RSV tumor than CAM under aerobic conditions. Under anaerobic conditions the difference was not as pronounced: (a) Lactate accounted for 50 to 100 percent of C14 glucose metabolized by RSV tumor under both aerobic and anaerobic conditions, (b) About 25 percent of the glucose metabolized by CAM aerobically was recovered as lactate; anaerobically, 30 to 80 percent. With lower concentrations of glucose a greater percentage could be considered lactate from both tissues. Only 5 to 6 percent of the glucose used by RSV tumor was recovered as CO2, while there was 50 to 60 percent from CAM. About 5 percent of the glucose used by RSV tumor was recovered in fat. This was 10 to 20 times the amount recovered as glycogen. Very little C14 glucose was recovered as glycogen or fatty acids in CAM. Lactate selectively suppressed oxygen uptake of RSV tumor. Proposed mechanisms of the Crabtree effect are discussed with regard to the data presented.
P-040 Dihydropyrimidine Dehydrogenase (DPD) and Thymidylate Synthase (TYMS) Germline Pharmacogenomics Role in Predicting Fluoropyrimidines Toxicity in Patients with Gastrointestinal (GI) Malignancies
Authors: M. Khushman, P. Hosein, D. Cameron, D. Clarkson, T. Butler, M. Vu, C. Norden, W. Baliem, V. Jones, S. Bhadkamkar, C. Nelson, F. Lee, A. Singh, W. Taylor
Journal: Annals of Oncology (2016)
Outcome of children with all who started a search for a matched donor
Authors: C Manzitti, Mg Valsecchi, C Micalizzi, F Locatelli, A Busca, A Pession, A Prete, G Giorgiani, E Lanino, A Balduzzi, S Cesaro, Ap Iori, S Galimberti, L Garbarino, E Mazzolari, M Rabusin, G Dini
Journal: Blood (1999)
Threshold for surgery to reduce ovarian cancer risk should be lowered, suggests study
Authors: Susan Mayor
Journal: BMJ (2016)

The threshold for surgery in which the ovaries and fallopian tubes are removed to reduce the risk of ovarian cancer in premenopausal women older than 40 should be lowered from the current lifetime risk of over 10% to 4% or lower, a cost effectiveness study has shown.1

Salpingo-oophorectomy is the most effective method for reducing the risk of ovarian cancer in premenopausal women …
c-Myc Modulation and Acetylation Is a Key HDAC Inhibitor Target in Cancer
Authors: Angela Nebbioso, Vincenzo Carafa, Mariarosaria Conte, Francesco Paolo Tambaro, Ciro Abbondanza, Joost Martens, Matthias Nees, Rosaria Benedetti, Isabella Pallavicini, Saverio Minucci, Guillermo Garcia-Manero, Francesco Iovino, Gabriella Lania, Concetta Ingenito, Valeria Belsito Petrizzi, Hendrik G. Stunnenberg, Lucia Altucci
Journal: Clinical Cancer Research (2016)

Purpose: Histone deacetylase inhibitors (HDACi) are promising anticancer drugs. Although some HDACi have entered the clinic, the mechanism(s) underlying their tumor selectivity are poorly understood.Experimental Design and Results: Using gene expression analysis, we define a core set of six genes commonly regulated in acute myeloid leukemia (AML) blasts and cell lines. MYC, the most prominently modulated, is preferentially altered in leukemia. Upon HDACi treatment, c-Myc is acetylated at lysine 323 and its expression decreases, leading to TRAIL activation and apoptosis. c-Myc binds to the TRAIL promoter on the proximal GC box through SP1 or MIZ1, impairing TRAIL activation. HDACi exposure triggers TRAIL expression, altering c-Myc-TRAIL binding. These events do not occur in normal cells. Excitingly, this inverse correlation between TRAIL and c-Myc is supported by HDACi treatment ex vivo of AML blasts and primary human breast cancer cells. The predictive value of c-Myc to HDACi responsiveness is confirmed in vivo in AML patients undergoing HDACi-based clinical trials.Conclusions: Collectively, our findings identify a key role for c-Myc in TRAIL deregulation and as a biomarker of the anticancer action of HDACi in AML. The potential improved patient stratification could pave the way toward personalized therapies. Clin Cancer Res; 23(10); 2542-55. ©2016 AACR.
Targeting of Discoidin Domain Receptor 2 (DDR2) Prevents Myofibroblast Activation and Neovessel Formation During Pulmonary Fibrosis
Authors: Hu Zhao, Huan Bian, Xin Bu, Shuya Zhang, Pan Zhang, Jiangtian Yu, Xiaofeng Lai, Di Li, Chuchao Zhu, Libo Yao, Jin Su
Journal: Molecular Therapy (2016)

Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-β and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression. In addition, we confirmed that late treatment of the injured mice with specific siRNA against DDR2 or its kinase inhibitor exhibited therapeutic efficacy against lung fibrosis. Thus, this study not only elucidated novel mechanisms by which DDR2 controls the development of pulmonary fibrosis, but also provided candidate target for the intervention of this stubborn disease. Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. Herein, we demonstrated that discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase that predominantly transduces signals from fibrillar collagens, plays a critical role in the induction of fibrosis and angiogenesis in the lung. In vitro cell studies showed that DDR2 can synergize the actions of both transforming growth factor (TGF)-β and fibrillar collagen to stimulate lung fibroblasts to undergo myofibroblastic changes and vascular endothelial growth factor (VEGF) expression. In addition, we confirmed that late treatment of the injured mice with specific siRNA against DDR2 or its kinase inhibitor exhibited therapeutic efficacy against lung fibrosis. Thus, this study not only elucidated novel mechanisms by which DDR2 controls the development of pulmonary fibrosis, but also provided candidate target for the intervention of this stubborn disease.
Systematic Analysis of Cell-of-Origin, Sequencing and Genomic Imbalances Identifies a Distinct Subset of Rituximab Treated Diffuse Large B-Cell Lymphoma with an Inferior Survival
Authors: Rajan Dewar, Julia Friedman, Daniel Xia, Timothy George Lens, Asha Guttapalli, Phillip Michaels, Venkata Thodima, Sitharthan Kamalakaran, Jane Houldsworth, Robin Joyce
Journal: Blood (2015)
Acute Lymphoblastic Leukemia Occurring in Patient with Acute Myeloid Leukaemia: An Unrelated Leukemia Rather Than a Therapy-Related Malignancy. About 2 Cases.
Authors: Chadi El-Nawakil, Richard Garand, Stephane Vigouroux, Jean-Luc Harousseau, Patrice Chevallier
Journal: Blood (2006)
Induction of Protein Kinase C Translocation and Cell Differentiation in ML-1 Human Myeloblastic Leukemic Cells by Tumor Necrosis Factor-α, Transforming Growth Factor-β, or Tetradecanoylphorbol Acetate
Authors: X P Guan, R A Hromchak, A Bloch
Journal: Cancer Communications (1989)

Tumor necrosis factor-alpha and transforming growth factor-beta, like 12-O-tetradecanoylphorbol 13-acetate, induce differentiation of ML-1 human myeloblastic leukemia cells along the monocyte path. As measured at 5 min following exposure of the cells to either of these agents, extensive translocation of protein kinase C from the cytosolic to the membrane fraction occurred. A correlation was observed to exist between protein kinase C translocation, cell differentiation, and cessation of cell growth induced by transforming growth factor-beta and tumor necrosis factor-alpha.
Le Groupe de Travail Finlandais sur la Résistance Antimicrobienne (FiRe)
Authors: A Nissinen, P Huovinen
Journal: Eurosurveillance (2000)

Cree en 1991, le reseau FiRe (Finnish Study Group for Antimicrobial Resistance) a mis au point une methode standardisee de routine pour tester la sensibilite des bacteries aux antibiotiques. Cette methode permet d’obtenir des resultats fiables et comparables que ce soit a des fins diagnostiques ou epidemiologiques. D’apres les derniers resultats, la proportion de Streptococcus pneumoniae resistant aux macrolides est en augmentation et on observe une baisse de sensibilite aux fluoroquinolones dans les souches de salmonella d’origine etrangere. Cependant, la prevalence des SARM demeure faible en Finlande et Mycobacterium tuberculosis multiresistant est rare.
Authors’ reply to Thomas and colleagues
Authors: Nicholas A Buckley, Andrew H Dawson, Geoffrey K Isbister
Journal: BMJ (2016)

We agree with Thomas and colleagues that evidence to date has shown the updated guidance on acetylcysteine to be an expensive strategy with no demonstrable net benefit: frequent adverse effects of acetylcysteine possibly outweigh the postulated small reduction in severe hepatotoxicity.1 2

Moreover, the change has generated conflicting advice on threshold doses for initiating treatment. Current …
Mechanical Ventilation and Disuse Atrophy of the Diaphragm
Authors: Stephen H Loring
Journal: New England Journal of Medicine (2008)

The Author Replies: Because of their inherent complexity and widespread distribution, medical devices will occasionally malfunction, fail, or cause unexpected adverse events. It is challenging to predict the long­term performance of implant­ ed devices on the basis of bench testing or pre­ marketing clinical trials of short duration. Thus, for selected life­sustaining products, postmarket­ ing studies of sufficient size and duration must be required of manufacturers. Unfortunately, when questions first arose about the performance of the Medtronic Sprint Fidelis ICD lead, the available postmarketing data were insufficient to allow an accurate evaluation of the device’s performance. Over the ensuing months, tens of thousands of additional patients underwent im­ plantation of the lead, only to be notified of its recall a short time later. There is no “deeper” problem than the un­ necessary exposure of patients to an underper­ forming permanently implanted medical device. Schultz outlines several important questions that must be answered in order to strengthen the device­approval and postmarketing­monitoring processes. In addition, technological advances such as remote, wireless device monitoring will, in some cases, facilitate collection of the needed performance data. More critical, however, is the need for a philosophical shift — from a medical­ device industry that primarily reacts to perfor­ mance failures to one that better anticipates them.
Holbrook Kohrt: In Memoriam (1977–2016)
Authors: Roch Houot, Russell Pachynski, Debra K. Czerwinski, Matthew J. Goldstein, Idit Sagiv-Barfi, Joshua Brody, Antonia M. Müller, Aurélien Marabelle
Journal: Clinical Cancer Research (2016)

![][1] 

On Wednesday, February 24, 2016, Holbrook Kohrt, MD, PhD, assistant professor at the Stanford University School of Medicine, died at the age of 38 of complications from severe hemophilia. His premature departure is a terrible loss for family and friends, for his patients, and
The DST and posttraumatic stress disorder
Authors: H Kudler, J Davidson, K Meador, S Lipper, T Ely
Journal: American Journal of Psychiatry (1987)

The dexamethasone suppression test (DST) was administered to 28 male combat veterans with posttraumatic stress disorder. Six subjects (21%) were nonsuppressors. The nonsuppression rates for the subgroups with and without major depressive disorder according to the Research Diagnostic Criteria were 50% and 6%, respectively. The authors conclude that cortisol nonsuppression is rare in posttraumatic stress disorder unless there is concomitant major depression.
Let’s stop fooling ourselves. In RA, only ACR/EULAR criteria define remission and equate with absence of disease!
Authors: Maarten Boers
Journal: Annals of the Rheumatic Diseases (2016)

I read with interest the report on the C-EARLY study.1 The study has been performed well, and the data support the conclusions. I do, however, take issue with the definition of the chosen endpoint of ‘sustained remission’, that is, a DAS28<2.6 at weeks 40 and 52. First, a period of 12 weeks is arbitrary and, in my view, rather short for a claim of ‘sustained remission’, but this is not my major worry. The new American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria for rheumatoid arthritis …
PWE-092 Systemic tpa for acute splanchnic vein thrombosis: Abstract PWE-092 Table 1
Authors: D Patch, A Marshall, J O'Beirne, P Chowdary, M Sekhar, R Westbrook, D Thorburn, B Davidson, D Yu
Journal: Gut (2015)

<h3>Introduction</h3> Acute portal mesenteric vein thrombosis, when extensive, is associated with catastrophic complications of gut infarction, short bowel syndrome, PN dependence and death. The absence of a satisfactory therapeutic regimen has prompted the recommendation for alternative therapies (Hepatology 2010;51:210–218). Based on the safety profile of prolonged low dose tPA in children with extensive deep vein thrombosis, we have developed a ward-based TPA protocol to be used in patients with acute splanchnic vein thrombosis and symptoms/radiological signs of gut ischaemia. This treatment algorithm was approved by RFH DTC. <h3>Method</h3> Alteplase is commenced at a dose of 0.05 mg/kg/hr in patients with acute splanchnic vein thrombosis, after informed consent and an MDT decision involving surgery/radiology/hepatology. The standard contraindications to tPA apply. Monitoring involves 12 hrly FBC, clotting, fibrinogen. Thromboelastography/ROTEM were included as exploratory investigations. t-PA may be continued for 72 h. Contrast enhanced CT is performed at 48 h, or earlier if clinically indicated. TIPS is indicated if thrombus/symptoms persist at 72 h. <h3>Results</h3> To-date, 6 patients have been treated with this regimen. Aetiology of thrombosis was Chiari malformation (1) previously undiagnosed JAK2+ve MPD (2) local sepsis (1) and unknown (2) (see Table 1). Three patients had complete radiologic normalisation of their splanchnic circulation, 2 of whom also required TIPS due to persistent PVT. Two patients re-permeated their SMV with complete resolution of clinical symptoms and radiological signs of gut ischaemia, but with persistent PV thrombus. One patient did not have a radiological response, although their pain resolved. No patient required surgery for gut ischaemia. All patients survived and were discharged with normal enteric function. Two patients had their infusion interrupted; one for an arterial line puncture site bleed, and one for worsening gut symptoms (infusion re-started). <h3>Conclusion</h3> This early experience suggests that systemic tPA in patients with acute PMVT and symptoms/signs of gut ischaemia can be used to achieve resolution of thrombus and symptoms and avoid catastrophic complications of gut infarction. We propose that tPA is of value in a multi-modality approach to the management of acute splanchnic vein thrombosis. <h3>Disclosure of interest</h3> None Declared.
Reply to Saritas and Ustundag
Authors: Hiroshi Kawakami, Kazumichi Kawakubo, Yoshimasa Kubota, Masaki Kuwatani, Naoya Sakamoto
Journal: Endoscopy (2016)

We thank Drs. Saritas and Ustundag for their interest and valuable comments [1] on our recent article comparing the yield of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) and endoscopic transpapillary stenting (ETS) in patients with malignant distal biliary obstruction [2].
The Multifaceted Haptoglobin in the Context of Adipose Tissue and Metabolism
Authors: Margherita Maffei, Ilaria Barone, Gaia Scabia, Ferruccio Santini
Journal: Endocrine Reviews (2016)

Obesity is a low chronic inflammatory state because several inflammatory factors are increased in obese subjects, this having important implications for the onset of obesity-associated complications. The source of most of these inflammatory molecules is white adipose tissue (WAT), which upon excessive weight gain, becomes infiltrated with macrophages and lymphocytes and undergoes important changes in its gene expression. Haptoglobin (Hp), a typical marker of inflammation in clinical practice, main carrier of free hemoglobin, and long known to be part of the hepatic acute phase response, perfectly sits in the intersection between obesity and inflammation: it is expressed by adipocytes and its abundance in WAT and in plasma positively relates to the degree of adiposity. In the present review, we will analyze causes and consequences of Hp expression and regulation in WAT and how these relate to the obesity/inflammation paradigm and comorbidities.
A patient-derived xenograft (PDX) platform to optimize omics-driven precision medicine in bladder cancer.
Authors: Chong-xian Pan, Hongyong Zhang, Clifford Tepper, Paramita Ghosh, Sheri Kuslak-Meyer, Susan D. Airhart, David R. Gandara, Edison T. Liu, Ralph deVere White
Journal: Journal of Clinical Oncology (2014)

4536 Background: Almost all cancers harbor multiple genetic alterations as determined by omics technologies, but most of these alterations are not driver ones critical for tumorigenesis. Hence, the efficacy of targeted therapy matching those alterations is still disappointing in most patients. We developed PDXs that share essentially the same genetic background as the parental cancers, and use this platform to optimize omics-drive precision medicine. Methods: PDXs were developed by direct implantation of fresh clinical cancer specimens in immunocompromised NSG mice (Jackson Laboratory, Sacramento, CA). Whole exome, transcriptome and microRNA sequencing was performed, followed by computational biological analysis to identify druggable genetic alterations that were further validated with immunofluorescence (IF) and immunohistochemical (IHC) staining. Efficacy tests together with mechanistic analysis were performed in NSG mice carrying PDXs. Results: So far, 21 PDXs have been established with an engraftment rate of 41 % (13/42) for invasive bladder cancer. The fidelity of PDXs was confirmed with cell morphology, tissue microarray IHC/IF staining and comparison of mutations in parental cancers and PDXs. Exome sequencing showed that 2 of the first 8 PDXs harbored PIK3CA mutations at the highly conserved helical and kinase domains. Transcriptome sequencing and IHC/IF staining revealed overexpression of several tyrosine kinase receptors. Of the first 8 PDXs, 5 had HER2/Neu overexpression (3+ by IHC), 5 fibroblast growth factor receptor 3 (FGFR3), and 4 EphB4 overexpression. Compared to the progression-free survival (PFS) of 9.5 days in the control arm, matched therapy with an FGFR3 inhibitor BGJ398 prolonged PFS to 18.5 days (p=2.61 X 10-6) in PDXs overexpressing FGFR3. Based on the miRNA profiling, a miRNA expression signature was identified that highly correlated with clinical response to chemotherapy (p=0.02) and accurately predicted response for defined responders (24/25 patients) or non-responders (11/11 patients). Conclusions: PDXs can potentially be used for efficacy assessment and mechanistic studies that can guide the design of precision cancer medicine.