tbuckley/cabot-search huggingface dataset:
Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)
Authors: Ioana R. Preston, Kari E. Roberts, Dave P. Miller, Ginny P. Sen, Mona Selej, Wade W. Benton, Nicholas S. Hill, Harrison W. Farber
Journal: Circulation (2015)

Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH.Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients.No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.
Prognostic significance of NPM1 mutation-modulated microRNA−mRNA regulation in acute myeloid leukemia
Authors: Y-C Chiu, M-H Tsai, W-C Chou, Y-C Liu, Y-Y Kuo, H-A Hou, T-P Lu, L-C Lai, Y Chen, H-F Tien, E Y Chuang
Journal: Leukemia (2015)
Patterns of relapse and subsequent management following high-dose chemotherapy with autologous haematopoietic support in relapsed or refractory Hodgkin's lymphoma: A two centre study
Authors: J. Shamash, S.M. Lee, J.A. Radford, A.Z.S. Rohatiner, J. Chang, G.R. Morgenstern, J.H. Scarffe, D.P. Deakin, T.A. Lister
Journal: Annals of Oncology (2000)
Community-acquired bacterial meningitis in adults in the Netherlands, 2006–14: a prospective cohort study
Authors: Merijn W Bijlsma, Matthijs C Brouwer, E Soemirien Kasanmoentalib, Anne T Kloek, Marjolein J Lucas, Michael W Tanck, Arie van der Ende, Diederik van de Beek
Journal: The Lancet Infectious Diseases (2015)
Increasing trends of gonorrhoea and syphilis and the threat of drug-resistant gonorrhoea in Europe
Authors: M Van de Laar, G Spiteri
Journal: Eurosurveillance (2012)

Preview this article: Increasing trends of gonorrhoea and syphilis and the threat of drug-resistant gonorrhoea in Europe, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/17/29/art20225-en-1.gif
International Adaptations of NCCN Clinical Practice Guidelines in Oncology
Authors: Robert W Carlson, Jonathan K Larsen, Joan McClure, C Lyn Fitzgerald, Alan P Venook, Al B Benson, Benjamin O Anderson
Journal: Journal of the National Comprehensive Cancer Network (2014)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) are evidence- and consensus-based clinical practice guidelines addressing malignancies that affect more than 97% of all patients with cancer in the United States. The NCCN Guidelines are used extensively in the United States and globally. Use of the guidelines outside the United States has driven the need to adapt the guidelines based on local, regional, or national resources. The NCCN Guidelines Panels created, vetted, and continually update the NCCN Guidelines based on published scientific data on cancer detection, diagnosis, and treatment efficacy. The guidelines are developed within the context of commonly available resources, methods of payment, societal and cultural expectations, and governmental regulations as they exist in the United States. Although many of the cancer management recommendations contained in the NCCN Guidelines apply broadly from a global perspective, not all do. Disparities in availability and access to health care exist among countries, within countries, and among different social groups in the same country, especially regarding resources for cancer prevention, early detection, and treatment. In addition, different drug approval and payment processes result in regional variation in availability of and access to cancer treatment, especially highly expensive agents and radiation therapy. Differences in cancer risk, predictive biomarker expression, and pharmacogenetics exist across ethnic and racial groups, and therefore across geographic locations. Cultural and societal expectations and requirements may also require modification of NCCN Guidelines for use outside the United States. This article describes the adaptation process, using the recent Latin American adaptation of the 2013 NCCN Guidelines for Colorectal Cancer as an example.
Bichat guidelines for the clinical management of glanders and melioidosis and bioterrorism-related glanders and melioidosis
Authors: P Bossi, A Tegnell, A Baka, F van Loock, J Hendriks, A Werner, H Maidhof, G Gouvras
Journal: Eurosurveillance (2004)

Glanders and melioidosis are two infectious diseases that are caused by Burkholderia mallei and Burkholderia pseudomallei respectively. Infection may be acquired through direct skin contact with contaminated soil or water. Ingestion of such contaminated water or dust is another way of contamination. Glanders and melioidosis have both been studied for weaponisation in several countries in the past. They produce similar clinical syndromes. The symptoms depend upon the route of infection but one form of the disease may progress to another, or the disease might run a chronic relapsing course. Four clinical forms are generally described: localised infection, pulmonary infection, septicaemia and chronic suppurative infections of the skin. All treatment recommendations should be adapted according to the susceptibility reports from any isolates obtained. Post-exposure prophylaxis with trimethoprim-sulfamethoxazole is recommended in case of a biological attack. There is no vaccine available for humans.
Activated human T lymphocytes express MHC class I heavy chains not associated with beta 2-microglobulin.
Authors: E Schnabl, H Stockinger, O Majdic, H Gaugitsch, I J Lindley, D Maurer, A Hajek-Rosenmayr, W Knapp
Journal: The Journal of Experimental Medicine (1990)

We present here the molecular characterization of a new activation-induced surface structure on human T lymphocytes, termed LA45, with high homology (93% at protein level) to MHC class I molecules. Antigen modulation and sequential immunoprecipitation experiments revealed that LA45 and HLA class I proteins do not crossreact with the corresponding antibodies. Furthermore, LA45 is not associated with beta 2-m. On the other hand, we could show that the separation of HLA-A,B,C and beta 2m molecules, induced by SDS-denaturation, leads to a conformational change in the heavy chain in such a way that it becomes reactive with LA45. The 90/45 kD LA45 proteins thus appear to be non-beta 2m-associated MHC class I alpha chains that are selectively expressed by activated but not by resting human T lymphocytes.
UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO
Authors: S Goyama, J Schibler, A Gasilina, M Shrestha, S Lin, K A Link, J Chen, S P Whitman, C D Bloomfield, D Nicolet, S A Assi, A Ptasinska, O Heidenreich, C Bonifer, T Kitamura, N N Nassar, J C Mulloy
Journal: Leukemia (2015)
Differential effects of antibodies to vascular cell adhesion molecule-1 and distinct epitopes of the alpha4 integrin in HgCl2-induced nephritis in Brown Norway rats.
Authors: E Escudero, M Nieto, A Martín, A Molina, R R Lobb, F Sanchez-Madrid, F Mampaso
Journal: Journal of the American Society of Nephrology (1998)

Four distinct epitopes (A, B1, B2, and C) have been functionally defined on the human alpha4 integrin. In this study, two cross-reactive antihuman alpha4 monoclonal antibodies (mAb) (HP2/1 and HP2/4 specific for epitopes B1 and B2, respectively) were used to functionally characterize the rat VLA-4 subunit and to define similar functional epitopes in this rodent species. It was found that B1 and B2 anti-alpha4 mAb completely block adhesion to fibronectin, but the inhibition of adhesion to vascular cell adhesion molecule-1 (VCAM-1) with HP2/1 mAb was lower than with HP2/4 mAb. It was also observed that epitope B2 HP2/4 mAb induced homotypic aggregation in rat lymphocytes, whereas epitope B1 HP2/1 mAb did not. Using the HgCl2 model of nephritis, this study shows the protective effect of both anti-alpha4 mAb against infiltration of the renal interstitium by leukocytes. Nevertheless, HP2/1 mAb, but not HP2/4 mAb, virtually abolished the anti-glomerular basement membrane antibody synthesis and glomerular deposits. These findings indicate the dual but independent role played by alpha4 integrins in both extravasation of leukocytes and in the production of antibodies. Finally, this study demonstrates that anti-rat VCAM-1 mAb showed a positive reactivity of the renal vascular endothelium and, most importantly, that administration of anti-VCAM-1 antibodies completely abrogated the interstitial cell infiltrates without affecting anti-glomerular basement membrane antibody production. These results confirm the important role played by VLA-4/VCAM-1 pathway in leukocyte infiltration, and further support the dual and independent role of alpha4 integrins in both renal infiltration and autoantibody synthesis in this model of renal disease.
Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study
Authors: Dianne Carey, Rebekah Puls, Janaki Amin, Marcelo Losso, Praphan Phanupak, Sharne Foulkes, Lerato Mohapi, Brenda Crabtree-Ramirez, Heiko Jessen, Suresh Kumar, Alan Winston, Man-Po Lee, Waldo Belloso, David A Cooper, Sean Emery
Journal: The Lancet Infectious Diseases (2015)
Pediatric Hematology-Oncology.
Journal: Annals of Internal Medicine (1980)

Drug 'repurposing', that is, using old drugs for new indications, has been proposed as a more efficient strategy for drug development than the current standard of beginning with novel agents.In this review, we explore the scope of drug repurposing in pediatric hematology oncology and in pediatrics in general.Drugs commonly used in children were identified using the Harriet Lane Handbook (HLH) and searched in PubMed for different uses.Additional drugs were identified by searching PubMed and Google.comfor 'drug repurposing' or 'drug repositioning'.Almost 10% of drugs with primary uses in pediatrics have been repurposed in pediatric hematology oncology or pediatrics.The observant clinician, pharmacologist and translational bioinformatician, as well as structural targeting, will have a role in discovering new repurposing opportunities.
Premenstrual flares of pyoderma gangrenosum controlled with use of a combined oral contraceptive and antiandrogen (ethinyl estradiol/drospirenone)
Authors: N. Jourabchi, S.M. Rhee, G.S. Lazarus
Journal: British Journal of Dermatology (2015)

The effect of sex hormones on pyoderma gangrenosum (PG) has not been reported. We report the case of a 34-year-old woman with chronic PG leg ulcers who was found to have recurring, premenstrual flares of PG. Her PG flares were controlled with the use of ethinyl estradiol/drospirenone.
Pain analyses from the phase III randomized ALSYMPCA study with radium-223 dichloride (Ra-223) in castration-resistant prostate cancer (CRPC) patients with bone metastases.
Authors: Sten Nilsson, A. Oliver Sartor, Oyvind S. Bruland, Fang Fang, Anne-Kirsti Aksnes, Chris Parker
Journal: Journal of Clinical Oncology (2013)

5038 Background: Bone metastases (mets), present in &gt; 90% of patients (pts) with CRPC, may cause severe pain. In a phase 2 dose-response study with a single injection of Ra-223, pain response was seen in up to 71% of CRPC pts with painful bone mets (Nilsson 2012). In the phase 3 ALSYMPCA study, which included 921 CRPC pts with bone mets randomized 2:1 to receive 6 injections of Ra-223 (50 kBq/kg IV) q4wk or matching placebo (Ra-223, n = 614; placebo, n = 307), Ra-223 significantly improved overall survival vs placebo (median 14.9 vs 11.3 mo; HR = 0.695) and was well tolerated. Post hoc analyses of pain parameters in ALSYMPCA are presented. Methods: The Cox proportional hazards model was used to analyze time to initial opioid use and time to EBRT. Pts with no opioid use at baseline were included in the pain analyses. All pts were included in the analysis for the prespecified endpoint time to EBRT. Concomitant opioid use was recorded from first study drug injection to 12 weeks after last injection. Pain-related QOL was analyzed based on the sum of 4 questions within FACT-P prostate cancer subscale (PCS) (Cella 2009) using ANCOVA. Results: Baseline pain characteristics were similar between the treatment groups (approximately 55% of pts had moderate to severe pain and opioid use based on WHO ladder for cancer pain). Time to EBRT was significantly longer with Ra-223 vs placebo (HR = 0.670; 95% CI, 0.525-0.854). Despite a longer observation time, fewer Ra-223 pts (50%) than placebo pts (62%) reported bone pain as an AE. At baseline, 269 Ra-223 pts and 139 placebo pts did not use opioids. Median time to initial opioid use was significantly longer in the Ra-223 group, with a risk reduction of 38%, compared to placebo (HR = 0.621; 95% CI, 0.456-0.846). Fewer Ra-223 pts (36%) than placebo pts (50%) required opioids for pain relief. The QOL pain score indicated reduced pain for Ra-223 pts relative to placebo pts at week 16 (P = 0.001). Ra-223 pts had significant pain reduction relative to baseline at weeks 16 (P &lt; 0.001 ) and 24 (P = 0.001). Conclusions: These results provide consistent evidence that, in addition to prolonging survival, Ra-223 reduces pain and opioid use in CRPC pts with bone mets. Clinical trial information: NCT00699751.
Dietary protein restriction in chronic renal failure
Authors: W E Mitch
Journal: Journal of the American Society of Nephrology (1991)

Two findings prompted investigators to examine the effects of dietary manipulation on progression of chronic renal failure: dietary protein restriction is an effective method of ameliorating uremic symptoms and the course of renal insufficiency in an individual patient is predictable. Results from studies of patients and animals with chronic renal failure suggested that a low-protein, phosphorus-restricted diet could slow the rate of loss of renal function. In evaluating these studies, three questions should be considered. First, is the diet nutritionally adequate? Second, has dietary compliance been monitored and achieved? Third, is there evidence that restricting the diet will change the rate of loss of renal function? The scientific basis for each of these questions is addressed in this review.
Single Cell Network Profiling (SCNP) Assay Reveals B Cell Receptor Signaling Heterogeneity In the Context of ZAP-70 Expression In Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Keith Shults, Eric Evensen, Maria Teresa Scupoli, Roberta Zanotti, Xiaohua (Robert) Xin, Alessandra Cesano
Journal: Blood (2010)
Sex-Based Outcomes of Darunavir-Ritonavir Therapy
Authors: Judith Currier, Dawn Averitt, Debbie Hagins, Carmen D. Zorrilla, Judith Feinberg, Robert Ryan, Ron Falcon, Alan Tennenberg, Joseph Mrus, Kathleen Squires
Journal: Annals of Internal Medicine (2010)

Women with HIV-1 infection are underrepresented in clinical trials of antiviral drugs for HIV treatment. In this trial of darunavir–ritonavir, treatment-experienced HIV-positive women were recruite...
Tumor profiling of biliary tract carcinomas to reveal distinct molecular alterations and potential therapeutic targets.
Authors: Randall F. Holcombe, Joanne Xiu, Michael J. Pishvaian, Sherri Z. Millis, Zoran Gatalica, Sandeep K. Reddy, Jason K. Sicklick, Paul T. Fanta, Santosh Kesari, Michael Morse
Journal: Journal of Clinical Oncology (2015)

285 Background: Extrahepatic cholangiocarcinoma (EHCC), intrahepatic cholangiocarcinoma (IHCC), and gallbladder carcinoma (GBCA) are rare tumors with poor prognosis that tend to be chemo-resistant. The underlying molecular alterations and their correlation with altered responses to therapies are not well understood. We hypothesized that delineation of different molecular alterations in the cancer types might potentially yield different therapeutic options. Methods: 815 cases (126 EHCC, 434 IHCC, 244 GBCA, 11 NOS) were tested by a commercial multiplatform profiling service (Caris Life Sciences, Phoenix, AZ). Tests included sequencing (Sanger, NGS), gene amplification (CISH/FISH), and protein expression (IHC). Results: 24 of 47 genes tested had mutations, with the highest rates in TP53 (28%), KRAS (18%), IDH1 (9%), and SMAD4 (6%). BRCA1/2 mutations were seen in 3/41 (7.3%) and 5/40 (12.5%) cases. Overall,IHC showed high TOPO1, TOP2A, PD-1, SPARC and PD-L1 in 56%, 49%, 40%, 39% and 15% of cases and low RRM1, ERCC1 and TS in 82%, 72% and 79%, respectively, suggesting potential utility of chemotherapeutic and immunomodulatory agents targeting these alterations in selected cases. Mutually exclusive protein loss of chromatin modifiers BAP1 and PBRM1 were seen in 17% and 27%. ROS1 break-apart FISH showed negative results in 16 cases tested. Comparing the three carcinomas (EHCC, IHCC and GBCA, Table), EHCC had the highest KRAS mutation rate; IHCC had the highest IDH1 mutation; GBCA and EHCC had significantly higher TP53 mutation and HER2 amplification than IHCC.IDH1 and TP53 mutations were mutually exclusive, and IDH1-mutated IHCC had higher P-glycoprotein expression than TP53-mutated IHCC (82% vs. 37%). GBCA had high TOP2A by FISH and IHC, and a high loss of PBRM1(all p&lt;0.05). Conclusions: Multiplatform cancer profiling reveals distinctbiomarker characteristics of biliary tract carcinomas, offering insights into disease biology and suggests potential sensitivity to novel and conventional therapies. Further analyses with clinical correlation are warranted. [Table: see text]
Is it time to move beyond the “O” in early COPD?
Authors: David M. Mannino, Barry J. Make
Journal: European Respiratory Journal (2015)

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally [1] and is the focus of primary and tertiary prevention programmes [2, 3]. Primary prevention has focused on reduction of risk factors, such as tobacco smoke exposure [4] whereas tertiary prevention has focused on reducing exacerbations or improving symptoms among patients with established disease [5]. Missing from prevention approaches are secondary prevention strategies that find disease because it becomes clinically apparent. The US Preventive Services has recommended that spirometry (which detects obstruction) not be used to screen for COPD [6] and recommendation was confirmed in a guideline document from the American College of Physicians, the American College of Chest Physicians, the American Thoracic Society and the European Respiratory Society [7]. The reasons for this recommendation are complex but one of the factors is that, while spirometry can detect mild airflow limitation, not all people with this limitation go on to develop more severe airflow limitation and its clinical consequences or, stated more simply, early COPD may not be the same as mild COPD. Obstruction may not be present in early COPD <http://ow.ly/TqC3E>
Adolescent Health 4 Health of the world's adolescents: a synthesis of internationally comparable data
Authors: George C Patton, Carolyn Coffey, Claudia Cappa, Dorothy Currie, Leanne Riley, Fiona Gore, Louisa Degenhardt, Dominic Richardson, Nan Astone, Adesola O Sangowawa, Ali Mokdad, Jane Ferguson
Journal: The Lancet (2012)
A bispecific chimeric antigen receptor molecule enhances T cell activation through dual immunological synapse formation and offsets antigen escape in glioblastoma
Authors: Meenakshi Hegde, Zakaria Grada, Antonella Pignata, Amanda Wakefield, Kristen Fousek, Kevin Bielamowicz, Kevin Chow, Vita Brawley, Tiara Byrd, Stephen Gottschalk, Malini Mukherjee, Winfried S Wels, Matthew Baker, Giapietro Dotti, Jordan Orange, Nabil Ahmed
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Antigen escape tumor cell variants prevail in tumors recurring after treatment with chimeric antigen receptor (CAR) T cells with a single specificity. Recurrent tumors preserve alternative non-targeted tumor associated antigens. A bispecific CAR will mitigate antigen escape
Cutaneous infection caused by Bacillus anthracis in Larissa, Thessaly, Central Greece, July 2012
Authors: A Stefos, N K Gatselis, A Goudelas, M Mpakarosi, J Papaparaskevas, G N Dalekos, E Petinaki
Journal: Eurosurveillance (2012)

In July 2012, a confirmed case of cutaneous anthraxinfection in a stockbreeder in the prefecture of Larissa, Thessaly, Central Greece was reported. The investigation revealed five related deaths in animals (two dogs and three sheep). Control measures have been taken immediately in order to prevent further spread in humans and animals.