tbuckley/cabot-search huggingface dataset:
von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia
Authors: Georgios N. Kalambokis, Aikaterini Oikonomou, Leonidas Christou, Nikolaos I. Kolaitis, Epameinondas V. Tsianos, Dimitrios Christodoulou, Gerasimos Baltayiannis
Journal: Journal of Hepatology (2016)
P1-134: Clinical Experience of Simultaneous Multitarget Irradiation using Tomotherapy in Pulmonary Metastasis
Authors: Chul Seung Kay, Yeon Sil Kim, Jeong Won Jang, Si Hyun Bae, Jong Yeong Choi, Seung Kew Yoon, Se Jeong Oh, Ihl Bong Choi
Journal: Journal of Thoracic Oncology (2007)
28. Intravenous Administration of Lentiviral Vectors Expressing Hyperactive Factor IX Converts Severe Into Mild Hemophilia B in a Canine Model
Authors: Alessio Cantore, Michela Milani, Tongyao Liu, Patrizia Della Valle, Armando D'Angelo, Thierry VandenDriessche, Marinee Chuah, Haiyan Jiang, Timothy Nichols, Luigi Naldini
Journal: Molecular Therapy (2015)

Lentiviral vectors (LVs) are attractive vehicles for liver-directed gene therapy by virtue of their ability to stably integrate in the genome of target cells and the lack of pre-existing immunity against vector components in most humans. Over the past years, we have developed a LV platform that can achieve stable transgene expression in the liver, induce transgene-specific immune tolerance and establish correction of hemophilia in mouse models upon systemic administration. This LV is designed to stringently target transgene expression to hepatocytes through transcriptional and microRNA-mediated regulation. We then investigated the efficacy and safety profile of portal vein administration of LVs expressing wild-type, codon-optimized (c.o.) or c.o. and hyperactive factor IX (FIX) in a canine model of hemophilia B. We produced large-scale batches of LVs qualified for in vivo administration and treated adult hemophilia B dog by portal vein administration. We observed long-term stable reconstitution of canine FIX activity up to 1% of normal and significant amelioration of the clinical phenotype in 3 treated dogs (>9 years cumulative follow up). LV infusion was associated with transient signs of inflammation and mild hepatotoxicity, which could be abrogated by pretreatment with anti-inflammatory drugs. There was no detectable long-term toxicity or development of FIX inhibitors. In the perspective of clinical translation and to increase therapeutic efficacy, we next treated an 11-kg, hemophilia B dog by peripheral vein administration of LVs expressing the c.o. and hyperactive canine FIX at a 5-fold higher dose than those previously administered. At the current follow-up (3 months after gene therapy) FIX activity is 6-9% of normal. Intravenous LV administration, coupled with a 1-day anti-inflammatory and anti-histamine pre-treatment, induced mild and selflimiting leukopenia and elevation of aminotransferases. Treatment of more hemophilia B dogs is underway to confirm and extend these results. Overall, our studies, which suggest comparable efficacy of LV by both portal and peripheral vein administration, position LV-mediated liver gene therapy for further pre-clinical development and clinical translation. LVs may thus complement other available vectors to address some of the outstanding challenges posed by liver gene therapy of hemophilia and conceivably other diseases.
Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial
Authors: Jonathan A Ledermann, Philipp Harter, Charlie Gourley, Michael Friedlander, Ignace Vergote, Gordon Rustin, Clare Scott, Werner Meier, Ronnie Shapira-Frommer, Tamar Safra, Daniela Matei, Anitra Fielding, Stuart Spencer, Philip Rowe, Elizabeth Lowe, Darren Hodgson, Mika A Sovak, Ursula Matulonis
Journal: The Lancet Oncology (2016)
Simple blood test for heart failure should be more widely available, say MPs
Authors: Jacqui Wise
Journal: BMJ (2016)

All clinical commissioning groups in England should ensure that a simple blood test to measure natriuretic peptide levels is widely available to speed up the diagnosis of heart failure, a parliamentary report recommends.1

Raised levels of natriuretic peptides in the blood can indicate whether a patient has heart failure, as well as the severity of the condition. The NT-proBNP blood test costs under £28 and is recommended by the National Institute for Health and Care Excellence (NICE). Patients with a very high level of natriuretic peptide in …
Kidney Outcomes 5 Years After Pediatric Cardiac Surgery
Authors: Jason H. Greenberg, Michael Zappitelli, Prasad Devarajan, Heather R. Thiessen-Philbrook, Catherine Krawczeski, Simon Li, Amit X. Garg, Steve Coca, Chirag R. Parikh
Journal: JAMA Pediatrics (2016)

Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high short-term morbidity and mortality; however, the long-term kidney outcomes are unclear.To assess long-term kidney outcomes after pediatric cardiac surgery and to determine if perioperative AKI is associated with worse long-term kidney outcomes.This prospective multicenter cohort study recruited children between ages 1 month to 18 years who underwent cardiopulmonary bypass for cardiac surgery and survived hospitalization from 3 North American pediatric centers between July 2007 and December 2009. Children were followed up with telephone calls and an in-person visit at 5 years after their surgery.Acute kidney injury defined as a postoperative serum creatinine rise from preoperative baseline by 50% or 0.3 mg/dL or more during hospitalization for cardiac surgery.Hypertension (blood pressure ≥95th percentile for height, age, sex, or self-reported hypertension), microalbuminuria (urine albumin to creatinine ratio >30 mg/g), and chronic kidney disease (serum creatinine estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 or microalbuminuria).Overall, 131 children (median [interquartile range] age, 7.7 [5.9-9.9] years) participated in the 5-year in-person follow-up visit; 68 children (52%) were male. Fifty-seven of 131 children (44%) had postoperative AKI. At follow-up, 22 children (17%) had hypertension (10 times higher than the published general pediatric population prevalence), while 9 (8%), 13 (13%), and 1 (1%) had microalbuminuria, an eGFR less than 90 mL/min/1.73 m2, and an eGFR less than 60 mL/min/1.73 m2, respectively. Twenty-one children (18%) had chronic kidney disease. Only 5 children (4%) had been seen by a nephrologist during follow-up. There was no significant difference in renal outcomes between children with and without postoperative AKI.Chronic kidney disease and hypertension are common 5 years after pediatric cardiac surgery. Perioperative AKI is not associated with these complications. Longer follow-up is needed to ascertain resolution or worsening of chronic kidney disease and hypertension.
Phase II trial of bevacizumab with fotemustine in recurrent glioblastoma: Final results of a multicenter study of AINO (Italian Association of Neuro-oncology).
Authors: R. Soffietti, E. Trevisan, R. Ruda, L. Bertero, C. Bosa, M. G. Fabrini, I. Lolli
Journal: Journal of Clinical Oncology (2011)

2027 Background: Bevacizumab has shown activity in recurrent glioblastoma (GBM), and few data are available on the combination of bevacizumab and nitrosoureas, that represent the standard cytotoxic option. Fotemustine (FTM) is a nitrosourea with elevated lipophilic properties. Methods: In this phase II study patients with GBM recurrent after surgery, radiation therapy, and concomitant/adjuvant temozolomide were elegible. The treatment consisted of an induction phase with BV at 10 mg/kg intravenously on day 1 and 15 and fotemustine (FTM) at 75mg/m2intravenously on day 1 and 8, followed after 3 week interval by a maintenance phase with BV at 10 mg/kg i.v. and FTM 75mg/ m2 every 3 weeks until tumor progression or unacceptable toxicity. Patients had undergone clinical and MRI assessment 1 month after the start of treatment and thereafter every 2 months. The primary endpoint was progression-free survival at 6 months (PFS6), whereas secondary endpoints were response rate (RR), based on RANO criteria, progression-free (PFS) and overall survival (OS), and safety. Results: From April 2008 until November 2010, 54 patients (males 35, females 19, median age 57) were enrolled. PFS6, PFS12 and mPFS were 44%, 21% and 5.29 months respectively. mOS was 9.13 months with 77.4% and 31% of patients surviving at 6 and 12 months respectively. Response rates were as follows: 2CR (4%), 24 PR (44%), 22 SD (41%) and 6 PD (11%). A significant neurological improvement was observed in 57 % of patients, being steroids reduced or interrupted in 64%. 44/54 (81%) patients have progressed and patterns of progression were local in 29/44 (66%), multicentric 10/44 (23%), gliomatosis 3/44 (6%) and isolated leptomeningeal spread 2/44 (5%). 12/54 (22%) patients with grade 3/4 piastrinopenia/leukopenia discontinued fotemustine, whereas 4/54 (7.4%)discontinued bevacizumab (1 stroke, 1 intratumoral haemorrhage, 1 GI perforation and 1 pulmonary embolism). Conclusions: Combination of bevacizumab and fotemustine in glioblastomas recurrent after standard radiotherapy + temozolomide is safe and promising. The analysis of MGMT methylation status is ongoing.
EGFR–Co-Mutated Advanced NSCLC and Response to EGFR Tyrosine Kinase Inhibitors
Authors: Megan B. Barnet, Sandra O’Toole, Lisa G. Horvath, Christina Selinger, Bing Yu, Chiu Chin Ng, Michael Boyer, Wendy A. Cooper, Steven Kao
Journal: Journal of Thoracic Oncology (2016)
Early Identification of Patients With Out-of-Hospital Cardiac Arrest With No Chance of Survival and Consideration for Organ Donation
Authors: Patricia Jabre, Wulfran Bougouin, Florence Dumas, Pierre Carli, Corinne Antoine, Laurent Jacob, Benjamin Dahan, Frankie Beganton, Jean-Philippe Empana, Eloi Marijon, Nicole Karam, Alexandre Loupy, Carmen Lefaucheur, Daniel Jost, Alain Cariou, Frédéric Adnet, Thomas D. Rea, Xavier Jouven
Journal: Annals of Internal Medicine (2016)

In patients with out-of-hospital cardiac arrest (OHCA), care requirements can conflict with the need to promptly focus efforts on organ donation in patients who are pronounced dead.To evaluate objective criteria for identifying patients with OHCA with no chance of survival during the first minutes of cardiopulmonary resuscitation to enable prompt orientation toward organ donation.Retrospective assessment using OHCA data from 2 registries and 1 trial.France (Paris Sudden Death Expertise Center [SDEC] prospective cohort [2011 to 2014] and PRESENCE multicenter cluster randomized trial [ClinicalTrials.gov: NCT01009606] [2009 to 2011]) and the United States (King County, Washington, prospective cohort [2006 to 2011]).1771 patients from the Paris SDEC 1-year cohort (2011 to 2012) and 5192 from the validation cohorts.Evaluation of 3 objective criteria (OHCA not witnessed by emergency medical services personnel, nonshockable initial cardiac rhythm, and no return of spontaneous circulation before receipt of a third 1-mg dose of epinephrine), survival rate at hospital discharge among patients meeting these criteria, performance of the criteria, and number of patients eligible for organ donation.In the Paris SDEC 1-year cohort, the survival rate among the 772 patients with OHCA who met the objective criteria was 0% (95% CI, 0.0% to 0.5%), with a specificity of 100% (CI, 97% to 100%) and a positive predictive value of 100% (CI, 99% to 100%). These results were verified in the validation cohorts. Ninety-five (12%) patients in the Paris SDEC 1-year cohort may have been eligible for organ donation.Several patients had unknown outcomes.Three objective criteria enable the early identification of patients with OHCA with essentially no chance of survival and may help in decision making about the organ donation process.French Ministry of Health.
P3-186: Dose escalation by tomotherapy in non-small cell lung cancer - early clinical experiences -
Authors: Chang G. Lee, Ik J. Lee, Jae H. Cho, Ki C. Keum, Yong B. Kim, Se W. Yoo, Yang K. Suh, Song Y. Kim, Gwi E. Kim
Journal: Journal of Thoracic Oncology (2007)
Dietary intervention with lactulose is linked to band-specific changes in community fingerprinting profiles of the human faecal microbiota
Authors: Vicky De Preter, Marie Joossens, Tom Vanhoutte, Greet Van Staeyen, Diederik Esser, Geert Huys, Peter Vandamme, Paul Rutgeerts, Kristin Verbeke
Journal: Gut (2007)
Nitric oxide inhalation decreases myocardial injury in a porcine model of cardiac ischemia and reperfusion
Authors: XS Liu, Yanming Huang, J Santos, M Swinnen, Marijke Pellens, Hilde Gillijns, U Leuven, M Scherrer-Crosbie, MJ Semigran, Frans Van de Werf, KD Bloch, Stefan Janssens
Journal: Circulation (2005)
T(8;22)(q24;q11) In a Context of Complex Karyotype In Two Patients with B-Cell Lymphoma with Features Intermediate Between Burkitt Lymphoma and Diffuse Large B Cell Lymphoma B (LB/LDCGB)
Authors: Teresa Vallespi, Margarita Ortega, Anny Jaramillo, Laura Lopez-Andreoni, Noemi Martínez-Morgado, Carmen Sánchez, Francesc Bosch
Journal: Blood (2010)
Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois
Authors: Bruce K. Tan, Aiko I. Klingler, Julie A. Poposki, Whitney W. Stevens, Anju T. Peters, Lydia A. Suh, James Norton, Roderick G. Carter, Kathryn E. Hulse, Kathleen E. Harris, Leslie C. Grammer, Robert P. Schleimer, Kevin C. Welch, Stephanie S. Smith, David B. Conley, Robert C. Kern, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2016)
Sorafenib plus chemotherapy versus chemotherapy alone in advanced pancreatic cancer: A randomized phase II trial.
Authors: S. Cascinu, R. Berardi, A. F. Sobrero, R. Labianca, P. Bidoli, S. Siena, D. Ferraris, S. Barni, R. Cengarle, M. Monteforte
Journal: Journal of Clinical Oncology (2010)

4066 Background: No standard treatment is available for advanced pancreatic cancer (PC). Although gemcitabine is used with the purpose of symptom palliation, there is no clear evidence of a significant survival increase. Attempts at improving results by combining gemcitabine with other cytotoxic drugs failed to obtain any advantage. KRAS and BRAF mutations are present in approximately 90% and 5% of the PCs, respectively. Sorafenib is an inhibitor of the RAS/RAF signaling pathway showing inhibition of proliferation of pancreatic tumor cell lines containing KRAS or BRAF mutations. It may be combined with gemcitabine and cisplatin without any pharmacokinetic interaction or enhanced toxicity. Therefore,a phase II randomized trial was designed to explore the role of sorafenib in combination with chemotherapy. Methods: Patients with histologically proven, locally advanced or metastatic pancreatic adenocarcinoma, chemonaive, and ECOG 0-2 were eligible. Subjects wererandomized in a 1:1 ratio to receive cisplatin 25 mg/m2/day and gemcitabine 1,000 mg/m2/day on d1-8q21 days in combination with sorafenib, at 400 mg (2 tablets × 200 mg each) orally, twice daily continuously (arm A), or gemcitabine/cisplatin alone (arm B). The primary efficacy end point was progression-free survival (PFS); other efficacy end points were response rate (RR) and overall survival. Results: 114 patients were enrolled. Patients characteristics are summarized in the Table. At a median follow-up of 13.4 months, 35 patients progressed in arm A and 38 in arm B. Median PFS was 4.9 months and 3.3 months respectively (HR=1.01;0.65–1.56 CI 95%). Objective RR was 6.9% in arm A and 7.1% in arm B. Rate of responders/stable disease was 58.6% in arm A and 53.6% in arm B (p=0.47). Hematological and hepatic toxicity was the cause of discontinuation in 6 (10.3%) patients in arm A and 5 (8.9%) in arm B. Conclusions: Addition of sorafenib to chemotherapy does not seem to significantly improve PFS and response rate in advanced PC. The analysis of the molecular alterations of the RAS/RAF pathway is ongoing. Characteristics Sorafenib/chemotherapy (58) Chemotherapy (56) M/F 36/22 30/26 Median age (yrs) 66.6 65.1 Locally advanced 16 22 Metastatic 42 34 ECOG 0-1 40 40 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, AstraZeneca, Bayer, Merck Serono, Onyx, Pfizer, Roche, sanofi-aventis Amgen, AstraZeneca, Bayer, Merck Serono, Onyx, Pfizer, Roche, sanofi-aventis
Comparative Effectiveness of Diabetic Oral Medications Among HIV-Infected and HIV-Uninfected Veterans
Authors: Jennifer H. Han, Kirsha Gordon, Julie A. Womack, Cynthia L. Gibert, David A. Leaf, David Rimland, Maria C. Rodriguez-Barradas, Gregory P. Bisson
Journal: Diabetes Care (2016)

Type 2 diabetes is increasingly common in HIV-infected individuals. The objective of this study was to compare the glycemic effectiveness of oral diabetic medications among patients with and without HIV infection.A longitudinal cohort study was conducted among HIV-infected and uninfected veterans with type 2 diabetes initiating diabetic medications between 1999 and 2010. Generalized estimating equations were used to compare changes in hemoglobin A1c (HbA1c) through the year after medication initiation, adjusting for baseline HbA1c level and clinical covariates. A subanalysis using propensity scores was conducted to account for confounding by indication.A total of 2,454 HIV-infected patients and 8,892 HIV-uninfected patients initiated diabetic medications during the study period. The most commonly prescribed medication was metformin (n = 5,647, 50%), followed by a sulfonylurea (n = 5,554, 49%) and a thiazolidinedione (n = 145, 1%). After adjustment for potential confounders, there was no significant difference in the change in HbA1c level among the three groups of new users. HIV infection was not significantly associated with glycemic response (P = 0.24). Black and Hispanic patients had a poorer response to therapy compared with white patients, with a relative increase in HbA1c level of 0.16% (95% CI 0.08, 0.24) [1.7 mmol/mol (0.9, 2.6)] (P < 0.001) and 0.25% (0.11, 0.39) [2.7 mmol/mol (1.2, 4.3)] (P = 0.001), respectively.We found that glycemic response was independent of the initial class of diabetic medication prescribed among HIV-uninfected and HIV-infected adults with type 2 diabetes. The mechanisms leading to poorer response among black and Hispanic patients, who make up a substantial proportion of those with HIV infection and type 2 diabetes, require further investigation.
Stem cell–derived models to improve mechanistic understanding and prediction of human drug‐induced liver injury
Authors: Christopher Goldring, Daniel J. Antoine, Frank Bonner, Jonathan Crozier, Chris Denning, Robert J. Fontana, Neil A. Hanley, David C. Hay, Magnus Ingelman‐Sundberg, Satu Juhila, Neil Kitteringham, Beatriz Silva‐Lima, Alan Norris, Chris Pridgeon, James A. Ross, Rowena Sison Young, Danilo Tagle, Belen Tornesi, Bob van de Water, Richard J. Weaver, Fang Zhang, B. Kevin Park
Journal: Hepatology (2016)

Current preclinical drug testing does not predict some forms of adverse drug reactions in humans. Efforts at improving predictability of drug‐induced tissue injury in humans include using stem cell technology to generate human cells for screening for adverse effects of drugs in humans. The advent of induced pluripotent stem cells means that it may ultimately be possible to develop personalized toxicology to determine interindividual susceptibility to adverse drug reactions. However, the complexity of idiosyncratic drug‐induced liver injury means that no current single‐cell model, whether of primary liver tissue origin, from liver cell lines, or derived from stem cells, adequately emulates what is believed to occur during human drug‐induced liver injury. Nevertheless, a single‐cell model of a human hepatocyte which emulates key features of a hepatocyte is likely to be valuable in assessing potential chemical risk; furthermore, understanding how to generate a relevant hepatocyte will also be critical to efforts to build complex multicellular models of the liver. Currently, hepatocyte‐like cells differentiated from stem cells still fall short of recapitulating the full mature hepatocellular phenotype. Therefore, we convened a number of experts from the areas of preclinical and clinical hepatotoxicity and safety assessment, from industry, academia, and regulatory bodies, to specifically explore the application of stem cells in hepatotoxicity safety assessment and to make recommendations for the way forward. In this short review, we particularly discuss the importance of benchmarking stem cell–derived hepatocyte‐like cells to their terminally differentiated human counterparts using defined phenotyping, to make sure the cells are relevant and comparable between labs, and outline why this process is essential before the cells are introduced into chemical safety assessment. (H epatology 2017;65:710‐721).
Endoscopic ultrasound-guided fine needle biopsy through the interstices of a colonic stent for the diagnosis of metastatic breast cancer using a forward-viewing linear echoendoscope
Authors: Woojin Jeong, Dimitri Trembath, Todd Baron
Journal: Endoscopy (2016)

Malignancies of extracolonic origin can be the cause of colorectal obstruction. Acute colorectal obstruction generally requires rapid decompression. Self-expandable metal stent (SEMS) placement is a nonsurgical alternative for palliation of malignant extracolonic obstruction [1]. Knowing the pathology of the underlying cause of the obstruction allows management to be appropriately directed for the stented patient. Pathological confirmation of malignancy by endoscopic biopsy in patients with extracolonic obstruction is difficult and the presence of an existing stent can hamper the ability to obtain diagnostic tissue [2] [3].
In vivo genome editing as a potential treatment strategy for inherited retinal dystrophies
Authors: Mert Yanik, Brigitte Müller, Fei Song, Jacqueline Gall, Franziska Wagner, Wolfgang Wende, Birgit Lorenz, Knut Stieger
Journal: Progress in Retinal and Eye Research (2016)

In vivo genome editing represents an emerging field in the treatment of monogenic disorders, as it may constitute a solution to the current hurdles in classic gene addition therapy, which are the low levels and limited duration of transgene expression. Following the introduction of a double strand break (DSB) at the mutational site by highly specific endonucleases, such as TALENs (transcription activator like effector nucleases) or RNA based nucleases (clustered regulatory interspaced short palindromic repeats - CRISPR-Cas), the cell's own DNA repair machinery restores integrity to the DNA strand and corrects the mutant sequence, thus allowing the cell to produce protein levels as needed. The DNA repair happens either through the error prone non-homologous end-joining (NHEJ) pathway or with high fidelity through homology directed repair (HDR) in the presence of a DNA donor template. A third pathway called microhomology mediated endjoining (MMEJ) has been recently discovered. In this review, the authors focus on the different DNA repair mechanisms, the current state of the art tools for genome editing and the particularities of the retina and photoreceptors with regard to in vivo therapeutic approaches. Finally, current attempts in the field of retinal in vivo genome editing are discussed and future directions of research identified.
From Obamacare to Hillarycare — Democrats’ Health Care Reform Agenda
Authors: Jonathan Oberlander
Journal: New England Journal of Medicine (2016)

Interview with Dr. Paul Ginsburg on what the 2016 election will mean for health care reform. (10:16)Download If Hillary Clinton wins the presidency, Democrats can advance health care reform by making health plans more affordable in order to achieve further gains in coverage, by stabilizing the marketplaces, and by seeking ways to slow medical spending over the long term.