tbuckley/cabot-search huggingface dataset:
Updates on phase1b/2 trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus checkpoint inhibitors for the treatment of unresectable stage 3 or 4 melanoma.
Authors: Yousef Zakharia, Joseph J. Drabick, Samir Khleif, Robert R. McWilliams, David Munn, Charles J. Link, Nicholas N. Vahanian, Eugene Kennedy, Montaser F. Shaheen, Olivier Rixe, Mohammed M. Milhem
Journal: Journal of Clinical Oncology (2016)

3075 Background: IDO is an enzyme that catalyzes tryptophan to kynurenine. Tryptophan depletion enhances the function of the suppressive Treg and inhibits the effector T cells. Kynurenine metabolites may augment the suppressive effect on the immune responses. The normal physiologic function of IDO is the regulation of acquired local and peripheral immune tolerance. In cancer, IDO can either be expressed directly by the tumor cells, or induced indirectly in host antigen presenting cells by the presence of tumor. In these settings, the IDO pathway mediates an acquired immune tolerance towards tumors, allowing tumors to thwart an immune response by the host. Therefore, IDO is an attractive target. Anti- CTLA-4 (ipilimumab) and anti-PD-1 (pembrolizumab and nivolumab) are monoclonal antibodies that block CTLA-4/ PD-1, enhancing immune responses against tumors. Tumor models have shown synergistic effect with anti-CTLA-4 and anti-PD-1 treatments in combination with indoximod providing a rationale for this trial. Methods: Metastatic melanoma patients were treated in a standard design (3+3) dose escalation of oral indoximod twice daily (BID) with ipilimumab (3mg/kg q3 weeks x 4 doses) in Phase 1b. In Phase 2, indoximod is given with provider choice of Ipilimumab, pembrolizumab or nivolumab. In the event of progression, the provider can change therapy from one checkpoint inhibitor (anti-CTLA-4 or anti-PD-1) to another while continuing indoximod. Primary objective is overall response rate, secondary objectives median progression free and overall survival. Results: To date, 45 patients of a planned 105 are enrolled of which 9 patients comprised the Phase 1b cohort without DLT. The recommended Phase 2 dose was 1200 mg BID. 1 patient in Phase 1 demonstrated an ongoing CR currently at 11 months and 6 out of 9 patients are still alive (9-14 month from enrollment) and receiving additional treatment after coming off study. No SAEs or changes in ipilimumab dose due to indoximod addition were documented. Conclusions: The Phase 1b part has been successfully concluded without significant toxicities. Phase 2 is ongoing. Updated data to be presented. Clinical trial information: NCT02073123.
Can Targeted HCV Direct-Acting Antiviral Treatment as Prevention Reverse the HCV Epidemic Amongst Men who Have Sex with Men in the UK - Epidemiological and Modelling Insights
Authors: N.K. Martin, A. Thornton, M. Hickman, C. Sabin, M. Nelson, G.S. Cooke, T.C.S. Martin, V. Delpech, M. Ruf, H. Price, Y. Azad, E. Thomson, P. Vickerman
Journal: Journal of Hepatology (2016)
The Farnesoid-X-Receptor Agonist Obeticholic Acid Further Increases Biliary Excretion of Asymmetric Dimethylarginine during Hepatic Ischemia/Reperfusion Injury
Authors: L.G. Di Pasqua, C. Berardo, V. Rizzo, L. Adorini, P. Richelmi, M. Vairetti, A. Ferrigno
Journal: Journal of Hepatology (2016)
You Can Lead a Horse to Water, But Can You Pay to Make Him Drink? An Ethical Analysis of Research on Using Incentives to Promote Patient Health
Authors: Ponni Perumalswami, Andrea Branch, Rosamond Rhodes
Journal: The American Journal of Bioethics (2016)

In the mid 1980s, advances in vaccine technology led to the development of a safe and highly effective vaccine for the prevention of hepatitis B virus (HBV) infection (Zajac 1986; Andre 1989; Szmun...
Falls are leading cause of injury deaths among older people, US study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

Falls are the leading cause of fatal and non-fatal injuries among adults aged 65 years and older in the United States, a Centers for Disease Control and Prevention study has found.1

The study, published in Morbidity and Mortality Weekly Report , noted that in 2014 around 27 000 US adults in this age group died because of falling and 2.8 million were treated in emergency departments for fall …
Interferon (INF)-Free Antiviral Therapy in Cirrhotic Patients Infected with Hepatitis C on the Waiting List for Liver Transplantation. Efficacy and Impact on Delisting and Liver Function
Authors: J.M. Pascasio, C. Vinaixa, M.T. Ferrer, J. Colmenero, A. Rubin, L. Castells, M.L. Manzano, S. Lorente, M. Testillano, F.X. Xiol, E. Molina, L. González-Dieguez, E. Otón, S. Pascual, B. Santos, J.I. Herrero, M. Salcedo, J.L. Montero, G. Sánchez-Antolín, I. Narváez-Rodriguez, F. Nogueras, A. Giráldez, C. Fernández-Carrillo, X. Forns, M. Prieto, M.C. Londoño
Journal: Journal of Hepatology (2016)
Correlations Between Ofatumumab Exposure and Treatment Outcomes for Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Frontline Ofatumumab, Fludarabine, and Cyclophosphamide Chemoimmunotherapy
Authors: William G. Wierda, Roxanne C. Jewell, Thomas J. Kipps, Jan Dürig, Laimonas Griskevicius, Stephan Stilgenbauer, Lukas Smolej, Georg Hess, Francisco J. Hernandez-Ilizaliturri, Swaminathan Padmanabhan, Lei Fang, Michele M. Gorczyca, Geoffrey W. Chan, Ira V. Gupta, Steen Lisby
Journal: Blood (2011)
RIG-I Inhibits Hepatitis E Virus Replication by Simultaneously Activating JAK-STAT and NFKB Pathways
Authors: L. Xu, W. Wang, X. Zhou, Y. Wang, Y. Yin, L.J.W. Van Der Laan, D. Sprengers, H.J. Metselaar, M.P. Peppelenbosch, Q. Pan
Journal: Journal of Hepatology (2016)
The Role of Development Research Funders in Promoting Equity in Research Consortia
Authors: Sunisha Neupane, Renaud F. Boulanger, Peter Taylor
Journal: The American Journal of Bioethics (2016)

The importance of North–South partnerships for capacity building in research has long been recognized (Nakabugo et al. 2010). Over the past two decades or so, the ethics of such partnerships have c...
First Analysis of HOVON-65/GMMG-HD4 Randomized Phase III Trial Comparing Bortezomib, Adriamycine, Dexamethasone (PAD) Vs VAD as Induction Treatment Prior to High Dose Melphalan (HDM) in Patients with Newly Diagnosed Multiple Myeloma (MM)
Authors: P. Sonneveld, B. van der Holt, I. G.H. Schmidt-Wolf, U. Bertsch, L. el Jarari, Hans-Jürgen Salwender, S. Zweegman, E. Vellenga, J. Schubert, I. W. Blau, GSK Jie, B. Beverloo, A. Jauch, D. Hose, R. Schaafsma, M. J. Kersten, M. Delforge, O. de Weerdt, R. van der Griend, P. W. Wijermans, Hans Martin, H. van der Velde, Henk M. Lokhorst, H. Goldschmidt
Journal: Blood (2008)
Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities
Authors: Giovanni Musso, Maurizio Cassader, Solomon Cohney, Franco De Michieli, Silvia Pinach, Francesca Saba, Roberto Gambino
Journal: Diabetes Care (2016)

Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferator–activated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium–glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium.
Retreatment of Sofosbuvir-Including Regimen Failures in the Real Life
Authors: A. Laurain, P. Sultanik, L. Kramer, J.-F. Mertitet, E. Boueyre, V. Mallet, P. Sogni, H. Fontaine, A. Rosenberg, A. Vallet-Pichard, S. Pol
Journal: Journal of Hepatology (2016)
P0211 : Human microfibril-associated protein 4 (MFAP4) in ascites fluid predicts survival and risk of complications in patients with advanced cirrhosis
Authors: M. Kjaergaard, B.S. Madsen, M. Thiele, A. Malchow-Møller, A. Schlosser, G.L. Sørensen, U. Holmskov, A. Krag
Journal: Journal of Hepatology (2015)
Pralatrexate (10-Propargyl-10-Deazaaminopterin (PRX)), a Novel Antifolate, Effects Durable Complete Remissions (CR) in Patients with a Diversity of Drug Resistant T-Cell Lymphomas with Minimal Toxicity.
Authors: Owen O’Connor, P. A. Hamlin, E. Neylon, C. Moskowitz, C. S. Portlock, D. J. Straus, A. Noy, B. Cortelli, A. D. Zelenetz, M. Fleisher, D. D.Sarasohn, F.M. M. Sirotnak, S. Horwitz
Journal: Blood (2005)
Effectiveness of Ledipasvir/Sofosbuvir and Ombitasvir/ Paritaprevir/Ritonavir/Dasabuvir in Treatment-Naïve and –Experienced U.S. Veterans with Genotype 1 Hepatitis C Infection
Authors: M. Fuchs, V. Forte, D. Tassone, S. Owens, C. Garcia, B. Obolewicz, C. Solomon, H. Gilles, E. Gavis, D. Heuman
Journal: Journal of Hepatology (2016)
Telephone-based CBT reduced insomnia severity more than menopause education in menopausal women
Authors: Robert P. Kauffman
Journal: Annals of Internal Medicine (2016)

Source Citation McCurry SM, Guthrie KA, Morin CM, et al. Telephone-based cognitive behavioral therapy for insomnia in perimenopausal and postmenopausal women with vasomotor symptoms: a MsFLASH randomized clinical trial. JAMA Intern Med. 2016;176:913-20. 27213646
Interval between first palliative care consultation and death in patients with advanced cancer
Authors: B. El Osta, J. Palmer, T. Paraskevopoulos, B. Pei, L. Roberts, V. Poulter, R. Chacko, E. Bruera
Journal: Journal of Clinical Oncology (2007)

9028 Background: Most referrals to acute palliative care (PC) services occur late in the trajectory of the disease, although an earlier intervention can decrease patients’ (pts) symptoms distress. The purpose of this study was to determine the time interval between first palliative care consultation (PC1) and death (D) in pts diagnosed with advanced cancer (aCA) at our comprehensive cancer center and whether such interval has increased over time. Methods: The study group was 2,868 consecutive pts who had their PC1 during a 30-month period. We reviewed the charts for information about demographics, cancer type, date of cancer diagnosis, aCA diagnosis, PC1, and D. aCA was defined as locally recurrent or metastatic. Results: 1,404 pts (49%) were female, 1,791 (62%) were &lt; 65 years old, 2,563 (89%) had solid cancer, and 2,004 (70%) were white. The median PC1-D, aCA- PC1, and aCA-D intervals were 40, 114, and 243 days respectively. The median PC1-D interval (days) was: 47 for pts with solid cancer vs 14 for pts with hematological malignancy (p &lt; 0.0001); 44 for pts &lt; 65 years old vs 36 for pts = 65 years old (p = 0.002); 45 for females vs 37 for males (p = 0.004); 40 for white pts vs 41 for pts from other ethnicities (p = 0.42). The median PC1-D interval in 5 consecutive half-years was 46, 56, 42, 41, and 34 days respectively (p = 0.02). The total number of pts referred for PC1 in this period increased 20%, from 544 to 654. The ratio of PC involvement period in the aCA-D interval (PC1-D/aCA-D) decreased from 0.30 to 0.26 over the 5 half-year periods (p = 0.0004) ( Table ). Conclusions: Patients with solid cancers, younger pts, and females pts were referred earlier to acute PC. Referral timing was not affected by ethnicity. The interval between first palliative care consult and death has decreased over time. Education is needed among referring physicians to increase this interval. Further research on increasing acute PC access and its impact on PC1-D interval is needed. [Table: see text] No significant financial relationships to disclose.
Supplemental Feedings for the High-Risk Preterm Infants—Reply
Authors: Marita de Waard, Willemijn E. Corpeleijn, Johannes B. van Goudoever
Journal: JAMA Pediatrics (2016)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 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 Pediatrics journal
Analysis of prognostic factors of pediatric-type sarcomas in adult patients.
Authors: H. Ahn, J. Um, J. Lee, W. Kim, D. Lim, J. Park
Journal: Journal of Clinical Oncology (2010)

10094 Background: Pediatric-type sarcomas such as Ewing's sarcoma/primitive neuroectodermal tumor family (EWS/PNET) and rhabdomyosracoma (RMS) are relatively uncommon in adult patients (pts). Optimal treatment strategies for this population remain controversial and there have been debates on whether adults do worse than pediatric pts with the same stage of disease. Methods: To identify prognostic factors, we retrospectively reviewed clinical data on pts with pediatric type sarcoma older than 15 years at a single institution. Results: Seventy-five consecutive patients from February 1995 to October 2005 were identified from the database at the Samsung Medical Center, Seoul, Korea. Forty-five patients (60.0%) of 75 patients were male. Median age of patients was 30-year old with range of 15–74. Forty patients (53.3%) were diagnosed as EWS/PNET, 32 patients (42.7%) as RMS and 3 patients (3%) as DSRCT. Median overall survival (OS) for all patients was 39 months (95% CI. 13.0-65.0 months) and median event-free survival (EFS) for all patients was 19 months (95% CI. 5.0-33.0). Multivariate analysis revealed that age over 30, IRS III/IV and poor performance status were significant independent prognostic factors for poor OS, whereas IRS III/IV was the only prognostic factors for EFS. In subset analysis, only pts younger than 30 years showed favorable outcomes in pts group with IRS I/II. Conclusions: Although the limits of this retrospective study are self-evident, we identified the prognostic variables enable risk-adapted therapies for this rare adult sarcoma group, which should be further investigated. Also, our data would suggest that pediatric treatment protocols are feasible for the adult pts so optimal therapy should be given to the pts. No significant financial relationships to disclose.
Corneal Epithelial Stem Cells Repopulate the Donor Area within 1 Year from Limbus Removal for Limbal Autograft
Authors: Massimo Busin, Claudia Breda, Marina Bertolin, Cristina Bovone, Diego Ponzin, Stefano Ferrari, Vanessa Barbaro, Hossein Mostafa Elbadawy
Journal: Ophthalmology (2016)
Standards for Acquisition, Measurement, and Reporting of Intravascular OCT (IVOCT) Studies. A Consensus Report from the International Working Group for Intravascular OCT Standardization and Validation
Authors: Guillermo J. Tearney, Evelyn Regar, Akasaka Takashi, Tom Adriaenssens, Giovanni Jacopo Ughi
Journal: Journal of the American College of Cardiology (2011)
Liver Stiffness Improvement in Subjects with Advanced Chronic Hepatitis C Treated with Direct Antiviral Agents
Authors: N. Gamal, F. Conti, M. Mastroroberto, A. Scuteri, C. Cursaro, V. Guarneri, R. Di Donato, G. Vitale, P. Andreone
Journal: Journal of Hepatology (2016)
Association of epithelial mesenchymal transition (EMT) markers and outcome measures in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib.
Authors: N. B. Shah, M. J. Fidler, K. K. Walters, E. Braun, S. Basu, H. Harasty, J. Coon, M. Pool, T. A. Hensing, P. D. Bonomi
Journal: Journal of Clinical Oncology (2010)

7550 Background: Our objective was to explore potential relationships to clinical outcomes of advanced NSCLC erlotinib treated patients (pts) with EMT markers e-cadherin (e-cad) and vimentin (vim). Methods: This is a retrospective study which included erlotinib treated advanced NSCLC pts who had adequate tissue to perform molecular analyses for e-cad (Santa Cruz Biotechnology, G-10) and vim (DAKO, Clone V9) expression by immunohistochemistry (IHC). The IHC was performed using the Ventana Benchmark automated staining system with the iView DAB detection chemistry. Expression was scored semi-quantitatively for frequency (0-4) and intensity (0-4) of tumor cells staining positive. Results: 115 pts had interpretable results for e-cad and 122 pts had interpretable results for vimentin. E-cad negative patients (ecad frequency < = 0) had a median progression free interval (PFS) of 1.2 mo vs 2.4 mo (p = 0.00978) for ecad positive patients (ecad frequency > 0) while the median overall survival (OS) was 2.4 mo vs 7.3 mo (p = 0.000928) for ecad negative and positive patients, respectively. For the vim positive patients (vim frequency > 0) a median progression free interval of 1.6 mo vs. 2.9 mo (p = 0.00277) for vim negative patients (vim < = 0). The median overall survival (OS) difference was not statistically significant for vim positive and negative patients respectively. When compared to other variables including smoking status, gender, and histology of tumor, only e-cad expression was a better predictor of overall survival (p = 0.0015 with hazard ratio ([HR] of 0.34) for all variables except smoking (p = 0.0043) (HR 2.7). Conclusions: Our results suggest improved PFS for patients treated with erlotinib therapy with increased e-cad expression and minimal vimentin expression regardless of gender or histology. OS was also significant in the e-cad expression group. Further analysis of EMT markers is ongoing with EGFR exon 19 and 21 mutations, FISH analyses for EGFR, chromosome 7, PTEN, PI3KCA. The EMT pathway may prove to be a potential target for therapy alone or in combination with EGFR inhibitors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, OSI Genentech, OSI
Regional myocardial systolic function measured with myocardial velocity imaging improves with the transplantation of autologous bone marrow-derived stem cells in patients with large acute myocardial infarction
Authors: Lieven Herbots, E Eroglu, Daisy Thijs, Javier Ganame, Piet Claus, Steven Dymarkowski, Jan Bogaert, Marie-Christine Herregods, Frans Van de Werf, Frank Rademakers, Jan D'hooge, Stefan Janssens
Journal: Circulation (2005)
Pharmacokinetically Guided Dosing of Oral Drugs: True Precision Oncology?
Authors: Moshe C. Ornstein, Brian I. Rini
Journal: Clinical Cancer Research (2016)

Higher plasma concentrations of tyrosine kinase inhibitors (TKI), such as pazopanib, are associated with improved clinical outcomes. However, TKI pharmacokinetics exhibit significant interpatient variability, resulting in inconsistent and unpredictable plasma drug levels. An individualized dosing approach based on patient pharmacokinetics data and toxicity can potentially optimize plasma concentrations of pazopanib. Clin Cancer Res; 22(23); 5626-8. ©2016 AACRSee related article by Verheijen et al., p. 5738.
Sustained Virological Response after Interferon-Based Therapy for Chronic Hepatitis C and its Association with Reduced All-Cause Mortality and Liver-Related Mortality
Authors: L.M. Nyberg, X. Li, S.-J. Yang, T. Craig Cheetham, K. Chiang, J. Pio, S. Caparosa, Z. Younossi, A. Nyberg
Journal: Journal of Hepatology (2016)
Analysis of NRF2-KEAP1 Pathway and Metabolic Reprogramming in Two Distinct Models of Rat Liver Proliferation
Authors: L. Cabras, C. Orrù, A. Perra, A. Morandi, G.M. Ledda-Columbano, A. Columbano, M.A. Kowalik
Journal: Journal of Hepatology (2016)
Inhibition of Hyaluronic Acid in Hepatocarcinogenesis: A Novel Approach to Target CD44 and Other Cancer Stem Cell Populations
Authors: C.H.C. Sukowati, B. Anfuso, S. Ie, C. Avellini, O. Radillo, A. Raseni, E. Fiore, G. Mazzolini, C. Tiribelli
Journal: Journal of Hepatology (2016)
The G9A Histone Methyltransferase BIX-01294 Reactivates ε-Globin Expression and Blocks Erythroid Differentiation in Primary Baboon Erythroid Progenitor Cell Cultures
Authors: Virryan Banzon, Vinzon Ibanez, Kestis Vaitkus, Tatiana Kousnetzova, Joseph Desimone, Donald Lavelle
Journal: Blood (2008)
True Collagen Type III Formation (Pro-C3) is Predictive of Outcome in HCV Patients with Advanced Liver Fibrosis with in the Trent Study
Authors: D.J. Leeming, G. Dolman, M.J. Nielsen, M.A. Karsdal, K. Patel, W. Irving, I.N. Guha
Journal: Journal of Hepatology (2016)
IGG4-Related Disease is Associatied with CD4+ T Cell Activation and Regulation
Authors: T. Cargill, E. Culver, M. Makuch, C. Manganis, C. Willberg, R. Sadler, E. Vermeulen, L. Lighaam, A. Llibre, L. Swadling, C. Evans, C. Green, A. Kurioka, A. Brown, C. de Lara, M. van Ham, P. Klenerman, T. Rispens, E. Barnes
Journal: Journal of Hepatology (2016)
Ledipasvir/Sofosbuvir for 12 or 24 Weeks Is Safe and Effective in Kidney Transplant Recipients with Chronic Genotype 1 or 4 Hcv Infection
Authors: M. Colombo, A. Aghemo, L. Liu, R. Hyland, C. Yun, D. Brainard, J. McHutchison, M. Bourlière, M. Peck-Radosavljevic, M. Manns, S. Pol
Journal: Journal of Hepatology (2016)