tbuckley/cabot-search huggingface dataset:
Antimalarial Drugs as Immune Modulators: New Mechanisms for Old Drugs
Authors: Jie An, Mark Minie, Tomikazu Sasaki, Joshua J. Woodward, Keith B. Elkon
Journal: Annual Review of Medicine (2016)

The best known of the naturally occurring antimalarial compounds are quinine, extracted from cinchona bark, and artemisinin (qinghao), extracted from Artemisia annua in China. These and other derivatives are now chemically synthesized and remain the mainstay of therapy to treat malaria. The beneficial effects of several of the antimalarial drugs (AMDs) on clinical features of autoimmune disorders were discovered by chance during World War II. In this review, we discuss the chemistry of AMDs and their mechanisms of action, emphasizing how they may impact multiple pathways of innate immunity. These pathways include Toll-like receptors and the recently described cGAS-STING pathway. Finally, we discuss the current and future impact of AMDs on systemic lupus erythematosus, rheumatoid arthritis, and devastating monogenic disorders (interferonopathies) characterized by expression of type I interferon in the brain.
Parkinsonism Driven by Antipsychotics Originates from Dopaminergic Control of Striatal Cholinergic Interneurons
Authors: Geetika Kharkwal, Karen Brami-Cherrier, José E. Lizardi-Ortiz, Alexandra B. Nelson, Maria Ramos, Daniel Del Barrio, David Sulzer, Anatol C. Kreitzer, Emiliana Borrelli
Journal: Neuron (2016)
Facteurs de risque d’obstruction des prothèses biliaires métalliques chez les malades avec une sténose tumorale hilaire.
Authors: J. Branche
Journal: Endoscopy (2016)

Le traitement endoscopique des tumeurs hilaires est complexe avec un résultat parfois décevant. Les prothèses métalliques ont une meilleure efficacité que les prothèses plastiques, leur calibre permettant une perméabilité prolongée. L’obstruction des prothèses reste un problème majeur, lié à la croissance tumorale, à l’hyperplasie muqueuse ou à du sludge. De fait, la qualité de vie des malades peut être altérée ce d’autant que la reprise endoscopique est souvent difficile.
Can program evaluation be saved from its enthusiasts?
Authors: J Zusman
Journal: American Journal of Psychiatry (1976)

Program evaluation--the use of scientific techniques to measure the value of an agency's work--has become the focus of major attention and enthusiasm in mental health service planning and administration. However, the author points out that completed program evaluation studies are few in number and provide no evidence of great impact on the operation of programs or agencies and that unrealistic enthusiasm for program evaluation can lead to unrealistic rejection when performance fails to reach promise. He concludes that program evaluation should be applied only when it can have an impact, i.e., in a limited number of carefully selected cases.
CHOP/CHOP-Like-14 Vs. CHOP/CHOP-Like-21 For Patients With Aggressive Lymphoma – a Systematic Review and Meta-Analysis Of Randomized Controlled Trials
Authors: Liat Vidal, Ronit Gurion, Ron Ram, Ofer Shpilberg, Pia Raanani, Anat Gafter-Gvili
Journal: Blood (2013)
Mesenteric Angiography
Authors: J Wittenberg, C A Athanasoulis, J H Shapiro, L F Williams
Journal: New England Journal of Medicine (1971)

AIM: To assess if certain triaging rules could be established to optimize the yield of mesenteric angiography. METHODS: Medical records of 101 patients were retrospectively reviewed and parameters relating to age, gender, pulse rate, blood pressure, serum hemoglobin, intensive care unit(ICU) admission, and the number of packed red blood cells(PRBC) transfused in the 12 and 24 h prior to the angiography were tabulated in two groups with positive and negative angiography results. RESULTS: We found no correlation between gender, pulse rate, blood pressure or serum hemoglobin and positivity of the mesenteric angiogram. But patients with positive angiogram were found to be on average 7 years older(73.2 years vs 65.9 years old)(P = 0.02). Angiogram was positive in 39.3 %(11/28) of patientsadmitted in ICU vs 23.2%(17/73) who were admitted elsewhere in the hospital(P = 0.03). In the 12 and 24 h prior to angiography, patients with a positive angiogram received a mean of 2.7 ± 2.3 and 3.3 ± 2.6 units of PRBC s respectively, while patients with a negative angiogram had a mean of 1.6 ± 1.9(P = 0.02) and 2.1 ± 2.6 units(P = 0.04) received respectively in the same period. CONCLUSION: Older age, ICU admission, having received at least 4 units PRBC over 12 h or 5 units over 24 h prior to angiogram are leading indicators for a positive study.
Randomized Trial on GvHD Prophylaxis with or without Anti-Human T-Lymphocyte Immunoglobulin ATG-Fresenius (ATG-F) in Allogeneic Hematopoietic Cell Transplantation from Matched Unrelated Donors: Final Long-Term Results after 8.6 Years Median Follow-up
Authors: Jürgen Finke, Claudia Schmoor, Wolfgang A Bethge, Hellmut Ottinger, Matthias Stelljes, Liisa Volin, Dominik Heim, Hartmut Bertz, Olga Grishina, Gerard Socie
Journal: Blood (2015)
Effect of Reduction of Iron (Fe) Stores on Cardiovascular and Cancer Outcomes in Patients with Advanced Peripheral Arterial Disease (PAD): VA Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST).
Authors: Leo R. Zacharski, Bruce Chow, Paula Howes, Philip Lavori, Galina Shamayeva, John Baron, Ronald Dalman, David Malenka, Keith Ozaki
Journal: Blood (2006)
A randomized, double-blind, placebo-controlled study of ibrutinib, a Bruton tyrosine kinase inhibitor, with nab-paclitaxel and gemcitabine in the first-line treatment of patients with metastatic pancreatic adenocarcinoma (RESOLVE).
Authors: Margaret A. Tempero, Lisa M Coussens, Lawrence Fong, Robert Manges, Priyanka Singh, Yunfeng Li, George W. Cole, Danelle Frances James, Josep Tabernero
Journal: Journal of Clinical Oncology (2016)

TPS2601 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and short survival. Nab-paclitaxel/gemcitabine (Nab-P/GCB) is a preferred front-line treatment regimen. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (ibr) demonstrates antitumor activity in preclinical PDAC models, due in part to modulation of the tumor microenvironment. Ibr treatment inhibits mast-cell degranulation and decreases tumor-associated inflammation and desmoplasia; simultaneously, ibrutinib enhances the presence and activity of cytotoxic T cells in tumors (Affara et al, Cancer Cell, 2014; Masso-Valles et al, Cancer Res, 2015; Gunderson et al, Cancer Discov, 2015). This study will evaluate the efficacy of ibr in combination with Nab-P/GCB. Methods: The randomized, multicenter, double-blind, phase 2/3 RESOLVE trial (NCT02436668; PCYC-1137-CA) compares ibr vs. placebo, in combination with Nab-P/GCB, in approximately 320 patients with previously untreated metastatic pancreatic carcinoma. Eligibility criteria include confirmed metastatic pancreas carcinoma within 6 weeks of randomization; adequate organ function; and Karnofsky performance score ≥ 70. Key exclusion criteria include previous treatment (chemotherapy for primary PDAC, BTK inhibitor), and history of stroke or intracranial hemorrhage within 6 months. Patients will be randomized to oral ibr (560 mg) or matched placebo given daily in combination with Nab-P (125 mg/m2) and GCB (1,000 mg/m2) on days 1, 8, and 15 of a 28-day cycle until disease progression or treatment is no longer tolerated. A safety run-in phase evaluates the ibr combination prior to the randomization phase of the study. The primary endpoint is progression-free survival; secondary endpoints include overall survival and safety. Enrollment in the trial is ongoing. Results: N/A Conclusions: N/A Clinical trial information: NCT02436668.
Islet Transplantation for Hypoglycemia Unawareness/Severe Hypoglycemia: Caveat Emptor
Authors: David M. Harlan
Journal: Diabetes Care (2016)

Current estimates are that 1.25 million Americans have type 1 diabetes (T1D) (1) caused by the gradual loss of nearly all pancreatic insulin-producing β-cells via a presumed T cell–mediated autoimmune process (2). Eventually, all with T1D display severely impaired endogenous insulin production (3) and are dependent upon injected insulin for survival. Because subcutaneously administered insulin displays sluggish “on” and delayed “off” kinetics compared with that from pancreatic β-cells, the glycemic control patients achieve using subcutaneous insulin is suboptimal. For too many individuals, chronic episodic hypoglycemia dulls the typical compensatory responses, leading to impaired hypoglycemia awareness. Absent the usual warning symptoms of a blood glucose too low to sustain higher cognitive functions, such individuals are susceptible to severe hypoglycemic events defined as those requiring assistance from others to recover. Some die as a result of severe and prolonged hypoglycemia (4). Severe hypoglycemia occurs with alarming frequency among patients with T1D (5).

Scientists have long dreamed of restoring endogenous insulin production for those with T1D. One approach has been allogeneic pancreas transplantation. However, most pancreatic tissue makes digestive enzymes, and any damage to the organ can lead to leakage and potentially serious complications. In the 1970s, investigators reasoned that isolated pancreatic islets (only about 2% of the pancreatic mass) might be transplanted via a percutaneous cannula avoiding surgical and other complications associated with pancreas transplantation (6).

Early clinical islet transplantation results, however, were disappointing (7). Then in 2000, Shapiro et al. (8) reported seven consecutive T1D patients achieving 1-year insulin independence following islet transplantation, but serious issues remained. For instance, the only currently viable islet source is cadaveric donors. In 2015, the U.S. had only ∼9,000 such donors, of which ∼1,300 were deemed suitable for pancreas transplantation (9). Also, islets suitable for transplant are successfully isolated from approximately …
In older adults, macrolide antibiotics were not linked to increased risk for ventricular arrhythmia
Authors: Henry S. Sacks
Journal: Annals of Internal Medicine (2016)

ACP Journal Club21 June 2016In older adults, macrolide antibiotics were not linked to increased risk for ventricular arrhythmiaHenry S. Sacks, PhD, MDHenry S. Sacks, PhD, MDIcahn School of Medicine at Mount Sinai, New York, New York, USA (H.S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2016-164-12-068 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationTrac MH, McArthur E, Jandoc R, et al. Macrolide antibiotics and the risk of ventricular arrhythmia in older adults. CMAJ. 2016;188:E120-9. https://pubmed.ncbi.nlm.nih.gov/26903359Clinical Impact RatingsGIM/FP/GP: Cardiology: Infectious Disease: References1 Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72. [PMID: 17278083] Google Scholar2 Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA. 2009;302:758-66. [PMID: 19690308] Google Scholar3 Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366:1881-90. [PMID: 22591294] Google Scholar4 Jespersen CM, Als-Nielsen B, Damgaard M, et al; CLARICOR Trial Group. Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial. BMJ. 2006;332:22-7. [PMID: 16339220] Google Scholar Author, Article, and Disclosure InformationAffiliations: Icahn School of Medicine at Mount Sinai, New York, New York, USA (H.S.S.)This article was published at Annals.org on 7 June 2016. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 June 2016Volume 164, Issue 12Page: JC68KeywordsAntibioticsArrhythmiaElderlyErythromycinFood and Drug AdministrationHealth careMortalityObservational studiesOutpatientsUpper respiratory tract infections ePublished: 21 June 2016 Issue Published: 21 June 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Comparison between Three Promising ß-emitting Radionuclides, <sup>67</sup>Cu, <sup>47</sup>Sc and <sup>161</sup>Tb, with Emphasis on Doses Delivered to Minimal Residual Disease
Authors: Christophe Champion, Michele A. Quinto, Clément Morgat, Paolo Zanotti-Fregonara, Elif Hindié
Journal: Theranostics (2016)

Radionuclide therapy is increasingly seen as a promising option to target minimal residual disease. Copper-67, scandium-47 and terbium-161 have a medium-energy β(-) emission which is similar to that of lutetium-177, but offer the advantage of having diagnostic partner isotopes suitable for pretreatment imaging. The aim of this study was to compare the efficacy of (67)Cu, (47)Sc and (161)Tb to irradiate small tumors.The absorbed dose deriving from a homogeneous distribution of (67)Cu, (47)Sc or (161)Tb in water-density spheres was calculated with the Monte Carlo code CELLDOSE. The diameters of the spheres ranged from 5 mm to 10 µm, thus simulating micrometastases or single tumor cells. All electron emissions, including β(-) spectra, Auger and conversion electrons were taken into account. Because these radionuclides differ in electron energy per decay, the simulations were run assuming that 1 MeV was released per µm(3), which would result in a dose of 160 Gy if totally absorbed.The absorbed dose was similar for the three radionuclides in the 5-mm sphere (146-149 Gy), but decreased differently in smaller spheres. In particular, (161)Tb delivered higher doses compared to the other radionuclides. For instance, in the 100-µm sphere, the absorbed dose was 24.1 Gy with (67)Cu, 14.8 Gy with (47)Sc and 44.5 Gy with (161)Tb. Auger and conversion electrons accounted for 71% of (161)Tb dose. The largest dose differences were found in cell-sized spheres. In the 10-µm sphere, the dose delivered by (161)Tb was 4.1 times higher than that from (67)Cu and 8.1 times that from (47)Sc.(161)Tb can effectively irradiate small tumors thanks to its decay spectrum that combines medium-energy β(-) emission and low-energy conversion and Auger electrons. Therefore (161)Tb might be a better candidate than (67)Cu and (47)Sc for treating minimal residual disease in a clinical setting.
An miRNA-mediated therapy for SCA6 blocks IRES-driven translation of the <i>CACNA1A</i> second cistron
Authors: Yu Miyazaki, Xiaofei Du, Shin-ichi Muramatsu, Christopher M. Gomez
Journal: Science Translational Medicine (2016)

Selective translational blockade of the CACNA1A second cistron using miRNAs may have potential for treating spinocerebellar ataxia type 6.
Social Paternalism in a Communitarian Context: Enhancing Individuals' Moral Deliberation Through a Communal “Moral Voice”
Authors: Vardit Ravitsky
Journal: The American Journal of Bioethics (2016)

The case of the de-ICD (Pullman and Hodgkinson 2016), in which a young man is rejecting a lifesaving intervention, insisting upon the removal of his implantable cardioverter defibrillator (ICD), pr...
CBIO-37DYNAMIC ROLE OF GTP-ENERGY METABOLISM IN GLIOMAGENESIS: DIAGNOSTIC AND THERAPEUTIC APPLICATIONS
Authors: Satoshi Kofuji, Mikako Warren, Kazutaka Sumita, Akiyoshi Hirayama, Annmarie Ramkissoon, Akshiv Malhotra, Hirofumi Yoshino, Luke Pater, Yair Gozal, Steven Gogela, Ady Kendler, Trisha Wise, Richard Curry, Ronald Warnick, Hiroaki Wakimoto, Biplab DasGupta, Lionel Chow, Tomoyoshi Soga, Craig Horbinski, Atsuo Sasaki
Journal: Neuro-Oncology (2015)

Identification of altered metabolic pathways in glioma, compared to primary glial tissue, has the potential to aid in the development of diagnosis and targeted therapies for glioma, and would increase our understanding of the malignant nature of glioma. Alterations in glucose metabolism in gliomas have been previously described. However, it remains unknown whether other metabolic alterations could serve as diagnostic indicator due to the lack of an identifying molecular marker. Using pathological, biochemical, and metabolomics analyses, we discovered a dramatic increase in the metabolism of GTP (guanosine triphosphate), an essential energy molecule for cell proliferation, in various glioma stages. We subsequently characterize the molecular mechanism underlying this switch in GTP metabolism. We also present data that a simple immunohistochemical assay can detect this switch in GTP metabolism and potentially serves as a functional marker for metabolic reprogramming of gliomas. Our data suggest that alternate GTP metabolic pathway is a potential novel therapeutic target for glioma.
Authors’ reply. Spotlight on measles 2010: Timely administration of the first dose of measles vaccine in the context of measles outbreak in France
Authors: D Floret
Journal: Eurosurveillance (2010)

Preview this article: Authors’ reply. Spotlight on measles 2010: Timely administration of the first dose of measles vaccine in the context of measles outbreak in France, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/15/41/art19686-en-1.gif
How clinical characteristics of recurrent/metastatic salivary gland malignancies (RMSGM) treated with first line chemotherapy (CT) impact on survival: multivariate analysis of 108 cases
Authors: M. Airoldi, M. Garzaro, M. Ceccarelli, C. Monagheddu, F. Pedani, E. Bellini, G. Fora, C. Bartoli, L. Raimondo, G. Pecorari
Journal: Annals of Oncology (2015)
Modified Dose Escalation Of Ruxolitinib: A Feasible Therapeutic Approach In The Management Of Myelofibrosis
Authors: Ali Tabarroki, Daniel Lindner, Valeria Visconte, Heesun J. Rogers, John Desamito, Hien K. Duong, Alan E. Lichtin, Anjali S. Advani, Ronald M. Sobecks, Tracy Cinalli, Kristin Dodd, Jing Ai, Yogen Saunthararajah, Matt Kalaycio, Brady L. Stein, Mikkael A. Sekeres, Ramon V. Tiu
Journal: Blood (2013)
Phase II trial of panitumumab (P) plus mytomicin C (M), 5-fluorouracil (5-FU), and radiation (RT) in patients with squamous cell carcinoma of the anal canal (SCAC): Safety and efficacy profile—VITAL study, GEMCAD 09-02 clinical trial.
Authors: Jaime Feliu, Rocio Garcia-Carbonero, Jaume Capdevila, Inmaculada Guasch, Vicente Alonso, Carlos Lopez, Pilar Garcia-Alfonso, Carmen Castañon, Laura Cerezo, Isabel Sevilla, Carles Conill, Begona Quintana-Angel, Maria Elena Sanchez, Jose Lopez-Torrcilla, Ismael Ghanem, Juan Maurel
Journal: Journal of Clinical Oncology (2014)

4034 Background: Standard of care for SCAC has remained unchanged over the past 4 decades. More than 80% of these tumors overexpress the EGFR receptor and <5% present KRAS mutations (Van Damme, BMC 2010). We therefore initiated a multicenter phase II study (NCT01285778) to assess the efficacy and tolerability of adding the EGFR inhibitor panitumumab to the standard M/5FU/RT regimen in patients with non-metastatic SCAC. Methods: Patients received P (6 mg/kg on day 1, every 2 weeks for 8 weeks), M (10mg/m2 q28 days x2) and 5-FU (1000mg/m2/day IV infusion days 1-4 q 28 days x 2) concurrently with RT 45 Gy (1,8 Gy per fraction) to the primary tumor, mesorectal, iliac and inguinal nodes, followed by a boost of 10-15 Gy to the primary tumor and affected lymph nodes. The trial was designed to include 58 pts with stage >T2N0 to have 80% power to detect an increment of 3y-DFS rate from 50% (Ajani, JAMA 2008) to 70%. Results: Between 1/2011 and 11/2013, 58 pts were accrued. To date, results of 36 patients are available (56% female, median age 54 years, VIH positive 6%, ECOG PS: 0 (44%)/1 (53%)/2 (3%), stage I (3%)/II (25%)/IIIA (19%)/IIIB (50%). Thirty-three (92%) patients developed G3/4 adverse events (Table 1). There were no toxic deaths. At 8 weeks, 56% pts experienced CR; 36% persistent but not progressive disease and 8% disease progression. At 24 weeks 55% had CR, 6% persistent but not progressive disease; 19% disease progression, and 20% had not been evaluated. Conclusions: The addition of P to M/5-FU/RT is a tolerable regimen with a good compliance and an acceptable safety profile. Full data of toxicity and post-treatment CR rate will be reported at ASCO Meeting. Clinical trial information: NCT01285778. Adverse events grade 1-2 no. patient (%) Adverse events grade 3 no. patient (%) Adverse events grade 4 no. patient (%) Anemia 5 (14%) 3 (8%) Neutropenia 4 (11%) 7 (19%) 3 (8%) Febril neutropenia 2 (6%) 2 (6%) Trombopenia 4 (11%) 2 (6%) Rash 28 (78%) 2 (6%) Radiodermatitis 11 (26%) 12 (33%) 2 (6%) Diarrhea 22 (61%) 8 (22%) 2 (6%) Vomiting 8 (22%) 1 (3%) Stomatitis 7 (19%) 1 (4%) Fatigue 17 (47%) 2 (6%) Pain 10 (28%) 3 (8%) Hypomagnesemia 8 (22%)
Scoring System Using Age, C-Reactive Protein, Hemoglobin, and Albumin (ACHA) For Predicting Outcomes Of Diffuse Large B-Cell Lymphoma In The Rituximab-Era
Authors: Hirotsugu Ariizumi, Bungo Saito, Eisuke Shiozawa, Yui Uto, Norimichi Hattori, Kouji Yanagisawa, Hidetoshi Nakashima, Hiroshi Harada, Hiraku Mori, Tsuyoshi Nakamaki
Journal: Blood (2013)
MX HOMOLOGOUS PROTEIN IN MONONUCLEAR CELLS FROM PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Peter von Wussow, Detlef Jakschies, Heinz Hochkeppel, Michel Horisberger, Klaus Hartung, Helmuth Deicher
Journal: Arthritis & Rheumatology (1989)

The 76-kd human interferon (IFN)-induced MX protein is the homolog to the murine protein, which is necessary and sufficient to provide adequate resistance to influenza virus infection in murine cells and in mice. Fifty-one patients with systemic lupus erythematosus (SLE) were screened for the presence of the MX homolog in mononuclear cells and for IFN and anti-IFN antibodies in serum. In 47 of 51 patients, significant levels of the MX homolog were found, while only 15 of 51 patients had measurable alpha-IFN in their serum. The IFN activity found in these sera was characterized as a partially acid-labile alpha-IFN, by means of acid-stability cross-reactivity on heterologous cells, trypsin sensitivity, and neutralization by homologous or heterologous antisera. Four of the patients had no detectable MX homolog in their leukocytes; 3 of these 4 possessed an anti-alpha-IFN antibody that was able to neutralize both a natural alpha-IFN preparation and the acid-labile IFN in SLE sera. Also, acid-labile alpha-IFN-containing SLE sera induced the MX homolog in vitro in mononuclear cells from healthy donors. These observations suggest that endogenously produced alpha-IFN is responsible for the observed induction of the MX homolog in SLE and that the IFN system is activated in more than 90% of SLE patients.
D6-07: A seventy two gene signature and survival in completely-resected non-small-cell lung cancer (NSCLC)
Authors: Nico van Zandwijk, Jacek Jassem, Giuseppe Giaccone, Henrik Dienemann, Thomas Muley, Jacek Niklinski, Egbert Smit, Miroslaw Kozlowski, Amelia Szymanowska, Sjaak Burgers
Journal: Journal of Thoracic Oncology (2007)
Doctors give patients potentially harmful procedures at end of life, global review finds
Authors: Ingrid Torjesen
Journal: BMJ (2016)

More than a third of dying elderly patients receive invasive treatments that are unlikely to benefit them and could even be harmful in the final weeks of life, a large global review published in the International Journal for Quality in Health Care has found.1

The review, led by researchers at the University of New South Wales in Sydney, Australia, reviewed 38 studies published from 1995 to 2015 …