tbuckley/cabot-search huggingface dataset:
Abstract 14578: Impact of Cystatin C and Microalbuminuria on Cognitive Impairment in the Population of Community-dwelling Japanese
Authors: Shoko Kono, Hisashi Adachi, Mika Enomoto, Ako Fukami, Eita Kumagai, Sachiko Nakamura, Yume Nohara, Nagisa Morikawa, Erika Nakao, Akiko Sakaue, Tomoko Tsuru, Yoshihiro Fukumoto
Journal: Circulation (2016)

Introduction: Cognitive impairment is an important element, which prescribes our healthy life, and the evaluation is an urgent task in the modern society. But it is difficult to estimate the early ...
PTH-007 Real world experience with rfa/emr in early oesophageal neoplasia
Authors: H Khan, S Cochrane
Journal: Endoscopy (2017)

<h3>Introduction</h3> Endoscopic resection and ablation treatment is the standard of care for barretts oesophagus and related early neoplasia. To evaluate the real world experience with EMR and RFA treatment at a single centre outside of clinical trials. <h3>Method</h3> Data was evaluated from a prospectively maintain charts of patients undergoing RFA/EMR treatment for Barretts and Early Oesophageal Cancer (EOC) (T1a and T1b). All patients with Barretts dysplasia referred through MDT from 2010–2015 were included in the study. <h3>Results</h3> A total of 91 patients The mean age of the patients undergoing RFA/EMR is 72±8, (Range: 47–92) years with predominance of male population (85%). The most common reason for referral was HGD (58%) followed by LGD (17%), T1a (16%), T1b (7%) and squamous dysplasia (2 and ). EMR was performed in in 75/91 (82%) patients in the study mostly in OEC patients (100%) followed by HGD (78%) and LGD (45%) patients. The disease was upstaged in 20% of study patients with 12 patients referred with HGD upstaged to T1a and 3 patients to T1b. Upstaging to HGD was observed in 3 patients with LGD. Only 3 patients had their disease down staged (x2: T1a to HGD and x1: HGD to LGD). RFA was performed in majority of the patients in our study (86.4%, n=76) with median RFA sessions of 2 (Range:1–6). The proportion of patients having RFA performed with final diagnosis of LGD, HGD, T1a and T1b was 92%, 95% and 91% and 30% respectively. A complete response (CR) defined as complete endoscopic and histological eradication of barretts oesophagus after HALO procedure was seen in 88% patients who completed the study (n=68). The excluded patients included those who did not opt for further RFA (n=6) sessions and patients which died of unrelated deaths (n=2). The CR is 100% in patients with LGD and T1a and 79% in HGD group. Out of 9 patients with T1b cancer, 7 had oesophagectomy done with none of the patient having cancer in resected specimen or had disease recurrence including 1 patient who had T1N1 cancer. CR was mostly seen in patients with prior EMR than who did not (79% vs. 21%). In all the non-CR (n=6), 80% had Barretts&gt;6 cms and 100% of incomplete responders had HGD. Nine patients (10%) had complications from HALO procedure with 6 patients requiring endoscopic dilatation of post RFA oesophageal stricture after CR and 2 having ulceration at previous RFA site precluding further RFA. Post RFA stricture was seen mostly in LGD patients than in HGD patients (23% vs. 5%) and 80% of these patients had a prior EMR. 1 patient had a suspected oesophageal perforation after a rescue EMR which was successfully sealed by OVESCO clip. There was no procedure related deaths. <h3>Conclusion</h3> RFA is a safe and effective procedure for management of early oesophageal neoplasia. <h3>Disclosure of Interest</h3> None Declared
Family court judge “ashamed” that NHS cannot find bed for suicidal teenager
Authors: Clare Dyer
Journal: BMJ (2017)

The UK will have “blood on its hands” if the NHS cannot find an immediate place for a 17 year old woman at acute risk of suicide, the senior family court judge in England and Wales has said.

James Munby, president of the High Court’s family division, said that he felt “ashamed and embarrassed ” that no place had been found for the woman on her release from youth custody on 14 August. Staff looking after her in a secure unit, where she was …
Intérêt de l’endoscopie haute résolution et de la chromoscopie dans la détection de la métaplasie intestinale et de la dysplasie sur endobrachyoesophage.
Authors: F Soussi, B Terris, Y Allanore, A Kahan, S Chaussade
Journal: Endoscopy (2004)

But: Le diagnostic d’endobrachy-oesophage (EBO) repose sur l’existence d’une métaplasie intestinale (MI) à l’examen histologique. L’endoscopie standard ne permet pas le diagnostic macroscopique de MI ou de dysplasie sévère et les recommandations actuelles reposent sur un protocole biopsique planimétrique souvent long et à risque d’erreur d’échantillonnage. L’endoscopie haute résolution (EHR) associée à la chromoscopie par acide acétique ou bleu de méthylène a été récemment proposée pour améliorer le diagnostic de MI. Nous rapportons les résultats préliminaires d’une étude évaluant les résultats de l’EHR associée à la chromoscopie par acide acétique puis bleu de méthylène dans le diagnostic de MI et de dysplasie sévère sur EBO. Patients et Méthodes: Neuf patients (4 hommes, 5 femmes, âge médian: 57 ans, extrêmes: 36–74 ans) suivis pour EBO court dont 4 avec une sclérodermie associée ont été inclus. Le protocole endoscopique (sous sédation complète chez 8 patients, et sur pièce opératoire fraîche chez un patient opéré pour adénocarcinome sur EBO) comportait un examen standard, puis en haute résolution (appareil Fujinon EC 450 ZH, grossissement 80 fois) avant et après instillation d’acide acétique à 1% par cathéter spray puis par coloration par du bleu de méthylène à 0,5%. Un capuchon spécialement dessiné pour ce protocole était systématiquement utilisé pour maintenir une distance constante de 2 mm entre l’endoscope et la surface de la muqueuse. Une à quatre zones par patient étaient analysées puis biopsiées. L’aspect observé était comparé à l’anatomopathologie. Chaque examen était enregistré sur magnétoscope numérique. Résultats: L’EHR couplée à la chromoscopie a permis d’identifier 3 aspects de la surface de la muqueuse (pit-pattern): type 1, aspect régulier et homogène; type 2, aspect villeux ou cérébriforme; type 3, aspect désorganisé avec disparition de l’aspect cérébriforme. Vingt-trois zones ont été analysées: 8 de type 1, 13 de type 2 et 2 de type 3. La coloration par l’acide acétique permettait de reconnaître ces 3 profils. L’utilisation du bleu de méthylène après l’acide acétique n’améliorait pas la visualisation du pit-pattern. La présence de MI selon l’aspect observé était le suivant: type 1, 0/8; type 2, 13/13 (100%); type 3, 0/2. L’existence d’une dysplasie sévèreétait répartie ainsi: type 1, 0/8; type 2, 0/13; type 3, 2/2 (100%). Conclusion: Dans cette série, 1) l’EHR couplée à la chromoscopie est efficace dans la détection de la MI; 2) cette technique apparaît réalisable en routine; 3) après confirmation sur un effectif plus large, l’EHR avec chromoscopie pourrait être utile dans la détection des zones de dysplasie sévère.
Left Ventricular Filling Pressure: An Independent Determinant of Post- Exercise Ventricular Dyssynchrony in Systolic Heart Failure Patients with Narrow Qrs Complex
Authors: 王怡智, 游治節, 黃瑞仁, 賴凌平, 林隆君, 蔡佳醍, 曾春典, 林俊立, Yi-Chih Wang, Chih-Chieh Yu, Juey-Jen Hwang, Ling-Ping Lai, Lung-Chun Lin, Chia-Ti Tsai, Chuen-Den Tseng, Jiunn-Lee Lin
Journal: Journal of the American College of Cardiology (2007)
03.06 Mer-mediated efferocytosis tempers arthritis by preventing neutrophil littering in the joint
Authors: Claire EJ Waterborg, Silke Beermann, Carla V Rothlin, Marije I Koenders, Miranda B Bennink, Peter M van der Kraan, Peter LEM van Lent, Frank HJ van den Hoogen, Greg Lemke, Fons AJ van de Loo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis is characterised by an inflammatory response in synovial joints, showing a predominant influx of neutrophils. These cells have a relative short life span and many of them undergo apoptosis. If they are not cleared, they undergo secondary necrosis and release their cell content which promotes inflammation. One receptor involved in the uptake of apoptotic cells, called efferocytosis, is the Mer tyrosine kinase receptor. In addition, Mer is involved in an anti-inflammatory natural feedback mechanism. One of the ligands for Mer is Protein S (Pros1). The local role of Mer during arthritis, however, has not been elucidated. <h3>Materials and methods</h3> One day after the booster injection of collagen-induced arthritis in mice, a commercially available antibody against Mer was injected intravenously or an adenovirus overexpressing <i>Pros1</i> was injected intra-articularly into the knee joints. Mice were euthanized at day 30 or 36, respectively. The KRN serum transfer model was induced by two injections of arthritic K/BxN serum on day 0 and 2 in either Mer-deficient mice or in wild type mice that overexpress <i>Pros1</i> in their knee joints. Mice were euthanized at day 7 or day 14, respectively. From all mice, serum was taken for cytokine profiling and knee joints were isolated for histology and immunohistochemistry. <h3>Results</h3> Overexpression of the Mer ligand <i>Pros1</i> resulted in reduced production of inflammatory mediators by the synovial cells of arthritic mice in addition to diminished joint pathology. Conversely, inhibiting Mer-mediated efferocytosis by either antibodies or <i>Mertk</i> ablation resulted in aggravation of arthritis, exhibited by increased inflammation and tissue destruction. Additionally, these mice had an increased percentage of active Caspase-3 positive cells in their joints, a marker for apoptotic cells, and higher serum levels of IL-16C, a cytokine released by secondary necrotic neutrophils. On the contrary, <i>Pros1</i> overexpression led to reduced numbers of apoptotic and secondary necrotic neutrophils. <h3>Conclusions</h3> To conclude, activation of Mer plays a unique, protective role in controlling the severity and resolution of inflammation in experimental arthritis. Our data suggest that promoting Mer-mediated uptake of apoptotic cells in the arthritic joint might be therapeutically beneficial.
02.09 Identification of a novel pro-inflammatory T cell epitope from his-trna-synthetase associated with interstitial lung disease in anti-jo-1 positive patients
Authors: Angeles Shunashy Galindo-Feria, Inka Albrecht, Antonella Notarnicola, Maryam Dastmalchi, Anatoly Dubnovitsky, Tatiana Sandalova, Genadiy Kozhukh, Lars Rönnblom, Adnane Achour, Vivianne Malmström, Ingrid E Lundberg
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Previous studies have demonstrated that CD4<sup>+</sup> T cells from peripheral blood of anti-histidyl-tRNA synthetase (anti-His-tRNA) also known as anti-Jo-1 positive patients proliferate in response to stimulation with full-length His-tRNA and a N-terminal fragment comprising residues 1–60. In this study we present a novel epitope that identifies patients with moderate-severe interstitial lung disease (ILD). <h3>Materials and Methods</h3> Sixteen anti-Jo-1 positive patients with antisynthetase syndrome followed at the Karolinska University Hospital were enrolled. As controls we included HLA-DRB1*03-positive healthy individual (HCs, n=8). Peripheral blood mononuclear cells were isolated by Ficoll-Hypaque density centrifugation and <i>in vitro</i> stimulated with: a) full length His-tRNA protein; b) a novel HLA-DR*03:01 binding peptide from native His-tRNA; c) an altered peptide ligand (APL) variant of His-tRNA designed to prevent recognition by HLA-DR3/His-tRNA-specific TCRs. T cell activation was assessed by CD40L up-regulation and expression of pro-inflammatory cytokines (IFN-g, IL-2 and IL-17A) by flow cytometry. Clinical and laboratory data were documented and analysed by Student's T test or Mann-Withney U-test. <h3>Results</h3> At the time of blood sampling the patients had a mean age of 58 years (48–83 years), median disease duration of 50 months (11–70 months), MMT8 score 80 (79-80), HAQ 0.25 (0 13-0.75). Eighty-four percent were female, 13/16 patients had ILD and 13/16 had muscle weakness. T cell activation towards the novel His-tRNA peptide was observed in 2/16 anti-Jo-1 positive patients. When stimulating with the APL, no T cell activation was observed in one of the patients that was reactive for the peptide. For evaluation of pro-inflammatory features, the His-tRNA-specific T cells displayed significant up-regulated levels of IFN-γ (p&lt;0.05) compared to HC (p&lt;0.05). Additionally, 1/8 HCs displayed a modest response to both the novel His-tRNA peptide and the full length His-tRNA protein. In this context only IL-2 was observed. The patients that showed an upregulation of CD40L had a moderate-severe clinical progression of ILD. <h3>Conclusion</h3> In this study, we demonstrate the presence of His-tRNA-reactive CD4<sup>+</sup> T cells in peripheral blood from anti-Jo-1 positive patients and a novel His-tRNA peptide, characterised by the expression of IFN-g. This phenotype seemed to correlate to a moderate-severe clinical progression of ILD.
Intrathecal 2-hydroxypropyl-β-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1–2 trial
Authors: Daniel S Ory, Elizabeth A Ottinger, Nicole Yanjanin Farhat, Kelly A King, Xuntian Jiang, Lisa Weissfeld, Elizabeth Berry-Kravis, Cristin D Davidson, Simona Bianconi, Lee Ann Keener, Ravichandran Rao, Ariane Soldatos, Rohini Sidhu, Kimberly A Walters, Xin Xu, Audrey Thurm, Beth Solomon, William J Pavan, Bernardus N Machielse, Mark Kao, Steven A Silber, John C McKew, Carmen C Brewer, Charles H Vite, Steven U Walkley, Christopher P Austin, Forbes D Porter
Journal: The Lancet (2017)
07.08 Contribution of mthfr gene polymorphisms in primary sjögren’s syndrome related lymphomagenesis
Authors: Sofia Fragkioudaki, Adrianos Nezos, Aggeliki A Saetta, Nikolaos Drakoulis, Vasilis L Souliotis, Petros P Sfikakis, Athanasios G. Tzioufas, Michael Voulgarelis, Michael Koutsilieris, Mary K Crow, Haralampos M Moutsopoulos, Clio P Mavragani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Among systemic autoimmune disorders, primary Sjogren's syndrome (pSS) has the highest risk for non-Hodgkin lymphoma (NHL) development. Two common polymorphisms, the C677T and A1298C, of the methylene-tetrahydrofolate reductase (MTHFR) gene, an enzyme essential in DNA synthesis, repair and methylation, have been reported to influence susceptibility to both autoimmune diseases and NHL. The aim of this study was to investigate the possible contribution of MTHFR variants in pSS-related lymphomagenesis. <h3>Materials and methods</h3> 262 pSS patients without NHL (pSS), 94 pSS patients with NHL [pSS-lymphoma, of which 75 had mucosa-associated lymphoid tissue (MALT) and 19 non-MALT] as well as 600 healthy controls (HC) of similar age and sex distribution were genotyped by PCR-based assays for the detection of the MTHFR gene polymorphisms (C677T and A1298C). To further evaluate the functional consequences of MTHFR variants, global DNA methylation levels were assessed by bisulphite pyrosequencing of the LINE-1 retroelement promoter in genomic DNA derived from 55 salivary gland tissues from pSS patients. Additionally, DNA double strand breaks -a marker of intrinsic DNA damage as a result of defective DNA repair- were determined in peripheral blood mononuclear cells isolated from 13 pSS patients, using comet assay. <h3>Results</h3> The frequency of MTHFR polymorphisms did not differ among pSS, pSS-lymphoma patients and HC. However, further data analysis according to the lymphoma subtype revealed increased frequency of C677T TT genotype and T allele in the pSS non-MALT group compared to pSS patients [OR(95% CI): 2.13 (1.06–4.30), p=0.03] and HC [OR(95% CI): 1.93 (1.01–3.68), p=0.04], respectively. On the other hand, the prevalence of the A1298C C allele was reduced among pSS non-MALT individuals compared to both pSS patients [OR(95% CI): 0.29 (0.10–0.83), p=0.01] and HC [OR(95% CI): 0.25 (0.09–0.70), p=0.004]. Of interest, MTHFR C677T TT genotype was associated with reduced global DNA methylation levels (TT vs CC: 71.57±5.43 vs 75.56±4.13, p=0.045), while MTHFR A1298C AA genotype carriers displayed elevated comet assay units levels, implying intrinsic DNA damage (AA vs AC: 14.41±4.38 vs 7.89±5.54, p=0.04). <h3>Conclusions</h3> The current report supports the contribution of MTHFR genetic variants in non-MALT NHL development in the setting of pSS, possibly through defective DNA methylation and repair mechanisms.
Breast Cancer Immunotherapy: Facts and Hopes
Authors: Leisha A. Emens
Journal: Clinical Cancer Research (2017)

Abstract Immunotherapy is revolutionizing the management of multiple solid tumors, and early data have revealed the clinical activity of programmed cell death-1/programmed death ligand-1 (PD-1/PD-L1) antagonists in small numbers of patients with metastatic breast cancer. Clinical activity appears more likely if the tumor is triple negative, PD-L1+, and/or harbors higher levels of tumor-infiltrating leukocytes. Responses to atezolizumab and pembrolizumab appear to be durable in metastatic triple-negative breast cancer (TNBC), suggesting that these agents may transform the lives of responding patients. Current clinical efforts are focused on developing immunotherapy combinations that convert nonresponders to responders, deepen those responses that do occur, and surmount acquired resistance to immunotherapy. Identifying biomarkers that can predict the potential for response to single-agent immunotherapy, identify the best immunotherapy combinations for a particular patient, and guide salvage immunotherapy in patients with progressive disease are high priorities for clinical development. Smart clinical trials testing rational immunotherapy combinations that include robust biomarker evaluations will accelerate clinical progress, moving us closer to effective immunotherapy for almost all patients with breast cancer. Clin Cancer Res; 24(3); 511–20. ©2017 AACR.
Doctors are told to use hepatitis B vaccine sparingly because of global shortage
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Doctors have been told to use the hepatitis B vaccine sparingly, and only for people at highest immediate risk of infection, because of a global shortage.

Public Health England—with NHS England, the Department of Health, and the manufacturer GlaxoSmithKline—said that the measures are expected to last until the beginning of 2018.

Guidance from Public Health England says that the highest priority for vaccination are babies born to mothers infected with hepatitis B, because they have the highest risk of …
Association of Dissemination of an Educational Communication Tool With Docusate Administration
Authors: Darren Pasay, Micheal Guirguis, Rhonda Shkrobot, Jeremy Slobodan, Lauren Bresee
Journal: JAMA Internal Medicine (2017)

A clear message and call to action can affect the use of a medication with limited efficacy.To assess the association of the dissemination of an educational document about the lack of efficacy of docusate with docusate administration and whether changing docusate administration was associated with a change in administration of comparable laxatives.In this quasi-experimental, pre-post study of all acute care and continuing care facilities serviced by Alberta Health Services in Alberta, Canada, an interrupted time series analysis was performed to examine the association of an educational communication tool with docusate administration from June 1, 2014, through May 31, 2016.A Drugs & Therapeutics Backgrounder was disseminated to all pharmacists in December 2014. Backgrounders are academic detailing tools to assist pharmacists in supporting drug stewardship and are supplemented by online, interactive webinars.This study examined whether a decrease in docusate administration across the organization occurred after release of the backgrounder. Messaging in the backgrounder stated that, unless clinically necessary, docusate should not be replaced by another medication. This study assessed whether that message was accepted by measuring administration of comparable laxatives. Study medication administration is reported as defined daily doses (DDDs) per 1000 inpatient-days (PDs). Rates were compared for the 6 months before the intervention and 3, 6, 12, and 18 months after intervention.Among the 111 acute care facilities (8500 beds) and 24 000 long-term care beds of the Alberta Health Services, predicted docusate administration decreased from preintervention (474 DDDs/1000 PDs) to 3 months (321 DDDs/1000 PDs; 95% CI, 304-465 DDDs/1000 PDs), 6 months (296 DDDs/1000 PDs; 95% CI, 277-456 DDDs/1000 PDs), 12 months (251 DDDs/1000 PDs; 95% CI, 207-499 DDDs/1000 PDs), and 18 months (214 DDDs/1000 PDs; 95% CI, 148-536 DDDs/1000 PDs). Administration of the comparable laxatives did not statistically significantly change (preintervention: 627 DDDs/1000 PDs; 18 months after intervention: 702 DDDs/1000 PDs; 95% CI, 295-694 DDDs/1000 PDs; P = .13).A communication document supported by live presentations was associated with decreased administration of docusate up to 6 months, with a leveling of the association after 1 year. Significant systemic change can be achieved without extensive and complex interventions if the evidence and messaging are aligned.
Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A): two randomised, phase 2, open-label trials
Authors: Edward J Gane, Stephen Pianko, Stuart K Roberts, Alexander J Thompson, Stefan Zeuzem, Eli Zuckerman, Ziv Ben-Ari, Graham R Foster, Kosh Agarwal, Alex L Laursen, Jan Gerstoft, Wei Gao, Hsueh-Cheng Huang, Brian Fitzgerald, Doreen Fernsler, Jerry J Li, Anjana Grandhi, Hong Liu, Feng-Hsiu Su, Shuyan Wan, Zhen Zeng, Huei-Ling Chen, Frank J Dutko, Bach-Yen T Nguyen, Janice Wahl, Michael N Robertson, Eliav Barr, Wendy W Yeh, Rebeca M Plank, Joan R Butterton, Rafael Esteban
Journal: The Lancet. Gastroenterology & hepatology (2017)
Endoplasmic reticulum-mitochondria tethering in neurodegenerative diseases
Authors: Yi Liu, Xiongwei Zhu
Journal: Translational Neurodegeneration (2017)

Endoplasmic reticulum (ER) and mitochondria are tubular organelles with a characteristic "network structure" that facilitates the formation of inter-organellar connections. As a result, mitochondria-associated ER membranes (MAMs), a subdomain of the ER that is tightly linked to and communicates with mitochondria, serve multiple physiological functions including lipid synthesis and exchange, calcium signaling, bioenergetics, and apoptosis. Importantly, emerging evidence suggests that the abnormality and dysfunction of MAMs have been involved in various neurodegenerative disorders including Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. This review will focus on the architecture and function of MAMs and its involvement in the neurodegenerative diseases.