tbuckley/cabot-search huggingface dataset:
Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration
Authors: Lijuan Zhang, Jianhai Du, Sally Justus, Chun-Wei Hsu, Luis Bonet-Ponce, Wen-Hsuan Wu, Yi-Ting Tsai, Wei-Pu Wu, Yading Jia, Jimmy K. Duong, Vinit B. Mahajan, Chyuan-Sheng Lin, Shuang Wang, James B. Hurley, Stephen H. Tsang
Journal: Journal of Clinical Investigation (2016)

Retinitis pigmentosa (RP) encompasses a diverse group of Mendelian disorders leading to progressive degeneration of rods and then cones. For reasons that remain unclear, diseased RP photoreceptors begin to deteriorate, eventually leading to cell death and, consequently, loss of vision. Here, we have hypothesized that RP associated with mutations in phosphodiesterase-6 (PDE6) provokes a metabolic aberration in rod cells that promotes the pathological consequences of elevated cGMP and Ca2+, which are induced by the Pde6 mutation. Inhibition of sirtuin 6 (SIRT6), a histone deacetylase repressor of glycolytic flux, reprogrammed rods into perpetual glycolysis, thereby driving the accumulation of biosynthetic intermediates, improving outer segment (OS) length, enhancing photoreceptor survival, and preserving vision. In mouse retinae lacking Sirt6, effectors of glycolytic flux were dramatically increased, leading to upregulation of key intermediates in glycolysis, TCA cycle, and glutaminolysis. Both transgenic and AAV2/8 gene therapy–mediated ablation of Sirt6 in rods provided electrophysiological and anatomic rescue of both rod and cone photoreceptors in a preclinical model of RP. Due to the extensive network of downstream effectors of Sirt6, this study motivates further research into the role that these pathways play in retinal degeneration. Because reprogramming metabolism by enhancing glycolysis is not gene specific, this strategy may be applicable to a wide range of neurodegenerative disorders.
Midpregnancy and cord blood immunologic biomarkers, HLA genotype, and pediatric celiac disease
Authors: Karl Mårild, Maria Vistnes, German Tapia, Øivind Midttun, Per M. Ueland, Marte K. Viken, Per Magnus, Jens P. Berg, Lars C. Stene, Ketil Størdal
Journal: Journal of Allergy and Clinical Immunology (2016)
FRI0285 Sensitivity To Change of Nailfold Videocapillaroscopy and Relationship with Disease Progression
Authors: J. Avouac, E. Toniolo, G. Lepri, C. Hurabielle, A. Vallet, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Nailfold videocapillaroscopy (NVC) is a simple, non-invasive and inexpensive imaging technique that allows a detailed assessment of skin microcirculation. Although NVC has face and content validity for the detection of microvascular damages related to systemic sclerosis (SSc), its sensitivity to change has not been assessed in detail. <h3>Objectives</h3> Our aim was to determine in a prospective cohort the merit of NVC to detect meaningful changes over time and whether these changes are associated with disease progression. <h3>Methods</h3> A prospective cohort of 140 SSc patients was recruited over a 12-month period and was followed up on an annual basis for 3 years. NVC was performed at inclusion and repeated once a year by four investigators (ET, GL, CH and AV) according to a standardized procedure. NVC pictures were analysed by one investigator (JA) and classified as early, active and late patterns. Organ progression was defined according to validated definitions. The worsening of the Medsger severity scale (from category 1–2 to category 3–4) was considered as a marker of disease progression. <h3>Results</h3> 140 SSc patients were included (111 women, 56±11 year-old, disease duration of 9±8 years). A change of NVC pattern was observed in 29 SSc patients (21%) during the follow-up period.At least 3 annual NVC evaluations were available for each patient. A progression from a normal or early NVC pattern to an active NVC pattern was detected in 15 patients (10%). Patients who progressed to the active NVC pattern were significantly less at risk to develop ischemic digital ulcers (DU) during follow-up (hazard ratio, HR: 0.78, 95% Confidence Interval, CI 0.17–0.95). A progression to a late NVC pattern was observed in 14 patients (10%). Progression to a late NVC pattern was associated with the occurrence of new ischemic DU (HR: 4.51, 95% CI 1.68–12.14), lung vascular progression (HR: 5.12 95% CI 1.23–21.27), progression of skin fibrosis (HR: 3.70, 95% CI 1.14–11.94) and the worsening of Medsger disease severity scale (HR: 4.47, 95% CI 1.63–12.26). <h3>Conclusions</h3> Change of the NVC pattern was observed in 21% of patient with SSc during a follow-up of 3 years. NVC has the ability to detect meaningful changes over time associated with markers of disease progression. Our results support the use of NVC for the routine follow-up of SSc patients in order to improve their risk stratification. NVC might be used in the future to select high-risk patients and change to a late NVC pattern might be regarded as potential surrogate marker for disease severity. <h3>Disclosure of Interest</h3> None declared
PWE-147 The Use of Angiography with A View to Embolisation In Non Variceal Gastrointestinal Haemorrhage Uncontrolled with Endoscopic Therapy, A 10 Year Experience at A Teaching Hospital
Authors: S Esmaily, S Paremal, J Dean, J Greenaway, B Disney
Journal: Gut (2016)

<h3>Introduction</h3> Gastrointestinal (GI) bleeding is a common medical emergency. The incidence is 1.33/1000 population, approximately 85,000 cases/year. The NCEPOD review of GI haemorrhage emphasised the role of embolisation in patients with GI bleeding who have failed endoscopic therapy. Transcatheter arterial embolisation (TAE) has been shown to be as effective as emergency surgery in the treatment of refractory acute non variceal upper GI bleeding (ANVGIB) with reduced 30 day mortality rates. The study aim was to review the utilisation and outcomes of patients undergoing emergency angiography (EA) with a view to embolisation in ANVGIB not amendable to, or controlled by, endoscopic therapy. <h3>Methods</h3> A retrospective analysis of patients undergoing EA for ANVGIB between January 2005 and February 2016 was performed. Patients were identified from endoscopy and radiology databases. Endoscopy reports and discharge letters were reviewed electronically. Successful embolisation was deemed when extravasation had stopped and/or no bleeding post embolisation. <h3>Results</h3> Over the study period, 22412 patients were diagnosed with GI bleeding. 57.9% (12967/22412) had an endoscopy. EA was performed in 107/12967 (0.83%) of patients undergoing endoscopy due to uncontrolled GI bleeding. Mean age was 69 years for males and 74 years for females (range 30–98); 74/107 were male. EA and embolization was performed in hours in 71% of cases and out of hours in 29%. Pre-angiography endoscopy report was available in 86/107 patients. The commonest endoscopic diagnosis was duodenal ulcer which was present in 25.6% (22/86) of the cases. A normal upper GI endoscopy was noted in 20.9% (18/86) of patients. Lower GI bleeding was the cause in 17.4% (15/86) of patients. Other causes included; unidentified bleeding point, dieulafoy lesion, gastric ulcer. Of those patients undergoing angiography 54/106 (50.9%) had TAE. TAE was deemed successful in 90.7% (49/54) of cases. Surgical intervention was necessary in 2/5 of the unsuccessful cases. The 30 day mortality for the patients undergoing angiography with or without intervention was 18/107 (16.8%). 57% (61/107) were alive at 1 year. <h3>Conclusion</h3> The results demonstrate that angiography and embolisation is a valuable tool in the management of GI bleeding not controlled by endoscopic therapy with a high success rate avoiding the need for surgery in the majority of cases. Our figures are comparable to published studies. The results support the need for 24/7 access to interventional radiology which is part of the recommendations from the NCEPOD review of the care received by patients who had a severe gastrointestinal haemorrhage. <h3>Disclosure of Interest</h3> None Declared
Host Interferon gamma Production and STAT-1 Signalling Is Crucial for Minor Antigen Mediated Rejection of High Grade Lymphoma.
Authors: Madhusudhanan Sukumar, Andrea Wilke, Eva Jaeger, Josef Mautner, Joachim Ellwart, Hans-Jochem Kolb, Georg W. Bornkamm, Armin Gerbitz
Journal: Blood (2007)
Early Initiation of Defibrotide in Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Following Hematopoietic Stem Cell Transplantation Improves Day +100 Survival
Authors: Paul G. Richardson, Angela R. Smith, Brandon M. Triplett, Nancy A. Kernan, Stephan A. Grupp, Joseph H. Antin, Leslie E. Lehmann, Maja Miloslavsky, Robin L. Hume, Alison L. Hannah, Bijan Nejadnik, Robert J. Soiffer
Journal: Blood (2015)
Thymoglobulin Decreases the Need for Immunosuppression at 12 Months after Myeloablative and Nonmyeloablative Unrelated Donor Transplantation: CBMTG 0801, a Randomized, Controlled Trial
Authors: Irwin Walker, Kirk R. Schultz, Cynthia L. Toze, Holly Margaret Kerr, John Moore, David Szwajcer, Stephen Ronan Foley, John Kuruvilla, Tony Panzarella, Félix Couture, Jean Roy, Stephen Couban, Gerald Devins, Gizelle Popradi, Stephanie J. Lee, Jason Tay, Thomas J. Nevill, Mohamed Elemary, Genevieve Gallagher
Journal: Blood (2014)
CD38 Regulates Homing and Engraftment of CLL Cells,
Authors: Tiziana Vaisitti, Sara Serra, Valentina Audrito, Chris Pepper, Davide Rossi, Giovanni D'Arena, Luca Laurenti, Antonella Zucchetto, Valter Gattei, Gianluca Gaidano, Fabio Malavasi, Silvia Deaglio
Journal: Blood (2011)
Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy
Authors: Anna Rita Cantelmo, Lena-Christin Conradi, Aleksandra Brajic, Jermaine Goveia, Joanna Kalucka, Andreas Pircher, Pallavi Chaturvedi, Johanna Hol, Bernard Thienpont, Laure-Anne Teuwen, Sandra Schoors, Bram Boeckx, Joris Vriens, Anna Kuchnio, Koen Veys, Bert Cruys, Lise Finotto, Lucas Treps, Tor Espen Stav-Noraas, Francesco Bifari, Peter Stapor, Ilaria Decimo, Kim Kampen, Katrien De Bock, Guttorm Haraldsen, Luc Schoonjans, Ton Rabelink, Guy Eelen, Bart Ghesquière, Jalees Rehman, Diether Lambrechts, Asrar B. Malik, Mieke Dewerchin, Peter Carmeliet
Journal: Cancer Cell (2016)
Efficacy and Safety of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) Therapy with Rituximab Maintenance in Patients with Untreated Low-Grade Follicular Lymphoma.
Authors: John William Sweetenham, Karel Dicke, John Arcaroli, Karen Kogel, Tahir M. Rana, Laura L. Rice
Journal: Blood (2004)
The Effects Of Hydrogen Sulphide On Adipocyte Viability In Human Adipocyte and Adipocyte Derived Mesenchymal Stem Cells Culture Under Ischemic Conditions
Authors: Andac Aykan, Serdar Ozturk, Ferit Avcu, Ismail Sahin, Ali Ugur Ural, Rahsan Ilikci, Selcuk Isik
Journal: Blood (2013)
Left Ventricular Assist Device Induced Coagulation and Platelet Activation and the Effect of Current Anticoagulant Therapy Regimen
Authors: Alexander Service, Walter Jeske, Jeanine M. Walenga, Vicki Escalante, Linda Dusek, Michael Ashbrook, Jeffrey Schwartz, Alain Heroux, Mamdouh Bakhos
Journal: Blood (2012)
Reliable Detection of Abl Tyrosine Kinase Domain Mutations to &lt;1% Using NGS Data Quality Parsing and Corroboration of Overlapping Paired-End Sequences
Authors: Jacqueline Dickson, Nick Kennedy, Leanne M. Cork, Letizia Foroni, Corinne A. Hedgley, Mhairi Copland, Tessa L. Holyoake, Stephen G. O'Brien, Bernard Ramashoye
Journal: Blood (2015)
Human Cord Blood Progenitors with High Aldehyde Dehydrogenase Activity Improve Vascular Density in a Model of Acute Myocardial Infarction
Authors: Claus Sondergaard, David Hess, Dustin Maxwell, Ivana Rosova, Carla Weinheimer, Attila Kovacs, Michael Creer, David Piwnica-Worms, Lene Pederson, Jan Nolta
Journal: Blood (2008)
SAT0485 Prevalence of Autoimmune Diseases in HIV-Infected Patients in Mexico: Table 1
Authors: E. Martín Nares, J.F. Andrade Villanueva, L.A. González Hernández, J.J. Torres Ruiz, D. Gόmez Martín, O. Morado Aramburo
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Autoimmune diseases (AD) in patients with HIV have been observed since the beginning of the HIV/AIDS pandemic. Epidemiologic studies have reported a prevalence of rheumatic and autoimmune manifestations ranging from 1–72%, including only systemic (SAD) and articular AD (AAD), and not organ-specific AD (OSAD)<sup>[1]</sup>. Prevalence of AD in patients with HIV infection in Mexico has not been fully addressed. <h3>Objectives</h3> The aim of this study was to assess the prevalence of AD in HIV-infected patients. <h3>Methods</h3> We performed a retrospective study in two tertiary referral centers in Mexico. All subjects seen from june 15th 2003 to june 15th 2014 with a confirmed diagnosis of HIV infection and a diagnosis of an AD were included. We extracted demographic data, HIV infection history, and AD history from the clinical record <h3>Results</h3> A total of 5876 HIV-infected patients were seen during the study period. Eighty one AD were found in 77 patients (prevalence: 1.31%). Eight (9.9%) were SAD, 12 (14.8%) AAD and 61 (75.3%) OSAD (Table 1). Four patients (5.2%) had 2 AD. Fifty eight were male (75.3%). Mean age at diagnosis of AD was 34.8 years. In twenty two (27.2%) AD preceded HIV infection, in 23 (28.4%) HIV infection was diagnosed simultaneously with the AD, in 36 (44.4%) AD developed after HIV infection. Mean CD4 T lymphocyte count in patients with a simultaneous diagnosis of HIV infection and AD was 287 cel/μl, only one with undetectable viral load; mean CD4 T lymphocyte count in patients who developed AD after HIV infection was 353 cel/μl, half with undetectable viral load. Sixteen patients were classified with AIDS at AD diagnosis. Five (6.2%) AD were a consequence of immune reconstitution inflammatory syndrome (IRIS); prevalence of autoimmune IRIS was 0.08%. Prevalence of HBV and HCV coinfection was 5.2% and 2.6% respectively. Immunosuppressive treatment was used in 87% of patients. <h3>Conclusions</h3> This is the first study to address solely AD without combining non-autoimmune musculoskeletal entities and the largest cohort to date. Prevalence of AD in HIV-infected patients in Mexico was low (1.31%) and OSAD was the most frequent. AD were diagnosed in all stages of HIV infection. Prevalence of HBV and HCV coinfection and autoimmune IRIS was very low. Prospective studies are needed to identify risk factors for the development of autoimmune IRIS. <h3>References</h3> Patel N, Patel N, Espinoza LR. HIV infection and rheumatic diseases: the changing spectrum of clinical enigma. Rheum Dis Clin North Am. 2009;35(1):139–161. <h3>Disclosure of Interest</h3> None declared
Neutrophil extracellular traps formation and degradation rate during autoimmunity - preliminary results
Authors: Michal Pruchniak, Magda Arazna, Urszula Demkow
Journal: European Respiratory Journal (2014)

Friend or foe? This is often asked question when it comes to Neutrophil Extracellular Traps (NETs) studies. At the time of their discovery they were considered to be protectors of our well being. Excellent pathogen fighting skills were described as purely beneficial. But not so long after that it was revealed that they can be responsible for immune system hyperactivity and provoke certain diseases, i.e. acute respiratory distress syndrome (ARDS), alveolar damage or pulmonary edema.  The aim of our study is to evaluate NETs formation magnitude of neutrophils derived from patients with autoimmunity with respect to healthy controls. Moreover NETs degradation rate was also measured.  Neutrophils were obtained from 20 patients with Wegeners Granulomatosis as well as from 20 healthy volunteers. After administration of PMA, a potent Netosis activator, the released NETs were fluorometrically quantified for three hours. In order to check degradation rate in time, to samples containing artificial NETs patients9 sera was added. In addition to kinetic assays microscopical visualisation was also performed.  Quantitative studies showed that neutrophils derived from patients with immune system hyperactivity released approximately 15% more DNA than control group (p  Also NETs degradation rate is slightly diminished (p  Our study shows that neutrophils derived from patients with immune system hyperactivity are more potent to create extracellular trap and also NET-clearance is altered. Thus, we can suspect that exacerbation of autoimmune diseases is connected with this novel cell death type. The clinical significance of this phenomenon is yet to be evaluated.
PWE-071 The Majority of H. Pylori Infected Subjects Have Reduced Intragastric Acidity and Parietal Cell Density which is Most Marked Close to The Gastroesophageal Junction: Abstract PWE-071 Table 1
Authors: D Mitchell, M Derakhshan, A Wirz, C Orange, D Hughes, S Ballantyne, J Going, K McColl
Journal: Gut (2016)

<h3>Introduction</h3> A negative association exists between <i>H. pylori</i> infection and both gastroesophageal reflux disease and oesophageal adenocarcinoma. The great majority of the <i>H. pylori</i> infected population are asymptomatic, so we studied healthy volunteers to determine if the infection is associated with changes to the acid secretory capacity of gastric mucosa which may protect individuals from acid reflux. <h3>Methods</h3> We studied 31 <i>H</i><i>. pylori</i> positive and 29 <i>H</i><i>. pylori</i> negative volunteers, matched for age and gender. Jumbo biopsies were taken at eleven pre-determined gastric locations. High resolution pHmetry (12 sensors at 11 mm intervals) and manometry (36 sensors at 7.5 mm intervals) was performed fasted and after a standardised meal. The position of the squamocolumnar junction, marked with two endoscopically placed radio-opaque clips, was visualised radiologically relative to the probes. The biopsy specimens were scored for inflammation and stained with monoclonal antibody to H<sup>+</sup>/K<sup>+</sup>ATPase for counting parietal cell (PC) density. <h3>Results</h3> In the fasting period, at all sensors more than 1.1 cm below the peak LES pressure the median pH was less acidic in <i>H. pylori </i>positives (Table 1). After a meal, intragastric acidity was less in <i>H. pylori</i> positives compared to negatives at sensors 2.2 to 4.4 cm below the peak LES pressure (all p &lt; 0.05), which are the sensors closest to the gastroesophageal junction (GOJ). Median PC density (IQR) at mid-greater curve of gastric body was 233 (96) for <i>H. pylori</i> positives and 352 (76) for negatives (p &lt; 0.001). PC density was lower in <i>H. pylori</i> positives in 10 out of the 11 gastric locations (all p &lt; 0.01). Positive CagA status was associated with reduced intragastric acidity, but had no effect on PC density or mucosal inflammation when compared to CagA negative<i> H. pylori</i> positives. <h3>Conclusion</h3> The majority of <i>H. pylori</i> infected subjects have reduced intragastric acidity and PC density compared to the uninfected population and the reduction in acidity is most marked close to the GOJ. This may explain the negative association between <i>H. pylori</i> infection and both gastroesophageal reflux disease and oesophageal adenocarcinoma. <h3>Disclosure of Interest</h3> None Declared
Synergistic Preclinical Activity of Bortezomib with Suberoylanilide Hydroxamic Acid (SAHA) in Primary Effusion Lymphoma (PEL)
Authors: Shruti Bhatt, Brittany Ashlock, Ngoc Toomey, Enrique Mesri, Juan Carlos Ramos, Izidore S Lossos
Journal: Blood (2011)
Serum Asymmetric Dimethylarginine (ADMA) Levels Predict Steroid-Refractory Gvhd before Allogeneic Stem Cell Transplantion
Authors: Sascha Dietrich, Aleks Radukjovic, Michael Hess, Ute Hegenbart, Anthony D. Ho, Peter Dreger, Thomas Luft
Journal: Blood (2014)
Chronic Myelogenous Leukemia in the Era of Tyrosine Kinase Inhibitors: Is Sokal Score Still a Valid Predictor of Prognosis?
Authors: Shivi Jain, Kireet Agrawal, Abhijai Singh, Shinoj Pattali, Augustin Haidau, Paula Kovarik, Rose Catchatourian
Journal: Blood (2012)
PTH-152 The Patient Perspective of a Nurse-Led Inflammatory Bowel Disease (IBD) Telephone Helpline Service
Authors: N Rezwan, D West, G Tun, A Shirazi-Nejad, K Kapur, D Bullas, A Soliman, V Sathyanarayana, R Atkinson, E Said
Journal: Gut (2016)

<h3>Introduction</h3> Barnsley Hospital NHS Foundation Trust (BHFT) has approximately 1300 IBD patients. All patients have access to an IBD helpline (as recommended by IBD standards<sup>1</sup>) which is answered by an IBD specialist nurse between 12.30–13.30 pm, Monday to Friday. The specialist nurse assesses the symptoms of the patient, answers questions, gives reassurance and advice, and arranges follow-up, hospital admission, or alterations in prescription. The patients’ perspective of the helpline was analysed in this study. <h3>Methods</h3> To evaluate the patients’ view of the nurse-led IBD telephone helpline at BHFT. Patient views were collected by questionnaire. Questions explored the accessibility of the service, the clinical competency of the specialist nurse, and what the patient thought was useful. 134 patients attended the nurse-led IBD clinic from November 2015 to January 2016. 37 responses (28%) were received and analysed. <h3>Results</h3> 54% of the responses were anonymous. 24% of respondents did not use the helpline. 100% of those who used the helpline found the service valuable: 86% had positive feedback; 14% had negative feedback; 100% agreed that the specialist nurse had sufficient clinical knowledge and experience to answer all questions. Positive comments included: The knowledge that help and advice was readily available was reassuring and provoked less anxiety. Being able to talk about the disease to someone who understands. Easier access to imaging, endoscopy, outpatient services, inpatient admission, and the gastroenterologists compared to GPs Discussion of treatment options when in dilemma. The negative comments concerned the popular demand of the service, leading to long wait times before calls were answered, and the lack of cover for sickness and leave. <h3>Conclusion</h3> The IBD helpline is an invaluable service to the patients. It answers any immediate concerns, prioritises unwell patients in the community, and facilitates prompt investigation and clinical review. Additional investment in the service will optimise the accessibility of the helpline to the local IBD population. <h3>Reference</h3> 1 Service Standards for the healthcare of people who have Inflammatory Bowel Disease (IBD), IBD Standards Group, 2009, Standard 11A. <h3>Disclosure of Interest</h3> None Declared