tbuckley/cabot-search huggingface dataset:
Is optimising gout treatment the key to closing the mortality gap in gout patients?
Authors: Robin M ten Brinck, Emma C de Moel, Joy A van der Pol, Sjoerd van Beest, Anoek de Koning, Tom W J Huizinga
Journal: Annals of the Rheumatic Diseases (2017)

With great interest we read the extended report of Fisher et al 1 on the unclosing premature mortality gap in gout and we congratulate the authors on their extensive work. In their population-based cohort study, the authors found that among the patients with gout, the level of premature mortality remained unimproved over the past 16 years. However, there are a few issues that, in our opinion, merit attention concerning the conclusions that were drawn from the data:

1.  The authors hypothesise that proper urate control could have cardiovascular–metabolic–renal benefits, and thus optimising gout treatment would reduce mortality. However, the authors have chosen ‘all-cause mortality’ as their outcome, most likely because disease-related mortality was not available.2 In rheumatoid arthritis (RA), the main cause for premature mortality is cardiovascular death, with poor clinical RA status prognostic of premature mortality, and thus the closing mortality gap may very well be due to tighter disease …
A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant
Authors: John A. Ronald, Byung-Su Kim, Gayatri Gowrishankar, Mohammad Namavari, Israt S. Alam, Aloma D'Souza, Hidekazu Nishikii, Hui-Yen Chuang, Ohad Ilovich, Chih-Feng Lin, Robert Reeves, Adam Shuhendler, Aileen Hoehne, Carmel T. Chan, Jeanette Baker, Shahriar S. Yaghoubi, Henry F. VanBrocklin, Randall Hawkins, Benjamin L. Franc, Salma Jivan, James B. Slater, Emily F. Verdin, Kenneth T. Gao, Jonathan Benjamin, Robert Negrin, Sanjiv Sam Gambhir
Journal: Cancer Research (2017)

Abstract A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2′-deoxy-2′-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893–902. ©2017 AACR.
Prognostic factors in synovial sarcoma
Authors: O. O. Castillo Fernandez, M. Pacheco, M. Lim, C. Singh
Journal: Journal of Clinical Oncology (2009)

e21525 Background: Synovial sarcoma (SS) is a relatively rare type of soft tissue sarcoma. Several prognostic factors have been described that modulate patients’ outcome. The aim of this study was to identify prognostic factors in patients with SS. Methods: A retrospective analysis was performed on clinical and histopathological data of patients treated at National Oncology Institute (Panama) between 1995 - 2007. Demographic, clinical, pathological, and therapeutic variables were reviewed. Overall survival and recurrence-free survival were analyzed using Kaplan-Meier and log-rank tests. Results: Twenty seven patients were analyzed, 56% male and 44% female, median age was 28. Tumour site; extremities based 85%, truncal 15%. Median tumour size was 8cm. Presentation; non-metastatic 84%, metastatic 16%. Histological type; monophasic 78%, biphasic 22%. Mitosis/10HPF; twenty and more 33%, less than twenty 67%. Necrosis; absent 63%, less than half 30%, and more than half 7%. Histological grade (FNCLLC); grade 2 48%, grade 3 52%. Surgery; limb sparing surgery 52%, amputation 48%. Treatment: adjuvant treatment 52% (3 chemotherapy only, 7 radiation therapy, 4 both). 90% were doxorubicin based regimens. The median follow up was 25 months. 63% of tumours recurred and 33% of patients died. Univariate analysis revealed a significant positive relationship between histological grade and overall survival (p&lt;0.05). In patients with localized disease, time to recurrence decreased with histological grade (p=0.05 ns). Conclusions: High histological grade is an adverse prognostic factor for overall survival in patients with SS. No significant financial relationships to disclose.
Validation de biomarqueurs d'imagerie diagnostiques des maladies inflammatoires chroniques de l'intestin par endomicroscopie confocale
Authors: J Brégeon, M Neunlist, E Coron
Journal: Endoscopy (2016)

De nombreuses maladies gastro-intestinales inflammatoires sont caractérisées par des changements structurels de la muqueuse. Ces modifications sont en corrélation avec la gravité de la maladie, et peuvent être un facteur prédictif d'évolution ou de réponse au traitement. Parmi les principales caractéristiques structurelles utilisées pour le diagnostic des lésions coliques de la muqueuse, l'étude du profil des puits de cryptes (PPC) est largement reconnue. Les méthodes de détection du PPC restent essentiellement descriptives, bien que des études récentes aient montré qu'une approche quantitative et informatisée de l'analyse d'image augmentait la sensibilité de la classification et diminuait les variations d'analyses entre opérateurs. Parmi les méthodes utilisées pour imager la muqueuse intestinale, l'endomicroscopie confocale (EMC) est une technique innovante et en temps réelle. L'EMC est une technique d'imagerie endoscopique permettant l'examen de la muqueuse digestive à un niveau cellulaire. À ce jour, bien qu'il y ait des études ayant établies des classifications qualitatives par l'EMC des maladies inflammatoires intestinales (MICI), peu d'études ont effectué une analyse quantitative de ces modifications. Le pouvoir diagnostique de l'EMC pour évaluer les changements structurels de la muqueuse dans les maladies inflammatoires de l'intestin reste inconnu.
Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence
Authors: Caterina Tezze, Vanina Romanello, Maria Andrea Desbats, Gian Paolo Fadini, Mattia Albiero, Giulia Favaro, Stefano Ciciliot, Maria Eugenia Soriano, Valeria Morbidoni, Cristina Cerqua, Stefan Loefler, Helmut Kern, Claudio Franceschi, Stefano Salvioli, Maria Conte, Bert Blaauw, Sandra Zampieri, Leonardo Salviati, Luca Scorrano, Marco Sandri
Journal: Cell Metabolism (2017)

Mitochondrial dysfunction occurs during aging, but its impact on tissue senescence is unknown. Here, we find that sedentary but not active humans display an age-related decline in the mitochondrial protein, optic atrophy 1 (OPA1), that is associated with muscle loss. In adult mice, acute, muscle-specific deletion of Opa1 induces a precocious senescence phenotype and premature death. Conditional and inducible Opa1 deletion alters mitochondrial morphology and function but not DNA content. Mechanistically, the ablation of Opa1 leads to ER stress, which signals via the unfolded protein response (UPR) and FoxOs, inducing a catabolic program of muscle loss and systemic aging. Pharmacological inhibition of ER stress or muscle-specific deletion of FGF21 compensates for the loss of Opa1, restoring a normal metabolic state and preventing muscle atrophy and premature death. Thus, mitochondrial dysfunction in the muscle can trigger a cascade of signaling initiated at the ER that systemically affects general metabolism and aging.
Education in action: evaluating kids concussion infographics
Authors: Christine Provvidenza, Jason Carmichael, Nick Reed
Journal: British Journal of Sports Medicine (2017)

Objective To assess the impact of infographics on enhancing concussion knowledge and their effectiveness as a knowledge translation (KT) strategy. Design Prospective, post-survey design to assess a KT strategy. Setting Community and hospital based education events. Participants Individuals across various stakeholder groups were invited to provide feedback on six infographics. Data (N=106) was collected from youth (52%) and adults (48%), representing five stakeholder groups: athletes, students, teachers, healthcare trainees and healthcare professionals. Intervention Six infographics were created to provide salient information about concussion for a multi-stakeholder audience. Outcome measures A survey was designed to gather information about the value and utility of the infographics as a KT strategy and to determine additional knowledge needs. Main results Ninety percent of participants identified that the infographics met their knowledge needs, and 84% of participants indicated that the infographics gave them new knowledge related to sleep, myths and facts, and signs and symptoms. Participants indicated that they intend to use the infographics to build knowledge (91%), educate others (52%), and cope with concussion (26%). Feedback provided about the infographic format was positive, and suggestions for future topics were offered. Conclusions Infographics are a potentially effective KT strategy that meets knowledge needs and appeals to many different audiences. Participants identified that they want to learn more about areas including concussion recovery and management. Data collection is ongoing and continues to inform the value of infographics as a KT strategy. This study is part of a broader education initiative to optimise paediatric concussion knowledge. Competing interests None.
Evaluation of the HS-1000 acoustic neuromonitoring device in the diagnosis and assessment of sports-induced concussion
Authors: Allen Sills, Timothy Lee, Tricia Kwiatkowski, Thomas Swanson, Guy Weinberg
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate the correlation between data collected from the HS-1000 multi-modality brain monitoring device and standard neurological, psychomotor, and neuropsychological diagnostics in the assessment of acute sports-induced concussion. Design Prospective, open-label, non-randomised study. Setting Collegiate athletes were recruited at the Vanderbilt Sports Concussion Centre, Nashville, TN. Participants Sixty-four subjects across concussed (n 1 =14) and healthy control (n 2 =50) arms were consented. Interventions and assessment of risk factors Eligible subjects suffering recent concussion and age/gender-matched healthy controls were enrolled into the study. Participants in both groups were monitored for at least 15min per recording with the HS-1000. Concussed subjects were recorded 4 times relative to time of concussion injury: acute/baseline, 48 hr, 1 wk, 1 mo. Healthy control subjects were recorded at 2 time points: baseline, 2 wk. Outcome measures Standard clinical diagnostics and demographic information were collected from all study participants. As per current clinical standards and their assigned group, concussed subjects received Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), Modified Balance Assessment Scale (mBESS), and total clinical symptom index scores. MathWorks MATLAB™ (Matrix Laboratory) engineering software was used to interpret signals and calculate sensitivity-specificity as a function of predictive accuracy with clinically confirmed concussion status. Main results Post-processing of HS-1000 signals identified concussed athletes with a sensitivity-specificity of 86.1% and 91%, respectively. Conclusions The HS-1000 demonstrated strong predictive accuracy compared with clinical diagnosis. Improved statistical power through greater sampling sizes and the development of a real-time diagnostic algorithm suggests this technology holds promise in the assessment and diagnosis of sports-induced concussion. Competing interests None.
Abuse-Deterrent Opioid Formulations — Putting the Potential Benefits into Perspective
Authors: William C. Becker, David A. Fiellin
Journal: New England Journal of Medicine (2017)

Focusing on preventing intentional abuse of prescription opioids may distract prescribers, patients, and policymakers from considering the limited evidence supporting long-term opioid use for chronic pain and the other risks associated with all opioid formulations.
Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge
Authors: Kathy J. Jenkins, Adolfo Correa, Jeffrey A. Feinstein, Lorenzo Botto, Amy E. Britt, Stephen R. Daniels, Marsha Elixson, Carole A. Warnes, Catherine L. Webb
Journal: Circulation (2007)

Prevention of congenital cardiovascular defects has been hampered by a lack of information about modifiable risk factors for abnormalities in cardiac development. Over the past decade, there have been major breakthroughs in the understanding of inherited causes of congenital heart disease, including the identification of specific genetic abnormalities for some types of malformations. Although relatively less information has been available on noninherited modifiable factors that may have an adverse effect on the fetal heart, there is a growing body of epidemiological literature on this topic. This statement summarizes the currently available literature on potential fetal exposures that might alter risk for cardiovascular defects. Information is summarized for periconceptional multivitamin or folic acid intake, which may reduce the risk of cardiac disease in the fetus, and for additional types of potential exposures that may increase the risk, including maternal illnesses, maternal therapeutic and nontherapeutic drug exposures, environmental exposures, and paternal exposures. Information is highlighted regarding definitive risk factors such as maternal rubella; phenylketonuria; pregestational diabetes; exposure to thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis. Caveats regarding interpretation of possible exposure-outcome relationships from case-control studies are given because this type of study has provided most of the available information. Guidelines for prospective parents that could reduce the likelihood that their child will have a major cardiac malformation are given. Issues related to pregnancy monitoring are discussed. Knowledge gaps and future sources of new information on risk factors are described.
Condensed versus standard schedule of high-dose cytarabine consolidation therapy with pegfilgrastim growth factor support in acute myeloid leukemia
Authors: S Jaramillo, A Benner, J Krauter, H Martin, T Kindler, M Bentz, H R Salih, G Held, C-H Köhne, K Götze, M Lübbert, A Kündgen, P Brossart, M Wattad, H Salwender, B Hertenstein, D Nachbaur, G Wulf, H-A Horst, H Kirchen, W Fiedler, A Raghavachar, G Russ, S Kremers, E Koller, V Runde, G Heil, D Weber, G Göhring, K Döhner, A Ganser, H Döhner, R F Schlenk
Journal: Blood Cancer Journal (2017)

The aim of this cohort study was to compare a condensed schedule of consolidation therapy with high-dose cytarabine on days 1, 2 and 3 (HDAC-123) with the HDAC schedule given on days 1, 3 and 5 (HDAC-135) as well as to evaluate the prophylactic use of pegfilgrastim after chemotherapy in younger patients with acute myeloid leukemia in first complete remission. One hundred and seventy-six patients were treated with HDAC-135 and 392 patients with HDAC-123 with prophylactic pegfilgrastim at days 10 and 8, respectively, in the AMLSG 07-04 and the German AML Intergroup protocol. Time from start to chemotherapy until hematologic recovery with white blood cells >1.0 G/l and neutrophils >0.5 G/l was in median 4 days shorter in patients receiving HDAC-123 compared with HDAC-135 (P<0.0001, each), and further reduced by 2 days (P<0.0001) by pegfilgrastim. Rates of infections were reduced by HDAC-123 (P<0.0001) and pegfilgrastim (P=0.002). Days in hospital and platelet transfusions were significantly reduced by HDAC-123 compared with HDAC-135. Survival was neither affected by HDAC-123 versus HDAC-135 nor by pegfilgrastim. In conclusion, consolidation therapy with HDAC-123 leads to faster hematologic recovery and less infections, platelet transfusions as well as days in hospital without affecting survival.
Abstract 43: Activation of the Nuclear Receptor Coactivator PGC-1α Mediates an Atheroprotective Effect
Authors: Cathal McCarthy, Declan Mooney, Monica de Gaetano, William James, Desmond J Fitzgerald, Orina Belton
Journal: Circulation Research (2012)

Supplementing dietary chow with conjugated linoleic acid (CLA) induces marked regression of pre-established murine atherosclerosis, in contrast to other PPAR agonists. The finding suggests that there are unidentified endogenous pathways that suppress the progression or promote the regression of atherosclerosis. Identifying these pathways in the mouse and their homologues in humans may help elucidate the mechanisms of the disease and targets for future therapies. Here, we provide evidence that CLA inhibits foam cell formation via regulation of the nuclear receptor co-activator, PGC-1α in a manner that differs from PPAR activation. Gene expression analysis was performed in the aorta of ApoE -/- mice following induction of atherosclerosis and dietary supplementation with/without CLA. CLA induced dramatic regression of the cholesterol-induced atherosclerosis. PGC-1α was identified as a ‘hub’ gene within a cluster of genes induced by CLA in the aorta of the ApoE -/- during regression. PGC-1α protein was also found in murine and human atherosclerotic plaque, where it was localised to macrophage/foam cells. In a mouse macrophage cell line exposed to oxLDL, CLA induced PGC-1α and several genes in the network in an isomer specific fashion, including RORαand ABCA1. CLA also induced the PGC-1α target genes Cyp7b1 and UCP-1, and PPAR. CLA inhibited foam cell formation in the same cells exposed to oxLDL and suppressed the expression of the scavenger receptors, SRA-1 and CD36. Expression of the PGC-1α in macrophages had similar effects. Thus, over-expression of PGC-1α limited the accumulation of oxLDL and subsequent foam cell formation, while deletion of the gene promoted foam cell formation in bone marrow derived macrophages upon exposure to oxLDL. Moreover, deletion of PGC-1α prevented the inhibition of macrophages/foam cell formation by CLA. The nuclear receptor co-activator PGC-1α is a hub gene in a network of genes activated in the aorta during CLA-induced regression of atherosclerosis and mediates CLA’s inhibition of foam cell formation. PGC-1α is also is also expressed in human plaques where its expression is inversely associated with disease progression, raising the possibility that this pathway if activated could regulate human atherosclerosis.
Efficacité du traitement endoscopique dans la prise en charge des fistules digestives anastomotiques après chirurgie pour cancer de l'œsophage
Authors: C Servajean, JM Gonzalez, M Gasmi, BX D'journo, M Leone, JC Grimaud, M Barthet
Journal: Endoscopy (2016)

La fistule anastomotique est l'une des principales complications de l'œsophagectomie pour cancer de l'œsophage ou de la jonction œso-cardiale. Elle serait responsable de 40% des décès en post-opératoire de cette chirurgie. La prise en charge endoscopique de ces fistules est devenue une alternative face à la reprise chirurgicale ou au traitement conservateur. L'objectif principal était d'évaluer l'efficacité primaire et secondaire du traitement endoscopique, définie par la guérison de la fistule. Les objectifs secondaires étaient d'évaluer le délai entre la chirurgie, le diagnostic et l'endoscopie, le nombre d'endoscopies total, le matériel utilisé, les complications, le taux de mortalité, et de déterminer des facteurs prédictifs de succès par une analyse uni et multivariée.
Home-based maintenance tele-rehabilitation reduces the risk for acute exacerbations of COPD, hospitalisations and emergency department visits
Authors: Maroula Vasilopoulou, Andriana I. Papaioannou, Georgios Kaltsakas, Zafeiris Louvaris, Nikolaos Chynkiamis, Stavroula Spetsioti, Eleni Kortianou, Sofia Antiopi Genimata, Anastasios Palamidas, Konstantinos Kostikas, Nikolaos G. Koulouris, Ioannis Vogiatzis
Journal: European Respiratory Journal (2017)

Pulmonary rehabilitation (PR) remains grossly underutilised by suitable patients worldwide. We investigated whether home-based maintenance tele-rehabilitation will be as effective as hospital-based maintenance rehabilitation and superior to usual care in reducing the risk for acute chronic obstructive pulmonary disease (COPD) exacerbations, hospitalisations and emergency department (ED) visits. Following completion of an initial 2-month PR programme this prospective, randomised controlled trial (between December 2013 and July 2015) compared 12 months of home-based maintenance tele-rehabilitation (n=47) with 12 months of hospital-based, outpatient, maintenance rehabilitation (n=50) and also to 12 months of usual care treatment (n=50) without initial PR. In a multivariate analysis during the 12-month follow-up, both home-based tele-rehabilitation and hospital-based PR remained independent predictors of a lower risk for 1) acute COPD exacerbation (incidence rate ratio (IRR) 0.517, 95% CI 0.389–0.687, and IRR 0.635, 95% CI 0.473–0.853), respectively, and 2) hospitalisations for acute COPD exacerbation (IRR 0.189, 95% CI 0.100–0.358, and IRR 0.375, 95% CI 0.207–0.681), respectively. However, only home-based maintenance tele-rehabilitation and not hospital-based, outpatient, maintenance PR was an independent predictor of ED visits (IRR 0.116, 95% CI 0.072–0.185). Home-based maintenance tele-rehabilitation is equally effective as hospital-based, outpatient, maintenance PR in reducing the risk for acute COPD exacerbation and hospitalisations. In addition, it encounters a lower risk for ED visits, thereby constituting a potentially effective alternative strategy to hospital-based, outpatient, maintenance PR.