tbuckley/cabot-search huggingface dataset:
OC-018 The role of a point of care test (iga/igg-deamidated gliadin peptide) in predicting histological remission in coeliac disease on a gluten free diet
Authors: Lau, PD Mooney, WL White, MA Rees, M Burden, SH Wong, DS Sanders
Journal: Gut (2017)

Introduction  Coeliac disease (CD) is a chronic inflammatory enteropathy treated with a gluten free diet (GFD). Non adherence can lead to symptoms and complications such as osteoporosis and malabsorption. Moreover, patients with persistent villous atrophy are twice as likely to develop lymphoproliferative malignancies compared to those who achieve mucosal healing. Therefore, the optimal assessment of treatment response is the evaluation of duodenal histology. However, there is little consensus in the UK on routine follow up biopsy. Duodenal biopsy requires a gastroscopy which is invasive and can be poorly tolerated. There is currently no reliable surrogate marker for histological remission in our daily clinical practice. We aimed to assess the role of a finger prick point of care test (POCT), Simtomax (IgA/IgG-deamidated gliadin peptide, Tillotts Pharma, Rheinfelden, Switzerland), in predicting histological remission in CD.  Method  We prospectively recruited patients with known CD attending for a gastroscopy with duodenal biopsy for the assessment of histological remission. IgA-endomysial antibodies (EMA), IgA-tissue transglutaminase antibodies (TTG), total IgA levels and the POCT were performed in all patients at endoscopy. Patients also completed a validated GFD adherence questionnaire devised by Biagi et al. which gives a 5 point score (0–4), with the highest score indicating strict dietary adherence. A gastroscopy was performed with quadrantic biopsies taken from the second part of the duodenum and one from the duodenal bulb. We compared all surrogate markers to the gold standard of duodenal histology.  Results  A total of 217 (70% female, age range 16–83, median age 53) patients with CD on a GFD (median duration 6 years) were recruited from 2013–2017. Eighty-five (39.2%) patients had persistent villous atrophy. The POCT was the most sensitive surrogate marker for predicting villous atrophy (p=0.0005).   Conclusion  Of all clinically available surrogate markers, the POCT was the most sensitive in predicting villous atrophy. The POCT has the additional advantage of convenience being a finger prick test, providing rapid results within 10 min. In combination with clinical and dietetic assessments, the POCT could aid clinical decision making on the necessity of follow-up duodenal biopsy within the same consultation.  Disclosure of Interest  M. Lau: None Declared, P. Mooney: None Declared, W. White: None Declared, M. Rees: None Declared, M. Burden: None Declared, S. Wong: None Declared, D. Sanders Conflict with: Professor Sanders has received educational research grants from Dr Schaer (a gluten-free food manufacturer) and Tillotts Pharma (producer of a point of care test for celiac disease) for investigator led studies. Dr Shaer and Tillott’s Pharma did not have any input in the study design, access to study data, interpretation of the findings or drafting of the manuscript.
Palliative chemoradiotherapy versus radiotherapy alone for dysphagia in advanced oesophageal cancer: a multicentre randomised controlled trial (TROG 03.01)
Authors: Michael G Penniment, Paolo B De Ieso, Jennifer A Harvey, Sonya Stephens, Heather-Jane Au, Christopher J O'Callaghan, Andrew Kneebone, Samuel Y Ngan, Iain G Ward, Rajarshi Roy, Jennifer G Smith, Tirath Nijjar, James J Biagi, Liam A Mulroy, Rebecca Wong
Journal: The Lancet. Gastroenterology & hepatology (2017)
Double-clip counter-traction using a rubber band is a useful and adaptive tool for colonic endoscopic submucosal dissection
Authors: Jérémie Jacques, Aurélie Charissoux, Romain Legros, Arnaud Tailleur, Jérôme Rivory, Jérémie Albouis, Mathieu Pioche
Journal: Endoscopy (2017)

The colon is the most technically challenging location for endoscopic submucosal dissection (ESD) of large, superficial, precancerous and cancerous lesions [1]. Appropriate exposure of the submucosal space can be very difficult, even when performed by experts, owing to the thinness of the submucosal space in this location and because the gravitational assistance is not constant. Moreover, the presence of colonic loops, bowel and respiratory movements, and position modifications resulting from insufflation increase the difficulty of performing ESD in this location.
Complement Inhibition Using Eculizumab Overcomes Platelet Transfusion Refractoriness in Allo-Immunized Patients Receiving HLA Mismatched Platelets
Authors: Phuong T. Vo, Enkhtsetseg Purev, Kamille A West, Michael Hochman, Emily C. McDuffee, Tatyana Worthy, Lisa Cook, Catalina Ramos, Brian Wells, Willy A. Flegel, Sharon Adams, Robert N. Reger, Georg Aue, Richard W. Childs
Journal: Blood (2016)
Hypomethylation of Decitabine Improved Outcomes of Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia
Authors: Zhiyong Peng, Xiaoqin Feng, Yuelin He, Yuchen Lin, Jianyun Liao, Xuedong Wu, Jiaqi Chen, Chunfu Li
Journal: Blood (2017)
Abstract 19033: Cardiac Epi-Metabolic Signature Revealed by Integrated Omics Approach in Diabetic Patients: Rescue by Active DNA Demethylation via TET-TDG Complex Reactivation
Authors: Francesco Spallotta, Chiara Cencioni, Sandra Atlante, Davide Garella, Mattia Cocco, Mattia Mori, Raffaella Mastrocola, Carsten Kuenne, Stefan Guenther, Simona Nanni, Valerio Azzimato, Sven Zukunft, Angela Kornberger, Antonella Di Stilo, Manuela Aragno, Fabio Martelli, Antonella Farsetti, Ingrid Fleming, Thomas Braun, Andres Beiras-Fernandez, Bruno Botta, Massimo Collino, Massimo Bertinaria, Andreas M Zeiher, Carlo Gaetano
Journal: Circulation (2016)

Introduction & Hypothesis: Diabetes is one of the major risk factor for cardiovascular diseases. Prolonged exposure to uncontrolled hyperglycaemia in the heart induces dramatic metabolic changes th...
PhIP-DNA adducts as a biomarker for prostate carcinogenesis
Authors: Deliang Tang, Jason Liu, Adnan T. Savera, Andrew Rundle, Christine Neslund-Dudas, Jie Yu, James J. Yang, Benjamin A. Rybicki
Journal: Cancer Research (2006)

2057  2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine in the human diet, and is formed during the cooking of meat. PhiP-DNA adducts provide a measure of chemical-specific genetic damage that has been associated with increased risk of cancer. This study examined the relationship between PhiP-DNA adducts measured by immunohistochemistry in nontumorous and tumorous prostatic epithelial cells. Study subjects were 125 men who underwent prostatectomy and were part of the Henry Ford Health System, in Detroit, Michigan. . The mean level of PhiP-DNA adducts in prostatic epithelial nontumor cells was significantly higher than the mean level of PhiP-DNA adducts in tumor cells (0.055 units) (p
How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial
Authors: Silvio E. Inzucchi, Bernard Zinman, David Fitchett, Christoph Wanner, Ele Ferrannini, Martin Schumacher, Claudia Schmoor, Kristin Ohneberg, Odd Erik Johansen, Jyothis T. George, Stefan Hantel, Erich Bluhmki, John M. Lachin
Journal: Diabetes Care (2017)

In the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial involving 7,020 patients with type 2 diabetes and established cardiovascular (CV) disease, empagliflozin given in addition to standard of care reduced the risk of CV death by 38% versus placebo (hazard ratio [HR] 0.62 [95% CI 0.49, 0.77]). This exploratory mediation analysis assesses the extent to which treatment group differences in covariates during the trial contributed to CV death risk reduction with empagliflozin.Effects of potential mediators, identified post hoc, on the HR for CV death with empagliflozin versus placebo were analyzed by Cox regression models, with treatment group adjusted for the baseline value of the variable and its change from baseline or updated mean (i.e., considering all prior values), each as a time-dependent covariate. HRs were compared with a model without adjustment for covariates. Multivariable analyses also were performed.Changes in hematocrit and hemoglobin mediated 51.8% and 48.9%, respectively, of the effect of empagliflozin versus placebo on the risk of CV death on the basis of changes from baseline, with similar results in analyses on the basis of updated means. Smaller mediation effects (maximum 29.3%) were observed for uric acid, fasting plasma glucose, and HbA1c. In multivariable models, which incorporated effects of empagliflozin on hematocrit, fasting glucose, uric acid, and urine albumin:creatinine ratio, the combined changes from baseline provided 85.2% mediation, whereas updated mean analyses provided 94.6% mediation of the effect of empagliflozin on CV death.In this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo.
Mandibuloacral dysplasia: A premature ageing disease with aspects of physiological ageing
Authors: Vittoria Cenni, Maria Rosaria D’Apice, Paolo Garagnani, Marta Columbaro, Giuseppe Novelli, Claudio Franceschi, Giovanna Lattanzi
Journal: Ageing Research Reviews (2017)

Mandibuloacral dysplasia (MAD) is a rare genetic condition characterized by bone abnormalities including localized osteolysis and generalized osteoporosis, skin pigmentation, lipodystrophic signs and mildly accelerated ageing. The molecular defects associated with MAD are mutations in LMNA or ZMPSTE24 (FACE1) gene, causing type A or type B MAD, respectively. Downstream of LMNA or ZMPSTE24 mutations, the lamin A precursor, prelamin A, is accumulated in cells and affects chromatin dynamics and stress response. A new form of mandibuloacral dysplasia has been recently associated with mutations in POLD1 gene, encoding DNA polymerase delta, a major player in DNA replication. Of note, involvement of prelamin A in chromatin dynamics and recruitment of DNA repair factors has been also determined under physiological conditions, at the border between stress response and cellular senescence. Here, we review current knowledge on MAD clinical and pathogenetic aspects and highlight aspects typical of physiological ageing.
Response by Mittal et al to Letter Regarding Article, “Neutrophil Activation of Endothelial Cell-Expressed TRPM2 Mediates Transendothelial Neutrophil Migration and Vascular Injury”
Authors: Manish Mittal, Saroj Nepal, Yoshikazu Tsukasaki, Claudie M. Hecquet, Dheeraj Soni, Chinnaswamy Tiruppathi, Asrar B. Malik, Jalees Rehman
Journal: Circulation Research (2017)
Asthma phenotypes: do cough and wheeze predict exacerbations in persistent asthma?
Authors: Jaymin B. Morjaria, Alan S. Rigby, Alyn H. Morice
Journal: European Respiratory Journal (2017)

Little is known of the long-term symptom profile in uncontrolled asthma and whether symptoms can predict distinct phenotypes. The primary objective of these analyses was to assess diurnal profile of cough and wheeze in an uncontrolled asthma population. Secondary outcomes were to examine how these symptom profiles influence response to treatment.Twice-daily electronically recorded data from 1701 patients were examined in relation to the population demographics. Reliever treatment with salbutamol was then compared with extra-fine beclometasone/formoterol maintenance and reliever therapy (MART). Exacerbation frequency was then correlated with the symptom profile.Symptoms were commoner in older patients with an increased body mass index. In most patients, reported cough and wheeze were closely correlated (r=0.73). Two phenotypes of cough- and wheeze-predominant patients were identified; the former were overweight, older females and the latter older males. Diurnal symptoms of cough and wheeze were similarly attenuated by both therapies. MART reduced exacerbation frequency by a third compared with salbutamol, and this effect was greatest in patients with fewest reported symptoms.While cough and wheeze are highly correlated in uncontrolled asthma, some patients predominantly have cough whereas others wheeze. Symptoms and exacerbation frequency appear poorly associated, suggesting an alternative pathophysiology. MART may be the preferred option in those with fewest symptoms.
Abstract 14365: Home Morning Systolic BP Should be Below 125mmHg in Patients With Type 2 Diabetes
Authors: Kazuo Eguchi, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2016)

Introduction: Home BP target level in patients with type 2 diabetes (T2DM) is not established. Hypothesis: We tested the hypothesis that appropriate home morning systolic BP cutoff value is 125mmHg...
High and low sodium intakes are associated with incident chronic kidney disease in patients with normal renal function and hypertension
Authors: Chang-Yun Yoon, Juhwan Noh, Jinae Lee, Youn Kyung Kee, Changhwan Seo, Misol Lee, Min-Uk Cha, Hyoungnae Kim, Seohyun Park, Hae-Ryong Yun, Su-Young Jung, Jong Hyun Jhee, Seung Hyeok Han, Tae-Hyun Yoo, Shin-Wook Kang, Jung Tak Park
Journal: Kidney International (2017)
The RA-MAP Consortium: a working model for academia–industry collaboration
Authors: Andrew P. Cope, Michael R. Barnes, Alexandra Belson, Michael Binks, Sarah Brockbank, Francisco Bonachela-Capdevila, Claudio Carini, Benjamin A. Fisher, Carl S. Goodyear, Paul Emery, Michael R. Ehrenstein, Neil Gozzard, Ray Harris, Sally Hollis, Sarah Keidel, Marc Levesque, Catharina Lindholm, Michael F. McDermott, Iain B. McInnes, Christopher M. Mela, Gerry Parker, Simon Read, Ayako Wakatsuki Pedersen, Frederique Ponchel, Duncan Porter, Ravi Rao, Anthony Rowe, Peter Schulz-Knappe, Matthew A. Sleeman, Deborah Symmons, Peter C. Taylor, Brian Tom, Wayne Tsuji, Denny Verbeeck, John D. Isaacs
Journal: Nature Reviews Rheumatology (2017)
Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T-cell lymphoma
Authors: Tayla B. Heavican, Alyssa Bouska, Jiayu Yu, Waseem Lone, Catalina Amador, Qiang Gong, Weiwei Zhang, Yuping Li, Bhavana J. Dave, Maarja-Liisa Nairismägi, Timothy C. Greiner, Julie Vose, Dennis D. Weisenburger, Cynthia Lachel, Chao Wang, Kai Fu, Jadd M. Stevens, Soon Thye Lim, Choon Kiat Ong, Randy D. Gascoyne, Edoardo Missiaglia, Francois Lemonnier, Corinne Haioun, Sylvia Hartmann, Martin Bjerregård Pedersen, Maria Antonella Laginestra, Ryan A. Wilcox, Bin Tean Teh, Noriaki Yoshida, Koichi Ohshima, Masao Seto, Andreas Rosenwald, German Ott, Elias Campo, Lisa M. Rimsza, Elaine S. Jaffe, Rita M. Braziel, Francesco d’Amore, Giorgio Inghirami, Francesco Bertoni, Laurence de Leval, Philippe Gaulard, Louis M. Staudt, Timothy W. McKeithan, Stefano Pileri, Wing C. Chan, Javeed Iqbal
Journal: Blood (2019)
High court finds that tribunal treated GP too leniently
Authors: Clare Dyer
Journal: BMJ (2017)

The General Medical Council has won a High Court ruling that a medical practitioners’ tribunal treated a GP too leniently when deciding whether his fitness to practise was impaired.

A High Court judge ruled that the basis on which the tribunal decided that Muhammed Moazzam Chaudhary’s fitness to practise was impaired was too narrow and failed to take account of the need to maintain proper professional standards and public confidence in the profession.

Complications arose after Chaudhary had carried out a ritual circumcision of a two month old baby in 2008 and he engaged in a number of deceptions while trying to put matters right.

The judge, Mr Justice Jay, quashed the finding of impairment but …
Mitosis interference of cancer cells during anaphase by electric field from NovoTTF-100A: An update.
Authors: Sze Xian Lee, Adrian Tunkyi, Eric Wong, Kenneth D. Swanson
Journal: Journal of Clinical Oncology (2012)

e21078 Background: The NovoTTF-100A is a device that emits an alternating electric field (TTField) that kills mitotic cells and has been FDA-approved for the treatment of recurrent glioblastoma. Exposure to the TTField resulted in impaired cytokinesis and asymmetric chromosome segregation. To further elucidate its mechanism of action, we performed experiments using synchronized tumor cells and TTField-treated xenografts. Methods: Biochemical analysis of cell cycle-specific proteins, timelapse movies, and immunoflourescence microsopy were used to examine the effects of TTField on synchronized tumor cells. Xenografts treated with TTField were analyzed for the presence of phospho-Histone H3 and cell cycle-specific epitopes. Results: Cells exposed to TTField as they transited through M-phase exhibited persistence of phospho-Histone H3 while Securin levels decreased, suggesting that these cells transit through metaphase to anaphase but were delayed in mitotic exit. Immunoflourescence of treated cells showed evidence of impaired cytokinesis together with disordered separation of chromosomes from metaphase plates. Lagging chromosomes, dispersion of chromosomes, chromosomes decondensation in the absence of cytokinesis, and asymmetric chromosomal segregation were also observed in treated samples. The number of 4N cells increased following TTField exposure compared to parallel cultures that had entered the G 1 -phase of the cell cycle indicating a failure of mitosis. Exposed cells showed no detectable p53 induction indicating that cell death is achieved by a p53-independent mechanism. Lastly, immunostaining of treated xenografts for phospho-Histone H3 revealed the presence of significantly higher numbers of immunopositive mitotic figures compared to untreated samples. Conclusions: These data suggest that TTField exposure resulted in defective entry into anaphase and interfered with orderly exit from mitosis, a mechanism of mitotic perturbation that differs from currently used spindle poisons. NovoTTF-100A may therefore exhibit synergism when combined with conventional cancer treatments. Supported in part by a grant from NovoCure, Inc. and A Reason To Ride research fund.
Association between infrastructure and observed quality of care in 4 healthcare services: A cross-sectional study of 4,300 facilities in 8 countries
Authors: Hannah H. Leslie, Zeye Sun, Margaret E. Kruk
Journal: PLoS Medicine (2017)

Background It is increasingly apparent that access to healthcare without adequate quality of care is insufficient to improve population health outcomes. We assess whether the most commonly measured attribute of health facilities in low- and middle-income countries (LMICs)—the structural inputs to care—predicts the clinical quality of care provided to patients. Methods and findings Service Provision Assessments are nationally representative health facility surveys conducted by the Demographic and Health Survey Program with support from the US Agency for International Development. These surveys assess health system capacity in LMICs. We drew data from assessments conducted in 8 countries between 2007 and 2015: Haiti, Kenya, Malawi, Namibia, Rwanda, Senegal, Tanzania, and Uganda. The surveys included an audit of facility infrastructure and direct observation of family planning, antenatal care (ANC), sick-child care, and (in 2 countries) labor and delivery. To measure structural inputs, we constructed indices that measured World Health Organization-recommended amenities, equipment, and medications in each service. For clinical quality, we used data from direct observations of care to calculate providers' adherence to evidence-based care guidelines. We assessed the correlation between these metrics and used spline models to test for the presence of a minimum input threshold associated with good clinical quality. Inclusion criteria were met by 32,531 observations of care in 4,354 facilities. Facilities demonstrated moderate levels of infrastructure, ranging from 0.63 of 1 in sick-child care to 0.75 of 1 for family planning on average. Adherence to evidence-based guidelines was low, with an average of 37% adherence in sick-child care, 46% in family planning, 60% in labor and delivery, and 61% in ANC. Correlation between infrastructure and evidence-based care was low (median 0.20, range from −0.03 for family planning in Senegal to 0.40 for ANC in Tanzania). Facilities with similar infrastructure scores delivered care of widely varying quality in each service. We did not detect a minimum level of infrastructure that was reliably associated with higher quality of care delivered in any service. These findings rely on cross-sectional data, preventing assessment of relationships between structural inputs and clinical quality over time; measurement error may attenuate the estimated associations. Conclusion Inputs to care are poorly correlated with provision of evidence-based care in these 4 clinical services. Healthcare workers in well-equipped facilities often provided poor care and vice versa. While it is important to have strong infrastructure, it should not be used as a measure of quality. Insight into health system quality requires measurement of processes and outcomes of care.
Abstract 16011: Prospective Associations of Left Atrial Size and Function With Cardiovascular Disease in American Indians: The Strong Heart Study
Authors: Maria G Karas, Shuo Xu, Elisa T Lee, Lyle G Best, Dedra Buchwald, Barbara V Howard, Mary J Roman, Richard B Devereux, Jorge R Kizer
Journal: Circulation (2016)

Introduction:  Left atrial (LA) volume is associated with incident cardiovascular disease (CVD) in studies involving referral populations. Fewer studies have examined the association of measures of LA function with CVD events in community-based cohorts without clinically apparent disease.   Methods:  We investigated the relations and predictive value of LA volume index (LAVI=LA volume/body surface area), LA emptying fraction (LAEF= [Max LA Volume - Min LA Volume]/Max LA Volume) and LA function index (LAFI=[LAEFxLV outflow tract velocity time integral]/LAVI) with CVD events (coronary heart disease, stroke, heart failure) in a population-based cohort study of American Indians with high prevalences of obesity and diabetes. We excluded participants with clinical CVD, atrial fibrillation and Echo valvular disease, leaving 2,753 participants for analysis (age 59±8 years, 65% women). Stored Echos were reviewed in a random subset of 2,128 participants, 1,899 of whom had measurable maximal and minimal LA volumes. LA volume was measured using the modified biplane area-length method.   Results:  During median f/u of 13.5 yrs, 595 CVD events occurred. After adjustment for age, sex, BMI, systolic BP, hypertensive medication, diabetes, smoking, total and HDL cholesterol, eGFR, albuminuria, CRP, and LA diameter, LAVI (HR per SD increment 1.12, 95% CI 1.01-1.23) and LAFI (HR per SD decrement 1.19 [1.08-1.32]) were significantly associated with CVD events, but LAEF was not (HR per SD decrement 1.09 [0.99-1.19]). These risk estimates were unchanged after additional adjustment for LV mass index, LV regional or global function, transmitral E/A, and MAC. LAVI and LAFI modestly improved risk prediction when added to a clinical model (c-index 0.767 and 0.768, respectively, vs. 0.761), as well as a model containing clinical and other Echo predictors (c-index 0.776 and 0.777 vs. 0.771). Addition of LAFI to LAVI in the latter model, however, did not further improve prediction (c-index 0.777 vs. 0.776).   Conclusion:  In this sample of American Indians, LAVI and LAFI were associated with CVD independent of clinical risk factors, LA diameter, and other Echo predictors. Both measures improved risk prediction, although there was no evidence of incremental value when LAFI was added to LAVI.
Polycystic liver disease: The interplay of genes causative for hepatic and renal cystogenesis
Authors: Tatyana V. Masyuk, Anatoliy I. Masyuk, Nicholas F. LaRusso
Journal: Hepatology (2017)

Masyuk, Tatyana V. Ph.D.1,†; Masyuk, Anatoliy I. Ph.D.1,†; LaRusso, Nicholas F. M.D.1 Author Information