tbuckley/cabot-search huggingface dataset:
Ligation-assisted endoscopic submucosal resection with apical mucosal incision to treat gastric subepithelial tumors originating from the muscularis propria
Authors: Dingguo Zhang, Qiuling Lin, Ruiyue Shi, Lisheng Wang, Jun Yao, Yanhui Tian
Journal: Endoscopy (2018)

Abstract Background This study aimed to evaluate the clinical efficacy, safety, and feasibility of performing endoscopic submucosal resection with a ligation device (ESMR-L) after apical mucosal incision (AMI) for the treatment of gastric subepithelial tumors originating from the muscularis propria (SET-MPs). Methods 14 patients with gastric SET-MPs were treated by ESMR-L with AMI between December 2016 and May 2017. The complete resection rate, operation duration, and postoperative complications were collected. All patients were followed for 2 – 6 months. Results The complete resection rate was 100 %, the mean tumor size was 10.71 ± 3.45 mm (7 – 18 mm), and the median operative time was 18.5 minutes. Perforation occurred in four patients, with all lesions being completely repaired endoscopically. No delayed bleeding or peritoneal signs were observed. No residual lesions or recurrence were found during the follow-up period. Conclusions AMI with ESMR-L appears to be an efficient and simple method for the histological diagnosis of gastric SET-MPs, but it carries a high perforation rate and cannot guarantee cure.
HIF2α in the uterine stroma permits embryo invasion and luminal epithelium detachment
Authors: Leona Matsumoto, Yasushi Hirota, Tomoko Saito-Fujita, Norihiko Takeda, Tomoki Tanaka, Takehiro Hiraoka, Shun Akaeda, Hidetoshi Fujita, Ryoko Shimizu-Hirota, Shota Igaue, Mitsunori Matsuo, Hirofumi Haraguchi, Mayuko Saito-Kanatani, Tomoyuki Fujii, Yutaka Osuga
Journal: Journal of Clinical Investigation (2018)

Although it has been reported that hypoxia inducible factor 2 α (Hif2a), a major transcriptional factor inducible by low oxygen tension, is expressed in the mouse uterus during embryo implantation, its role in pregnancy outcomes remains unclear. This study aimed to clarify functions of uterine HIF using transgenic mouse models. Mice with deletion of Hif2a in the whole uterus (Hif2a-uKO mice) showed infertility due to implantation failure. Supplementation with progesterone (P4) and leukemia inhibitory factor (LIF) restored decidual growth arrest and aberrant position of implantation sites in Hif2a-uKO mice, respectively, but did not rescue pregnancy failure. Histological analyses in Hif2a-uKO mice revealed persistence of the intact luminal epithelium, which blocked direct contact between stroma and embryo, inactivation of PI3K-AKT pathway (embryonic survival signal), and failed embryo invasion. Mice with stromal deletion of Hif2a (Hif2a-sKO mice) showed infertility with impaired embryo invasion and those with epithelial deletion of Hif2a (Hif2a-eKO mice) showed normal fertility, suggesting the importance of stromal HIF2α in embryo invasion. This was reflected in reduced expression of membrane type 2 metalloproteinase (MT2-MMP), lysyl oxidase (LOX), VEGF, and adrenomedullin (ADM) in Hif2a-uKO stroma at the attachment site, suggesting that stromal HIF2α regulates these mediators to support blastocyst invasion. These findings provide new insight that stromal HIF2α allows trophoblast invasion through detachment of the luminal epithelium and activation of an embryonic survival signal.
OP0191 All-cause mortality and cardiovascular death in hydroxychloroquine users in rheumatoid arthritis patients – a population based danish cohort study
Authors: K. Soeltoft, J. Hallas, M.C.M. Wasko, A.B. Pedersen, S.P. Ulrichsen, T. Ellingsen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with a marked increase in cardiovascular comorbidity and mortality(.<sup><sup>1</sup></sup> The increased risk is present from the earliest stages of the disease and evidence suggests an overlap in the pathogenic features leading to RA and atherosclerosis. Hydroxychloroquine (HCQ) is used to treat RA in combination with methotrexate and has been associated with decreased risk of type II diabetes and dyslipidaemia among RA patients. Also HCQ has improved survival rates when used to treat other inflammatory diseases, e.g. systemic lupus erythematosus(.<sup><sup>1</sup></sup> The evidence regarding RA patients is scarce. <h3>Objectives</h3> We wish to examine whether HCQ would affect the incidence rates of cardiovascular diseases, type II diabetes, cardiac – and all-cause mortality among Danish RA patients in an observational cohort study. <h3>Methods</h3> We identified all incident RA patients during the period of 2004 through 2014 in Denmark. HCQ initiators were compared with non-users of HCQ, stratified on rheumatoid factor positivity. Each HCQ initiator was matched to a non-HCQ initiator by their propensity score (PS). In the PS all relevant available cardiovascular drugs and comorbidities were included. All together we had 3,742 RA patients in each group. <h3>Results</h3> We found a significant reduction in all-cause mortality and cardiovascular related death among HCQ initiators, with a hazard ratio of 0.83 (95% confidence interval [CI] 0.71–0.97) and 0.78 (95% CI: 0.61 to 0.99), respectively. We did not find any association between HCQ use and development of type II diabetes or specific ischaemic events (myocardial infarctions and ischaemic strokes). <h3>Conclusions</h3> The beneficial properties on survival seen with HCQ use in other inflammatory diseases seem also applicable to RA patients. These results needs confirmation in a randomised setting but justifies the use of HCQ in combination with other conventional synthetic disease-modifying antirheumatic drugs even though the effect of HCQ, <i>per se</i>, on RA disease activity is limited. <h3>Reference</h3> [1] Rempenault C, Combe B, Barnetche T, Gaujoux-Viala C, Lukas C, Morel J, et al. Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: A systematic review and meta-analysis. Ann Rheum Dis2018Jan;77(1):98–103. <h3>Disclosure of Interest</h3> None declared
Association of Gestational Diabetes and Type 2 Diabetes Exposure In Utero With the Development of Type 2 Diabetes in First Nations and Non–First Nations Offspring
Authors: Brandy A. Wicklow, Elizabeth A. C. Sellers, Atul K. Sharma, Kristine Kroeker, Nathan C. Nickel, Wanda Philips-Beck, Garry X. Shen
Journal: JAMA Pediatrics (2018)

Type 2 diabetes is increasing worldwide, disproportionately affecting First Nations (FN) people. Identifying early-life determinants of type 2 diabetes is important to address the intergenerational burden of illness.To investigate the association of in utero exposure to gestational diabetes and type 2 diabetes, stratified by FN status, with the development of type 2 diabetes in offspring.This cohort study was derived from the linkage of a pediatric diabetes clinical database and a population-based research data repository in Manitoba, Canada. Mother-infant dyads with a hospital birth or midwifery report in the data repository between April 1, 1984, and April 1, 2008, were identified. The dates of analysis were August through December 2017. Children identified with type 1 diabetes, monogenic diabetes, or secondary diabetes were excluded.Primary exposures included maternal gestational diabetes or type 2 diabetes and FN status.The primary outcome was incident type 2 diabetes in offspring by age 30 years.In this cohort study of 467 850 offspring (mean follow-up, 17.7 years; 51.2% male), FN status and diabetes exposure were associated with incident type 2 diabetes in offspring after adjustment for sex, maternal age, socioeconomic status, birth size, and gestational age. Type 2 diabetes exposure conferred a greater risk to offspring compared with gestational diabetes exposure (3.19 vs 0.80 cases per 1000 person-years, P < .001). Compared with no diabetes exposure, any diabetes exposure accelerated the time to the development of type 2 diabetes in offspring by a factor of 0.74 (95% CI, 0.62-0.90) for gestational diabetes and a factor of 0.50 (95% CI, 0.45-0.57) for type 2 diabetes. First Nations offspring had a higher risk compared with non-FN offspring (0.96 vs 0.14 cases per 1000 person-years, P < .001). First Nations offspring had accelerated type 2 diabetes onset by a factor of 0.52 (95% CI, 0.49-0.55) compared with non-FN offspring. Neither interaction between FN and type 2 diabetes (0.92; 95% CI, 0.80-1.05) nor interaction between FN and gestational diabetes (0.97; 95% CI, 0.77-1.20) was significant (P = .21 and P = .75, respectively).Important differences exist in offspring risk based on type of diabetes exposure in utero. These findings have implications for future research and clinical practice guidelines, including early pregnancy screening and follow-up of the offspring.
THU0697 Risk of major congenital malformations associated with exposure to conventional synthetic disease modifying antirheumatic drugs in women with inflammatory arthritis: a population-based cohort study
Authors: M.A. De Vera, E.C. Sayre, N.W. Tsao, A. Howren
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Prior studies of perinatal exposure to conventional synthetic disease modifying antirheumatic drugs (csDMARDs) and risk of major congenital malformations (MCM) have often lacked comparator groups and specific timing of medication exposure. <h3>Objectives</h3> To evaluate the association between csDMARD use before and during pregnancy and risk of MCM. <h3>Methods</h3> We conducted a population-based, retrospective cohort study using British Columbia administrative data from 01/01/2002 and 12/31/2012 on all physician visits, hospital admissions, and dispensed medications, linked to a perinatal registry with valid information on date of conception. We created a pregnancy cohort of women with inflammatory arthritis (IA) using a case definition of 2 ICD9 codes≥2 months and ≤2 years apart for rheumatoid arthritis, systemic autoimmune rheumatic diseases, ankylosing spondylitis, juvenile idiopathic arthritis, and psoriatic arthritis. We categorised csDMARDs according to accepted safety profiles: Group 1 - antimalarials, cyclosporine-A, gold, and sulfasalazine; and Group 2 - methotrexate, leflunomide, cyclophosphamide, azathioprine, chlorambucil, penicillamine, mycophenolate mofetil, and minocycline. We defined exposure over two periods: binary use (yes/no) during the 90 days preconception and first trimester of pregnancy. The outcome was occurrence of ≥1 MCM identified at birth. We used logistic regression models fitted with generalised estimating equations. <h3>Results</h3> There were 598 pregnancies in 503 women (32±5 years), and 5651 pregnancies in 4086 women (31±5 years) in the csDMARDs exposed and unexposed groups, respectively. The adjusted odds ratio (OR) for exposure to csDMARDs preconception and during pregnancy and risk of MCM was 1.60 (95% CI, 1.19, 2.14) (table 1). In subgroup analyses, risk of MCM births was highest in those exposed to Group 2 csDMARDs during pregnancy (OR 3.63, 95% CI, 1.21, 10.92). For methotrexate specifically, we observed an OR of 1.62 (95% CI, 0.53, 4.91). <h3>Conclusions</h3> We found associations with exposure to csDMARDs before and during pregnancy, namely the first trimester, with MCMs. These have implications for informing women with IA who are pregnant or planning to become pregnant. <h3>Disclosure of Interest</h3> None declared
The trauma call
Authors: Simon J Mercer, Elizabeth V Kingston, Clinton P L Jones
Journal: BMJ (2018)

### What you need to know

Trauma is the leading cause of death for people under 40 in the UK, and a major cause of debilitating long-term injuries.1 Major trauma usually refers to a seriously injured patient or a patient with multiple injuries requiring a coordinated multidisciplinary approach to their care. Twenty percent of patients in the UK survive severe trauma. 2 An audit of the major trauma services in England identified deficiencies in care contributing to high in-hospital mortality in trauma patients.2 Typically, such patients are managed in the emergency department after a trauma call is put out to assemble a trauma team. The trauma team must rapidly assess seriously injured patients and start treatment in a timely manner.

Here we aim to help clinicians familiarise themselves with the essentials of managing patients with major trauma as part of a team in an emergency department, drawing from our experience, and from 2017 guidelines from the UK’s National Institute for Health and Care Excellence (NICE) for head injury and major trauma. The practice and team constitution may differ based on resources and organisation of health services in different countries, however we expect the basic principles of organising and responding as a trauma team will be relevant.

Trauma teams are assembled rapidly by …
Nutrition disparities and the global burden of malnutrition
Authors: Rafael Perez-Escamilla, Odilia Bermudez, Gabriela Santos Buccini, Shiriki Kumanyika, Chessa K Lutter, Pablo Monsivais, Cesar Victora
Journal: BMJ (2018)

Strategies to tackle stunting, obesity, and micronutrient deficiencies must take into account the inequities in which these diseases are rooted, argue <b>Rafael Perez-Escamilla and colleagues</b>
SAT0112 Guideline-based care improves outcomes that matter to patients: tighter control, less suffering, and greater well-being over the past decade in canadian ra patients
Authors: S. J. Bartlett, O. Schieir, M.-F. Valois, B. Haraoui, G. Boire, C. Thorne, C. Hitchon, D. Tin, E. C. Keystone, J. Pope, V. P. Bykerk
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Best practice recommendations can increase the quality of care and improve clinical outcomes, however, the impact of guideline-based care on outcomes that matter most to early RA patients before and after implementation of treat to target (T2T) recommendations has not been evaluated. <h3>Objectives:</h3> We compared changes over the first year of treatment in outcomes valued most by RA patients: 1) in relation to disease activity; and 2) prior (2007-10) and subsequent (2011-16) to the release of T2T and Canadian RA Recommendations. <h3>Methods:</h3> Data included early RA adults enrolled in CATCH (<b>C</b>anadian Early <b>A</b>r<b>T</b>hritis <b>C</b>o<b>H</b>ort) between 2007-16 who met 1987/2010 RA criteria with active disease at enrolment. Treatment was at the discretion of the rheumatologist and cohort investigators met annually to discuss ways to improve outcomes. We compared changes in DAS28, pain (0-10), fatigue (0-10), patient global (0-10), and HAQ-DI at 6 and 12 months prior to and after the release of guidelines using Cochran-Armitage trend tests and regression. <h3>Results:</h3> The sample included 1942 adults who were mostly female (72%) with a mean (SD) age of 55 (15), 2 (2) comorbidities, and symptom duration of 6 (3) months. At enrollment, almost all (95%) were in DAS28 moderate disease activity [MDA; 42%] or high disease activity [HDA; 53%], and were initially treated with csDMARDS (92%) and MTX (75%). CDAI, DAS28 and PROs by DAS28 disease levels are shown in the Table. <h3>Conclusions:</h3> Results from this large country-wide study suggest that T2T results in better disease control in the first year of RA with similar improvements in pain, fatigue, and disability--symptoms that patients identify as important--resulting in greater overall well-being. These data offer additional evidence supporting the importance of early identification and rapid control of RA to improve long-term outcomes and QOL. <h3>Acknowledgements:</h3> Sponsors: Amgen &amp; Pfizer-Founding sponsors 2007+; UCB, AbbVie 2011+; Medexus 2013+; Eli Lilly, Sanofi- Genzyme 2016+; Merck 2017+; BMS 2011-2014, Hoffmann-LaRoche, Janssen 2011-2016 <h3>Disclosure of Interest:</h3> None declared
ASXL1/EZH2 mutations promote clonal expansion of neoplastic HSC and impair erythropoiesis in PMF
Authors: Ioanna Triviai, Silke Zeschke, Jan Rentel, Marios Spanakis, Theo Scherer, Razif Gabdoulline, Victoria Panagiota, Felicitas Thol, Michael Heuser, Carol Stocking, Nicolaus Kröger
Journal: Leukemia (2018)
SAT0017 The rheumatoid factor response is composed of multiple reactivities against different epitopes
Authors: W. Falkenburg, J. Koers, P. Oijevaar-de Heer, D. van Schaardenburg, G. Wolbink, T. Rispens
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a complex autoimmune disorder in which autoantibodies likely play an important role. Rheumatoid factors (RFs) are autoantibodies that bind to the constant domain (Fc) of immunoglobulin G (IgG). It is known that they can bind in various ways; most RA patients probably have multiple types of RFs that all bind different parts of antibodies. It is presently unknown how this differs between patients. Furthermore, it is possible that RF responses in RA have a different reactivity pattern compared to those present in other diseases and in RF +healthy donors. Currently, these RA-specific RFs have not yet been identified. <h3>Objectives</h3> To develop a method to identify and dissect different RF responses, to classify the RF response in different stages of RA, and to characterise differences in reactivity between RF responses in the context of RA and RF responses in other diseases or healthy donors. <h3>Methods</h3> Variants of human IgG antibodies to which only a few different types of RFs can bind at a time were generated and used as target antibodies in newly developed ELISA-based RF assays. RF responses were analysed in healthy donors, arthralgia patients at risk for RA and RA patients at different disease stages. <h3>Results</h3> RF responses in all cohorts were shown to be primarily directed against epitopes at the interface of the second and third IgG heavy chain domains (CH2-CH3) and the tip of the CH3 domain. The generated target antibodies were able to separate these RF responses and discriminate them from RF responses targeting epitopes outside these reactivity hotspots. Furthermore, certain RF responses against the CH2-CH3 interface were shown to depend on the presence of a single specific amino acid residue. Pilot experiments using the target antibodies in clinical cohorts revealed that, in arthralgia patients and RA patients at various disease stages, the pattern of RF reactivity differs between individual patients as well as between cohorts. The degree to which an RF response against the CH2-CH3 interface depends on the single specific amino acid residue varied substantially between patients. One particular RF response pattern, RFs binding only the CH3 domain, was found exclusively in non-RA patients and healthy donors. <h3>Conclusions</h3> Using newly developed target IgGs, RF responses against different epitopes can be characterised. RF response patterns differ between RA and non-RA cohorts and between RA patients. These new tools may lead to identification of RA-specific RF responses and provide more insight into the pathogenic role of these autoantibodies. <h3>Disclosure of Interest</h3> None declared
AB1377 Is the patient global health assessment reliable in juvenile idiopathic arthritis (JIA)?
Authors: R. Trachtman, C.M. Wang, J. Szymonifka, K.B. Onel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> JIA is a chronic autoimmune disease that poses many challenges. There is increasing recognition of the importance of patient-reported outcomes (PROs) and newer PROs are being developed and more widely utilised both in clinical care and in research, However, their performance and reliability remain unclear. <h3>Objectives</h3> This study seeks to evaluate:<sup>1</sup> performance of the patient global health assessment (PGA) compared to standard disease activity measures in children with JIA,<sup>2</sup> correlations of the PGA with socioeconomic status (SES) in JIA, and<sup>3</sup> relationship between PGA and physician global health assessment in JIA. <h3>Methods</h3> A convenience sample of patients with JIA (n=47) aged 2–18 were recruited from a single centre. Patients aged ≥10 years completed the questionnaire, and parents of patients aged 2–9 completed a proxy questionnaire for their child. Correlations between<sup>1</sup> the PGA and disease activity, as measured by the Juvenile Disease Activity Score-71 (JADAS-71),<sup>2</sup> the PGA and physician global health assessment, and<sup>3</sup> the physician global health assessment and the JADAS-71 were evaluated using Spearman correlation coefficients. PGAs were compared by age, sex, insurance status, race, and ethnicity; and differences between PGA and physician global health assessments were compared using Wilcoxon rank-sum tests. <h3>Results</h3> 16 parents and 31 patients completed the assessments (table 1). There was a moderate correlation between PGA and JADAS-71 (r=0.503, p&lt;0.001), and PGA and physician global health assessments (r=0.503, p=0.002). There was a stronger correlation between physician global health assessments and JADAS-71. PGA median scores and IQRs appeared to be higher among patients with Medicaid insurance, non-white race, and Hispanic ethnicity, with the greatest difference seen in the category of race (Table 2). There were no differences between patient and physician assessments across all groups except among patients with Medicaid (difference median=−1.25) and Hispanic patients (difference median=2). <h3>Conclusions</h3> Our results demonstrate that physician global health assessment had a stronger correlation with standard disease activity measures than the PGA. These scores were higher in patients who were non-White race, Hispanic, and had Medicaid insurance; however, these were not statistically significant. These data indicate that the PGA is fairly stable across groups, and can be used reliably for disease monitoring. <h3>Disclosure of Interest</h3> None declared
Problematic End Points in a Trial of Topical Fluorouracil, 5%, for Chemoprevention of Keratinocyte Carcinoma—Reply
Authors: Martin A. Weinstock, Robert A. Lew, Fiona M. Shaw
Journal: JAMA Dermatology (2018)

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The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates
Authors: Natalie I Mazur, Deborah Higgins, Marta C Nunes, José A Melero, Annefleur C Langedijk, Nicole Horsley, Ursula J Buchholz, Peter J Openshaw, Jason S McLellan, Janet A Englund, Asuncion Mejias, Ruth A Karron, Eric AF Simões, Ivana Knezevic, Octavio Ramilo, Pedro A Piedra, Helen Y Chu, Ann R Falsey, Harish Nair, Leyla Kragten-Tabatabaie, Anne Greenough, Eugenio Baraldi, Nikolaos G Papadopoulos, Johan Vekemans, Fernando P Polack, Mair Powell, Ashish Satav, Edward E Walsh, Renato T Stein, Barney S Graham, Louis J Bont
Journal: The Lancet Infectious Diseases (2018)