tbuckley/cabot-search huggingface dataset:
Treatment of systemic lupus erythematosus: don’t forget hydroxychloroquine
Authors: Martin Michaud, Florian Catros, Sophie Ancellin, Francis Gaches
Journal: Annals of the Rheumatic Diseases (2019)

Treatment of systemic lupus erythematosus: don't forget hydroxychloroquineWe read with interest the last 2019 update of the European League Against Rheumatism recommendations for the management of systemic lupus erythematosus (SLE). 1 We agree with the comment by Gabriel Figueroa-Parra et al concerning the lack of mention of chloroquine as major treatment in SLE. 2 Concerning survival, the LUMINA study group also showed that use of hydroxychloroquine (HCQ) was associated with a greater survival rate in 608 patients with SLE. 3 Ruiz-Irastorza et al confirmed these results in 232 patients with SLE. 4 The 15-year survival rate was 0.95 for patients using HCQ versus 0.68 for patients without antimalarial therapy.Finally, use of HCQ was also independently associated with a greater survival in a population of patients with SLE with nephritis. 5he LUpus in MInorities, NAture versus nurture (LUMINA) study group also showed that patients without HCQ had higher damage scores and were more likely to have renal disease or central nervous system disease and use of HCQ was associated with a reduced risk of developing new damage in multivariate analysis. 3The Canadian Hydroxychloroquine Study Group realised a double-blinded, placebo-controlled study that included patients with SLE to compare HCQ with placebo. 6The risk of SLE flares (including major flares) increased by 2.5 at the end of the 6-months follow-up period in the placebo group compared with the HCQ group.During the additional 3 years follow-up study, use of HCQ reduced major flares by 57%. 7Meinao et al published another double-blind placebo-controlled trial with chloroquine diphosphate steroid requirements and SLE Disease Activity Index score were higher in the placebo group and the flare risk was 4.6 times greater in the placebo group. 8oreover, patients with lower blood HCQ concentrations have greater SLE disease activity and have a greater risk of disease flare. 9 10During pregnancy, HCQ use is essential.][13] In conclusion, HCQ is still in 2019, the cornerstone of the treatment of SLE.
Partial Aortic Valve Leaflet Fusion Is Related to Deleterious Alteration of Proximal Aorta Hemodynamics
Authors: Andrea Guala, Jose Rodriguez-Palomares, Laura Galian-Gay, Gisela Teixido-Tura, Kevin M. Johnson, Oliver Wieben, Augusto Sao Avilés, Arturo Evangelista
Journal: Circulation (2019)
PTH-028 Use of PPIS in acute non-variceal upper GI bleeds in a university teaching hospital
Authors: Anjum Gardezi, Clare Tibbats, Usama Aslam, Laura Chase, Heba Fahmy
Journal: Endoscopy (2018)

<h3>Introduction</h3> Acute non-variceal upper GI bleeds are a common presentation to UK hospitals. NICE guidelines state patients should not receive treatment with proton pump inhibitors (PPI) prior to endoscopy<sup>1</sup>, as the 2010 Cochrane review<sup>2</sup> showed no reduction in mortality, re-bleeding or need for surgery. The review did however show a reduction in the requirement for endoscopic therapy.<sup>2</sup> <h3>Methods</h3> We carried out a retrospective review of 763 patients who received an upper GI endoscopy for non-variceal bleeding between September 2010 and September 2013 at Cardiff and Vale University health board. Patients were divided into 2 groups depending on the receipt of PPI's pre-endoscopy. We then compared outcomes for both groups including mortality, need for surgery, re-bleeding and need for intervention at endoscopy. <h3>Results</h3> Our data showed 77% of patients were treated with a PPI pre-endoscopy despite NICE guidelines. There was not a significant difference in death rates (9% vs 14%, p=0.91), need for surgery (3% vs 2% p=0.28) or re-bleeding (6% vs 8% p=0.37) in these patients. Our data does show a significant reduction in the need for endoscopic intervention (p=0.014) in patients pre-treated with a PPI. <h3>Conclusion</h3> Use of PPI pre-endoscopy is not detrimental to patient outcomes and our data supports the existing evidence base suggesting a reduction in the need for endoscopic intervention<sup>2</sup>. Further study is needed to evaluate the cost effectiveness of PPI use pre-endoscopy. <h3>References</h3> . NICE Guidelines. https://www.nice.org.uk/guidance/cg141/chapter/1-Guidance . Sreedharan A, et al. Proton Pump Inhibitor treatment initiated prior to endoscopic diagnosis in upper GI bleeding, Cochrane review 2010.
Time to Change From Do-Not-Resuscitate Orders to Emergency Care Treatment Plans
Authors: Gavin D. Perkins, Zoe Fritz
Journal: JAMA Network Open (2019)

Christoph Becker, MD; Leopold Lecheler, MD; Seraina Hochstrasser, MD; Kerstin A. Metzger, MD; Madlaina Widmer, MD; Emanuel B. Thommen, MD; Katharina Nienhaus, MD; Hannah Ewald, MPH; Christoph A. Meier, MD; Florian Rueter, MD; Rainer Schaefert, MD; Stefano Bassetti, MD; Sabina Hunziker, MD, MPH
ERCP with overtube-assisted enteroscopy in patients with Roux-en-Y gastric bypass anatomy: a systematic review and meta-analysis
Authors: Jagpal Singh Klair, Mahendran Jayaraj, Viveksandeep Thoguluva Chandrasekar, Harshith Priyan, Joanna Law, Arvind R. Murali, Dhruv Singh, Michael Larsen, Shayan Irani, Richard Kozarek, Andrew Ross, Rajesh Krishnamoorthi
Journal: Endoscopy (2020)

Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastric bypass (RYGB) anatomy is challenging. Overtube-assisted enteroscopy (OAE) is usually needed to perform ERCP in these patients. There is significant variation in the reported rates of success and adverse events across published studies. We performed a systematic review and meta-analysis to reliably estimate the pooled rates of success and adverse events. Methods We performed a systematic search of multiple electronic databases through February 2020 to identify studies reporting outcomes of OAE-ERCP in post-RYGB patients. The pooled rates of enteroscopy success, technical success, and adverse events were estimated for OAE-ERCP. The pooled rates of success and adverse events were also estimated for ERCP using double-balloon enteroscopes (DBE) alone. Results 10 studies reporting a total of 398 procedures were included in the meta-analysis. The pooled rates of enteroscopy and technical success of OAE-ERCP were 75.3 % (95 % confidence interval [CI] 64.5 – 83.6) and 64.8 % (95 %CI 53.1 – 74.9) respectively. The pooled rate of adverse events was 8.0 % (95 %CI 5.2 – 12.2). The pooled rates of enteroscopy and technical success of DBE-ERCP (four studies) were 83.5 % (95 %CI 68.3 – 92.2) and 72.5 % (95 %CI 52.3 – 86.4), respectively. The pooled rate of adverse events with DBE-ERCP was 9.0 % (95 %CI 5.4 – 14.5). Substantial heterogeneity was noted. Conclusions OAE-ERCP appears to be effective and safe in post-RYGB patients. Among the currently available techniques, OAE-ERCP is the least invasive approach in this challenging group of patients. Future studies comparing the effectiveness and safety of alternative novel techniques, such as endosonography-directed transgastric ERCP, with OAE-ERCP are needed.
Macrolide Resistance in MORDOR I — A Cluster-Randomized Trial in Niger
Authors: Thuy Doan, Ahmed M Arzika, Armin Hinterwirth, Ramatou Maliki, Lina Zhong, Susie Cummings, Samarpita Sarkar, Cindi Chen, Travis C Porco, Jeremy D Keenan, Thomas M Lietman
Journal: New England Journal of Medicine (2019)

Trial in NigerTo the Editor: Mass administration of azithromycin reduced childhood mortality in the trials MORDOR (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) I 1,2 and MORDOR II (conducted by Keenan et al., published in this issue of the Journal 3 ).However, antibiotic resistance remains a major concern, and MORDOR I did not include assessments of morbidity.We randomly selected 3371 children aged 1 to 59 months from the same pool of 30 Nigerien communities involved in MORDOR I (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).The children were randomly assigned to receive either azithromycin or placebo, which were distributed twice a year over 2 years, as in MORDOR I (for details, see the protocol, available at NEJM.org).The mean (±SD) coverage with azithromycin and placebo was 79±8% and 82±6%, respectively.Ethical approval was obtained from the University of California, San Francisco, Committee for Human Research and the Ethics Committee of the Niger Ministry of Health.We obtained oral consent from guardians before treatment and before collection of nasopharyngeal and rectal swabs.No incentives were offered.All analyses were conducted at the community level.We compared the proportions of macrolideresistant pneumococcus in the children in the azithromycin group and those in the placebo group with the use of broth dilution assays of pneumococcus isolated from nasopharyngeal swabs collected at 24 months (6 months after the fourth twice-yearly treatment).Pneumococcus isolation and resistance testing were performed according to standard protocols at ARUP (a ref-
Mini-invasive treatment of sump syndrome: OverStitch choledochoduodenostomy revision
Authors: Antonino Granata, Michele Amata, Alberto Martino, Dario Ligresti, Sergio Li Petri, Calogero Ricotta, Mario Traina
Journal: Endoscopy (2019)

A 72-year-old woman, who was unfit for surgery, was admitted with recurrent cholangitis. She had a history of cholecystectomy and side-to-side choledochoduodenostomy (CDD) for huge impacted stones. In the previous year, she had undergone multiple endoscopic retrograde cholangiopancreatographies (ERCPs) with endoscopic sphincterotomy, incomplete stone extractions, and plastic stent placement in a local hospital. Magnetic resonance cholangiography showed multiple stones throughout the biliary tree, which was dilated up to 4 cm, along with an incarcerated plastic stent.
The Shape of the Concentration–Response Association between Fine Particulate Matter Pollution and Human Mortality in Beijing, China, and Its Implications for Health Impact Assessment
Authors: Meilin Yan, Ander Wilson, Michelle L. Bell, Roger D. Peng, Qinghua Sun, Weiwei Pu, Xiaomei Yin, Tiantian Li, G. Brooke Anderson
Journal: Environmental Health Perspectives (2019)

Background: Studies found approximately linear short-term associations between particulate matter (PM) and mortality in Western communities. However, in China, where the urban PM levels are typically considerably higher than in Western communities, some studies suggest nonlinearity in this association. Health impact assessments (HIA) of PM in China have generally not incorporated nonlinearity in the concentration–response (C-R) association, which could result in large discrepancies in estimates of excess deaths if the true association is nonlinear. Objectives: We investigated nonlinearity in the C-R associations between with PM with aerodynamic diameter ≤2.5μm (PM2.5) and mortality in Beijing, China, and the sensitivity of HIA to linearity assumptions. Methods: We modeled the C-R association between PM2.5 and cause-specific mortality in Beijing, China (2009–2012), using generalized linear models (GLM). PM2.5 was included through either linear, piecewise-linear, or spline functions to investigate evidence of nonlinearity. To determine the sensitivity of HIA to linearity assumptions, we estimated PM2.5-attributable deaths using both linear- and nonlinear-based C-R associations between PM2.5 and mortality. Results: We found some evidence that, for nonaccidental and circulatory mortality, the shape of the C-R association was relatively flat at lower concentrations of PM2.5, but then had a positive slope at higher concentrations, indicating nonlinearity. Conversely, the shape for respiratory mortality was positive and linear at lower concentrations of PM2.5, but then leveled off at the higher concentrations. Estimates of excess deaths attributable to short-term PM2.5 exposure were, in some cases, very sensitive to the linearity assumption in the association, but in other cases robust to this assumption. Conclusions: Our results demonstrate some evidence of nonlinearity in PM2.5–mortality associations and that an assumption of linearity in this association can influence HIAs, highlighting the importance of understanding potential nonlinearity in the PM2.5–mortality association at the high concentrations of PM2.5 in developing megacities like Beijing. https://doi.org/10.1289/EHP4464
Prevalence of Advanced Liver Fibrosis in Patients With Severe Psoriasis
Authors: Catriona M. Maybury, Heather F. Porter, Ewa Kloczko, Michael Duckworth, Alice Cotton, Kate Thornberry, Tracy Dew, Martin Crook, Sarah Natas, Rosa Miquel, Cathryn M. Lewis, Terry Wong, Catherine H. Smith, Jonathan N. Barker
Journal: JAMA Dermatology (2019)

Advanced liver fibrosis is a precursor to cirrhosis, a leading cause of mortality. People with severe psoriasis are at risk for liver disease, but our understanding of advanced fibrosis in individuals with psoriasis is limited.To describe the prevalence of and evaluate the clinical factors associated with advanced liver fibrosis in people with severe psoriasis.The Co-morbidities in Severe Psoriasis study, a prospective observational cohort study in a large center serving London and Southeast England, was conducted from October 18, 2012, to April 2, 2015; 400 adults with severe psoriasis (Psoriasis Area Severity Index score, ≥10) were recruited from outpatient clinics. Statistical analysis was conducted from October 2, 2016, to March 3, 2017.The primary outcome was a diagnosis of advanced liver fibrosis determined by transient elastography, a noninvasive criterion standard test. Clinical factors evaluated included psoriasis-specific and metabolic indices, alcohol use, and methotrexate exposure.Of 400 patients recruited (108 women and 289 men; mean [SD] age, 49.5 [13] years), 333 had a successful transient elastography scan and were included in final analysis. Forty-seven patients (14.1%; 95% CI, 10.4%-17.9%) had advanced liver fibrosis as diagnosed by transient elastography. The clinical factors that produced the best-fit model for advanced fibrosis were central obesity (waist circumference), insulin resistance, aspartate aminotransferase level, platelet count, psoriasis disease severity, and reduced alcohol use (R2 = 0.54).Findings from this study suggest that advanced fibrosis is common in severe psoriasis. Abdominal obesity (by waist circumference) and insulin resistance were associated with the presence of advanced fibrosis. Longitudinal work to characterize the hepatic sequelae of central obesity, insulin resistance, and inflammation as well as the influence of systemic drugs (methotrexate and biologics) will inform future personalized therapeutic decision-making.ClinicalTrials.gov identifier: NCT02174367.
Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial
Authors: Alexander Dimitri Miras, Belén Pérez-Pevida, Madhawi Aldhwayan, Anna Kamocka, Emma Rose McGlone, Werd Al-Najim, Harvinder Chahal, Rachel L Batterham, Barbara McGowan, Omar Khan, Veronica Greener, Ahmed R Ahmed, Aviva Petrie, Samantha Scholtz, Stephen R Bloom, Tricia M Tan
Journal: The Lancet Diabetes & Endocrinology (2019)
Spatial distribution of IL4 controls iNKT cell-DC crosstalk in tumors
Authors: Lu Wang, Zhilan Liu, Lili Wang, Qielan Wu, Xiang Li, Di Xie, Huimin Zhang, Yongdeng Zhang, Lusheng Gu, Yanhong Xue, Ting Yue, Gang Liu, Wei Ji, Haiming Wei, Tao Xu, Li Bai
Journal: Cellular and Molecular Immunology (2019)

The spatiotemporal distribution of cytokines orchestrates immune responses in vivo, yet the underlying mechanisms remain to be explored. We showed here that the spatial distribution of interleukin-4 (IL4) in invariant natural killer T (iNKT) cells regulated crosstalk between iNKT cells and dendritic cells (DCs) and controlled iNKT cell-mediated T-helper type 1 (Th1) responses. The persistent polarization of IL4 induced by strong lipid antigens, that is, α-galactosylceramide (αGC), caused IL4 accumulation at the immunological synapse (IS), which promoted the activation of the IL4R-STAT6 (signal transducer and activator of transcription 6) pathway and production of IL12 in DCs, which enhanced interferon-γ (IFNγ) production in iNKT cells. Conversely, the nonpolarized secretion of IL4 induced by Th2 lipid antigens with a short or unsaturated chain was incapable of enhancing this iNKT cell-DC crosstalk and thus shifted the immune response to a Th2-type response. The nonpolarized secretion of IL4 in response to Th2 lipid antigens was caused by the degradation of Cdc42 in iNKT cells. Moreover, reduced Cdc42 expression was observed in tumor-infiltrating iNKT cells, which impaired IL4 polarization and disturbed iNKT cell-DC crosstalk in tumors.
Risk of post-colonoscopy colorectal cancer in Denmark: time trends and comparison with Sweden and the English National Health Service
Authors: Lasse Pedersen, Roland Valori, Inge Bernstein, Karen Lindorff-Larsen, Charlotte Green, Christian Torp-Pedersen
Journal: Endoscopy (2019)

Abstract Background The post-colonoscopy colorectal cancer (PCCRC) rate is a key quality indicator for colonoscopy. Previously published PCCRC rates have been difficult to compare owing to differences in methodology. The primary aim of this study was to compare Danish PCCRC rates internationally and to calculate Danish PCCRC rates using the World Endoscopy Organization (WEO) consensus method for future comparison. The secondary aim was to identify factors associated with PCCRC. Methods National registries were used to examine the risk of PCCRC. The Danish 3-year rate of PCCRC (PCCRC-3yr) was calculated using previously published methods from England, Sweden, and the WEO. Poisson regression analysis was performed to identify factors associated with PCCRC. Results The Danish PCCRC-3yr was significantly higher than the rate in the English NHS (relative risk [RR] 1.12, 95 % confidence interval [CI] 1.05 – 1.19) and Sweden (RR 1.15, 95 %CI 1.06 – 1.24). The Danish PCCRC-3yr based on the WEO consensus method fell from 22.5 % in 2001 to 7.9 % in 2012. The multivariable Poisson regression model found PCCRC to be significantly associated with diverticulitis (RR 3.25, 95 %CI 2.88 – 3.66), ulcerative colitis (RR 3.44, 95 %CI 2.79 – 4.23), hereditary cancer (age &lt; 60 years: RR 7.39, 95 %CI 5.77 – 9.47; age ≥ 60 years: RR 3.81, 95 %CI 2.74 – 5.31), and location in the transverse (RR 1.57, 95 %CI 1.28 – 1.94) and ascending colon (RR 1.85, 95 %CI 1.64 – 2.08). Conclusions The PCCRC-3yr was higher in Denmark than in comparable countries. Differences in colonoscopist training, background, and certification are possible contributing factors. A review of colonoscopist training and certification in Denmark, and continuous audit and feedback of colonoscopist performance may reduce PCCRC-3yr.
A child with a congenital hand anomaly
Authors: Jenny Wright, Mark Pickford, Asit Khandwala
Journal: BMJ (2019)

A 5 month old infant attended a paediatric hand clinic with his parents. The presenting complaint was a duplicated thumb on his right hand. The anomaly was first detected on a routine baby check by a paediatric SHO, who referred the infant to a paediatric hand surgeon.

The child’s parents confirmed that the baby was born at term and was otherwise clinically well. There was no family history of congenital hand abnormalities.

On examination, the patient had two well formed thumbs on his right hand (fig 1); each with a nail plate. Both thumbs were reduced in size compared with the contralateral thumb and both had poorly defined interphalangeal joint creases (fig 1a), indicative of reduced mobility. The radial sided thumb was axially deviated (ulnarwards), whereas the ulnar sided thumb was well aligned.



Fig 1 
Photograph of …
Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model
Authors: Bryan B. Hsu, Travis E. Gibson, Vladimir Yeliseyev, Qing Liu, Lorena Lyon, Lynn Bry, Pamela A. Silver, Georg K. Gerber
Journal: Cell Host & Microbe (2019)

Highlights•Phages can coexist over time with targeted gut bacteria•Phages induce cascading effects on microbiota species that are not directly targeted•Phage-induced bacterial modulation impacts the gut metabolome•Phages can modulate metabolites, which are known to affect the mammalian hostSummaryThe human gut microbiome is comprised of densely colonizing microorganisms including bacteriophages, which are in dynamic interaction with each other and the mammalian host. To address how bacteriophages impact bacterial communities in the gut, we investigated the dynamic effects of phages on a model microbiome. Gnotobiotic mice were colonized with defined human gut commensal bacteria and subjected to predation by cognate lytic phages. We found that phage predation not only directly impacts susceptible bacteria but also leads to cascading effects on other bacterial species via interbacterial interactions. Metabolomic profiling revealed that shifts in the microbiome caused by phage predation have a direct consequence on the gut metabolome. Our work provides insight into the ecological importance of phages as modulators of bacterial colonization, and it additionally suggests the potential impact of gut phages on the mammalian host with implications for their therapeutic use to precisely modulate the microbiome.Graphical abstract
Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors
Authors: Samuel Chung, Nathalie Baumlin, John S. Dennis, Robert Moore, Sebastian F. Salathe, Phillip L. Whitney, Juan Sabater, William M. Abraham, Michael D. Kim, Matthias Salathe
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Electronic cigarette (e-cig) use has been widely adopted under the perception of safety. However, possibly adverse effects of e-cig vapor in never-smokers are not well understood.Objectives: To test the effects of nicotine-containing e-cig vapors on airway mucociliary function in differentiated human bronchial epithelial cells isolated from never-smokers and in the airways of a novel, ovine large animal model.Methods: Mucociliary parameters were measured in human bronchial epithelial cells and in sheep. Systemic nicotine delivery to sheep was quantified using plasma cotinine levels, measured by ELISA.Measurements and Main Results:In vitro, exposure to e-cig vapor reduced airway surface liquid hydration and increased mucus viscosity of human bronchial epithelial cells in a nicotine-dependent manner. Acute nicotine exposure increased intracellular calcium levels, an effect primarily dependent on TRPA1 (transient receptor potential ankyrin 1). TRPA1 inhibition with A967079 restored nicotine-mediated impairment of mucociliary parameters including mucus transport in vitro. Sheep tracheal mucus velocity, an in vivo measure of mucociliary clearance, was also reduced by e-cig vapor. Nebulized e-cig liquid containing nicotine also reduced tracheal mucus velocity in a dose-dependent manner and elevated plasma cotinine levels. Importantly, nebulized A967079 reversed the effects of e-cig liquid on sheep tracheal mucus velocity.Conclusions: Our findings show that inhalation of e-cig vapor causes airway mucociliary dysfunction in vitro and in vivo. Furthermore, they suggest that the main nicotine effect on mucociliary function is mediated by TRPA1 and not nicotinic acetylcholine receptors.
Abstract 20413: Microrna-195 Promotes Apoptosis in Cardiomyocytes by Down-Regulating Sirt1
Authors: Huaqing Zhu, Yixin Yang, Tianqing Peng
Journal: Circulation (2010)

Background: Saturated free fatty acids induce apoptosis in cardiomyocytes, which is implicated in diabetic cardiomyopathy. However, the underlying mechanisms remain not fully understood. MiRNAs are...