tbuckley/cabot-search huggingface dataset:
Abstract 16329: Multimorbidity and Quality of Life in Heart Failure Patients With Poor Self-care Behavior
Authors: Shiho Matsuoka, Miyuki Tsuchihashi-Makaya, Akiko Okada, Takahiro Kayane, Michiyo Yamada, Rumi Wakabayashi, Miyuki Yazawa
Journal: Circulation (2015)

Introduction: Multimorbidity, the co-occurrence of various chronic conditions, is of major concern in patients with heart failure (HF) because it is associated with impaired quality of life (QOL) and adverse outcomes. Effective self-care is an essential adjunct to evidence-based medical treatment aimed at delaying progression of HF. Hypothesis: This study investigated the relationships between multimorbidity, QOL and level of self-care in HF patients. Methods: Study subjects completed questionnaires on HF-related quality of life (Minnesota Living with Heart Failure questionnaire), HF-related self-care behaviors (European Heart Failure Self-Care Behavior Scale), HF-related knowledge (Japanese heart failure knowledge scale) and depression symptoms. Comorbidities and other clinical and social characteristics were also assessed. Analyses of covariance and multivariate linear regression were used to assess associations between multimorbidity and QOL. Results: A total of 231 outpatients with HF were assessed; 119 with poor self-care (self-care score&lt; 34) and 112 with adequate self-care (self-care score≥34); mean age 65.8 ± 13.9 and 69.8 ± 13.7 years, respectively. Of these patients, 57.6% had three or more additional chronic conditions; the most prevalent being hypertension (56.0%) and chronic kidney disease (46.6%). Patients with multimorbidity had worse QOL than patients without (P &lt; 0.01). Subjects with poor self-care and multimorbidity had worse QOL than those without multimorbidity (P &lt; 0.01); however, there was no association between multimorbidity and QOL in patients with adequate self-care. Multivariate analysis controlling for the effects of other variables showed that multimorbidity was an independent determinant of QOL overall and in poor self-care patients (sβ = 0.15, P = 0.04; sβ = 0.28, P &lt; 0.01, respectively). However, in patients with adequate self-care, multimorbidity was not associated with QOL. Conclusions: Multimorbidity is an independent determinant of QOL in HF patients with poor self-care. To improve their QOL, both reinforcement of adequate self-care behavior regarding their HF and a multidimensional approach to enhancing self-management of their comorbidities are needed.
Drug companies are unwilling to share information on trial protocols, study finds
Authors: Anne Gulland
Journal: BMJ (2018)

Drug companies are withholding information on trial protocols, a study has found, as half of commercially sponsored trial protocols contain redactions.

The authors of the study, published in the Journal of the Royal Society of Medicine ,1 requested access to trial protocols approved by a research ethics committee in Denmark from October 2012 to March 2013. They requested access to 78 commercial and non-commercial protocols under freedom of information rules, but gaining access was difficult: despite the researchers’ assurances that …
CARD14-associated papulosquamous eruption: A spectrum including features of psoriasis and pityriasis rubra pilaris
Authors: Brittany G. Craiglow, Lynn M. Boyden, Ronghua Hu, Marie Virtanen, John Su, Gabriela Rodriguez, Catherine McCarthy, Paula Luna, Margarita Larralde, Stephen Humphrey, Kristen E. Holland, Marcia Hogeling, Benjamin Hidalgo-Matlock, Bruno Ferrari, Esteban Fernandez-Faith, Beth Drolet, Kelly M. Cordoro, Anne M. Bowcock, Richard J. Antaya, Kurt Ashack, Richard J. Ashack, Richard P. Lifton, Leonard M. Milstone, Amy S. Paller, Keith A. Choate
Journal: Journal of the American Academy of Dermatology (2018)
Reply to Federico Gheza, Simone Crivellaro, and Gian Luca Baiocchi's Letter to the Editor re: Lee C. Zhao, Aaron C. Weinberg, Ziho Lee, et al. Robotic Ureteral Reconstruction Using Buccal Mucosa Grafts: A Multi-institutional Experience. Eur Urol 2018;73:419–26. Robotic Ureteral Reconstruction with Buccal Mucosal Graft: A Call Not To Lose Momentum
Authors: Aaron Weinberg, Lee Zhao
Journal: European Urology (2018)
Abstract 15816: Normal Distribution of Wall Shear Stress in the Coronary Arteries
Authors: Anna Starikov, Guanglei Xiong, James K Min
Journal: Circulation (2015)

Introduction: The ability to detect hemodynamically significant coronary artery disease non-invasively has been a goal that has the potential to improve patient care significantly. New non-invasive approaches using coronary CT angiograms (CCTAs) have been proposed and appear to show some promise. Hypothesis: One such method is the measurement of measuring wall shear stress (WSS), the tangential force of flowing blood against the artery wall, using computational fluid dynamics (CFD). However, in order to deem this technique useful in clinical practice, the normal values must first be defined. These values have been minimally reported and are limited to the left coronary tree. Methods: We ran a CFD simulation of WSS on 3-D reconstructions of the coronary arteries derived from the CCTAs of 35 patients with either no disease or non-obstructive (&lt; 50%) stenosis from the DeFACTO trial, a multi-center study. The resulting model was segmented according to the Society of Cardiovascular CT guidelines, separating the proximal and distal parts of each artery as well as the major side branches. The segments were composed of WSS values at hundreds of points along the vessel wall. The median value was taken as a representative of each segment. Results: The average values were calculated and varied significantly from one another, especially the proximal and distal parts of the same artery, as showing in Figure 1. Conclusions: These results establish the first known WSS distribution within all of the coronary arteries and serve as a foundation for defining a cut-off for abnormal values. Importantly, they also illuminate the variability of WSS that occurs even throughout a single artery and suggests that perhaps multiple abnormal cutoffs need to be established to evaluate WSS based on the location of the stenosis.
Real-World Safety and Efficacy of Fluid-Filled Dual Intragastric Balloon for Weight Loss
Authors: Abhishek Agnihotri, Amy Xie, Christopher Bartalos, Vladimir Kushnir, Sameer Islam, Ebtesam Islam, Mark Lamet, Ari Lamet, Ramin Farboudmanesch, Bergein F Overholt, Johnny Altawil, Dayna S. Early, Michael Bennett, Abigail Lowe, Daniel K. Mullady, Christine Sade Adeyeri, Mohamad El Zein, Priya Mishra, Lea Fayad, Margo Dunlap, Andreas Oberbach, Lawrence J. Cheskin, Anthony N. Kalloo, Mouen A. Khashab, Vivek Kumbhari
Journal: Clinical Gastroenterology and Hepatology (2018)
<i>AHRR</i> hypomethylation, lung function, lung function decline and respiratory symptoms
Authors: Jakob B. Kodal, Camilla J. Kobylecki, Signe Vedel-Krogh, Børge G. Nordestgaard, Stig E. Bojesen
Journal: European Respiratory Journal (2018)

Epigenome-wide association studies have shown a consistent association between smoking exposure and hypomethylation in the aryl hydrocarbon receptor repressor ( AHRR ) gene (cg05575921). We tested the hypothesis that AHRR hypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms in the general population. AHRR methylation extent was measured in 9113 individuals from the 1991–1994 examination of the Copenhagen City Heart Study, using bisulfite-treated leukocyte DNA. Spirometry at the time of blood sampling was available for all individuals. Lung function was measured again for 4532 of these individuals in 2001–2003. Cross-sectionally, a 10% lower methylation extent was associated with a 0.2 z-score (95% CI 0.1–0.2) lower forced expiratory volume in 1 s (FEV 1 ) after multivariable adjustment including smoking. Hypomethylation was also associated with a lower z-score for both forced vital capacity (FVC) and FEV 1 /FVC. In prospective analyses, individuals in the lowest versus highest tertile of methylation extent had a steeper decline in FEV 1 /height 3 (p for examination×methylation interaction=0.003) and FVC/height 3 (p=0.01), but not FEV 1 /FVC (p=0.08). Multivariable-adjusted odds ratios per 10% lower methylation extent were 1.31 (95% CI 1.18–1.45) for chronic bronchitis and 1.21 (95% CI 1.13–1.30) for any respiratory symptoms. AHRR hypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.
Narrow-Band Imaging (NBI) versus coloration Lugol dans la détection du carcinome de l'oesophage dans une population à haut risque: un essai contrôlé randomisé multicentrique en situation de vraie vie
Authors: M Gruner, M Pioche, C Masliah, F Dewaele, E Metiver, D Luet, M Kaassis, E Coron, M Le Rhun, S Lecleire, M Antonietti, JL Legoux, P Renkes, AL Tarrerias, P Rey, B Prost, D Pere-Verge, C Cellier, G Rahmi, E Samaha, S Fratte, B Guerrier, T Ponchon
Journal: Endoscopy (2018)

Le Narrow-Band Imaging (NBI) est aussi sensible que le Lugol pour la détection du cancer épidermoïde de l'oesophage (CEO). Le NBI apparaît néanmoins plus spécifique que le Lugol dans les centres experts mais des données dans les centres de gastro-entérologie (incluant des centres non experts) sont manquantes. Nous avons mené une étude multicentrique, randomisée, prospective comparant la spécificité du Lugol et du NBI dans la détection des CEO et des dysplasies de haut grade (DHG) en pratique quotidienne (centres experts et non experts).
Hypothalamic ER–associated degradation regulates POMC maturation, feeding, and age-associated obesity
Authors: Geun Hyang Kim, Guojun Shi, Diane R.M. Somlo, Leena Haataja, Soobin Song, Qiaoming Long, Eduardo A. Nillni, Malcolm J. Low, Peter Arvan, Martin G. Myers, Ling Qi
Journal: Journal of Clinical Investigation (2018)

Pro-opiomelanocortin (POMC) neurons function as key regulators of metabolism and physiology by releasing prohormone-derived neuropeptides with distinct biological activities. However, our understanding of early events in prohormone maturation in the ER remains incomplete. Highlighting the significance of this gap in knowledge, a single POMC cysteine-to-phenylalanine mutation at position 28 (POMC-C28F) is defective for ER processing and causes early onset obesity in a dominant-negative manner in humans through an unclear mechanism. Here, we report a pathologically important role of Sel1L-Hrd1, the protein complex of ER-associated degradation (ERAD), within POMC neurons. Mice with POMC neuron–specific Sel1L deficiency developed age-associated obesity due, at least in part, to the ER retention of POMC that led to hyperphagia. The Sel1L-Hrd1 complex targets a fraction of nascent POMC molecules for ubiquitination and proteasomal degradation, preventing accumulation of misfolded and aggregated POMC, thereby ensuring that another fraction of POMC can undergo normal posttranslational processing and trafficking for secretion. Moreover, we found that the disease-associated POMC-C28F mutant evades ERAD and becomes aggregated due to the presence of a highly reactive unpaired cysteine thiol at position 50. Thus, this study not only identifies ERAD as an important mechanism regulating POMC maturation within the ER, but also provides insights into the pathogenesis of monogenic obesity associated with defective prohormone folding.
Health experts urge UK and EU to “put patients first” in Brexit talks
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Health experts have urged the UK and the European Union to “put patients first” during Brexit negotiations, amid fears that the supply of new drugs will be disrupted when the UK leaves the EU.

In a briefing paper1 published on 29 January, the Brexit Health Alliance, a coalition of NHS, medical research, industry, and patient and public health organisations, warned that failure to reach a deal could delay or …
A Novel Severity Assessment Scoring System for Hidradenitis Suppurativa
Authors: Schapoor Hessam, Lisa Scholl, Michael Sand, Lutz Schmitz, Sarah Reitenbach, Falk G. Bechara
Journal: JAMA Dermatology (2018)

The variation in both clinical appearance and responses to diverse treatment options emphasize the importance of an accurate, clinically relevant, yet easy-to-use scoring system in hidradenitis suppurativa.To propose and provide validation data for the newly designed Severity Assessment of Hidradenitis Suppurativa score.We prospectively assessed disease severity using Hurley staging and the modified Hidradenitis Suppurativa Score in 355 patients referred to Ruhr-University Bochum Department of Dermatology between March 2016 and June 2017. We also assessed disease severity via the Severity Assessment of Hidradenitis Suppurativa score.Evaluation and assessment of convergent validity and responsiveness to treatment of the Severity Assessment of Hidradenitis Suppurativa score.Eighty-eight of the 355 patients (134 [37.7%] men and 221 [62.3%] women with a median [IQR] age of 40 [30-49] years) were classified as Hurley stage I, 221 were Hurley stage II, and 46 were Hurley stage III, with an overall median modified Hidradenitis Suppurativa Score of 31 (interquartile range [IQR], 19.3-53). The median total Severity Assessment of Hidradenitis Suppurativa score was 6 (IQR, 4-9), significantly different among the 3 Hurley groups. The median SAHS score for patients in Hurley stage I was 5 (IQR, 3-6), 6 (IQR, 5-9) for patients in Hurley stage II, and 9 (IQR, 7-12) for patients in Hurley stage III (P < .001, Kruskal-Wallis test). Correlation analysis showed a significant correlation between the modified Hidradenitis Suppurativa Score and the Severity Assessment of Hidradenitis Suppurativa score (r = 0.79, P < .001). Disease severity assessment before and after 3 months of conservative systemic treatment showed a significant correlation between the Severity Assessment of Hidradenitis Suppurativa score and modified Hidradenitis Suppurativa Score. Both the mHSS (P = .001) and the SAHS score (P < .001) significantly differed between the baseline visit (median mHSS, 33 [IQR, 24-52]; median SAHS score, 6 [IQR, 5-9]) and the 3-month visit (median mHSS, 28 [IQR, 15-43.5]; median SAHS score, 5 [IQR, 4-6.3]). The 2 patient-reported items demonstrated excellent test-retest reliability with intraclass correlation coefficient values greater than 0.8.Our validation data demonstrated that the Severity Assessment of Hidradenitis Suppurativa score is a disease severity instrument that significantly correlates with Hurley staging and the modified Hidradenitis Suppurativa Score, and is responsive enough to measure treatment outcome.
Safety of Vaginal Mesh Surgery Versus Laparoscopic Mesh Sacropexy for Cystocele Repair: Results of the Prosthetic Pelvic Floor Repair Randomized Controlled Trial
Authors: Jean-Philippe Lucot, Michel Cosson, Georges Bader, Philippe Debodinance, Cherif Akladios, Delphine Salet-Lizée, Patrick Delporte, Denis Savary, Philippe Ferry, Xavier Deffieux, Sandrine Campagne-Loiseau, Renaud de Tayrac, Sébastien Blanc, Sandrine Fournet, Arnaud Wattiez, Richard Villet, Marion Ravit, Bernard Jacquetin, Xavier Fritel, Arnaud Fauconnier
Journal: European Urology (2018)

Laparoscopic mesh sacropexy (LS) or transvaginal mesh repair (TVM) are surgical techniques used to treat cystoceles. Health authorities have highlighted the need for comparative studies to evaluate the safety of surgeries with meshes.To compare the rate of complications, and functional and anatomical outcomes between LS and TVM.Multicenter randomized controlled trial from October 2012 to April 2014 in 11 French public hospitals. Women with cystocele stage ≥2 (pelvic organ prolapse quantification), aged 45-75 yr, without previous prolapse surgery.Synthetic nonabsorbable mesh placed in the vesicovaginal space, sutured to the promontory (LS) or maintained by arms through pelvic ligaments (TVM).Rate of surgical complications ≥grade II according to the modified Clavien-Dindo classification at 1 yr. Secondary outcomes were reintervention rate, and functional and anatomical results.A total of 130 women were randomized in LS and 132 in TVM; five women withdrew before intervention, leaving 129 in LS and 128 in TVM. The rate of complications ≥grade II was lower after LS than after TVM, but did not meet statistical significance (17% vs 26%, treatment difference 8.6% [95% confidence interval, CI -1.5 to 18]; p=0.088). The rate of complications of grade III or higher was nonetheless significantly lower after LS (LS=0.8%, TVM=9.4%, treatment difference 8.6% [95% CI 3.4%; 15%]; p=0.001). LS was converted to TVM in 6.3%. The total reoperation rate was lower after LS but did not meet statistical significance (LS=4.7%, TVM=10.9%, treatment difference 6.3% [95% CI -0.4 to 13.3]; p=0.060). There was no difference in symptoms, quality of life, improvement, composite definition of success, anatomical results rates between groups except for the vaginal apex and length, and dyspareunia (in favor of LS).LS is a valuable option for primary repair of cystocele in sexually active patients. LS is safer than TVM, but may not be feasible in all cases. Both techniques offer same functional outcomes, success rates, and anatomical outcomes, but sexual function is better preserved by LS.Our study demonstrates that laparoscopic sacropexy (LS) is a valuable option for primary repair of cystocele. LS offers equivalent success rates to vaginal mesh procedures, but is safer with a lower rate of complications and reoperations, and sexual function is better preserved.
Incremental Value of Subtended Myocardial Mass for Identifying FFR-Verified Ischemia Using Quantitative CT Angiography
Authors: Dong Hyun Yang, Soo-Jin Kang, Hyun Jung Koo, Jihoon Kweon, Joon-Won Kang, Tae-Hwan Lim, Joonho Jung, Namkug Kim, June-Goo Lee, Seungbong Han, Jung-Min Ahn, Duk-Woo Park, Seung-Whan Lee, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park, Gary S. Mintz, Young-Hak Kim
Journal: JACC. Cardiovascular imaging (2018)
Dual-Targeted Theranostic Delivery of miRs Arrests Abdominal Aortic Aneurysm Development
Authors: Xiaowei Wang, Amy Kate Searle, Jan David Hohmann, Ao Leo Liu, Meike-Kristin Abraham, Jathushan Palasubramaniam, Bock Lim, Yu Yao, Maria Wallert, Eefang Yu, Yung-Chih Chen, Karlheinz Peter
Journal: Molecular Therapy (2018)

Abdominal aortic aneurysm (AAA) is an often deadly disease without medical, non-invasive treatment options. The upregulation of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium provides an early target epitope for a novel biotechnological theranostic approach. MicroRNA-126 was used as a therapeutic agent, based on its capability to downregulate VCAM-1 expression in endothelial cells and thereby reduces leukocyte adhesion and exerts anti-inflammatory effects. Ultrasound microbubbles were chosen as carriers, allowing both molecular imaging as well as targeted therapy of AAA. Microbubbles were coupled with a VCAM-1-targeted single-chain antibody (scFvmVCAM-1) and a microRNA-126 mimic (M126) constituting theranostic microbubbles (TargMB-M126). TargMB-M126 downregulates VCAM-1 expression in vitro and in an in vivo acute inflammatory murine model. Most importantly, using TargMB-M126 and ultrasound-guided burst delivery of M126, the development of AAA in an angiotensin-II-induced mouse model can be prevented. Overall, we describe a unique biotechnological theranostic approach with the potential for early diagnosis and long-sought-after medical therapy of AAA.
Roles of Smoothened (Smo), the major signal transducer of the hedgehog pathway, in the development of intestinal tumors
Authors: Sumimasa Arimura, Masahiro Aoki, Makoto Taketo
Journal: Cancer Research (2008)

4948   The Hedgehog (Hh) signaling pathway is known to play crucial roles in the development and/or progression of several types of human cancers. However, contribution of the Hh pathway in colorectal cancer remains controversial. In this study, we investigated the involvement of the Hh pathway components in intestinal tumor development using genetic mouse models and cultured human colon cancer cell lines. Interestingly, expression of Smoothened (Smo), the major signal transducer of the Hh pathway, was markedly elevated in the adenoma epithelial cells of the intestinal polyps in Apc(+/Δ716) mice, a mouse model of familial adenomatous polyposis (FAP), as compared with the normal intestinal tissue of the same mice. Increased SMO expression was also observed in a subset of human colon cancer cell lines. Importantly, siRNA-induced SMO knockdown strongly inhibited proliferation of the colon cancer cell lines that highly express SMO (SMO-high cells), but not that of the cells that express SMO at low level. Cell cycle analysis by flow cytometry showed that SMO knockdown induced G1 cell cycle arrest in the SMO-high cells, which was accompanied by alteration of G1-S phase regulators. SMO knockdown in the SMO-high cells also suppressed β-catenin/Tcf-dependent reporter gene activity, as well as the endogenous β-catenin expression, indicating a functional link between SMO and the Wnt signaling in colon cancer cells. To further explore the possible link between Smo and the Wnt signaling in intestinal tumor development, we crossed Apc(+/Δ716) mice with Smo(+/-) mice. Importantly, the size of small intestinal and colonic polyps was significantly decreased in the Apc(+/Δ716)Smo(+/-) compound mutant mice, as compared with that of polyps in the littermate Apc(+/Δ716) mice. The intestinal polyps of Apc(+/Δ716)Smo(+/-) mice showed a collapsed morphology at the top, which was not observed in the Apc(+/Δ716) mice, and the BrdU labeling index was reduced in the intestinal adenoma cells of Apc(+/Δ716) Smo(+/-) mice as compared with those of Apc(+/Δ716) mice. These results suggest that SMO plays essential roles in proliferation of a subset of human colon cancer cell lines in vitro, and that Smo haploinsufficiency suppresses the expansion of intestinal polyps in the Apc(+/Δ716) mice in vivo. SMO can thus be a potential target for prevention/therapy of FAP and colorectal cancer.
P105 Endoplasmic reticulum stress mediates dermal fibrosis
Authors: S O’reilly
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Systemic sclerosis is an autoimmune idiopathic connective tissue disease. The cells mainly responsible are the myofibroblasts that secrete copious amount of extracellular matrix molecules such as collagen. Endoplasmi reticulum stress is induced by a variety of stressors including misfolded proteins, this leads to a classic stress response and activation of X Box Binding Protien-1 (XBP-1) and ATF-6. This is induced in a variety of situations from multiple stressors and is a conserved pathway. Its role in systemic sclerosis is unknown. <h3>Objectives</h3> To examine the role of endoplasmic reticulum stress in systemic sclerosis. <h3>Methods</h3> Healthy dermal fibroblasts were treated with the ER stress inducing agent thaspigargin or nothing and then lysed and various proteins such as XBP-1 and ATF measured along with collagen by western blotting and reprobed for a loading control. In some experiments small interfering RNA against XBP-1, a mediator of ER stress, was transfected and treated with thaspigargin or non targeting controls. Also the belomycin mouse model of fibrosis was used and ATF6 mRNA was measured using qRT-PCR. <h3>Results</h3> The classic ER stress inducer thaspigargin induced collagen expression in dermal fibroblasts as well as the markers of ER stress XBP-1 and ATF-6. The ER stress induced collagen expression in dermal fibroblasts was reduced with the reduction of XBP-1 in these cells using small interfering RNA compared to non targeting siRNA. The bleomycin model of skin fibrosis revealed increased ATF-6 mRNA levels compared to vehicle control tissue. <h3>Conclusions</h3> Endoplasmic reticulum stress appears to regulated collagen expression in the skin and is involved in the bleomycin mouse model of disease. Targeting such a pathway may be useful in the disease. <h3>Disclosure of interest</h3> None declared