tbuckley/cabot-search huggingface dataset:
Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial)
Authors: Mohammad Shafi Kuchay, Sonal Krishan, Sunil Kumar Mishra, Khalid Jamal Farooqui, Manish Kumar Singh, Jasjeet Singh Wasir, Beena Bansal, Parjeet Kaur, Ganesh Jevalikar, Harmendeep Kaur Gill, Narendra Singh Choudhary, Ambrish Mithal
Journal: Diabetes Care (2018)

OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors have been shown to reduce liver fat in rodent models. Data regarding the effect of SGLT-2 inhibitors on human liver fat are scarce. This study examined the effect of empagliflozin (an SGLT-2 inhibitor) on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) by using MRI-derived proton density fat fraction (MRI-PDFF). RESEARCH DESIGN AND METHODS Fifty patients with type 2 diabetes and NAFLD were randomly assigned to either the empagliflozin group (standard treatment for type 2 diabetes plus empagliflozin 10 mg daily) or the control group (standard treatment without empagliflozin) for 20 weeks. Change in liver fat was measured by MRI-PDFF. Secondary outcome measures were change in alanine transaminase (ALT), aspartate transaminase (AST), and γ-glutamyl transferase (GGT) levels. RESULTS When included in the standard treatment for type 2 diabetes, empagliflozin was significantly better at reducing liver fat (mean MRI-PDFF difference between the empagliflozin and control groups −4.0%; P &amp;lt; 0.0001). Compared with baseline, significant reduction was found in the end-of-treatment MRI-PDFF for the empagliflozin group (16.2% to 11.3%; P &amp;lt; 0.0001) and a nonsignificant change was found in the control group (16.4% to 15.5%; P = 0.057). The two groups showed a significant difference for change in serum ALT level (P = 0.005) and nonsignificant differences for AST (P = 0.212) and GGT (P = 0.057) levels. CONCLUSIONS When included in the standard treatment for type 2 diabetes, empagliflozin reduces liver fat and improves ALT levels in patients with type 2 diabetes and NAFLD.
Patient Education on Patellofemoral Pain
Authors: Christian J. Barton, Sinéad Holden, Michael Skovdal Rathleff
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 18026: Impact of Cyp2c19 Variants and Epoxyeicosatrienoic Acids on Microvascular Angina
Authors: Tomonori Akasaka, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2016)

Background:  Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the impact of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction.   Methods and Results:  We examined CYP2C19 genotypes in patients with MVA (n=71) and healthy subjects as control (n=71). MVA was defined as absence of coronary artery stenosis and epicardial spasms, and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of -functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P=0.007) and high sense C-reactive protein (hs-CRP) levels (0.127±0.142 vs. 0.086±0.097mg/dL; P=0.043) than that of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180±0.107 vs. 0.106±0.149mg/dL, P=0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM (10.9±1.64 vs. 14.2±5.39ng/mL,  P =0.019 (11,12-DHET); 15.2±4.39 vs. 17.9±4.73ng/mL, P=0.025 (14,15-DHET)).   Conclusions:  CYP2C19 variants is associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction.
AB0093 Natural polymer-based hydrogels for cartilage regeneration
Authors: E. Montell, L. García-Fernández, A. Torrent, J. San Román
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Cartilage is a tough, flexible tissue found throughout the body. It can become damaged because of a sudden injury, such as a sports injury, or gradual wear and tear (osteoarthritis). Injured articular cartilage has a poor regenerative capability, for this reason, tissue engineering may provide a fundamental therapeutic solution to repair cartilage injury. Human articular cartilages are composed of dense extracellular matrix and chondrocytes. One of the major components in the extracellular matrix is hyaluronic acid. The combination of hyaluronic acid with other natural polymers to prepare hydrogel scaffolds may be potentially useful in many tissue engineering applications, including cartilage regeneration. <h3>Objectives</h3> We propose the synthesis of hydrogels based on hyaluronic acid and chitosan by a new strategy of synthesis using di-isocyanates to obtain an interpenetrated network of chitosan and hyaluronic acid. <h3>Methods</h3> Different kinds of hydrogels were synthesised using hyaluronic acid (Bioibérica, Spain), natural polymers (gelatine, chitosan) and stabilised with diisocianates. The hydrogels were charged with chondroitin sulfate (Bioibérica, Spain). <h3>Morphological Characterisation</h3> The hydrogels were characterised by scanning electron microscopy and energy dispersive X-ray microscopy in order to study the morphology and the composition of the hydrogels. <h3>Hydrogel Swelling</h3> Dynamic swelling experiments were performed by placing discs of stabilised hydrogels in PBS at 37.0°C, and measuring their weight gain as a function of time. <h3>Biocompatibility</h3> Cytotoxicity <i>in vitro</i> assays (MTT) and cell adhesion tests (Alamar Blue) were performed on the hydrogels using different cell lines to corroborate the biocompatibility of the hydrogels. <h3>Results</h3> All the synthesised hydrogels presented a high interconnected porosity. The studied hydrogels swelled around 200%. After five hours equilibrium was reached and this equilibrium depended on the ratio hyaluronic acid/natural polymer increasing with the amount of hyaluronic acid present on the hydrogel. MTT assay indicated that the extracts collected at different times from the hydrogels were not cytotoxic and could be considered biocompatible. Cell adhesion assay demonstrated that the hydrogels supported cell adhesion and proliferation, and this behaviour was better on SC-loaded hydrogels. <h3>Conclusions</h3> Hydrogels based on hyaluronic acid and natural polymers are proposed as scaffolds for tissue engineering. The presence of interconnected porous and the good swelling properties, as well as the biocompatibility, represent a great advantage for application in cartilage regeneration. The addition of drugs or glycosaminoglycans is being studied to improve the cartilage regeneration. <h3>Disclosure of Interest</h3> None declared
OP0194 The association between serum uric acid and arterial stiffness in a low-risk, large population of middle-aged korean
Authors: J. Hwang, J.H. Hwang, Y. Eun, H. Kim, J. Lee, J.K. Ahn
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Arterial stiffness occurs because of biologic ageing and arteriosclerosis, and is most commonly measured by pulse-wave velocity. Several studies have reported that high serum uric acid may contribute to the development of a number of metabolic and haemodynamic abnormalities, and multivariate analyses in epidemiologic studies have suggested that hyperuricemia is an independent risk factor for arterial stiffness in those with comorbidities such as diabetes, hypertension, and chronic kidney disease. However, there are few reports about the association between SUA and arterial stiffness in apparently healthy populations. <h3>Objectives</h3> We aimed to investigate the association between serum uric acid (SUA) and arterial stiffness as evaluated by brachial ankle pulse wave velocity (baPWV) in a low-risk, large, middle-aged Korean population. <h3>Methods</h3> We conducted a cross-sectional study of 66,917 Koreans (38 170 men, 28 747 women) who received yearly screening with available PWV and SUA results. None of the participants had coronary heart disease, diabetes, or hypertension. SUA was divided into quintiles for assessment of its association with baPWV by multiple linear regression analysis. <h3>Results</h3> The average SUA level was 5.23±1.4 mg/dl, and SUA values were higher in men than in women (6.1±1.2 mg/dl vs 4.1±0.8 mg/dl). In multiple regression analysis, PWV was significantly higher in SUA quintiles 2–5 compared to the lowest group (reference) (coefficient=11.52, 18.19, 24.73, and 31.02 cm/s, respectively). In female subjects, the average difference (cm/s) of PWV between quintiles 2–5 and quintile 1 of SUA was 13.1, 22.9, 34.6, and 32.1, respectively. Fully adjusted linear coefficient β (S.E.) was 6.62 (0.70) and 12.43 (1.33) in all participants and female subjects, respectively (p&lt;0.001). In contrast, there was a J-shaped association between PWV and SUA quintile among males. When modelled continuously, each 1 mg/dl higher SUA level was associated with 0.27 higher baPWV (p&lt;0.001) in the adjusted analysis. <h3>Conclusions</h3> These findings indicate that higher SUA levels could have an unfavourable impact on arterial stiffness as measured by baPWV in a low-risk, large, middle-aged Korean population. <h3>Disclosure of Interest</h3> None declared
FRI0245 Predictors for clinically diagnosed gout – 30 years follow-up in the malmÖ preventive project cohort, sweden
Authors: M.C Kapetanovic, P. Nilsson, C. Turesson, M. Englund, N. Dalbeth, L. Jacobsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Gout is the most common form of inflammatory arthritis worldwide. Hyperuricemia is a crucial risk factor. The relative importance of other risk factors is slightly more controversial. <h3>Objectives</h3> Our aim was to identify predictors for clinical gout cohort from a population survey, the Malmö Preventive Project (MPP) – a large-scale screening and case finding program in Malmö, Sweden. <h3>Methods</h3> A total of 33 346 individuals (67% men, mean age 46 years, mean follow-up 28 years) were screened 1974–1992. The survey included: <i>A Questionnaire</i> (alcohol consumption, smoking); <i>A Physical Examination</i> and <i>Laboratory tests</i>. The Malmö modification of Michigan alcoholism screenings test (Mm-MAST) was used to identify alcohol risk consumption (Mm-MAST score ≥2). Subjects were followed to date of first gout diagnosis, death, migration from area, or December 2014. All gout diagnoses given at visits to physicians in primary or specialised care were identified by linking MPP cohort to regional Skåne Healthcare Register and to National Patient Register. Possible risk factors/markers at baseline associated with incident gout were analysed using Cox-regression models. <h3>Results</h3> In total, 1275 individuals (3.8%); 1014 men (4.5%) and 261 women (2.4%) were diagnosed with gout. In both sexes, baseline s-UA &gt;405 (age-adjusted) was the strongest factor associated with incident gout. Higher age, higher BMI, higher s-triglycerides, hypertension and smoking were also associated with gout in both sexes. Mm-MAST score ≥2 was associated with gout only in men while higher ESR was associated with gout only in women (table 1). <h3>Conclusions</h3> In this large cohort of middle-age individuals, hyperuricemia, higher age, hypertriglyceridemia and higher BMI were associated with incident gout in both sexes. Alcohol risk consumption predicted gout only in men. Higher ESR, as a possible marker of chronic inflammation, was a significant predictor only in women. <h3>Disclosure of Interest</h3> None declared
Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells
Authors: Timotheus Y.F. Halim, Batika M.J. Rana, Jennifer A. Walker, Bernhard Kerscher, Martin D. Knolle, Helen E. Jolin, Eva M. Serrao, Liora Haim-Vilmovsky, Sarah A. Teichmann, Hans-Reimer Rodewald, Marina Botto, Timothy J. Vyse, Padraic G. Fallon, Zhi Li, David R. Withers, Andrew N.J. McKenzie
Journal: Immunity (2018)

The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+Tnfsf4fl/fl mice). Moreover, Il7raCre/+Tnfsf4fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish.
Комплексна терапія гастроезофагеальної рефлюксної хвороби у поєднанні з тривожно-депресивними станами в учасників антитерористичної операції
Authors: G.V. Osyodlo, M.V. Radushynska, V.G. Gurianov
Journal: GASTROENTEROLOGY (2018)

Мета. Встановлення частоти і вираженості тривожно-депресивних розладів в учасників антитерористичної операції (АТО), хворих на гастроезофагеальну рефлюксну хворобу (ГЕРХ) із різними ендо­скопічними формами, та оцінювання впливу психокорегуючих препаратів при їх додатковому призначенні. Матеріали та методи. Для оцінки психічного стану 108 військовослужбовців — учасників АТО, хворих на ГЕРХ, чоловічої статі у перший день загальноклінічного обстеження використовувалася госпітальна шкала тривоги і депресії HADS за градацією визначення тривоги і депресії. Як психокорегуючі засоби було обрано сульпірид і флуоксетин. Результати. У результаті дослідження психоемоційні розлади мали місце у 108 (100 %) військовослужбовців — учасників АТО. Астеноневротичний синдром встановлено у 14 (35 %) хворих на неерозивну рефлюксну хворобу (НЕРХ) та у 28 (41,2 %) пацієнтів з ерозивною формою ГЕРХ (ЕРХ), тривожно-депресивний синдром діагностовано у 26 (65 %) військовослужбовців із НЕРХ та 40 (58,8 %) чоловіків, хворих на ЕРХ. При проведенні аналізу не виявлено зв’язку ефективності лікування з ендоскопічною формою ГЕРХ при застосуванні як сульпіриду (p = 0,87), так і флуоксетину (p = 0,40). Встановлено, що застосування флуоксетину дає можливість знизити (p = 0,02) ризик недосягнення ефекту: від 38,2 % (95% вірогідний інтервал (ВІ) 22,3–55,6 %) при лікуванні сульпіридом до 9,1 % (95% ВІ 1,7–21,6 %) при лікуванні флуоксетином. Висновки. Комплексне призначення стандартної терапії з корекцією психоемоційних проявів дозволяє покращити перебіг ГЕРХ, сприяє більш швидкій регресії клінічних проявів. Порівняння клінічної ефективності додаткового призначення психотропних препаратів показало переваги флуоксетину (відносний ризик = 0,24 (95% ВІ 0,07–0,76)) порівняно з сульпіридом.
Elimination of melanoma by sortase A-generated TCR-like antibody-drug conjugates (TL-ADCs) targeting intracellular melanoma antigen MART-1
Authors: Jun Lai, Yun Wang, Shan-Shan Wu, Ding Ding, Ze-Yu Sun, Ying Zhang, Jie Zhou, Zhan Zhou, Ying-Chun Xu, Li-Qiang Pan, Shu-Qing Chen
Journal: Biomaterials (2018)
Abstract A02: Succinate dehydrogenase deficiency in a PDGFRA mutated gastrointestinal stromal tumor
Authors: Martin G. Belinsky, Lori Rink, Kathy K. Cai, Biao Luo, Yan Zhou, Margaret von Mehren
Journal: Clinical Cancer Research (2018)

Abstract Most gastrointestinal stromal tumors harbor mutually exclusive gain-of-function mutations in the receptor tyrosine kinase (RTK) KIT (70-80%) or in the related receptor PDGFRA (~10%). Mutations in PDGFRA are most commonly found in the TK domain encoded by exon 18, conferring resistance to approved tyrosine kinase inhibitors (TKI). A more recently defined subset of GIST exhibit deficiencies in the succinate dehydrogenase (SDH) enzyme complex as a result of genetic or epigenetic inactivation of one of the four SDH subunit genes (SDHA-D). SDH-deficient GISTs generally lack mutations in KIT and PDGFRA and do not respond to imatinib (IM), although these GISTs may respond to TKIs targeting VEGFR, such as sunitinib and regorafenib. Whole-exome sequencing (WES) of two GISTs from a single case carrying the IM-resistant exon 18 PDGFRA mutation D842V was carried out to identify additional potential targets for therapy. Surprisingly, a somatic mutation in exon 4 of the SDHB subunit gene (c.291_292delCT, p.I97Mfs*21) was identified in both tumors. Sanger sequencing confirmed the presence of this inactivating mutation, and immunohistochemistry for the SDHB subunit demonstrated that these tumors were in fact SDH deficient. IHC for the SDHB subunit across a panel of ~100 GIST cases failed to detect SDH deficiency in other GISTs with RTK mutations. To our knowledge this is the first reported case of an SDH-deficient GIST harboring a gain-of-function mutation in the PDGFRA receptor, and this finding has implications for the molecular-based classification and treatment of GIST. Citation Format: Martin G. Belinsky, Lori Rink, Kathy K. Cai, Biao Luo, Yan Zhou, Margaret von Mehren. Succinate dehydrogenase deficiency in a PDGFRA mutated gastrointestinal stromal tumor [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A02.
Evaluation of genotoxicity related to oral methylene blue chromoendoscopy
Authors: Alessandro Repici, Camilla Ciscato, Michael Wallace, Prateek Sharma, Andrea Anderloni, Silvia Carrara, Milena Di Leo, Cesare Hassan
Journal: Endoscopy (2018)

Abstract Background An oral formulation of methylene blue with colonic delivery (MB-MMX) has been developed to increase detection of colorectal polys during colonoscopy. Traditionally, there have been safety concerns regarding DNA damage when methylene blue is exposed to white light. The aim of this study was to evaluate DNA damage in colonic mucosa after MB-MMX chromoendoscopy. Methods This was an open-label phase II safety study to assess for genotoxicity on colorectal biopsies of patients undergoing two sequential colonoscopies before and after an oral dose of 200 mg MB-MMX added to their bowel prep. Analysis of a biomarker of double-stranded DNA breaks, γH2AX, was performed on biopsy specimens. Results Ten patients were included in the study. The mean expression of γH2AX ± 95 % confidence intervals of the 50 biopsies before and after MB-MMX administration were 0.58 ± 0.08 and 0.62 ± 0.09, respectively (P = 0.24). None of the analyzed samples showed excess positive γH2AX expression, confirming the absence of DNA damage on biopsies after methylene blue exposure. No deaths or serious adverse events occurred. Conclusions An oral dose of 200 mg of MB-MMX did not result in any detectable DNA damage.
Screening for Cardiovascular Disease Risk With Electrocardiography
Authors: R. Sacha Bhatia, Paul Dorian
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Regulation of Skeletal Homeostasis
Authors: Mone Zaidi, Tony Yuen, Li Sun, Clifford J Rosen
Journal: Endocrine Reviews (2018)

Landmark advances in skeletal biology have arisen mainly from the identification of disease-causing mutations and the advent of rapid and selective gene-targeting technologies to phenocopy human disease in mice. Here, we discuss work on newly identified mechanisms controlling the remodeling of bone, communication of bone cells with cells of other lineages, and crosstalk between bone and vital organs as these relate to the therapeutic targeting of the skeleton.
Is It Possible to Establish the Extent of Resection of Glioblastoma With 18F-Fluorocholine PET/CT?
Authors: Ana María García Vicente, Julian Perez-Beteta, Manuel Calvo García, Maikal Villena Martín, Angel Soriano Castrejón
Journal: Clinical Nuclear Medicine (2018)

Abstract Defining high-grade glioma resectability is a challenge; and currently, it is based on anatomical imaging. However, complete removal of contrast-enhancing tumor is difficult to define in MRI. We present three cases of patients diagnosed with high-grade glioma. Brain MRI and 18 F-fluorocholine PET/CT were performed before and after surgery to establish the extent of resection (EOR) and residual volume. Postoperative brain MRI and PET parameters showed discordant results in all the reported cases. PET was able to assess properly the EOR; however, the rules for the EOR establishment and its prognostic implication should be validated in prospective studies.