tbuckley/cabot-search huggingface dataset:
P091 Effects of biologics on IL-17A and TNF induced cytokine secretion on synovial fibroblasts from rheumatoid and psoriatic arthritis patients
Authors: K Frommer, S Rehart, U Müller-Ladner, E Neumann
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are both rheumatic autoimmune diseases, which share a number of similarities but also display differences. For example, the anti-IL17A biologic secukinumab turned out to be more effective in PsA than in RA. The anti-TNF biologic adalimumab on the other hand is equally indicated for both diseases. Synovial fibroblasts (SF) are one of the key effector cell types in the pathophysiology of RA and PsA. <h3>Objectives</h3> We therefore investigated whether the effect of the two cytokines IL-17A and TNF-α as well as the effect of their corresponding biologics differs between RASF and PsASF, thus contributing to the difference seen in the therapeutic response. The effect of the IL-17A homolog IL-17F was also analyzed. <h3>Methods</h3> SF were isolated from patients with PsA or RA, each undergoing surgery. SF from RA and PsA patients were stimulated with recombinant IL-17A, IL-17F and TNF-α alone or with respective combinations. Dose-response curve analysis was performed with IL-17A. The biologics secukinumab and adalimumab were used to block the effects on the SF. As a measure of the proinflammatory response, secretion of the cytokine IL–6 was quantified using an immunoassay. <h3>Results</h3> RASF as well as PsASF responded to IL-17A (IL-17A: 13.7-fold vs 6.9–fold; n=3), while IL-17F alone caused no induction of IL-6 secretion in either SF type. However, when used in combination with TNF-α, both IL-17 isoforms, IL–17A and IL-17F, increased IL-6 secretion due to a strong synergistic effect with TNF-α. Surprisingly, these effects were notably stronger for RASF than for PsASF (IL-17A: 544-fold vs 127-fold, IL-17F: 54-fold vs 27-fold; n=3). However, adalimumab and secukinumab were similarly effective in abolishing the synergistic effect of IL-17A and TNF-α in RASF as well as PsASF. <h3>Conclusions</h3> SF appear not to contribute to the differences in the therapeutic effectiveness of the anti-IL17A biologic secukinumab as the response to IL-17A alone and IL-17A together with TNF–α is not stronger for PsASF than for RASF. Furthermore, secukinumab was similarly effective for both SF types. The data also suggest that in a proinflammatory milieu with increased TNF levels IL-17A as well as IL-17F play a role in the SF-mediated pathophysiology of PsA and, therefore, approaches targeting TNF are effective in both diseases. <h3>Acknowledgements</h3> Supported by an unrestricted educational grant from Celgene GmbH. <h3>Disclosure of Interest</h3> K. Frommer Grant/research support from: unrestricted educational grant from Celgene GmbH, S. Rehart: None declared, U. Müller-Ladner: None declared, E. Neumann: None declared.
Evolutionary Rate Correlation between Mitochondrial-Encoded and Mitochondria-Associated Nuclear-Encoded Proteins in Insects
Authors: Zhichao Yan, Gongyin Ye, John H Werren
Journal: Molecular Biology and Evolution (2019)

The mitochondrion is a pivotal organelle for energy production, and includes components encoded by both the mitochondrial and nuclear genomes. Functional and evolutionary interactions are expected between the nuclear- and mitochondrial-encoded components. The topic is of broad interest in biology, with implications to genetics, evolution, and medicine. Here, we compare the evolutionary rates of mitochondrial proteins and ribosomal RNAs to rates of mitochondria-associated nuclear-encoded proteins, across the major orders of holometabolous insects. There are significant evolutionary rate correlations (ERCs) between mitochondrial-encoded and mitochondria-associated nuclear-encoded proteins, which are likely driven by different rates of mitochondrial sequence evolution and correlated changes in the interacting nuclear-encoded proteins. The pattern holds after correction for phylogenetic relationships and considering protein conservation levels. Correlations are stronger for both nuclear-encoded OXPHOS proteins that are in contact with mitochondrial OXPHOS proteins and for nuclear-encoded mitochondrial ribosomal amino acids directly contacting the mitochondrial rRNAs. We find that ERC between mitochondrial- and nuclear-encoded proteins is a strong predictor of nuclear-encoded proteins known to interact with mitochondria, and ERC shows promise for identifying new candidate proteins with mitochondrial function. Twenty-three additional candidate nuclear-encoded proteins warrant further study for mitochondrial function based on this approach, including proteins in the minichromosome maintenance helicase complex.
Maryland Total Cost of Care Model
Authors: Katherine J. Sapra, Katie Wunderlich, Howard Haft
Journal: JAMA (2019)

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
Identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients
Authors: Eun-Sook Park, Ah Ram Lee, Doo Hyun Kim, Jeong-Hoon Lee, Jeong-Ju Yoo, Sung Hyun Ahn, Heewoo Sim, Soree Park, Hong Seok Kang, Juhee Won, Yea Na Ha, Gu-Choul Shin, So Young Kwon, Yong Kwang Park, Byeong-Sun Choi, Yun Bin Lee, Nakcheol Jeong, Yohan An, Young Seok Ju, Su Jong Yu, Hee Bok Chae, Kyung-Sang Yu, Yoon Jun Kim, Jung-Hwan Yoon, Fabien Zoulim, Kyun-Hwan Kim
Journal: Journal of Hepatology (2019)
The impact of sequencing PD-1/PD-L1 inhibitors and stereotactic radiosurgery for patients with brain metastasis
Authors: Rupesh Kotecha, Joseph M Kim, Jacob A Miller, Aditya Juloori, Samuel T Chao, Erin S Murphy, David M Peereboom, Alireza M Mohammadi, Gene H Barnett, Michael A Vogelbaum, Lilyana Angelov, John H Suh, Manmeet S Ahluwalia
Journal: Neuro-Oncology (2019)

The response of brain metastases (BM) treated with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICIs; programmed cell death 1 and its ligand) is of significant interest.Patients were divided into cohorts based on ICI sequencing around SRS. The primary outcome was best objective response (BOR) that was lesion specific. Secondary outcomes included overall objective response (OOR), response durability, radiation necrosis (RN), and overall survival (OS).One hundred fifty patients underwent SRS to 1003 BM and received ICI. Five hundred sixty-four lesions (56%) treated with concurrent ICI (±5 half-lives) demonstrated superior BOR, OOR, and response durability compared with lesions treated with SRS and delayed ICI. Responses were best in those treated with immediate (±1 half-life) ICI (BOR: -100 vs -57%, P < 0.001; complete response: 50 vs 32%; 12-month durable response: 94 vs 71%, P < 0.001). Lesions pre-exposed to ICI and treated with SRS had poorer BOR (-45%) compared with ICI naive lesions (-63%, P < 0.001); best response was observed in ICI naive lesions receiving SRS and immediate ICI (-100%, P < 0.001). The 12-month cumulative incidence of RN with immediate ICI was 3.2% (95% CI: 1.3-5.0%). First radiographic follow-up and best intracranial response were significantly associated with longer OS; steroids were associated with inferior response rates and poorer OS (median 10 vs 25 mo, P = 0.002).Sequencing of ICI around SRS is associated with overall response, best response, and response durability, with the most substantial effect in ICI naive BM undergoing immediate combined modality therapy. First intracranial response for patients treated with immediate ICI and SRS may be prognostic for OS, whereas steroids are detrimental.
Interdisciplinary COPD intervention in primary care: a cluster randomised controlled trial
Authors: Jenifer Liang, Michael J. Abramson, Grant Russell, Anne E. Holland, Nicholas A. Zwar, Billie Bonevski, Ajay Mahal, Paula Eustace, Eldho Paul, Kirsten Phillips, Narelle S. Cox, Sally Wilson, Johnson George
Journal: European Respiratory Journal (2019)

We evaluated the effectiveness of an interdisciplinary, primary care-based model of care for chronic obstructive pulmonary disease (COPD).A cluster randomised controlled trial was conducted in 43 general practices in Australia. Adults with a history of smoking and/or COPD, aged ≥40 years with two or more clinic visits in the previous year were enrolled following spirometric confirmation of COPD. The model of care comprised smoking cessation support, home medicines review (HMR) and home-based pulmonary rehabilitation (HomeBase). Main outcomes included changes in St George's Respiratory Questionnaire (SGRQ) score, COPD Assessment Test (CAT), dyspnoea, smoking abstinence and lung function at 6 and 12 months.We identified 272 participants with COPD (157 intervention, 115 usual care); 49 (31%) out of 157 completed both HMR and HomeBase. Intention-to-treat analysis showed no statistically significant difference in change in SGRQ at 6 months (adjusted between-group difference 2.45 favouring intervention, 95% CI -0.89-5.79). Per protocol analyses showed clinically and statistically significant improvements in SGRQ in those receiving the full intervention compared to usual care (difference 5.22, 95% CI 0.19-10.25). No statistically significant differences were observed in change in CAT, dyspnoea, smoking abstinence or lung function.No significant evidence was found for the effectiveness of this interdisciplinary model of care for COPD in primary care over usual care. Low uptake was a limitation.
Abstract P018: Poincare Plot Asymmetry is Associated With Sudden Cardiac Death in the Community: The Atherosclerosis Risk in Community Study
Authors: Aron Bender, Muammar Kabir, Jason Thomas, David German, Srini Mukundan, Christopher Hamilton, Nona Sotoodehnia, Wendy Post, Scott Solomon, Elsayed Soliman, David Siscovick, Larisa Tereshchenko
Journal: Circulation (2018)

Introduction: Poincare plot asymmetry has been associated with sustained ventricular tachyarrhythmias, implicating involvement of the autonomic nervous system. An association between sudden cardiac death (SCD) and Poincare plot asymmetry has not previously been studied in a general population cohort. Porta index measures time asymmetry in heart rate variability (HRV), corresponding to disproportionate relative tachycardic predominance. Hypothesis: We hypothesized that increasing tachycardic asymmetry as measured by Porta Index is associated with SCD. Methods: We analyzed 10-second ECG in 14,247 participants across 5 visits in the Atherosclerosis Risk in Communities (ARIC) cohort (mean age 54.1±5.87y; 6,380 [45%] men; 10,569 [74%] white, 1,582 [11%] with prevalent cardiovascular disease (CVD)). Participants with atrial fibrillation, premature contractions, sinoatrial (SA) or atrioventricular (AV) blocks II-III were excluded. Only normal sinus beats were included in the semi-automated analysis. Accuracy of automated R-peak detection was manually validated. SCD, non-SCD, and non-cardiac death served as competing outcomes in a Fine and Gray competing risk model. Results: Overall, there was larger variability in Porta index within the same participant from visit to visit (50.0±12.1) than between different participants (50.0±8.4). Over median follow-up of 24.4 years, there were 497 SCDs (incidence 1.66 [95% CI 1.52-1.82], 742 non-SCD (incidence 2.48 [95%CI 2.31-2.67], and 3,753 non-cardiac deaths (incidence 12.6 [95% CI 12.1-13.0]) per 1,000 person-years. In time-updated analysis, Porta index was independently associated with increased risk of SCD (HR 1.13 [1.04-1.23]). Neither non-sudden cardiac death nor non-cardiac death are associated with Porta ndex. Conclusion: Time-updated Poincare Plot asymmetry as measured by Porta index, reflecting tachycardic runs longer than bradycardic runs, is independently associated with SCD in the community. Poincare plot asymmetry requires further study.
PTH-035 Coffee ground vomit:does it justify an urgent endoscopy?
Authors: Aria Khani, Yulia Maksunova, Mehul Patel, Kalpesh Besherdas
Journal: Endoscopy (2018)

<h3>Introduction</h3> Coffee ground vomit is vomit that looks subjectively like coffee grounds. It is thought to occur due to the presence of coagulated blood in the vomit and hence is a common indication for inpatient admission and thereafter endoscopy. In an increasingly stretched inpatient endoscopy service it is important not to over burden it with endoscopies that could be performed safely as an outpatient. Therefore, our aim is to evaluate the need for inpatient gastroscopy in patients who are deemed to have coffee ground vomiting. We hypothesise that patients with coffee ground vomiting do not have significant upper gastro intestinal bleeding requiring endoscopic intervention. <h3>Methods</h3> A single centre, retrospective analysis was performed on patients endoscopied for the primary indication of coffee ground vomiting. Data was collected and scrutinised from the Electronic Patient Records (EPR) and Unisoft endoscopy-reporting tool at Barnet and Chase Farm Hospitals, Royal Free London for 12 months of 2017. Gastroscopy reports were studied to see whether endoscopic therapy was required (defined as use of adrenaline injection, banding, clips, haemospray or gold probe). EPR was subsequently used to assess whether these patients had a significant drop in their haemoglobin (Hb) defined as a Hb drop ≤20 g/dl. Two independent researchers carried this out. <h3>Results</h3> There were 2618 gastroscopies during the study period. Of these, 37 were indicated due to coffee ground vomiting with 29 being performed as an inpatient. Of these 29 patients, 27 (93%) had a significant drop in their Hb level prior to gastroscopy. One (3%) patient required endoscopic therapy. This patient had significant co-morbidty of ischaemic heart disease, hypertension, aortic valve replacement as well as a drop in Hb. In total, 12 patients had a diagnosis of oesophagitis, 3 had erosive gastritis, 3 non erosive gastritis, 1 oesophageal ulcer, 3 duodenal ulcers, 3 non erosive duodenitis, 1 pyloric ulcer and 1 hiatus hernia. 4 gastroscopies were completely normal. There were no patients with cancer diagnosis. Each diagnosis was reported separately if the report contained more than one diagnosis. <h3>Conclusions</h3> From this study we conclude that in the majority of patients endoscoped for coffee ground vomit do not require intervention during endoscopy. This study confirms our hypothesis and adds weight to the notion that patients with coffee ground vomiting do not necessarily require inpatient gastroscopy despite a significant Hb drop. If findings from this study were to be repeated in other centres we may be able to discharge stable patients with coffee ground vomiting to early OPD endoscopy thus reducing length of stay and pressure on already stretched inpatient emergency workload.
Hospital admissions in children with acute respiratory disease in Portugal
Authors: J. Borges, M. Valente Rosa, R.M. Fernandes, P.J. Nogueira, T. Bandeira
Journal: Pulmonology (2019)

© 2019 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, ˜ S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
TCT-813 Long-term performance of a transfemorally implantable nonmetallic, retrievable and repositionable aortic valve in patients with severe aortic stenosis 4 Year Follow-Up of the 22 F-Direct Flow Medical Valve
Authors: Klaudija Bijuklic, Thilo Tuebler, Hendrik Treede, Hermann Reichenspurner, Reginald Low, Eberhard Grube, Joachim Schofer
Journal: Journal of the American College of Cardiology (2012)
Governmental liability for negligent treatment. 1
Authors: A. R. Holder
Journal: JAMA (1973)

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
A Case of Radioactive Iodine Uptake Found in Artificial Eye
Authors: Il-Hyun Kim, Joon-Kee Yoon, Su Jin Lee, Eugene Jeong, Young-Sil An
Journal: Clinical Nuclear Medicine (2019)

Radioactive iodine (RAI) therapy is widely used as an adjunctive treatment in patients with differentiated thyroid cancer. Although I has high avidity in the functioning thyroid, and in differentiated thyroid cancer lesions, physiological and nonspecific uptake of I in healthy or benign tissue may contribute to false-positive findings on an I scan. Here, we present an interesting image of RAI uptake in the eye region post-RAI treatment, which has been identified as tear contamination in the artificial eye.
Stewart Adams: pharmacologist who discovered ibuprofen
Authors: Marika Davies
Journal: BMJ (2019)

Stewart Adams believed that those involved in the discovery of new drugs should be the first to take them—later restrictions on this practice, in his opinion, took the excitement out of research. Searching for a painkiller to treat rheumatoid arthritis in the early 1960s, he was the first to step forward to try compound 1472. He did not have high hopes for the new drug—there had been plenty of disappointments over the years—but it would become one of the world’s most popular medicines, better known as ibuprofen.

Adams’s interest in finding a painkiller for use in rheumatoid arthritis was sparked in 1952, at a lecture by the Nobel prize winner Philip Hench on the discovery of cortisone. Adams was struck by the “miraculous effects” of the steroid, which could drastically improve the quality of life of patients bedbound by rheumatoid arthritis. But cortisone (and aspirin, the other treatment of choice in rheumatoid arthritis at the time) had serious side effects. Adams saw the need for a “non-cortisone-like compound” to treat the inflammatory …
P063/O11 Inhibition of arginase-1 expression by the transcription factor Fra-1 in macrophages exacerbates rheumatoid arthritis inflammation
Authors: N Hannemann, S Cao, A Schnelzer, J Jordan, M Eberhardt, U Schleicher, S Uebe, A Ekici, J Rech, T Bäuerle, C Bogdan, J Vera, G Schett, A Bozec
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> The activator protein (AP)-1 transcription factor family, especially its subfamily of FOS proteins (cFos, FosB, Fra-1 and Fra-2) are associated to the regulatory network of macrophage responses. Moreover, it is well known that macrophages are central player during rheumatoid arthritis (RA). <h3>Objectives</h3> This study aims to delineate the role of Fra-1 in macrophages during the acute destructive inflammatory phase of RA. <h3>Methods</h3> Therefore, we applied the serum-induced arthritis (K/BxN) model to Fra-1 deficient mice controlled by the Mx1 promoter (Fra-1<sup>ΔMx</sup>) or the LysM promoter (Fra-1<sup>ΔLysM</sup>). Moreover, we performed <i>in vitro</i> analyses of macrophage polarization in wildtype and Fra-1 deficient macrophages, as well as micro-arrays and ChIP sequencing analyses to delineate Fra-1 targets in activated macrophages. We completed our analysis by studying Fra-1 expression in RA patients' synovium. <h3>Results</h3> Fra-1 mutant mice had decreased arthritis severity compared to their littermate wildtype mice. The alleviated arthritis was accompanied to increased arginase-1 (Arg1) expression and activity in the joints, suggesting that its anti-inflammatory features milder RA inflammation. Sorting of immune cell populations revealed macrophages as the major source of Arg1, which was increased in Fra-1 mutant mice. Mechanistically, Fra-1 transcriptionally inhibited Arg1 expression in macrophages. Moreover, inhibition of Arginase in Fra-1 mutant mice restored a full blunt inflammatory RA response and the supplementation of mice with l-arginine, leading to increased arginase activity in the joint, is sufficient to milder arthritis. Synovium histological sections from RA patients showed a correlation between Arg1, Fra-1 and the DAS28 score, confirming that increased Arg1 activity is of benefit also for human inflammatory joint disease. <h3>Conclusions</h3> Our data show for the first time that Fra-1 is a pivot between pro- and anti-inflammatory macrophage. By inhibiting Arg1 activity, Fra-1 exacerbates RA inflammation and joint destruction. <h3>Disclosure of Interest</h3> None declared.
Utility of Cricoid Pressure—Reply
Authors: Aurélie Birenbaum, David Hajage, Bruno Riou
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal