tbuckley/cabot-search huggingface dataset:
Local icariin application enhanced periodontal tissue regeneration and relieved local inflammation in a minipig model of periodontitis
Authors: Xiuli Zhang, Nannan Han, Guoqing Li, Haoqing Yang, Yangyang Cao, Zhipeng Fan, Fengqiu Zhang
Journal: International Journal of Oral Science (2018)

Periodontitis is an inflammatory autoimmune disease. Treatment should alleviate inflammation, regulate the immune reaction and promote periodontal tissue regeneration. Icariin is the main active ingredient of Epimedii Folium, and it is a promising compound for the enhancement of mesenchymal stem cell function, promotion of bone formation, inhibition of bone resorption, alleviation of inflammation and regulation of immunity. The study investigated the effect of icariin on periodontal tissue regeneration in a minipig model of periodontitis. The minipig model of periodontitis was established. Icariin was injected locally. The periodontal clinical assessment index, a computed tomography (CT) scan, histopathology and enzyme-linked immune sorbent assay (ELISA) were used to evaluate the effects of icariin. Quantitative analysis results 12 weeks post-injection demonstrated that probing depth, gingival recession, attachment loss and alveolar bone regeneration values were (3.72 ± 1.18) mm vs. (6.56 ± 1.47) mm, (1.67 ± 0.59) mm vs. (2.38 ± 0.61) mm, (5.56 ± 1.29) mm vs. (8.61 ± 1.72) mm, and (25.65 ± 5.13) mm 3 vs. (9.48 ± 1.78) mm 3 in the icariin group and 0.9% NaCl group, respectively. The clinical assessment, CT scan, and histopathology results demonstrated significant enhancement of periodontal tissue regeneration in the icariin group compared to the 0.9% NaCl group. The ELISA results suggested that the concentration of interleukin-1 beta (IL-1β) in the icariin group was downregulated compared to the 0.9% NaCl group, which indicates that local injection of icariin relieved local inflammation in a minipig model of periodontitis. Local injection of icariin promoted periodontal tissue regeneration and exerted anti-inflammatory and immunomodulatory function. These results support the application of icariin for the clinical treatment of periodontitis.
FRI0167 Expression levels of il-17, il-22 and il-23 receptors in four osteoblast models and the effects of il-17, il-22 and il-23 on osteoblasts
Authors: J.-R. Zhang, S.-M. Dai
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that chiefly affects the sacroiliac joints and the spine. Radiographs reveal erosive changes at the corners of the vertebral bodies in the early stages of disease, and outgrowth of bony spurs known as syndesmophytes in the later stages. Some data imply a pivotal role of IL-23/IL-17 axis in the regulation of bone homeostasis However, it remains unknown whether IL-17, IL-22 or IL-23 has any direct effects on osteoblasts or new bone formation in AS. <h3>Objectives</h3> To examine the expressions of IL-17, IL-22, and IL-23 receptors in four osteoblast models and the effects of IL-17, IL-22, and IL-23 on osteoblasts. <h3>Methods</h3> Gene expression levels of receptors, alkaline phosphatase (ALP), osteocalcin (OCN), and Runt-related transcription factor 2 (Runx-2), were evaluated by RT-PCR and real-time RT-PCR. Proliferative responses and cell cycle analysis were detected by a CCK-8 assay and flow cytometry, respectively. ALP activity and ALP mass were detected by an ALP activity assay and ALP staining, respectively. <h3>Results</h3> In primary osteoblasts, only the IL-17 receptor was expressed. In C2C12, MC3T3-E1, and Saos-2 cells, the genes of IL-17, IL-22, and IL-23 receptors were not detectable. None of IL-17, IL-22, and IL-23 had an obvious effect on the proliferation of primary osteoblasts, but IL-17 exhibited an inhibitory effect on the gene expression of ALP, OCN, and Runx-2. The ALP activity and ALP mass of primary osteoblasts were downregulated by IL-17 treatment in a dose-dependent manner. <h3>Conclusions</h3> Primary osteoblasts constitutively express IL-17 receptors, but none of C2C12 cells, MC3T3-E1 cells, and Saos-2 cells express any receptors for IL-17, IL-22, and IL-23. IL-17 inhibits BMP-2-induced osteoblast differentiation. <h3>Disclosure of Interest</h3> None declared
David Oliver: Health tourism, immigration, and the NHS
Authors: David Oliver
Journal: BMJ (2018)

Results from a pilot scheme designed to clamp down on “health tourism” were reported by the London Evening Standard last month.1 As part of the scheme, which ran in 18 hospitals (11 in Greater London) over two months in autumn 2017, patients were required to show two forms of ID to prove that they were eligible for free NHS treatment. Checks carried out on 8894 patients found only 50 who were not eligible for free NHS treatment.

Overseas visitors are already eligible for free emergency care, and we have reciprocal arrangements with other EU countries for reimbursing healthcare costs, although the Public Accounts Committee did criticise the NHS in 2017 for a “chaotic approach” to chasing reimbursement from EU countries.2

One …
AB0622 Characteristics of systemic lupus erythematosus patients in malta; a population based cross-sectional cohort study
Authors: R. Magro, A.A. Borg
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that involves multiple systems including the skin, musculoskeletal, renal, neurological, haematologic, cardiovascular and respiratory systems. <h3>Objectives</h3> The aim of this study was to characterise the patients with systemic lupus erythematosus living in Malta, in terms of age of disease onset, BMI, co-morbidities, drug history, disease activity, damage and other factors including fatigue, sleep quality, depression, anxiety and vitamin D level. <h3>Methods</h3> The study consisted of a cross-sectional cohort study of all known SLE patients, over the age of 18, living in Malta. 92 patients who fulfilled the SLICC classification criteria for SLE, gave informed consent and an interview was carried out. Fatigue, anxiety, depression, sleep quality and disability were assessed respectively by filling in the following questionnaires: Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and modified Health Assessment Questionnaire (mHAQ). <h3>Results</h3> 92.4% of SLE patients studied were female. Table 1 summarises the characteristics of the SLE patients. 23.9% of SLE patients were in remission (SLEDAI-2K 0), while 52.2% had a low disease activity (SLEDAI-2K 1–5) at the time of the interview. 20.7% and 3.3% had a moderate (SLEDAI-2K 6–10) and high (SLEDAI-2K 11–19) disease activity respectively. A significant positive correlation was noted between function measured by mHAQ and SLEDAI (R=0.417, p=0.000). 56.5% were noted to have an abnormally high level of fatigue (FSS &gt;3.7). 6.5% were noted to have depression (HADS D&gt;10) and 35.9% had anxiety (HADS A&gt;10). 55.4% were noted to have poor sleep quality (PSQI &gt;5) and 26.1% had an abnormal level of function (mHAQ &gt;0.3). 15.2% were found to have vitamin D deficiency and 27.2% were vitamin D insufficient. <h3>Conclusions</h3> This is the first population based study on SLE to be carried out in Malta. The prevalence of SLE in Malta is estimated to be 25.5 patients per 1 00 000 and the estimated incidence is 1.05 patients per 1 00 000 per year. A high frequency of obesity and vitamin D deficiency and insufficiency were noted in SLE patients. Other unmet needs include an uncontrolled disease activity, fatigue, poor sleep quality and anxiety. <h3>Disclosure of Interest</h3> None declared
FRI0326 Immune cellular profile associated with different treatment outcome in patients with systemic lupus erythematosus on cyclophosphamide
Authors: G. Gabcova, M. Skacelova, Z. Mikulkova, P. Horak, S. Zehnalova, A. Smrzova, F. Mrazek, V. Smotkova Kraiczova, M. Kudelka, E. Kriegova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Cyclophosphamide (CFA) is an effective immunosuppressive drug used for treatment of severe manifestations of systemic lupus erythematosus (SLE). The knowledge about modulatory effect of CFA on circulating immune cells and its changes associated with treatment response is limited. <h3>Objectives</h3> To determine the effect of a cumulative dose of CFA on circulating immune cells in SLE patients and to assess its association with treatment outcome. <h3>Methods</h3> Using 6-colour flow cytometry (BD FACSCanto II) we analysed T and B lymphocytes, NK cells, neutrophils, and monocytes in peripheral blood from 11 SLE female patients. SLE patients were investigated before and after cumulative 1000 mg and 3000 mg of CFA dose. Patients subgroups were assessed according to the treatment response (n=5, good responders; n=6, poor responders); SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) was used to assess the disease activity. Healthy age-matched females (n=12) were included in the study. Statistics was done by GraphPad Prism and R statistical software package. <h3>Results</h3> Cumulative dose of 1000 mg of CFA resulted in decreased percentage of B lymphocytes (p=0.0004) and CD4 +T lymphocytes (p=0.02) and increased the percentage of total and CD8 +T lymphocytes (p=0.03; p=0.0003 respectively). After 3000 mg CFA, the percentage of B lymphocytes (p=0.002), naïve B lymphocytes (p=0.005), memory B lymphocytes (p=0.02) and CD4+/CD8 +ratio (p=0.01) decreased while the percentage of CD8 +T lymphocytes (p=0.0003), Tregs (p=0.01) and CD69 +NK cells (p=0.02) increased. CFA treatment in our patients resulted in reduction of B lymphocyte percentage reaching the values of healthy controls. In good responders, decreased percentage of B lymphocytes (p=0.04), CD4 +T lymphocytes (p=0.04), CD4+/CD8 +ratio (p=0.007) and increased percentage of CD8 +T lymphocytes (p=0.004), CD69 +NK cells (p=0.04) and nonclassical monocytes (p=0.04). In poorly responding patients percentage of CD8 +T lymphocytes (p=0.01), activation marker HLA-DR on both CD4 +and CD8+T lymphocytes (p=0.01; p=0.02 respectively), Tregs (p=0.02), memory B lymphocytes (p=0.03) were increased and percentage of total B lymphocytes was decreased (p=0.02). The analysis using advanced data mining methods for identification of treatment outcome related profiles are ongoing <h3>Conclusions</h3> Administration of CFA modulates several cell populations in SLE patients, whereas changes in B and T lymphocytes were associated with different treatment outcome. Whether the immune profile may predict the treatment response deserves further investigation. <h3>Acknowledgements</h3> MZ CR VES15–28659A, IGA_LF_2018_016 <h3>Disclosure of Interest</h3> None declared
AB0142 A regulatory ccr10+ cd8+ t cell population differentiates psoriatic arthritis from psoriasis limited to cutaneous involvement
Authors: E.F. Leijten, T.S. van Kempen, M.A. Olde Nordkamp, J.S. Mertens, C. Angiolilli, M.L. Boes, T.R. Radstake
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Few studies have compared the immune cell phenotype or function from patients with psoriatic arthritis (PsA) to patients with psoriasis limited to cutaneous involvement (Pso). Head-to-head comparisons of the immune cells in PsA and Pso can provide essential insights into the link between epithelial/cutaneous disease and rheumatic disease. <h3>Objectives</h3> Compare the immune cell phenotype and function from patients with PsA compared to Pso. <h3>Methods</h3> PBMCs were collected from 23 healthy controls, 21 patients with psoriasis in whom psoriatic arthritis was excluded by a rheumatologist (Pso), 23 patients with psoriatic arthritis (PsA) and 16 patients with ankylosing spondylitis. The Pso and PsA cohorts were free from immunomodulatory therapy and matched for demographics and skin severity. Extracellular and intracellular immunophenotyping using a highly standardised flow-cytometric approach detected over 110 different myeloid and lymphoid cell populations. Lesional and non-lesional skin biopsies and synovial fluid samples were collected from a subset of patients. <h3>Results</h3> The circulating immune cell composition showed a remarkable overlap in Pso and PsA, and only one specific cell population was different: CCR10 +CD8+T cells, being enriched in PsA PBMCs as compared to Pso PBMCs. Further phenotypic and functional evaluation characterised them as effector memory, CXCR3-CCR6-, co-expressing the skin homing markers CCR4 and CLA, but lacking the gut homing marker α4β7. Upon re-stimulation, CCR10 +CD8+T cells showed low IFNγ production, high IL-10 production and were enriched for FOXP3<sup>high</sup>CD25+ phenotype. Their frequencies in PBMCs were unrelated to joint disease activity and were stable throughout joint disease fluctuations. Synovial fluid displayed low frequencies of CCR10 +CD8+T cells whereas skin contained the most abundant CCR10 +CD8+T cell frequencies. Lesional psoriasis skin displayed relatively fewer CCR10 +CD8+T cells compared to non-lesional skin. <h3>Conclusions</h3> CCR10 +CD8+T cells have regulatory properties and differentiate Pso from PsA. Future studies are needed to uncover if aberrances in regulatory, cutaneous CD8 +T cells precede the transition to joint disease. <h3>Disclosure of Interest</h3> None declared
Bronchial Mucosa–Associated Lymphoid Tissue Lymphoma Staged by 11C-Methionine
Authors: Salvatore Annunziata, Annarosa Cuccaro, Alessio Rizzo, Silvia Chiesa, Francesco D'Alò
Journal: Clinical Nuclear Medicine (2018)

Abstract A 57-year-old man had a diagnosis of a bronchial mucosa–associated lymphoid tissue lymphoma in the left lung and monoclonal gammopathy. The patient underwent whole-body 11 C-methionine PET/CT, in order to evaluate the amino acid avidity of the lesion and to stage the bronchial mucosa–associated lymphoid tissue lymphoma. 11 C-methionine uptake was detected in the lung lesion and in the mediastinal lymph nodes.
SAT0659 Is synovial hypertrophy without doppler activity in rheumatoid arthritis joints sensitive to change? – results of a longitudinal ultrasound study
Authors: L. Terslev, M. Østergaard, J. Sexton, H.B. Hammer
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ultrasound (US) is used to assess diseases activity in rheumatoid arthritis (RA). Grey scale (GS) US shows the synovial hypertrophy (SH) and Doppler the amount of hyperemia which is believed to reflect disease activity. Some joints with SH may have no Doppler activity despite the use of high-end US equipment and these joints are generally believed to be inactive without potential to change. <h3>Objectives</h3> The aim was to investigate if joints with SH but no Doppler activity is sensitive to change during treatment with biological DMARD (bDMARD) in RA patients. <h3>Methods</h3> RA patients initiating or changing bDMARD treatment were included. US examination was performed at baseline, 3 and 6 months using Siemens Antares US equipment with Doppler settings for slow flow. 36 joints were evaluated at each visit. SH and Doppler activity was graded from 0–3 according to the US atlas by Hammer et al.(<sup>1</sup> The GS score for SH in joints without Doppler activity was registered for the individual joints using GS SH ≥1 as threshold. The changes were compared to changes in SH in joints with Doppler activity. <h3>Results</h3> 151 patients (82.8% women, 80.1% seropositive for anti-CCP) were included, with a mean (SD) age 51.4 (13.2) years, disease duration 9.9 (7.9) years. At baseline, 50.7% used prednisolone (mean (SD) 5 mg (4.68)). The patients had a mean (SD) baseline DAS28 of 4.5 (1.5). At baseline 23% of the joints had SH without Doppler activity and 23% of the joints had SH with Doppler activity. Doppler-negative joints had overall lower grades of SH (mean 1.2) than Doppler-positive joints (mean 2.2) at baseline using GS SH &gt;1 as cut-off. The improvement in SH was similar in Doppler-positive and Doppler-negative joints but when adjusting for the baseline score of SH, Doppler-negative joints had a higher tendency towards decrease than Doppler-positive joints for all grades (3 months: p&lt;0.0001; 6 months=0.0006). A weak correlation was found to changes in DAS 28(crp) (Doppler-negative joints:0.27 (p=0.001) and 0.18 (p=0.03) at 3 and 6 months respectively – Doppler-positive joints: 0.25 (p=0.004) and 0.33 (p=0.0002) at 3 and 6 months respectively). <h3>Conclusions</h3> SH in joints without Doppler activity improves during bDMARD, i.e is sensitive to change. Thus, SH without Doppler activity is not a sign of inactive disease. These findings document that both Doppler and SH should be evaluated when assessing disease activity by US. <h3>Reference</h3> [1] Hammer HB, Bolton-King P, Bakkeheim V, et al. Examination of intra and interrater reliability with a new ultrasonographic reference atlas for scoring of synovitis in patients with rheumatoid arthritis. Ann Rheum Dis2011;70:1995–8. <h3>Disclosure of Interest</h3> None declared
Prostate Imaging-Reporting and Data System Steering Committee: PI-RADS v2 Status Update and Future Directions
Authors: Anwar R. Padhani, Jeffrey Weinreb, Andrew B. Rosenkrantz, Geert Villeirs, Baris Turkbey, Jelle Barentsz
Journal: European Urology (2018)

The Prostate Imaging-Reporting and Data System (PI-RADS) v2 analysis system for multiparametric magnetic resonance imaging (mpMRI) detection of prostate cancer (PCa) is based on PI-RADS v1, accumulated scientific evidence, and expert consensus opinion.
Spending on shortages of generics rose sevenfold last year to £315m
Authors: Jacqui Wise
Journal: BMJ (2018)

Rapid price rises for some generic drugs forced clinical commissioning groups (CCGs) to spend an extra £315m (€357m; $422m) last year, placing their budgets under significant pressure, the National Audit Office (NAO) has found.1 In one case, the price of a generic antipsychotic drug rose by a factor of 70.

The report into NHS spending on generic drugs in primary care says a number of factors may have contributed to the price increases, including a fall in the value of sterling, supply problems, and wholesalers pushing up their profits. The derailing of CCG’s budgets by the price hikes was first reported in The BMJ in January.2

The NHS spent an estimated £4.3bn on generic drugs in 2016-17, of which £3.5bn was spent in primary care. In primary care, pharmacies buy drugs from wholesalers or manufacturers who determine their own prices. The …
PROMIDISα: A T-cell receptor α signature associated with immunodeficiencies caused by V(D)J recombination defects
Authors: Aurélie Berland, Jérémie Rosain, Sophie Kaltenbach, Vincent Allain, Nizar Mahlaoui, Isabelle Melki, Alice Fievet, Catherine Dubois d'Enghien, Marie Ouachée-Chardin, Laurence Perrin, Nathalie Auger, Funda Erol Cipe, Andrea Finocchi, Figen Dogu, Felipe Suarez, Despina Moshous, Thierry Leblanc, Alexandre Belot, Claire Fieschi, David Boutboul, Marion Malphettes, Lionel Galicier, Eric Oksenhendler, Stéphane Blanche, Alain Fischer, Patrick Revy, Dominique Stoppa-Lyonnet, Capucine Picard, Jean-Pierre de Villartay
Journal: Journal of Allergy and Clinical Immunology (2018)
Association of Obesity or Weight Change With Coronary Heart Disease Among Young Adults in South Korea
Authors: Seulggie Choi, Kyuwoong Kim, Sung Min Kim, Gyeongsil Lee, Su-Min Jeong, Seong Yong Park, Yeon-Yong Kim, Joung Sik Son, Jae-Moon Yun, Sang Min Park
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> Previous studies have shown a U- or J-shaped association of body mass index (BMI) or change in BMI with coronary heart disease (CHD) among middle-aged and elderly adults. However, whether a similar association exists among young adults is unclear. <h3>Objective</h3> To determine whether an association exists between BMI or BMI change with CHD among young adults. <h3>Design, Setting, and Participants</h3> This population-based longitudinal study used data obtained by the Korean National Health Insurance Service from 2002 to 2015. The study population comprised 2 611 450 men and women aged between 20 and 39 years who underwent 2 health examinations, the first between 2002 and 2003 and the second between 2004 and 2005. <h3>Exposures</h3> World Health Organization Western Pacific Region guideline BMI categories of underweight, normal weight, overweight, obese grade 1, and obese grade 2 derived during the first health examination and change in BMI calculated during the second health examination. <h3>Main Outcomes and Measures</h3> Body mass index (calculated as weight in kilograms divided by height in meters squared). Absolute risks (ARs), adjusted hazard ratios (aHRs), and 95% CIs for acute myocardial infarction or CHD during follow-up from 2006 to 2015. <h3>Results</h3> Data from 1 802 408 men with a mean (SD) age of 35.1 (4.8) years and 809 042 women with a mean (SD) age of 32.5 (6.3) years were included. The mean (SD) BMI was 23.2 (3.2) for the total population, 24.0 (3.0) for men, and 21.4 (2.9) for women. Compared with normal weight men, overweight (AR, 1.38%; aHR, 1.18 [95% CI, 1.14-1.22]), obese grade 1 (AR, 1.86%; aHR, 1.45 [95% CI, 1.41-1.50]), and obese grade 2 (AR, 2.69%; aHR, 1.97 [95% CI, 1.86-2.08]) men had an increased risk of CHD (<i>P</i> &lt; .001 for trend). Similarly, compared with normal weight women, overweight (AR, 0.77%; aHR, 1.34 [95% CI, 1.24-1.46]), obese grade 1 (AR, 0.95%; aHR, 1.52 [95% CI, 1.39-1.66]), and obese grade 2 (AR, 1.01%; aHR, 1.64 [95% CI, 1.34-2.01]) women had an increased risk of CHD (<i>P</i> &lt; .001 for trend). Compared with participants who maintained their weight at normal levels, those who became obese had elevated CHD risk among men (0.35% increase in AR; aHR, 1.35 [95% CI, 1.17-1.55]) and women (0.13% increase in AR; aHR, 1.31 [95% CI, 0.95-1.82]). Weight loss to normal levels among obese participants was associated with reduced CHD risk for men (0.58% decrease in AR; aHR, 0.77 [95% CI, 0.64-0.94]) and women (0.57% decrease in AR; aHR, 0.66 [95% CI, 0.45-0.98]). <h3>Conclusions and Relevance</h3> Obesity and weight gain were associated with elevated risk of CHD among young adults in this study. Studies that prospectively determine the association between weight change and CHD risk are needed to validate these findings.
Cytokine release syndrome
Authors: Alexander Shimabukuro-Vornhagen, Philipp Gödel, Marion Subklewe, Hans Joachim Stemmler, Hans Anton Schlößer, Max Schlaak, Matthias Kochanek, Boris Böll, Michael S. von Bergwelt-Baildon
Journal: Journal for ImmunoTherapy of Cancer (2018)

During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS). This review provides a comprehensive overview of the mechanisms underlying CRS pathophysiology, risk factors, clinical presentation, differential diagnoses, and prognostic factors. In addition, based on the current evidence we give practical guidance to the management of the cytokine release syndrome.