tbuckley/cabot-search huggingface dataset:
AB0144 Nmr based serum and synovial fluid metabolomics reveal similar metabolomic profile in patients with reactive arthritis and undifferentiated spondyloarthropathy
Authors: R. Misra, D. Dubey, S. Ahmed, S. Chaurasia, S. Chaudhary, A. Guleria, D. Kumar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Reactive arthritis (ReA)and undifferentiated spondyloarthropathy (USpA) have similar clinical picture, the former is prededed by mucosal infections and the latter do not meet criteria of well defined entity of seronegative spondyloarthropathy (SSA) We have shown that both ReA and uSpA have similar synovial fludid T cell response to salmonella antigens and cytokine profile. <h3>Objectives</h3> To investigate if the metabolic profiles of ReA in sera and synovial fluid are different from those of USpA <h3>Methods</h3> Standard defnitions were used to classify patients as ReA<sup>2</sup> and uSpA<sup>3</sup> Metabolic profiles in sera and synovial fluid samples were measured using 1D <sup>1</sup>H NMR spectroscopy and analysed using CHENOMX© software. The quantitative profiles between the groups were compared using Partial Least Square-Discriminatory Analysis (PLS-DA) and Q<sup>2</sup> parameter was used to assess the metabolic differences between the groups. <h3>Results</h3> The study involved 19 ReA and 13 USpA patients with median age 26 (21–33.75) years. Of 32 patients: 7 (22%) were females, three(12%) had monophasic illness, 16 (64%) polyphasic, and six(24%) persistent arthritis (follow-up data was not available for 7). 27% had monoarticular, 59% oligoarticular and 14% polyarticular involvement. Six had inflammatory backpain, three had oral ulcers, one dactylitis, but none had mucocutaneous manifestations. Two had asymptomatic sacroiliitis on radiographs. Compared to normal controls (n=18, median age=29 years, male:female=17:1), the sera of ReA/USpA patients were characterised by elevated levels of malonate, mannose, N-nitrosodimethylamine, and pyruvate, whereas 3-hydroxyisovalerate was decreased significantly (T-test p-value&lt;0.001). PLS-DA analysis between sera and synovial fluid samples showed clear demarcation with higher pyruvate and acetoacetate and lower aspartate, methanol, ethanol, and methylsuccinate in synovial fluid samples compared to sera (t-test p&lt;0.01). The PLS-DA analysis of sera showed little difference between ReA and USpA <b>(figure 1)</b> while that of synovial fluid showed Q<sup>2</sup> &lt;0 for all models. Further no significant metabolic differences in sera/synovial fluid were found between HLA-B27 positive and negative groups (Q<sup>2</sup> &lt;0 in all models). <h3>Conclusions</h3> ReA and USpA have indistinguishable metabolomics profiles in sera and synovial fluid reflecting similar metabolo-inflammatory pathways involved. <h3>References</h3> [1] Chaurasia S, Shasany AK, Aggarwal A, Misra R. 2016Aug;185(2):210–8. [2] Braun J, Kingsley G, et sl. Journal of Rheumatology2000;27:2185–92. [3] Sieper J, Rudwaleit M, et al. Ann Rheum Dis. 2009Jun;68(Suppl 2):ii1–44. <h3>Disclosure of Interest</h3> None declared
Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy
Authors: Amber J. Giles, Marsha-Kay N. D. Hutchinson, Heather M. Sonnemann, Jinkyu Jung, Peter E. Fecci, Nivedita M. Ratnam, Wei Zhang, Hua Song, Rolanda Bailey, Dionne Davis, Caitlin M. Reid, Deric M. Park, Mark R. Gilbert
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Corticosteroids are routinely utilized to alleviate edema in patients with intracranial lesions and are first-line agents to combat immune-related adverse events (irAEs) that arise with immune checkpoint blockade treatment. However, it is not known if or when corticosteroids can be administered without abrogating the efforts of immunotherapy. The purpose of this study was to evaluate the impact of dexamethasone on lymphocyte activation and proliferation during checkpoint blockade to provide guidance for corticosteroid use while immunotherapy is being implemented as a cancer treatment. <h3>Methods</h3> Lymphocyte proliferation, differentiation, and cytokine production were evaluated during dexamethasone exposure. Human T cells were stimulated through CD3 ligation and co-stimulated either directly by CD28 ligation or by providing CD80, a shared ligand for CD28 and CTLA-4. CTLA-4 signaling was inhibited by antibody blockade using ipilimumab which has been approved for the treatment of several solid tumors. The in vivo effects of dexamethasone during checkpoint blockade were evaluated using the GL261 syngeneic mouse intracranial model, and immune populations were profiled by flow cytometry. <h3>Results</h3> Dexamethasone upregulated CTLA-4 mRNA and protein in CD4 and CD8 T cells and blocked CD28-mediated cell cycle entry and differentiation. Naïve T cells were most sensitive, leading to a decrease of the development of more differentiated subsets. Resistance to dexamethasone was conferred by blocking CTLA-4 or providing strong CD28 co-stimulation prior to dexamethasone exposure. CTLA-4 blockade increased IFNγ expression, but not IL-2, in stimulated human peripheral blood T cells exposed to dexamethasone. Finally, we found that CTLA-4 blockade partially rescued T cell numbers in mice bearing intracranial gliomas. CTLA-4 blockade was associated with increased IFNγ-producing tumor-infiltrating T cells and extended survival of dexamethasone-treated mice. <h3>Conclusions</h3> Dexamethasone-mediated T cell suppression diminishes naïve T cell proliferation and differentiation by attenuating the CD28 co-stimulatory pathway. However, CTLA-4, but not PD-1 blockade can partially prevent some of the inhibitory effects of dexamethasone on the immune response.
Unexpected Benefits of Aging for Favorable Responses to PD-1 Blockade in Melanoma?
Authors: Graham Pawelec
Journal: Clinical Cancer Research (2018)

Abstract Immunosenescence might be expected to reduce the efficacy of checkpoint blockade, which depends on a functionally intact immune system. However, it seems that older patients with melanoma may respond better to anti-PD-1 treatment than younger patients, possibly due to their having fewer regulatory T cells relative to CD8+ T cells within tumor deposits. Clin Cancer Res; 24(21); 5193–4. ©2018 AACR. See related article by Kugel et al., p. 5347
Case 18-2018: A 45-Year-Old Woman with Hypertension, Fatigue, and Altered Mental Status
Authors: J. Carl Pallais, Andrew Z. Fenves, Michael T. Lu, Krzysztof Glomski
Journal: New England Journal of Medicine (2018)

A 45-year-old woman presented with hypertension, fatigue, and episodic confusion. After medications were administered, the blood pressure decreased but fatigue and confusion persisted. Four weeks later, pulmonary embolism developed. A diagnostic test was performed.
FRI0284 Altered patterns of histone acetylation point to mechanisms of transcriptional dysregulation in patients with systemic lupus erythematosus
Authors: B. Anić, A. Blažeković, D. Bosnić, M. Sentić, M. Mayer, M. Cerovec, K. Gotovac Jerčić, F. Borovečki
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic autoimmune disease designated by a heterogeneous course and systemic nature. It arises as a result of complex pathways, as well as the interaction of genetic and environmental factors, leading to the altered reactivity of the immune system that culminates in autoantibody formation. Epidemiological studies have shown an important role of the genetic component in the emergence of SLE and genome-wide association studies have identified more than 50 SLE-associated risk loci, pointing to a complex genetic background. <h3>Objectives</h3> The aim of the study was to further elucidate the genetic mechanisms influencing the development of SLE. <h3>Methods</h3> We performed chromatin immunoprecipitation experiments to ascertain the levels of histone acetylation in peripheral blood mononuclear cells collected from 5 recent onset and treatment naive SLE patients compared to 5 age and gender matched controls. <h3>Results</h3> The analysis revealed 16 379 significantly enriched genomic regions in control patients compared to 39 204 significantly enriched genomic regions in SLE patients. Among the SLE specific regions several pathways were significantly enriched including the adaptive immune system pathway, cytokine signalling in immune system, disease of immune system and inflammation mediated by chemokine and cytokine pathway. <h3>Conclusions</h3> The collective data point to a significant alteration of histone acetylation patterns in SLE patients possibly mediated by the DNA specific autoantibodies. The results of the study offer additional insight into the genetics of SLE pointing to putative mechanisms of transcriptional dysregulation. <h3>Disclosure of Interest</h3> None declared
Screening for Cardiovascular Disease Risk With Resting or Exercise Electrocardiography
Authors: Daniel E. Jonas, Shivani Reddy, Jennifer Cook Middleton, Colleen Barclay, Joshua Green, Claire Baker, Gary N. Asher
Journal: JAMA (2018)

Cardiovascular disease (CVD) is the leading cause of death in the United States.To review the evidence on screening asymptomatic adults for CVD risk using electrocardiography (ECG) to inform the US Preventive Services Task Force.MEDLINE, Cochrane Library, and trial registries through May 2017; references; experts; literature surveillance through April 4, 2018.English-language randomized clinical trials (RCTs); prospective cohort studies reporting reclassification, calibration, or discrimination that compared risk assessment using ECG plus traditional risk factors vs traditional risk factors alone. For harms, additional study designs were eligible. Studies of persons with symptoms or a CVD diagnosis were excluded.Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings.Mortality, cardiovascular events, reclassification, calibration, discrimination, and harms.Sixteen studies were included (N = 77 140). Two RCTs (n = 1151) found no significant improvement for screening with exercise ECG (vs no screening) in adults aged 50 to 75 years with diabetes for the primary cardiovascular composite outcomes (hazard ratios, 1.00 [95% CI, 0.59-1.71] and 0.85 [95% CI, 0.39-1.84] for each study). No RCTs evaluated screening with resting ECG. Evidence from 5 cohort studies (n = 9582) showed that adding exercise ECG to traditional risk factors such as age, sex, current smoking, diabetes, total cholesterol level, and high-density lipoprotein cholesterol level produced small improvements in discrimination (absolute improvements in area under the curve [AUC] or C statistics, 0.02-0.03, reported by 3 studies); whether calibration or appropriate risk classification improves is uncertain. Evidence from 9 cohort studies (n = 66 407) showed that adding resting ECG to traditional risk factors produced small improvements in discrimination (absolute improvement in AUC or C statistics, 0.001-0.05) and appropriate risk classification for prediction of multiple cardiovascular outcomes, although evidence was limited by imprecision, quality, considerable heterogeneity, and inconsistent use of risk thresholds used for clinical decision making. Total net reclassification improvements ranged from 3.6% (2.7% event; 0.6% nonevent) to 30% (17% event; 19% nonevent) for studies using the Framingham Risk Score or Pooled Cohort Equations base models. Evidence on potential harms (eg, from subsequent angiography or revascularization) in asymptomatic persons was limited.RCTs of screening with exercise ECG found no improvement in health outcomes, despite focusing on higher-risk populations with diabetes. The addition of resting ECG to traditional risk factors accurately reclassified persons, but evidence for this finding had many limitations. The frequency of harms from screening is uncertain.
Combined effects of synbiotic and sitagliptin versus sitagliptin alone in patients with nonalcoholic fatty liver disease
Authors: Saba Sayari, Hassan Neishaboori, Maryam Jameshorani
Journal: Clinical and Molecular Hepatology (2018)

See the commentary-article "Combination of synbiotic and sitagliptin in nonalcoholic fatty liver disease: Is it better than sitagliptin alone?" on page 299.
41 Rectal nsaids and selective pancreatic stenting significantly reduces acute pancreatitis in normal risk ercp
Authors: M Killian, S Maxudor, M Looby, D O’ Connor, W Stack
Journal: Gut (2017)

Background  In high-risk cases a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and selective pancreatic stenting may reduce the risk of post ERCP pancreatitis (PEP). However, studies on whether this practice reduces PEP in normal risk ERCPs have shown conflicting results.  Aim  To compare the rate of PEP for normal risk ERCP, where patients are administered rectal NSAIDs immediately following the procedure with selective pancreatic stenting (N/S), against the previous practice, which did not incorporate N/S.  Method  Consecutive ERCPs from 2009–2016 were analysed pre and post N/S. In the post N/S group rectal NSAIDS were administered immediately following the procedure. Pancreatic stents were used if the pancreatic duct was cannulated more than three times during the procedure. PEP was defined as post ERCP abdominal pain and a rise in amylase to at least twice the upper limit of normal. Statistical analysis was by paired t and McNemars tests.  Results  574 ERCP procedures were performed, of which 509 were successful (89%). 335 (58%) were female, with an average age of 67.7 (range16–94 years). 488 were therapeutic (96%). There were no statistically significant differences in the demographics of each group. 23 of 375 (6.1%) in the Pre N/S group developed PEP compared with 4 of 199 (2%) in the Post N/S group, p=0.02.  Conclusions  This study shows a further significant reduction of PEP in normal risk ERCP in a cohort of patients with a historically low PEP rate following the introduction of rectal NSAIDs and selective pancreatic stenting.
Abstract 15927: Plasma Proteomic Profiling Identifies Multiple Biomarkers Identifying Increased Risk for Arrhythmic Death in the Prediction of ARrhythmic Events With Positron Emission Tomography (PAREPET) Study
Authors: Jun Qu, Chengjian Tu, Jun Li, James A Fallavollita, Rebeccah F Young, Xiaomeng Shen, Bo An, John M Canty
Journal: Circulation (2013)

Background: Selection of patients to receive a primary prevention ICD is solely based on LV EF. Plasma biomarkers may compliment this but most have not been evaluated in predicting arrhythmic death...
Cardiovascular Outcomes Reported in Hemodialysis Trials
Authors: Emma O’Lone, Andrea K. Viecelli, Jonathan C. Craig, Allison Tong, Benedicte Sautenet, David Roy, William G. Herrington, Charles A. Herzog, Tazeen Jafar, Meg Jardine, Vera Krane, Adeera Levin, Jolanta Malyszko, Michael V. Rocco, Giovanni Strippoli, Marcello Tonelli, Angela Yee Moon Wang, Christoph Wanner, Faiez Zannad, Wolfgang C. Winkelmayer, Angela C. Webster, David C. Wheeler
Journal: Journal of the American College of Cardiology (2018)
AB1083 Clinical and densitometric characteristics in paediatric population with risk factors to develop low bone mass/osteoporosis
Authors: B. Magallares López, J. Betancourt, G. Fraga, E. Quesada-Masachs, M. López – Corbeto, M. Torrent, A. Marin, S. Herrera, E. Carreras, J. Casademont, H. Corominas, J. Malouf
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Low Bone Mass (LBM)/Paediatric Osteoporosis (Ped OP) is a disorder of unknown prevalence, partly due to the lack of diagnosis, associated with the absence of clinical manifestations of the disease until patients develop complications such as fractures, deformities or pain <h3>Objectives</h3> To describe the clinical and densitometric characteristics of the paediatric population with risk factors to develop LBM/Ped OP <h3>Methods</h3> We collected prospectively demographic and clinical data of patients aged 2 to 20 years, referred for bone health assessment due to the presence of a risk factors for LBM/Ped OP, including: inflammatory diseases, immunosuppressants and/or corticosteroids, malabsorptive diseases and chronic systemic disorders. We evaluated daily calcium intake and Bone Densitometry (DXA) was performed. We did also a vertebral morphometry <h3>Results</h3> Data were collected from 90 patients, with an average age of 9'9 years, 53% female, 82% Caucasian. The age distribution and calcium intake by age can be seen in table 1. There was a significant decrease in the compliance of the RDA with calcium with increasing age (p=0.01). No differences were found in the average daily calcium intake between the different diagnostic groups. The most frequent diagnoses were: Malabsorption:44.4%, JIA:20%, Nephropathies:17.8%, Haematological diseases:7.8% and Vasculitis: 4.4%. 18% of the sample had had a fracture (Fx), 44% of them had more than one, being the adolescents the group of greater prevalence. 3 cases met the criteria for fragility Fx (vertebral Fx). 20% of the patients were on systemic corticosteroids, with an average dose of 5.9 mg of prednisone (or equivalent)/day, and another 20% had previously received them. The total cumulative average corticosteroid dose in both groups was: 7 grams of prednisone, with an average exposure of 37 months. 29 patients (32%) received immunosuppressive treatment, of which 20% were methotrexate (alone or in combination with biological DMARD). Only 7% had supplements with Calcium and 14% with Vitamin D. 100% had a normal calcium, 82% a normal phosphate (rest slightly increased) and 11% were deficient in Vitamin D 13% of the sample had a LBM for their age assessed by DXA. The densitometric results can be seen in Table 2. <h3>Conclusions</h3> Calcium intake in children and young with at least 1 risk factor for LBM/Ped Op is lower than recommended, especially in the groups with the highest requirements. Up to 13% of this population have a BMO for their age and a 3'3% meets Ped OP criteria. Larger studies are needed to help us to identify paediatric patients who are candidates for bone health screening <h3>Disclosure of Interest</h3> None declared
What’s hot that the other lot got
Authors: Grace McDowell
Journal: Thorax (2018)

Continuous positive airway pressure (CPAP) is the gold standard treatment for obstructive sleep apnoea (OSA) but adherence to treatment can be poor. Telemedicine can provide remote access to adherence data, patient education platforms and enhance follow-up care. This four-arm randomised trial (Hwang et al. Am J Respir Crit Care Med  2018;197:117–26) assessed the impact of two interventions, web-based OSA education (Tel-Ed) and CPAP telemonitoring with automated messaging (Tel-TM), alone or in combination (Tel-both) in patients requiring CPAP for OSA and compared their effects on CPAP adherence at 90 days to usual care. CPAP usage was evaluated in 556 patients. Usage at 90 days was significantly higher in both the Tel-TM and Tel-both compared with usual care (both P=0.0002). Odds of achieving target adherence (≥70% days with CPAP usage ≥4 hours; the level set for reimbursement in US health system) were 2.4 times higher in Tel-both compared with usual care and 1.7 times in Tel-TM. Usage fell in all four groups but the decline was slower in the Tel-TM group. Tel-Ed improved clinic attendance but not usage. Telemonitoring with automated feedback messaging …
Abstract 11336: Different Mechanisms of Torsade de Pointes Arrhythmias in the Drug-induced Chronic AV Block Dog
Authors: Nele Vandersickel, Alexandre Bossu, Albert Dunnink, Marcel A van der Heyden, Veronique M Meijborg, Jet D Beekman, Jacques M de Bakker, Marc A Vos, Alexander V Panfilov
Journal: Circulation (2016)

Introduction: The arrhythmia Torsade de Pointes (TdP) is responsible for &gt;5% of all sudden cardiac deaths. However, the mechanism(s) underlying the TdPs is under debate. Clinical and experimental data suggest that TdP may be driven either by focal sources or by moving reentry. One way to study the mechanisms of TdP is to use the electrically remodeled canine heart after chronic AV block (CAVB), which has a high susceptibility for drug-induced TdPs. Methods: Five TdP-sensitive CAVB dogs were studied. In all animals, 66 needle electrodes were evenly distributed transmurally to record 240 unipolar local electrograms simultaneously. If the TdP was non-terminating after 10s, it was defibrillated. Software was developed to automatically detect activation times during the dofetilide-induced TdPs and to create 3D visualisations of the arrhythmia. For each episode of TdP, directed graphs of the wave propagation were created and loops were detected by using an iterative depth first search algorithm(Johnson). Interbeat intervals were computed by taking the average of the time intervals of activation for each electrode. Results: In total we analysed 53 TdPs: from those 9 were non-terminating (&gt; 50 beats) and 44 self terminating. In all non-terminating TdPs reentry loops were identified. In the 44 self terminating TdPs reentry loops were found only in 6 (20±10 beats) cases, while in the 38 (7±4 beats) other cases TdP was driven by focal sources. Secondly, during reentry, excitation fronts were constantly present in the heart, while during ectopic TdP there was always a pause between the end of the previous wave and the beginning of the next wave (121±51 ms) during which excitation fronts were absent. Thirdly, we found that the interbeat intervals were significantly smaller for the cases where reentry loops were detected, then in the cases of the ectopic TdPs (221±21 versus 310±96 ms). Finally, in all cases where reentry loops were detected, the signal of certain electrodes had significantly smaller amplitude than the average amplitude under normal pacing, which via computer simulations could be related to the cores of the reentry loops. Conclusions: In the non-terminating TdPs reentry is always present, while paroxysmal TdP was in most of the cases based on ectopic activity (86%).