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The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.). Supported by a grant (PI19/00545, to Dr. Martín) from the Ministry of Science and Innovation through the Carlos III Institute of Health–Fondo de Investigación Sanitaria; by a grant from the Biomedical Research Networking Center on Cardiovascular Diseases (to Drs. Martín, Sánchez-Madrid, and Ibáñez); by grants (S2017/BMD-3671-INFLAMUNE-CM, to Drs. Martín and Sánchez-Madrid; and S2017/BMD-3867-RENIM-CM, to Dr. Ibáñez) from Comunidad de Madrid; by a grant (20152330 31, to Drs. Martín, Sánchez-Madrid, and Alfonso) from Fundació La Marató de TV3; by grants (ERC-2011-AdG 294340-GENTRIS, to Dr. Sánchez-Madrid; and ERC-2018-CoG 819775-MATRIX, to Dr. Ibáñez) from the European Research Council; by grants (SAF2017-82886R, to Dr. Sánchez-Madrid; RETOS2019-107332RB-I00, to Dr. Ibáñez; and SAF2017-90604-REDT-NurCaMeIn and RTI2018-095928-BI00, to Dr. Ricote) from the Ministry of Science and Innovation; by Fondo Europeo de Desarrollo Regional (FEDER); and by a 2016 Leonardo Grant for Researchers and Cultural Creators from the BBVA Foundation to Dr. Martín. The National Center for Cardiovascular Research (CNIC) is supported by the Carlos III Institute of Health, the Ministry of Science and Innovation, the Pro CNIC Foundation, and by a Severo Ochoa Center of Excellence grant (SEV-2015-0505). Mr. Blanco-Domínguez is supported by a grant (FPU16/02780) from the Formación de Profesorado Universitario program of the Spanish Ministry of Education, Culture, and Sports. Ms. Linillos-Pradillo is supported by a fellowship (PEJD-2016/BMD-2789) from Fondo de Garantía de Empleo Juvenil de Comunidad de Madrid. Dr. Relaño is supported by a grant (BES-2015-072625) from Contratos Predoctorales Severo Ochoa para la Formación de Doctores of the Ministry of Economy and Competitiveness. Dr. Alonso-Herranz is supported by a fellowship from La Caixa–CNIC. Dr. Caforio is supported by Budget Integrato per la Ricerca dei Dipartimenti BIRD-2019 from Università di Padova. Dr. Das is supported by grants (UG3 TR002878 and R35 HL150807) from the National Institutes of Health and the American Heart Association through its Strategically Focused Research Networks. Sí

IMPORTANCE Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. OBJECTIVE To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. DATA SOURCES Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. STUDY SELECTION Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. DATA EXTRACTION AND SYNTHESIS In this prospectivemeta-analysis, risk of biaswas assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I-2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. MAIN OUTCOMES AND MEASURES The primary outcome measurewas all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. RESULTS A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P =.003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P

Presence of SARS-CoV-2 RNA in serum (viraemia) in COVID-19 patients has been related to poor prognosis and death. The aim of this study was to evaluate the ability of two commercial reverse real-time-PCR (rRT-PCR) kits, cobas® SARS-CoV-2 (Cobas® test) and TaqPath™ COVID-19 CE-IVD RT-PCR Kit (Taqpath™ test), to detect viraemia in COVID-19 patients and their implementation as routine diagnosis in microbiology laboratory. This retrospective cohort study was conducted with 203 adult patients admitted to Hospital Universitario de La Princesa, (89 Intensive Care Unit and 114 ward) with at least one serum sample collected in the first 48 hours from admission. A total 265 serum samples were included for study. Evaluation of both rRT-PCR techniques was performed comparing with the gold standard, a Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit; considering at least one target as a positive result. Comparison of Cobas® test and Taqpath™ test with the gold standard method, showed high values of specificity (93.75 and 92.19 respectively) and Positive Predictive Value (92.92 and 99.88 respectively). Nevertheless, sensitivity (53.72 and 73.63 respectively) and Negative Predictive Value (32.53 and 42.99 respectively) were lower; Kappa values were 0.35 for cobas® test and 0.56 for Taqpath™ test. For both techniques, differences of viraemia detection between the ICU and non-ICU patients were significant (p≤0.001). Consequently, SARS-CoV-2 viraemia positive results obtained by both rRT-PCR should be considered good tools and may help in handling COVID-19 patients. Moreover, these methods could be easily integrated in the routine laboratory COVID-19 diagnosis and may open new strategies based on an early COVID-19 treatment.

OBJECTIVE: Torque teno virus (TTV) is a highly prevalent non-pathogenic anellovirus whose plasma levels may be a biomarker of immunosuppression. The aim of this study was to assess whether specific immune-targeting with different biologic drugs may differentially modulate TTV viremia in arthritis patients.; METHODS: TTV DNA load was quantified by PCR in a cross-sectional sample of 79 patients with chronic arthritis on biologic therapy (abatacept, infliximab, rituximab or tocilizumab), 31 patients treated with conventional DMARDs (methotrexate and/or leflunomide), and 54 healthy individuals.Longitudinal changes in TTV load were analysed in a second group of 59 patients at baseline and 4-months after biologic therapy. Correlations between clinical or biological characteristics of recruited patients and TTV viremia were also analysed.; RESULTS: In the cross-sectional study, TTV load was significantly higher in patients who received abatacept, infliximab or tocilizumab compared to healthy individuals. Patients treated with rituximab or conventional DMARDs showed TTV loads similar to healthy controls. In the longitudinal study, an increase in the TTV load was observed after anti-TNF, tocilizumab, abatacept and rituximab, but not after secukinumab therapy. Correlations between TTV load and clinical variables such as disease duration, concomitant glucocorticoid or DMARDs therapy, lymphocytes or previous infections were not found. A non-significant trend towards higher TTV load was observed in therapy responders.; CONCLUSION: Patients with chronic arthritis on biologic but not on conventional DMARD or anti-IL17 therapy have increased TTV viremia. This observation provides a basis to prospectively explore the potential value of TTV load as a potential pharmacodynamic biomarker. Copyright © 2019 Elsevier Inc. All rights reserved.

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR's., Our study was supported by grants RD16/0012/0011 and PI14/00442 from the Ministerio de Economia y Competitividad (Instituto de Salud Carlos III; Spain) and cofunded by the Fondo Europeo de Desarrollo Regional (FEDER). Data from ACT-RAY clinical trial were kindly provided by Hoffmann-La Roche Ltd. No financial support was received from Hoffmann-La Roche Ltd Data from EMECAR and PROAR cohorts were provided by the Spanish Society of Rheumatology. No financial support was received from the Spanish Society of Rheumatology. None of these institutions played any role in the analysis or interpretation of data, nor were they involved in the writing of the manuscript. Roche and Sociedad Espanola de Reumatologia were involved in the collection of data from ACT-RAY, and EMECAR and PROAR, respectively. However, these funders had no role in study design, analysis, decision to publish, or preparation of the manuscript.

Objective Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors. Methods A baseline analysis was made of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and controls included in the CARMA project (CARdiovascular in RheuMAtology), a 10-year prospective study evaluating the risk of CV events in chronic inflammatory rheumatic diseases. A multivariate logistic regression model was performed using hyperlipoproteinaemia( a) (Lp(a) >50 mg/dl) as a dependent variable and adjusting for confounding factors. Results 19.2% (95% CI: 16.80-22.05) of the SpA patients [20.7% (95% CI: 16.91-24.82) of those with AS and 17.7% (95% CI: 14.15-21.75) of those with PsA] and 16.7% (95% CI: 13.23-20.86) of the controls had hyperlipoproteinaemia(a) (p=0.326). Adjusting for age and sex, SpA patients were more likely to have hyperlipoproteinaemia(a) than controls (OR: 1.43, 95% CI: 1.00-2.04; p=0.05), especially those with AS (OR: 1.81, 95% CI: 1.18-2.77; p=0.007). In the adjusted model, apolipoprotein B in all patients, non-steroidal anti-inflammatory drugs in AS, and female sex in PsA, were associated with hyperlipoproteinaemia(a). No disease-specific factors associated with hyperlipoproteinaemia(a) were identified. Conclusion SpA patients show a moderately increased risk of hyperlipoproteinaemia(a) compared to controls, especially those with AS. Lp(a) determination may be of interest to improve the CV risk assessment in SpA patients.

Objective. To investigate associations with rheumatoid arthritis (RA) of single-nucleotide polymorphisms (SNP) in 4 candidate genes, complement factor H (CFH), CD209 or DC-SIGN, eotaxin-3, and the MHC class II Transactivator (MHC2TA) genes. These SNP have been reported as important for RA (eotaxin-3 and MHC2TA) or for other immune-mediated diseases (CFH and CD209). Methods. Genotypes for the 7 selected SNP were obtained from 1587 patients with RA and 1570 controls of Spanish ancestry. Analyses were carried out after stratification for sex, erosions, rheumatoid factor, shared epitope, anti-cyclic citrullinated peptide antibodies, and the R620W PTPN22 SNP. Results. None of the comparisons between patients with RA and controls or between the different strata of patients according to disease features was significant. Conclusion. None of the SNP in CFH and CD209 showed evidence of association with RA. We (lid not replicate the association of eotaxin-3 with RA described in Koreans, or that of the MHC2T SNP. (First Release July 1 2009; J Rheumatol 2009;36:1590-5.- doi: 10.3899/jrheum.090022)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c+ conventional dendritic cells also followed this pattern, whereas CD141+ conventional and CD123hi plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.