Objective. To investigate the utility of serum BAFF, CXCL13, as biomarkers of disease activity in primary Sjögren's syndrome (pSS), their relationship with lymphocyte subpopulations and their accuracy to discriminate pSS from Sicca syndrome. Methods. We conducted an observational study on 66 pSS patients and 48 controls (25 with Sicca syndrome and 23 healthy volunteers). Serum levels of BAFF, IL-17 A/F, IL-18, IL-21, IL-22, CXCL13, TNF-R2 and PD-L2 were measured using a multiplex immunoassay. Lymphocyte subpopulations were analysed by flow cytometry. Disease activity of pSS was assessed with ES-SDAI at study inclusion. Results. Patients with pSS presented higher serum CXCL13 (364.7 vs. 205.2 pg/mL), IL-21 (43.2 vs. 0 pg/mL) and BAFF (1646 vs. 1369 pg/mL), and lower PD-L2 levels (1950PD-L2 levels ( .8 vs. 2792 to discriminate between pSS and Sicca syndrome (sensitivity 77.2% and specificity 86.4% using a cut-off of 1.7). Conclusion. CXCL13, BAFF, IL-21, and IL-22 are potential biomarkers of pSS activity and IL-21 and IL-22 are associated with disturbances of lym-phocyte subpopulations in pSS. The combination of serum CXCL13, BAFF, and PD-L2 levels allows discrimination between pSS and Sicca syndrome. than controls. ESSDAI was associated with BAFF, IL-18 and IL-22. Patients with ESSDAI >0 exhibited higher CXCL13, IL-21, IL-22 and TNF-R2 concentrations. IL-21 levels correlated with lower memory B-cell and higher naïve B-cell percentages and IL-22 levels correlated with increased circulating activated CD4 + T-cells. The combination of serum CXCL13, BAFF and PDL2 levels using the formula [ln(CXCL13)+ln(BAFF)]/ln(PD-L2) exhibit an

Summary Long-term observation of patients with ANCA-associated vasculitis (AAV) allows the identification of different longitudinal patterns of ANCA levels during follow-up. This study aimed to characterize these patterns and to determine their prognostic significance. All ANCA determinations performed in two university hospitals during a 2-year period were retrospectively reviewed. Patients were included in the analysis if they had high titers of anti-myeloperoxidase (anti-MPO) or anti-proteinase 3 (anti-PR3) antibodies at least once, ≥ 5 serial ANCA determinations and AAV diagnosed by biopsy or American College of Rheumatology (ACR) classification criteria. Patients’ time–course ANCA patterns were classified as monophasic, remitting, recurrent or persistent. Associations between ANCA patterns and prognostic variables (relapse rate and renal outcome) were analysed by univariate and multivariate statistics. A total of 99 patients [55 with microscopic polyangiitis (MPA), 36 with granulomatosis with polyangiitis (GPA) and eight with eosinophilic granulomatosis with polyangiitis (EGPA)] were included. Median follow-up was 9 years. Among patients diagnosed with MPA or GPA, recurrent or persistent ANCA patterns were associated with a higher risk of clinical relapse [hazard ratio (HR) = 3·7, 95% confidence interval (CI) = 1·5–9·1 and HR = 2·9, 95% CI = 1·1–8·0, respectively], independently of clinical diagnosis or ANCA specificity. In patients with anti-MPO antibodies, the recurrent ANCA pattern was associated with worsening renal function [odds ratio (OR) = 5·7, 95% CI = 1·2–26·0]. Recurrent or persistent ANCA patterns are associated with a higher risk of clinical relapse. A recurrent ANCA pattern was associated with worsening renal function in anti-MPO-associated vasculitis.

SUMMARYOBJECTIVETo develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of COVID-19, to identify patients at risk of critical outcomes.DESIGNNational multicenter cohort study.SETTINGData from the SEMI (Sociedad Española de Medicina Interna) COVID-19 Registry, a nationwide cohort of consecutive COVID-19 patients presenting in 132 centers between March 23 and May 21, 2020. Model development used data from hospitals with ≥300 beds, and validation used those from hospitals with <300 beds.PARTICIPANTSAdults (age ≥18 years) presenting with COVID-19 diagnosis.MAIN OUTCOME MEASUREComposite of in-hospital death, mechanical ventilation or admission to intensive care unit.RESULTSThere were 10,433 patients, 7,850 (main outcome rate 25.1%) in the model development cohort and 2,583 (main outcome rate 27.0%) in the validation cohort. The clinical variables in the final model were: age, cardiovascular disease, moderate or severe chronic kidney disease, dyspnea, tachypnea, confusion, systolic blood pressure, and SpO2 ≤93% or supplementary oxygen requirement at presentation. The model developed had C-statistic of 0.823 (95% confidence interval [CI] 0.813 to 0.834) and calibration slope of 0.995. The external validation had C-statistic of 0.792 (95% CI, 0.772 to 0.812) and calibration slope of 0.872. The model showed positive net benefit in terms of hospitalizations avoided for the predicted probability thresholds between 3% and 79%.CONCLUSIONSAmong patients presenting with COVID-19, easily-obtained basic clinical information had good discrimination for identifying patients at risk of critical outcomes, and the model showed good generalizability. A model-based online prediction calculator provided with this paper would facilitate triage of patients during the pandemic.

Introduction: Carbapenems are considered the treatment of choice for extended-spectrum β–lactamase (ESBL) or Amp-C β–lactamase-producing Enterobacteriaceae bacteremia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. Objective: To compare the 30 day-mortality and clinical failures associated with the use of carbapenems vs an alternative non-intravenous antibiotic for the definitive treatment of ESBL/Amp-C positive Enterobacteriaceae bacteremia. Methods: This is a 12-year retrospective study (2004 - 2015) including all patients with bacteremia due to ESBL/Amp-C-producing Enterobacteriaceae. Given the lack of randomization of the initial therapies, a propensity score for receiving carbapenems was calculated. Results: There were 1115 patients with a first episode of bacteremia due to E. coli or K. pneumoniae, of which 123 were ESBL/Amp C-positive (11%). There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (cotrimoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared to the carbapenem group, patients treated with the alternative regimen had a shorter hospital stay (median [IQR]: 7 days [5-10] vs 12 days [9-18], p<0,001). The use of an alternative non-IV treatment did not increase mortality (OR 0.27; 95% CI 0.05-1.61; p=.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95; 95% CI (0.94-26.01, p=.059). Conclusion: Alternative non-IV carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/Amp-C-positive Enterobacteriaceae bloodstream infections, allowing a reduction in carbapenem use. The use of cotrimoxazole in this setting has shown favourable results.

BackgroundAntineutrophil cytoplasmic antibodies (ANCA) are the serological marker of some idiopathic systemic vasculitides, predominantly involving small and medium-sized blood vessels, such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), which are known as the ANCA-associated vasculitis (AAV). Nevertheless, ANCA have been reported in a number of other conditions.ObjectivesTo retrospectively evaluate ANCA diagnostic accuracy in a cohort of unselected patients.MethodsFrom January 2014 to December 2016 a total of 6781 serum samples with a test request for ANCA were submitted to the Immunology Department of a 1.000-bed tertiary teaching hospital from Barcelona (Spain), from both inpatients and outpatients.Indirect immunofluorescence (IIF) was performed for all requests using a commercially available “Granulocyte Mosaic 13” (EUROIMMUN). IIF allowed recognition of three staining patterns: cytoplasmic (cANCA), perinuclear (pANCA) and atypical (xANCA). For the detection of antibodies against mieloperoxidase (MPO) and proteinase 3 (PR3) a chemiluminescent immuno-assay (CLIA) using commercially available ”QUANTA Flash MPO/PR3” (INOVA diagnostics) was performed in patients with positive IIF.We reviewed the clinical charts of patients that underwent ANCA testing and collected patients’ diagnoses, as established by their treating physician one year after sampling. In the event of multiple ANCA test in a single patient we include only the first test request (we excluded 1323 tests performed in 661 patients). We also excluded 184 patients with insufficient information and 306 ANCA tests with no diagnostic purpose. Therefore the study population includes 4968 patients.Statistical analysis was performed with Stata 14.2 (College Station, TX, USA). Diagnostic performance was assessed using sensitivity, specificity, positive likelihood ratio (LR+), positive and negative predictive values (PPV and NPV) and global efficiency. Confidence Intervals (CI) were calculated using Wilson method.ResultsOnly 34 patients (0.68%) received a diagnosis of AAV: 25 MPA, 6 GPA and 3 EGPA.Sensitivity[CI 95%]Specificity[CI 95%]LR+[CI 95%]PPV[CI 95%]NPV[CI 95%]Efficiency[CI 95%] Positive IIF94.1%87.6%7.65%99.95%87.7%[80.9–98.4][86.7–88.5][6.8–8.5][3.5–6.9][99.83–99.99][86.7–88.5]IIF Typical pattern91.2%96.9%2916.7%99.94%96.8%[77–97[96.3–97.3][24.1–35][12–22.7][99.82–99.98][96.3–97.3]cANCA/PR3 or pANCA/MPO76.5%99.1%83.836.6%99.84%98.9%[60–87.6][98.8–99.3][59.3–118.4][26.4–48.2][99.68–99.92][98.6–99.2]The majority (87.1%) of patients had a negative ANCA test and only 12.9% were found positive by IIF. Among 643 positive patients IIF pattern distribution was: 457 (71.1%) atypical, 108 (16.8%) perinuclear and 78 (12.1%) cytoplasmic pattern. Among patients with positive ANCA 32 (5%) had an AAV. Two patients with AAV had negative ANCA (one GPA and one EGPA).Data of diagnostic accuracy of ANCA for AAV are showed in table 1:ConclusionsANCA testing with commonly commercially availa...