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Metabolic syndrome (MS) is a combination of risk factors related to the development of mainly type 2 diabetes mellitus, cardiovascular disease (CVD) and nonalcoholic fatty liver disease (NAFLD). Its prevalence has increased worldwide, and healthcare systems will face major challenges in addressing this problem. The aim of this work was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on insulin resistance (IR) and obesity associated with MS in Wistar rats. The experimental design consisted of three groups of sucrose-induced MS rats: the MS group that consumed sucrose (MS-Suc; n=5), the MS group that ingested sucrose and HBOT (MS-Suc-HBOT; n=5), the MS group that did not consume sucrose and that received HBOT (MS-HBOT; n=5) and the control group. The rats received HBOT for 20 d at 2.4 atmospheres absolute (ATA) for 60 min. Subsequently, the rats were euthanized, and body fat weight, serum biochemical parameters and microscopic analysis of adipose tissue were determined. Rats with hyperoxia had decreased body weight, adipose tissue hypertrophy, and abdominal and epididymal fat. Likewise, markers of insulin resistance (glucose, insulin and HOMA-IR), biochemical parameters of dyslipidemia (cholesterol and triglycerides) and nonalcoholic fatty liver (AST and ALT) decreased; in contrast, compared to the control group, HBOT increased the 1/HOMA-IR, HOMA-βCell and McAuley indexes, which were related to the improvement in insulin sensitivity (p

BACKGROUND: Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells-the target for rituximab-in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status. METHODS: This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28. FINDINGS: Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI -11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [-1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [-5 to 10]) were not significantly different between treatment groups. INTERPRETATION: The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice. FUNDING: Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research. ispartof: LANCET vol:397 issue:10271 pages:305-317 ispartof: location:England status: published

Background: The potential association of the ABO blood group with the risk of COVID-19 and its severity has attracted a lot of interest since the start of the pandemic. While a number of studies have reported an increased risk associated with blood type A and a reduced risk with type O, other studies have did not found a significant effect. This study aimed to define the prevalence of different ABO blood groups in hospitalized COVID-19 patients in the Louisville, KY area and to investigate whether an association exists between the blood group and disease severity. Methods: This was a retrospective observational study of 380 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients were divided into four different groups according to their ABO blood type. Demographic characteristics and clinical variables, including laboratory data as well as clinical outcomes were compared. Results: Type O was the most common blood group among the hospitalized patients (51%) followed by type A (31%), B (14%) and AB (4%). The observed blood group distribution among the patients was not significantly different from the distribution expected when compared to a population of similar racial/ethnic composition. No significant associations were found between the blood group and comorbidities, inflammatory biomarkers as well as with recorded outcomes, including the mortality rate and the length of the hospital stay. Conclusions: The data from hospitalized patients in Louisville is is not consistent with the ABO blood group having a significant effect as a risk or severity factor for COVID-19, but it is representative in COVID-19 or its severity of its prevalence among different racial/ethnic populations.

Chronic obstructive pulmonary disease (COPD) is prevalent in patients infected with HIV. The purpose of this study was to test the hypothesis that systemic oxidation correlates with loss of lung function in subjects with COPD, and that HIV infection can contribute to creating such an environment. Subjects were recruited at the University of Louisville in the following groups: HIV-infected (n = 36), COPD (n = 32), HIV and COPD (n = 28), and uninfected controls with normal lung function (n = 34). HIV infection was assessed by viral load and CD4 cell counts. Pulmonary function was determined by spirometry, and plasma was collected for measurement of cysteine (Cys), cystine (CySS), glutathione (GSH) and GSH disulfide (GSSG) by HPLC followed by estimation of redox potentials (Eh) using the Nernst equation. Results showed that patients with COPD had more oxidized plasma Eh Cys/CySS than patients with normal lung function, but plasma Eh GSH/GSSG was unaltered. In addition, there was a correlation between the extent of plasma Eh Cys/CySS oxidation and loss of lung function, and this correlation remained even after correcting for age, sex, race and body mass index. HIV infection per se was not associated with increased oxidation of plasma Eh Cys/CySS, but plasma Eh Cys/CySS was more oxidized in patients with lower CD4-positve T cell counts. In patients with both HIV infection and COPD, there was a significant correlation between CD4 cell counts and lung function. Thus, systemic oxidation correlated with decreased lung function in subjects with COPD and decreased CD4 counts in subjects infected with HIV. Thus, factors contributing to plasma Eh Cys/CySS may represent novel mechanisms underlying the increased prevalence of COPD in people living with HIV.

espanolAims To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2 years of symptom evolution. Methods Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. Conclusions The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis. espanolObjetivos Describir la metodologia del Registro Espanol de Artritis Psoriasica de reciente comienzo de la Sociedad Espanola de Reumatologia (REAPSER), asi como sus fortalezas y limitaciones. El objetivo principal del proyecto es identificar factores pronosticos de la evolucion clinica y radiografica en una cohorte de pacientes que padecen artritis psoriasica (APs) diagnosticada con menos de 2 anos de evolucion. Material y metodo Estudio observacional, prospectivo (2 anos de seguimiento; periodicidad anual de las visitas), multicentrico. La intencion en la visita basal fue reflejar la situacion del paciente antes de que la evolucion de la enfermedad se viese modificada por los tratamientos pautados en los servicios de reumatologia. Los pacientes fueron invitados a participar consecutivamente en una de sus visitas habituales al reumatologo. El tamano muestral finalmente alcanzado fue de 211 pacientes. Se recogen datos sociodemograficos; de situacion laboral; historia familiar; antecedentes personales y comorbilidad; antropometricos; estilo de vida; uso de los servicios de salud; situacion clinica al diagnostico de APs; afectacion articular y dolor espinal; dolor y valoracion global de la enfermedad; entesitis, dactilitis y uveitis; afectacion cutanea y ungueal; situacion funcional y calidad de vida; evaluacion radiografica; determinaciones analiticas; tratamiento; brotes en esqueleto axial y periferico. Conclusiones El estudio REAPSER incluye una cohorte de pacientes con APs de inicio reciente reclutados antes de que la evolucion de la enfermedad se viese modificada por la prescripcion de FAME en los servicios de reumatologia. Se espera que la informacion exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros analisis.

Background Multiple criteria have been proposed to define community-acquired pneumonia (CAP) severity and predict ICU admission. Validity studies have found differing results. We tested four models to assess severe CAP built upon the criteria included in the 2007 IDSA/ATS guidelines, hypothesizing that a model providing different weights for each individual criterion may be of better predictability. Methods Retrospective analysis of a prospective cohort study of adult hospitalizations for CAP at nine hospitals in Louisville, KY from June 2014 to May 2016. Four models were tested. Model 1: original 2007 IDSA/ATS criteria. Model 2: modified IDSA/ATS criteria by removing multilobar infiltrates and changing BUN threshold to ≥30 mg/dL; adding lactate level >2 mmol/L and requirement of non-invasive mechanical ventilation (NIMV). CAP was severe with 1 major criterion or 3 minor criteria. Model 3: same criteria as model 2, CAP was severe with 1 major criterion or 4 minor criteria. Model 4: multiple regression analysis including the modified criteria as described in models 2 and 3 with a score assigned to each variable according to the magnitude of association between variable and need for ICU. Results 8284 CAP hospitalizations were included. 1458 (18%) required ICU. Model 4 showed highest prediction of need for ICU with an area under the curve of 0.91, highest accuracy, specificity, positive predictive value, and agreement among models. Conclusion Assigning differential weights to clinical predictive variables generated a score with accuracy that outperformed the original 2007 IDSA/ATS criteria for severe CAP and ICU admission.

Background Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. Methods This observational, prospective surveillance study recruited hospitalized adults aged ≥18 years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30 days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. Results Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged ≥65 years. Among patients aged 18–64 years PCV13 serotypes were detected in 3.8–5.3% of patients depending on their risk status. Conclusions After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population.

Background: MEFV mutations were documented in patients with palindromic rheumatism (PR) who do not meet Familial Mediterranean Fever (FMF) criteria, and RF and ACPA positive rheumatoid arthritis (RA) may start with PR. We retrospectively analyzed the clinical phenotype and disease evolution of patients with palindromic-like (PR-L) arthritis according to ACPA/RF and MEFV mutation status. Methods: MEFV genotyping was undertaken in 76 patients with PR-L arthritis as determined by short attacks ( < 7 days) and relapsing course. Characteristics of arthritis episodes, RF and ACPA positivity, and colchicine response were retrospectivelly collected. Patients were stratified according the presence of MEFV mutations and/or ACPA/RF status. Findings: 26.3% (20/76) of patients had MEFV mutations and 23 (30%) were ACPA and/or RF positive. After stratification, we can distinguish four groups of PR-L arthritis patients. Group I (MEFV +ve) with younger age of onset, short duration attacks ( 3 days, and 15 patients developed criteria of immune-mediated inflammatory (IMID), autoinflammatory or infectious disease. Group IV (MEFV +ve associated to pre-existing IMID) had very short-attacks (

Background and aim There is increasing interest regarding SARS-CoV-2 infection in patients with autoimmune and immune-mediated inflammatory diseases (AI/IMID) with some discrepancies in different cohorts about their risk and outcomes. The aim was to describe a multidisciplinary cohort of patients with AI/IMID and symptomatic SARS-CoV-2 infection in a single tertiary center and analyze sociodemographic, clinical, and therapeutic factors associated with poor outcomes. Methods A retrospective observational study was conducted from the 1st of March until May 29th, 2020 in a University tertiary hospital in Barcelona, Spain. Patients with an underlying AI/IMID and symptomatic SARS-CoV-2 infection were identified in our local SARS-CoV-2 infection database. Controls (2:1) were selected from the same database and matched by age and gender. The primary outcome was severe SARS-CoV-2 infection, which was a composite endpoint including admission to the intensive care unit (ICU), need for mechanical ventilation (MV), and/or death. Several covariates including age, sex, and comorbidities among others were combined into a multivariate model having severe SARS-CoV-2 as the dependent variable. Also, a sensitivity analysis was performed evaluating AID and IMID separately. Results The prevalence of symptomatic SARS-CoV-2 infection in a cohort of AI/IMID patients was 1.3%. Eighty-five patients with AI/IMID and symptomatic SARS-CoV-2 were identified, requiring hospitalization in 58 (68%) cases. A total of 175 patients admitted for SARS-CoV-2 (58 with AI/IMID and 117 matched-controls) were analyzed. In logistic regression analysis, a significant inverse association between AI/IMID group and severe SARS-CoV-2 (OR 0.28; 95% CI 0.12–0.61; p = 0.001), need of MV (OR 0.20; IC 95% 0.05–0.71; p = 0.014), and ICU admission (OR 0.25; IC 95% 0.10–0.62; p = 0.003) was found. Conclusions Patients with AI/IMID who require admission for SARS-CoV-2 infection have a lower risk of developing severe disease, including the need to stay in the ICU and MV., Highlights • Patients with AI/IMID fwho required admission for SARS CoV2 infection have a lower risk of developing severe disease. • Among patients with AID and IMID, there were no differences in terms of severity. • According to the 7-category ordinal scale, maximum oxygen requirement was lower among AI/IMID group.

BackgroundThe mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane.MethodsSynovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPHassociation was validated using immunofluorescence. External validation was performed on an independent dataset.ResultsAfter multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P P PHcells at baseline and a better response (P = 0.026). Lower TPHcells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r2 = 0.58,P = 0.005) and an association with response. TPHassociation with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040).ConclusionsA lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents.

Pneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5-10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a need to identify those patients most at risk. Also of importance, clinical symptoms alone do not distinguish viral from bacterial infection which may delay appropriate treatment and may contribute to short-term and long-term mortality. Biomarkers have the potential to provide point of care diagnosis, identify high-risk patients, and increase our understanding of the biology of disease. However, there have been mixed results on the diagnostic performance of many of the analytes tested to date. Urine represents a largely untapped source for biomarker discovery and is highly accessible. To test this hypothesis, we collected urine from hospitalized patients with community-acquired pneumonia (CAP) and performed a comprehensive screen for urinary tract microbiota signatures, metabolite, and cytokine profiles. CAP patients were diagnosed with influenza or bacterial (S. aureus and S. pneumoniae) etiologies and compared with healthy volunteers. Microbiome signatures showed marked shifts in taxonomic levels in patients with bacterial etiology versus influenza and CAP versus normal. Predictive modeling of 291 microbial and metabolite values achieved a +90% accuracy with LASSO in predicting specific pneumonia etiology. This study demonstrates that urine from patients hospitalized with pneumonia may serve as a reliable and accessible sample to evaluate biomarkers that may diagnose etiology and predict clinical outcomes.Author SummaryUrine has been classically considered sterile since most microorganisms are not readily culturable under healthy circumstances. Further, many pneumonia patients are immediately placed on antibiotics rendering culture-based techniques useless. However, the advent of next generation sequencing has enabled unprecedented analysis of the microbial communities – living or detected as free DNA – found in many niches of the human body. Here, we describe a urine microbiome as well as metabolites and cytokines measured in patients newly admitted to the hospital diagnosed with influenza or bacterial (S. aureus and S. pneumoniae) infection pneumonia, compared with healthy controls. Using these parameters alone, we were able to achieve high success in predicting patient pneumonia. This study provides a proof of concept that urine samples, which are easily accessible in outpatient and inpatient settings, could provide additional diagnostic insights to patient infectious status and future risk factor for complication.

Migrants represent a diverse population comprising workers, students, undocumented individuals, and refugees. Worldwide, approximately 1 billion people were considered migrants in 2016. Notably, about 65 million of these migrants were forcibly displaced from their homes, and 20 million were considered refugees. While the geopolitical consequences of such migration continue to be considered, less is known about the impact of these events on the respiratory health of migrants and refugees. In recognition of this knowledge gap, the American Thoracic Society and the European Respiratory Society brought together investigators with diverse and relevant expertise to participate in a workshop and develop a consensus on research needs on the respiratory health of migrants and refugees. The workshop focused on environmental and occupational hazards, chronic noninfectious diseases, and respiratory infectious diseases, which were presented by experts in three distinct sessions, each culminating with panel discussions. A writing committee collected summaries prepared by speakers and other participants, and the information was collated into a single document. Recommendations were formulated, and differences were resolved by discussion and consensus. The group identified important areas of research need, while emphasizing that reducing the burden of pulmonary, critical care, and sleep disorders in migrants and refugees will require a concerted effort by all stakeholders. Using best research practices, considering how research impacts policies affecting migrant and refugee populations, and developing new approaches to engage and fund trainees, clinical investigators, and public health practitioners to conduct high-quality research on respiratory health of migrants and refugees is essential.

Objectives To develop recommendations for the management of methotrexate (MTX) in psoriatic arthritis (PsA), based on best evidence and experience. Methods A group of 12 experts on MTX use was selected. The coordinators formulated 14 questions about the use of MTX in PsA patients (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed 12 preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence Based Medicine and the level of agreement with the Delphi technique (two rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). Results A total of 12 preliminary recommendations on the use of MTX were proposed, 9 of which were accepted. One was included in a different recommendation and other two were not voted on and were thereafter clarified in the main text. Conclusions These recommendations aim to answer frequent questions and help in decision making strategies when treating PsA patients with MTX.

The anti-interleukin-1 receptor antagonist, anakinra, was approved for the treatment of rheumatoid arthritis (RA) more than 12 years ago. However, its adverse effects are not well known. Areas covered: We review the safety profile of anakinra, analyzing clinical trials, observational studies, and registry data. Expert opinion: Due to its lower efficacy compared with other biological therapies approved for RA and its daily subcutaneous administration, anakinra is used only marginally for the treatment of RA. This has limited the experience with this drug in RA, with a lack of data from long-term observational studies or registries. From the five clinical trials performed, and given the unfeasibility of developing new studies of anakinra in RA, it may be concluded that site injection reactions, infections at higher doses (100 mg), and immunogenicity are the most frequent adverse events related to anakinra administration.

Our study demonstrated real-world, direct effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia following introduction into a routine immunization program among adults aged ≥65 years, many of whom had immunocompromising and chronic medical conditions., Background Following universal recommendation for use of 13-valent pneumococcal conjugate vaccine (PCV13) in US adults aged ≥65 years in September 2014, we conducted the first real-world evaluation of PCV13 vaccine effectiveness (VE) against hospitalized vaccine-type community-acquired pneumonia (CAP) in this population. Methods Using a test-negative design, we identified cases and controls from a population-based surveillance study of adults in Louisville, Kentucky, who were hospitalized with CAP. We analyzed a subset of CAP patients enrolled 1 April 2015 through 30 April 2016 who were aged ≥65 years and consented to have their pneumococcal vaccination history confirmed by health insurance records. Cases were defined as hospitalized CAP patients with PCV13 serotypes identified via culture or serotype-specific urinary antigen detection assay. Remaining CAP patients served as test-negative controls. Results Of 2034 CAP hospitalizations, we identified PCV13 serotypes in 68 (3.3%) participants (ie, cases), of whom 6 of 68 (8.8%) had a positive blood culture. Cases were less likely to be immunocompromised (29.4% vs 46.4%, P = .02) and overweight or obese (41.2% vs 58.6%, P = .01) compared to controls, but were otherwise similar. Cases were less likely to have received PCV13 than controls (3/68 [4.4%] vs 285/1966 [14.5%]; unadjusted VE, 72.8% [95% confidence interval, 12.8%−91.5%]). No confounding was observed during adjustment for patient characteristics, including immunocompromised status, body mass index, and history of influenza and pneumococcal polysaccharide vaccination (adjusted VE range, 71.1%−73.3%). Conclusions Our study is the first to demonstrate real-world effectiveness of PCV13 against vaccine-type CAP in adults aged ≥65 years following introduction into a national immunization program.

Objective To determine clinical and sonographic biomarkers predicting structural damage progression at 12 months of follow-up as measured by magnetic resonance imaging (MRI) in rheumatoid arthritis (RA) patients in clinical remission. Patients and methods We included patients with RA in clinical remission, defined as 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR) 6 months. Ultrasound scans of both hands and knees and MRI of the dominant hand were performed at baseline and at 12 months. Results Out of 55 patients, 42 completed the follow-up. Among them, 78% were female, aged (median) 54 years; disease duration was 93 months. In total, 12 (28%) patients were taking oral prednisone, 34 (81%) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 20 (47%) biological therapies. At baseline, 45% fulfilled criteria previously defined for ultrasound-defined active synovitis (UdAS) [PD (power Doppler) signal + synovial hyperplasia ≥2]. Multivariate analysis showed significant associations between baseline MRI erosion score, body mass index (BMI), disease duration, prednisone treatment, absence of biologic and csDMARDs, UdAS, and MRI erosion score progression after 12 months. In an exploratory analysis, serum levels of calprotectin correlated significantly with bone edema progression. Conclusions We identified clinical and sonographic markers of structural damage progression after 12 months follow-up in patients with RA in clinical remission. Meeting the criteria of ultrasound active synovitis, defined as simultaneous relevant synovial hyperplasia and PD, was associated with erosion progression after 12 months. Calprotectin was associated with bone edema, in an exploratory analysis.

International experts suggest tailoring antibiotic duration in community-acquired pneumonia (CAP) according to patients' characteristics. We aimed to assess the effectiveness of an individualized approach to antibiotic duration based on time in which CAP patients reach clinical stability during hospitalization. In a multicenter, non-inferiority, randomized, controlled trial hospitalized adult patients with CAP reaching clinical stability within 5 days after hospitalization were randomized to a standard vs. individualized antibiotic duration. In the Individualized group, antibiotics were discontinued 48 h after the patient reached clinical stability, with at least five days of total antibiotic treatment. Early failure within 30 days was the primary composite outcome. 135 patients were randomized to the Standard group and 125 to the Individualized group. The trial was interrupted by the safety committee because of an apparent inferiority of the Individualized group over the Standard treatment: 14 (11.2%) patients in the Individualized group experienced early failure vs. 10 (7.4%) patients in the Standard group, p = 0.200, at the intention-to-treat analysis. 30-day mortality rate was four-time higher in the Individualized group than the Standard group. Shortening antibiotic duration according to patients' characteristics still remains an open question.

Background Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. Methods This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Results During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. Conclusions The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.

To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care.Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain.Two hundred and one patients were included, 130 (64.7%) with 45 mg and 71 (35.3%) with 90 mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45 mg (58.1%) than 90 mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and 1 TNF blocker versus 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1 month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for 1 TNF blocker versus 2 TNF blocker users).UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90 mg and fewer lines of previous biologics achieved better and faster responses. Key Points • Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. • First cohort of patients with PsA comparing effectiveness of UST according to 45/90 mg dose.

Purpose: To report a case of cystoid macular edema (CME) secondary to juvenile idiopathic arthritis (JIA)-associated uveitis.Case report: 26-year-old female patient presented with CME in both eyes. CME became refractory and TCZ-IV was initiated. After 12 infusions was stopped because grade 1 neuropenia developed. On examination,visual acuity of the right eye was 20/80. Spectral domain optical coherence tomography (SD-OCT) of the right eye revealed CME. Subcutaneous (TCZ-SC) was initiated. After six injections of TCZ-SC, ophthalmic examination revealed no signs of active inflammation, and central foveal thickness decreased.Conclusion: TCZ-SC seems to have a role in the treatment of CME secondary to juvenile idiopathic arthritis (JIA)-associated uveitis.

Background Early clinical response (ECR) is a new endpoint to determine whether a drug should be approved for community-acquired bacterial pneumonia in the United States. The Omadacycline for Pneumonia Treatment In the Community (OPTIC) phase III study demonstrated noninferiority of omadacycline to moxifloxacin using this endpoint. This study describes the performance of the ECR endpoint and clinical stability relative to a posttreatment evaluation (PTE) of clinical success. Methods ECR was defined as symptom improvement 72–120 hours after the first dose of study drug (ECR window), no use of rescue antibiotics, and patient survival. Clinical success at PTE was an investigator assessment of success. Clinical stability was defined based on vital sign stabilization, described in the American Thoracic Society and Infectious Diseases Society of America community-acquired pneumonia treatment guidelines. Results During the ECR window, ECR was achieved in 81.1% and 82.7% of omadacycline and moxifloxacin patients, respectively. Similar numbers of patients achieved clinical stability in each treatment group (omadacycline 74.6%, moxifloxacin 77.6%). The proportion of patients with improved symptoms who were considered clinically stable increased across the ECR window (69.2–77.6% for omadacycline; 68.0–79.7% for moxifloxacin). There was high concordance (>70%) and high positive predictive value (>90%) of ECR and clinical stability with overall clinical success at PTE. Conclusions Omadacycline was noninferior to moxifloxacin, based on a new ECR endpoint. Clinical stability was similarly high when measured in the same time frame as ECR. Both ECR and clinical stability showed high concordance and high positive predictive value with clinical success at PTE. Clinical Trials Registration NCT02531438.

Background: Anti-carbamylated protein antibodies (Anti-CarP) represent a novel autoantibody family present in sera of patients with rheumatoid arthritis (RA) with high specificity. Objectives: To analyse the prevalence of Anti-CarP in an established RA cohort and evaluate their association with the presence of other autoantibodies and disease activity and severity. Methods: Cross-sectional study. Presence of Anti-CarP was analyzed in a cohort of patients with established RA (n: 158) by a home-made ELISA test using fetal calf serum. We investigated the demographic, radiological and current and at disease onset clinical features. Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) status were also assessed. Results: Anti-CarP were positive in 46.2% of the patients in our cohort and in 15.1%, 19.2% and 9.1% of the patients negative for ACPA, RF and both respectively. Demographic and clinical features are shown in table 1. The mean titer of ACPA (1361±1054 U/mL vs. 918 ± 1092 U/mL) and RF (258 ± 255 AU vs. 174 ± 205 AU) were significantly higher in Anti-CarP positive patients. No difference in symptoms at RA onset was observed. Current (24.7% vs. 11.8%) and previous (54.8% vs. 37.6%) smoking consumption were significantly associated with Anti-CarP antibodies. Anti-CarP positive patients presented a higher CRP values (1. 0±1.6 mg/dL vs. 0.5 ±0.8 mg/dL), swollen joint count (1.3±2.2 vs 0.7 ±1.8) and patient global health assessment VAS (34.8 ±21.5 mm vs. 26.4 ±17.1 mm); although no between-group differences in disease activity (DAS28, CDAI, SDAI and RAPID3) or demographic features were observed. Anti-CarP positive patients presented significant higher scores in Larsen index (23.6 ± 15.7 vs. 15.7 ± 12.6) and disability (HAQ-DI >1) (23.3% vs. 8.3%). Conclusion: Anti-CarP were present in approximately half of the RA cohort and were also detected in seronegative (RF and/or ACPA) patients. In our cohort, patients with Anti-CarP antibodies presented higher tobacco consumption and poorer disease outcomes. Disclosure of Interests: Raul Castellanos-Moreira Speakers bureau: For Lilly and Merk Sharp and Dohme, Sebastian C Rodriguez-Garcia: None declared, Virginia Ruiz: None declared, Oscar Camacho: None declared, Julio Ramirez: None declared, Andrea Cuervo: None declared, Cristina Garcia-Moreno: None declared, Rosa Morla: None declared, Jose Gomez Puerta Speakers bureau: BMS, Pfizer, Amgen, Juan D. Canete: None declared, Isabel Haro: None declared, Raimon Sanmarti Speakers bureau: PFIZER, SANOFI, LILLY, MSD, UCB, NOVARTIS, JANSSEN

Background: Patients with Rheumatoid Arthritis (RA) in remission will present flares during the evolution of the disease.Definitive biomarkers have not been identified to predict flares and radiographic progression (RP) in this kind of patients Objectives: To search biomarkers of clinical relapse and RP in patients with RA in clinical remission Methods: RA patients in clinical remission (DAS28-ESR 6 months) were selected.Clinical,epidemiological and serological data were analyzed.MRI of dominant hand,ultrasound assessment of knees and hands and serum levels of inflammation and angiogenesis biomarkers were evaluated at 0 and 48 weeks.Synovial biopsy was performed in patients with subclinical synovitis.Patients were follow-up for 5 years.Radiological data were collected.Clinical relapse was defined as the loss of remission status involving a therapeutic intervention.RP was defined as the change in the Sharp van der Heijde (SvH) index at 5 years >10.47 [SDD (minimum detectable change)]. Results: 60 patients in DAS28 remission. 1/3 also met remission criteria for SDAI(33.3%),CDAI(31.6%) and ACR(35%).78% were women,mean age 53 years. 82% were ACPA+.26% were taking oral prednisone,76% DMARDs and 45% biological therapies.48% met criteria for subclinical synovitis(UdAS:SH>2+PD)1. After 5 years of follow-up, 44(73%), 11(18%), 9(15%) and 10(17%) patients remained in remission according to DAS28,SDAI, DAI and ACR criteria,respectively. 29 patients (48%) had flares at any time during the 5 years. In the multivariate analysis, the variables that were related to clinical relapse were the BMI (OR 1.6 CI 95% 1.1-2.3), bone edema at baseline (OR 1.2,CI 95% 1-1.5), PD signal at 48w (OR 9.2,CI 95% 1.2-66.7) and the change in levels of CXCL16 (OR 1.04 CI 95% 0.9-1) and ESR (OR 3.6,CI 95% 1.1-12.2) between the first and latest evaluation (Rate). In the subgroup of 23 patients undergoing synovial biopsy, the number of mast cells was higher in those patients (n=10) who flared (p=0.02). 20 patients (33%) changed DMARDs or biological therapy. In the logistic regression analysis, BMI (OR 1.3 CI 95% 1-1.6), biological therapy (OR 17.8 CI 95% 2-167.1),progression of erosions measured by MRI (OR 1.1, CI 95% 1-1.3) and the rate of progression of calprotectin levels during the first year (OR 4.4,CI 95% 1.1-17.2) were the main factors that predicted the change in baseline therapy after 5 years of follow-up. Finally, only 6 patients (10%) had RP according to the SvH index and 7 (12%) had erosion progression.This small number of “progressors” did not allowed more exhaustive analysis of factors predicting RP.However,the number of macrophages and T cells at sinovial tissue (ST) was much higher in patients with RP.Likewise,the first-year rate of bone edema was significantly higher in patients suffering structural progression (p=0.04). Conclusion: 27% of RA patients lost clinical remission (DAS28) after 5 years of follow-up.BMI,baseline bone edema,PD signal at 12m and first-year rate of CXCL16 and VSG levels were predictors of joint flares. Baseline BMI, use of biological therapy,MRI erosions and calprotectin levels predicted the change of baseline therapy for RA. Only 10% of patients had RP along the study.Sinovial mast cells were associated with disease flares. Macrophages and T cells in ST were higher in patients with RP in an exploratory analysis. Reference [1] Ramirez J, Ruiz-Esquide V, Pomes I, Celis R, Cuervo A, Hernandez MV, et al. Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers. Arthritis Res Ther. 2014;16:R5. Disclosure of Interests: Julio Ramirez: None declared, Andrea Cuervo: None declared, Raquel Celis: None declared, Raul Castellanos-Moreira Speakers bureau: MSD, Lilly, Sebastian C Rodriguez-Garcia: None declared, Virginia Ruiz-Esquide: None declared, Jose Gomez Puerta Speakers bureau: BMS, Pfizer, Amgen, Raimon Sanmarti Speakers bureau: PFIZER, SANOFI, LILLY, MSD, UCB, NOVARTIS, JANSSEN, Juan D. Canete: None declared

IMPORTANCE Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. OBJECTIVE To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. INTERVENTIONS Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200mg (n = 588), or placebo (n = 587). MAIN OUTCOMES AND MEASURES The primary outcomewas incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase���polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. RESULTS The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5%vs 15.2%; odds ratio, 0.43 [95%CI, 0.28-0.68]; P < .001; absolute risk difference, ���6.6 [95%CI, ���10.7 to ���2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). CONCLUSIONS AND RELEVANCE Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy.

Purpose There is a scarcity of studies assessing the patient population admitted to the intensive care unit (ICU) with opioid overdose. We sought to characterize the epidemiologic features and outcomes of this patient population. Materials and methods This is a retrospective cohort study of adult patients admitted to the ICU at University of Louisville Hospital for opioid overdose. We reviewed each patient's hospital record for demographic data, comorbidities, opioid used, coingestions, and outcomes. Results We included 178 adult patients, of which 107 (60%) were females. The median age was 41 years (interquartile range [IQR], 23). Oxycodone and hydrocodone were the 2 most commonly abused opioids. Benzodiazepines were the most common drug coingested, followed by amphetamines. Tobacco smoking, chronic pain, and alcoholism were the most frequent comorbidities identified. Mental disorders were also common. Most patients required invasive mechanical ventilation (84.8%). Median ICU length of stay was 3 days. Eighteen patients (10.1%) died in the hospital, whereas 6 patients (3.4%) were discharged to a nursing home. Patients who had any coingestion were significantly more likely to undergo invasive mechanical ventilation (91% vs 77%; P = .014) and had longer ICU length of stay (3 [IQR, 2] vs 2 [IQR, 1.8] days; P = .024). Conclusion Opioid overdose is a common cause of ICU admission and affects a relatively young population. Most have respiratory failure requiring mechanical ventilation. It is associated with a relatively high inhospital mortality. Coingestions appear to have an impact on outcomes.

The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP). Several studies have used PCR to establish the importance of viruses in the aetiology of CAP.We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detectedviaPCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality.Our review included 31 studies. Most obtained PCRvianasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5–27.5%). In studies that obtained lower respiratory samples in >50% of patients, the proportion was 44.2% (95% CI 35.1–53.3%). The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32–3.31).Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection.

Background: Community-acquired pneumonia (CAP) is an important complication in patients with chronic obstructive pulmonary disease (COPD). This study aimed to define incidence, and outcomes of COPD patients hospitalized with pneumonia in the city of Louisville, and to estimate the burden of disease in the U.S. population. Methods: This was a secondary analysis of a prospective population-based cohort study of residents in Louisville, Kentucky, 40 years old and older, from June 1st, 2014 to May 31st , 2016. All adults hospitalized with CAP were enrolled. The annual incidence of pneumonia in COPD patients in Louisville was calculated and the total number of adults with COPD hospitalized in the U.S. was estimated. Clinical outcomes included time to clinical stability (TCS), length of hospital stay (LOS), and mortality. Results: From a Louisville population of 18,246 patients living with COPD, 3,419 pneumonia hospitalizations were documented during the two-year study. The annual incidence was 9,369 patients hospitalized with pneumonia per 100,000 COPD population, corresponding to an estimated 506,953 adults with COPD hospitalized due to pneumonia in the US. Median TCS and LOS were 2 and 5 days respectively. Mortality during hospitalization was 5.6%. The mortality of COPD patients at 30-days, 6-months, and 1-year was 11.9%,24.3%, and 33.0%, respectively. Conclusions: There was an annual incidence of 9,369 cases of hospitalized CAP per 100,000 COPD patients in the city of Louisville. This was an approximately 18-fold greater incidence of CAP in COPD patients than in those without COPD, resulting in a high morbidity and financial burden. Funding: This work was supported primarily by the Division of Infectious Diseases, University of Louisville, Kentucky. Partial support was given by Pfizer Inc. Declaration of Interest: There are no conflicts of interest for any of the authors in this manuscript. Ethical Approval: The study was approved by the University of Louisville (UofL) Institutional Review Board (IRB #11.0613) and by the research offices at each participating hospital. Study consents were waived.

With the aim to develop and validate a clinical + ultrasound (US) inflammation score in rheumatoid arthritis (RA) for use in clinical practice, a mixed-method study was conducted. The theoretical development of the index was achieved with qualitative methodology (discussion group and Delphi survey). Subsequently, a cross-sectional study was carried out to analyse issues related to scoring and validation of the new index. RA patients underwent clinical [28 swollen and tender joints count, patient and physician global assessment (PhGA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)], and US assessments [synovitis or tenosynovitis by grey-scale (GS) and power Doppler (PD) of 42 structures]. An index was created based on statistical models and expert interaction. Construct validity was tested by correlation with DAS28, SDAI, CDAI, and PhGA. Reliability was evaluated in a subgroup of patients with the intraclass correlation coefficient (ICC). US assessment, CRP, and swollen joints were the items that passed the prioritization phase (Delphi study). For the cross-sectional study, 281 patients were randomly divided into design (n = 141) and validation samples (n = 140). The combination of US sites chosen (7 bilaterally) detected the maximum proportion of synovitis and PD present. Three scoring methods were tested: semiquantitative (0-3 GS + 0-3 PD), dichotomous (0/1 GS + 0/1 PD), and qualitative (0/1 based on algorithm). All showed strong correlation with activity measures (? = 0.60), and reliability (ICC 0.89-0.93). The index with best parameters of validity, feasibility, and reliability was the qualitative. The final index chosen was the sum of swollen joint count, US qualitative score, and CRP. The UltraSound Activity score is a valid and reliable measure of inflammation in RA equal to the sum of 28 SJC, a simplified (0/1) US assessment of 11 structures and CRP. It is necessary further investigation to demonstrate additional value over existing indices.

Objective To analyse the prevalence of pre-existing palindromic rheumatism (PR) in patients with established rheumatoid arthritis (RA) and evaluate whether these patients have a distinctive clinical and serological phenotype. Methods Cross-sectional study in patients with established RA. Pre-existing PR was determined using a structured protocol and confirmed by retrospective review of medical records. Demographic, clinical, radiological, immunological and therapeutic features were compared in patients with and without PR. Results 158 patients with established RA (78% female) with a mean disease duration since RA onset of 5.1 ± 2.7 years were included. Pre-existing PR was recorded in 29 patients (18%). The median time from the onset of PR to progression to RA was 1.2 years. No between-group differences in demographic features, current disease activity radiographic erosive disease or disability were observed. Patients with PR had a higher prevalence of smoking (72% vs. 40%). Positive rheumatoid factor, anti-citrullinated peptide antibodies and anti-carbamylated protein antibodies were numerically higher in patients with PR. No differences in treatment were observed except for greater hydroxychloroquine use in patients with PR (38% vs. 6%). Palindromic flares persisted in a significant proportion of patients during the RA course, including patients in clinical remission or receiving biological DMARDs. Conclusion Eighteen percent of patients with RA had a history compatible with PR previous to RA onset. No specific clinical or serological phenotype was identified in these patients, although higher hydroxychloroquine use and smoking prevalence were identified. Palindromic flares may persist during the RA disease course despite treatment.

Aims: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2 years of symptom evolution. Methods: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. Conclusions: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis. (C) 2018 Elsevier Espafia, S.L.U. and Sociedad Espailola de Reumatologia y Colegio Mexicano de Reumatologia. All rights reserved.

ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.MethodsWe performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case–control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.ResultsWe identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDRConclusionThese findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

ObjectiveThe aim of this study was to evaluate the discriminant capability of the Patient Acceptable Symptom State (PASS) according to disease activity, remission/low disease activity indices and quality of life indices in patients with psoriatic arthritis (PsA).MethodsConsecutive patients with PsA were enrolled in this cross-sectional study. At each visit, the patients underwent a complete physical examination and their clinical/laboratory data were collected. Disease activity was assessed using the Disease Activity Score for Psoriatic Arthritis (DAPSA) and remission/low disease activity using the DAPSA minimal disease activity (MDA) and very low disease activity (VLDA) criteria. The Psoriatic Arthritis Impact of Disease (PsAID) and the Health Assessment Questionnaire-Disability Index scores were also collected. Finally, PASS was assessed by asking all patients to answer yes or no to a single question.ResultsPatients who answered yes to PASS showed a significantly better overall mean DAPSA score than those who were not in PASS. Furthermore, patients in PASS showed a significantly lower level of systemic inflammation, lower Leeds Enthesitis Index score, a significantly lower impact of disease (PsAID), lower pain and better function than patients who answered no to PASS. A moderate to good agreement was found between PASS, MDA, DAPSA low disease activity and PsAID score ≤4. Good sensitivity and specificity were found with PASS with respect to DAPSA low disease activity, and although PASS is sensitive in the identification of patients with MDA, DAPSA remission and VLDA it lacks of specificity.DiscussionThis study showed that PASS might be used as an alternative to determine disease activity in patients with PsA in real clinical practice, mainly in patients with low disease activity according to DAPSA criteria.

Objective Denosumab is an antiresorptive drug with demonstrated efficacy in the treatment of osteoporosis. However, discontinuation of this agent is associated with increased bone turnover and rapid bone loss, and more recently, with the development of vertebral fractures (VF) in some patients. Therefore, the aim of the study was to analyze the clinical characteristics, bone metabolism parameters and evolution of a group of patients who developed vertebral fractures after denosumab discontinuation. In addition, we reviewed the literature on this subject. Methods During a period of 28 months (September 2015–January 2018) 7 women presenting spontaneous vertebral fractures after denosumab discontinuation were attended in the Rheumatology Department of our centre. We analyzed their clinical characteristics, bone metabolism parameters and evolution and reviewed the literature related to this subject. Results The patients had received denosumab during 24–58 months (median 38), and developed a median of 5 VF per patient at 8–20 months (median 10) since the last dose of denosumab. Only 2 patients presented previous VF, and most (5 patients) received previous bisphosphonate treatment. After VF all restarted antiosteoporotic treatment with no further fractures during follow-up (median 19 months). Conclusions In this short series, previous bisphosphonate treatment does not seem to be a protective factor for the development of VF. The possible development of VF following discontinuation of denosumab must be taken into account in the clinical practice of physicians and dentists. Nonetheless, further studies are needed to improve the identification of patients at risk and the most adequate sequential treatment options.

Background Calprotectin is a biomarker of disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and predicts relapse in juvenile idiopathic arthritis. Higher drug trough serum levels are associated with a good response in patients treated with tumor necrosis factor inhibitors (TNFi). Power Doppler ultrasound synovitis is predictive of relapse and structural damage progression in patients in clinical remission. The purpose of this study was to analyze the accuracy of serum calprotectin levels, drug trough serum levels (TSL), and power Doppler (PD) activity as predictors of relapse in RA and PsA patients in remission or with low disease activity receiving TNFi. Methods This was a longitudinal, prospective, 1-year single-center study of 103 patients (47 RA, 56 PsA) receiving TNFi in remission or with low disease activity (28-joint Disease Activity Score (DAS28) ≤ 3.2). The predictive value of serum calprotectin, TNFi TSL, and PD were assessed using receiver operating characteristic (ROC) analyses. To illustrate the predictive performance of calprotectin, TNFi TSL, and PD score, Kaplan-Meier curves were constructed from baseline to relapse. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates and to fully adjust the association between calprotectin, TNFi TSL, and PD score with relapse. A generalized estimating equation model with an identity link for longitudinal continuous outcomes was used to assess the effect of covariates on TNFi TSL. Results Ninety-five patients completed 1 year of follow-up, of whom 12 experienced a relapse. At baseline, relapsers had higher calprotectin levels, lower TNFi TSL, and higher PD activity than nonrelapsers. ROC analysis showed calprotectin fully predicted relapse (area under the curve (AUC) = 1.00). TNFi TSL and PD had an AUC of 0.790 (95% confidence interval (CI) 0.691–0.889) and 0.877 (95% CI 0.772–0.981), respectively. Survival analyses and log rank tests showed significant differences between groups according to calprotectin serum levels (p

Background Denosumab (Dmab) is an antiresorptive treatment with demonstrated efficacy in osteoporosis. However, discontinuation of Dmab has been associated with rapid bone loss, and recently, the development of vertebral fractures (VF) in some patients. It is essential to identify the risk factors for these adverse events and follow its evolution. Objectives To analyse the clinical characteristics, parameters of bone metabolism and evolution of patients developing VF after Dmab discontinuation. Methods Six women with spontaneous VF after Dmab discontinuation were included (median age 66 years56–75). The clinical history, cause of osteoporosis, treatments received, fractures, Dmab treatment duration and discontinuation period were reviewed. Additionally, the clinical and densitometric evolution, and bone mineral parameters were also analysed after Dmab discontinuation. Results All the patients had postmenopausal osteoporosis, and one was receiving glucocorticoid treatment; 3/6 patients had previous fractures (2 VF and 1 calcaneus); 4/6 had previously received antiosteoporotic treatment (hormone replacement therapy, risedronate, alendronate, zoledronate [once or consecutively)] during 1–23 years. All had received Dmab for 24–53 months (median 37). The reasons for treatment discontinuation were: dental indication (1 patient), BMD improvement (T-score −1.2) (1 patient), poor adherence,1 prescription problems and/or delay in administration.3 The median bone mineral density T-scores prior to VF were −2.6 (-1.2/–4) at the lumbar spine and −3.0 (-0.6/–3.7) at the femoral neck. The mean time between the last Dmab dose and VF was 9.5 months,8–20 with a median of 5 VFs/patient.2–8 No patient showed 25-OH vitamin D Conclusions Discontinuation of Dmab is associated with an increase in bone turnover markers and bone loss which can be associated with the development of spontaneous VF. Previous bisphosphonate therapy does not seem to decrease this risk. Further studies are needed to assess the optimal antiresorptive treatment and its duration after Dmab discontinuation. Disclosure of Interest None declared

Background Kawasaki disease is an acute systemic vasculitis that predominantly affects young children and is rarely seen in adults. In the recent years, there have been a few cases in the literature reporting similar clinical picture in adults, especially in those with concurrent HIV, which lead us to present our findings and explore the illness further. Case report A 20-year-old African American female with congenital human immunodeficiency virus (HIV) infection, presented to the ER with complaints of chronic fatigue, fever ( T max 103 °F), arthralgia and sore throat since 2–3 weeks. She also had generalized pain, swelling and erythema of both hands and feet as well as conjunctival erythema with watery discharge since the same duration. An extensive infectious disease and rheumatologic work up in the hospital was negative. She had two prior admissions for similar complaints in less than a year with minimal response to NSAID and prednisone. The patient was started on a 5-day course of IV Immunoglobulin and Aspirin for suspected Kawasaki-like disease (KLD). She responded well and her symptoms resolved in a few days, strengthening our diagnosis. Conclusion It is a challenging task to diagnose Kawasaki-like disease in HIV infected adults due to a high likelihood of opportunistic infections or possible hypersensitivity to any one of the plethora of prescribed medications. A high suspicion of KLD is advised in HIV infected adults with severe immunosuppression and unexplained fever lasting > 5 days to ensure timely diagnosis and treatment.

The objective of this study was to measure plasma cytokine levels and blood neutrophil functions as well as clinical outcomes in hospitalized patients with community-acquired pneumonia (CAP) treated with or without macrolide use—a known modulator of inflammatory response. Subjects with CAP had peripheral blood analyzed for some neutrophil functions (degranulation of secretory vesicles and specific granules, respiratory burst response and phagocytosis) and ten cytokine levels measured in serum and sputum supernatants. Neutrophil function in healthy volunteers was also measured for reference. Values were measured on the day of enrollment, days 2–4 and 5–7, depending on a patient’s length of stay. Early and late clinical outcomes were also evaluated. All values were compared between those treated with or without a macrolide. A total of 40 subjects were in this study; 14 received macrolide treatment, and 26 did not. Neutrophil function in the macrolide group was not significantly different compared to the non-macrolide group. None of the median cytokine levels or IQRs were statistically significant between the groups. However, a trend toward decreased IL-6, IL-8, and IFN-γ levels, and favorable clinical outcomes were present in the macrolide group. This pilot study showed no statistical difference between cytokine levels or neutrophil activity for CAP patients prescribed a macrolide containing regimen. Considering the trend of lower cytokine levels in the macrolide group when comparing the 5- to 7-day time period with the non-macrolide group, a full study with an appropriate sample size may be warranted.

Summary Introduction Severe community-acquired pneumonia (CAP) portends a serious prognosis. The temporal trend in outcome of severe CAP is not well established. We evaluated the temporal trends in the outcomes of severe CAP. Methods This is a secondary analysis of 800 patients with severe CAP enrolled in the Community-Acquired Pneumonia Organization International Cohort. Severe CAP was defined as CAP requiring admission to the intensive care unit. Only patients admitted to the ICU upon hospital admission were included in this study. We assessed the trend in outcomes of these patients during three time periods: Period I (June 2001 to April 2004), Period II (May 2004 to January 31 2008), and Period III (February 2008 to February 2013). Results After adjustment for other variables, mortality was higher for patients admitted during Period II compared with Period I (RR: 1.46; 95% CI: 1.002 to 2.14; P value = 0.049), and for Period III compared with Period I (RR: 1.70; 95% CI: 1.15 to 2.50; P value = 0.008). No significant difference in length of stay or time to clinical stability was found among the three periods. Conclusion The mortality of patients with severe CAP increased over time in our study population. This finding has important health policy implications if confirmed by other studies.

Purpose of review The purpose of this review is to define what the best therapeutic approach is for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Recent findings Although two meta-analyses reported conflicting findings, recent retrospective studies reported higher success rates in patients with MRSA pneumonia treated with linezolid when compared to vancomycin. Only registration trials are available for some anti-MRSA antibiotics, such as telavancin, ceftaroline, and ceftobiprole. Scarce information is available regarding the best therapeutic approach for MRSA community-acquired pneumonia. Summary Linezolid seems to be a better choice than vancomycin for the treatment of MRSA ventilator-associated pneumonia. It is still unclear whether this affirmation holds for other forms of MRSA pneumonia. Further research is needed to define whether newer antibiotics are better alternatives than currently recommended agents.

Background Influenza-associated hospitalizations result in high morbidity and mortality. We sought to determine if early empiric anti-influenza therapy improves outcomes of hospitalized patients with influenza-associated lower respiratory tract infections (I-LRTIs). Methods This was a randomized, unblinded, trial of adult patients hospitalized with I-LRTIs in Kentucky during 2009-2012. Patients were randomized to group A (standard of care) or group B (standard of care plus oseltamivir as early as possible but within 24 hours of enrollment). The primary outcome was development of clinical failure (composite variable including failure to reach clinical improvement within 7 days, transfer to intensive care 24 hours after admission, or rehospitalization or death within 30 days). Intent-to-treat (ITT) (all LRTI) and per-protocol (PP) (I-LRTI) analyses were done. Results A total of 1107 patients were enrolled and included in the ITT analysis, 556 in group A and 551 in group B. The median time from symptom onset to hospital admission was 5 days (interquartile range, 5) for both groups; oseltamivir was initiated median day 6 in group B. There was no difference in the development of clinical failure (group A, 25%, and group B, 24%; P = .561). In the PP analysis, 11 of 45 (24%) patients in group A and 4 of 29 (14%) patients in group B had clinical failure (P = .414). Conclusions Initiation of oseltamivir more than 5 days after illness onset did not reduce clinical failures among hospitalized patients with I- LRTIs. However, we did not enroll our projected sample size of I-LRTI. Clinical trials registration NCT01248715.

Background Community-acquired pneumonia (CAP) has a potential complication of bacteremia. The objective of this study was to define the clinical outcomes of patients with CAP and bacteremia treated with and without a macrolide. Materials and methods Secondary analysis of the Community-Acquired Pneumonia Organization database of hospitalized patients with CAP. Patients with a positive blood culture were categorized based on the presence or absence of a macrolide in their initial antimicrobial regimen, and severity of their CAP. Outcomes included in-hospital all-cause mortality, 30-day mortality, length of stay, and time to clinical stability. Results Among 549 patients with CAP and bacteremia, 247 (45%) were treated with a macrolide and 302 (55%) were not. The primary pathogen was Streptococcus pneumoniae (74%). Poisson regression with robust error variance models were used to compare the adjusted effects of each study group on the outcomes. The unadjusted 30-day mortality was 18.4% in the macrolide group, and 29.6% in the non-macrolide group (adjusted relative risk (aRR)0.81; 95% confidence interval (CI)0.50–1.33; P = 0.41). Unadjusted in-hospital all-cause mortality was 7.3% in the macrolide group, and 18.9% in the non-macrolide group (aRR 0.54, 95% CI 0.30–0.98; P = 0.043). Length of stay and time to clinical stability were not significantly different. Conclusions In-hospital mortality, but not 30-day mortality, was significantly better in the macrolide group. Our data support the use of a macrolide in hospitalized patients with CAP and bacteraemia.