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Background Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season. Methods This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days. Results A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2–48.0%). Conclusions This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715

Pneumonia causes a significant burden of disease worldwide. Although all populations are at risk of pneumonia, those at extremes of age and those with immunosuppressive disorders, underlying respiratory disease, and critical illness are particularly vulnerable. Although clinical practice guidelines addressing the management and treatment of pneumonia exist, few of the supporting studies focus on the crucial contributions of the host in pneumonia pathogenesis and recovery. Such essential considerations include the host risk factors that lead to susceptibility to lung infections; biomarkers reflecting the host response and the means to pursue host-directed pneumonia therapy; systemic effects of pneumonia on the host; and long-term health outcomes after pneumonia. To address these gaps, the Pneumonia Working Group of the Assembly on Pulmonary Infection and Tuberculosis led a workshop held at the American Thoracic Society meeting in May 2018 with overarching objectives to foster attention, stimulate research, and promote funding for short-term and long-term investigations into the host contributions to pneumonia. The workshop involved participants from various disciplines with expertise in lung infection, pneumonia, sepsis, immunocompromised patients, translational biology, data science, genomics, systems biology, and clinical trials. This workshop report summarizes the presentations and discussions and important recommendations for future clinical pneumonia studies. These recommendations include establishing consensus disease and outcome definitions, improved phenotyping, development of clinical study networks, standardized data and biospecimen collection and protocols, and development of innovative trial designs.

Joven de 19 años que realiza intento de suicido en febrero de 2019, ingiriendo 04 bolsas de raticida “Klerat”. Llevado a Emergencia en la ciudad de Tarapoto (Región San Martín); le realizan lavado gástrico; recibe Fitomenadiona 2 dosis y lo envían a su casa. A los 11 días post- intoxicación presenta dolores osteomusculares, orina de color rojizo, se añade sangrado por las encías, epistaxis, hematomas, aumenta la gingivorragia y sensación de desvanecimiento; es llevado al Hospital de Yurimaguas. En los exámenes de laboratorio se encuentra: INR:9.7 y alteraciones en el Tiempo de Protrombina (TP):45 y Tiempo de Tromboplastina Parcial activada (TTPA): 60. Recibe tratamiento con Fitomenadiona y Ácido tranexámico. Por persistir gingivorragia escasa y alteraciones en la coagulación se hace la referencia al hospital Nacional Dos de Mayo de la ciudad de Lima. Donde se encuentra: INR: 11.5, TP:120 seg. TTPA: 86.5, Hb:12.2 Leucocitos:10.090 Plaquetas: 320.000, Orina: hematíes 5xc. Leucocitos:0-1 x c. Perfil hepático: Normal, Perfil lipídico: Normal, Rx. de Tórax. Normal, Dímero D: 0.14. Se realizan Pruebas de autoinmunidad, encontrando el Anticoagulante Lúpico: Positivo, siendo el resto de pruebas negativas. Se dio Tto. con Plasma Fresco congelado, crioprecipitados y Fitomenadiona. El examen de orina en CICOTOX encontró metabolitos de hidroxicumarinas POSITIVO. Estuvo hospitalizado por 2 meses, se logra la estabilización en el perfil de coagulación y el INR; dependientes del Tto. con Fitomenadiona. El control de orina en CICOTOX dio negativo a los 2 meses. El control del anticoagulante Lúpico a los 3 meses dio Positivo; a los 6 meses dio Negativo. Tuvo que continuar con Tto. de Fitomenadiona por 10 meses más (dic. 2019), hasta lograr la estabilización total del perfil de coagulación y el INR. Para darle el Alta.

Background Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. Methods This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). Results Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. Conclusions The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine., A novel urinary antigen detection assay substantially increased detection of non-pneumococcal conjugate vaccine 13 (PCV13) serotypes included in an investigational PCV20 among US adults with community-acquired pneumonia (CAP). PCV20 may address the burden of CAP due to the additional serotypes.

In 2019, the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) issued a substantial revision of the 2007 guideline on community-acquired pneumonia (CAP). Despite the fact that generalization of infectious disease guidelines is limited because of substantial geographic differences in microbiologic etiology and antimicrobial resistance, the ATS/IDSA guideline is frequently applied outside the United States. Therefore, this project aimed to give a perspective on the ATS/IDSA CAP recommendations related to the management of CAP outside the United States. For this, an expert panel composed of 14 international key opinion leaders in the field of CAP from 10 countries across five continents, who were not involved in producing the 2019 guideline, was asked to subjectively name the five most useful changes, the recommendation viewed most critically, and the recommendation that cannot be applied to their respective region. There was no formal consensus process, and the article reflects different opinions. Recommendations welcomed by most of the international pneumonia experts included the abandonment of the concept of “health-care-associated pneumonia,” the more restrictive indication for empiric macrolide treatment in outpatients, the increased emphasis on microbiologic diagnostics, and addressing the use of corticosteroids. Main criticisms included the somewhat arbitrary choice of a 25% resistance threshold for outpatient macrolide monotherapy. Experts from areas with elevated mycobacterial prevalence particularly opposed the recommendation of fluoroquinolones, even as an alternative.

Background Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. Research Question There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. Study Design and Methods This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. Results The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. Interpretation This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

Objective To generate a quality standard for the management of patients with psoriatic arthritis (PsA). Methods We employed qualitative methodology that included: (1) Two focus groups (one with patients with PsA and another with non-rheumatologist specialists involved in the care of PsA patients); (2) A narrative literature review of published documents related to the quality of care in PsA; (3) A nominal group meeting in which 15 expert rheumatologists generated and reached a consensus on a series of quality criteria, as well as formulas or quantifiable objective measures to evaluate them; (4) The Delphi method to establish the feasibility, priority and agreement with the quality criteria; (5) A final generation of standards of care and their attributes. A descriptive analysis of the results was carried out. Results A total of 59 standards of care was generated, 18 of mandatory compliance, grouped into 4 blocks according to specific objectives: (1) early diagnosis (n = 6); (2) optimising the management of the disease (n = 26); (3) multidisciplinary collaboration (n = 9); (4) monitoring improvement (n = 18). To assess compliance with these standards of care, in many cases, the medical records will be reviewed. Other sources will be the records of the service and hospital and bibliographic databases. Regarding the level of compliance, for some of the standards of care this is yes/no; for others, compliance ranges from 50% to 100% and, in this range, in many cases, compliance was 80%. Conclusions This set of standards of care should help improve quality of care in PsA patients.

Objectives: Racial/ethnic minority women have disproportionately lower breast cancer survival rates compared to white women. As minorities in the US are exposed to higher levels of discrimination, ...

Objectives 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 US 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 1 June 2014 to 31 May 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 United States 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 with COPD, 3419 pneumonia hospitalizations were documented during the 2-year study. The annual incidence was 9369 patients with pneumonia per 100 000 COPD population, corresponding to an estimated 506 953 adults with COPD hospitalized due to pneumonia in the United States. The incidence of CAP in patients without COPD was 509 (95% CI 485–533) per 100 000. COPD patients had a median (interquartile range) TCS and LOS of 2 (1–4) and 5 (3–9) days respectively. The mortality of COPD patients during hospitalization, at 30 days, 6 months and 1 year was 193 of 3419 (5.6%), 400 of 3374 (11.9%), 816 of 3363 (24.3%) and 1104 of 3349 (33.0%), respectively. Conclusions There was an annual incidence of 9369 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.

Objectives To define the current incidence, epidemiology, and mortality of older adult patients hospitalized with community-acquired pneumonia (CAP) in Louisville, KY and thus estimate the burden of CAP in the older adult population of the United States. To define risk factors associated with early and late outcomes. Design This was a secondary analysis of older adults (aged ≥65 years) from the University of Louisville Pneumonia Study, a prospective population-based cohort study of all hospitalized adults with CAP between June 1, 2014, and May 31, 2016. Setting The study took place in all nine acute care hospitals for adults in Louisville, KY. Participants Residents in the city of Louisville, KY, who were diagnosed with CAP between the inclusion dates were included and who were aged 65 years or older. Measurements Incidence of CAP and outcomes were measured. A total of nine risk factors were also assessed for any potential association with time to clinical stability, length of stay (LOS), and mortality. Results During the 2-year study, from a Louisville population of 102 264 adults aged 65 years or older, 4760 were hospitalized with CAP. The incidence of older adults hospitalized with CAP was 2093 per 100 000 population. This corresponds to 967 470 older adults in the United States hospitalized per year with CAP. The median time to clinical stability was 2 days, and the median LOS was 6 days. The 30-day all-cause mortality was 17%. The 1-year all-cause mortality was 38% (829 patients), which corresponds to 361 982 deaths in the United States with CAP in older adults. Conclusion The estimated burden of CAP in older adults is substantial in the United States. Nearly 1 million older adults are hospitalized for CAP, and over a third of those die within 1 year. J Am Geriatr Soc 68:1007-1014, 2020.

Background After hospitalization for community-acquired pneumonia (CAP), patients' clinical course may progress to clinical improvement, clinical failure, or nonresolving pneumonia. The epidemiology and outcomes of patients with CAP according to clinical course has not been well studied. The objective of this study was to characterize the incidence and outcomes for each clinical course of hospitalized patients with CAP. Methods This was a secondary data analysis of the University of Louisville Pneumonia Study. Clinical course was classified as improvement, failure, and nonresolving. Objective criteria were used to define improvement and failure during the first week of hospitalization. If neither group of criteria were met, the course was classified as nonresolving. Incidence for each clinical course was calculated. Mortality was evaluated at different time points through the first year. P Results A total of 7,449 patients were hospitalized with CAP during the study period. Improvement was documented in 5,732 patients (77%), failure was documented in 1,458 patients (20%), and nonresolving CAP was documented in 259 patients (3%). Mortality at 30 days was 6% for those who improved, 34% for those who failed, and 34% for those with nonresolving pneumonia. Mortality at 1 year was 23%, 52%, and 51%, respectively. Conclusions This study shows that > 75% of hospitalized patients with CAP will reach clinical improvement. One of two patients with clinical failure or nonresolving CAP may die 1 year after hospitalization. Understanding the pathogenesis of long-term mortality is critical to developing interventions.

PsA is characterized by a high prevalence of cardiovascular (CV) comorbidities. Recognizing these comorbidities is critical due to their influence on the quality of life and the choice of therapy. Imaging techniques also play an important role in the evaluation of the CV risk in psoriatic disease, improving the prediction of CV events when combined with clinical scores as a predictive tool. Meta-analyses point to a significant reduction in the incidence of CV events associated with the suppression of inflammatory activity when using systemic therapies. Consequently, the mortality rate in PsA patients has fallen in the last 40 years and is now similar to that of the general population, including cardiovascular causes. Obesity is an especially relevant CV comorbidity in patients with psoriatic disease, most of whom are overweight/obese. Body mass index (BMI) is a risk factor for PsA and a causal relationship with psoriasis has been demonstrated by Mendelian randomized studies. The study of fat distribution shows that patients with psoriasis are characterized by visceral fat accumulation, which correlates with CV risk measurements. These findings suggest that approaches to the prevention and treatment of psoriatic disease might come from targeting adiposity levels, in addition to the immune pathways. Weight loss treatment with low energy diets in patients with PsA has been associated with significant improvements in disease activity. Novel strategies using a multimorbidity approach, focused more on patients outcomes, are necessary to better address comorbidities, improve clinical outcomes and the quality of life of patients with psoriatic disease.

Key elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.

S. pneumoniae is a primary etiologic agent of CAP in immunocompromised adults (ICA). Data on clinical outcomes of ICA hospitalized with pneumococcal pneumonia (PP) is limited. The objectives of this study were (1) to define clinical presentation and outcomes of ICA hospitalized with PP and (2) to compare the data to non-immunocompromised adults (non-ICA) hospitalized with PP. This was a case–control study of ICA hospitalized with PP (cases) and non-ICA hospitalized with PP (controls). Data were collected on clinical presentation, treatment, and outcomes. Evaluated clinical outcomes included time to clinical stability (TCS), length of hospitalization (LOH), clinical failure (CF), cardiovascular events (CE), and in-hospital mortality (IHM). One ICA was matched to two non-ICA through propensity score matching. A total of 93 ICA hospitalized with PP and 186 non-ICA hospitalized with PP were evaluated. Antibiotic therapy was appropriate in all patients. Clinical outcomes for ICA versus non-ICA were as follows: TCS 2 days vs. 2 days (p = 0.392), LOH 5 days vs. 5 days (p = 0.067), CF 4% vs. 6% (p = 0.618), CE 10% vs. 6% (p = 0.375), and IHM 5% vs. 3% (p = 0.296). In hospitalized patients with PP who are treated with appropriate antibiotic therapy, the presence of an abnormal immune system does influence clinical outcomes.

Background Severity/mortality risk scores and disease characteristics may assist in deciding whether patients with community-acquired bacterial pneumonia (CABP) require outpatient treatment or hospitalization. The phase 3 OPTIC (Omadacycline for Pneumonia Treatment In the Community) study enrolled patients with Pneumonia Outcomes Research Team (PORT) risk class II–IV. Omadacycline demonstrated noninferiority to moxifloxacin in adults with CABP, at early clinical response (ECR) and posttreatment evaluation (PTE). We assessed efficacy of omadacycline versus moxifloxacin in these patients based on disease severity. Methods Patients were randomized 1:1 to receive intravenous (IV) omadacycline (100 mg every 12 hours for 2 doses followed by 100 mg daily [q24h], with optional transition to omadacycline 300 mg orally q24h after 3 days of IV treatment) or moxifloxacin IV 400 mg q24h (with optional transition to 400 mg orally q24h after 3 days of IV treatment). Total treatment duration was 7–14 days. We compared rates of early clinical success (72–120 hours after first dose) and investigator-assessed clinical success at PTE (5–10 days after last dose) in subgroups based (1) on severity/mortality risk scores (PORT, CURB-65, systemic inflammatory response syndrome, quick Sequential [Sepsis-related] Organ Failure Assessment, modified ATS, SMART-COP) and (2) on presence of baseline radiographic characteristics, chronic obstructive pulmonary disease (COPD)/asthma, or bacteremia. Results Altogether, 774 patients (omadacycline, n = 386; moxifloxacin, n = 388) were randomized. Clinical success rates (ECR/PTE) were similar between treatment groups (across all subgroups). Efficacy across treatment groups was similar in patients with baseline radiographic characteristics or COPD/asthma, but moxifloxacin had higher clinical success rates in patients with bacteremia. Conclusions Efficacy of omadacycline was similar to that of moxifloxacin, regardless of disease severity/mortality risk and disease characteristics.

To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA. In a nominal group meeting, the results of the SLR were discussed and a set of recommendations were proposed for a Delphi process. A total of 65 rheumatologists were invited to participate in the Delphi. Agreement was defined if ≥ 70% of the participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grade of recommendation was established based on the Oxford Evidence-Based Medicine categorisation. Particular clinical situations included monoarthritis, axial disease, or non-musculoskeletal manifestations. The SLR finally comprised 131 articles. A total of 16 recommendations were generated, all but 1 reached consensus. According to them, it is crucial to carefully analyse the impact of individual manifestations on patients (disability, quality of life, etc.), but also to recognise the impact of each drug singularities on selected clinical phenotypes to adopt the most appropriate treatment strategy. Early diagnosis and treatment to target approach, along with a close risk management, is also necessary. These recommendations are intended to complement gaps in national and international guidelines by helping health professionals address and manage particular clinical situations in PsA. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04877-5.

OBJECTIVE: To analyze outcomes and risk factors of cardiovascular events in a metropolitan coronavirus disease 2019 (COVID-19) database, and to perform a subgroup analysis in African American populations to determine whether outcomes and risk factors are influenced by race. DESIGN: Retrospective cohort analysis from March 9, 2020 to June 20, 2020. SETTING: Population-based study in Louisville, KY, USA. PARTICIPANTS: Seven hundred adult inpatients hospitalized with COVID-19. INTERVENTIONS: N/A. MEASUREMENTS AND MAIN RESULTS: This cohort consisted of 126 patients (18%) with cardiovascular events and 574 patients without cardiovascular events. Patients with cardiovascular events had a much higher mortality rate than those without cardiovascular events (45.2% v 8.7%, p < 0.001). There was no difference between African American and white patients regarding mortality (43.9% v 46.3%, p = 1) and length of stay for survivors (11 days v 9.5 days, p = 0.301). Multiple logistics regression analysis suggested that male, race, lower SaO2/FIO2, higher serum potassium, lower serum albumin, and number of cardiovascular comorbidities were highly associated with the occurrence of cardiovascular events in COVID-19 patients. Lower serum albumin and neoplastic and/or immune-compromised diseases were highly associated with cardiovascular events for African American COVID-19 patients. SaO2/FIO2 ratio and cardiovascular comorbidity count were significantly associated with cardiovascular events in white patients. CONCLUSIONS: Cardiovascular events were prevalent and associated with worse outcomes in hospitalized patients with COVID-19. Outcomes of cardiovascular events in African American and white COVID-19 patients were similar after propensity score matching analysis. There were common and unique risk factors for cardiovascular events in African American COVID-19 patients when compared with white patients.

Palindromic rheumatism (PR), a unique clinical entity, has a characteristic clinical presentation with a relapsing/remitting course. It is established that most patients with PR evolve to chronic disease, of which rheumatoid arthritis (RA) is by far the most common. The relationship between PR and RA is unclear, with similarities and differences between the two, and not all patients evolve to RA in the long-term. Therefore, PR is clearly a pre-RA stage for most, but not all, patients. Autoimmunity plays a substantial role in PR, with the same characteristic autoantibody profile observed in RA, although with some differences in the immune response repertoire. Autoinflammation may also be relevant in some cases of PR. Prognostic factors for RA progression are identified but their exact predictive value is not clear. There are several unmet needs in PR, such as the diagnostic criteria and clinical case definition, the pathogenic mechanisms involved in the unusual clinical course, and the evolution to RA, and our understanding of the therapeutic strategy that could best avoid progression to persistent and potentially destructive arthritis.

[Background]: A restricted response against citrullinated peptides/proteins, with less isotype usage, has been found in palindromic rheumatism (PR) in comparison with rheumatoid arthritis (RA). We hypothesized that this different antibody response may be observed for other post-translational modified proteins. We compared the prevalence and isotype usage of two specificities of anti-carbamylated peptide/protein antibodies (Anti-CarP) in patients with PR and RA., [Methods]: Cross-sectional study including 54 patients with pure PR and 53 patients with RA, matched by sex, age, disease duration and ACPA. Anti-CarP specificities were determined by home-made enzyme-linked immunosorbent assay tests using a synthetic chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) and fetal calf serum (FCS) homocitrullinated protein as antigens. IgG, IgA and IgM isotypes were measured., [Results]: Anti-CarP were positive (CFFHP or FCS) in 24% and 64% of patients with PR and RA, respectively (p, [Conclusion]: Anti-CarP are found in patients with PR but in a lower proportion and with a different isotype usage from in RA, suggesting a distinct B cell response to homocitrullinated antigens in PR., The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Hospital Clinic of Barcelona, Research, Innovation and Education Department (Grant # 37933 to RC) and the Spanish Ministry of Economy, Industry and Competitiveness and the European Regional Development Fund (Grant # RTI2018-094120-B-I00 to IH).

To compare long-term clinical, immunological, and radiographic outcomes between five sets of remission criteria (four clinical and one ultrasound (US)-based) in a cohort of RA patients in a clinical care setting.RA patients in remission (DAS28-ESR2.6) were selected. Hand US assessments were made, and serum levels of inflammation/angiogenesis biomarkers were determined at baseline. Changes in baseline treatment and radiographic progression, defined as the variation in the modified Sharp van der Heijde score (mSHS) at 5 years, were analyzed. Five concepts were used to define remission: DAS28-ESR2.6, SDAI3.3, CDAI2.8, Boolean criteria and Power Doppler score (PD)=0.Eighty-seven patients with DAS28-ESR2.6 were included. One-third fulfilled SDAI (33.3%), CDAI (31%), and Boolean (35.6%) remission criteria, and 25.3% had no PD signal in the US evaluation. 26 patients (29.9%) changed therapy, ranging from 13.6% (PD remission) to 33.3% (CDAI remission) (p=0.11). Serum levels of ANG (p=0.015) and TNFa (p=0.025) were significantly lower in patients with Boolean remission, whereas IL-18 levels were significantly lower in those with PD remission (p=0.049). Patients without PD in the US assessment had significantly-lower mSHS erosion progression (p=0.014) at 5 years.Patients with established RA in DAS28-ESR remission had comparable clinical and radiographic outcomes in SDAI, CDAI, and Boolean definitions in a clinical care setting. US remission remained the closest to structural damage abrogation. Key Points • This study provides real world data on long-term outcomes of five clinical and imaging remission criteria in rheumatoid arthritis. • DAS28-ESR remission criteria had comparable radiographic progression and clinical prognosis than more stringent criteria in clinical practice. • US-based remission was closest to structural damage abolishment.

Background Preventing severe complications of influenza such as hospitalization is a public health priority; however, estimates of influenza vaccine effectiveness (VE) against influenza-associated acute lower respiratory tract infection (LRTI) hospitalizations are limited. We examined influenza VE against influenza-associated LRTIs in hospitalized adult patients. Methods We retrospectively analyzed data from a randomized trial of oseltamivir treatment in adults hospitalized with LRTI in Louisville, Kentucky, from 2010 to 2013. Patients were systematically tested for influenza at the time of enrollment. We estimated VE as 1 – the adjusted odds ratio (aOR) of antecedent vaccination in influenza-positives vs negatives × 100%. Vaccination status was obtained by patient self-report. Using logistic regression adjusting for age, sex, season, timing of illness, history of chronic lung disease, and activities of daily living, we estimated VE against hospitalized influenza-associated LRTIs and community-acquired pneumonia (CAP) with radiographic findings of infiltrate. Results Of 810 patients with LRTI (median age, 62 years), 184 (23%) were influenza-positive and 57% had radiographically confirmed CAP. Among influenza-positives and -negatives, respectively, 61% and 69% were vaccinated. Overall, 29% were hospitalized in the prior 90 days and >80% had comorbidities. Influenza-negatives were more likely to have a history of chronic obstructive pulmonary disease than influenza-positives (59% vs 48%; P = .01), but baseline medical conditions were otherwise similar. Overall, VE was 35% (95% CI, 4% to 56%) against influenza-associated LRTI and 51% (95% CI, 13% to 72%) against influenza-associated radiographically confirmed CAP. Conclusions Vaccination reduced the risk of hospitalization for influenza-associated LRTI and radiographically confirmed CAP. Clinicians should maintain high rates of influenza vaccination to prevent severe influenza-associated complications.

Obesity has been shown to have a paradoxical benefit in a number of conditions, but the long-term effects in obesity after chronic obstructive pulmonary disease (COPD) exacerbation is still unclear. In this study, the effects of obesity on short- and long-term outcomes after a COPD exacerbation were evaluated. This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS): a prospective, randomized, unblinded clinical trial. Patients were included in the study if they were hospitalized for acute exacerbation of COPD. Obesity was noted as patients with BMI30. Clinical outcomes of time to clinical stability, length of stay, and mortality were compared. A total of 301 patients were included in the study, 122 (41%) patients were obese. There was no significant difference in the length of stay and time to clinical stability between patients with and without obesity. Mortality for patients with and without obesity was 3% and 3% at 30 days, 7% and 18% at six months, and 8% and 28% at one year, respectively. After adjusting with multivariable regression analysis, patients with obesity had a significant reduction in odds of dying at one year (adjusted odds ratio (aOR): 0.18; 95% CI: 0.06-0.58

Objectives: To analyze ultrasound (US) differences between rheumatoid arthritis (RA) patients according to their autoantibody status and characterize the clinical, immunological and radiological features associated with the US pattern of seropositive patients.Methods: We collected clinical and immunological data along with bilateral hand US images of RA patients. Serum biomarkers, MRI of dominant hand and immunostaining of synovial biopsies were performed.Results: Two hundred and five RA patients were collected (84.8% seropositive). No significant differences in disease activity/therapy were found according to autoantibodies status. An extreme proliferative US pattern, encompassing synovial hypertrophy grade II-III with Power Doppler signal that we called US Proliferative Synovitis (US PS) was present in 55.5% of seropositive and 16.1% of seronegative patients, (p=0.0001). In the multivariate analysis, erosions [OR 4.90 CI 95% (2.17-11.07). p=0.0001] and ACPA [OR 3.5 CI 95% (1.39-10.7), p=0.09] but not RF status [OR 0.74 CI 95% (0.31-1.71), p=0.483] were independently associated with the presence of US PS. Ninety-four per cent of joints with US PS scored 2-3 in RAMRIS synovitis sub-index. At synovial level, US PS was significantly associated with higher density of vessels (p=0.042). Moreover, significantly higher serum levels of angiogenic and inflammatory cytokines were found in patients with US PS. After a mean of 46 months of follow-up, US PS was independently associated with change of therapy (OR 2.63, 95% CI 1.20-5.77, p=0.016).Conclusions: ACPA+ RA was associated with US PS. This US pattern significantly detected erosive disease and an enhanced need to change therapy in the long-term.

Objective To compare long-term clinical and radiographic outcomes among five sets of remission criteria [four clinical and one Ultrasound (US)-based] in a cohort of RA patients in a clinical care setting. Methods RA patients in remission (DAS28-ESR

Objectives The influence of socioeconomic disparities on adults with pneumonia is not well understood. The objective of our study was to evaluate the relationship between community-level socioeconomic position, as measured by an area deprivation index, and the incidence, severity, and outcomes among adults with community-acquired pneumonia (CAP). Methods This was an ancillary study of a population-based, prospective cohort study of patients hospitalized with CAP in Louisville, Kentucky, from June 1, 2013, through May 31, 2015. We used a race-specific, block group–level area deprivation index as a proxy for community-level socioeconomic position and evaluated it as a predictor of CAP incidence, CAP severity, early clinical improvement, 30-day mortality, and 1-year mortality. Results The cohort comprised 6349 unique adults hospitalized with CAP. CAP incidence per 100 000 population increased significantly with increasing levels of area deprivation, from 303 in tertile 1 (low deprivation), to 467 in tertile 2 (medium deprivation), and 553 in tertile 3 (high deprivation) ( P < .001). Adults in medium- and high-deprivation areas had significantly higher odds of severe CAP (tertile 2 odds ratio [OR] = 1.2 [95% confidence interval (CI), 1.06-1.39]; tertile 3 OR = 1.4 [95% CI, 1.18-1.64] and 1-year mortality (tertile 2 OR = 1.3 [95% CI, 1.11-1.54], tertile 3 OR = 1.3 [95% CI, 1.10-1.64]) than adults in low-deprivation areas. Conclusions Compared with adults residing in low-deprivation areas, adults residing in high-deprivation areas had an increased incidence of CAP, and they were more likely to have severe CAP. Beyond 30 days of care, we identified an increased long-term mortality for persons in high-deprivation areas. Community-level socioeconomic position should be considered an important factor for research in CAP and policy decisions.

Objective: To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Methods: Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies. Results: We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p, Financial support from the Hospital Clinic of Barcelona, Research, Innovation and Education Department (Grant # 37 933 to RC-M and the Spanish Ministry of Economy, Industry and Competitiveness and the European Regional Development Fund (Grant # RTI2018-094120-B-I00 to IH).

Purpose of review The aim of this study was to discuss the literature on community-acquired pneumonia (CAP) in patients with chronic obstructive pulmonary disease (COPD). Recent findings Well designed studies show that COPD is the strongest risk factor for development of CAP. Lung microbiome, abnormal lung immunity and pathogen virulence are important components of the pathogenesis of CAP in COPD. The cause of CAP in patients with COPD is similar to that of non-COPD patients. However, patients with COPD are at an increased risk of infection by Gram-negative bacilli, including Pseudomonas aeruginosa. Empiric treatment regimens for CAP in COPD should contemplate the most common pathogens, and consideration should be given for the coverage of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus depending on the severity of CAP, severity of COPD or prior isolation of these pathogens. COPD has not been consistently shown to be an independent risk factor for worse short-term outcomes in patients with CAP. In a long-term study, COPD is associated with worse outcomes in these patients. Summary Research focused on lung microbiome and abnormal lug immunity in patients with COPD should be prioritized. Further clinical research should try to consolidate the role of additional treatment approaches such as immunomodulating medications in COPD patients with CAP.

Background: Patients infected with the novel coronavirus SARS-CoV-2 are frequently hospitalized with community-acquired pneumonia (CAP). The objective of this study was to define the clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 CAP in the city of Louisville, KY. Methods: This was a retrospective observational study of 700 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients with 1) a positive RT-PCR for SARS-CoV-2, 2) fever, cough, or shortness of breath, and 3) an infiltrate at chest imaging were defined as having SARS-CoV-2 CAP. Demographic characteristics of the study population were compared with census data from the city of Louisville. For each patient more than 500 variables were abstracted from electronic medical records and recorded using Research Electronic Data Capture software. Data was analyzed by descriptive and inferential statistics using R version 3.4.0. Results: SARS-CoV-2 CAP was identified in 632 (90%) patients hospitalized with COVID-19. The median age of the patients was 63 years, 53% were females, 31% were black and 12% Hispanic. The most frequent comorbidities were hypertension (56%), obesity (50%), and diabetes (33%). Mortality was 17% for the total population and 34% for the 249 patients admitted to ICU. For each category of race, ethnicity and comorbidities, the proportion of hospitalized patients with SARS-CoV-2 CAP was significantly different when compared to the Louisville population (p < 0.001). Conclusion: Patients of black race, Hispanic ethnicity, and patients with history of hypertension, obesity or diabetes are overrepresented among hospitalized patients with SARS-CoV-2 CAP when compared to the Louisville population. Hospitalized patients with SARS-CoV-2 CAP are likely to require ICU care, with death occurring in approximately one of six hospitalizations.

Introduction The aim of this study was to evaluate the impact of comorbidities on disease activity, patient’s impact of the disease, patient global assessment, and function in psoriatic arthritis (PsA). Methods Consecutive PsA patients were enrolled in this cross-sectional study. During the visit, the patients underwent a complete physical examination and clinical/laboratory data were collected, including type and number of comorbidities, recorded as simple comorbidity count (SCC). Disease activity was assessed using the Disease Activity Score for Psoriatic Arthritis (DAPSA) and the Minimal Disease Activity (MDA) was also evaluated. The Psoriatic Arthritis Impact of Disease (PsAID), the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Patient Global Assessment of disease activity (PtGA) were also collected. Results A total of 144 patients were enrolled. At least one comorbidity was registered in 104 (72.2%) patients. The SCC was associated with DAPSA (β = 1.48, p = 0.013), PsAID (β = 0.41, p

Objective To identify biomarkers of treatment change and radiographic progression in patients with RA under remission. Patients and methods RA patients in remission (DAS28-ESR 10.47 (small detectable change). Results Sixty patients were included, 81.6% were ACPA+ and 45% were taking biological DMARDs. At baseline, 66.6% had Power Doppler signal. After 5 years, 73.3% of patients remained in remission. Change of therapy was performed in 20 patients (33.3%) and was associated with BMI [odds ratio (OR) 1.3, 95% CI: 1, 1.7], lack of biological DMARD therapy (OR 24.7, 95% CI: 2.3, 257.2), first-year progression of MRI erosions (OR 1.2, 95% CI: 1, 1.3) and calprotectin serum levels (OR 2.8, 95% CI: 1, 8.2). Radiographic progression occurred in six (10%) patients. These patients had higher first-year progression of MRI erosions (P = 0.03) and bone oedema (P = 0.04). Among 23 patients undergoing synovial biopsy, mast cell density was independently associated with clinical flares. Conclusions One-third of RA patients lost clinical remission and changed therapy throughout the 5 years of follow-up, which was independently associated with BMI, lack of biological DMARDs therapy and first-year progression of MRI erosion score and calprotectin serum levels. Significant radiographic progression was uncommon.

IntroductionClinically diagnosed pneumonia in children is a leading cause of paediatric hospitalisation and mortality. The aetiology is usually bacterial or viral, but malaria can cause a syndrome indistinguishable from clinical pneumonia. There is no method with high sensitivity to detect a bacterial infection in these patients and, as result, antibiotics are frequently overprescribed. Conversely, unrecognised concomitant bacterial infection in patients with malarial infections occur with omission of antibiotic therapy from patients with bacterial infections. Previously, we identified two combinations of blood proteins with 96% sensitivity and 86% specificity for detecting bacterial disease. The current project aimed to validate and improve these combinations by evaluating additional biomarkers in paediatric patients with clinical pneumonia. Our goal was to describe combinations of a limited number of proteins with high sensitivity and specificity for bacterial infection to be incorporated in future point-of-care tests. Furthermore, we seek to explore signatures to prognosticate clinical pneumonia.Methods and analysisPatients (n=900) aged 2–59 months presenting with clinical pneumonia at two Gambian hospitals will be enrolled and classified according to criteria for definitive bacterial aetiology (based on microbiological tests and chest radiographs). We will measure proteins at admission using Luminex-based immunoassays in 90 children with definitive and 160 with probable bacterial aetiology, and 160 children classified according to the prognosis of their disease. Previously identified diagnostic signatures will be assessed through accuracy measures. Moreover, we will seek new diagnostic and prognostic signatures through machine learning methods, including support vector machine, penalised regression and classification trees.Ethics and disseminationEthics approval has been obtained from the Gambia Government/Medical Research Council Unit The Gambia Joint Ethics Committee (protocol 1616) and the institutional review board of Boston University Medical Centre (STUDY00000958). Study results will be disseminated to the staff of the study hospitals, in scientific seminars and meetings, and in publications.Trial registration numberH-38462.

Background HIV-positive patients on anti-retroviral therapy (ART) are at higher risk of developing many non-AIDS related chronic diseases, including chronic obstructive pulmonary disease (COPD), compared to HIV-negative individuals. While the mechanisms are not clear, a persistent pro-inflammatory state appears to be a key contributing factor. The aims of this study were to investigate whether HIV-positive patients without COPD present evidence of potentially predisposing abnormal pulmonary cytokine/chemokine environment and to explore the relationship between pulmonary and systemic cytokine levels. Methods This study included 39 HIV-seropositive and 34 HIV-seronegative subjects without COPD. All were subjected to outpatient bronchoscopy with bronchoalveolar lavage fluid (BALF) aspiration and blood sample collection. The levels of 21 cytokines and chemokines were measured in plasma and BALF using a bead-based multi-analyte assay. Results In plasma, HIV-infected patients showed significantly increased circulating levels of pro-inflammatory (TNFα) and Th1-associated cytokines (IL-12p70) as well as several chemokines (CXCL11 and CX3CL1). However, no statistically significant differences were found in the numbers of cells, the concentrations of protein and urea as well as cytokine levels in the BALFs of HIV-positive patients when compared to controls. Correlation analysis indicated a potential modulatory effect of the BMI in HIV-seropositive individuals. Conclusions While our results are consistent with the existence of a systemic pro-inflammatory state in HIV-infected patients, they did not detect significant differences in cytokine levels and other inflammatory markers in the lungs of HIV-positive individuals when compared to HIV-negative controls.

Background Community-acquired pneumonia (CAP), the most common pneumococcal infection, is a leading cause of morbidity and mortality among immunocompromised hosts. Although vaccination against Streptococcus Pneumoniae is recommended by international guidelines, most studies report a sub-optimal coverage. Objectives To describe the pneumococcal vaccination coverage, predictors for vaccination uptake and frequency of severe CAP and invasive pneumococcal disease during the study period. Methods We performed a cross-sectional study using electronic medical record data from October 2000 to October 2018, including patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and Ankylosing Spondylitis (AS), treated with biologic (bDMARD) and conventional synthetic DMARD (csDMARD) with or without glucocorticoids (GC), followed-up at a referral centre. Since pneumococcal vaccination guidelines have changed during the study period, patients who received at least one dose of any of the available vaccines were defined as being “ever-vaccinated” whereas those who received a complete scheme defined as one dose of conjugated vaccine and one of polysaccharide vaccine 8 weeks apart were defined as having “optimal vaccination”. Predictors of vaccination were analyzed using logistic regression modelling using a set of covariates selected according to the literature. Model assessment was done using Akaike information criterion. To analyze the frequency of severe infections we defined two outcomes: Severe CAP: An episode requiring hospitalization or intravenous antibiotic treatment Invasive pneumococcal disease (IPD): an infection confirmed by the isolation of the micro–organism from a normally sterile site (i.e. blood). Results A total of 279 patients were included, their main clinical features are shown in Table 1. The vaccination coverage was 38.7% and 13.3% overall when analyzing as “ever-vaccinated” and having “optimal vaccination” respectively. A 66% of patients were vaccinated in primary care with a 7% of optimal vaccination whereas the remaining ones received vaccination in referral centres with an 85.3% of optimal vaccination. After adjustment in a multivariate model, age, presence of bronchiectasis, history of severe CAP, current use of csDMARD or GC were predictors of being ever-vaccinated against Streptococcus Pneumoniae. (Table 2) During the study period, 27 (10%) episodes of severe CAP and 4 of IPD were identified, 8 of the former with evidence of pneumococcal infection (either positive urine antigens or isolation in sputum). Conclusion Pneumococcal vaccination coverage remains lower than expected with most patients vaccinated in primary care and not receiving the current recommended scheme. Age, bronchiectasis, history of severe CAP and current use of csDMARD or GC were independent predictors of receiving vaccination. The frequency of severe CAP and IPD was 10% and 1,43% within this cohort. Disclosure of Interests Sebastian C Rodriguez-Garcia: None declared, Raul Castellanos-Moreira Speakers bureau: MSD, Lilly, Victoria Hernandez: None declared, Roberto Gumucio: None declared, Anna Vilella: None declared, Carolina Garcia-Vidal Speakers bureau: Lilly, Pfizer, Juan D. Canete: None declared, Julio Ramirez: None declared, Raimon Sanmarti Speakers bureau: PFIZER, SANOFI, LILLY, MSD, UCB, NOVARTIS, JANSSEN, Jose A. Gomez-Puerta Consultant for: Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen, MSD, Pfizer, Roche

Background: The administration of intravenous biological therapies is based on the manufacturer’s instructions and the administration guidelines of Spanish Medicine Agency. We observed that a considerable amount of the solution remains in the tubing of the equipment after the administration of the drug. This amount depends on the drug and the solution used for the infusion. In the particular case of Infliximab is around 7% of the total solution to infuse, so it could potentially have a relevant therapeutic impact. Objectives: To assess the variation in serum trough levels of Infliximab after the systematic application of flush physiological serum after drug administration. Methods: The study was divided into two phases: a first phase in which the clinical and analytical variables (including the serum trough levels of infliximab) were measured before the application of the flush serum and a second stage in which the same variables were measured after the systematic implementation of an infusion of 50ml of 0.9% sodium chloride following the administration of infliximab. Results: A total of 35 patients were collected, including 6 rheumatoid arthritis (13.3%), 9 psoriatic arthritis (20%) and 20 ankylosing spondylitis (AS) (44.4%). Overall, 18 patients were women (40%), the mean age was 57.6 years (12.6) and the BMI was 30.5 (13.1). The mean dose of infliximab was 4.3 mg/kg (1.1) and the mean number of years of treatment was 10 (5). 23 patients were taking infliximab on monotherapy (51.1%). The mean serum trough levels of infliximab pre-intervention with the dragging serum was 3.13 mg/dl (3.1), while postintervention levels were 3.66 mg/dl (3.9) (p = 0.071). In the subgroup of patients with AS there was a significant decrease in BASDAI between the pre and post intervention visit (3.4 vs 2.6, p Conclusion: The use of flush serum after infliximab infusion increased serum drug levels. In the subgroup of patients with AS there was a clinically significant improvement measured by BASDAI. References: [1] Ficha tecnica de Inflectra®. Disponible en: https://cima.aemps.es/cima/pdfs/es/ft/98067002/FT_98067002.pdf [2] Ficha tecnica de Remicade®. Disponible en: https://cima.aemps.es/cima/dochtml/ft/99116001/FT_99116001.html [3] Grupo de Trabajo de Enfermeria de la Sociedad Espanola de Reumatologia (GTESER). Manual de terapias parenterales y procedimientos en el paciente reumatologico 2018. Madrid, 2018. [4] Herrero Massari F, Lozano Serrano V, Rodruiguez Arteaga E. Guia de Manejo de Farmacos Biologicos para Enfermeria en los Hospitales de Dia. 2010 [5] Moots RJ1, Xavier RM2, Mok CC3, Rahman MU4, Tsai WC5, Al-Maini MH6, Pavelka K7, Mahgoub E4, Kotak S4, Korth-Bradley J4, Pedersen R4, Mele L4, Shen Q4, Vlahos B4. The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study. PLoS One. 2017 Apr 27;12(4):e0175207. doi: 10.1371/journal.pone.0175207. eCollection 2017. [6] Pascual-Salcedo D1, Plasencia C, Ramiro S, Nuno L, Bonilla G, Nagore D, Ruiz Del Agua A, Martinez A, Aarden L, Martin-Mola E, Balsa A. Influence of immunogenicity on the efficacy of long-term treatment with infliximab in rheumatoid arthritis. Rheumatology (Oxford). 2011 Aug;50(8):1445-52. doi: 10.1093/rheumatology/ker124. Epub 2011 Mar 22. [7] Sociedad Espanola de Reumatologia. Inforeuma. Tratamientos: Infliximab. 2017. Disponible en: https://inforeuma.com/wp-content/uploads/2017/03/95_Infliximab_TRATAMIENTOS-A4-v03.pdf [8] Van Schouwenburg PA1, Rispens T, Wolbink GJ. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. Nat Rev Rheumatol. 2013 Mar;9(3):164-72. doi: 10.1038/nrrheum.2013.4. Epub 2013 Feb 12. Disclosure of Interests: Marta Bassas Palou: None declared, Cristina Gonzalez: None declared, Ana Atares: None declared, Raimon Sanmarti Speakers bureau: PFIZER, SANOFI, LILLY, MSD, UCB, NOVARTIS, JANSSEN, Julio Ramirez: None declared

Background: Ustekinumab (UST) is an anti- interleukin (IL) 12/23 monoclonal antibody that has been shown to be effective and safe in psoriatic arthritis (PsA) in two phases III clinical trials. However, we have very few UST data in a real- life setting. Objectives: To assess the effectiveness, safety and survival of UST among patients with PsA treated under routine clinical care. Methods: Retrospective and multicentric study. Epidemiological and clinical data were collected through the electronic medical record of all patients with PsA who started UST due to rheumatological indication in 14 hospitals of Catalonia and the Balearic Islands (Spain). Results: 152 patients were included, 116 (76.3%) with 45mg and 36 (23.8%) with 90mg. 55.9% were women, mean age 54.79 (12.5) years, and mean disease duration 209 months. 132 patients (87%) had oligo (30.3%) or polyarticular involvement (56.6%). 26.8% had enthesitis and 36.2% dactylitis. 48p(35.6%) had erosions. 94p (61.8%) had previously received another biological therapy, and 39 of them (38.8%) had received 2 or more. 54.6% of the patients were taking DMARDs and 39.5% glucocorticoids. The baseline DAS 28 was 3.97 (1.45), C reactive protein (CRP) was 2 mg/dl (2), SJC was 4.0 (5.4), and PASI was 6.5 (8.4). There were no significant differences in clinical and epidemiological data between patients at 45 or 90 mg except in obese patients (58.4% in 90mg vs 40% in 45mg, p = 0.038). Overall, there was a significant decrease in DAS28, SJC, TJC and PASI in the first month of treatment, with more pronounced improvement in skin (PASI and BSA) than in joints outcomes, where the curves reached a plateau at 6 months. There were no significant differences between joint and/or skin outcomes between 45 and 90 mg doses. Patients naive to biological therapy had an earlier skin improvement than patients with previous biological failure. Likewise, the improvement in joint outcomes was also faster in naive vs biological experienced patients (DAS28 and SJC 4m, p = 0.01 and 0.01, respectively). After an average of 19m of follow-up, 94 out of 152p (61.8%) continued with UST, 54.4% started at 45mg and 72.2% at 90mg (p = 0.04). 42p (28.2%) stopped UST due to joint inefficacy, 8p (5.4%) for skin inefficacy and 4 (2.7%) for adverse effect. Although survival was better in patients with fewer previous biological agents, no significant differences were achieved (p = 0.233 for naive and p = 0.072 for patients with 1 biological failure). Conclusion: This analysis demonstrates that UST, administered to PsA patients in a routine clinical care setting, is safe and effective in improving skin and joint outcomes. 61.2% of the patients continued with the treatment after an average of 19m of follow-up. Joint and skin outcomes reached significant differences from the first month. The efficacy seems faster in those patients with fewer lines of previous biological therapies. One third of the patients interrupted the therapy due to joint inefficacy. Acknowledgement: JANSSEN Disclosure of interests: Ana Belen azuaga-Pinango: None declared, Beatriz Frade-Sosa: None declared, ana Laiz Consultant for: Lilly, Novartis, abbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, abvvie, MSD, UCB and Janssen, Paula Estrada: None declared, Luciano Polino: None declared, Emma Beltran: None declared, Agueda Prior-Espanol: None declared, Lourdes Mateo Soria: None declared, Carme Moragues Pastor : None declared, agusti Sellas-Fernandez: None declared, aNA URRUTICOECHEA-ARANA: None declared, Mireia Moreno : None declared, Javier Garcia Miguel: None declared, Jose L Tandaipan: None declared, Manel Pujol: None declared, Vicenc Torrente Segarra : None declared, inmaculada Ros Vilamajo : None declared, Sergi Ordonez : None declared, Delia Reina-Sanz: None declared, andrea Cuervo: None declared, Juan D. Canete: None declared, Julio Ramirez: None declared

We read the article by Mankia et al on the distinct ultrasound (US) imaging phenotype in palindromic rheumatism (PR) with great interest.1 The authors found characteristic US findings in PR during flares that differ from those observed in patients with early rheumatoid arthritis (RA) or anti-cyclic citrullinated peptide (CCP)+ arthralgia. US extracapsular inflammation (periarticular inflammation, subcutaneous or peritendinous oedema), in most cases without joint synovitis, is the most frequent US finding in PR. These findings disappeared after acute attacks. The authors concluded that this imaging phenotype of extracapsular inflammation is specific for PR and may be distinguished from that observed in RA or persistent arthritis. They also suggest that true US intrasynovial inflammation may predict future RA in these patients. …

Background Composite scores developed in Rheumatoid arthritis (RA) not include all dimensions of disease activity. An index based on essential clinical plus a ultrasound (US) measures, focused on simplicity, with appropriate validation, would allow a better classification at different levels of disease activity than a clinical only or US only index. Objectives To develop and validate a mixed clinical-US inflammation score in RA for use in clinical practice. Methods Mixed methods. Experts elicited items reflecting inflammation which were prioritised by Delphi. Patients with RA with various grades of activity underwent clinical [28 swollen and tender joints counts, patient and physician global assessment (PhGA), erythrocyte sedimentation rate, and C-reactive protein (CRP)] and US assessments [synovitis or tenosynovitis by grey-scale (GS) and Power Doppler (PD) of 42 structures], blinded to the clinical assessment. An index was created after supported selection of US structures and scoring method. 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). Results US of joints and tendons, CRP, and swollen joints were the items that passed the prioritisation phase. Then, 281 patients were randomly divided into design (n=141) and validation analysis (n=140). The combination of US sites chosen detected the maximum proportion of GS and PD present. Were elected wrist, 2–3 MCP, Knee, tibio-talar and 2–3 MTP joints, and the following tendons: carpal extensor and flexor tendons, tibial posterior and peroneal. For scoring structures, three methods were tested: semiquantitative (0–3 GS +0–3 PD), dichotomous (0/1 GS +0/1 PD), and qualitative (0/1 based on algorithm [image 1]). All showed strong correlation with activity measures (rho ≥0.60), and reliability (ICC 0.89 to 0.93). The most feasible index, qualitative, was chosen. The proposed formula for USAS was: USAS=N° swollen joints+US score+CRP Conclusions USAS is a valid and reliable measure of inflammation in RA equal to the sum of 28 swollen joint count, a simplified (0/1) US assessment of 11 structures and CRP. Disclosure of Interest None declared

Background Among patients with RA in remission, subclinical synovitis (SS) has a prevalence of 45% and is associated with an increased risk of clinical relapse and progression to structural damage. US is a sensitive and accessible tool for evaluating SS 1,2,3 . Objectives To analyse US as a tool for evaluating SS in RA patients treated with tocilizumab (TCZ), in order to assess remission, and from there on propose therapeutic tapering. Methods Multicenter, 1 year follow up study in 45 patients with RA treated with TCZ. The project was aproved by Ethics Committees and all the patients gave their informed consent. At each visit: DAS28, SDAI, CDAI, mHAQ, US grey scale (GS) and Power Doppler (PD) parameters for 32 joints (J) and 28 tendons (T), with a semiquantitative scale from 0–3 points. A quantitative index was obtained for J and T in GS and PD and overall (EG +PD) for each patient/visit. SS was considered as the presence of synovitis with PD(+)≥2. Our intra and interobserver kappa index was 0.8. Results A significant reduction of all clinical indexes and US variables was observed in all patients. Patients were divided into two groups: remission (R) and no remission (NR) according to whether they achieved DAS28 ≤2.6 at 12 months. Group R achieved DAS28 ≤2.6 after mo 3, whereas US showed SS (GS+, PD >2) until mo 12. The final overall PD value in the R group was 0.6 (±0.9). Conclusions A significant number of patients achieve clinical remission within a few months of starting TCZ. The R group, achieved a good EULAR response since mo 3; a progressive improvement in PD, persisted until mo 12. We consider that these findings refer to SS. From our data we consider that dose tapering should not be initiated until at least 9 months from the start of remission. References [1] doi 10.1002/art.22190 [2] PMID 27050636 [3] doi 10.1093/rheumatology/kex084 Disclosure of Interest None declared

Background Tocilizumab (TCZ) is a humanised antibody that blocks IL-6 receptor. Despite its effectiveness in rheumatoid arthritis (RA), there are patients that do not respond to the IL-6R blockade. The immune characteristics that would explain this lack of response are not known. Objectives Our aim was to determine the tocilizumab-induced changes in CD4 +T cells of patients that achieve, or not, remission at 12 m. Methods Prospective, multicenter study in 47 RA patients treated with TCZ during one year following standard clinical practice. Demographic, disease and treatment characteristics were collected at each visit. Ultrasound (US) grey scale and power doppler were assessed for joints and tendons using a semiquantitative scale from 0–3 points. Phenotyping of T lymphocytes was determined by flow cytometry and the plasma cytokine concentration was quantified by ELISA. Results Forty seven patients were treated with a mean age of 54±11 y and 85% were women. Years of disease were 13±8. We segregated patients according to the DAS28-remission. 44% achieved remission at month 12. We observed that absolute counts of neutrophils and CD4 +T lymphocytes decreased significantly in the remission group but not in the other one. Both memory and naive CD4 +T cells decreased in the remission group. The analysis of T cells classified according to chemokine receptors showed that memory (29.1±4.0 vs 22.7±2.7 × 10 4 cells/mL; p=0.06) and naive (22.6±4.1 vs 17.2±2.8; p=0.04) CD4 +with CXCR3 +and with CCR4 +were the subsets that decreased significantly in the remission group but not in the non-remission group. Since the expression of chemokine receptors defines the different Th subpopulations, we analysed them in the two groups of patients. Th1 tended to decreased in the remission group (3.5±0.7 vs 2.5±0.4; p=0.06) and Th9 decreased significantly in both groups (R: 5.0±0.8 vs 2.5±0.3; p=0.006 and Non R 5.5±0.8 vs 3.1±0.4; p=0.001). In regard to the cytokines produced by CD4 +T lymphocytes, IL-17 (2.1±1.1 vs 1.2±0.5 ng/ml; p=0.04) and VEGF (0.5±0.2 vs 0.3±0.1 ng/ml; p=0.05) but not IL-6 and IL-22 changed significantly in the remission group. Interestingly, IL-17 and VEGF correlated with US findings before the initiation of the treatment (grey scale R=0.378, p=0.01 and R=0.322, p=0.03; power Doppler R=0.415, p=0.004 and R=0.320, p=0.03 respectively). Conclusions Tocilizumab induced changes in specific subsets of CD4 +T cells and their inflammatory associated cytokines in the remission group. Disclosure of Interest None declared