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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

Background Anti-carbamylated protein antibodies (anti-CarP) are a newly-identified antibody family present in the sera of rheumatoid arthritis (RA) patients whose specificity is close to that of ACPA but whose sensitivity is lower. Palindromic rheumatism (PR) is an intermittent form of arthritis that may progress to RA. Patients with PR may present the characteristic autoantibody profile seen in RA, even in the absence of evolution to RA. There are no studies on the presence of anti-CarP antibodies in PR. Objectives To analyse the prevalence of anti-CarP in patients with PR and evaluate their clinical phenotype and relationship with ACPA. Methods Patients diagnosed with PR attended by the Arthritis Unit, Rheumatology Service, Hospital Clinic of Barcelona were included according to the criteria of Guerne et al. Only patients considered as pure PR (patients without evidence of RA or other chronic rheumatic disease at the time of the first determination of anti-CarP) were analysed. An established RA control group was included. Anti-CarP were analysed by a home-made ELISA using a fibrin/chimeric filaggrin homocitrulinated peptide as antigen. IgG, IgA and IgM isotypes were measured. ACPA were analysed with a commercial CCP2 test. The clinical and therapeutic characteristics were compared according to anti-CarP positivity/negativity and to the clinical evolution, including the progression to RA during the follow-up. Results Anti-CarP were analysed in 54 patients with pure PR and 53 RA patients. Anti-CarP were detected in 16.7% and 37.7% (p: NS) of patients with PR and RA, respectively. All PR patients positive for anti-CarP were ACPA positive and had higher ACPA titers. IgG was the predominant isotype (100%), only one patient presented IgA (11.1%) and none IgM. In the RA group, the percentages of IgG, IgA and IgM were 55%, 50% and 40%, respectively, in anti-CarP positive patients. More anti-CarP positive patients developed RA (33.3% vs. 13.6%), although the difference was not significant, during a mean follow-up of 3.8±1.1 years. Remission at the last follow-up visit was more frequent in patients who were anti-CarP negative (22% vs. 60.5% p Conclusions This is the first study to demonstrate the presence of anti-CarP in patients with pure PR. Anti-CarP was associated with ACPA positivity and higher ACPA titers. Anti-CarP isotypes differed between PR and RA, with lower isotype use in PR. Anti-CarP positivity in PR patients could indicate a more refractory disease, with lower rates of remission and greater predisposition to evolve to RA. Acknowledgements This study was supported by two awards granted by Hospital Clinic de Barcelona, Research, Innovation and Education Department (Sonia Cabrera-Villalba, Premi Fi de residencia: Emili Letang 052012; Raul Castellanos-Moreira, Premi Fi de residencia: Emili Letang 379_33_PFR_ 250760_2017). Disclosure of Interest None declared

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.

Background Community-acquired pneumonia (CAP) is a respiratory disease that is responsible for an estimated 3.5 million worldwide deaths annually. In the last few years, it has been hypothesized that CAP is implicated in the development of diseases in other systems such as renal and cardiovascular. Until this moment, multiple studies evaluating incidence of acute myocardial infarction (AMI) in patients with CAP exist, but data are still unclear. Our objective was to summarize several studies available regarding incidence of Acute Myocardial Infarction (AMI) in patients with CAP and to compare such value with the incidence of AMI in the general population. Methods We conducted a systematic review of articles published between January 1980 and January 2019 in the PubMed and PubMed Central databases. Studies describing the incidence of AMI in patients with CAP were included. We extracted their diagnostic criteria for CAP and AMI, and their AMI follow-up periods. In addition to this, we calculated cumulative incidence of AMI in patients with CAP and compared such value with the general population. Results 1841 studies were identified (Figure 1), of which 10 studies were included in our review (Figure 2). From a forest plot-random effects model, the cumulative incidence of AMI among patients hospitalized due to CAP was 2,440 per 100,000 (95% CI: 1,780; 3,320) (Figure 3). Using the age-adjusted incidence of 649 cases of CAP per 100,000 adults described by Ramirez et al., we estimated that 16 per 100,000 adults will have an AMI associated with CAP (95% CI: 12;22) per year in the US Moreover, Yeh et al. found that the incidence of AMI in the general population was 208 per 100,000 people, comparing this value, to the values obtained in our meta-analysis of 2,440 acute myocardial infarctions by 100, 000 people, we can infer that adult patients hospitalized due to CAP have an 11.7-fold increase from the general population for risk of MI. Conclusion A higher risk of AMI was observed among adults hospitalized with CAP compared with the general population. Results must be carefully analyzed given the heterogeneity of the studies. At a clinical level, this increase in AMI incidence in patients with CAP should be taken into account in order to give the best therapeutic management to such patients. Disclosures All authors: No reported disclosures.

The main purpose of this paper is to present an analytical approach of the self-proclaimed “new socialism of the XXI Century” in the context of the transformations undertaken by the so-called “Bolivarian revolution”.The reforms undertaken by referring to the ideology of XXI century socialism in these countries were characterized by an intensification of the process of transformation of the state structure and the relations between the state and society, continuing with the nationalization of sectors of the economy, the centralizing of the political apparatus of State administration.However, in the last four years, in some countries where the socialism of the XXI Century has been implemented, the civilian population has been demonstrating against this type of regime. Resumen El objetivo principal de este trabajo es presentar un enfoque analítico del autoproclamado "nuevo socialismo del siglo XXI" en el contexto de las transformaciones emprendidas por la llamada "revolución bolivariana". Las reformas emprendidas al referirse a la ideología del socialismo del siglo XXI en estos países se caracterizó por una intensificación del proceso de transformación de la estructura estatal y las relaciones entre el Estado y la sociedad, continuando con la nacionalización de sectores de la economía, la centralización del aparato político de la administración del Estado. Sin embargo, en los últimos cuatro años, en algunos países donde se ha implementado el socialismo del siglo XXI, la población civil se ha estado manifestando en contra de este tipo de régimen.

Resumen Introduccion La Organizacion de Neumonia adquirida en la Comunidad (CAPO, siglas en ingles: Community Acquired Pneumonia Organization) es un estudio observacional internacional en 130 hospitales de un total de 31 paises, para evaluar la gestion actual de los pacientes hospitalizados con neumonia adquirida en la comunidad (NAC). Utilizando la base de datos centralizada de CAPO, se realizo este subestudio con el objetivo de evaluar el grado de cumplimiento con las guias nacionales en Venezuela, para definir en que areas se puede intervenir para mejorar la atencion del paciente hospitalizado con NAC. Metodos En este estudio retrospectivo observacional, se usaron indicadores de calidad para evaluar la atencion de pacientes hospitalizados con NAC en 8 centros de Venezuela. El nivel de cumplimiento fue clasificado como optimo (> 90%), intermedio (60-90%), y bajo ( Resultados Se enrolaron 454 pacientes con NAC. El tratamiento empirico administrado dentro de las 8 horas de la admision fue optimo (96%), el resto de los indicadores mostraron un bajo nivel de cumplimiento ( Conclusiones Podemos decir que existen muchas areas en el manejo de las NAC en Venezuela que no se efectuan de acuerdo a las guias nacionales de la SOVETHORAX1. En todo proceso de mejora de calidad la primera etapa es la evaluacion de la diferencia entre lo recomendado y lo que se efectua en la practica clinica diaria. Este estudio cumple con este primer paso, pero el desafio a futuro es implementar los procesos necesarios para mejorar el manejo de la NAC en Venezuela.

Introduction The Community-Acquired Pneumonia Organization (CAPO) is an international observational study in 130 hospitals, with a total of 31 countries, to assess the current management of hospitalized patients with community-acquired pneumonia (CAP). Using the centralized database of CAPO was decided to conduct this study with the aim of evaluating the level of adherence with national guidelines in Venezuela, to define in which areas an intervention may be necessary to improve the quality of care of hospitalized patients with CAP. Methods In this observational retrospective study, quality indicators were used to evaluate the management of hospitalized patients with CAP in 8 Venezuelan's centers. The care of the patients was evaluated in the areas of: hospitalization, oxygen therapy, empiric antibiotic therapy, switch therapy, etiological studies, blood cultures indication, and prevention. The compliance was rated as good (>90%), intermediate (60%–90%), or low ( Results A total of 454 patients with CAP were enrolled. The empiric treatment administered within 8 h of the patient arrival to the hospital was good (96%), but the rest of the indicators showed a low level of adherence ( Conclusion We can say that there are many areas in the management of CAP in Venezuela that are not performed according to the national guidelines of SOVETHORAX.1 In any quality improvement process the first step is to evaluate the difference between what is recommended and what is done in clinical practice. While this study meets this first step, the challenge for the future is to implement the processes necessary to improve the management of CAP in Venezuela.

Background PsA has a higher heritability than PsV, indicating the existence of additional PsA-specific genetic factors. To date, however, the specific genetic basis underlying PsA is poorly understood. Objectives The objective the present study was to identify new genetic variation specifically associated with PsA risk. Methods In order to characterize the genetic basis of PsA, we performed a GWAS meta-analysis at the single-marker level as well as at the pathway level (GWPA). A cohort of 835 PsA patients and 1,558 controls from the Spanish population was genotyped for >550,000 SNPs. GWAS data from a second cohort of 1,430 PsA patients and 1,417 controls from the North American population was also used. In order to confirm the specificity of the new genetic variation associated with PsA risk, we analyzed the association with purely cutaneous psoriasis (PsC, n=614) and rheumatoid arthritis (RA, n=1,191). We performed a pharmacogenetic analysis to investigate the new PsA-specific pathways as a source for drug discovery in PsA. Results GWAS meta-analysis identified a new association between B3GNT2 gene and PsA (P Conclusions The present study represents an important step towards the characterization of the genetic factors specific to PsA risk. Disclosure of Interest None declared

Background Interstitial lung disease (ILD) is an extra-articular manifestation of Rheumatoid Arthritis (RA), has been related with a poor prognosis. However, there is a lack of clinical data regarding its evolution with different treatment approaches. Objectives Our aim was to assess clinical features and evolution of ILD in a cohort of RA patients from a tertiary hospital Methods Single-centre retrospective observational study including all patients diagnosed with ILD with a previous or posterior diagnosis of RA evaluated from January 2007 to December 2016 in the Rheumatology Department of a university hospital. Variables analysed: age, sex, smoking status, duration of RA, presence and titers of ACPA (antiCCP2) and rheumatoid factor (RF), presence of erosions, use of glucocorticoids (GC), synthetic and biological DMARDs before and after ILD diagnosis and presence of other extra-articular manifestations. We also analysed: duration of ILD, HRCT (High Resolution Computed Tomography) patterns and pulmonary function tests (PFT) at baseline and during follow-up to assess the evolution of the disease. The PFT results were evaluated according to the American Thoracic Society/European Respiratory Society definitions (1). Results Twenty-one patients (18 women) were included, mean age 68. 4±11.9, mean RA duration 12.3±8.2 years. 9.5% were current smokers and 33.3% former smokers. 61.9% were ACPA + (52.4% with high basal titers, median ACPA titers: 698) and 81% RF+ (47.6% with high basal titers). 71.4% had erosions and 5 patients (23.8%) had extra-articular manifestations, mainly rheumatoid nodules. RA diagnosis was made after that of ILD in 4 patients; mean elapsed time 1.56±1.26 years. In the other 17 patients, the mean duration of RA until ILD diagnosis was 11.2±7.2 years. Currently 17 subjects (85%) receive GC; 4 (19%) in monotherapy and 11 (57.9%) synthetic DMARDs (5 methotrexate, 3 leflunomide (LEF), 1 hydroxychloroquine (HCQ) and 2 with double therapy (HCQ/AZA and HCQ/LEF)). Four patients are currently treated with biological therapy (2 abatacept (ABA), 1 rituximab and 1 etanercept (ETN)), all of them in monotherapy. Five patients received TNFi prior to ILD diagnosis (3 ETN, 1 infliximab and 1 adalimumab). Biological therapy was withdrawn in 3 cases and switched to ABA in the two remaining ones. The median duration of EPID was 2.5 (range 0.7–11.9) years. HRCT patterns were: non-specific interstitial pneumonia (NSIP) 52.9%, usual interstitial pneumonia (UIP) 17.6%, cryptogenic organized pneumonia (COP)11. 8%, and other patterns 17.7%. 14 patients had baseline and follow-up PFT: 9 (64.3%) remained stable; 3 (21.4%) improved and 2 (14.3%) worsened (1 had received previous ETN). There was a trend for worsening of PFT in patients with UIP pattern. No patient died from ILD during this period Conclusions In our RA-ILD cohort, NSIP was the most common HRCT pattern and PFT remained stable in most patients during follow-up. Five patients (23.8%) had received TNFi prior to ILD diagnosis and only one of them showed worsening of PFT during ETN treatment, with clinical improvement after withdrawal. References Pellegrino R et al. Eur Respir J. 2005;26:94868. Disclosure of Interest None declared

Background During the development of recommendations and implementation aids of the GECOAx project, the importance of avoiding certain situations was highlighted. Objectives To recognize what prescriptions, risk assessments, or preventive strategies are wrong practices and should thus be avoided in clinical practice. To establish not to do recommendations in the management of the comorbidity of AxSpA. Methods A multidisciplinary group was selected [10 rheumatologists, 1 internist, 1 cardiologist, 1 gastroenterologist, 1 psychologist and 2 family physicians]. With the support of 3 methodologists, and after interactions aimed to edit a document for the management of comorbidity launched by the same panel, a list of Not to do recommendations was issued. In a discussion meeting, evidence was provided to support the recommendations, items without sufficient basis were removed, and the final list was produced. Results A summary list of Not to do recommendations (Table 1) was issued. Conclusions These recommendations aim to avoid making common mistakes in clinical practice and to help better management of frequent comorbidity in patients with AxSpA. Acknowledgements This project was funded by Merck Sharp & Dohme Spain. Merck Sharp & Dohme had no influence on either the development of the project or the final content of the manuscript. Disclosure of Interest None declared

Background Some studies have described a higher rate of osteoporosis in axial spondyloarthritis (AxSpA). However, there are still some doubts about whether vertebral fractures (VF) should be a concern in AxSpA patients Objectives To evaluate the prevalence and incidence of VF in AxSpA Methods A systematic review was performed in Medline, Embase and Cochrane Library databases limited to studies published from Jan/2006 to Dec/2015) in Spanish, Italian and English. Search strategy combined synomyms of AxSpA, fractures, plus a filter study type. We selected cross-sectional or longitudinal studies estimating the prevalence and/or incidence of VF in adult AxSpA patients Results The search retrieved 3944 references which after screening by title and abstract ended in 90 studies to study in depth. Finally, 12 estudies were included. The majority of the studies evaluated the VF prevalence, and only 2 studies evaluated the incidence of VF. Prevalence estimates depended on VF definitions, varying between 4.1% (clinically diagnosed VF) and 32.4% (morphometric fracture by Genant definition). Table 1 shows all studies included and their data Conclusions The published studies that focus on VF in AxSpA are very heterogeneous, but in general showed a slight increase in the VF prevalence. More studies are need focused on VF incidence in AxSpA Acknowledgements Funding: This Project was funded by Merck Sharp & Dohme Spain. Merck Sharp & Dohme did not influenced neither the development of the review nor the confection of the abstract. Disclosure of Interest None declared

Background The management of comorbidity in patients with axial spondyloarthritis (Ax-SpA) needs improvement; the implementation of clinical practice guidelines is still deficient and heterogeneous. Objectives To prioritise comorbidities in Ax-SpA and to elaborate practical aids for their identification and follow-up. Methods A multidisciplinary panel [10 rheumatologists (6 experts in Ax-SpA), 2 family doctors, 1 internist, 1 cardiologist, 1 gastroenterologist, 1 psychologist and 3 methodologists] prioritised, in a discussion group, a list of comorbidities based on frequency and impact. Each comorbidity was discussed largely and systematic reviews were performed to support or discard items. In a second meeting, items to be included were presented, discussed, and those with lower priority disregarded. Results The panel produced a checklist for health professionals and another for patients. Each item is supported by arguments and references. Table 1 shows, schematically, the items included in the checklists. Conclusions These checklists are intended to facilitate the systematic evaluation of co-morbidity associated with Ax-SpA, thus allowing an earlier detection and better control and management of these patients by the rheumatologist. Acknowledgements This project was funded by Merck Sharp & Dohme Spain. Merck Sharp & Dohme had no influence on either the development of the project or the final content of the abstract. Disclosure of Interest None declared

Resumen Objetivo Analizar la frecuencia y caracteristicas de la reduccion de dosis de farmacos biologicos en una cohorte de pacientes con artritis cronica, en condiciones de practica clinica de un hospital de tercer nivel. Material y metodos Estudio descriptivo y transversal, que incluyo a todos los pacientes visitados consecutivamente durante 6 meses(junio de 2011-noviembre de 2011) por un solo investigador, con pacientes que habian recibido al menos una dosis de farmaco biologico durante el ano 2011. Resultados Se incluyeron 153 pacientes: artritis reumatoide (AR) (n = 82), espondilitis anquilosante (n = 29), artritis psoriasica (n = 20)y grupo miscelanea (n = 22) con una evolucion media de 14,9 ± 7,7 anos. En el momento del analisis, 70 pacientes (45,7%) estaba con dosis reducida (un 50% en el grupo miscelanea; un 50% en artritis psoriasica; un 48,2% en espondilitis anquilosante, y un 42,6% en AR). El tiempo medio de reduccion de dosis fue de 17,4 ± 17,5 meses. Los farmacos biologicos mas utilizados a dosis reducidas fueron: etanercept, adalimumab y tocilizumab; el 57,6, el 54,9 y el 40 respectivamente de los pacientes tratados con estos agentes lo hacian a dosis reducidas. Los pacientes con dosis reducidas en comparacion con aquellos con dosis normales tenian un mismo tiempo de evolucion de la enfermedad, pero recibian menos FAME, glucocorticoides y AINE, con un tiempo similar de uso del agente biologico. Los pacientes con AR y dosis reducidas tenian, en el momento del analisis, mayores indices de remision que los pacientes con dosis normales (82,9 vs. 34%, p Conclusion En nuestra practica clinica, el 45,7% de los pacientes con artritis cronica reciben terapia biologica a dosis reducidas, tras haber alcanzado la remision o baja actividad a dosis estandares, manteniendo la mayoria de ellos un buen control de la enfermedad.

Background Historically, endemic Klebsiella pneumoniae carbapenemase (KPC) has accounted for the majority of carbapenem-resistant Enterobacteriaceae (CRE) in Los Angeles County (LAC). The LAC Department of Public Health (DPH) initiated enhanced CRE surveillance in 2016 to determine CRE prevalence and track emerging non-KPC resistance mechanisms (IMP, NDM, OXA, and VIM) among CRE to describe characteristics and identify local epidemiology for novel multi-drug-resistant organism (N-MDRO) infection and colonization. Methods CRE isolates were voluntarily submitted by local clinical laboratories for mechanism detection by LAC Public Health Laboratory via MALDI-TOF and Nanosphere BC-GN. Baseline isolates were collected in 2016. Results are then presented by year through 2018. For N-MDRO cases, LACDPH interviewed healthcare facility (HCF) staff and cases to obtain case characteristics. Data were analyzed via Microsoft Access and SAS. Results CRE surveillance isolates were voluntarily submitted by 31 labs representing 34% (34/96) LAC hospitals and 1 large regional lab serving 60% of skilled nursing facilities from January 2016 to December 2018. LACDPH tested 1438 CRE isolates during the study period, 1168 (81%) were carbapenemase producing (CP). The proportion of CP CRE and KPC CRE declined over the study period (Table 1). NDM was the most common non-KPC (n = 30) followed by OXA (n = 28). The proportion of CRE with no genotypic marker increased over the course of the study. Case characteristics were obtained from 41 non-KPC CP CRE cases; median age was 66 years (range: 6–94 years); 12 (29%) expired. Among the 41 cases, 20 (49%) had a central line; 11 (27%) had surgery; 14 (34%) had antibiotics in the 6 months prior to culture date. Of the 41 cases, 11 (27%) had international healthcare exposure within 12 months with an invasive procedure and/or antibiotics. Conclusion Surveillance in a large urban setting suggests the molecular epidemiology of CRE is changing, with declining prevalence of KPC, increasing metallo-β-lactamase CP, and large proportion of isolates without resistance markers detected. Given the worrisome trends in non-KPC CRE, more systematic surveillance is warranted, potentially using more robust molecular epidemiology. Disclosures All authors: No reported disclosures.

Background: Stromal derived factor-1α (sdf-1α), a chemoattractant chemokine, plays a major role in tumor growth, angiogenesis, metastasis, and in embryogenesis. The sdf-1α signaling pathway has also been shown to be important for somite rotation in zebrafish (Hollway et al., 2007). Given the known similarities and differences between zebrafish and Xenopus laevis somitogenesis, we sought to determine whether the role of sdf-1α is conserved in Xenopus laevis. Results: Using a morpholino approach, we demonstrate that knockdown of sdf-1α or its receptor, cxcr4, leads to a significant disruption in somite rotation and myotome alignment. We further show that depletion of sdf-1α or cxcr4 leads to the near absence of β-dystroglycan and laminin expression at the intersomitic boundaries. Finally, knockdown of sdf-1α decreases the level of activated RhoA, a small GTPase known to regulate cell shape and movement. Conclusion: Our results show that sdf-1α signaling regulates somite cell migration, rotation, and myotome alignment by directly or indirectly regulating dystroglycan expression and RhoA activation. These findings support the conservation of sdf-1α signaling in vertebrate somite morphogenesis; however, the precise mechanism by which this signaling pathway influences somite morphogenesis is different between the fish and the frog. Developmental Dynamics 243:509–526, 2014. © 2013 Wiley Periodicals, Inc.

In this paper, we present a clock recovery system implemented on field programmable gate array and integrated to the Gigabit Ethernet media converter for PMMA SI-POF developed within the framework of the POF-PLUS EU Project. We demonstrate timing synchronizing using only one sample per symbol from a highly distorted and attenuated 2-PAM signal without requiring any sort of preequalization. This is achieved by means of a hybrid analog-digital PLL with a timing error detector based on a modified version of the Muller and Mueller algorithm, a loop filter, and a VCXO.

There is little recent information on sex-specific outcomes of patients with community-acquired pneumonia (CAP). The objective of this study was to determine whether female sex is associated with better clinical outcomes in hospitalised patients with CAP. A secondary analysis was conducted by the Community Acquired Pneumonia Organization regarding male and female patients with CAP from 80 hospitals in 17 countries from June 1, 2001 to August 2, 2011. Outcomes were time to clinical stability, length of stay and in-hospital and 28-day mortality. Propensity-adjusted, multivariate regression models were used to predict the probability of occurrence of each of the study outcomes. There were 6718 patients in this study, of whom 40% were female. The adjusted hazard ratio (HR) for time to clinical stability was 0.91 (95% CI 0.85-0.97; p=0.005). The adjusted HR for length of stay was 0.94 (95% CI 0.88-1.01; p=0.089). The adjusted risk ratio for in-hospital mortality was 1.04 (95% CI 0.86-1.24; p=0.717), and for 28-day mortality was 1.15 (95% CI 1.02-1.30; p=0.018). This study demonstrates that the epidemiology of CAP may be changing, and that females have worse outcomes for CAP than males. They are more likely to take longer to reach clinical stability, have longer hospital stays and are 15% more likely to have died after 28 days. Current pneumonia scoring systems may need to be revised regarding female mortality risk.

Background Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals. Methods This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as < 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value Results A total of 70 women and 90 men were included in the study. Median age was 41 years (19) for women and 34 years (19) for men (P < 0.001). Virologic suppression was documented in 76% of women and 64% of men (p 0.166). Immune recovery was documented in 60% of women and 68% of men (p 0.323). Multivariate analysis of virologic success is shown in Figure 1 and immunologic recovery is shown in Figure 2. Conclusion In our study, gender was not found to be associated with differences in response to ART. As expected, drug abuse continues to be an independent variable associated with lack of virologic suppression. If one of the goals of treatment is to achieve a rapid immunologic response, our study may indicate that regimens containing protease inhibitors should be the ones selected. Disclosures All authors: No reported disclosures.

SummaryBackgroundThe Pneumonia Severity Index (PSI) and CRB-65 are scores used to predict mortality in patients with community-acquired pneumonia (CAP). It is unknown how well either score predicts time to clinical stability in hospitalized patients with CAP. Thus, it is also not known which score predicts time to clinical stability better.MethodsA secondary analysis of 3087 patients from the Community-Acquired Pneumonia Organization (CAPO) database was performed. Time-dependent receiver-operator characteristic (ROC) curves for time to clinical stability were calculated for the PSI and CRB-65 scores at day seven of hospitalization. Secondary outcomes were to assess the relationship of the PSI and CRB-65 to in-hospital mortality and length of stay (LOS). ROC curves for LOS and mortality were calculated.ResultsThe area under the ROC curve (AUC) for time to clinical stability by day seven was 0.638 (95% CI 0.613, 0.660) when using the PSI, and 0.647 (95% CI 0.619, 0.670) while using the CRB-65. The difference in AUC values was not statistically significant (95% CI for difference of −0.03 to 0.01). However, the difference in the AUC values for discharge within 14 days (0.651 for PSI vs 0.63 for CRB-65, 95% CI for difference 0.001–0.049), and 28-day in-hospital mortality (0.738 for PSI vs 0.69 for CRB-65, 95% CI for difference 0.02–0.082) were both statistically significant.ConclusionsThis study demonstrates a moderate ability of both the PSI and CRB-65 scores to predict time to clinical stability, and found that the predictive accuracy of the PSI was equivalent to that of the CRB-65 for this outcome.

In this paper we present the latest results from the POF-PLUS EU Project, demonstrating record transmission of a Gigabit Ethernet compliant stream over 75m of 1mm PMMA SI-POF with 2.5 dB system margin, and over 50 m with 7 dB system margin, in both cases using commercial RC-LED. We believe this is an unprecedented results, showing for the first time that the target distance of 50 meters is reachable with a large system margin. The results were made possible by a careful optimization of the physical layer architecture, which is explained in detail in this paper. The system is experimentally demonstrated over realistic digital stream at the transmitter and real time processing at the receiver.

We report the resistance rates of Staphylococcus aureus to non-beta-lactam antimicrobials from The Surveillance Network Database-USA (Eurofins-Medinet, Chantilly, VA). Specimens studied were from lower respiratory tract, wounds, and blood. Patients were stratified by age group and patient setting. There were 2,053,219 isolates of S. aureus and 973,116 of methicillin-resistant S. aureus (MRSA). The MRSA rate increased until 2004 and then leveled off. MRSA showed decreasing resistance to tetracycline and trimethoprim-sulfamethoxazole (TMP-SMX). By age group, the greatest MRSA rate increase was for individuals 17 years and younger. Non-beta-lactam antimicrobials and particularly TMP-SMX should be considered therapeutic options for staphylococcal infections.

Xenopus laevis offers unprecedented access to the intricacies of muscle development. The large, robust embryos make it ideal for manipulations at both the tissue and molecular level. In particular, this model system facilitates the ability to fate map early muscle progenitors, visualize cell behaviors associated with somitogenesis, and examine the role of signaling pathways that underlie induction, specification, and differentiation of cells that comprise the musculature system. Several characteristics that are unique to X. laevis include myogenic waves with distinct gene expression profiles and the late formation of dermomyotome and sclerotome. Furthermore, myogenesis in the metamorphosing frog is biphasic, facilitating regeneration studies. In this review, we describe the morphogenetic movements that shape the somites and discuss signaling and transcriptional regulation during muscle development and regeneration. With recent advances in gene editing tools, X. laevis remains a premier model organism for dissecting the complex mechanisms underlying the specification, cell behaviors, and formation of the musculature system.

The aim of the present study was to define the prevalence, characteristics, risk factors and impact on clinical outcomes of acute myocardial infarction (AMI) versus other cardiovascular events (CVEs) in patients with community-acquired pneumonia (CAP).This was an international, multicentre, observational, prospective study of CAP patients hospitalised in eight hospitals in Italy and Switzerland. Three groups were identified: those without CVEs, those with AMI and those with other CVEs.Among 905 patients, 21 (2.3%) patients experienced at least one AMI, while 107 (11.7%) patients experienced at least one other CVE. Patients with CAP and either AMI or other CVEs showed a higher severity of the disease than patients with CAP alone. Female sex, liver disease and the presence of severe sepsis were independent predictors for the occurrence of AMI, while female sex, age >65 years, neurological disease and the presence of pleural effusion predicted other CVEs. In-hospital mortality was significantly higher among those who experienced AMI in comparison to those experiencing other CVEs (43% versus 21%, p=0.039). The presence of AMI showed an adjusted odds ratio for in-hospital mortality of 3.57 (p=0.012) and for other CVEs of 2.63 (p=0.002).These findings on AMI versus other CVEs as complications of CAP may be important when planning interventional studies on cardioprotective medications.

To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels.We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]).Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with ≥1 swollen joint (1.74 μg/ml versus 3.04 μg/ml; P = 0.010). Using DAS28 ≥2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was ≥2.47 μg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (ρ = -0.671, P 0.001) and IFX (ρ = -0.729, P = 0.017).Calprotectin may more accurately discriminate disease activity in RA patients receiving TNFi than acute-phase reactants, even in patients with low inflammatory activity.

The aim of the present study was to define the prevalence, characteristics, risk factors and impact on clinical outcomes of acute myocardial infarction (AMI) versus other cardiovascular events (CVEs) in patients with community-acquired pneumonia (CAP). This was an international, multicentre, observational, prospective study of CAP patients hospitalised in eight hospitals in Italy and Switzerland. Three groups were identified: those without CVEs, those with AMI and those with other CVEs. Among 905 patients, 21 (2.3%) patients experienced at least one AMI, while 107 (11.7%) patients experienced at least one other CVE. Patients with CAP and either AMI or other CVEs showed a higher severity of the disease than patients with CAP alone. Female sex, liver disease and the presence of severe sepsis were independent predictors for the occurrence of AMI, while female sex, age >65 years, neurological disease and the presence of pleural effusion predicted other CVEs. In-hospital mortality was significantly higher among those who experienced AMI in comparison to those experiencing other CVEs (43% versus 21%, p=0.039). The presence of AMI showed an adjusted odds ratio for in-hospital mortality of 3.57 (p=0.012) and for other CVEs of 2.63 (p=0.002). These findings on AMI versus other CVEs as complications of CAP may be important when planning interventional studies on cardioprotective medications., Acute myocardial infarction is associated with specific risk factors and accounts for worse outcomes in CAP patients http://ow.ly/QhT2t

Several national and international organizations have developed and published guidelines for the treatment of patients with community-acquired pneumonia (CAP). Guidelines from Europe, the US, Canada and Latin America classify patients in different groups based on the severity of pneumonia, site of care and presence of risk factors for resistant organisms. The initial antibacterial therapy is designed to cover only the likely organisms able to infect a particular group of patients. An evaluation of current guidelines indicates that there are significant similarities in regard to classification of patients and initial antibacterial therapy. One objective of this review is to present the clinician with a practical approach to antibacterial selection based on current published guidelines for CAP.

Members of the receptor-like kinase gene family play crucial regulatory roles in many aspects of plant development, but the ligands to which they bind are largely unknown. In Arabidopsis, the receptor kinase CLAVATA1 (CLV1) binds to the small secreted polypeptide CLV3, and three proteins act as key elements of a signal transduction pathway that regulates shoot apical meristem maintenance. To better understand the signal transduction mechanisms involving small polypeptides, we are studying 25 Arabidopsis CLV3/ESR (CLE) proteins that share a conserved C-terminal domain with CLV3 and three maize ESR proteins. Members of the CLE gene family were identified in database searches and only a few are known to be expressed. We have identified an additional member of the CLE gene family in Arabidopsis, which is more similar in gene structure to CLV3 than the other CLE genes. Phylogenetic analysis reveals that few of the putative CLE gene products are closely related, suggesting there may be little functional overlap between them. We show that 24 of the 25 Arabidopsis CLE genes are transcribed in one or more tissues during development, indicating that they do encode functional products. Many are widely expressed, but others are restricted to one or a few tissue types. We have also determined the sub-cellular localization of several CLE proteins, and find that they are exported to the plasma membrane or extracellular space. Our results suggest that the Arabidopsis CLE proteins, like CLV3, may function as secreted signaling molecules that act in diverse pathways during growth and development.

This study investigated the potential anti-inflammatory activity of 3 macrolide antibiotics, clarithromycin, roxithromycin, and azithromycin, in an in vitro model of transendothelial migration (TEM). Human umbilical vein endothelial cells (HUVECs) were seeded in Transwell inserts, treated with serial dilutions of the antibiotics, and infected with Chlamydia pneumoniae or stimulated with tumor necrosis factor (TNF)-alpha. In HUVECs infected with C. pneumoniae or stimulated with TNF-alpha, both azithromycin and roxithromycin caused significant decreases in neutrophil and monocyte TEM, compared with antibiotic-free controls. Clarithromycin had no detectable effect in either group. Azithromycin caused significant decreases in interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1, whereas roxithromycin significantly decreased IL-8. This study indicates heterogeneity in the anti-inflammatory activity of these antibiotics. Mechanisms of monocyte and neutrophil TEM inhibition by azithromycin and roxithromycin are unclear but may be partially due to inhibition of IL-8 and MCP-1 production.

Background The burden of disease for US adult patients hospitalized with community-acquired pneumonia (CAP) due to S. pneumoniae (Sp) PCV13 vaccine types (VT) is not known. The objective of this study was to determine the incidence, patients’ characteristics, length of stay and mortality for US adults hospitalized with CAP due to Sp-PCV13VT. Methods This was a prospective observational study of adults hospitalized between October 7, 2013 and September 30, 2016 with radiographically confirmed CAP in 19 centers in the US. Patients were included if the following 5 criteria were met: 1) Age 18 years and older; 2) Presence of two or more of the following: fever, hypothermia, chills or rigors, pleuritic chest pain, cough, sputum production, dyspnea, tachypnea, malaise, and abnormal auscultatory findings suggestive of pneumonia; 3) Radiographic finding consistent with pneumonia; 4) Able to provide urine sample; 5) Signed informed consent. The presence of Sp-PCV13VT was investigated using a Luminex-based urinary antigen detection (UAD) assay or serotyping from a positive Sp isolate. Data on patients’ characteristics, length of stay (LOS) and in-hospital mortality (IHM) were collected. Results From a total of 12,055 hospitalized patients with CAP, VT Sp-PCV13 was detected in 552 patients via UAD or culture (4.6%). Among patients hospitalized with CAP due to Sp-PCV13VT, median age was 64 years, and the most common comorbidities were chronic obstructive pulmonary disease (46.2%) and diabetes (27.3%). Median LOS was 6 days, and IHM was 5.4%. There were no clinically significant differences when this population was compared with the population of patients with non-PCV13 VT Sp-CAP. Conclusion In approximately 5% of US adults hospitalized with CAP, the etiologic agent is VT Sp-PCV13. Clinical characteristics and outcomes in this population were similar when compared with the general population of hospitalized patients with CAP. In conclusion, this study indicates a persistent burden of disease for adult patients hospitalized with CAP due to vaccine preventable Sp serotypes. Disclosures All authors: No reported disclosures.

Objectives: Critical limb ischemia complicates peripheral artery disease leading to tissue damage and amputation. We hypothesized that modifying adipose stromal cells (ASCs) to overexpress human vascular endothelial growth factor 165 (VEGF) would limit ischemic muscle damage to a larger extent than nonmodified ASCs. Approach and Results: Rabbits with critical hindlimb ischemia were injected with allogeneic abdominal fat-derived ASCs transfected with plasmid-VEGF165 (ASCs-VEGF; n=10). Additional rabbits received nontransfected ASCs (ASCs; n=10) or vehicle (placebo; n=10). One month later, ASCs-VEGF rabbits exhibited significantly higher density of angiographically visible collaterals and capillaries versus placebo (both P