Fondo De Investigacion Sanitaria Research Articles

Machine-Learning Model for Mortality Prediction in Patients with Community-Acquired Pneumonia: Development and Validation Study

Background: Pneumonia is the leading infectious cause of mortality globally. Artificial intelligence tools and techniques such as machine learning (ML) are increasingly seen as a suitable manner to increase the prediction capacity of currently available tools in infectious diseases. However, studies evaluating the efficacy of ML methods in enhancing the predictive capacity of existing scores for community-acquired pneumonia (CAP) are limited. We aimed to apply a causal probabilistic network (CPN) model (SepsisFinder) to predict 30-day mortality in patients with CAP. As secondary objective, we pursued validating the ML model using a large cohort of CAP patients. Methods: This was a derivation-validation retrospective study to test the CPN model in its prediction of 30-day mortality in patients hospitalised with CAP. The derivation cohort comprised all consecutive adults with CAP admitted between 2003 and 2016 to a university hospital in Barcelona, Spain. For the validation cohort, we included all consecutive patients with CAP admitted to a university hospital in Valencia, Spain between 2012 and 2018. Findings: The derivation cohort comprised 4,531 patients whilst the validation cohort had 1,034 patients. In the derivation cohort, the AUC of SepsisFinder, CURB-65, SOFA, PSI and qSOFA were 0.801, 0.759, 0.671, 0.799 and 0.642, respectively, for 30-day mortality prediction. In the validation study, the AUC of SepsisFinder was 0.826, concordantly with the AUC (0.801) in the derivation data (p=0.51). The AUC of SepisFinder was significantly higher than those of CURB-65 (0.764, p=0.03) and qSOFA (0.729, p=0.005). However, it did not differ significantly from PSI (0.830, p=0.92) and SOFA (0.771, p=0.14). Interpretation: Sepsisfinder shows potential for improving mortality prediction amongst patients with CAP using structured health data. Additional external validation studies should be conducted to support generalisability. Funding: CIBER de Enfermedades Respiratorias (CIBERES CB06/06/0028), and by 2009 Support to Research Groups of Catalonia 911, IDIBAPS. Declaration of Interest: Dr Cilloniz is the recipient of the SEPAR fellowship 2018, and a grant from the Fondo de Investigacion Sanitaria (PI19/00207). LW is employed on a consulting basis and is a shareholder of Treat Systems ApS. MM is CEO and a shareholder of Treat Systems ApS. Treat Systems ApS is a manufacturer of medical device software for decision support in the field of infectious diseases and clinical microbiology, including TREAT-Lab. All other authors have nothing to declare. Ethical Approval: Institutional approval was provided by the Ethics Committee of the University Hospital La Fe of Valencia (XXXXXXX) and the Comite Etic d’Investigacio Clinica of the Hospital Clinic of Barcelona (2011/0219), which waived the need for informed consent. All data set were anonymously analyzed, and the study was performed following current recommendation of the Declaration of Helsinki.

High circulating SDF-1and MCP-1 levels and genetic variations in CXCL12, CCL2 and CCR5: Prognostic signature of immune recovery status in treated HIV-positive patients.

BackgroundThe underlying mechanisms of incomplete immune reconstitution in treated HIV-positive patients are very complex and may be multifactorial, but perturbation of chemokine secretion could play a key role in CD4+T-cell turnover.MethodsWe evaluated the circulating baseline and 48-week follow-up concentrations of SDF-1/CXCL12, fractalkine/CX3CL1, MCP-1/CCL2, MIP-α/CCL3, MIP-β/CCL4 and RANTES/CCL5, and we estimated their association with CXCL12, CX3CR1, CCR2, CCL5 and CCR5 single nucleotide polymorphisms (SNPs) to investigate multiple chemokine-chemokine receptor signatures associated with immune dysregulation preceding poor immune recovery.FindingsThe circulating concentrations and gene expression patterns of SDF-1/CXCL12 (CXCL12 rs1801157) and MCP-1/CCL2 (CCR2 rs1799864_814) were associated with immune recovery status. CCR2 rs1799864_814 and CCR5 rs333_814 (Δ32) determine the baseline plasma RANTES and MIP-α concentrations, respectively, in participants with poor immune response.InterpretationSDF-1/CXCL12 and MCP-1/CCL2 could be considered prognostic markers of immune failure despite suppressive antiretroviral therapy. The strong linkage disequilibrium (LD) between CCR2 rs1799864_814 and CCR5 rs1800024 indicated that the alleles of each gene are inherited together more often than would be expected by chance.FundingThis work was supported by Fondo de Investigacion Sanitaria and SPANISH AIDS Research Network (ISCIII-FEDER); AGAUR and Gilead Fellowship. FV and YMP are supported by grants from the Programa de Intensificación (ISCIII) and Servicio Andaluz de Salud, respectively. JVG,EY and LR are supported by the 10.13039/501100004587Instituto de Salud Carlos III (ISCIII). AR is supported by Departament de Salut, Generalitat de Catalunya and by the Instituto de Salud Carlos III (ISCIII).

Clinical Outcomes of Patients with COVID-19 and Chronic Inflammatory and Autoimmune Rheumatic Diseases: A Multicentric Matched-Cohort Study

Background: The impact of chronic inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here we compare the outcomes of a cohort of rheumatic patients with a matched control cohort to identify potential risk factors for severe illness. Methods: In this comparative cohort study, we systematically identified hospital PCR+ COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or autoimmune/immunomediated diseases (AI/IMID). Non-rheumatic controls were randomly sampled 1:1, and matched by age, sex, and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, ICU admission, or serious complications. We assessed the association between the outcome and potential prognostic variables, adjusted by COVID treatment, using logistic regression. Findings: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 [IQR 53-78] and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and AI/IMID (40%). Patients were on treatment with glucocorticoids (40%), conventional synthetic disease modifying antirheumatic drugs (csDMARD) (57%), targeted synthetic or biological (ts/bDMARD) (23%), or other immunosuppressants (12%). Most patients (74%) had been hospitalised, and the risk of severe COVID was 31·6% in the rheumatic and 28·1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular, or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe were increased age (OR 5·31; CI 3·14-8·95), male sex (2·13; CI 1·35-3·36) and having an AI/IMID (OR 1·98; CI 1·15-3·41). Interpretation: In patients with chronic inflammatory rheumatic diseases aging, sex and having an AI/IMID but not IA nor previous immunosuppressive therapies were associated with severe COVID-19. Funding Statement: The RIER network was supported by Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III (RD16/0012 RETICS program) and cofinanced by the European Regional Development Fund. Declaration of Interests: None of the authors have competing interests to declare. Ethics Approval Statement: The study was approved by Comite de Etica de la Investigacion del Hospital Universitario 12 de Octubre, CEIm number: 20/160.

Mesothelial Origin of Creeping Fat Progenitors in Crohn's Disease

Background: Our understanding of the origin of human adipose tissue is limited. In this regard, the development of in Crohn's disease is particularly puzzling. The mesothelium has recently emerged as a source of visceral adipose tissue in rodents. We therefore sought to investigate the mesothelial properties of human visceral and subcutaneous adipose tissue and progenitor cells. Additionally, we explored whether the dysfunctional environment of obesity and Crohn's disease influences adipose tissue and the mesothelial/mesenchymal properties of its precursors. Methods: We used a tandem transcriptomic/proteomic approach to evaluate mesothelial and mesenchymal markers in adipose tissue, both in subjects covering a wide range of body-mass index and in patients with Crohn's disease. We also isolated adipose tissue precursors (adipose-derived stem cells) from lean, obese and Crohn's disease fat depots and assessed their mesothelial/mesenchymal properties. Findings: Several mesothelial signature genes (LRRN4, MSLN, KRT8, CDH1, and WT1) were significantly upregulated in human visceral fat when compared to equivalent subcutaneous tissue. These data were corroborated at the protein level by proteomic analysis. No significant differences in mesothelial gene expression were found in visceral fat tissue between lean, obese and morbid-obese subjects and patients with Crohn's disease. However adipose-derived stem cells from mesenteric creeping fat had a markedly distinct mesothelial gene profile as compared with equivalent lean-derived cells, with significantly higher expression of the hallmark mesothelial genes MSLN and WT1, supporting a mesothelial nature of these cells. Interpretation: We present the first direct evidence for a mesothelial signature for human visceral adipose tissue and its progenitor cells, specifically for creeping fat in Crohn's disease. Funding Statement: This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities (PI14/00228 and PI17/01503 to JV, SAF2015-65019-R to SF-V, BFU2015-70454-REDT and BFU2017- 90578-REDT to SF-V and MMM, BFU2016-76711-R to MMM and PI15/00143 and PI18/00037 to CS) co-financed by the European Regional Development Fund (ERDF). The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) (CB07708/0012) is an initiative of the Instituto de Salud Carlos III. AM is a recipient of a postdoctoral fellowship from FJCI-2014-23060 and IJCI-2016-30572. SF-V acknowledges support from the Miguel Servet tenure-track program (CP10/00438 and CPII16/00008) of the Fondo de Investigacion Sanitaria, co-financed by the ERDF. C.S. acknowledges support from the ‘‘Ramon y Cajal’ program from MINECO (RYC2013-13186), cofinanced by the ERDF. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All participants gave their informed consent, and the study was reviewed and approved by the ethics and research committee of University Hospital Joan XXIII in accordance with the tenets of the Helsinki Declaration. Participants of the fat sampling gave their informed written consent. The ethics and research committee of the Hospital Clinico Virgen de la Victoria approved the protocol.

MRNA Biomarker in Anal Cytology: A Feasible Approach for Anal Cancer Screening in Men Who Have Sex with Men Living with HIV

Background: There is a growing interest in developing screening strategies for anal cancer to target high-risk populations. However, cytological and molecular evaluation of anal samples is challenging. We aimed to determine the feasibility of detecting, in anal liquid-based cytology samples, the mRNA of three biomarkers involved in the cell cycle disturbance elicited by human papillomavirus (HPV) infection. The accuracy of this approach in the identification of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia grade 2-3 (HSIL/AIN2-3) was also evaluated. Methods: Two-hundred and fifteen anal cytologies from men having sex with men living with human immunodeficiency virus were evaluated. Patients showing concordant cytological and anoscopy-directed biopsy diagnosis were selected: 70 with a negative cytology and HPV test, 70 with cytology and biopsy showing low-grade SIL (LSIL/AIN1) and 75 with cytology and biopsy of HSIL/AIN2-3. CDKN2A/p16, MKI67 and TOP2A mRNA expression was analyzed by reverse transcription qPCR. HPV detection was performed using the Xpert HPV Assay (Cepheid, Sunnyvale, CA). Adequate material for mRNA analysis was obtained from 199/215 (92.6%) samples. Results: mRNA expression for the three biomarkers was significantly higher in HSIL/AIN2-3 compared with LSIL/AIN1 or negative samples. The estimated specificity for the identification of HSIL/AIN2-3 for a sensitivity established at 70% was 44.7% (95% confidence interval [95%CI] 36.5-53.2) for TOP2A and MKI67 and 54.5% (95%CI 46.0-62.8%) for CDKN2A/p16. Conclusions: mRNA detection of cell biomarkers in anal liquid-based cytology is feasible. Further studies are warranted to confirm the possible role of strategies based on mRNA detection in the secondary prevention of anal cancer. Funding Statement: This work was supported by the Instituto de Salud Carlos III (ICSIII)-Fondo de Investigacion Sanitaria and ERDF ‘One Way to Europe’ (grants PI15/00546 and PI17/00772). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by the institutional ethical review board.

Lung function in early adulthood and health in later life: a transgenerational cohort analysis

Early life events can affect health in later life. We hypothesised that low lung function (FEV1 <80% predicted) in early adulthood (25-40 years) is associated with higher prevalence and earlier incidence of respiratory, cardiovascular, and metabolic abnormalities, and premature death. In this cohort analysis, we tested this hypothesis using data from the Framingham Offspring Cohort (FOC) and validated our observations in CARDIA (an independent cohort) and GenIII (which includes the direct descendants of FOC participants). These were three general population cohorts that included men and women, who were regularly and prospectively followed up to collect extensive clinical, physiological, biological, and imaging information. Main outcomes were prevalence (in early adulthood) and incidence (during follow-up) of comorbidity, and all-cause mortality. χ2 test, unpaired t test, Fisher's exact test, and Cox proportional hazards models were used for data analysis. Differential dropout rates during follow-up were regarded as a potential source of bias. We found that 111 (10%) of 1161 participants in FOC, 338 (13%) of 2648 participants in CARDIA, and 71 (4%) of 1912 participants in GenIII had FEV1 of less than 80% predicted at the age of 25-40 years. These individuals also had higher prevalence of respiratory, cardiovascular, and metabolic abnormalities in early adulthood; higher and earlier (about a decade) incidence of comorbidities during follow-up (39 years vs 47 years in FOC; 30 years vs 37 years in CARDIA, p<0·0001); and higher all-cause mortality than individuals with normal lung function in early adulthood (in FOC, hazard ratio 2·3 [95% CI 1·4-3·7], p=0·001), which was independent of, but additive with, cumulative smoking exposure. In GenIII, we observed that individuals with at least one parent stratified as having low lung function in early adulthood in FOC (n=115) had lower FEV1 in early adulthood (10% had FEV1 of less than 80% predicted; this proportion was 3% in those with both parents classified as normal in FOC [n=248]; p<0·0001); and early adulthood FEV1 of GenIII participants was related (R2=0·28, p<0·0001) to FOC parents' average FEV1 in early adulthood. Low peak lung function in early adulthood is common in the general population and could identify a group of individuals at risk of early comorbidities and premature death. Fondo de Investigacion Sanitaria, Sociedad Española de Neumologia y Cirurgia Torácica, Formació Personal Investigador, Agencia de Gestió d'Ajuts de Recerca 2016, and AstraZeneca Foundation Young Researcher Award.

Correction for Guinea et al., Aspergillus citrinoterreus, a New Species of Section Terrei Isolated from Samples of Patients with Nonhematological Predisposing Conditions.

Volume 53, no. 2, p. [611–617][1], 2015. Page 617: The second paragraph of the Acknowledgments section should read “This study was supported by grants MS09/00055 and PI11/00167 from the Fondo de Investigacion Sanitaria (FIS, Instituto de Salud Carlos III, Madrid, Spain, Plan Nacional de I+D+I

Correction for Escribano et al., Microsatellite (STRAf) Genotyping Cannot Differentiate between Invasive and Colonizing Aspergillus fumigatus Isolates.

Volume 53, no. 2, p. [667–670][1], 2015. Page 669: The second paragraph of the Acknowledgments section should read “This study was supported by grants CP09/00055 and PI11/00167 from the Fondo de Investigacion Sanitaria (FIS, Instituto de Salud Carlos III, Madrid, Spain) and by the European

Corrigendum to “First detection of Aspergillus fumigatus azole resistant strain due to Cyp51A TR46/Y121F/T289A in an azole-naive patient in Spain” [New Microbes New Infect 6 (2015) 33–34

[This corrects the article DOI: 10.1016/j.nmni.2015.04.005.].

Ibrutinib in combination with Rituximab for Relapsed Mantle Cell Lymphoma: An Update for a Phase II Clinical Trial

is an efficient strategy to counteract NF-kB activity, with synergistic antitumoral and pro-apoptotic activities with IRAK inhibition, related to the downregulation of MCL-1. Acknowledgments: Fondo de Investigacion Sanitaria PI12/01536 (to A. L.-G.). This work was carried out at the Esther Koplowitz Center, Barcelona. Grant from Hospital Clinic de Barcelona. 908 Ibrutinib in combination with Rituximab for Relapsed Mantle Cell Lymphoma: An Update for a Phase II Clinical Trial Table 1 The best response related to Ki-67 All n (%) Ki-67 < 50% Ki-67 ‡ 50% Evaluable Patients 50 37 12 ORR 44 (88%) 37 (100%) 6 (50%) CR 22 (44%) 20 (54%) 2 (16%) PR 22 (44%) 17 (46%) 4 (34%) SD 3 (6%) 0 (0%) 3 (25%) PD 3 (6%) 0 (0%) 3 (25%) Duration of Response NR NR NR PFS NR NR NR Michael (Luhua) Wang, MD, Hun Lee, MD, Hubert Chuang, MD, PhD, Nicolaus Wagner-Bartak, MD, Fredrick Hagemeister, MD, Jason R. Westin, MD, Luis Fayad, MD, Felipe Samaniego, MD, MPH, Francesco Turturro, MD, Wendy Chen, Maria Badillo, MSN, Krystle J. Nomie, PhD, Maria DeLa Rosa, Donglu Zhao, MD, Alicia Addison, Ken Young, MD, Richard Champlin, MD, Jorge E. Romaguera, MD, Liang Zhang, MD, PhD Department of Lymphoma/Myeloma, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Lymphoma/ Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hematology, Institute of Hematology and Oncology, Harbin, China; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center,

Coprophagia in a patient with borderline personality disorder

This study was funded in part by the National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD), Fondo de Investigacion Sanitaria (FIS) [grant number PI060092]; Fondo de Investigacion Sanitaria FIS [grant number RD06/0011/0016]; ETES [grant number PI07/90207]; the Conchita Rabago Foundation, the Harriet and Esteban Vicente Foundation, the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBERSAM (Intramural Project, P91B; Rio Hortega CM08/00170 –Dr. Hilario Blasco-Fontecilla), the Alicia Koplowitz foundation, and the National Institutes of Health, USA [grant number K24MH072712]

Elaboration of indicators to assess coordination across levels of care

Introduction: Improvement in coordination across care levels has become one of the priorities for responding to emerging challenges in health care. However, indicators to evaluate comprehensively coordination have been limitedly developed. Aim: To present a set of indicators to comprehensively measure informational and managerial coordination across care levels. Methods: A systematic review of literature to identify indicators was conducted in May 2010. Indicators were analysed to identify attributes of coordination and then, classified according to the 14th International Conference on Integrated Care, Brussels, April 2-4 2014 International Journal of Integrated Care – Volume 14, 01 October – URN:NBN:NL:UI:10-1-116185– http://www.ijic.org/ type, dimension and attribute they address. Indicators were then discussed within an expert team, and adapted or newly developed and its relevance, scientific soundness and feasibility examined. Results: 52 indicators were identified, which addressed 11 attributes. Final set of was composed by 21 indicators: Information transfer is evaluated based on information flow (4) and adequacy of shared information (3). Managerial coordination indicators evaluate care consistency through diagnostic testing (2) and medication (1), care provision at the most appropriate level (2), completion of diagnostic path (1), and follow-up –communication, and follow-up after hospital discharge(4) and accessibility across care levels (4). Conclusion: A set indicators to analyse coordination across care levels has been elaborated, which could be employed to detect strengths and weakness in coordination as well as to benchmarking among providers. Financing, Fondo de Investigacion Sanitaria Carlos III (PI10/00348); European Regional Development Fund (FEDER)

On the chest size of Kebara 2

This research was funded by the Spanish Ministry of Economy and Competitiveness (CGL2012-37279, MINECO), the Leakey Foundation, and PI10/02089 ( Fondo de Investigacion Sanitaria) Ministry of Health, Spain.

Sleep related breathing disorders (SRBD) in patients with chiari type I malformation before and after posterior fossa decompression

Introduction The symptoms in Chiari malformation type I (CM-I) have different presentations, and depends on certain malformation components. Posterior Fosse Decompression (PFD) is certainly first line therapy in CM-I. There are a few case reports demonstrating that effective surgical treatment of CM leads to normalization of SRBD, and the recurrence of SRBD may be an early indicator of recurrence of CM. The aim of this study is to examine the occurrence of sleep apneas in patients with CM I and the impact of decompression surgery on sleep- disordered breathing. Materials and methods Correlative 22 patients with CM-I (11 women and 10 men) with middle age of 39,2 ± 14,2 years with pathological nocturnal polisomnography (PSG) (RDI > 5) underwent a new PSG 3 to 6 month after PFD. Results When we compare sleepiness and Sleep architecture before and after surgery we did not obtain statistically significantly differences in the sleep parameters. Respiratory sleep disorders were predominantly obstructive hypopnea during the supine position. We observe a significant improvement of the total sleep time RDI after surgery (27.5 ± 21.9 & 13.2 ± 18.3), in REM-RDI (30.2 ± 24.9 & 14.1 ± 20.2), and NREM-RDI (22.5 ± 25.0 & 5.7 ± 10.6). After surgery we obtain normal values in RDI ( Conclusion Posterior decompression fosse in Patients with CM-I had a significant improvement of sleep and sleep disordered breathing. Acknowledgements This work has been supported in part by the Fondo de Investigacion Sanitaria (Instituto de Salud Carlos III) with grant PI07/0681, co-financed by the European Regional Development Fund (ERDF) and awarded to Dr. M.A. Poca.

Correction: ISG15 Regulates Peritoneal Macrophages Functionality against Viral Infection

There are errors in the Funding section. The correct funding information is as follow: This work was supported by grants from a FIS grant PI11/00127 (Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and Ministry of Health of Spain, State secretary of R+D and FEDER/FSE), Comunidad de Madrid UAM-CM-CCG10-4911 and UAM-Banco de Santander to SG. This work was also partly supported by NIAID grant U19AI083025 to AG-S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Immunotherapeutic and toxic effects of a triple fusion protein encompassing apolipoprotein A-I, IL-15 and IL-15Ra sushi domain

Event Abstract Back to Event Immunotherapeutic and toxic effects of a triple fusion protein encompassing apolipoprotein A-I, IL-15 and IL-15Rα sushi domain María C. Ochoa1*, Jessica Fioravanti1, Inmaculada Rodriguez2, Sandra Hervas-Stubbs1, Guillermo Mazzolini3, Jesus Prieto1, Pedro Berraondo1 and Ignacio Melero1, 2 1 Fundation for medical applied research, Spain 2 University Hospital of Navarra, Spain 3 Austral university, Argentina Interleukin 15 (IL-15) effects on CD8 T and NK lymphocytes hold promise to treat cancer. Fusion proteins have been engineered to provide IL-15 receptor alpha (IL-15Rα) mediated trans-presentation to lymphocytes and extend the plasma half-life of the cytokine. In this study, we report on a triple fusion protein combining apolipoprotein A-I, IL-15 and IL-15Rα’s sushi domain. Apolipoprotein A-I conveys IL-15 to high-density lipoproteins (HDL), from which the cytokine is trans-presented by the IL-15Rα´s sushi domain. Such a construction was tested by hydrodynamic gene transfer to the liver of mice. Lethal toxicity was observed upon injection of 10μg of the expression plasmid. Mice died from an acute lymphocytic pneumonitis in which T and NK cells dominate a severe inflammatory infiltrate. Importantly, mice devoid of NK cells were not susceptible to such toxicity and mice lacking granzymes A and B also survived the otherwise lethal gene transfer. Lower plasmid doses (<2.5μg) were tolerated and dramatically increased the numbers of NK and memory CD8 T lymphocytes in the liver, spleen and lungs, to the point of rescuing the deficiency of such lymphocyte subsets in IL-15Rα-/- mice. Doses of plasmid within the therapeutic window successfully treated metastatic tumor models, including B16OVA lung metastasis of melanoma and MC38 colon cancer liver metastasis. Sushi-IL15-Apo as a recombinant protein was also bioactive in vivo, became conjugated to HDL and displayed immuno-therapeutic effects against metastatic disease. Acknowledgements Financial support was from MEC/MICINN (SAF2005-03131 and SAF2008-03294 SAF2011-22831), Departamento de Salud del Gobierno de Navarra, European Commission 7th Framework Program (ENCITE) SUDOE-IMMUNONET, Fundacion Mutua Madrileña, Fondo de Investigacion Sanitaria (FIS PI10/00264) and “UTE for project FIMA”. MCO and PB received contracts from Fondo de Investigación Sanitaria. SH-S received contract from Ministerio de Educacion y Ciencia. Keywords: Interleukin-15, interleukin-15 alpha subunit, Apolipoprotein A-I, cancer immunotherapy, Natural Killer cells Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Ochoa MC, Fioravanti J, Rodriguez I, Hervas-Stubbs S, Mazzolini G, Prieto J, Berraondo P and Melero I (2013). Immunotherapeutic and toxic effects of a triple fusion protein encompassing apolipoprotein A-I, IL-15 and IL-15Rα sushi domain. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00766 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 13 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. María C Ochoa, Fundation for medical applied research, Pamplona, Spain, mochnie@unav.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers María C Ochoa Jessica Fioravanti Inmaculada Rodriguez Sandra Hervas-Stubbs Guillermo Mazzolini Jesus Prieto Pedro Berraondo Ignacio Melero Google María C Ochoa Jessica Fioravanti Inmaculada Rodriguez Sandra Hervas-Stubbs Guillermo Mazzolini Jesus Prieto Pedro Berraondo Ignacio Melero Google Scholar María C Ochoa Jessica Fioravanti Inmaculada Rodriguez Sandra Hervas-Stubbs Guillermo Mazzolini Jesus Prieto Pedro Berraondo Ignacio Melero PubMed María C Ochoa Jessica Fioravanti Inmaculada Rodriguez Sandra Hervas-Stubbs Guillermo Mazzolini Jesus Prieto Pedro Berraondo Ignacio Melero Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Anaphylactic reaction to clarithromycin in a child

200 grains/m ofPoaceae, and between 10 and 15 grains/m of Urticaceae. The use of nonparametric methods provided more informative estimations than traditional linear approaches for continuous environmental factors. The advantage of this innovative approach is that we do not need to make any a priori assumption about the functional form of the relationship. In comparison with categorical analyses, this method can be more efficient (3), also removing the need to select cut-off points for categories in an opportunistic manner. We observed evident nonlinearities for the estimated relationships between airborne pollen levels with allergenic capacity and risk of asthma emergency room admissions, updating our previous results (5) and being similar to those described for grass pollen in England (6). Note that GAMs are very conservative at the extremes of the curve, having wide confidence intervals, as the Fig. 1 shows. This is because usually there are few observations at the extremes of the exposure factor, and because of a slight boundary effect inherent in all flexible methods. Furthermore, results can be presented only in relation to a reference category. Then a graphical distortion can lead to misinterpretations as well as the arbitrary selection of the reference point (3). However, the highest risk of asthma morbidity in Madrid was that related to the highest airborne pollen levels when abruptly released into Madrid s environment. This study was funded by the Advisory Committee to the Madrid Regional Asthma Prevention & Control Programme (Comision Asesora del Programa Regional de Prevencion y Control del Asma de la Comunidad de Madrid). Aurelio Tobias had a postgraduate fellowship of Universidad Autonoma de Madrid. Marc Saez was partially funded by Fondo de Investigacion Sanitaria, FIS 00/0010–02.

Routine Laboratory Screening Among Newly Admitted Psychiatric Patients: Is It Worthwhile?

This study compared the prevalence of abnormal results of laboratory tests routinely performed among newly hospitalized psychiatric patients in Spain and the cost-effectiveness of such tests. Routine biochemical tests were performed for 510 newly hospitalized psychiatric patients. For all tests, this study examined the prevalence of values outside the normal range and compared the number needed to screen to find one abnormal result (NNSAR=1/prevalence of abnormal results in the studied population) with the direct cost spent to find one abnormal result (DCSAR=NNSAR x direct cost per test). The prevalence of values outside the normal range ranged from 1% for free thyroxine (FT4) to 36% for total cholesterol. The NNSAR ranged from 2.8 for total cholesterol to 127.3 for FT4. The DCSAR ranged from .38 international dollars of 2000 (I$) for chloride to 402.27 I$ for FT4. There were large differences in the prevalence of abnormal results (NNSAR) and cost-effectiveness (DCSAR) for the laboratory tests routinely performed among newly admitted psychiatric patients.

Routine Laboratory Screening Among Newly Admitted Psychiatric Patients: Is It Worthwhile?

Routine Laboratory Screening Among Newly Admitted Psychiatric Patients: Is It Worthwhile?

150 Differencial Distribution of Cell Death in Hypoxic-Ischemic Brain Injury in Preterm Lambs

The brain damage produced during the hypoxic-ischemic event is one of the major causes of mortality and neurological morbidity in premature and term newborns. The aim of this work was to evaluate the distribution of cell death in the first hours after HI brain injury in fetal lambs. Fifteen near-term lambs at 80–90% of gestation were assigned to two hypoxic-ischemic groups with or without life support (3 h), and a healthy one. Hypoxia-ischemia was induced by partial cord occlusion of the umbilical cord (60min). Lambs were sacrificed and brain fixed by perfusion. Light and transmission electron microscopy, and the TUNEL method for apoptosis were performed. In both treated groups we have observed scattered neurons with necrotic changes and oligodendrocytes-like cells with apoptosis. Necrotic cells were located mainly in subcortical areas whereas apoptotic cells were placed in white and gray matter of cortical areas. Our results suggest that cell death by necrosis involves elements which participate in extrapiramidal pathway and that apoptotic cells were implicated in cortical pathway alteration. Thus, the hipoxic-ischemic injury would produce a disorder in the common final pathway and motor impairment in preterm lambs. This work has been supported by grants from Fondo de Investigacion Sanitaria, Ministerio de Sanidad (FIS01/0110–2), and from the Universidad del Pais Vasco (1/UPV075.327-E-14885/2002 and 9/UPV00077.327–15330/2003 HILARIO).