El diagnóstico en reumatología

Indicaciones básicas del diagnóstico de las enfermedades reumática

Automatic decision support system based on SAR data for oil spill detection

This is the accepted manuscript of the following article: Mera, D., Cotos, J., Varela-Pet, J., G. Rodríguez, P. and Caro, A. (2014). Automatic decision support system based on SAR data for oil spill detection. Computers & Geosciences, 72, pp.184-191Global trade is mainly supported by maritime transport, which generates important pollution problems. Thus, effective surveillance and intervention means are necessary to ensure proper response to environmental emergencies. Synthetic Aperture Radar (SAR) has been established as a useful tool for detecting hydrocarbon spillages on the oceans surface. Several Decision Support Systems have been based on this technology. This paper presents an automatic oil spill detection system based on SAR data which was developed on the basis of confirmed spillages and it was adapted to an important international shipping route off the Galician coast (northwest Iberian Peninsula). The system was supported by an adaptive segmentation process based on wind data as well as a shape oriented characterization algorithm. Moreover, two classifiers were developed and compared. Thus, image testing revealed up to 95.1% candidate labeling accuracy. Shared-memory parallel programming techniques were used to develop algorithms in order to improve above a 25% of the system processing timeThe authors wish to thank the financial support provided by the ‘Deputación da Coruña’ under the ‘Bolsas de Investigación 2013’ programmeS

All-trans retinoic acid inhibits migration and invasiveness of rheumatoid fibroblast-like synoviocytes

[Abstract] Fibroblast-like synoviocytes (FLSs) are pivotal in inflammation and joint damage of rheumatoid arthritis (RA). They acquire an active and aggressive phenotype, displaying increased migration and invasiveness and contributing to perpetuate synovial inflammation and destruction of cartilage and bone. The main current therapies of RA are focused against inflammatory factors and immune cells; however, a significant percentage of patients do not successfully respond. Combined treatments with drugs that control inflammation and that reverse the pathogenic phenotype of FLS could improve the prognosis of these patients. An unexplored area includes the retinoic acid, the main biologic retinoid, which is a candidate drug for many diseases but has reached clinical use only for a few. Here, we explored the effect of all-trans retinoic acid (ATRA) on the aggressive phenotype of FLS from patients with RA. RA FLSs were treated with ATRA, tumor necrosis factor (TNF), or TNF+ATRA, and cell migration and invasion were analyzed. In addition, a microarray analysis of expression, followed by gene-set analysis and quantitative polymerase chain reaction validation, was performed. We showed that ATRA induced a notable decrease in FLS migration and invasion that was accompanied by complex changes in gene expression. At supraphysiological doses, many of these effects were overridden or reverted by the concomitant presence of TNF. In conclusion, these results have demonstrated the therapeutic potential of retinoic acid on RA FLS provided TNF could be counterbalanced, either with high ATRA doses or with TNF inhibitors. SIGNIFICANCE STATEMENT All-trans retinoic acid (ATRA) reduced the rheumatoid arthritis (RA) fibroblast-like synoviocyte migration and invasiveness and down-regulated gene expression of cell motility and migration genes. At supraphysiological doses, some of these effects were reverted by tumor necrosis factor. Therefore, ATRA could be an RA drug candidate that would require high doses or combined treatment with anti-inflammatory drugs.Instituto de Salud Carlos III; PI1701660Instituto de Salud Carlos III; PI1401153Instituto de Salud Carlos III (RETICS); RD16/0012/001

Identificación de las emociones en las diferentes etapas de cáncer infantil

El presente trabajo de grado tiene como propósito identificar las emociones en pacientes que estén comenzando y hayan terminado el tratamiento de cáncer infantil. Este estudio presenta un enfoque cualitativo, en el cual la recolección de información se realizó mediante dos instrumentos, entrevistas semiestructuradas aplicadas a pacientes y cuidadores y talleres de suscitación de emociones realizados con los niños diagnosticados. La selección de los cuatro participantes se realizó a conveniencia debido a que había mayor disponibilidad y acceso a la población en la Fundación Segundos de Vida, la cual alberga niños y adolescentes con cáncer en la ciudad de Bogotá. El análisis de la información se estructuro en dos niveles: intrasujetos e intersujetos, para así lograr observar diferencias y/o convergencias entre los sujetos en las diferentes etapas del cáncer infantil.The purpose of this paper is to identify emotions in patients who are beginning or have finished the treatment of childhood cancer. This study presents a qualitative approach, in which the collection of information was carried out using as a method the semi-structured interview, contextual analysis and workshops adapted for the population. The selection of participants was carried out at convenience because there was a greater availability and access to the population at the Segundos de Vida Foundation, which houses children and adolescents with cancer in the city of Bogotá. An analysis of the interviews was conducted, which focused on comparing the intersubject and intrasubject results in order to observe differences and / or convergences between the subjects in the different stages of childhood cancer.Psicólogo (a)Pregrad

Ultrasonographic assessment of enthesitis in HLA-B27 positive patients with rheumatoid arthritis, a matched case-only study

Introduction HLA-B27 has a modifier effect on the phenotype of multiple diseases, both associated and non-associated with it. Among these effects, an increased frequency of clinical enthesitis in patients with Rheumatoid Arthritis (RA) has been reported but never explored again. We aimed to replicate this study with a sensitive and quantitative assessment of enthesitis by using standardized ultrasonography (US). Methods The Madrid Sonography Enthesitis Index (MASEI) was applied to the US assessment of 41 HLA-B27 positive and 41 matched HLA-B27 negative patients with longstanding RA. Clinical characteristics including explorations aimed to evaluate spondyloarthrtitis and laboratory tests were also done. Results A significant degree of abnormalities in the entheses of the patients with RA were found, but the MASEI values, and each of its components including the Doppler signal, were similar in HLA-B27 positive and negative patients. An increase of the MASEI scores with age was identified. Differences in two clinical features were found: a lower prevalence of rheumatoid factor and a more common story of low back pain in the HLA-B27 positive patients than in the negative. The latter was accompanied by radiographic sacroiliitis in two HLA-B27 positive patients. No other differences were detected. Conclusion We have found that HLA-B27 positive patients with RA do not have more enthesitis as assessed with US than the patients lacking this HLA allele. However, HLA-B27 could be shaping the RA phenotype towards RF seronegativity and axial involvement.The study was supported by grants 10CSA918040PR from the Xunta de Galicia (http://www.sergas.e/MostrarContidos_N3_T01.aspx?IdPaxina=10142) and PI08/0744 of the Instituto de Salud Carlos III (http://www.isciii.es/) that are partially financed by the European Regional Development Fund of the European UnionS

Particular association of clinical and genetic features with autoimmunity to citrullinated α-enolase in rheumatoid arthritis.

OBJECTIVE: To confirm that the presence of anti-citrullinated alpha-enolase peptide 1 (anti-CEP-1) antibodies identifies a subgroup of patients with rheumatoid arthritis (RA). METHODS: DNA and serum samples were obtained from 451 patients with RA and 279 healthy control subjects, all of whom were of Spanish ancestry. Antibodies to cyclic citrullinated peptide (CCP) and CEP-1 were measured by enzyme-linked immunosorbent assay. HLA-DRB1 and the R620W single-nucleotide polymorphism of PTPN22 were genotyped. RESULTS: Anti-CEP-1 and anti-CCP antibodies were observed in 26.8% and 71.2% of the patients with RA, respectively. Most of the patients (86.6%) with anti-CEP-1 antibodies also had anti-CCP antibodies. Erosive arthritis, rheumatoid factor (RF) positivity, and the presence of the HLA shared epitope (especially the DRB1*04 alleles) were disproportionately associated with the group of patients with both antibodies. In addition, evidence of a significant interaction between the shared epitope and the risk allele of PTPN22 was observed only in these patients. In contrast, the association with these clinical and genetic features was weaker in patients with anti-CCP antibodies but lacking anti-CEP-1 antibodies. These results were obtained in patients in whom the prevalence of RA risk factors differed from that in other previously studied patients. CONCLUSION: We observed that autoimmunity against citrullinated alpha-enolase may identify a subset of patients with a higher frequency of joint erosions and RF positivity. In addition, we confirmed the disproportionately large effect of the susceptibility alleles of HLA-DRB1 and their interaction with PTPN22 in this subset of patients. These results extend, confirm, and generalize the evidence supporting the specificity of the anti-CEP-1 antibody-positive subgroup of patients with RA among anti-CCP antibody-positive patients with RA

Inflammatory myopathy in the context of an unusual overlapping laminopathy

Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery–Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot–Marie–Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported. This study aimed to determine the genetic basis of an overlapping syndrome in a patient with heart disease, myopathy, and features of lipodystrophy, combined with severe metabolic syndrome. We evaluated a 54-year-old woman with rheumatoid arthritis, chronic hypercortisolism (endogenous and exogenous), and a history of cured adrenal Cushing syndrome. The patient presented with a complex disorder, including metabolic syndrome associated with mild partial lipodystrophy (Köbberling-like); mild hypertrophic cardiomyopathy, with Wolff–Parkinson– White syndrome and atrial fibrillation; and limb-girdle inflammatory myopathy. Mutational analysis of the LMNA gene showed a heterozygous c.1634G>A (p.R545H) variant in exon 10 of LMNA. This variant has previously been independently associated with FPLD2, EDMD2, LGMD1B, and heart disease. We describe a new, LMNA-associated, complex overlapping syndrome in which fat, muscle, and cardiac disturbances are related to a p.R545H variant.This work was funded by the Instituto de Salud Carlos III (grant number: PI081449) and the European Regional Development Fund, FEDER. In addition, SRG was awarded a Research Fellowship granted by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP)S

Non-Canonical WNT5A Signaling Through RYK Contributes to Aggressive Phenotype of the Rheumatoid Fibroblast-Like Synoviocytes

We hypothesized that WNT5A could contribute to the enhanced migration and invasiveness of rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), which is one of the incompletely understood aspects of the RA FLS aggressive phenotype. This hypothesis is based on the previous evidence of a WNT5A role in both, RA and cell migration. Migration and invasion of RA FLS were assessed after incubation with recombinant Wnt5a (rWnt5a) or silencing of the endogenous WNT5A expression. The expression of WNT5A, WNT receptors, cytokines, chemokines, and metalloproteinases was quantified with RT-PCR. The WNT pathway was explored with gene silencing, antibody and pharmacological inhibition followed by migration assays and phosphoprotein western blots. Here, we reported that rWnt5a promoted migration and invasion of RA FLS, whereas knockdown of the endogenous WNT5A reduced them. These effects were specific to the RA FLS since they were not observed in FLS from osteoarthritis (OA) patients. Also, rWnt5a induced the expression of IL6, IL8, CCL2, CXCL5, MMP1, MMP3, MMP9, and MMP13 from baseline or potentiating the TNF induction, WNT5A signaling required the RYK receptor and was mediated through the WNT/Ca(2+) and the ROCK pathway. These pathways involved the RYK and ROCK dependent activation of the p38, ERK, AKT, and GSK3beta kinases, but not the activation of JNK. Together these findings indicate that WNT5A contributes to the enhanced migration and invasiveness of RA FLS through RYK and the specific activation of ROCK and downstream kinases

ME20-S as a Potential Biomarker for the Evaluation of Uveal Melanoma

PURPOSE: We previously identified the presence of the melanocyte-specific secreted (ME20-S) glycoprotein in secretomes of uveal melanoma (UM) cultures. The aim of this study was to test for the presence and levels of ME20-S in the serum of patients with choroidal nevi and UM and correlate these levels with individual clinical data. METHODS: Serum ME20-S levels were determined by ELISA in 111 patients distributed into four categories (53 choroidal nevi, 30 untreated UM, 11 10-year disease-free [DF] UM, 17 hepatic metastatic UM) and 32 age- and sex-matched controls. ME20-S levels were correlated with individual clinical data. RESULTS: The UM and the metastatic groups showed significantly higher levels of serum ME20-S than the other groups (P < 0.001). ME20-S levels in the DF patients did not differ from those in the control group. In addition, log-transformed serum ME20-S levels showed a positive correlation with the thickness of the lesion mass in UM patients (regression coefficient 0.0689, 95% confidence interval 0.0689-0.1123, R2 = 27.1%). CONCLUSIONS: Elevated ME20-S serum levels are associated with tumor size and advanced stages of UM while low levels are characteristic of DF patients. ME20-S might be a promising serum marker for UM and useful for monitoring metastatic disease

Further Insights into the Gut Microbiota of Cow’s Milk Allergic Infants: Analysis of Microbial Functionality and Its Correlation with Three Fecal Biomarkers

Cow’s milk allergy (CMA) is one of the most prevalent food allergies in children. Several studies have demonstrated that gut microbiota influences the acquisition of oral tolerance to food antigens at initial stages of life. Changes in the gut microbiota composition and/or functionality (i.e., dysbiosis) have been linked to inadequate immune system regulation and the emergence of pathologies. Moreover, omic sciences have become an essential tool for the analysis of the gut microbiota. On the other hand, the use of fecal biomarkers for the diagnosis of CMA has recently been reviewed, with fecal calprotectin, α-1 antitrypsin, and lactoferrin being the most relevant. This study aimed at evaluating functional changes in the gut microbiota in the feces of cow’s milk allergic infants (AI) compared to control infants (CI) by metagenomic shotgun sequencing and at correlating these findings with the levels of fecal biomarkers (α-1 antitrypsin, lactoferrin, and calprotectin) by an integrative approach. We have observed differences between AI and CI groups in terms of fecal protein levels and metagenomic analysis. Our findings suggest that AI have altered glycerophospholipid metabolism as well as higher levels of lactoferrin and calprotectin that could be explained by their allergic status.This research was funded by Instituto de Salud Carlos III (PI17/01087 and PI20/01366) and Fundación Sociedad Española de Alergia e Inmunología Clínica (FSEAIC_2016). It was co-funded by the European Regional Development Fund “Investing in your future” for the thematic network and co-operative research centers ARADyAL RD16/0006/0015 and RD16/0006/0026. T.B-T is supported by FPI-CEU predoctoral fellowship. D.B. acknowledges financial support from Instituto de Salud Carlos III (PI19/00044)