Potential relation of cardiovascular risk factors to disease activity in patients with axial spondyloarthritis

Background: Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA. Methods: A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity. Results: A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 [beta coefficient 0.3 (95% confidence interval (CI) 0.1-0.5), p = 0.001] and ?2 [beta coefficient 0.5 (95% CI 0.3-0.7), p = 0.000] CV risk factors compared with those without CV risk factors. Similarly, patients with 1 [OR 2.00 (95%CI 0.99-4.02), p = 0.053] and ?2 [OR 3.39 (95%CI 1.82-6.31), p = 0.000] CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ?2 over 1 CV risk factor. Conclusion: Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner.Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/ or publication of this article: This research was funded by a grant to MAG-G from the Instituto de Salud Carlos III (ISCIII) (Fondo de Investigación Sanitaria grants PI06/0024, PI09/00748, PI12/00060, PI15/00525, PI18/00043) and the ISCIII RETICS programs (RD12/0009 and RD16/0012)

Molecular characterization of imported and autochthonous dengue in northeastern spain

Dengue is the most significant arbovirus worldwide and a public health threat to nonendemic areas in which Aedes vectors are present. Autochthonous dengue transmission has been reported in several European countries in the last decade. Infected travelers from endemic regions arriving to areas colonized by Aedes albopictus in Europe need to be monitored in surveillance and control programs. We aimed to perform molecular characterization of RT-PCR-positive dengue cases detected in Catalonia, northeastern Spain, from 2013 to 2018. The basic demographic information and the geographical regions of importation were also analyzed. One-hundred four dengue cases were studied (103 imported infections and the first autochthonous case in our region). The dengue virus strains detected were serotyped and genotyped using molecular methods, and phylogenetic analyses were conducted. All four dengue serotypes were detected in travelers, including up to 10 different genotypes, reflecting the global circulation of dengue in endemic areas. The primary travel-related case of the 2018 autochthonous transmission was not identified, but the molecular analysis revealed dengue serotype 1, genotype I of Asian origin. Our results highlight the diversity of imported dengue virus strains and the role of molecular epidemiology in supporting arbovirus surveillance programs

Vaspin in atherosclerotic disease and cardiovascular risk in axial spondyloarthritis: a genetic and serological study

Background: Vaspin is a novel anti-inflammatory adipokine associated with cardiovascular (CV) disease and inflammation in chronic inflammatory conditions different from axial spondyloarthritis (axSpA). Given the high incidence of CV disease (mainly due to accelerated atherosclerosis) exhibited by axSpA patients, we wondered if vaspin could also be a key molecule in this process. However, data on the role of vaspin regarding atherosclerotic disease in the context of axSpA is scarce. For this reason, we aimed to evaluate the implication of vaspin, at the genetic and serological level, in subclinical atherosclerosis and CV risk in axSpA. Methods: This study included 510 patients diagnosed with axSpA. Carotid ultrasound (US) was performed to evaluate the presence of subclinical atherosclerosis. Three vaspin gene variants (rs2236242, rs7159023, and rs35262691) were genotyped by TaqMan probes. Serum vaspin levels were assessed by enzyme-linked immunosorbent assay. Statistical analysis was performed using STATA® v.11.1. Results: Serum vaspin levels were significantly higher in female patients than in males and also in obese patients when compared to those with normal weight (p < 0.05). At the genetic level, we disclosed that the minor allele of rs2236242 (A) was associated with lower serum vaspin levels in axSpA, while the rs7159023 minor allele (A) was linked to higher serum levels (p < 0.05). When the three polymorphisms assessed were combined conforming haplotypes, we disclosed that the TGC haplotype related to high serum levels of vaspin (p = 0.01). However, no statistically significant association was observed between vaspin and markers of subclinical atherosclerosis, both at the genetic and serological level. Conclusions: Our results revealed that vaspin is linked to CV risk factors that may influence on the atherosclerotic process in axSpA. Additionally, we disclosed that serum vaspin concentration is genetically modulated in a large cohort of patients with axSpA.This work was partially supported by funds of a NEXT-VAL grant (NVAL17/10) (Instituto de Investigación Sanitaria IDIVAL) awarded to FG. RL-M is a recipient of a Miguel Servet type I programme fellowship (grant CP16/00033) from the “Instituto de Salud Carlos III” (ISCIII) and co-funded by the European Social Fund, ESF). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) from ISCIII and co-funded by the European Regional Development Fund. VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL18/01). LL-G is supported by funds of a Miguel Servet type I programme fellowship from ISCIII (grant CP16/00033, co-funded by the ESF). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10

Rheumatoid arthritis response to treatment across IgG1 allotype - anti-TNF incompatibility: a case-only study.

INTRODUCTION: We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA). METHODS: The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria. RESULTS: An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication. CONCLUSIONS: Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA

Innovaciones y mejoras en el proyecto tutoría entre compañeros. Curso 2015-2016

Memoria ID-0137. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2015-2016

Characterization of a Large Outbreak by CTX-M-1-Producing Klebsiella pneumoniae and Mechanisms Leading to In Vivo Carbapenem Resistance Development

All extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae isolates from patients admitted to and adult intensive care unit were prospectively documented from 2002 to 2005, when a large outbreak (51 patients affected) of multiresistant ESBL-producing Klebsiella pneumoniae infection was detected. The involvement of a single K. pneumoniae clone was demonstrated by pulsed-field gel electrophoresis. In addition to the ESBL-mediated resistance, the epidemic strain uniformly showed cross-resistance to ciprofloxacin, gentamicin, tobramycin, trimethoprim-sulfamethoxazole, and tetracycline, whereas resistance to the β-lactam-β-lactamase inhibitor combinations was variable. The ESBL involved was CTX-M-1, as demonstrated by isoelectric focusing, PCR amplification, and sequencing. CTX-M-1 as well as the aminoglycoside resistance determinants were encoded in a 50-kb plasmid that could be transferred to Escherichia coli only by transformation. In two of the infected patients, carbapenem resistance development (MICs of 8 to 12, 16, and >32 μg/ml for imipenem, meropenem, and ertapenem, respectively) was documented, both in clinical samples and in intestinal colonization studies. The analysis of the outer membrane proteins of the carbapenem-susceptible and -resistant isolates revealed that the former expressed only one of the two major porins, OmpK36, whereas the latter did not express either of them. In one of the cases, the lack of expression of OmpK36 was demonstrated to be mediated by the interruption of the coding sequence by the insertion sequence IS26. This is the first report of a large outbreak of CTX-M-1-producing Enterobacteriaceae and, curiously, the first documented description in the literature of CTX-M-1 in K. pneumoniae, despite the fact that this enzyme has been found in multiple species. Furthermore, we document and characterize for the first time carbapenem resistance development in CTX-M-1-producing Enterobacteriaceae