Ramipril Improves Endothelial Function and Increases the Number of Endothelial Progenitor Cells in Patients With Systemic Lupus Erythematosus.

BACKGROUND/OBJECTIVES: Endothelial dysfunction and reduced number of endothelial progenitor cells (EPCs) in peripheral blood are contributing factors to cardiovascular disease in systemic lupus erythematosus (SLE) patients. Endothelial progenitor cell proliferation is regulated by vascular endothelial growth factor (VEGF). Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality in patients with coronary heart disease. METHODS: This was a randomized trial including 37 female SLE patients without cardiovascular risk factors allocated into 2 groups: 19 patients received ramipril 10 mg/d for 12 weeks (IG) and 18 patients maintained without ramipril (CG). Endothelial function was assessed by brachial artery ultrasound measuring flow-mediated dilation, and EPCs were quantified by flow cytometry and cell culture, at baseline and after 12 weeks. Serum VEGF levels were measured by enzyme-linked immunosorbent assay. Statistical analysis was intention to treat. p < 0.05 was considered significant. RESULTS: After 12 weeks, higher flow-mediated dilation (6.17% vs. 11.14%, p < 0.001) was observed in IG, without change in CG (5.37% vs. 5.02%, p = 0.630). Higher number of EPC colony-forming units was also observed in IG (21.3 ± 10.4 vs. 31.6 ± 8.5, p < 0.001), without difference in CG ( p = 0.714). No difference was found in EPCs evaluated by flow cytometry. Vascular endothelial growth factor level increased after 12 weeks in IG ( p = 0.048), with no difference in CG ( p = 0.661). CONCLUSION: Ramipril improved endothelial function and increased the numbers of EPCs evaluated by cell culture and VEGF levels in SLE patients without cardiovascular risk factors. These data suggest that angiotensin-converting enzyme inhibitor bring an extra benefit beyond the hypotensive action and should be considered as a preferred antihypertensive drug in SLE patients.

Effect of probiotics on gastrointestinal symptoms and immune parameters in systemic sclerosis: a randomized placebo-controlled trial.

OBJECTIVES: Changes in the intestinal microbiota have been associated with the pathogenesis of SSc. Probiotics act by modulating the microbiome and the immune response. This study aimed to evaluate the efficacy of probiotics on gastrointestinal (GI) symptoms and immune responses in SSc patients. METHODS: Patients with SSc with a moderate-severe total score on the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA GIT 2.0) instrument were randomly assigned to receive a daily dose of probiotics (Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophillus and Bifidobacterium lactis, 109 colony-forming units per capsule) or placebo for 8 weeks. The primary endpoint was improvement in the UCLA GIT 2.0 total score after 8 weeks. Secondary outcomes included changes in Th1, Th2, Th17 and regulatory T cell circulating levels and in the HAQ Disability Index (HAQ-DI) score. Parameters were assessed at baseline and after 4 and 8 weeks of treatment. RESULTS: A total of 73 patients were randomized to receive probiotics (n = 37) or placebo (n = 36). After 8 weeks, there was no difference in the UCLA GIT 2.0 score between the two groups. At week 8, the probiotic group showed a significant decrease in the proportion of Th17 cells compared with placebo (P = 0.003). There was no difference in the proportion of Th1, Th2 and regulatory T cells or in the HAQ-DI score between the groups. CONCLUSION: Probiotics did not improve GI symptoms in SSc patients. The reduction in Th17 cell levels suggests an immunomodulatory effect of probiotics on SSc. TRIAL REGISTRATION: ClinicalTrials.gov (http://clinicaltrials.gov), NCT02302352.

Evaluation of the effect of sildenafil on the microvascular blood flow in patients with systemic sclerosis: a randomised, double-blind, placebo-controlled study.

OBJECTIVES: To evaluate the effect of sildenafil as add-on therapy on the microvascular blood flow in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). METHODS: In this double-blind, placebo-controlled study, 41 patients with RP secondary to SSc were randomly assigned to receive oral sildenafil 100 mg/day (21 patients, mean age 47.2 years) or placebo (20 patients, mean age 41.6 years) for 8 weeks. Patients were evaluated at baseline, 8 weeks after treatment, and 2 weeks after the end of the treatment. The primary outcome measures were the mean changes in finger blood flow (FBF) measured using laser Doppler imaging before and after cold stimulus at 8 weeks of treatment. Secondary endpoints included frequency and duration of RP attacks, Visual Analog Scale (VAS) score for RP severity, Raynaud's condition score, and serum levels of VEGF and endothelial progenitor cells (EPCs). RESULTS: After 8 weeks of treatment, the sildenafil group presented a significantly higher mean percentage change from baseline in FBF before cold stimulus (p=0.026), and in FBF after cold stimulus (p=0.028) compared with the placebo group. There was a significant improvement in the duration of RP and in the percentage change from baseline to week 8 in the RP VAS score in sildenafil compared with placebo. There were no changes in EPCs and VEGF levels after treatment in either group. CONCLUSIONS: Sildenafil improved digital blood flow and RP symptoms in SSc patients after 8 weeks of treatment, and might be a good therapeutic option for secondary RP.

Identification of NF-κB and PLCL2 as new susceptibility genes and highlights on a potential role of IRF8 through interferon signature modulation in systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) and primary biliary cirrhosis (PBC) are rare polygenic autoimmune diseases (AIDs) characterized by fibroblast dysfunction. Furthermore, both diseases share some genetic bases with other AIDs, as evidenced by autoimmune gene pleiotropism. The present study was undertaken to investigate whether single-nucleotide polymorphisms (SNPs) identified by a large genome-wide association study (GWAS) in PBC might contribute to SSc susceptibility. METHODS: Sixteen PBC susceptibility SNPs were genotyped in a total of 1,616 patients with SSc and 3,621 healthy controls from two European populations (France and Italy). RESULTS: We observed an association between PLCL2 rs1372072 (odds ratio (OR) = 1.22, 95% confidence interval (CI) 1.12 to 1.33, P adj = 7.22 × 10(-5)), nuclear factor-kappa-B (NF-κB) rs7665090 (OR = 1.15, 95% CI 1.06 to 1.25, P adj = 0.01), and IRF8 rs11117432 (OR = 0.75, 95% CI 0.67 to 0.86, P adj = 2.49 × 10(-4)) with SSc susceptibility. Furthermore, phenotype stratification showed an association between rs1372072 and rs11117432 with the limited cutaneous subgroup (lcSSc) (P adj = 4.45 × 10(-4) and P adj = 0.001), whereas rs7665090 was associated with the diffuse cutaneous subtype (dcSSc) (P adj = 0.003). Genotype-mRNA expression correlation analysis revealed that the IRF8 protective allele was associated with increased interferon-gamma (IFN-γ) expression (P = 0.03) in patients with SSc but decreased type I IFN (IFIT1) expression in patients and controls (P = 0.02). In addition, we found an epistatic interaction between NF-κB and IRF8 (OR = 0.56, 95% CI 0.00 to 0.74, P = 4 × 10(-4)) which in turn revealed that the IRF8 protective effect is dependent on the presence of the NF-κB susceptibility allele. CONCLUSIONS: An analysis of pleiotropic genes identified two new susceptibility genes for SSc (NF-κB and PLCL2) and confirmed the IRF8 locus. Furthermore, the IRF8 variant influenced the IFN signature, and we found an interaction between IRF8 and NF-κB gene variants that might play a role in SSc susceptibility.

Decreased numbers of endothelial progenitor cells in patients in the early stages of systemic sclerosis.

INTRODUCTION: Microangiopathy and endothelial dysfunction are present in the early stages of systemic sclerosis (SSc). Defective vasculogenesis mediated by bone marrow-derived endothelial progenitor cells (EPCs) might be involved in the vascular abnormalities found in SSc. OBJECTIVES: To evaluate the circulating EPC levels and EPC subtypes via flow cytometry and early outgrowth colony-forming units (CFUs) in patients with SSc compared to healthy subjects. METHODS: Thirty-nine female SSc patients (30 in the early stages of SSc) and 44 age-matched healthy women were included. Peripheral blood EPCs were quantified using flow cytometry and by counting the early outgrowth CFUs. RESULTS: The EPCs quantified with flow cytometry and the CFU numbers were significantly lower in SSc patients than in control subjects (155.1 ± 95.1 vs. 241.3 ± 184.2 EPC/10(6) lymphomononuclear cells, p=0.011; 15.4 ± 8.6 vs. 23.5 ± 10.9 CFU, p<0.001; respectively), as well as in the group of patients in the early stages of SSc compared to the controls. Patients with digital ulcers had significantly higher CFU counts than those without ulcers (p=0.013). Among patients with the scleroderma pattern on nailfold capillaroscopy, patients with the late pattern had significantly lower EPC levels than those with the early and active patterns (p=0.046). There were no significant correlations of EPCs or CFU levels with RP duration. CONCLUSIONS: The present study revealed decreased EPCs in SSc patients, including those with early disease onset. These findings suggest that defective vasculogenesis occurs in the early phases of the disease. Therefore, EPCs might be an important therapeutic target for the prevention of vascular complications in SSc patients.

Thymopoiesis and regulatory T cells in healthy children and adolescents.

OBJECTIVES: The purpose of this study was to investigate the association between T cell receptor excision circle levels in peripheral blood mononuclear cells and regulatory T cells that co-express CD25 and Foxp3 in healthy children and adolescents of different ages. MATERIALS AND METHODS: The quantification of signal-joint T-cell receptor excision circle levels in the genomic DNA of peripheral blood mononuclear cells was performed using real-time quantitative PCR. The analysis of CD4, CD8, CD25, and Foxp3 expression was performed using flow cytometry. RESULTS: Ninety-five healthy controls (46 females and 49 males) ranging in age from 1 to 18 years were analyzed. The mean T-cell receptor excision circle count in all individuals was 89.095 ± 36.790 T-cell receptor excision circles per microgram of DNA. There was an inverse correlation between T-cell receptor excision circles counts and age (r = -0.846; p<0.001) as well as between the proportion of CD4(+)CD25(+)Foxp3(+) T cells and age (r = -0.467; p = 0.04). In addition, we observed a positive correlation between the amount of CD4(+)CD25(+)Foxp3(+) T cells and the amount of T-cell receptor excision circles per microgram of DNA in individuals of all ages (r = -0.529; p = 0.02). CONCLUSIONS: In this study, we observed a decrease in the thymic function with age based on the fact that the level of T-cell receptor excision circles in the peripheral blood positively correlated with the proportion of regulatory T cells in healthy children and adolescents. These findings indicate that although T-cell receptor excision circles and regulatory T cells levels decrease with age, homeostasis of the immune system and relative regulatory T cells population levels are maintained in the peripheral blood.

Thymopoiesis and regulatory T cells in healthy children and adolescents

OBJECTIVES: The purpose of this study was to investigate the association between T cell receptor excision circle levels in peripheral blood mononuclear cells and regulatory T cells that co-express CD25 and Foxp3 in healthy children and adolescents of different ages. MATERIALS AND METHODS: The quantification of signal-joint T-cell receptor excision circle levels in the genomic DNA of peripheral blood mononuclear cells was performed using real-time quantitative PCR. The analysis of CD4, CD8, CD25, and Foxp3 expression was performed using flow cytometry. RESULTS: Ninety-five healthy controls (46 females and 49 males) ranging in age from 1 to 18 years were analyzed. The mean T-cell receptor excision circle count in all individuals was 89.095¡36.790 T-cell receptor excision circles per microgram of DNA. There was an inverse correlation between T-cell receptor excision circles counts and age (r = -0.846; p<0.001) as well as between the proportion of CD4+CD25+Foxp3+ T cells and age (r = -0.467; p = 0.04). In addition, we observed a positive correlation between the amount of CD4+CD25+Foxp3+ T cells and the amount of Tcell receptor excision circles per microgram of DNA in individuals of all ages (r = -0.529; p = 0.02). CONCLUSIONS: In this study, we observed a decrease in the thymic function with age based on the fact that the level of T-cell receptor excision circles in the peripheral blood positively correlated with the proportion of regulatory T cells in healthy children and adolescents. These findings indicate that although T-cell receptor excision circles and regulatory T cells levels decrease with age, homeostasis of the immune system and relative regulatory T cells population levels are maintained in the peripheral blood.

Errores de enfermería en la atención hospitalaria / Errors of care nursing during hospital staying

Resumen

Los errores ocurren en todas las profesiones, forman parte de la condición humana, sin embargo, son más visibles en el área de la atención a la salud; por ser una de las más complejas y estar llena de incertidumbres. El error debe verse de forma intrainstitucional y no tanto individual o por profesión, por lo que la comunicación debe ser anónima para establecer medidas y estrategias globales con el propósito de reducir al máximo los daños al paciente. Aun cuando la formación del profesional de enfermería ha sido y sigue siendo con expectativas idealistas de perfección, se les socializa para ejercer, sin permitirse tener errores; lo que puede obstaculizar el reconocimiento y aceptación constructiva de los errores propios, o bien puede generar una tendencia a encubrirlos cuando dichos errores sean inevitables. Por tal motivo, este documento pretende crear una cultura acerca del error, como es aprender del error, teniendo una actitud más crítica: analizar los diferentes tipos de errores y los efectos que pueden tener sobre los pacientes de tal forma que se implementen estrategias de prevención.

Summary

Mistakes happen in all professions, they are part of the human condition, however, these are more visible in the area of health care, for being one of the most complex and full of uncertainties. Error should be seen intrainstitutionally rather than individually or by profession, so that communication should be limited to establishing steps and strategies in order to minimize the harm caused to the patient. Although nurse training has been and keeps idealistic expectations of perfection, it is socialized to be practiced, not affording mistakes which may hinder the recognition and acceptancing mistakes constructively, or generate a tendency to cover them up when these errors inevitably occur. Therefore this document seeks to create a conscience about, learning in from errors, taking a more critical attitude: analyzing the different types of errors and potential effects on patients so that prevention strategies can be implemented.