No evidence of association between common autoimmunity STAT4 and IL23R risk polymorphisms and non-anterior uveitis.

OBJECTIVE: STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. METHODS Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. RESULTS No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). CONCLUSION Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10(-8), OR  = 1.22, CI 95%  = 1.14-1.30; rs2004640: P  = 4.60×10(-7), OR  = 0.84, CI 95%  = 0.78-0.90; rs10488631: P  = 7.53×10(-20), OR  = 1.63, CI 95%  = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10(-22), OR  = 1.75, CI 95%  = 1.56-1.97) better explained the observed association (likelihood P-value  = 1.48×10(-4)), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.

Off-label uses of anti-TNF therapy in three frequent disorders: Behçet's disease, sarcoidosis, and noninfectious uveitis.

Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series.

Preinfarction angina prior to first myocardial infarction does not influence long-term prognosis: a retrospective study with subgroup analysis in elderly and diabetic patients.

BACKGROUND AND HYPOTHESIS Although prodromal angina occurring shortly before an acute myocardial infarction (MI) has protective effects against in-hospital complications, this effect has not been well documented after initial hospitalization, especially in older or diabetic patients. We examined whether angina 1 week before a first MI provides protection in these patients. METHODS A total of 290 consecutive patients, 143 elderly (>64 years of age) and 147 adults (<65 years of age), 68 of whom were diabetic (23.4%) and 222 nondiabetic (76.6%), were examined to assess the effect of preceding angina on long-term prognosis (56 months) after initial hospitalization for a first MI. RESULTS No significant differences were found in long-term complications after initial hospitalization in these adult and elderly patients according to whether or not they had prodromal angina (44.4% with angina vs 45.4% without in adults; 45.5% vs 58% in elderly, P < 0.2). Nor were differences found according to their diabetic status (61.5% with angina vs 72.7% without in diabetics; 37.3% vs 38.3% in nondiabetics; P = 0.4). CONCLUSION The occurrence of angina 1 week before a first MI does not confer long-term protection against cardiovascular complications after initial hospitalization in adult or elderly patients, whether or not they have diabetes.

Popliteal pseudoaneurysm after unicompartmental knee replacement: a case report.

Popliteal pseudoaneurysm is a rare but important complication of knee arthroplasties. To our knowledge, this complication has not been reported previously in the literature after unicompartmental knee arthroplasty. Apart from intraoperatively caused arterial injuries, obese patients and other previous cardiovascular diseases may be potential factors of risks for pseudoaneurysm in knee surgeries. As it is an uncommon complication and it has inconspicuous symptoms, both diagnosis and treatment can be delayed. This means that a high level of suspicion is necessary to prevent serious complications derived from pseudoaneurysms. LEVEL OF EVIDENCE Level IV.

Al lado con la persona afectada por la enfermedad de Alzheimer en Huelva : instrumentos de mejora de la atención

Documento relacionado: Al lado, itinerario de atención compartida : Demencias, Alzheimer (http://hdl.handle.net/10668/487). Publicado en la página web de la Consejería de Salud y Bienestar Social: Consejería de Salud y Bienestar Social / Profesionales / Salud Pública / 'Al Lado' con... / 'Al Lado' con las personas afectadas por Alzheimer.

Could radiotherapy effectiveness be enhanced by electromagnetic field treatment?

One of the main goals in radiobiology research is to enhance radiotherapy effectiveness without provoking any increase in toxicity. In this context, it has been proposed that electromagnetic fields (EMFs), known to be modulators of proliferation rate, enhancers of apoptosis and inductors of genotoxicity, might control tumor recruitment and, thus, provide therapeutic benefits. Scientific evidence shows that the effects of ionizing radiation on cellular compartments and functions are strengthened by EMF. Although little is known about the potential role of EMFs in radiotherapy (RT), the radiosensitizing effect of EMFs described in the literature could support their use to improve radiation effectiveness. Thus, we hypothesized that EMF exposure might enhance the ionizing radiation effect on tumor cells, improving the effects of RT. The aim of this paper is to review reports of the effects of EMFs in biological systems and their potential therapeutic benefits in radiotherapy.

Development of a new tool for assessing health-related quality of life in patients with primary hyperparathyroidism.

BACKGROUND Several studies in recent years have evaluated Health Related Quality of Life (HRQoL) of patients with primary hyperparathyroidism (PHPT). No disease specific questionnaires are available to assess the impact of the disease. The aim of this research is to describe the development of a new disease specific Quality of Life (QoL) questionnaire for use specifically with PHPT patients. METHODS A conceptual model was developed describing the impact of the disease and its symptoms on QoL domains. A literature review was conducted to identify the most relevant domains. A focus group with experts was used to validate the domains; 24 patients were also interviewed to complement the information from the patient's perspective. A content analysis of the interviews was performed to identify items related with the impact of the disease, leading to PHPQoL-V.1 which was presented to a sample of 67 patients. Reliability was assessed by Cronbach's coefficient alpha and item-total score correlations. Validity was assessed by a factor analysis performed to determine the number of domains. Rasch analysis was carried out in order to refine the questionnaire items. RESULTS 259 items were extracted from the interviews that were subsequently reduced to 34 items. Cronbach's coefficient alpha was 0.92. The factor analysis extracted two domains (physical and emotional). After Rasch analysis the questionnaire PHPQoL-V.2 kept 16 items (9 physical and 7 emotional). The questionnaire was developed in a Spanish population and the final version was translated to English through translation and back-translation. CONCLUSION The first disease specific HRQoL questionnaire for PHPT patients (PHPQoL-16) has been developed. Validation studies designed to assess measurement properties of this tool are currently underway.

Guía de práctica clínica para la prevención y cuidados de las úlceras arteriales

Publicaciones complementarias: Folleto: Guía de prevención y cuidado de las úlceras arteriales para personas cuidadoras. Folleto desplegable: Guía rápida de consulta para la prevención y cuidados de las úlceras arteriales.

HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV.

BACKGROUND Multiple Sclerosis (MS) is an autoimmune demyelinating disease that occurs more frequently in women than in men. Multiple Sclerosis Associated Retrovirus (MSRV) is a member of HERV-W, a multicopy human endogenous retroviral family repeatedly implicated in MS pathogenesis. MSRV envelope protein is elevated in the serum of MS patients and induces inflammation and demyelination but, in spite of this pathogenic potential, its exact genomic origin and mechanism of generation are unknown. A possible link between the HERV-W copy on chromosome Xq22.3, that contains an almost complete open reading frame, and the gender differential prevalence in MS has been suggested. RESULTS MSRV transcription levels were higher in MS patients than in controls (U-Mann-Whitney; p = 0.004). Also, they were associated with the clinical forms (Spearman; p = 0.0003) and with the Multiple Sclerosis Severity Score (MSSS) (Spearman; p = 0.016). By mapping a 3 kb region in Xq22.3, including the HERV-W locus, we identified three polymorphisms: rs6622139 (T/C), rs6622140 (G/A) and rs1290413 (G/A). After genotyping 3127 individuals (1669 patients and 1458 controls) from two different Spanish cohorts, we found that in women rs6622139 T/C was associated with MS susceptibility: [χ2; p = 0.004; OR (95% CI) = 0.50 (0.31-0.81)] and severity, since CC women presented lower MSSS scores than CT (U-Mann-Whitney; p = 0.039) or TT patients (U-Mann-Whitney; p = 0.031). Concordantly with the susceptibility conferred in women, rs6622139*T was associated with higher MSRV expression (U-Mann-Whitney; p = 0.003). CONCLUSIONS Our present work supports the hypothesis of a direct involvement of HERV-W/MSRV in MS pathogenesis, identifying a genetic marker on chromosome X that could be one of the causes underlying the gender differences in MS.

Día mundial de la diabetes 2014: la prevención comienza con un desayuno saludable

Boletín semanal para profesionales sanitarios de la Secretaría General de Calidad, Innovación y Salud Pública de la Consejería de Igualdad, Salud y Políticas Sociales

Influencia de un programa de actividad física en niños y adolescentes obesos con apnea del sueño; protocolo de estudio.

Recent studies show an alarming increase in the rate of overweight / obesity among the infant - juvenile population. Obesity in childhood is associated with a significant number of complications, such as sleep apnea syndrome, insulin resistance and type 2 diabetes, hypertension, cardiovascular disease and some cancers. It is estimated that the prevalence of sleep apnea in children is 2-3% in the general population, while in obese adolescents, varies between 13% and 66%, according to various studies. It is associated with impairment of neurocognitive function, behavior, cardiovascular system, metabolic disorders and growth. Sleep apnea is a serious public health problem that increases when children and adolescents are overweight or obese. We hypothesize that aerobic endurance exercise can be an effective treatment for obesity and apnea at the same time. The aim of this study was to determine the influence of physical activity in children and adolescents with overweight / obesity in sleep apnea. An observational, descriptive, prospective, longitudinal study will be carried out in children with sleep apnea and obesity. The universe will be made up of 60 children and adolescents aged between 10 and 18 years, attending the endocrinology service for suffering of obesity in the Hospital Clinico San Cecilio of Granada during the period September 2012-September 2013. The smple will consist of children and adolescents that meet these characteristics and to hom their arents/tutors have authorized through the informed consent. Sleep apnea in children wil be measured by polysomnography and sleep quality questionnaire. There will also be a nutritional assessment by a food frequency questionnaire and an anthropometric assessment. Among the expected results are the lower overweight and obesity in children through the physical activity program. To reduce apnea and to improve sleep quality

Temsirolimus in overtreated metastatic renal cancer with subsequent use of sunitinib: A case report.

During the last decade, we have been developing new therapeutic strategies for the treatment of renal cancer, based on knowledge derived from molecular biology. We report a case of long-term renal metastatic cancer progression despite therapy with sunitinib and interleukin, which are the most active drugs in renal cancer. Disease stabilization for 58 weeks was achieved upon sequential use of temsirolimus, following the occurrence of disease progression during angiogenic therapy. The patient demonstrated excellent tolerance without marked symptoms for 10 months. Hypothyroidism and mumps-related adverse events were present. The survival time from diagnosis to lung metastasis was 8 years. Thus, this case demonstrates promising therapeutic effects of the sequential use of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors during different stages of the disease.

PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia.

We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN) and other renal lesions related to prolonged cold ischemia/reperfusion (IR) in kidneys preserved at 4°C in University of Wisconsin (UW) solution. Material and Methods. We used 30 male Parp1(+/+) wild-type and 15 male Parp1(0/0) knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ) at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ). We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp1(0/0) knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.