New insights into the genetic component of non-infectious uveitis through an Immunochip strategy.

BACKGROUND: Large-scale genetic studies have reported several loci associated with specific disorders involving uveitis. Our aim was to identify genetic risk factors that might predispose to uveitis per se, independent of the clinical diagnosis, by performing a dense genotyping of immune-related loci. METHODS: 613 cases and 3693 unaffected controls from three European case/control sets were genotyped using the Immunochip array. Only patients with non-infectious non-anterior uveitis and without systemic features were selected. To perform a more comprehensive analysis of the human leucocyte antigen (HLA) region, SNPs, classical alleles and polymorphic amino acid variants were obtained via imputation. A meta-analysis combining the three case/control sets was conducted by the inverse variance method. RESULTS: The highest peak belonged to the HLA region. A more detailed analysis of this signal evidenced a strong association between the classical allele HLA-A*2902 and birdshot chorioretinopathy (p=3.21E-35, OR=50.95). An omnibus test yielded HLA-A 62 and 63 as relevant amino acid positions for this disease. In patients with intermediate and posterior uveitis, the strongest associations belonged to the rs7197 polymorphism, within HLA-DRA (p=2.07E-11, OR=1.99), and the HLA-DR15 haplotype (DRB1*1501: p=1.16E-10, OR=2.08; DQA1*0102: p=4.37E-09, OR=1.77; DQB1*0602: p=7.26E-10, OR=2.02). Outside the HLA region, the MAP4K4/IL1R2 locus reached statistical significance (rs7608679: p=8.38E-07, OR=1.42). Suggestive associations were found at five other loci. CONCLUSIONS: We have further interrogated the association between the HLA region and non-infectious non-anterior uveitis. In addition, we have identified a new non-HLA susceptibility factor and proposed additional risk loci with putative roles in this complex condition.

Specific association of IL17A genetic variants with panuveitis.

BACKGROUND/AIMS: A pathogenic role of Th17 cells in uveitis has become clear in recent years. Therefore, in the present study, we aimed to evaluate the possible influence of the IL17A locus on susceptibility to non-anterior uveitis and its main clinical subgroups. METHODS: Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), selected by tagging, were genotyped using TaqMan assays in 353 Spanish patients with non-anterior uveitis and 1851 ethnically matched controls. RESULTS: The case/control analysis yielded a consistent association between two of the analysed genetic variants, rs8193036 and rs2275913, and the presence of panuveitis under a dominant model (pFDR=2.86E-03, OR=2.26, 95% CI 1.42 to 3.59 and pFDR=0.033, OR=1.83, 95% CI 1.13 to 2.97, respectively). Subsequently, a specific association of both polymorphisms with the diffuse form of the disease was evident in the subphenotype analysis when considering this same genetic model (panuveitis vs posterior and intermediate uveitis: rs8193036, p=0.020; rs2275913, p=0.038). Independent effects of rs8193036 and rs2275913 were observed by conditional regression analysis. CONCLUSIONS: Polymorphisms within the IL17A locus show a novel association with panuveitis. Our data agree with the elevated levels of this cytokine that are found in patients with uveitis, supporting a crucial role of Th17 cells in this pathology. SUBTITLE: Our results clearly evidenced the role of IL17A as a novel genetic risk factor for panuveitis, thus suggesting the implication of Th17 cells in the extensive inflammation of the uveal tract that occurs in this subtype of uveitis.

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.

Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.

OBJECTIVE: Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS: Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS: A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION: Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.

Evaluation of the IL2/IL21, IL2RA and IL2RB genetic variants influence on the endogenous non-anterior uveitis genetic predisposition.

BACKGROUND: Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. METHODS: A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. RESULTS: A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P(-value)=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. CONCLUSION: Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility.

Análisis de la experiencia de prohibir el uso de tabaco en la Unidad de Agudos del Hospital de Jerez / Smoking ban in the acute psychiatric unit of Jerez Hospital: analysis of the implementation process

El uso del tabaco en la Unidades Psiquiátricas de Agudos ha sido, hasta hace bien poco, una anomalía generalizada en los establecimientos sanitarios. En el presente trabajo se describe la experiencia llevada a cabo en la Unidad Psiquiátrica de Agudos del Hospital de Jerez de la Frontera (Cádiz) para prohibir totalmente el uso del tabaco en sus instalaciones. Además, se analizan las distintas etapas del proceso que llevó a dicha prohibición, así como los obstáculos y las medidas tomadas para solventarlos. Finalmente, se aportan datos del coste de la medida y de los beneficios aportados(AU)

Smoking in psychiatric inpatient units has been, until recently, a widespread anomaly among health settings. A total smoking ban was implemented in the Acute Psychiatric Unit at Jerez Hospital (Cadiz) and this experience is here described. Different stages of the implementation process, caveats and ways of sorting them out, are then described. Finally, cost and advantages are also presented(AU)

[Risk factors for preterm deliveries in a public hospital]. / Factores asociados con el parto prematuro entre 22 y 34 semanas en un hospital público de Santiago.

BACKGROUND: Preterm births are responsible for 75 to 80% of perinatal mortality. AIM: To determine the factors associated with preterm births, using maternal clinical data, laboratory results and pathological placental findings. PATIENTS AND METHODS: Retrospective study of 642 preterm single births at 22-34 weeks' gestation. Four hundred and seven cases with pathological placental studies were included. Births were subdivided into preterm births as a consequence of a medical indication and spontaneous births with or without premature rupture of membranes (PROM). Risk factors for preterm births were classified as maternal, fetal, placental, indeterminable and unclassifiable. RESULTS: The proportions of preterm births were spontaneous 69% (with PROM 27% and with intact membranes 42%) and medically indicated births 31%. A risk factor associated with prematurity was identified in 98 and 85% of medically indicated and spontaneous births, respectively. Ascending bacterial infection (ABI) was the most frequently associated factor with spontaneous preterm delivery in 51% of women (142/280, p < 0.01) and with preterm births of less than 30 weeks in 52% of women (82/157, p < 0.01). Vaginal or urinary infection with Group B Streptococcus, was the most common clinical condition associated with ABI related deliveries. Hypertension was present in 94 of 127 medically indicated preterm deliveries (preeclampsia in 62% and chronic hypertension in 12%), and in 29% (preeclampsia 24%) of preterm births of more than 30 weeks. Congenital anomalies were mainly associated with a maternal age over 35 years in 15% (14/92) of women. The frequency of placental diseases was higher in spontaneous preterm deliveries (14%) and in pregnancies of more than 30 weeks in (14%). CONCLUSIONS: ABI was the most common factor associated with spontaneous preterm births at 2234 weeks, while preeclampsia is the most common factor associated with medically indicated preterm births.

Factores asociados con el parto prematuro entre 22 y 34 semanas en un hospital público de Santiago / Risk factors for preterm deliveries in a public hospital

Background: Preterm births are responsible for 75 to 80% of perinatal mortality. Aim: To determine the factors associated with preterm births, using maternal clinical data, laboratory results and pathological placental findings. Patients and Methods: Retrospective study of 642 preterm single births at 22-34 weeks' gestation. Four hundred and seven cases with pathological placental studies were included. Births were subdivided into preterm births as a consequence of a medical indication and spontaneous births with or without premature rupture of membranes (PROM). Risk factors for preterm births were classified as maternal, fetal, placental, indeterminable and unclassifiable. Results: The proportions of preterm births were spontaneous 69% (with PROM 27% and with intact membranes 42%) and medically indicated births 31%. A risk factor associated with prematurity was identified in 98 and 85% of medically indicated and spontaneous births, respectively. Ascending bacterial infection (ABI) was the most frequently associated factor with spontaneous preterm delivery in 51% of women (142/280, p < 0.01) and with preterm births of less than 30 weeks in 52% of women (82/157, p < 0.01). Vaginal or urinary infection with Group B Streptococcus, was the most common clinical condition associated with ABI related deliveries. Hypertension was present in 94 of 127 medically indicated preterm deliveries (preeclampsia in 62% and chronic hypertension in 12%), and in 29% (preeclampsia 24%) of preterm births of more than 30 weeks. Congenital anomalies were mainly associated with a maternal age over 35 years in 15% (14/92) of women. The frequency of placental diseases was higher in spontaneous preterm deliveries (14%) and in pregnancies of more than 30 weeks in (14%). Conclusions: ABI was the most common factor associated with spontaneous preterm births at 2234 weeks, while preeclampsia is the most common factor associated with medically indicated preterm births.

Engrosamiento endometrial en la post menopausia / Endometrial thickening in postmenopausal

En los últimos años, dado el aumento de la obesidad, enfermedades crónicas como diabetes e hipertensión y el envejecimiento de la población, entre otras cosas, se ha observado una tendencia en el aumento de la patología endometrial maligna. Es por eso la preocupación en cuanto al diagnóstico y manejo oportunos de ésta...

Ganglioneuroma retroperitoneal en la infancia / Retroperitoneal ganglioneuroma in childhood

OBJETIVO: Presentación de un caso de ganlioneuroma retroperitoneal descubierto incidentalmente en una niña de 4 años de edad. MÉTODO: Se realizó estudio por imagen mediante ecografía y tomografía computerizada. La pieda quirúrgica fue analizada mediante estudio macroscópico y técnicas inmunohistoquímicas. RESULTADOS: Las técnicas de imagen identificaron una tumoración retroperitoneal independiente del riñón y de la suprarrenal izquierda. Histológicamente se observaba una proliferación fascicular con áreas fibrilares y mixoides con células ganglionares maduras. Estas células eras positivas para el neurofilamento y la enolasa neuronal específica. La evolución fue buena, sin recidivas hasta la actualidad. CONCLUSIÓN: El ganglioneuroma es una tumoración totalmente diferenciada, poco frecuente, que debe ser diferenciada del neuroblastoma (AU)