Diffusion tensor imaging metrics associated with future disability in multiple sclerosis.

The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.

Gadolinium-enhanced brain lesions in multiple sclerosis relapse.

OBJECTIVE: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. METHODS: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. RESULTS: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0-4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p=0.002). CONCLUSION: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario.

Gadolinium-enhanced brain lesions in multiple sclerosis relapse / Lesiones cerebrales captantes de gadolinio en el brote de los pacientes con esclerosis múltiple

Objective: To study the clinico-radiological paradox in multiple sclerosis (MS) relapse by analyzing the number and location of gadolinium-enhanced (Gd+) lesions on brain MRI before methylprednisolone (MP) treatment. Methods: We analyzed brain MRI from 90 relapsed MS patients in two Phase IV multicenter double-blind randomized clinical trials that showed the noninferiority of different routes and doses of MP administration. A 1.5- or 3-T brain MRI was performed at baseline before MP treatment and within 15 days of symptom onset. The number and location of Gd+ lesions were analyzed. Associations were studied using univariate analysis. Results: Sixty-two percent of patients had at least 1 Gd+ brain lesion; the median number was 1 (interquartile range 0–4), and 41% of patients had 2 or more lesions. The most frequent location of Gd+ lesions was subcortical (41.4%). Gd+ brain lesions were found in 71.4% of patients with brainstem-cerebellum symptoms, 57.1% with spinal cord symptoms and 55.5% with optic neuritis (ON). Thirty percent of patients with brain symptoms did not have Gd+ lesions, and only 43.6% of patients had symptomatic Gd+ lesions. The univariate analysis showed a negative correlation between age and the number of Gd+ lesions (p = 0.002). Conclusion: Most patients with relapse showed several Gd+ lesions on brain MRI, even when the clinical manifestation was outside of the brain. Our findings illustrate the clinico-radiological paradox in MS relapse and support the value of brain MRI in this scenario. (AU)

Objetivo: Estudiar la paradoja clínico-radiológica en el brote de la esclerosis múltiple (EM) mediante el análisis de lesiones captantes de gadolinio (Gd+) en la RM cerebral antes del tratamiento con metilprednisolona (MP). Métodos: Analizamos la RM cerebral basal de 90 pacientes con EM en brote de 2 ensayos clínicos aleatorizados multicéntricos fase IV que demostraron la no inferioridad de diferentes vías y dosis de MP, realizadas antes del tratamiento con MP y en los 15 días siguientes a la aparición de los síntomas. Se analizaron el número y la localización de las lesiones Gd+. Se estudiaron las asociaciones mediante análisis univariado. Resultados: El 62% de los pacientes tenía al menos una lesión Gd+ cerebral y el 41% de los pacientes tenía 2 o más lesiones. La localización más frecuente fue la subcortical (41,4%). Se encontraron lesiones Gd+ cerebrales en el 71,4% de los pacientes con síntomas de tronco cerebral o cerebelo, en el 57,1% con síntomas medulares y en el 55,5% con neuritis óptica. El 30% de los pacientes con síntomas cerebrales no tenían lesiones Gd+ y sólo el 4,.6% de los pacientes tenían lesiones Gd+ sintomáticas. El análisis univariante mostró una correlación negativa entre la edad y el número de lesiones Gd+ (p = 0,002). Conclusiones: La mayoría de los pacientes en brote mostraron varias lesiones Gd+ en la RM cerebral, incluso cuando la manifestación clínica fue medular u óptica. Nuestros hallazgos ilustran la paradoja clínico-radiológica en el brote de la EM y apoyan el valor de la RM cerebral en este escenario. (AU)

Risk factors of severe COVID-19 in people with multiple sclerosis : A systematic review and meta-analysis.

OBJECTIVES: To gather, synthesize, and meta-analyze data regarding the risk factors associated with a severe course of COVID-19 among patients with multiple sclerosis (pwMS). METHODS: MEDLINE, Embase, Scopus, and WoS were searched in May 2021. Briefly, the eligibility criteria included: 1) studies assessing COVID-19 severity among adult pwMS; 2) definitive diagnoses or high clinical suspicion of COVID-19; 3) a categorization of COVID-19 severity into at least two categories; 4) quantitative effect size and precision measurements; and 5) English language; and 6) clear effect size/precision measures. internal validity of studies was assessed using the NIH Quality Assessment Tools. A list of possible risk factors was created based on the search results and was later used in extraction, synthesis, and meta-analysis of the data. RESULTS: Thirteen studies were included in the syntheses. Outcome measures were either extracted from the papers, obtained from the primary researchers or calculated manually. The meta-analyses showed a significantly (P<0.05) increased odds of a severe COVID-19 in pwMS with all of the assessed risk factors, except smoking and most DMTs. CONCLUSION: This study facilitates evidence-based risk/benefit assessments in practice. Older men with progressive MS on anti-CD20 therapies are more at risk of an unfortunate COVID-19 outcome.

Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español / Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement

ANTECEDENTES: La reciente aparición de terapias de alta efectividad para el tratamiento de la esclerosis múltiple (EM), con potencial riesgo de complicaciones infecciosas, obliga plantear estrategias de prevención y minimización de riesgos. La vacunación constituye una parte esencial del manejo de estos pacientes. Este consenso recoge una serie de pautas y escenarios prácticos de vacunación en pacientes adultos con EM candidatos a tratamiento inmunosupresor. METODOLOGÍA: Se llevó a cabo un consenso de tipo formal. Tras definir el alcance del documento, se realizó una búsqueda bibliográfica de vacunación en pacientes con EM, así como guías de vacunación específicas de pacientes inmunosuprimidos y en tratamiento biológico con otras enfermedades. Para la formulación de las recomendaciones se empleó la metodología de Modified Nominal Group Technique. DESARROLLO: La vacunación en pacientes candidatos a tratamiento inmunosupresor se debe plantear antes de iniciar un tratamiento inmunosupresor siempre que la situación clínica del paciente lo permita. Se recomendarán tanto aquellas indicadas en el calendario vacunal del adulto, como algunas específicas, en función de la inmunidad previa. Si ya está instaurado el tratamiento inmunosupresor las vacunas vivas atenuadas estarán contraindicadas. Para aquellas vacunas que dispongan de un correlato de protección se recomienda monitorizar la respuesta serológica transcurridos de uno a 2 meses de la última dosis

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose

Recommendations for vaccination in patients with multiple sclerosis who are eligible for immunosuppressive therapies: Spanish consensus statement. / Recomendaciones para la vacunación en pacientes con esclerosis múltiple candidatos a terapias inmunosupresoras: documento de consenso español.

BACKGROUND: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments. METHODOLOGY: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations. DEVELOPMENT: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose.

Spatiotemporal shoreline dynamics of Marismas Nacionales, Pacific coast of Mexico, based on a remote sensing and GIS mapping approach.

Within the last few decades, tropical coastal systems such as beaches, dunes, and mangrove forests have experienced high annual rates of loss worldwide due to natural and anthropogenic impacts. Historical remote sensing data have been used to map and monitor these fragile systems, as well as to track specific events through time. The purpose of this study was to examine coastal trends along Marismas Nacionales in Mexico, which is the largest wetland complex of the western coast of the Pacific Ocean. The opening of the Cuautla Canal in 1976 and the construction of several hydroelectric power dams have severely impacted this wetland system. Shoreline variability was estimated based on representative remote sensing images over half a century (1970 to 2019). Results indicate that, after 49 years, 805 ha of beach deposits have been lost in the Cuautla Canal and at the beach ridge region that should otherwise be an accretional coastal zone. Conversely, the southern section of the study site shows 406 ha of constant accretion during the same period due to the presence of the unobstructed San Pedro River. Our study highlights the adverse effects of engineering projects, such as inlets and hydroelectric dams throughout tropical coastal systems that have strongly depended on freshwater input from upstream rivers.

Angioleiomiosarcoma de clítoris. Presentación de caso / Clitoral angio-leiomyosarcoma: Case report

El carcinoma vulvar es una entidad poco frecuente; representa el 3-5% de los tumores genitales malignos en la mujer. El 90% de ellos corresponden a carcinomas epidermoides, seguidos de los melanomas, enfermedad de Paget, enfermedad de Bowen, carcinomas basales y sarcomas. El leiomiosarcoma es la forma de presentación más frecuente de este último grupo. Se presenta un caso de una mujer adulta joven, 29 años, mestiza, que acude con una tumoración a nivel del clítoris, con el antecedente de exéresis de una tumoración benigna a nivel del labio mayor 3años antes. La lesión se mostraba móvil, ulcerada, muy dolorosa y sin adenopatías locales ni regionales. Se procede a la escisión total de la lesión y el estudio histológico informó un angioleiomiosarcoma de clítoris. Se envía el caso a Instituto de Oncología para confirmación diagnóstica y terapéutica, confirmándose el diagnóstico y la terapéutica. En 2años la paciente no ha tenido recidiva tumoral

Vulvar carcinoma is rare, and represents 3-5% of the all gynaecological cancers. Epidermoid carcinoma accounts for 90% of them, followed by melanoma, Paget́s disease, Boweńs disease illness, basal carcinoma and sarcomas. The leiomyosarcoma is the most frequent type of sarcoma. The case is presented of a 29 year-old woman that suffered from clitoral tumour. She was treated for a benign lesion in the labia majora 3years ago. In the current referral, she presented with pain and an ulcerated lesion, without local or regional adenopathies. The total excision was referred for a histological study, and the results showed an angio-leiomyosarcoma of the clitoris. Two years later, the patient showed no signs of residual lesion

Comparison of two high doses of oral methylprednisolone for multiple sclerosis relapses: a pilot, multicentre, randomized, double-blind, non-inferiority trial.

BACKGROUND AND PURPOSE: Oral or intravenous methylprednisolone (≥500 mg/day for 5 days) is recommended for multiple sclerosis (MS) relapses. Nonetheless, the optimal dose remains uncertain. We compared clinical and radiological effectiveness, safety and quality of life (QoL) of oral methylprednisolone [1250 mg/day (standard high dose)] versus 625 mg/day (lesser high dose), both for 3 days] in MS relapses. METHODS: A total of 49 patients with moderate to severe MS relapse within the previous 15 days were randomized in a pilot, double-blind, multicentre, non-inferiority trial (ClinicalTrial.gov, NCT01986998). The primary endpoint was non-inferiority of the lesser high dose by Expanded Disability Status Scale (EDSS) score improvement on day 30 (non-inferiority margin, 1 point). The secondary endpoints were EDSS score change on days 7 and 90, changes in T1 gadolinium-enhanced and new/enlarged T2 lesions on days 7 and 30, and safety and QoL results. RESULTS: The primary outcome was achieved [mean (95% confidence interval) EDSS score difference, -0.26 (-0.7 to 0.18) at 30 days (P = 0.246)]. The standard high dose yielded a superior EDSS score improvement on day 7 (P = 0.028). No differences were observed in EDSS score on day 90 (P = 0.352) or in the number of T1 gadolinium-enhanced or new/enlarged T2 lesions on day 7 (P = 0.401, 0.347) or day 30 (P = 0.349, 0.529). Safety and QoL were good at both doses. CONCLUSIONS: A lesser high-dose oral methylprednisolone regimen may not be inferior to the standard high dose in terms of clinical and radiological response.

Unveiled electric profiles within hydrogen bonds suggest DNA base pairs with similar bond strengths.

Electrical forces are the background of all the interactions occurring in biochemical systems. From here and by using a combination of ab-initio and ad-hoc models, we introduce the first description of electric field profiles with intrabond resolution to support a characterization of single bond forces attending to its electrical origin. This fundamental issue has eluded a physical description so far. Our method is applied to describe hydrogen bonds (HB) in DNA base pairs. Numerical results reveal that base pairs in DNA could be equivalent considering HB strength contributions, which challenges previous interpretations of thermodynamic properties of DNA based on the assumption that Adenine/Thymine pairs are weaker than Guanine/Cytosine pairs due to the sole difference in the number of HB. Thus, our methodology provides solid foundations to support the development of extended models intended to go deeper into the molecular mechanisms of DNA functioning.

[Response to treatment with interferon beta in patients with multiple sclerosis. Validation of the Rio Score]. / Respuesta al tratamiento con interferon beta en pacientes con esclerosis multiple. Validacion del Rio Score.

INTRODUCTION: Different criteria have been proposed for the response to treatment with interferon beta, and the Rio Score is one of the most widely used. The aim of this study was to validate the usefulness of the Rio Score in an independent cohort. PATIENTS AND METHODS: A multi-centre, prospective, longitudinal study was conducted on patients with relapsing-remitting multiple sclerosis treated with interferon beta. The patients were classified according to the presence of attacks, active lesions (new in T2 or gadolinium enhancing lesions) in magnetic resonance imaging, a confirmed increase in disability or combinations of these variables (attacks, increase on the Expanded Disability Status Scale and active lesions) after one year's treatment. Regression analysis was used in order to identify the response-predicting variables after a three-year follow-up. RESULTS: The sample consisted of 249 patients with relapsing-remitting multiple sclerosis. The logistic model confirmed that the presence of two (odds ratio = 6.6; CI 95% = 2.7-16.1; p < 0.0001) or three (odds ratio = 8.5; CI 95% = 1.6-46; p < 0.01) positive variables during the first year of treatment were indicative of a significant risk of activity (attacks or progression) in the next two years. CONCLUSIONS: The usefulness of the Rio Score is confirmed, in an independent cohort, as a means of identifying patients with a higher risk of developing clinical activity or progression of disability during treatment with interferon beta.

TITLE: Respuesta al tratamiento con interferon beta en pacientes con esclerosis multiple. Validacion del Rio Score.Introduccion. Se han propuesto diferentes criterios de respuesta al tratamiento con interferon beta, y el Rio Score es uno de los mas utilizados. El objetivo de este estudio fue validar la utilidad del Rio Score en una cohorte independiente. Pacientes y metodos. Estudio multicentrico, prospectivo y longitudinal de pacientes con esclerosis multiple remitente recurrente tratados con interferon beta. Los pacientes fueron clasificados basandose en la presencia de brotes, lesiones activas (nuevas en T2 o lesiones que captaban gadolinio) en la resonancia magnetica, incremento confirmado de la discapacidad o combinaciones de estas variables (brotes, incremento en la Expanded Disability Status Scale y lesiones activas) tras un año de tratamiento. Se utilizo un analisis de regresion con el fin de identificar las variables de prediccion de respuesta despues de un seguimiento de tres años. Resultados. Se incluyo a 249 pacientes con esclerosis multiple remitente recurrente. El modelo logistico confirmo que la presencia de dos (odds ratio = 6,6; IC 95% = 2,7-16,1; p < 0,0001) o tres (odds ratio = 8,5; IC 95% = 1,6-46; p < 0,01) variables positivas durante el primer año de tratamiento conferia un riesgo significativo de actividad (brotes o progresion) en los siguientes dos años. Conclusiones. Se confirma, en una cohorte independiente, la utilidad del Rio Score para identificar a pacientes con un mayor riesgo de desarrollar actividad clinica o progresion de la discapacidad durante el tratamiento con interferon beta.

Efecto del cobre y del cadmio sobre la respuesta inmune innata del pez Colossoma macropomum / Copper and cadmium effects on the innate immune response of the fish Colossoma macropomum

En este trabajo se evaluó la respuesta inmunológica celular inespecífica del pez Colossoma macropomum (Cuvier, 1818) expuestoaconcentracionessubletalesde cobreycadmio,atravésde la determinación de la viabilidad celular, la quimiotaxis, la fagocitosis y la muerte bacteriana en células inmunocompetentes extraídasdelriñóncefálico,lasangreyel hígado.Lospecesfueron expuestos por separado a 0,5 mg/L de cloruro de cobre y 1,0 mg/L de cloruro de cadmio durante 28 días; después de la exposición, se depuraron por el mismo período. La viabilidad celular se mantuvo entre 99-94%. La exposición al cadmio causó una reducción significativa en la respuesta quimiotáctica de granulocitos en los tejidos evaluados. Tanto los peces expuestos a cobre como los expuestos a cadmio presentaron una disminución significativa en la respuesta fagocítica de granulocitos. En sangre, el cadmio afectó la efectividad de los granulocitos de inducir muerte bacteriana; el cobre sin embargo, afectó la efectividad de inducir muerte bacteriana en los granulocitos provenientes del hígado. Los peces expuestos a cadmio presentaron un incremento significativo en los niveles de cortisol sérico y una disminución de esta hormona en los peces expuestos a cobre. Estos resultados demuestran que la exposición crónica a los metales cobre y cadmio produce una inhibición de la respuesta inmune inespecífica en el pez Colossoma macropomum (AU)

The non-specific immune response was evaluated thought cellular viability, quimiotaxis, phagocytosis and bacterial killing by PMN of innate immune cells providing of blood, head kidney and liver of freshwater fish Colossoma macropomum. Fish were exposed to 0.5 mg/L copper chloride and 1.0 mg/L cadmium chloride for 28 days; finalized the exposure, the fishes were depurated for 28 days. The cellular viability was between 94-99%, being observed the lowest values in both Cd-exposed and Cu-exposed fishes. A decrease in quimiotatic responses was found in granulocytes of the evaluated tissues. We observed a decrease in phagocytic response in both copper exposed fish and cadmium exposed fish on the three evaluated tissues. Cadmium reduced the effectiveness to induce bacterial killing in blood granulocytes; however, copper reduced the response in granulocytes of the hepatic tissue. The serum cortisol level was increased in Cd-exposed fish: on the contrary, it was decreased in Cu-exposed fish. These results suggest that chronic exposure to cadmium and copper of the fish Colossoma macropomum decreased the innate immunological response (AU)

ANKRD55 and DHCR7 are novel multiple sclerosis risk loci.

Multiple sclerosis (MS) shares some risk genes with other disorders hallmarked by an autoimmune pathogenesis, most notably IL2RA and CLEC16A. We analyzed 10 single-nucleotide polymorphisms (SNPs) in nine risk genes, which recently emerged from a series of non-MS genome-wide association studies (GWAS), in a Spanish cohort comprising 2895 MS patients and 2942 controls. We identified two SNPs associated with MS. The first SNP, rs6859219, located in ANKRD55 (Chr5), was recently discovered in a meta-analysis of GWAS on rheumatoid arthritis (RA), and emerged from this study with genome-wide significance (odds ratio (OR) = 1.35; P = 2.3 × 10(-9)). The second SNP, rs12785878, is located near DHCR7 (Chr11), a genetic determinant of vitamin D insufficiency, and showed a size effect in MS similar to that recently observed in Type 1 diabetes (T1D; OR = 1.10; P = 0.009). ANKRD55 is a gene of unknown function, and is flanked proximally by the IL6ST-IL31RA gene cluster. However, rs6859219 did not show correlation with a series of haplotype-tagging SNPs covering IL6ST-IL31RA, analyzed in a subset of our dataset (D'< 0.31; r(2)< 0.011). Our results expand the number of risk genes shared between MS, RA and T1D.

White matter abnormalities in primary Sjögren syndrome.

OBJECTIVE: To describe the main characteristics of patients with primary Sjögren syndrome (SS) and white matter abnormalities (WMA) seen by a specialist SS unit. METHODS: The study cohort included 321 consecutive patients fulfilling the 2002 classification criteria for primary SS. We retrospectively analyzed the results of neuroimaging studies performed in patients who presented with neurological symptoms. Patients were further evaluated by three neurologists to determine fulfillment of the McDonald criteria for the diagnosis of multiple sclerosis (MS). RESULTS: Fifty-one (16%) patients had at least one neuroimaging study, and 25 of these had WMA. WMA were classified as vascular pathological changes in 21 patients: 10 had multiple small focal lesions, 7 had beginning confluence of lesions and 4 had diffuse involvement of the entire region. WMA were classified as inflammatory/demyelinating lesions (MS-like) in 4 patients who fulfilled the MRI Barkhof criteria. Patients with inflammatory/demyelinating lesions were younger (53.7 vs. 73.5 years, P = 0.001) and had a lower frequency of hypertension (25% vs. 86%, P = 0.031) and altered glomerular filtration rate (0% vs. 70%, P = 0.047) in comparison with patients with vascular lesions. The multivariate age-sex adjusted model including the seven variables which were statistically significant in the univariate analysis (antimalarial therapy, leukopenia, anti-La/SSB antibodies, diabetes, hypertension, metabolic syndrome and HDL-c levels) identified hypertension (P = 0.019) and HDL-c levels (P = 0.032) as independent predictors of WMA in primary SS patients. CONCLUSION: Neuroimaging studies disclosed WMA in 49% of patients with primary SS and suspected neurological involvement. WMA were identified as vascular pathological changes in 80% of the patients, and hypertension and HDL-c levels as predictive factors for this association.

Does gender matter in glioblastoma?

BACKGROUND The clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery. METHODS We reviewed all consecutive GBM patients operated on in our hospital between January 2000 and December 2008. RESULTS A total of 216 patients with GBM were identified. Fifty-five (25%) did not receive any treatment after surgery. Univariate analysis showed that factors associated with no further treatment after surgery were older than 60 years (p=0.002), of female gender (p=0.03), had a KPS<70 (p<0.001) and had had a biopsy (p<0.001). Multivariate analysis indicated that age =60 years and KPS <70 were independent predictors of no further treatment after surgery. Gender was not an independent variable. However, women in the whole series were older than 60 years (p=0.01), and they had a worse KPS (p=0.02) and more biopsies (p=0.04) than men. In the whole group, median survival time was 10.4 months for men (n=125) vs. 7.2 months for women (n=91), log rank p<0.04. This difference was not observed in the group that was treated after surgery. CONCLUSIONS One out of four patients could not be treated after surgery. Independent predictors were older age and low KPS. These poor risk variables were more frequent in women and their survival was therefore lower than men in our series.

Does gender matter in glioblastoma?

BACKGROUND The clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery. METHODS We reviewed all consecutive GBM patients operated on in our hospital between January 2000 and December 2008. RESULTS A total of 216 patients with GBM were identified. Fifty-five (25%) did not receive any treatment after surgery. Univariate analysis showed that factors associated with no further treatment after surgery were older than 60 years (p=0.002), of female gender (p=0.03), had a KPS<70 (p<0.001) and had had a biopsy (p<0.001). Multivariate analysis indicated that age =60 years and KPS <70 were independent predictors of no further treatment after surgery. Gender was not an independent variable. However, women in the whole series were older than 60 years (p=0.01), and they had a worse KPS (p=0.02) and more biopsies (p=0.04) than men. In the whole group, median survival time was 10.4 months for men (n=125) vs. 7.2 months for women (n=91), log rank p<0.04. This difference was not observed in the group that was treated after surgery. CONCLUSIONS One out of four patients could not be treated after surgery. Independent predictors were older age and low KPS. These poor risk variables were more frequent in women and their survival was therefore lower than men in our series (AU)

[HLA-DRB1 typing in Caucasians patients with neuromyelitis optica]. / HLA-DRB1 en pacientes caucasicos con neuromielitis optica.

INTRODUCTION: The existence of antibodies to aquaporin-4 (AQP-4-ab) has identified neuromyelitis optica (NMO) and multiple sclerosis (MS) as different diseases. Although HLA-DRB1 alleles contribute to MS risk, recent studies suggest that HLA back-ground differs between patients with NMO or MS in non-Caucasians populations. Our study was aimed to analyze HLA-DRB1 distribution in Caucasians NMO patients. SUBJECTS AND METHODS: We recruited a cohort of 22 NMO patients (73% were AQP-4-ab positive), 228 MS patients and 225 healthy controls from Spain and we genotyped the HLA-DRB1 locus. Then, we performed a pool analysis using reported data from 45 NMO patients (53% were AQP-4-ab positive), 156 MS patients and 310 healthy controls from Caucasian French population. RESULTS: In the Spanish cohort, NMO was associated with increased frequency of DRB1*10 allele compared with MS (odds ratio, OR = 15.1; 95% confidence interval, 95% CI = 3.26-69.84; p = 0.012). In the pooled analysis, by comparison with healthy controls, NMO was associated with increased frequency of DRB1*03 allele (OR = 2.27; 95% CI = 1.44-3.58; p < 0.0008) which was related to AQP-4-ab seropositivity (OR = 2.74; 95% CI = 1.58-4.77; p < 0.0008). By contrast, MS was associated with increased frequency of DRB1*15 allele (OR = 2.09; 95% CI = 1.62-2.68; p < 0.0008) and decreased frequency of DRB1*07 allele (OR = 0.58; 95% CI = 0.44-0.78; p < 0.0008). CONCLUSIONS: Caucasian patients with NMO and MS have a different HLA-DRB1 allelic distribution. DRB1*03 allele seems to contribute to NMO seropositivity. Multicenter collaborative efforts are needed to adequately address the genetic contribution to NMO susceptibility.

Contaminación sonora en centros públicos de educación primaria de Albacete / Noise pollution in primary education public centres of Albacete

Objetivo: determinar el nivel sonoro continuo equivalente al que se ve sometido un escolar en su actividad diaria en centros públicos de educación primaria de Albacete. Material y método: estudio observacional descriptivo y transversal en once centros públicos de educación primaria de Albacete. Variable dependiente: nivel sonoro continuo equivalente al que se ve sometido el escolar (Leq en dBA). Variables independientes: colegio y lugares del colegio. Las mediciones se han realizado utilizando medidores de sonido Bruel & Kjaer type 2.226 con trípode. Se calcularon intervalos de confianza para un 95% de seguridad. Resultados: el nivel sonoro medio equivalente en las aulas de los niños con edades entre tres y cinco años tuvo unos valores medios de 75 dBA, para edades de seis a siete años fue de 66 dBA y para edades entre 8 y 11 años fue de 69 dBA. La media de la distribución muestral(de 3 a 11 años) fue de 70 dBA. El nivel sonoro medio equivalente en el pasillo a la salida de los escolares tuvo un valor medio de 71 dBA y de 83 dBA en el patio en el momento del recreo. Conclusiones: los niveles sonoros continuos equivalentes obtenidos superan los límites establecidos por la legislación vigente para centros educativos, por tanto, los escolares están sometidos a sonidos elevados en su actividad escolar (AU)

Objective: to determine the on going noise level equivalent to the one experienced by a student in his or her daily activity in public primary schools of Albacete.Material and method: cross-sectional descriptive observational study in 11 public primary schools of Albacete. Dependent variable: ongoing noise level equal to that experienced by the student (Leq indBA). Independent variables: school and places in the school. The measurement shave been performed using type 2.226 Bruel & Kjaer sound measurers with tripod. 95% Confidence intervals were calculated. Results: the average noise level equivalent to that in the classrooms of children between the age of three and five had a mean value of 75 dBA, for ages between six and seven it was 66 dBA and for ages between 8 and 11 it was 69 dBA. The sample distribution mean (ages between 3 and 11) was 70 dBA. The average noise level equivalent in the hallway at the end of the school day had a mean value of 71 dBA and 83 dBA in the playground during break.Conclusions: the equivalent on going noise levels obtained exceed the limits established by the current legislation for schools. Therefore,students are exposed to elevated noise during their school activity (AU)

Replication of top markers of a genome-wide association study in multiple sclerosis in Spain.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune origin, triggered by genetic and environmental risk factors. A recent genome-wide association study conducted on MS identified new biallelic markers outside the HLA (human leucocyte antigen) region involved in disease susceptibility: rs1109670 (DDEF2); rs1458175 (PDZRN4); rs1529316 and rs2049306 (CSMD1); rs16914086 (TBC1D2); rs1755289 (SH3GL2); rs1841770 (ZIC1); rs651477 (EN1); rs7607490 (TRIB2); rs397020 (C20orf46); rs908821 (SLC25A36); rs7672826 (MGC45800) and rs9523762 (GPC5). We aimed at replicating these top association signals in a Spanish cohort of 2863 MS patients and 2930 sex- and age-matched controls. Only rs9523762 mapping in the GPC5 gene was significantly associated (G allele, P=1.6 × 10(-5); odds ratio (95% confidence interval)=1.23 (1.12-1.36)), supporting a role for this proteoglycan in MS predisposition. The independent replication of association signals to validate data generated by genome-wide association scans is a first step in the effort to improve patient care.

The autoimmune disease-associated KIF5A, CD226 and SH2B3 gene variants confer susceptibility for multiple sclerosis.

Genome-wide association studies (GWAS) have revealed that different diseases share susceptibility variants. Twelve single-nucleotide polymorphisms (SNPs) previously associated with different immune-mediated diseases in GWAS were genotyped in a Caucasian Spanish population of 2864 multiple sclerosis (MS) patients and 2930 controls. Three SNPs were found to be associated with MS: rs1678542 in KIF5A (P=0.001, odds ratio (OR)=1.13, 95% confidence interval (CI)=1.05-1.23); rs3184504 in SH2B3 (P=0.00001, OR=1.19, 95% CI=1.10-1.27) and rs763361 in CD226 (P=0.00007, OR=1.16, 95%CI=1.08-1.25). These variants have previously been associated with rheumatoid arthritis and type 1 diabetes. The SH2B3 polymorphism has additionally been associated with systemic lupus erythematosus. Our results, in addition to validating some of these loci as risk factors for MS, are consistent with shared genetic mechanisms underlying different immune-mediated diseases. These data may help to shape the contribution of each pathway to different disorders.