NFL during acute spinal cord lesions in MS: a hurdle for the detection of inflammatory activity.

INTRODUCTION: Levels of neuro-filament light chain (NFL) correlate with clinical and radiological activity in multiple sclerosis (MS) and have been used as a surrogate biomarker of axonal destruction related to inflammatory activity. The main objective of this work is to explore the specific contribution of acute inflammation within the spinal cord to the elevation of NFL levels. PATIENTS AND METHODS: MS patients with a baseline study of NFL at diagnosis of the disease and a brain and spinal cord MRI scan were selected. Patients were classified according to the presence, number and location of gadolinium enhancing lesion (GEL) and the relationship between NFL levels and both brain and spinal cord GEL were explored. RESULTS: Seventy-seven patients were selected. NFL levels were significantly higher in patients with only one GEL restricted to the brain than those without GEL (1702 pg/ml vs 722.7 pg/mL, p = 0.03) and correlated with number. However, no differences were seen among patients with GEL limited to the spinal cord and those without GEL (735.2 pg/ml vs 722.7 pg/mL). CONCLUSION: Our study reaffirms the value of NFL levels in monitoring asymptomatic inflammatory activity in the brain measured by GEL. However, NFL concentration is not as useful when only inflammatory activity occurs in the spinal cord.

Trace element contamination in fish impacted by bauxite red mud disposal in the Cassidaigne canyon (NW French Mediterranean).

From 1966 to 2015, the Gardanne alumina refinery discharged some 20 million tons of bauxite residue (called red mud) into the Cassidaigne Canyon (northwest French Mediterranean) with impacts on local ecosystem functioning. Although these red muds contained high levels of trace elements (TE), in particular titanium (Ti), vanadium (V), aluminum (Al) and arsenic (As), surprisingly, their impacts on fish contamination levels and the risk related to fish consumption have been little studied until now. Here, 11 trace elements (Al, As, Cd, Cr, Co, Cr, Mn, Ni, Pb, Ti and V) were analyzed in muscle and, when possible, liver, from 1308 fish of 26 species from an impacted zone in the vicinity of the Cassidaigne Canyon and a reference zone, unaffected by red mud disposals. Moreover, 66 arsenic speciation analyses were performed. Although the impact of human activities on the levels of fish contamination by trace elements is generally not easy to assess in situ because it is blurred by interaction with biological effects, we highlighted significant contamination of the fish species collected from the Cassidaigne Canyon, especially by the main trace elements attributable to the discharges of the Gardanne alumina refinery, namely Al, V and Ti. Moreover, inorganic toxic As concentrations were higher in the impacted zone. The results of this baseline research also confirmed the concern previously raised regarding Hg in Mediterranean organisms and that trace element contamination levels in fish are generally negatively related to fish length for all TE except Hg.

Efficacy and safety of rituximab in relapsing and progressive multiple sclerosis: a hospital-based study.

INTRODUCTION: Rituximab is considered as a potential therapeutic option in relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness and safety of rituximab in MS. PATIENTS AND METHODS: Observational study of effectiveness (clinical and radiological) and safety of rituximab in RRMS and PMS. RESULTS: A total of 90 rituximab-treated patients were collected: 31 RRMS and 59 PMS All patients had an active disease despite standard treatment. The annualized relapse rate (ARR) the year before rituximab was 0.86, 53.3% of patients had gadolinium enhanced lesion, and mean Expanded Disability Status Scale (EDSS) had increased from 4.2 to 4.9. During treatment, the ARR was reduced an 88.4% (p < 0.001). A significant decrease of EDSS to 4.6 was observed (p = 0.01) after 1 year of treatment, which remained stable during the second year in both groups. There was no evidence of disease activity in 70% of total sample, 74.2% of RRMS, and 67% of the PMS patients. Infusion-related symptoms were the most prevalent side effect (18.8%) and most were mild. Three thrombotic events were detected. CONCLUSION: Rituximab could be an effective and safe treatment in aggressive RRMS. Some selected PMS patients could also benefit from this treatment.

Daclizumab in multiple sclerosis. / Daclizumab en la esclerosis multiple.

INTRODUCTION: Daclizumab is a monoclonal antibody directed against the CD25 subunit of the interleukin-2 receptor, investigated as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The present review addresses how the drug was developed, the known mechanism of action of the drug and the up-to-date data of efficacy and safety. DEVELOPMENT: Daclizumab has shown superiority in prevention of relapses against placebo and low-dose interferon beta-1a at a level that puts it on par with the rest of current first-line drugs. The effect on the progression of the disease and on neurodegeneration parameters, however, is not clear. On the other hand, it presents safety problems (mainly risk of autoimmunity phenomena including fulminant hepatopathy and encephalitis) that have supposed eventually its withdrawn from marketing. Daclizumab introduces a new mechanism of action through the blocking of a key interleukin in immune regulation and its effect on a population of cells with regulatory ability, such as the NK CD56(bright) cells. CONCLUSIONS: Daclizumab has shown efficacy in slowing the inflammatory process of multiple sclerosis, although the appearance of potentially serious side effects has not allowed its use to significantly impact current clinical practice. The development of new drugs in multiple sclerosis must be contingent on maintaining or improving the risk-benefit profile with respect to those already in use.

TITLE: Daclizumab en la esclerosis multiple.Introduccion. El daclizumab es un anticuerpo monoclonal dirigido contra la subunidad CD25 del receptor de la interleucina-2, investigado como terapia modificadora de la evolucion de la enfermedad en la esclerosis multiple. La presente revision aborda como se desarrollo el farmaco, cual es su mecanismo de accion conocido y los datos que se han obtenido hasta la fecha acerca de su eficacia y seguridad. Desarrollo. El daclizumab ha mostrado superioridad en prevencion de brotes frente a placebo e interferon beta-1a de baja dosis en un nivel que lo situa a la par del resto de farmacos de primera linea actuales. El efecto sobre la progresion de la enfermedad y sobre parametros de neurodegeneracion, no obstante, no esta aclarado. Por otro lado, presenta problemas de seguridad (riesgo de reacciones autoinmunes que incluyen hepatopatia fulminante y encefalitis) que han supuesto finalmente su retirada del mercado. El daclizumab introduce un nuevo mecanismo de accion a traves del bloqueo de una interleucina clave en la regulacion inmune y por su efecto sobre una poblacion de celulas con capacidad reguladora, como son las celulas NK CD56(bright). Conclusiones. El daclizumab ha demostrado eficacia para frenar el proceso inflamatorio de la esclerosis multiple, aunque la aparicion de efectos secundarios potencialmente graves no ha permitido que su uso impacte de manera significativa en la practica clinica actual. El desarrollo de nuevos farmacos en la esclerosis multiple debe estar supeditado a mantener o mejorar el perfil riesgo-beneficio respecto a los ya en uso.

[Treatment of relapsing-remitting multiple sclerosis with fingolimod in routine clinical practice]. / Tratamiento de la esclerosis multiple remitente recurrente con fingolimod en la practica clinica habitual.

INTRODUCTION: Fingolimod is a selective immunosuppressant that targets the S1P receptor, and is indicated in the treatment of aggressive relapsing-remitting multiple sclerosis (RRMS) and following treatment failure with first-order drugs. AIM: To investigate the safety and effectiveness of fingolimod under the conditions of routine clinical practice. PATIENTS AND METHODS: We conducted an observational study with prospective follow-up of patients with RRMS who received fingolimod from January 2011 until February 2014. Data assessed were the annualised relapse rate (ARR), disability measured by the Expanded Disability Status Scale (EDSS), magnetic resonance activity and the appearance of side effects. RESULTS: Our sample consisted of 122 patients, 79.5% of them females and with a mean age of 26.8 years. They were classified, according to the last treatment received, as being: naive (aggressive RRMS; n = 17), previous treatment failure (n = 67) and withdrawal of natalizumab due to risk of progressive multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 ± 15.9 months, the ARR and the appearance of new lesions with gadolinium enhancement were reduced in both the naive and the previous treatment failure groups. There were no differences between the various subgroups as regards the progression of EDSS or the time elapsed until the first attack or treatment failure. The risk of treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p = 0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022). CONCLUSIONS: Fingolimod is an effective and well-tolerated drug under conditions of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal bands is predictive of a poor response to fingolimod.

TITLE: Tratamiento de la esclerosis multiple remitente recurrente con fingolimod en la practica clinica habitual.Introduccion. El fingolimod es un inmunosupresor selectivo dirigido contra el receptor SP-1, indicado en el tratamiento de la esclerosis multiple remitente recurrente (EMRR) agresiva y tras el fracaso del tratamiento con farmacos de primera linea. Objetivo. Investigar la seguridad y efectividad del fingolimod en condiciones de practica clinica habitual. Pacientes y metodos. Estudio observacional con seguimiento prospectivo de pacientes con EMRR que recibieron fingolimod desde enero de 2011 hasta febrero de 2014. Se evaluo la tasa anual de brotes (TAB), la discapacidad medida por la escala expandida del estado de discapacidad (EDSS), la actividad en la resonancia magnetica y la aparicion de efectos adversos. Resultados. Incluimos 122 pacientes, el 79,5% mujeres y con una edad media de 26,8 antilde;os. Se clasificaron segun el ultimo tratamiento recibido en: naive (EMRR agresiva; n = 17), fracaso a terapias previas (n = 67) y retirada de natalizumab por riesgo de leucoencefalopatia multifocal progresiva (n = 38). Tras un seguimiento medio de 29,9 ± 15,9 meses, se redujo de forma significativa la TAB y la aparicion de nuevas lesiones con realce de gadolinio en el grupo naive y el de fracaso a terapias previas. No ha habido diferencias en la evolucion de la EDSS ni en el tiempo hasta el primer brote o el fracaso terapeutico entre los diferentes subgrupos. El riesgo a fracaso terapeutico es mayor con la EDSS basal > 3 (hazard ratio: 4,24; p = 0,001) y presencia de bandas oligoclonales IgM (hazard ratio: 2,45; p < 0,022). Conclusiones. El fingolimod es un farmaco eficaz y seguro en la EMRR en condiciones de practica clinica habitual. Tener una EDSS basal > 3 y bandas oligoclonales IgM predice una mala respuesta al fingolimod.

Significant clinical worsening after natalizumab withdrawal: Predictive factors.

We aimed to single out multiple sclerosis (MS) cases with poor outcome after natalizumab withdrawal and to identify predictive variables. We ascertained 47 withdrawals, and compared their pre- and post-natalizumab periods. We objectively defined significant clinical worsening after natalizumab withdrawal as a 2-step increase in Expanded Disability Status Scale (EDSS). We performed regression models. As a group, post-natalizumab annualized relapse rate (ARR) was lower in the post-natalizumab period, and there were no differences in the mean number of gadolinium (Gd)-enhancing lesions between pre- and post-natalizumab magnetic resonance imaging (MRI). Corticosteroid treatment did not change the outcomes. Eight patients (19%) presented significant clinical worsening after natalizumab withdrawal, which was predicted by a higher baseline EDSS and a 1-step EDSS increase while on natalizumab.

Clinical evaluation of rituximab treatment for neuromyelitis optica.

INTRODUCTION: Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immune-mediated or involving humoural immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital. METHODS: Retrospective study of patients with neuromyelitis optica treated with rituximab 1000mg on days 1 and 15, repeated every 6 to 8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions. RESULTS: Six patients were treated; all were women with a median age of 46 years (range, 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated. CONCLUSION: Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica.

Are red mullet efficient as bio-indicators of mercury contamination? A case study from the French Mediterranean.

Mercury (Hg) is one of the main chemicals currently altering Mediterranean ecosystems. Red mullet (Mullus barbatus and M. surmuletus) have been widely used as quantitative bio-indicators of chemical contamination. In this study, we reassess the ability of these species to be used as efficient bio-indicators of Hg contamination by monitoring during 18 months Hg concentrations in muscle tissue of mullet sampled from 5 French Mediterranean coastal areas. Mean concentrations ranged between 0.23 and 0.78 µg g(-1) dry mass for both species. Values were consistent with expected contamination patterns of all sites except Corsica. Results confirmed that red mullets are efficient bio-indicators of Hg contamination. Nevertheless, the observed variability in Hg concentrations calls for caution regarding the period and the sample size. Attention should be paid to environmental and biologic specificities of each studied site, as they can alter the bioaccumulation of Hg, and lead to inferences about environmental Hg concentrations.

Development of type 2 diabetes mellitus thirty-one years after Billroth II in a patient asking for diabetes surgery.

INTRODUCTION: Diabetes surgery in obese and slim patients seems to be a superior alternative to the current medical treatment. Gastric bypass is an alternative treatment for diabetes. Nevertheless, there are still doubts whether diabetes can recur if you gain weight or if the effects are maintained over time. Other questions refer to the type of surgery to make the bypass limb length or reservoir size for the resolution of the Diabetes Mellitus. PRESENTATION OF CASE: Male patient 69-year-old came to us in order to perform tailored One Anastomosis Gastric Bypass (BAGUA) to treat his type 2 diabetes mellitus and metabolic syndrome. He has a history of peptic ulcer treated with subtotal gastrectomy and Billroth II reconstruction 49 years ago. He currently is not obese and developed diabetes 31 years after surgery. DISCUSSION: Globally there are no reports of patients with normal BMI that after performing gastric bypass developed diabetes mellitus. There are cases where obese diabetic patients after gastric bypass improve or remits the T2DM, but it relapses due to insufficient weight loss or gain it. The patient with gastric bypass Billroth II type, should not developed diabetes. He is normal weight and not had weight gain that could be linked to the development of diabetes. CONCLUSIONS: The results generated by bariatric surgery are encouraging, but still do not clarify the precise way how surgery produces rapid improvement of systemic metabolism as in diabetes, but in our patient, the effect was quite different because the gastric bypass had no protective effect against diabetes.

INTRODUCCIÓN: La cirugía de la diabetes en pacientes obesos y delgados parece ser una alternativa superior al tratamiento médico actual. El bypass gástrico es un tratamiento alternativo al tratamiento médico actual. Sin embargo, todavía hay dudas sobre si la diabetes puede reaparecer si hay aumento de peso o si se mantienen los efectos en el tiempo. Otras preguntas se refieren al tipo de cirugía para hacer la longitud del remanente gástrico o el tamaño del reservorio para la resolución de la Diabetes Mellitus. Presentación del caso: Paciente masculino de 69 años de edad, vino a nosotros con el fin de realizar el bypass gástrico de una anastomosis a medida (BAGUA) para tratar su diabetes mellitus tipo 2 y el síndrome metabólico. Tiene antecedentes de úlcera péptica tratado con gastrectomía subtotal y reconstrucción tipo Billroth II hace 49 años. Actualmente él no es obeso y desarrolló diabetes 31 años después de la cirugía. DISCUSIÓN: A nivel mundial no hay reportes de pacientes con IMC normal que después de realizar un bypass gástrico desarrollaron diabetes mellitus. Hay casos en que los pacientes diabéticos obesos después del bypass gástrico mejoran o remite la DMT2, pero reaparece debido a la pérdida de peso insuficiente o reganancia de él. El paciente con un bypass gástrico tipo Billroth II, no debió desarrollar diabetes. Él tiene peso normal y no ha aumentado de peso que podría estar relacionado con el desarrollo de diabetes. CONCLUSIÓN: Los resultados generados por la cirugía bariátrica son alentadores, pero aún no aclaran la forma precisa cómo la cirugía produce una rápida mejoría del metabolismo sistémico como la diabetes, pero en nuestro paciente, el efecto fue muy diferente debido a que el bypass gástrico no tuvo un efecto protector contra la diabetes.

Mercury in organisms from the Northwestern Mediterranean slope: importance of food sources.

Mercury (Hg) is a global threat for marine ecosystems, especially within the Mediterranean Sea. The concern is higher for deep-sea organisms, as the Hg concentration in their tissues is commonly high. To assess the influence of food supply at two trophic levels, total Hg concentrations and carbon and nitrogen stable isotope ratios were determined in 7 species (4 teleosts, 2 sharks, and 1 crustacean) sampled on the upper part of the continental slope of the Gulf of Lions (Northwestern Mediterranean Sea), at depths between 284 and 816 m. Mean Hg concentrations ranged from 1.30±0.61 to 7.13±7.09 µg g(-1) dry mass, with maximum values observed for small-spotted catshark Scyliorhinus canicula. For all species except blue whiting Micromesistius poutassou, Hg concentrations were above the health safety limits for human consumption defined by the European Commission, with a variable proportion of the individuals exceeding limits (from 23% for the Norway lobster Nephrops norvegicus to 82% for the blackbelly rosefish Helicolenus dactylopterus). Measured concentrations increased with increasing trophic levels. Carbon isotopic ratios measured for these organisms demonstrated that settling phytoplanktonic organic matter is not only the main source fueling trophic webs but also the carrier of Hg to this habitat. Inter- and intraspecific variations of Hg concentrations revealed the importance of feeding patterns in Hg bioaccumulation. In addition, biological parameters, such as growth rate or bathymetric range explain the observed contamination trends.

Changes of body composition in patients with BMI 23-50 after tailored one anastomosis gastric bypass (BAGUA): influence of diabetes and metabolic syndrome.

BACKGROUND: The use of bariatric surgery to treat diabetes mellitus (DM) requires procedures developed for morbid obese in patients with normal and over-weight. Therefore, we started tailoring one anastomosis gastric bypass (BAGUA) adapted to each patient. This study analyzes changes in body composition (BC) of patients with BMI 23-50 after BAGUA as well as influence of DM and MS. METHODS: We studied 79 (37 diabetic and 42 non-diabetic) patients (BMI 23-50) who completed all evaluation appointment (preoperative, 10 days, 1, 3, 6, and 12 months) after tailored BAGUA for obesity, diabetes, or diabesity. Patients were classified according to BMI (23-29, 30-34, 35-50) and bearing or not diabetes. Variables are components of BC as well as DM and MS. RESULTS: Preoperatively, mean values of weight varied 37 kg (78-115 kg), muscle mass (MM) 8 kg (54-62 kg), while fat mass (FM) 30 kg (22-53 kg). Basal metabolism (BM) was higher in diabetic. After surgery, percentage (%) of excess weight loss (%EWL) ranged from 76 % (BMI 35-50) to 128 % (BMI 23-29), FM 56 % (BMI 23-29) to 65 % (BMI 35-50), without differences bearing DM. MM 12 % (non-diabetics BMI 30-34) to 17 % (diabetics BMI 35-50) and visceral fat (VF) 50 % (diabetics BMI 30-34) to 56 % (non-diabetics BMI 35-50). CONCLUSIONS: After tailored BAGUA, MM maintains steady while FM is highly reduced and variable. BM is reduced in all groups. Diabetics lose less weight and VF but more MM than non-diabetic patients. Preoperative presence of MS influences the changes in BC.

Clinical experiences with cannabinoids in spasticity management in multiple sclerosis.

INTRODUCTION: Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS. METHODS: Retrospective observational study with patients treated with inhaled THC/CBD between April 2008 and March 2012. Descriptive patient and treatment variables were collected. Therapeutic response was evaluated based on the doctor's analysis and overall impression. RESULTS: Of the 56 patients who started treatment with THC/CBD, 6 were excluded because of missing data. We evaluated 50 patients (42% male) with a median age 47.8 years (25.6-76.8); 38% were diagnosed with primary progressive MS, 44% with secondary progressive MS, and 18% with relapsing-remitting MS. The reason for prescribing the drug was spasticity (44%), pain (10%), or both (46%). Treatment was discontinued in 16 patients because of ineffectiveness (7 patients), withdrawal (4), and adverse effects (5). The median exposure time in patients whose treatment was discontinued was 30 days vs 174 days in those whose treatment continued at the end of the study. THC/CBD was effective in 80% of patients at a median dose of 5 (2-10) inhalations/day. The adverse event profile consisted of dizziness (11 patients), somnolence (6), muscle weakness (7), oral discomfort (2), diarrhoea (3), dry mouth (2), blurred vision (2), agitation (1), nausea (1), and paranoid ideation (1). CONCLUSIONS: THC/CBD appears to be a good alternative to standard treatment as it improves refractory spasticity in MS and has an acceptable toxicity profile.

Improvement of C peptide zero BMI 24-34 diabetic patients after tailored one anastomosis gastric bypass (BAGUA).

BACKGROUND: Although bariatric surgery proved to be a very effective method in the treatment of patients in whose pancreas still produce insulin (type 2 diabetes), the accompanied metabolic syndrome and their diabetes complications, there is no information on the effect of this type of surgery in BMI24-34 patients when pancreas do not produce insulin at all (type 1, LADA and long term evolution type 2 diabetes among others). PATIENTS AND METHODS: We report preliminary data of a serie of 11 patients all with a C-peptide values below 0.0 ng/ml. They were followed for 6 to 60 months (mean 19 months) after surgery. We studied the changes in glycemic control, evolution of the metabolic syndrome and diabetes complications after one anastomosis gastric bypass (BAGUA). RESULTS: All values relative to glycemic control were improved HbA1c (from 8.9 ± 0.6 to 6.7 ± 0.2%), FPG (Fasting Plasma Glucose) [from 222.36 ± 16.87 to 94 ± 5 (mg/dl)] as well as the daily insulin requirement of rapid (from 40.6 ± 12.8 to 0 (U/d) and long-lasting insulin (from 41.27 ± 7.3 U/day to 15.2 ± 3.3 U/day). It resolved 100% of the metabolic syndrome diseases as well as severe hypoglycaemia episodes present before surgery and improved some serious complications from diabetes like retinopathy, nephropathy, neuropathy, peripheral vasculopathy and cardiopathy. CONCLUSIONS: Tailored one anastomosis gastric bypass in BMI 24-34 C peptide zero diabetic patients eliminated the use of rapid insulin, reduced to only one injection per day long-lasting insulin and improved the glycemic control. After surgery disappear metabolic syndrome and severe hypoglycaemia episodes and improves significantly retinopathy, neuropathy, nephropathy, peripheral vasculopathy and cardiopathy.

Introducción: Aunque la cirugía bariátrica ha demostrado ser un método muy eficaz en el tratamiento de pacientes diabéticos cuyo páncreas aún es capaz de producir insulina (diabetes tipo 2), así como del síndrome metabólico y las complicaciones relacionadas con la diabetes, no hay información sobre el efecto de este tipo de cirugía en pacientes IMC 24-34 cuando el páncreas no produce insulina en absoluto (tipo 1, tipo LADA y diabetes tipo 2 de larga evolución, entre otros). Métodos: Presentamos datos preliminares de una serie de 11 pacientes todos con valores de Péptido C < 0,0 ng/ml. El seguimiento postoperatorio varia de 6 y 60 meses (media 19 meses). Estudiamos los cambios en el control de la glucemia, evolución del síndrome metabólico y complicaciones relacionadas con la diabetes tras bypass de una anastomosis (BAGUA). Resultados: Mejoraron todos los valores relativos al control glucémico HbA1c (de 8,9 ± 0,6 a 6,7 ± 0,2%), FPG (Glucosa Plasmática Ayunas) (de 222,36 ± 16,87 a 94 ± 5 (mg/dl)) así como el requerimiento diario de insulina, tanto de insulina rápida (de 40,6 ± 12,8 a 0 U/día) como de insulina retardada (41,27 ± 7,3 U/día a 15,2 ± 3,3 U/día). Se resolvieron el 100% de las comorbilidades estudiadas y se mejoraron algunas complicaciones graves derivadas de la diabetes como retinopatía o nefropatía. Conclusiones: El bypass gástrico de una anastomosis adaptado a pacientes diabéticos IMC24-34 con péptido C cero elimina el uso de insulina de acción rápida, reduce a una sola inyección diaria la insulina retardada y mejora el control glucémico. Tras la cirugía desaparecen el síndrome metabólico y los episodios severos de hipoglucemia, y mejora significativamente la retinopatía, neuropatía, nefropatía, vasculopatía periférica y cardiopatía.

[Endothelial dysfunction: role in the maternal syndrome of preeclampsia and long-term consequences for the cardiovascular system]. / Dysfonction endothéliale: rôle dans le syndrome maternel de la prééclampsie et conséquences à long terme pour le système cardiovasculaire.

Preeclampsia is a pregnancy disorder being a leading cause of maternal and fetal mortality and morbidity. It is a complex multisystem disease characterized by hypertension and proteinuria. In preeclampsia the placenta releases factors into the maternal circulation which cause a systemic endothelial dysfunction. Here, we review data demonstrating the central role played by the endothelium in the development of the maternal syndrome of preeclampsia. We present also original data showing how circulating factors present in the plasma of preeclamptic women can alter the transcriptome of endothelial cells. The expression of genes involved in essential functions such as vasoregulation, oxidative stress, apoptosis and cell proliferation show differential expression when endothelial cells are exposed to preeclamptic or normal pregnancy plasma. We conclude by discussing the growing evidences that the alterations of the endothelium during preeclampsia are linked to an increased risk of cardiovascular diseases latter on life. Therefore, a better understanding of the modifications undergone by the endothelial cells during preeclampsia is essential to develop new therapeutic approaches to both, manage preeclampsia and to prevent the long-term sequelae of the disease on women cardiovascular system.

Clinical impact of early brain atrophy in clinically isolated syndromes.

BACKGROUND: The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged. OBJECTIVES: We aimed to determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS. METHODS: We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions. RESULTS: The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (- 0.65% versus + 0.059%; p < 0.001). PBVC decreases below - 0.817% independently predicted shorter times to a second attack. CONCLUSIONS: Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.

[Recommendations for the clinical use of motor evoked potentials in multiple sclerosis]. / Recomendaciones para la utilización clínica del estudio de potenciales evocados motores en la esclerosis múltiple.

OBJECTIVE: To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. METHOD: We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. RESULTS: MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. CONCLUSIONS: Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space.

Resolution of diabetes mellitus and metabolic syndrome in normal weight 24-29 BMI patients with One Anastomosis Gastric Bypass.

INTRODUCTION: Diabetes mellitus type 2 (DMT2) is a major cause of death in the world. The medical therapy for this disease has had enormous progress, but it still leaves many patients exposed to the complications developed from the disease. It is well known the beneficial effects of bariatric surgery in obese diabetic patients, however it is important to investigate if the same principles of bariatric surgery that improve diabetes in obese patients, could be applied to non obese normal weight diabetics. MATERIAL AND METHODS: Thirteen diabetic patients operated by One Anastomosis Gastric Bypass (BAGUA), were evaluated in the preoperative period and 1,3 and 6 months after surgery. Body weight and composition, Fasting Plasma Glucose, HbA1c levels, blood pressure and serum lipids levels were analyzed, as well as the monitoring of the immediate postoperative treatment necessities for Diabetes and other metabolic syndrome comorbidities. RESULTS: After the surgery the 77% of the patients resolves its T2DM, 46% from surgery, and rest noted an significant improvement of the disease in spite of having a C peptide level near to zero some of the patients. The comorbidities, mainly hypertension and lipid abnormalities experience improvement early. All patients reduce their weight and the amount of fat mass until values consistent with their age and height. CONCLUSIONS: The One Anastomosis Gastric Bypass leads to resolution or improvement of T2DM in non obese normal weight patients. The best results are obtained in patients with few years of diabetes, without or short term use of insulin treatment and high C-peptide levels.

Prevalence of thoracic vertebral fractures in Spanish patients hospitalized in Internal Medicine Departments. Assessment of the clinical inertia. (PREFRAMI study).

PURPOSE: To study the prevalence of vertebral fractures (VF), the associated risk factors and the degree of diagnosis and prescription upon discharge in a series of hospitalized medical patients ≥50 years of age. METHODS: A cross-sectional, multicentre and observational study in which a prevalence cut-off was carried out concerning patients admitted to six Internal Medicine departments in Malaga (Spain). The main variables were the existence of a fracture in the spine lateral x-ray, the inclusion of the diagnosis of a fracture in the discharge report, and the establishment of anti-osteoporotic treatment at discharge. RESULTS: 254 patients were included (mean age 66.4±14.9 years). The prevalence of VF was of 14.2% (36 cases). Patients with VF presented with a higher mean age, compared to those without VF (70.14 vs. 65.7 years) (p=0.035). The means contrast for the FRAX index variable (major osteoporotic and hip fracture), grouping according to the presence of VF, did not show any statistical significance (p=0.369 and p=0.788, respectively). Only in 8.3% of the discharge reports of patients with VF had the diagnosis of VF and/or osteoporosis been recorded and the prescription of anti-osteoporotic drugs been included. CONCLUSIONS: A high prevalence of asymptomatic VF is verified in medical inpatients ≥50 years of age. The FRAX index did not turn out to be predictive of the presence of VF in this population. There is an underdiagnosis of osteoporotic VF in the coding at hospital discharge. Action protocols are necessary to avoid clinical inactivity regarding this entity.

Prototype of an auto-calibrating, context-aware, hybrid brain-computer interface.

We present the prototype of a context-aware framework that allows users to control smart home devices and to access internet services via a Hybrid BCI system of an auto-calibrating sensorimotor rhythm (SMR) based BCI and another assistive device (Integra Mouse mouth joystick). While there is extensive literature that describes the merit of Hybrid BCIs, auto-calibrating and co-adaptive ERD BCI training paradigms, specialized BCI user interfaces, context-awareness and smart home control, there is up to now, no system that includes all these concepts in one integrated easy-to-use framework that can truly benefit individuals with severe functional disabilities by increasing independence and social inclusion. Here we integrate all these technologies in a prototype framework that does not require expert knowledge or excess time for calibration. In a first pilot-study, 3 healthy volunteers successfully operated the system using input signals from an ERD BCI and an Integra Mouse and reached average positive predictive values (PPV) of 72 and 98% respectively. Based on what we learned here we are planning to improve the system for a test with a larger number of healthy volunteers so we can soon bring the system to benefit individuals with severe functional disability.