Intravenous immunoglobulin to prevent myasthenic crisis after thymectomy and other procedures can be omitted in patients with well-controlled myasthenia gravis

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by a Fondo de Investigación Sanitaria (FIS-FEDER) (grants PI16-01673 and PI19/00593) and an Interlaken Research Award Programme (2012-12094537).Background: Myasthenic crisis (MC) is a potentially life-threatening complication of myasthenia gravis. Its precipitating factors include surgical procedures, particularly thymectomy. The role of preoperative intravenous immunoglobulin (IVIg) in preventing MC in patients scheduled for thymectomy and other surgery with general anaesthesia is unknown. Our objective was to test the hypothesis that preoperative IVIg is effective in preventing myasthenic crisis in patients with myasthenia gravis scheduled for surgery under general anaesthesia, including thymectomy. Methods: A prospective, randomized, double-blind, single-centre study was conducted over a 4-year period. The treatment group received IVIg, 0.4 g/kg/day preoperatively for 5 consecutive days, and the placebo group received saline solution under the same conditions. The two groups were age-matched, with similar functional status, and Myasthenia Gravis Foundation of America class. All patients had well-controlled myasthenia gravis with minimal manifestations before surgery. The primary outcome measured was MC. Intubation times, time in the recovery room, number of postoperative complications, and days of hospitalization were the secondary outcomes measured. Results: A total of 47 patients were randomized, 25 to the IVIg group and 22 to placebo. There were 19 men and 28 women, with a mean age of 58.6 years, mean body mass index of 27.8 kg/m, and mean acetylcholine receptor antibodies of 12.9 nmol/l. The mean forced vital capacity was 84.4%. The mean quantitative myasthenia gravis sum score was 6.3. Ten patients (five in each arm) had a history of MC. Thymectomy was performed in 16 patients. Only one patient in the placebo group presented with MC requiring non-invasive ventilation (but no reintubation) for 6 days. Neither differences between groups in the univariate analysis nor risk factors for MC in the multivariate analysis were found. Conclusions: Preoperative IVIg to prevent MC does not appear to be justified in well-controlled myasthenia gravis patients. This study provides class I evidence that preparation with IVIg to prevent MC is not necessary in well-controlled myasthenia gravis patients scheduled for surgery with general anaesthesia

Intravenous immunoglobulin to prevent myasthenic crisis after thymectomy and other procedures can be omitted in patients with well-controlled myasthenia gravis

Immunoglobulin; Myasthenia; ThymectomyInmunoglobulina; Miastenia; TimectomíaImmunoglobulina; Miastènia; TimectomiaBACKGROUND: Myasthenic crisis (MC) is a potentially life-threatening complication of myasthenia gravis. Its precipitating factors include surgical procedures, particularly thymectomy. The role of preoperative intravenous immunoglobulin (IVIg) in preventing MC in patients scheduled for thymectomy and other surgery with general anaesthesia is unknown. Our objective was to test the hypothesis that preoperative IVIg is effective in preventing myasthenic crisis in patients with myasthenia gravis scheduled for surgery under general anaesthesia, including thymectomy. METHODS: A prospective, randomized, double-blind, single-centre study was conducted over a 4-year period. The treatment group received IVIg, 0.4 g/kg/day preoperatively for 5 consecutive days, and the placebo group received saline solution under the same conditions. The two groups were age-matched, with similar functional status, and Myasthenia Gravis Foundation of America class. All patients had well-controlled myasthenia gravis with minimal manifestations before surgery. The primary outcome measured was MC. Intubation times, time in the recovery room, number of postoperative complications, and days of hospitalization were the secondary outcomes measured. RESULTS: A total of 47 patients were randomized, 25 to the IVIg group and 22 to placebo. There were 19 men and 28 women, with a mean age of 58.6 years, mean body mass index of 27.8 kg/m2, and mean acetylcholine receptor antibodies of 12.9 nmol/l. The mean forced vital capacity was 84.4%. The mean quantitative myasthenia gravis sum score was 6.3. Ten patients (five in each arm) had a history of MC. Thymectomy was performed in 16 patients. Only one patient in the placebo group presented with MC requiring non-invasive ventilation (but no reintubation) for 6 days. Neither differences between groups in the univariate analysis nor risk factors for MC in the multivariate analysis were found. CONCLUSIONS: Preoperative IVIg to prevent MC does not appear to be justified in well-controlled myasthenia gravis patients. This study provides class I evidence that preparation with IVIg to prevent MC is not necessary in well-controlled myasthenia gravis patients scheduled for surgery with general anaesthesia.This work was funded by a Fondo de Investigacion Sanitaria (FIS-FEDER) (grants PI16-01673 and PI19/00593) and an Interlaken Research Award Programme (2012-12094537

The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals

Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer's disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability

Importancia del consumo de agua en la salud y la prevención de la enfermedad: Situación actual

Aunque el agua es un nutriente esencial para la vida y el componente más abundante de nuestro cuerpo, recibe escasa atención en las recomendaciones dietéticas y las guías clínicas. Existen inconvenientes para determinar las cifras óptimas, tanto para la cantidad de agua que debe contener el cuerpo como para su ingesta. La ingesta y eliminación del agua dependen de factores no constantes y difíciles de medir, a su vez compensados por la capacidad del organismo para la homeostasis. Dada la falta de evidencia científica para el establecimiento de recomendaciones, se han estimado las “ingestas adecuadas” (para mantener un estado de hidratación adecuado) utilizando datos de ingestas de agua en grupos de personas sanas. La Autoridad Europea de Seguridad Alimentaria (EFSA) también considera la osmolaridad deseable en la orina para estimar la ingesta adecuada de agua en los adultos. Los estudios clínicos han mostrado en general beneficios con una hidratación adecuada y perjuicios con sus desequilibrios, ya sean cuantitativos (deshidratación y sobrehidratación) o cualitativos (agua extracelular e intracelular). Desafortunadamente, estos estudios son escasos y suelen tener diseños deficientes, ya sean transversales, de casos y controles o prospectivos, utilizando muestras pequeñas o métodos indirectos para evaluar el estado de hidratación. En este artículo se presenta información de actualización respecto a: 1) la adherencia a las recomendaciones de consumo de agua y sugerencias para mejorarla; 2) técnicas disponibles para medir el estado de hidratación y sus aplicaciones clínicas; 3) efectos de la hidratación/deshidratación en las actividades físicas o cognitivas y en las enfermedades crónicas; y 4) normativa española sobre calidad y salubridad del agua. Water is an essential nutrient for life and the most abundant component in the human body. However, its dietary recommendations or clinical management guidelines do not receive as much attention as they deserve. In addition, there are some obstacles to establishing optimal values, both for the amount of water the body must contain and for water ingestion. Water intake and elimination depend on unsteady factors that are difficult to measure and, at the same time, compensated by the body’s ability to regulate homeostasis. Since scientific evidence is lacking for establishing recommenda-tions, “adequate intakes” (to maintain an adequate hydration state) have been estimated using data on water intake from groups of healthy people. The European Food Safety Authority (EFSA) also considers desirable the use of urine osmolarity to estimate the adequacy of water intake in adults. Clinical studies have generally shown the benefits of adequate hydration and the damage caused by water imbalance, whether quantitative (dehydration and overhydration) or qualitative (extracellular and intracellular water). Unfortunately, these studies are few and often have poor cross-sectional, case-control, or prospective designs, and use small samples or indirect methods to assess hydration status. This article presents up-to-date information on subjects such as: 1) compliance with water consumption recommendations and suggestions for improvement; 2) techniques available to measure hydration status and their clinical applications; 3) effects of hydration/dehydration on physical or cognitive activities and chronic diseases; and 4) existing Spanish regulations on the quality and salubrity of water

Is reduction in appetite beneficial for body weight management in the context of overweight and obesity? Yes, according to the SATIN (Satiety Innovation) study

New dietary-based concepts are needed for treatment and effective prevention of overweight and obesity. The primary objective was to investigate if reduction in appetite is associated with improved weight loss maintenance. This cohort study was nested within the European Commission project Satiety Innovation (SATIN). Participants achieving ≥8% weight loss during an initial 8-week low-energy formula diet were included in a 12-week randomised double-blind parallel weight loss maintenance intervention. The intervention included food products designed to reduce appetite or matching controls along with instructions to follow national dietary guidelines. Appetite was assessed by ad libitum energy intake and self-reported appetite evaluations using visual analogue scales during standardised appetite probe days. These were evaluated at the first day of the maintenance period compared with baseline (acute effects after a single exposure of intervention products) and post-maintenance compared with baseline (sustained effects after repeated exposures of intervention products) regardless of randomisation. A total of 181 participants (forty-seven men and 134 women) completed the study. Sustained reduction in 24-h energy intake was associated with improved weight loss maintenance (R 0·37; P = 0·001), whereas the association was not found acutely (P = 0·91). Suppression in self-reported appetite was associated with improved weight loss maintenance both acutely (R −0·32; P = 0·033) and sustained (R −0·33; P = 0·042). Reduction in appetite seems to be associated with improved body weight management, making appetite-reducing food products an interesting strategy for dietary-based concepts

Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease

Blood biomarkers indicating elevated amyloid-β (Aβ) pathology in preclinical Alzheimer's disease are needed to facilitate the initial screening process of participants in disease-modifying trials. Previous biofluid data suggest that phosphorylated tau231 (p-tau231) could indicate incipient Aβ pathology, but a comprehensive comparison with other putative blood biomarkers is lacking. In the ALFA+ cohort, all tested plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL and Aβ42/40) were significantly changed in preclinical Alzheimer's disease. However, plasma p-tau231 reached abnormal levels with the lowest Aβ burden. Plasma p-tau231 and p-tau217 had the strongest association with Aβ positron emission tomography (PET) retention in early accumulating regions and associated with longitudinal increases in Aβ PET uptake in individuals without overt Aβ pathology at baseline. In summary, plasma p-tau231 and p-tau217 better capture the earliest cerebral Aβ changes, before overt Aβ plaque pathology is present, and are promising blood biomarkers to enrich a preclinical population for Alzheimer's disease clinical trials

Dietary glycemic index and glycemic load are positively associated with risk of developing metabolic syndrome in middle-aged and elderly adults

© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society. Objectives To evaluate how glycemic index (GI) and glycemic load (GL) are associated with the metabolic syndrome (MetS) and its features in middle-aged and elderly adults at high cardiovascular risk. Design Prospective, longitudinal, population-based cohort. Setting PREvenciõn con DIeta MEDiterránea study. Participants Men and women (N = 6,606) divided into three age groups (<65, 65-74, ≥75). Measurements Energy and nutrient intake was evaluated using a validated 137-item food frequency questionnaire. MetS and its features were defined in accordance with the criteria of the American Heart Association and National Heart, Lung, and Blood Institute. Results A positive association was observed between GI and MetS prevalence in the youngest and middle age groups for participants without diabetes mellitus, but no relationship was found for those with diabetes mellitus. During the median follow-up of 4.8 years, higher GI and GL were related to greater risk of MetS in the middle age group, independent of the presence of diabetes mellitus. Changes in dietary GI were associated with risk of developing the high fasting glucose component of the MetS in the oldest age category, and changes in dietary GL were associated with risk of developing abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and high blood pressure in the youngest age category. Conclusion Dietary GI and GL have a potential role in the development of MetS and associated clinical features, with particular age-dependent considerations.Funded by: Centro Nacional de Investigaciones Cardiovasculares. Grant Number: 06/2007; Instituto de Salud Carlos III; Fondo de Investigación Sanitaria PI. Grant Number: 07/0473; Ministerio de Ciencia e Innovación. Grant Numbers: AGL-2009–13906-C02, AGL2010–22319-C03; Ministerio de Sanidad-Plan Nacional de Drogas. Grant Number: 2010/087; Fondo de Investigaciones Sanitarias. Grant Number: PI1002658 Fundación Mapfre 2010 Government of the Basque Country. Grant Number: IT386–10 University of the Basque Country. Grant Number: UFI 11/32 Catalan government Miguel Servet. Grant Number: 06/00100Peer Reviewe

Reactive astrogliosis is associated with higher cerebral glucose consumption in the early Alzheimer's continuum

PURPOSE: Glial activation is one of the earliest mechanisms to be altered in Alzheimer's disease (AD). Glial fibrillary acidic protein (GFAP) relates to reactive astrogliosis and can be measured in both cerebrospinal fluid (CSF) and blood. Plasma GFAP has been suggested to become altered earlier in AD than its CSF counterpart. Although astrocytes consume approximately half of the glucose-derived energy in the brain, the relationship between reactive astrogliosis and cerebral glucose metabolism is poorly understood. Here, we aimed to investigate the association between fluorodeoxyglucose ([18F]FDG) uptake and reactive astrogliosis, by means of GFAP quantified in both plasma and CSF for the same participants. METHODS: We included 314 cognitively unimpaired participants from the ALFA + cohort, 112 of whom were amyloid-β (Aβ) positive. Associations between GFAP markers and [18F]FDG uptake were studied. We also investigated whether these associations were modified by Aβ and tau status (AT stages). RESULTS: Plasma GFAP was positively associated with glucose consumption in the whole brain, while CSF GFAP associations with [18F]FDG uptake were only observed in specific smaller areas like temporal pole and superior temporal lobe. These associations persisted when accounting for biomarkers of Aβ pathology but became negative in Aβ-positive and tau-positive participants (A + T +) in similar areas of AD-related hypometabolism. CONCLUSIONS: Higher astrocytic reactivity, probably in response to early AD pathological changes, is related to higher glucose consumption. With the onset of tau pathology, the observed uncoupling between astrocytic biomarkers and glucose consumption might be indicative of a failure to sustain the higher energetic demands required by reactive astrocytes

Plasma metabolites associated with homeostatic model assessment of insulin resistance: metabolite-model design and external validation

Different plasma metabolites have been related to insulin resistance (IR). However, there is a lack of metabolite models predicting IR with external validation. The aim of this study is to identify a multi-metabolite model associated to the homeostatic model assessment (HOMA)-IR values. We performed a cross-sectional metabolomics analysis of samples collected from overweight and obese subjects from two independent studies. The training step was performed in 236 subjects from the SATIN study and validated in 102 subjects from the GLYNDIET study. Plasma metabolomics profile was analyzed using three different approaches: GC/quadrupole-TOF, LC/quadrupole-TOF, and nuclear magnetic resonance (NMR). Associations between metabolites and HOMA-IR were assessed using elastic net regression analysis with a leave-one-out cross validation (CV) and 100 CV runs. HOMA-IR was analyzed both as linear and categorical (median or lower versus higher than the median). Receiver operating characteristic curves were constructed based on metabolites’ weighted models. A set of 30 metabolites discriminating extremes of HOMA-IR were consistently selected. These metabolites comprised some amino acids, lipid species and different organic acids. The area under the curve (AUC) for the discrimination between HOMA-IR extreme categories was 0.82 (95% CI: 0.74–0.90), based on the multi-metabolite model weighted with the regression coefficients of metabolites in the validation dataset. We identified a set of metabolites discriminating between extremes of HOMA-IR and able to predict HOMA-IR with high accuracy