24 research outputs found

    Estudio de la aterosclerosis intracraneal de gran arteria mediante resonancia magnética de alta resolución de pared arterial

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    La patología cerebrovascular representa la tercera causa de muerte en los países occidentales, y la primera de discapacidad en el adulto [1]. En concreto en España, el ictus supone la primera causa de muerte en la mujer y la segunda en el hombre [2], y debido al progresivo envejecimiento de la población española y europea, se prevé que su repercusión socioeconómica sea también creciente, lo cual hace necesario mejorar tanto a nivel de prevención primaria como secundaria, evitando la progresión y la complicación de la enfermedad cerebrovascular según su etiología de base. La arteriosclerosis intracraneal es una causa importante de ictus en todo el mundo [4], especialmente en los países asiáticos. En nuestro país supone la causa responsable de un 8-10% de los ictus isquémicos, siendo pacientes con un riesgo de recurrencia clínica anual del 12% [5,6] a pesar de tratamiento médico intensivo en prevención secundaria [3]. Su agresividad clínica y su elevado riesgo de recurrencia hacen necesaria la identificación de nuevos marcadores de la presencia de arteriosclerosis intracraneal que nos permitan predecir el riesgo de progresión y de recurrencia clínica de estos pacientes, individualizando así su riesgo. Varios estudios señalan que la prevalencia de la arterioesclerosis intracraneal ha sido infraestimada [4,5], probablemente debido a que los métodos diagnósticos hasta ahora utilizados para su detección, como son el Doppler-Duplex, angio-RM o angio-TC, únicamente son capaces de identificar la enfermedad en fases avanzadas y sólo valoran el interior del vaso, dando lugar al infradiagnóstico de esta entidad. Sin embargo, la reciente introducción de la resonancia magnética de alta resolución (HRMRI) ha permitido el estudio de la pared arterial e, incluso, podría ser capaz de identificar los distintos componentes de la placa [4,7,10,11,15]. Esto podría ser una posible forma de caracterizar así su estabilidad de forma no invasiva, permitiéndonos identificar a los pacientes con mayor riesgo de recurrencia clínica, y así tratarles de forma más agresiva. Sin embargo, al no existir suficientes estudios necrópsicos para establecer una correlación de esos hallazgos radiológicos con sus equivalentes histológicos, hasta ahora esta relación se ha establecido por extrapolación de características de otras arterias como la carótida extracraneal o las coronarias. Entre los marcadores estudiados, se ha postulado que el realce postcontraste (RPC) puede ser un marcador de actividad inflamatoria de la placa [16]. Sin embargo, el significado de este hallazgo a nivel intracraneal permanece aún sin resolverOtroGrado en Medicin

    Identification of prefoldin amplification (1q23.3-q24.1) in bladder cancer using comparative genomic hybridization (CGH) arrays of urinary DNA

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    Array-CGH represents a comprehensive tool to discover genomic disease alterations that could potentially be applied to body fluids. In this report, we aimed at applying array-CGH to urinary samples to characterize bladder cancer. Methods: Urinary DNA from bladder cancer patients and controls were hybridized on 44K oligonucleotide arrays. Validation analyses of identified regions and candidates included fluorescent in situ hybridization (FISH) and immunohistochemistry in an independent set of bladder tumors spotted on custom-made tissue arrays (n = 181). Results: Quality control of array-CGH provided high reproducibility in dilution experiments and when comparing reference pools. The most frequent genomic alterations (minimal recurrent regions) among bladder cancer urinary specimens included gains at 1q and 5p, and losses at 10p and 11p. Supervised hierarchical clustering identified the gain at 1q23.3-q24.1 significantly correlated to stage (p = 0.011), and grade (p = 0.002). The amplification and overexpression of Prefoldin (PFND2), a selected candidate mapping to 1q23.3-q24.1, correlated to increasing stage and tumor grade by means of custom-designed and optimized FISH (p = 0.013 and p = 0.023, respectively), and immunohistochemistry (p ≤0.0005 and p = 0.011, respectively), in an independent set of bladder tumors included in tissue arrays. Moreover, PFND2 overexpression was significantly associated with poor disease-specific survival (p ≤0.0005). PFND2 was amplified and overexpressed in bladder tumors belonging to patients providing urinary specimens where 1q23.3q24.1 amplification was detected by array-CGH. Conclusions: Genomic profiles of urinary DNA mirrowed bladder tumors. Molecular profiling of urinary DNA using array-CGH contributed to further characterize genomic alterations involved in bladder cancer progression. PFND2 was identified as a tumor stratification and clinical outcome prognostic biomarker for bladder cancer patientsSupported by grants (SAF2009-13035 and SAF2012-40206) from the Spanish Ministry of Education and Culture (to Dr Sánchez-Carbayo). Virginia López is recipient of a predoctoral award from the Spanish Ministry of Education and Cultur

    Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis

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    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown etiology and poorly understood pathophysiology. There is no specific biomarker either for diagnosis or prognosis. The aim of our study was to investigate differentially expressed proteins in the CSF and serum from patients with ALS to determine their role in the disease process and evaluate their utility as diagnostic or prognostic biomarkers. We performed mass spectrometry in the CSF from 3 patients with ALS and 3 healthy controls (HCs). The results were compared with motor cortex dysregulated transcripts obtained from 11patients with sporadic ALS and 8 HCs. Candidate proteins were tested using ELISA in the serum of 123 patients with ALS, 30 patients with Alzheimer disease (AD), 28 patients with frontotemporal dementia (FTD), and 102 HCs. Patients with ALS, AD, and FTD were prospectively recruited from January 2003 to December 2020. A group of age-matched HCs was randomly selected from the Sant Pau Initiative on Neurodegeneration cohort of the Sant Pau Memory Unit. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and osteopontin (Spp1) were differentially expressed in the CSF and the motor cortex transcriptome of patients with ALS compared with that in HCs (p < 0.05). NOD2 and Spp1 levels were significantly higher in sera from patients with ALS than in HCs (p < 0.001). Receiver operating characteristic analysis showed an area under the curve of 0.63 for NOD2 and 0.81 for Spp1. NOD2 levels were significantly lower in patients with AD and FTD than in patients with ALS (p < 0.0001), but we found no significant differences in Spp1 levels between patients with ALS, AD (p = 0.51), and FTD (p = 0.42). We found a negative correlation between Spp1 levels and ALS functional rating scale (r = −0.24, p = 0.009). Our discovery-based approach identified NOD2 as a novel biomarker in ALS and adds evidence to the contribution of Spp1 in the disease process. Both proteins are involved in innate immunity and autophagy and are increased in the serum from patients with ALS. Our data support a relevant role of neuroinflammation in the pathophysiology of the disease and may identify targets for disease-modifying treatments in ALS. Further longitudinal studies should investigate the diagnostic and prognostic value of NOD2 and Spp1 in clinical practice

    Remote Monitoring of Treatment Response in Parkinson's Disease: The Habit of Typing on a Computer

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    The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting.This study was conducted with research funds from Michael J. Fox Foundation for Parkinson's Research Grant 10860.Peer reviewe

    Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS

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    Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases. Diagnostic groups comprised patients with TDP-43 proteinopathy ALS, 4R tauopathy progressive supranuclear palsy, behavior variant FTD (bvFTD) as a group with either tau or TDP-43 pathology, and healthy controls. EV tau ratios were low in progressive supranuclear palsy and high in bvFTD with tau pathology. EV TDP-43 levels were high in ALS and in bvFTD with TDP-43 pathology. Both markers discriminated between the diagnostic groups with area under the curve values &gt;0.9, and between TDP-43 and tau pathology in bvFTD. Both markers strongly correlated with neurodegeneration, and clinical and neuropsychological markers of disease severity. Findings were replicated in an independent validation cohort of 292 patients including 34 genetically confirmed cases. Taken together, the combination of EV TDP-43 levels and EV 3R/4R tau ratios may aid the molecular diagnosis of FTD, FTD spectrum disorders and ALS, providing a potential biomarker to monitor disease progression and target engagement in clinical trials.</p

    Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

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    Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

    Detecting motor impairment in early Parkinson's disease via natural typing interaction with keyboards: Validation of the neuroQWERTY approach in an uncontrolled at-home setting

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    Background: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease and one of the most common forms of movement disorder. Although there is no known cure for PD, existing therapies can provide effective symptomatic relief. However, optimal titration is crucial to avoid adverse effects. Today, decision making for PD management is challenging because it relies on subjective clinical evaluations that require a visit to the clinic. This challenge has motivated recent research initiatives to develop tools that can be used by nonspecialists to assess psychomotor impairment. Among these emerging solutions, we recently reported the neuroQWERTY index, a new digital marker able to detect motor impairment in an early PD cohort through the analysis of the key press and release timing data collected during a controlled in-clinic typing task. Objective: The aim of this study was to extend the in-clinic implementation to an at-home implementation by validating the applicability of the neuroQWERTY approach in an uncontrolled at-home setting, using the typing data from subjects’ natural interaction with their laptop to enable remote and unobtrusive assessment of PD signs. Methods: We implemented the data-collection platform and software to enable access and storage of the typing data generated by users while using their computer at home. We recruited a total of 60 participants; of these participants 52 (25 people with Parkinson’s and 27 healthy controls) provided enough data to complete the analysis. Finally, to evaluate whether our in-clinic-built algorithm could be used in an uncontrolled at-home setting, we compared its performance on the data collected during the controlled typing task in the clinic and the results of our method using the data passively collected at home. Results: Despite the randomness and sparsity introduced by the uncontrolled setting, our algorithm performed nearly as well in the at-home data (area under the receiver operating characteristic curve [AUC] of 0.76 and sensitivity/specificity of 0.73/0.69) as it did when used to evaluate the in-clinic data (AUC 0.83 and sensitivity/specificity of 0.77/0.72). Moreover, the keystroke metrics presented a strong correlation between the 2 typing settings, which suggests a minimal influence of the in-clinic typing task in users’ normal typing. Conclusions: The finding that an algorithm trained on data from an in-clinic setting has comparable performance with that tested on data collected through naturalistic at-home computer use reinforces the hypothesis that subtle differences in motor function can be detected from typing behavior. This work represents another step toward an objective, user-convenient, and quasi-continuous monitoring tool for PD

    Immune Response and Safety of SARS-CoV-2 mRNA-1273 Vaccine in Patients With Myasthenia Gravis

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    Evidence regarding the safety and efficacy of messenger RNA (mRNA) vaccines in patients with myasthenia gravis (MG) after immunosuppressive therapies is scarce. Our aim is to determine whether the mRNA-1273 vaccine is safe and able to induce humoral and cellular responses in patients with MG. We performed an observational, longitudinal, prospective study including 100 patients with MG of a referral center for MG in our country, conducted from April 2021 to November 2021 during the vaccination campaign. The mRNA-1273 vaccine was scheduled for all participants. Blood samples were collected before vaccination and 3 months after a second dose. Clinical changes in MG were measured using the MG activities of daily life score at baseline and 1 week after the first and second doses. A surveillance of all symptoms of coronavirus disease 2019 (COVID-19) was conducted throughout the study. Humoral and cellular immune responses after vaccination were assessed using a spike-antibody ELISA and interferon gamma release assay in plasma. The primary outcomes were clinically significant changes in MG symptoms after vaccination, adverse events (AEs), and seroconversion and T-cell immune response rates. Ninety-nine patients completed the full vaccination schedule, and 98 had 2 blood samples taken. A statistically significant worsening of symptoms was identified after the first and second doses of the mRNA-1273 vaccine, but this was not clinically relevant. Mild AEs occurred in 14 patients after the first dose and in 21 patients after the second dose. Eighty-seven patients developed a humoral response and 72 patients showed a T-cell response after vaccination. A combined therapy with prednisone and other immunosuppressive drugs correlated with a lower seroconversion ratio (OR = 5.97, 95% CI 1.46-24.09, p = 0.015) and a lower T-cell response ratio (OR = 2.83, 95% CI 1.13-7.13, p = 0.024). Our findings indicate that the mRNA vaccination against COVID-19 is safe in patients with MG and show no negative impact on the disease course. Patients achieved high humoral and cellular immune response levels. This study provides Class IV evidence that patients with MG receiving the mRNA-1273 vaccine did not show clinical worsening after vaccination and that most of the patients achieved high cellular or immune response levels
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