Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
BMC Neurol ; 20(1): 75, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126977

RESUMO

BACKGROUND: Neuroprotection and promotion of remyelination represent important therapeutic gaps in multiple sclerosis (MS). Acute optic neuritis (ON) is a frequent MS manifestation. Based on the presence and properties of sphingosine-1-phosphate receptors (S1PR) on astrocytes and oligodendrocytes, we hypothesized that remyelination can be enhanced by treatment with fingolimod, a S1PR modulator currently licensed for relapsing-remitting MS. METHODS: MOVING was an investigator-driven, rater-blind, randomized clinical trial. Patients with acute unilateral ON, occurring as a clinically isolated syndrome or MS relapse, were randomized to 6 months of treatment with 0.5 mg oral fingolimod or subcutaneous IFN-ß 1b 250 µg every other day. The change in multifocal visual evoked potential (mfVEP) latency of the qualifying eye was examined as the primary (month 6 vs. baseline) and secondary (months 3, 6 and 12 vs. baseline) outcome. In addition, full field visual evoked potentials, visual acuity, optical coherence tomography as well as clinical relapses and measures of disability, cerebral MRI, and self-reported visual quality of life were obtained for follow-up. The study was halted due to insufficient recruitment (n = 15), and available results are reported. RESULTS: Per protocol analysis of the primary endpoint revealed a significantly larger reduction of mfVEP latency at 6 months compared to baseline with fingolimod treatment (n = 5; median decrease, 15.7 ms) than with IFN-ß 1b treatment (n = 4; median increase, 8.15 ms) (p <  0.001 for interaction). Statistical significance was maintained in the secondary endpoint analysis. Descriptive results are reported for other endpoints. CONCLUSION: Preliminary results of the MOVING trial argue in support of a beneficial effect of fingolimod on optic nerve remyelination when compared to IFN-ß treatment. Interpretation is limited by the small number of complete observations, an unexpected deterioration of the control group and a difference in baseline mfVEP latencies. The findings need to be confirmed in larger studies. TRIAL REGISTRATION: The trial was registered as EUDRA-CT 2011-004787-30 on October 26, 2012 and as NCT01647880 on July 24, 2012.

3.
Minerva Anestesiol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32000470

RESUMO

BACKGROUND: Presurgical cognitive impairment (PreCI) is frequently seen in older age, but the influence on postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) remains unclear. The present study sought to determine the association between PreCI, POD and POCD with special focus to different PreCI domains. METHODS: We analyzed 934 patients with complete baseline neurocognitive assessment. PreCI was determined as cognitive performance of at least 2 standard deviation (SD) below the mean performance of non-surgical controls. POD was assessed according to the Diagnostic and Statistical Manual of Mental Disorders 4 (DSM-4). POCD at 3 months follow-up was calculated by the reliable change index (RCI). Associations between PreCI and POD or POCD were assessed using multivariable logistic regression models adjusted for age, sex, randomization, ASA status, type of anesthesia and type of surgery. RESULTS: PreCI was significantly associated with POD [OR 1.936 (95%CI 1.119 to 3.348); p=0.015] and POCD [OR 3.091 (95%CI 1.287 to 7.426); p=0.012]. Patients with coincident PreCI and POD were significantly more likely to develop POCD [OR 6.131 (95%CI 1.476 to 22.364); p=0.007]. Differentiation between no PreCI, amnestic and non-amnestic PreCI revealed a sole influence of amnestic PreCI on POD and POCD. CONCLUSIONS: Patients ≥ 60 years with PreCI were more likely to develop POD and POCD, respectively. The odds for POCD were highest in patients with PreCI whom also suffered from POD. Amnestic rather than non-amnestic PreCI might play a key role in the development of POD and POCD. These results warrant further pathophysiological investigations and demand preventive strategies.

4.
Trials ; 21(1): 3, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898518

RESUMO

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. METHODS: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20-40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. DISCUSSION: Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03508414. Retrospectively registered on 25 April 2018.

5.
Anesth Analg ; 130(2): 341-351, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30855340

RESUMO

BACKGROUND: Skeletal muscle failure in critical illness (intensive care unit-acquired weakness) is a well-known complication developing early during intensive care unit stay. However, muscle weakness during the perioperative setting has not yet been investigated. METHODS: We performed a subgroup investigation of a prospective observational trial to investigate perioperative muscle weakness. Eighty-nine patients aged 65 years or older were assessed for handgrip strength preoperatively, on the first postoperative day, at intensive care unit discharge, at hospital discharge, and at 3-month follow-up. Functional status was evaluated perioperatively via Barthel index, instrumental activities of daily living, Timed Up and Go test, and functional independence measure. After exclusion of patients with intensive care unit-acquired weakness or intensive care unit stay of ≥72 hours, 59 patients were included into our analyses. Of these, 14 patients had additional pulmonary function tests preoperatively and on postoperative day 1. Blood glucose was measured intraoperatively every 20 minutes. RESULTS: Handgrip strength significantly decreased after surgery on postoperative day 1 by 16.4% (P < .001). Postoperative pulmonary function significantly decreased by 13.1% for vital capacity (P = .022) and 12.6% for forced expiratory volume in 1 second (P = .001) on postoperative day 1. Handgrip strength remained significantly reduced at hospital discharge (P = .016) and at the 3-month follow-up (P = .012). Perioperative glucose levels showed no statistically significant impact on muscle weakness. Instrumental activities of daily living (P < .001) and functional independence measure (P < .001) were decreased at hospital discharge, while instrumental activities of daily living remained decreased at the 3-month follow-up (P = .026) compared to preoperative assessments. CONCLUSIONS: Perioperatively acquired weakness occurred, indicated by a postoperatively decreased handgrip strength, decreased respiratory muscle function, and impaired functional status, which partly remained up to 3 months.

6.
Urol Int ; : 1-9, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801153

RESUMO

INTRODUCTION: Patients with consistent suspicion for prostate cancer (PCa) and multiple negative prebiopsies prior to multiparametric magnetic resonance imaging (mpMRI) are still frequently evaluated for an image-guided biopsy and are reported with heterogeneous detection rates. The inclusion of a systematic biopsy (SB) is also still recommended with predominant sampling within the posterior/peripheral zone of the prostate. The aim of this study was (I) to evaluate PCa detection rates using a modified 10 core SB template including anterior biopsies in combination with mpMRI/ultrasound fusion-guided targeted biopsy (TB) in patients with 3 or more negative prebiopsies and (II) to compare mpMRI index lesion localization with histologically confirmed locali-zation from associated prostatectomy samples. METHODS: Overall 1,337 consecutive patients underwent sensor-based registration TB of the prostate and a subsequent 10-core SB between January 2012 and December 2015 at our institution. For this study, 101 patients with ≥3 negative prebiopsies and prostate imaging - reporting data system lesions ≥3 were pooled prospectively and underwent TB and a modified SB including 2 ventral (anterior) biopsies. Detection rates were estimated for the modified SB, TB, and its combination. A subgroup analysis of 35 patients undergoing prostatectomy was performed by a head-to-head comparison of mpMRI index lesion and histologically confirmed PCa index lesion localization. RESULTS: The overall detection rate for PCa was 54.5%. The combination of TB and SB detected 14 (25.4%) more cases missed by TB alone (p < 0.001) and 7 (12.7%) more cases missed by SB alone (p = 0.016), respectively. A postoperative Gleason upgrade was seen in 12/35 (34.3%) cases within the TB group and in 14/35 (40.0%) in the SB group, respectively. The subgroup analysis showed a predominant location of PCa index lesions anteriorly at the level of the midgland. The MRI detection rate of the anteriorly located index lesions was 70.4% (15/21 cases) with a clinically significant Gleason score (≥3 + 4 = 7a [International Society of Urological Pathology grade 2]) in 80.9%. Interestingly a modified SB template detected 90.5% (19/21) of the anteriorly located index lesions. CONCLUSION: Our data suggest that in patients with multiple prebiopsies PCa seems to be predominantly located anteriorly. We suggest the general integration of anterior biopsies despite TB in repeat biopsy patients.

7.
Anasthesiol Intensivmed Notfallmed Schmerzther ; 54(11-12): 652-667, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31805585

RESUMO

Perioperative neurocognitive disorders (pNCD) are relevant to long term treatment outcome after elective surgery. The detection of pNCD is challenging and based on extended neuropsychological testing that often is not feasible due to economy driven time constraints during preoperative risk assessment. Only recently new recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery facilitated the transition of the former research diagnosis postoperative cognitive dysfunction (POCD) as a clinical diagnosis based on DSM-5 criteria. In our article we provide an overview of the new recommended diagnostic criteria for pNCD based on the publication by the Nomenclature Consensus Working Group in November 2018. We discuss ideas for the implementation of clinical routine pNCD screening in patients aged 70 years or older with elective surgery and possible options for further support of patients screened positively and their families and care givers.


Assuntos
Anestesia , Transtornos Cognitivos , Delírio , Idoso , Anestesia/efeitos adversos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Delírio/diagnóstico , Delírio/etiologia , Humanos , Transtornos Neurocognitivos , Complicações Pós-Operatórias
8.
Int J Obes (Lond) ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31819201

RESUMO

BACKGROUND: Physical activity improves insulin sensitivity in obesity. Hypoxia training is claimed to augment this effect. We tested the hypothesis that normobaric hypoxia training would improve insulin sensitivity in obese patients with metabolic syndrome. METHODS: In a randomized controlled trial, 23 obese men with metabolic syndrome who were not informed of the FiO2 conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO2 21%) conditions or hypoxia (n = 12; FiO2 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual V̇O2max. Assessment of myocellular insulin sensitivity by euglycemic hyperinsulinemic clamp was performed in 21 of these subjects before and after 6 weeks of training. Comprehensive phenotyping also included biopsies of subcutaneous adipose tissues. RESULTS: The intermittent moderate physical exercise protocol did not substantially change the myocellular insulin sensitivity within 6 weeks under normoxic conditions (ISIClamp: 0.035 (IQR 0.016-0.075) vs. 0.037 (IQR 0.026-0.056) mg* kg-1 *min-1/(mU* l-1); p = 0.767). In contrast, ISIClamp improved during hypoxia training (0.028 (IQR 0.018-0.035) vs. 0.038 (IQR 0.024-0.060) mg * kg-1 *min-1/(mU *l-1); p < 0.05). Between group comparison of ISIClamp change revealed a small difference between groups (Cohen's d = 0.26). Within the hypoxic group, improvement of ISIClamp during training was associated with individual increase of circulating vascular endothelial growth factor (VEGF) levels (r = 0.678, p = 0.015), even if mean VEGF levels were not modified by any training condition. Atrial natriuretic peptide (ANP) system components were not associated with increased ISIClamp during hypoxic training. CONCLUSIONS: Physical training under hypoxic conditions could partially augment the favorable effects of exercise alone on myocellular insulin sensitivity in obese men with metabolic syndrome. Concomitant changes in VEGF might represent an underlying pathophysiological mechanism.

9.
BMJ Open ; 9(10): e032695, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666276

RESUMO

INTRODUCTION: Haemophagocytic lymphohistiocytosis (HLH) in adults is characterised by toxic immune activation and a sepsis-like syndrome, leading to high numbers of undiagnosed cases and mortality rates of up to 68%. Early diagnosis and specific immune suppressive treatment are mandatory to avoid fatal outcome, but the diagnostic criteria (HLH-2004) are adopted from paediatric HLH and have not been validated in adults. Experimental studies suggest biomarkers to sufficiently diagnose HLH. However, biomarkers for the diagnosis of adult HLH have not yet been investigated. METHODS AND ANALYSIS: The HEMICU (Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients) study aims to estimate the incidence rate of adult HLH among suspected adult patients in intensive care units (ICUs). Screening for HLH will be performed in 16 ICUs of Charité - Universitätsmedizin Berlin. The inclusion criteria are bicytopaenia, hyperferritinaemia (≥500 µg/L), fever or when HLH is suspected by the clinician. Over a period of 2 years, we expect inclusion of about 100 patients with suspected HLH. HLH will be diagnosed if at least five of the HLH-2004 criteria are fulfilled, together with an expert review; all other included patients will serve as controls. Second, a panel of potential biomarker candidates will be explored. DNA, plasma and serum will be stored in a biobank. The primary endpoint of the study is the incidence rate of adult HLH among suspected adult patients during ICU stay. Out of a variety of measured biomarkers, this study furthermore aims to find highly potential biomarkers for the diagnosis of adult HLH in ICU. The results of this study will contribute to improved recognition and patient outcome of adult HLH in clinical routine. ETHICS AND DISSEMINATION: The institutional ethics committee approved this study on 1 August 2018 (Ethics Committee of Charité - Universitätsmedizin Berlin, EA4/006/18). The results of the study will be disseminated in an international peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03510650.

10.
Stroke ; 50(11): 3213-3219, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31526121

RESUMO

Background and Purpose- NMDAR1-abs (anti-N-Methyl-D-Aspartate receptor GluN1 antibodies), predominantly known in the context of autoimmune encephalitis, have been observed in serum of healthy individuals. A previous study found smaller stroke magnetic resonance imaging lesion growth in seropositive patients, suggesting a neuroprotective effect of these antibodies. The impact of NMDAR1-abs seropositivity on long-term functional outcome and recurrent vascular events and death after first-ever stroke remains unclear. Methods- Data from the Prospective Cohort with Incident Stroke-Berlin were used. NMDAR1-abs (ie, IgM, IgA, and IgG) were measured in serum within 7 days after first stroke. Outcomes of interest included modified Rankin Scale at one year and the time-to-event of a combined end point (recurrent stroke, myocardial infarction, and all-cause mortality) within 3 years. We calculated odds ratios from adjusted partial proportional odds models and subsequently compared outcome of patients with low titers (1:10; 1:32; and 1:100), and high titers (1:320; 1:1000) to seronegative patients. Furthermore, we estimated hazard ratios for a secondary vascular event or death in NMDAR1-abs seropositive compared to seronegative patients in models adjusted for confounders. Results- The analyses included 583 patients with antibody measurements (39% female, median National Institutes of Health Stroke Scale:2, IQR:1-4), and NMDAR1-abs were observed in 76 (13%) patients. NMDAR1-abs seroprevalence was not associated with functional outcome (odds ratio=1.27; 95% CI, 0.77-2.09); sub-group analyses, however, showed worse outcome in patients with high titers (odds ratio=3.47; 95% CI, 1.54-7.80). Seropositive patients had an increased risk for a secondary vascular event or death (hazard ratios =1.83, 95% CI, 1.10-3.05). Conclusions- In our study, NMDAR1-abs seropositivity was not associated with functional outcome at one year after stroke, however, high titers (≥1:320) were associated with poor functional outcome. Furthermore, NMDAR1-abs seropositivity was associated with increased cardiovascular risk within 3 years after first stroke, independently from other risk factors. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01363856.

11.
Minerva Anestesiol ; 85(11): 1201-1210, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486622

RESUMO

BACKGROUND: Hyperglycemia frequently occurs during major surgery and is associated with adverse postoperative outcomes. This study aimed to investigate the influence of intraoperative hyperglycemia on incidences of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). METHODS: Eighty-seven patients aged ≥65 years undergoing elective surgery were included in this prospective observational subproject of the BioCog study. Blood glucose (BG) levels were measured every 20 minutes intraoperatively. Hyperglycemia was defined as BG levels ≥150 mg·dL-1. Patients were assessed for POD twice daily until postoperative day 7. The occurrence of POCD was determined three months after surgery. Multivariable logistic regression was used to identify associations between hyperglycemia and POD as well as POCD. Secondary endpoints comprised duration of hyperglycemia, maximum glucose level (Glucosemax) and differences between diabetic and non-diabetic patients. RESULTS: POD occurred in 41 (47.1%), POCD in five (15.2%) patients. In two separate multivariable logistic regression models, hyperglycemia was significantly associated with POD (OR 3.86 [CI 95% 1.13, 39.49], P=0.044) but not POCD (3.59 [NaN, NaN], P=0.157). Relative duration of hyperglycemia was higher in POD patients compared to patients without POD (20 [0; 71] % versus 0 [0; 55] %, P=0.075), whereas the maximum glucose levels during surgery were similar between the two groups. Considering only non-diabetic patients, relative duration of hyperglycemia (P=0.003) and Glucosemax (P=0.015) were significantly higher in patients with POD. CONCLUSIONS: Intraoperative hyperglycemia was independently associated with POD but not POCD. Relative duration of hyperglycemia appeared thereby to also play a role. Especially hyperglycemic non-diabetic patients might be at high risk for POD.

12.
Acta Anaesthesiol Scand ; 63(10): 1282-1289, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31283835

RESUMO

BACKGROUND: Post-operative delirium (POD) and post-operative neurocognitive disorder (NCD) are frequently seen in the elderly. Development of biomarkers for pre-operative risk prediction is of major relevance. As inflammation present before surgery might predispose to POD and post-operative NCD development, we aim to determine associations between pre-operative C-reactive protein (CRP) and the incidence of POD and post-operative NCD. METHODS: In this observational study, we analyzed 314 patients enrolled in the SuDoCo trial, who had a pre-operative CRP measurement the day before surgery. Primary outcomes were POD assessed according DSM-4 from day 1 until day 7 after surgery and post-operative NCD assessed 3 months after surgery. We conducted multivariable logistic regression analysis adjusted for age, sex, randomization, body mass index, MMSE, ASA status, infection/autoimmune disease/malignoma and types of surgery to determine associations between CRP with POD and post-operative NCD, respectively. RESULTS: Pre-operative CRP was independently associated with POD [OR 1.158 (95% CI 1.040, 1.291); P = .008]. Patients with CRP values ≥5 mg/dL had a 4.8-fold increased POD risk [OR 4.771 (95% CI 1.765, 12.899; P = .002)] compared to patients with lower CRP values. However, no association was seen between pre-operative CRP and post-operative NCD [OR 0.552 (95% CI 0.193, 1.581); P = .269]. CONCLUSIONS: Pre-operative CRP levels were independently associated with POD but not post-operative NCD after three months. Moreover, higher pre-operative CRP levels showed higher risk for POD. This strengthens the role of inflammation in the development of POD. Assessment of CRP before surgery might allow risk stratification of POD. TRIAL REGISTRATION: This study was registered with ISRCTN Register 36437985 on 02 March 2009.

13.
PLoS Biol ; 17(4): e3000188, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30964856

RESUMO

The need for replication of initial results has been rediscovered only recently in many fields of research. In preclinical biomedical research, it is common practice to conduct exact replications with the same sample sizes as those used in the initial experiments. Such replication attempts, however, have lower probability of replication than is generally appreciated. Indeed, in the common scenario of an effect just reaching statistical significance, the statistical power of the replication experiment assuming the same effect size is approximately 50%-in essence, a coin toss. Accordingly, we use the provocative analogy of "replicating" a neuroprotective drug animal study with a coin flip to highlight the need for larger sample sizes in replication experiments. Additionally, we provide detailed background for the probability of obtaining a significant p value in a replication experiment and discuss the variability of p values as well as pitfalls of simple binary significance testing in both initial preclinical experiments and replication studies with small sample sizes. We conclude that power analysis for determining the sample size for a replication study is obligatory within the currently dominant hypothesis testing framework. Moreover, publications should include effect size point estimates and corresponding measures of precision, e.g., confidence intervals, to allow readers to assess the magnitude and direction of reported effects and to potentially combine the results of initial and replication study later through Bayesian or meta-analytic approaches.


Assuntos
Pesquisa Biomédica/métodos , Reprodutibilidade dos Testes , Projetos de Pesquisa/estatística & dados numéricos , Animais , Teorema de Bayes , Pesquisa Biomédica/estatística & dados numéricos , Interpretação Estatística de Dados , Humanos , Modelos Estatísticos , Probabilidade , Publicações , Tamanho da Amostra
14.
Brain Behav ; 9(5): e01271, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30912272

RESUMO

BACKGROUND AND PURPOSE: Brain perfusion measurement in the subacute phase of stroke may support therapeutic decisions. We evaluated whether arterial spin labeling (ASL), a noninvasive perfusion imaging technique based on magnetic resonance imaging (MRI), adds diagnostic and prognostic benefit to diffusion-weighted imaging (DWI) in subacute stroke. METHODS: In a single-center imaging study, patients with DWI lesion(s) in the middle cerebral artery (MCA) territory were included. Onset to imaging time was ≤7 days and imaging included ASL and DWI sequences. Qualitative (standardized visual analysis) and quantitative perfusion analyses (region of interest analysis) were performed. Dichotomized early outcome (modified Rankin Scale [mRS] 0-2 vs. 3-6) was analyzed in two logistic regression models. Model 1 included DWI lesion volume, age, vascular pathology, admission NIHSS, and acute stroke treatment as covariates. Model 2 added the ASL-based perfusion pattern to Model 1. Receiver-operating-characteristic (ROC) and area-under-the-curve (AUC) were calculated for both models to assess their predictive power. The likelihood-ratio-test compared both models. RESULTS: Thirty-eight patients were included (median age 70 years, admission NIHSS 4, onset to imaging time 67 hr, discharge mRS 2). Qualitative perfusion analysis yielded additional diagnostic information in 84% of the patients. In the quantitative analysis, AUC for outcome prediction was 0.88 (95% CI 0.77-0.99) for Model 1 and 0.97 (95% CI 0.91-1.00) for Model 2. Inclusion of perfusion data significantly improved performance and outcome prediction (p = 0.002) of stroke imaging. CONCLUSIONS: In patients with subacute stroke, our study showed that adding perfusion imaging to structural imaging and clinical data significantly improved outcome prediction. This highlights the usefulness of ASL and noninvasive perfusion biomarkers in stroke diagnosis and management.


Assuntos
Encéfalo , Imagem de Difusão por Ressonância Magnética/métodos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Imagem de Perfusão/métodos , Marcadores de Spin , Acidente Vascular Cerebral , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Gravidade do Paciente , Valor Preditivo dos Testes , Prognóstico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia
15.
Nat Sci Sleep ; 10: 337-344, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498381

RESUMO

Background: The first night effect (FNE) is a polysomnography (PSG) habituation effect in the first of several consecutive in-laboratory PSGs (I-PSGs). The FNE is caused by the discomfort provoked by electrodes and cables and the exposure to an unfamiliar environment. A reverse FNE (RFNE) with an improved sleep in the first night is characteristic of insomnia, presumably because the video PSG in the sleep laboratory leads to a decrease in the negatively toned cognitive activity. Therefore, two or more I-PSGs are required for an accurate diagnosis. Although the FNE is well documented in I-PSG, little is known about the FNE and the RFNE in home-based PSGs (H-PSGs). Methods: This is a retrospective analysis of a recently published cross-sectional study using H-PSG. Sixty-three consecutive patients suffering from multiple sclerosis (MS) were investigated by two consecutive H-PSGs without video. The differences between the first and second H-PSGs were analyzed. The patients were classified into four subgroups: no sleep disorder, insomnia, sleep-related breathing disorders (SRBDs), and periodic limb movement disorder or restless legs syndrome (PLMD/RLS). Results: MS patients suffering from insomnia showed no RFNE. MS patients with SRBD or PLMD/RLS showed no reduced sleep efficiency but significantly less slow wave sleep. Furthermore, SRBD patients showed significantly less non-rapid eye movement (NREM) sleep, and PLMD/RLS patients were significantly awake longer in the first night after sleep onset (increased wake-after-sleep-onset time) and showed a higher rapid eye movement (REM) latency. Conclusion: SRBD and PLMD/RLS patients showed a significant FNE. Two consecutive H-PSGs are required in these patients to obtain a precise hypnogram even in the ambulatory field. In MS patients suffering from insomnia, no RFNE was found, and in insomnia patients one H-PSG seems to be sufficient.

16.
Clin Epidemiol ; 10: 853-862, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30100759

RESUMO

Background: Age-related cognitive impairment is rising in prevalence but is not yet fully characterized in terms of its epidemiology. Here, we aimed to elucidate the role of obesity, diabetes and hypertension as candidate risk factors. Methods: Original baseline data from 3 studies (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis of cross-sectional associations of diabetes, hypertension, blood pressure, obesity (body mass index [BMI] ≥30 kg/m2) and BMI with presence of cognitive impairment in log-binomial regression analyses. Cognitive impairment was defined as scoring more than 2 standard deviations below controls on at least one of 5-11 cognitive tests. Underweight participants (BMI<18.5 kg/m2) were excluded. Results were pooled across studies in fixed-effects inverse variance models. Results: Analyses totaled 1545 participants with a mean age of 61 years (OCTOPUS) to 70 years (SuDoCo). Cognitive impairment was found in 29.0% of participants in DECS, 8.2% in SuDoCo and 45.6% in OCTOPUS. In pooled analyses, after adjustment for age, sex, diabetes and hypertension, obesity was associated with a 1.29-fold increased prevalence of cognitive impairment (risk ratio [RR] 1.29; 95% CI 0.98, 1.72). Each 1 kg/m2 increment in BMI was associated with 3% increased prevalence (RR 1.03; 95% CI 1.00, 1.06). None of the remaining risk factors were associated with impairment. Conclusion: Our results show that older people who are obese have higher prevalence of cognitive impairment compared with normal weight and overweight individuals, and independently of co-morbid hypertension or diabetes. Prospective studies are needed to investigate the temporal relationship of the association.

17.
Radiother Oncol ; 128(2): 229-235, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29699833

RESUMO

PURPOSE OR OBJECTIVE: A homogeneity index (HI) measures the uniformity of a dose distribution within a given target volume. Traditional HIs only use a limited number of dose-volume histogram data-points for calculation. A voxel-based homogeneity index (VHI) is proposed which utilizes the entire information of the three-dimensional dose distribution. We compared the VHI with existing HIs and analyzed if VHI results were associated with treatment outcomes in patients who underwent therapeutic WBRT. MATERIAL AND METHODS: The VHI analyzes deviations from the prescribed dose in each voxel of the target volume. We retrospectively analyzed WBRT treatment plans. Overall survival (OS), CNS progression-free-survival (CNS PFS) and hazard rates were compared for tertile-split levels of the VHI using the Kaplan-Meier methods and multivariable Cox-regression analysis. RESULTS: WBRT treatment plans (n = 770) were used for HIs comparison. OS and CNS PFS were assessed for 430 patients. The VHI showed a higher sensitivity for dose inhomogeneities. Lower OS and CNS PFS were observed for higher levels of VHIUnderdosage, particularly in patients with good performance status (KPS >70%) (OS: Log-rank P = .007, HR = 1.37 95%CI [1.09, 1.72]). CONCLUSION: Higher sensitivity and feasibility to assess treatment plan quality using the VHI were demonstrated. First clinical implications were found in terms of compromised OS/CNS PFS for WBRT with radiation underdosage.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Irradiação Craniana/mortalidade , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Resultado do Tratamento
18.
PLoS One ; 13(1): e0190811, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29381701

RESUMO

BACKGROUND: In acute ischemic stroke the status of collateral circulation is a critical factor in determining outcome. We propose a less invasive alternative to digital subtraction angiography for evaluating collaterals based on dynamic-susceptibility contrast magnetic resonance imaging. METHODS: Perfusion maps of Tmax and cerebral blood flow (CBF) were created for 35 patients with baseline occlusion of a major cerebral artery. Volumes of hypoperfusion were defined as having a Tmax delay of > 4 seconds (Tmax4s) and > 6 seconds (Tmax6s) and a CBF drop below 80% of healthy, contralateral tissue. For each patient a ratio between the volume of the CBF and the Tmax based perfusion deficit was calculated. Associations with collateral status and radiological outcome were assessed with the Mann-Whitney-U test, uni- and multivariable logistic regression analyses as well as area under the receiver-operator-characteristic (ROC) curve. RESULTS: The CBF/Tmax volume ratios were significantly associated with bad collateral status in crude logistic regression analysis as well as with adjustment for NIHSS at admission and baseline infarct volume (OR = 2.5 95% CI[1.2-5.4] p = 0.020 for CBF/Tmax 4s volume ratio and OR = 1.6 95% CI[1.0-2.6] p = 0.031 for CBF/Tmax6s volume ratio). Moreover, the ratios were significantly correlated to final infarct size (Spearman's rho = 0.711 and 0.619, respectively for the CBF/Tmax4s volume ratio and CBF/Tmax6s volume ration, all p<0.001). The ratios also had a high area under the ROC curve of 0.93 95%CI[0.86-1.00]) and 0.90 95%CI[0.80-1.00]respectively for predicting poor radiological outcome. CONCLUSIONS: In the setting of acute ischemic stroke the CBF/Tmax volume ratio can be used to differentiate between good and insufficient collateral circulation without the need for invasive procedures like conventional angiography.


Assuntos
Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Circulação Colateral , Acidente Vascular Cerebral/fisiopatologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos Retrospectivos
19.
Europace ; 20(11): 1758-1765, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29165559

RESUMO

Aims: Therapeutic oral anticoagulation on hospital admission reduces morbidity and mortality after acute ischaemic stroke in patients with atrial fibrillation (AF). The underlying mechanism is not fully understood. In order to assess the impact of INR-level on admission on stroke volume, lesion pattern and the frequency of intracranial arterial occlusion, we analysed serial MRI measurements in AF patients suffering acute ischaemic stroke. Methods and results: This subgroup analysis of the prospective '1000Plus' study included patients with acute ischaemic stroke and known AF or a first episode of AF in hospital. All patients underwent serial brain magnetic resonance imaging. Stroke patients were categorized as follows: Group1, phenprocoumon intake, international normalized ratio (INR) ≥1.7 on admission, no thrombolysis; Group2, INR < 1.7 on admission, thrombolysis; and Group3, INR < 1.7, no thrombolysis. In 98 AF patients {77 ± 9 years, 60% male; median National Institute of Health Stroke Scale [NIHSS] score on admission 5 (interquartile range [IQR] 2-8)} with known AF before admission, territorial infarction was less often found in Group 1 (n = 20) compared with Group 2 + 3 (20% vs. 47%, P = 0.022). Arterial occlusion rate on admission differed among groups (30%, 75%, and 35%, respectively, P = 0.004) but not between Group 1 vs. Group 2 + 3 (30% vs. 45%, P = 0.31). Median FLAIR volume on Days 5-7 was lower in Group1 compared with Group 2 (n = 20) [3.2 cm3 (IQR 1.1-11.3) vs. 18.6 cm3 (IQR 8.2-49.4); P = 0.009] but not compared with Group 2 + 3 [7.8 cm3 (IQR 1.6-25.9); P = 0.23]. An INR ≥ 1.7 on admission was not associated with smaller stroke volume in multivariable regression analysis. Adding 57 patients with a first AF episode during the in-hospital stay, similar results were observed in 155 AF patients. Conclusion: In this AF cohort, an INR ≥ 1.7 at stroke onset affects lesion pattern but does not affect significantly lower stroke volume and the frequency of arterial occlusion on admission.


Assuntos
Arteriopatias Oclusivas , Fibrilação Atrial , Isquemia Encefálica/diagnóstico por imagem , Acidente Vascular Cerebral , Varfarina/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/prevenção & controle , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/patologia , Feminino , Alemanha/epidemiologia , Humanos , Coeficiente Internacional Normatizado/métodos , Tempo de Internação , Imagem por Ressonância Magnética/métodos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
20.
Neurol Neuroimmunol Neuroinflamm ; 5(1): e423, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29259998

RESUMO

Objective: To conduct a randomized, sham-controlled phase I/IIa study to evaluate the safety and preliminary efficacy of deep brain H-coil repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) and the primary motor cortex (MC) in patients with MS with fatigue or depression (NCT01106365). Methods: Thirty-three patients with MS were recruited to undergo 18 consecutive rTMS sessions over 6 weeks, followed by follow-up (FU) assessments over 6 weeks. Patients were randomized to receive high-frequency stimulation of the left PFC, MC, or sham stimulation. Primary end point was the safety of stimulation. Preliminary efficacy was assessed based on changes in Fatigue Severity Scale (FSS) and Beck Depression Inventory scores. Randomization allowed only analysis of preliminary efficacy for fatigue. Results: No serious adverse events were observed. Five patients terminated participation during treatment due to mild side effects. Treatment resulted in a significant median FSS decrease of 1.0 point (95%CI [0.45,1.65]), which was sustained during FU. Conclusions: H-coil rTMS is safe and well tolerated in patients with MS. The observed sustained reduction in fatigue after subthreshold MC stimulation warrants further investigation. ClinicalTrialsgov identifier: NCT01106365. Classification of evidence: This study provides Class III evidence that rTMS of the prefrontal or primary MC is not associated with serious adverse effects, although this study is underpowered to state this with any precision.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA