关键词： cardiac arrest   CT   EEG   MR   Neurological prognostication   Out-of-hospital   SSEP  

摘要： Background: Neurological prognostication is an essential part of post-resuscitation care in out-of-hospital cardiac arrest (OHCA). This study aims to assess the use of computed tomography (CT) and magnetic resonance imaging (MR) of the head, electroencephalography (EEG), and somatosensory evoked potentials (SSEP) in neurological prognostication in resuscitated OHCA patients and factors associated with their use in Danish tertiary and non-tertiary centers from 2005 to 2013 and associations with outcome. Methods: We used the Danish Cardiac Arrest Registry to identify patients >= 18 years of age admitted to intensive care units due to OHCA of presumed cardiac etiology. CT 0-20 days and MR, SSEP, and EEG >= 2-20 days post OHCA were considered related to prognostication. Incidence and factors associated with procedures were assessed by multiple Cox regression with death as competing risk. Results: Use of CT, MR, EEG, and SSEP increased during the study period (CT: 51%-67%, HRCT: 1.06, CI: 1.03-1.08, MR: 2%-5%, P = .08, EEG: 6%-33%, HREEG: 1.25, CI: 1.19-1.30, SSEP: 4%-15%, HRSSEP: 1.23, CI: 1.15-1.32). EEG and SSEP were more used in tertiary centers than non-tertiary (HREEG: 1.86, CI: 1.51-2.29, HRSSEP: 4.44, CI: 2.86-6.89). Use of CT, SSEP, and EEG were associated with higher 30-day mortality, and MR was associated with lower (HRCT: 1.15, CI: 1.01-1.30, HRMR: 0.53, CI: 0.37-0.77, HRSSEP: 1.90, CI: 1.57-2.32, HREEG: 1.75, CI: 1.49-2.05). Conclusion: Use of neurological prognostication procedures increased during the study period. EEG and SSEP were more used in tertiary centers. CT, EEG and SSEP were associated with increased mortality.

关键词： Cardiac arrest   Targeted temperature management   Meta-analysis  

摘要： This study was aimed at a serial evaluation of the prognostic values of initial shockable rhythm, bystander cardiopulmonary resuscitation (CPR) and gender for neurological outcome and survival in adults treated with targeted temperature management (TTM) following cardiac arrest (CA). PubMed, Embase and the Cochrane Library were searched for eligible studies. Pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate prognostic values using RevMan 5.3. The outcomes were favorable neurological outcome (defined as cerebral performance category of 1 and 2) and survival. Seventeen studies were subjected to the meta-analysis. Favorable neurological outcome was associated with significantly higher odds of an initial shockable rhythm (OR: 7.63, 95%Cl: 6.51-8.96), bystander CPR (OR: 1.44, 95%CI: 1.14-1.82), male (OR: 1.39, 95%CI: 1.20-1.61). Survival was associated with higher odds of an initial shockable rhythm (OR: 4.88, 95%CI: 3.18-4.79), higher odds of bystander CPR (OR: 1.71, 95%Cl: 1.05-2.77). No significant association was found between survival and male. In adult patients treated with TTM, initial shockable rhythm, bystander CPR and male sex were associated with a higher likelihood of favorable neurological outcome. Initial shockable rhythm and bystander CPR were associated with a higher likelihood of survival. These factors could help in identifying patients who are eligible for (C) 2018 Elsevier Inc. All rights reserved.

关键词： biomarkers   genes   genotype   neurological outcomes   TBI  

摘要： Diagnostic and prognostic biomarkers of traumatic brain injury (TBI) are actively being pursued;potential candidates include glial fibrillary acid protein (GFAP), S100 calcium-binding protein B (S100B), and ubiquitin C-terminal hydrolase L1 (UCHL1), two of which the United States Food and Drug Administration (FDA) recently approved for marketing of blood tests for adult concussion. The relationship between biomarker-encoding genes and TBI outcomes remains unknown. This pilot study explores variation in 18 single nucleotide polymorphisms (SNPs) in biomarker-encoding genes as predictors of neurological outcome in a population of adults with severe TBI. Participants (n=305) were assessed using the Glasgow Outcome Scale (GOS) at 3, 6, 12, and 24 months post-injury. Multivariate logistical regression was used to calculate the odds ratio (OR) and determine the odds of having a lower score on the GOS (=1-2 vs. 3-5) based on variant allele presence, while controlling for confounders. Possession of the variant allele of one S100B SNP (rs1051169) was associated with higher scores on the GOS at 3 months (OR=0.39;p=0.04), 6 months (OR=0.34;p=0.02), 12 months (OR=0.32;p=0.02), and 24 months (OR=0.30;p=0.02) post-severe TBI. The relationship among these polymorphisms, protein levels, and biomarker utility, merits examination. These findings represent a novel contribution to the evidence that can inform future studies aimed at enhancing interpretation of biomarker data, identifying novel biomarkers, and ultimately harnessing this information to improve clinical outcomes and personalize care.

关键词： Human stem cell transplant   Neurological complications   Viral infections   Next generation sequencing  

摘要： Background: Neurological complications (NC) in allogeneic hematopoietic stem cell transplant (HSCT) recipients lead to long-term sequelae and result in significant morbidity and mortality. Since risk factors for NC include viral infection or reactivation, virome inspection after HSCT might be helpful to the clinical management of patients after HSCT. Objectives and study design: In this study we investigated whether any viruses are found in association with NC after HSCT. For this purpose, unbiased next generation sequencing (NGS) was used to characterize nucleic acid (NA) content in cerebrospinal fluid (CSF) taken at time of NC in 35 HSCT patients. Virome definition in CSF from non-transplanted subjects (controls) was also tested to define the commensal flora. Results and conclusions: A higher number of reads/contigs mapped to viruses in patients compared to the controls (7,626 vs 235). Besides bacteriophages, Torque teno virus (TTV) was also identified in both controls and patients. Interestingly, a significantly higher number of TTV-like sequences was detected in the patient samples (7,236 vs 9), showing similarities to distinct genotypes;3/2,575, 2/1,692 and 2/2,969 contigs/reads mapped to TTV11, TTV13 and Torque teno midi virus, respectively. In conclusion, unbiased NGS demonstrated to be a suitable approach to characterize the virome in samples containing limiting amounts of NA. The higher TTV levels and genetic diversity found in CSF of subjects with NC after HSCT might suggest a possible association between TTV reactivation and the disorder. However, further studies are needed to evaluate the possible role of TTV on NC in HSCT patients.

关键词： Coxsackievirus A6   Hand-foot-and-mouth disease   Novel   Recombination   Epidemiology   Hong Kong  

摘要： Background: Coxsackievirus A6 (CV-A6) represents the predominant enterovirus serotype in Hong Kong, but its epidemiology in our population was unknown. Objectives: To examine the clinical and molecular epidemiology of CV-A6 and detect emerging recombinant strains in Hong Kong. Study design: Nasopharyngeal aspirates (NPAs) from patients with febrile or respiratory illness were subject to RT-PCR for CV-A6 and sequencing of 5'-NCR and VP1. CV-A6-positive samples were further subject to 2C and 3D gene sequencing. Complete genome sequencing was performed on potential recombinant strains. Results: Thirty-six (0.35%) NPAs were positive for CV-A6 by 5'-NCR RT-PCR and sequencing, 28 of which confirmed by partial VP1 gene sequencing. Among the 28 patients (mainly young children) with CV-A6 infection, hand-foot-and-mouth disease (HFMD) (43%), herpangina (18%) and tonsillitis (11%) were the most common diagnoses. Seven (25%) patients had neurological manifestations, including febrile seizures, encephalitis and meningitis. VP1 gene analysis showed that 24 CV-A6 strains circulating in Hong Kong belonged to genotype D5, while 4 strains belonged to D4. Further 2C and 3D gene analysis revealed eight potential recombinant strains. Genome sequencing of five selected strains confirmed four recombinant strains: HK459455/2013 belonging to recombination group RJ arisen from CV-A6/CV-A4, HK458288/2015 and HK446377/2015 representing novel group RL arisen from CV-A6/CV-A4, and HK462069/2015 representing novel group RM arisen from CV-A6/EV-A71. Recombination breakpoints located at 3D were identified in the latter three recombinant strains, with HK462069/2015 (from a child with encephalitis) having acquired 3D region from EV-A71. Conclusions: We identified novel recombinant CV-A6 strains in Hong Kong, with 3D being a common recombination site.

关键词： Autoimmune epilepsy   Drug-resistant epilepsy   Epilepsy   Neuronal autoantibodies  

摘要： BackgroundAutoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic *** determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the ***-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were *** antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive *** factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

关键词： aortic stenosis   neurological events   stroke   surgical aortic valve replacement   transcatheter aortic valve replacement  

摘要： BACKGROUND Neurological events after aortic valve interventions are associated with increased mortality and morbidity. Transcatheter aortic valve replacement (TAVR) is increasingly offered for tower-risk patients with severe aortic stenosis, previously considered candidates for surgical aortic valve replacement (SAVR). Differences in post-procedural neurological events have important implications in treatment allocation. OBJECTIVES The authors sought to analyze the neurological events in the randomized SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial. METHODS Patients with severe, symptomatic aortic stenosis at intermediate surgical risk were randomized 1:1 to TAVR or SAVR. The rates of neurological events and quality of life were analyzed at 30 days, and 6 and 12 months post-procedure in a modified intention-to-treat population (mean age 79.8 + 6.2 years;N = 1,660). RESULTS The rates of early (30-day) stroke and post-procedural encephalopathy were higher after SAVR versus TAVR (5.4% vs. 3.3%;p = 0.031;and 7.8% vs. 1.6%;p < 0.001, respectively). At 12 months, the rate of stroke was not different between SAVR and TAVR (6.9% vs. 5.2%;p = 0.136). Early stroke and early encephalopathy resulted in an elevated mortality at 12 months in both treatment groups. Quality of life after an early stroke was significantly tower in SAVR versus TAVR patients at 30 days and was similar at 6 and 12 months. CONCLUSIONS The early stroke rate was lower after TAVR than SAVR. In patients with early strokes, QOL improved earlier after TAVR. At 12-month follow-up, stroke rates and QOL were not different between TAVR and SAVR patients. (C) 2018 by the American College of Cardiology Foundation.

关键词： aortic stenosis   stroke   surgical aortic valve replacement   transcatheter aortic valve replacement  

摘要： Corresponding Author

关键词： Rodent models   Inhibitors   Peptides and proteins   Central nervous system   Selectivity  

摘要： The serine hydrolase monoacylglycerol lipase (MGLL) converts the endogenous cannabinoid receptor agonist 2-arachidonoylglycerol (2-AG) and other monoacylglycerols into fatty acids and glycerol. Genetic or pharmacological inactivation of MGLL leads to elevation in 2-AG in the central nervous system and corresponding reductions in arachidonic acid and eicosanoids, producing antinociceptive, anxiolytic, and antineuroinflammatory effects without inducing the full spectrum of psychoactive effects of direct cannabinoid receptor agonists. Here, we report the optimization of hexafluoroisopropyl carbamate-based irreversible inhibitors of MGLL, culminating in a highly potent, selective, and orally available, CNS-penetrant MGLL inhibitor, 28 (ABX-1431). Activity-based protein profiling experiments verify the exquisite selectivity of 28 for MGLL versus other members of the serine hydrolase class. In vivo, 28 inhibits MGLL activity in rodent brain (ED50 = 0.5-1.4 mg/kg), increases brain 2-AG concentrations, and suppresses pain behavior in the rat formalin pain model. ABX-1431 (28) is currently under evaluation in human clinical trials.

关键词： MGLL gene   Tourette Syndrome   Lipid Metabolism   Neurodegenerative Diseases   Endocannabinoids   Neurologic Disorders   Monoacylglycerol Lipases  

摘要： Monoacylglycerol lipase (MGLL or MAGL) is a critical point of regulation of both endocannabinoid and eicosanoid signaling pathways in the brain, thereby providing novel therapeutic opportunities for neurological and neurodegenerative diseases. In this issue Cisar et al. disclose the discovery, optimization, and initial preclinical profiling of ABX-1431, a covalent, irreversible MGLL inhibitor. Activity-based protein profiling was key to the discovery of ABX-1431. ABX-1431 is a first-in-class experimental drug that was well-tolerated and safe in phase 1 clinical studies. Data from an exploratory phase lb study indicate that it has the potential to treat symptoms of adult patients with syndrome of Gilles de la Tourette. ABX-1431 is currently entering clinical phase 2 studies for this neurological disorder as well as for other indications, such as neuromyeltis optica and multiple sclerosis.