关键词： Depatuxizumab mafodotin   Glioblastoma   Lomustine   Patient-reported outcomes   Phase II   Quality of life   Randomised   Temozolomide   Visual disorders  

摘要： Background: In the EORTC 1410/ INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-edrug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis. Patients and methods: Patients (n Z 260) were randomised 1:1:1 to receive either Depatux-M 1.25 mg/kg or 1.0 mg/kg intravenously every 2 weeks with oral temozolomide (TMZ) 150 mg/ m(2), Depatux-M alone, or TMZ or oral lomustine (CCNU) 110 mg/ m(2) ( TMZ/CCNU). HRQoL outcomes were recorded using the EORTC core Quality of Life QLQ-C30, and brain cancer-specific QLQ-BN20 questionnaires. Questionnaires were completed at baseline, weeks 8 and 16, and month 6, and changes from baseline to each time point were calculated. NDFS was defined as time to first deterioration in World Health Organisation performance status. Results: Compliance with HRQoL was 88.1% at baseline and decreased to 37.9% at month 6. Differences from baseline between Depatux-M arms and TMZ/CCNU in global health/QoL status throughout treatment did not reach clinical relevance (>= 10 points). Self-reported visual disorders deteriorated to a clinically relevant extent with Depatux-M arms versus TMZ/CCNU at all timepoints (mean differences range: 24.6-35.1 points). Changes from baseline for other HRQoL scales and NDFS were generally similar between treatment arms. Conclusions: Depatux-M had no impact on HRQoL and NDFS in patients with EGFRamplified recurrent glioblastoma, except for more visual disorders, an expected side- effect of the study drug. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： Blind   Functional magnetic resonance imaging   Motor imagery   Supplementary motor area   Cerebellum  

摘要： In people with normal sight, mental simulation (motor imagery) of an experienced action involves a multisensory (especially kinesthetic and visual) emulation process associated with the action. Here, we examined how long-term blindness influences sensory experience during motor imagery and its neuronal correlates by comparing data obtained from blind and sighted people. We scanned brain activity with functional magnetic resonance imaging (fMRI) while 16 sighted and 14 blind male volunteers imagined either walking or jogging around a circle of 2 m radius. In the training before fMRI, they performed these actions with their eyes closed. During scanning, we explicitly instructed the blindfolded participants to generate kinesthetic motor imagery. After the experimental run, they rated the degree to which their motor imagery became kinesthetic or spatio-visual. The imagery of blind people was more kinesthetic as per instructions, while that of the sighted group became more spatio-visual. The imagery of both groups commonly activated bilateral frontoparietal cortices including supplementary motor areas (SMA). Despite the lack of group differences in degree of brain activation, we observed stronger functional connectivity between the SMA and cerebellum in the blind group compared to that in the sighted group. To conclude, long-term blindness likely changes sensory emulation during motor imagery to a more kinesthetic mode, which may be associated with stronger functional coupling in kinesthetic brain networks compared with that in sighted people. This study adds valuable knowledge on motor cognition and mental imagery processes in the blind.

关键词： Therapeutic hypothermia   Targeted temperature management   Cardiac arrest   Pre-hospital   Outcome  

摘要： Objective: Survival after pre-hospital cardiac arrest (PHCA) remains low. Pre-hospital therapeutic hypothermia (PTH) is believed to improve patient's outcomes, but data on efficacy and safety remains scarce. Herein, we aimed to assess the influence of PTH on survival, neurological outcome, and adverse effects in patients with PHCA. Materials and methods: A literature search of PubMed CENTRAL, EMBASE, and The Cochrane Central Register of Controlled Trials databases from inception to August 2019 was conducted and retrieved abstracts were independently assessed by two reviewers. The primary outcome was survival to hospital discharge with a favorable neurological outcome. Secondary outcomes were survival to hospital discharge and temperature upon hospital *** safety outcomes included pulmonary edema and recurrent arrest during transport to the hospital. We also considered a favorable neurological function to hospital discharge or longest post arrest follow-up. Results: Eleven studies including 4891 patients were included into final analysis. The survival to hospital discharge did not differ between PTH and control group (RR 1.02;95%Cl 0.93 to 1.12). Among 4891 participants (2466 in PTH group and 2425 in control group), 1087 participants (564 vs. 523, respectively) had a favorable neurological outcome. Pulmonary edema occurred in 320 cases in PTH group and 273 in control group with significant heterogeneity (RR 0.90, 95%CI 0.59-138;12 = 80%). The pooled results showed a significant difference in rearrests between the PTH and control group (RR 1.19;95%CI 1.00 to 1.42). Conclusion: Our analysis demonstrates that PTH does not improve survival at discharge or neurological outcome. (C) 2020 Elsevier Inc. All rights reserved.

摘要： Purpose This study aimed to identify the genetic cause of a new multiple congenital anomalies syndrome observed in three individuals from two unrelated families. Methods Clinical assessment was conducted prenatally and at different postnatal stages. Genetic studies included exome sequencing (ES) combined with single-nucleotide polymorphism (SNP) array based homozygosity mapping and trio ES. Dermal fibroblasts were used for functional assays. Results A clinically recognizable syndrome characterized by severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet was identified. Additional features included eye abnormalities, hearing impairment, and electroencephalogram anomalies. ES detected different homozygous truncating variants in MAPKAPK5 in both families. Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization. Conclusion Our data indicate that loss-of-function variants in MAPKAPK5 result in a severe developmental disorder and reveal a major role of this gene in human brain, heart, and limb development.

关键词： COVID-19   Education   Neurosurgery   New York City   Pandemic   Redeployment  

摘要： Coronavirus disease 2019 (COVID-19) has disrupted lives and indelibly impacted the practice of medicine since emerging as a pandemic in March 2020. For neurosurgery departments throughout the United States, the pandemic has created unique challenges across subspecialties in devising methods of triage, workflow, and operating room safety. Located in New York City, at the early epicenter of the COVID-19 crisis, the Weill Cornell Medicine Department of Neurological Surgery was disrupted and challenged in many ways, requiring adaptations in clinical operations, workforce management, research, and education. Through our department's collective experience, we offer a glimpse at how our faculty and administrators overcame obstacles, and transformed in the process, at the height of the COVID-19 pandemic.

摘要： Background The objective was to determine the association between perioperative risk factors and brain imaging abnormalities on neurologic outcome in neonates with hypoplastic left heart syndrome (HLHS) or d-Transposition of the great arteries (d-TGA) who underwent cardiac surgery including cardiopulmonary bypass. Methods A retrospective analysis of neonates with HLHS or d-TGA undergoing cardiac surgery including cardiopulmonary bypass between 2009 and 2017 was performed. Perioperative risk factors and Andropoulos' Brain Injury Scores from pre- and postoperative brain magnetic resonant images (MRI) were correlated to outcome assessments on patients between 5 and 23 months of age. Neurologic outcome was measured using the Pediatric Stroke Outcome Measure (PSOM) and Pediatric Version of the Glasgow Outcome Scale-Extended (GOS-E). Results Fifty-three neonates met our enrollment criteria (24 HLHS, 29 d-TGA). Mechanical ventilation > 12 days and DHCA > 40 min were associated with worse outcome. MRI measures of brain injuries were not associated with worse outcome by PSOM or GOS-E. Conclusion For HLHS and d-TGA patients, duration of mechanical ventilation and DHCA are associated with adverse neurologic outcome. Neonatal brain MRI commonly demonstrates acquired brain injuries, but the clinical impact of these abnormalities are not often seen before 2 years of age. Impact Acquired brain injury is common in high-risk neonates with CHD but poor neurological outcome was not predicted by severity of injury or lesion subtype. Longer stay in ICU is associated with postoperative brain injuries on MRI. Total duration of ventilation > 12 days is predictive of adverse neurological outcome scores. DHCA > 40 min is associated with adverse neurological outcome scores. Neurological outcome before 2 years of age is more affected by the clinical course than by cardiac diagnosis.

关键词： anti-oxidant   anti-cholinesterase   alpha-amylase   alpha-glucosidase   pancreatic lipase   mechanical parameters  

摘要： BACKGROUND: Obesity and type 2 diabetes mellitus are the most extended current chronic diseases and also Alzheimer pathology which is a progressive degenerative neurological disorder. Therefore, finding effective enzyme inhibitors responsible for the development of these diseases are essential. Therefore, the aim of this study was to investigate the impact of fruit puree (Cydonia oblonga,Ziziphus jujubeandMalus domestica) and pomegranate juice cultivar ('Mollar de Elche' and 'Wonderful') of dried pomegranate sheets (DS) on the inhibition of enzymes associated with metabolic (alpha-amylase, alpha-glucosidase, and pancreatic lipase activity), and neurological disorder (acetylcholinesterase and butyrylcholinesterase activity). Quality properties (colour coordinates, texture properties and sensory characteristics) of DS were also studied. In addition, it was researched the effect of storage conditions (4 months at 4 and 20 degrees C) on phenolic content. RESULTS: DS from jujube had the highest antioxidant capacity and were characterized by the highest storage stability with respect to phenolic compounds. The alpha-amylase and alpha-glucosidase half maximal inhibitory concentration (IC50, in mg mL(-1)) inhibition of DS ranged from 107 to 216 and from 55.2 to values indicating no effect, respectively. The inhibition toward pancreatic lipase (IC50 < 5 mg mL(-1)), acetylcholinesterase (ranged 9.15-22.2%) and butyrylcholinesterase (ranged 20.6-48.6%) was increased with the presence of total flavonoids and hydroxycinnamic acids content (identifying mainly in DS from quinces). It is noteworthy that none of the samples presented off-flavour notes, supporting the high quality of the products. CONCLUSION: DS can be an innovative supplement to a diet as a snack used in the prevention of neurological changes and disorders of carbohydrate and lipid metabolism. (c) 2020 Society of Chemical Industry

摘要： Pregnancy and early childhood are periods with high plasticity in neurological development. Environmental perturbations during these sensitive windows can have lifelong developmental consequences. This review summarizes key findings relevant to the effects of air pollution on neurological development. Mounting evidence suggests that exposure to air pollution, both during pregnancy and childhood, is associated with childhood developmental outcomes ranging from changes in brain structures to subclinical deficits in developmental test scores, and, ultimately, developmental disorders such as attention-deficit/hyperactivity disorders or autism spectrum disorders. Although the biological mechanisms of effects remain to be elucidated, multiple pathways are probably involved and include oxidative stress, inflammation, and/or endocrine disruption. Given the alarming global increase in developmental disorders in recent years, and increased human exposures to pollution, it is critical to reduce personal and community-level exposures through tight collaboration of interdisciplinary and multi-level bodies including community partners, physicians, industry partners, policy makers, public health practitioners, and researchers.

摘要： Aims To investigate current awareness and practices of neurological prognostication in comatose cardiac arrest (CA) patients. Methods An anonymous questionnaire was distributed to 1600 emergency physicians in 75 hospitals which were selected randomly from China between January and July 2018. Results 92.1% respondents fulfilled the survey. The predictive value of brain stem reflex, motor response and myoclonus was confirmed by 63.5%, 44.6% and 31.7% respondents, respectively. Only 30.7% knew that GWR value < 1.1 indicated poor prognosis and only 8.1% know the most commonly used SSEP N20. Status epilepticus, burst suppression and suppression were considered to predict poor outcome by only 35.0%, 27.4% and 20.9% respondents, respectively. Only 46.7% knew NSE and only 24.7% knew S-100. Only a few respondents knew that neurological prognostication should be performed later than 72 hours from CA either in TTM or non-TTM patients. In practice, the most commonly used method was clinical examination (85.4%). Only 67.9% had used brain CT for prognosis and 18.4% for MRI. NSE (39.6%) was a little more widely used than S-100 beta (18.0%). However, SSEP (4.4%) and EEG (11.4%) were occasionally performed. Conclusions Neurological prognostication in CA survivors had not been well understood and performed by emergency physicians in China. They were more likely to use clinical examination rather than objective tools, especially SSEP and EEG, which also illustrated that multimodal approach was not well performed in practice.