SETTING AND PARTICIPANTS: We are recruiting study participants from 12 tertiary care hospitals in 10 countries on 5 continents.
PARTICIPANTS: We are enrolling patients ≥65 years of age, requiring hospital admission after non-cardiac surgery, who have an anticipated length of hospital stay of at least 2 days after elective non-cardiac surgery that occurs under general or neuraxial anaesthesia.
PRIMARY AND SECONDARY OUTCOME MEASURES: Patients are recruited before elective non-cardiac surgery, and their cognitive function is measured using the Montreal Cognitive Assessment (MoCA) instrument. After surgery, a brain MRI study is performed between postoperative days 2 and 9 to determine the presence of acute brain infarction. One year after surgery, the MoCA is used to assess postoperative cognitive function. Physicians and patients are blinded to the MRI study results until after the last patient follow-up visit to reduce outcome ascertainment bias.We will undertake a multivariable logistic regression analysis in which the dependent variable is the change in cognitive function 1 year after surgery, and the independent variables are acute perioperative covert stroke as well as other clinical variables that are associated with cognitive dysfunction.
CONCLUSIONS: The NeuroVISION study will characterise the epidemiology of covert stroke and its clinical consequences. This will be the largest and the most comprehensive study of perioperative stroke after non-cardiac surgery.
TRIAL REGISTRATION NUMBER: NCT01980511; Pre-results.
METHODS: In this three-year longitudinal study, 125 subjects (77 PD patients and 48 spousal/sibling controls) underwent clinical, biochemical and body composition assessments using dual-energy X-ray absorptiometry.
RESULTS: Patients were older than controls (65.6 ± 8.9 vs. 62.6 ± 7.1, P = 0.049), with no significant differences in gender, comorbidities, dietary intake and physical activity. Clinically significant weight loss (≥5% from baseline weight) was recorded in 41.6% of patients, with a doubling of cases (6.5 to 13.0%) classified as underweight at study end. Over three years, patients demonstrated greater reductions in BMI (mean -1.2 kg/m2, 95%CI-2.0 to -0.4), whole-body fat percentage (-2.5% points, 95%CI-3.9 to -1.0), fat mass index (FMI) (-0.9 kg/m2, 95%CI-1.4 to -0.4), visceral fat mass (-0.1 kg, 95%CI-0.2 to 0.0), and subcutaneous fat mass (-1.9 kg, 95%CI-3.4 to -0.5) than in controls, with significant group-by-time interactions after adjusting for age and gender. Notably, 31.2% and 53.3% of patients had FMI<3rd (severe fat deficit) and <10th centiles, respectively. Muscle mass indices decreased over time in both groups, without significant group-by-time interactions. Multiple linear regression models showed that loss of body weight and fat mass in patients were associated with age, dyskinesia, psychosis and constipation.
CONCLUSIONS: We found progressive loss of weight in PD patients, with greater loss of both visceral and subcutaneous fat, but not muscle, compared to controls. Several associated factors (motor and non-motor disease features) were identified for these changes, providing insights on possible mechanisms and therapeutic targets.
METHODS: A multi-ethnic cohort of PD patients from Malaysia (n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry.
RESULTS: Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK-PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and "loss of the swallow tail" sign, were documented.
CONCLUSIONS: This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK-PINK1. It also further supports the pathogenicity of the p. Leu347Pro variant.
SETTING: A single centre study, Malaysia.
PARTICIPANTS: Adults aged between 18 and 60 years with mTBI as a result of road traffic accident, with no previous history of head trauma, minimum of 9 years education and abnormal cognition at 3 months will be included. The exclusion criteria include pre-existing chronic illness or neurological/psychiatric condition, long-term medication that affects cognitive/psychological status, clinical evidence of substance intoxication at the time of injury and major polytrauma. Based on multiple estimated calculations, the minimum intended sample size is 50 participants (Cohen's d effect size=0.35; alpha level of 0.05; 85% power to detect statistical significance; 40% attrition rate).
INTERVENTIONS: Intervention group will receive individualised structured cognitive rehabilitation. Control group will receive the best patient-centred care for attention disorders. Therapy frequency for both groups will be 1 hour per week for 12 weeks.
OUTCOME MEASURES: Primary: Neuropsychological Assessment Battery-Screening Module (S-NAB) scores. Secondary: Diffusion Tensor Imaging (DTI) parameters and Goal Attainment Scaling score (GAS).
RESULTS: Results will include descriptive statistics of population demographics, CogniPlus cognitive program and metacognitive strategies. The effect of intervention will be the effect size of S-NAB scores and mean GAS T scores. DTI parameters will be compared between groups via repeated measure analysis. Correlation analysis of outcome measures will be calculated using Pearson's correlation coefficient.
CONCLUSION: This is a complex clinical intervention with multiple outcome measures to provide a comprehensive evidence-based treatment model.
ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Research Ethics Committee UMMC (MREC ID NO: 2016928-4293). The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences.
TRIAL REGISTRATION NUMBER: NCT03237676.
MATERIALS AND METHODS: Cardiovascular risk factors (CRFs) were estimated using the 30-year Framingham Risk Score in 73 childhood leukemia survivors (median age: 25; median years from diagnosis: 19) and 78 healthy controls (median age: 23). Radial arterial stiffness was measured using pulse wave analyzer, while endothelial activation markers were measured by soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). Retinal fundus images were analyzed for central retinal artery/vein equivalents (CRAE/CRVE) and arteriolar-venular ratio (AVR).
RESULTS: cALL survivors had higher CRF (P<0.0001), arterial stiffness (P=0.001), and sVCAM-1 (P=0.007) compared with controls. Survivors also had significantly higher CRVE (P=0.021) while AVR was significantly lower (P=0.026) in survivors compared with controls, compatible with endothelial dysfunction. In cALL survivors with intermediate risk for CVD, CRAE, and AVR are significantly lower, while sVCAM-1 and sICAM-1 are significantly higher when compared with survivors with low CVD risk after adjusting with covariates (age, sex, and smoking status).
CONCLUSIONS: cALL survivors have an increased risk of CVD compared with age-matched peers. The survivors demonstrated microvasculopathy, as measured by retinal vascular analysis, in addition to physical and biochemical evidence of endothelial dysfunction. These changes predate other measures of CVD. Retinal vessel analysis may be utilized as a robust screening tool for identifying survivors at increased risk for developing CVD.
METHODS: Fifty-one patients with childhood MB were seen at University Malaya Medical Center. Data from 43 patients were analyzed; eight patients were excluded because their families refused treatment after surgery.
RESULTS: Headache and vomiting were the most common presenting symptoms, and the mean interval between symptom onset and diagnosis was 4 weeks. Fourteen patients presented with metastatic disease. Five-year progression-free survival (± SE) for patients ≥ 3 years old was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) in the high-risk group and 68.6% ± 18.6% (95% CI, 40.3% to 100%) in the average-risk group, and 5-year overall survival (± SE) in these two groups was 41.7% ± 14.2% (95% CI, 21.3% to 81.4%) and 58.3% ± 18.6% (95% CI, 31.3% to 100%), respectively. Children younger than 3 years old had 5-year progression-free and overall survival rates (± SE) of 47.6% ± 12.1% (95% CI, 28.9% to 78.4%) and 45.6% ± 11.7% (95% CI, 27.6% to 75.5%), respectively. Time to relapse ranged from 4 to 132 months. Most patients who experienced relapse died within 1 year. Febrile neutropenia, hearing loss, and endocrinopathy were the most common treatment-related complications.
CONCLUSION: The survival rate of childhood MB in Malaysia is inferior to that usually reported in the literature. We postulate that the following factors contribute to this difference: lack of a multidisciplinary neuro-oncology team, limited health care facilities, inconsistent risk assessment, insufficient data in the National Cancer Registry and pathology reports, inadequate long-term follow-up, and cultural beliefs leading to treatment abandonment.
MATERIAL AND METHODS: Forty-two glioma patients were subjected to MRI using a standard tumor protocol with diffusion tensor imaging (DTI). The tumor and peritumor regions were delineated using snake model with reference to structural and diffusion MRI. A preprocessing pipeline of the structural MRI image, DTI data, and tumor regions was implemented. Tractography was performed to delineate the white matter (WM) tracts in the selected tumor regions via probabilistic fiber tracking. DTI indices were investigated through comparative mapping of WM tracts and tumor regions in low-grade gliomas (LGG) and high-grade gliomas (HGG).
RESULTS: Significant differences were seen in the planar tensor (Cp) in peritumor regions; mean diffusivity, axial diffusivity and pure isotropic diffusion in solid-enhancing tumor regions; and fractional anisotropy, axial diffusivity, pure anisotropic diffusion (q), total magnitude of diffusion tensor (L), relative anisotropy, Cp and spherical tensor (Cs) in solid nonenhancing tumor regions for affected WM tracts. In most cases of HGG, the WM tracts were not completely destroyed, but found intact inside the tumor.
DISCUSSION: Probabilistic fiber tracking revealed the existence and distribution of WM tracts inside tumor core for both LGG and HGG groups. There were more DTI indices in the solid nonenhancing tumor region, which showed significant differences between LGG and HGG.