Mild Cognitive Impairment among Type II Diabetes Mellitus Patients Attending University Teaching Hospital

BACKGROUND: Type II diabetes mellitus (TIIDM) has been associated with structural and functional changes in the brain. TIIDM is commonly associated with obesity, insulin resistance, hypertension, and dyslipidemia, all of which can have negative impact on brain. AIM: The aim of the study was to study the risk of mild cognitive impairment (MCI) among both diabetics and non-diabetics and to identify risk factors to MCI among both groups. METHODS: Two comparative cross-sectional studies were carried out enrolling 100 diabetics and 100 age, sex, and education matching non-diabetics. Cognitive function was assessed using Montreal Cognitive Assessment (MoCA) test and risk factors for MCI were assessed. RESULTS: The subjective complaint of memory impairment among diabetics was significantly higher (34%) compared to non-diabetics (13.0%), p < 0.05. The mean of objective MoCA score was significantly lower among diabetics (25.9 ± 2.5) compared to non-diabetics (27.4 ± 2.4), p < 0.001. The rate of MCI was significantly higher among TIIDM patients (22%) compared to non-diabetics (9%), p < 0.01 and odds ratio (OR) 2.8 (95% confidence interval 1.2–6.5). Among the two studied groups, the rate of MCI was significantly higher among those aged over 50 years compared to younger age as well as among hypertensive compared to non-hypertensive persons, (p < 0.05). Among diabetics, the MCI was significantly higher among those with secondary education, having heart diseases, longer duration of DM, or repeated hypoglycemia attack, p < 0.05. A healthy diet, brain training, and social activities were found to be significantly associated with normal cognition. Logistic analysis revealed that diabetics aged above 50 was the only significant predicting factor for MCI with an OR 2.9 (95% CI: 3.8–123.3), p < 0.001. CONCLUSION: TIIDM is significantly associated with 3-times increasing risk of having MCI compared to non-diabetics. The age, hypertension, cardiovascular diseases, duration of diabetes, and frequency of hypoglycemic episodes are risk factors for cognitive impairment. A healthy diet, brain training, and social activities were associated with better cognitive function

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients

Neurotrophic tyrosine receptor kinase gene fusions (NTRK) are oncogenic drivers present at a low frequency in most tumour types (80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring NTRK gene fusions. In Phase I/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an NTRK gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered.Medicine, Faculty ofNon UBCPathology and Laboratory Medicine, Department ofReviewedFacultyResearche

Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk

Background: The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis.Aim: The aim of this study is to investigate the effect of “selected” genetic variants within the leukotriene (LT) pathway and other variants on the development of CAD.Methods: CAD was detected by cardiac catheterization. Logistic regression was performed to investigate the association of smoking and selected susceptibility variants in the LT pathway including ALOX5AP, LTA4H, LTC4S, PON1, and LTA as well as CYP1A1 on CAD risk while controlling for age, gender, BMI, family history, diabetes, hyperlipidemia, and hypertension.Results: rs4769874 (ALOX5AP), rs854560 (PON1), and rs4646903 (CYP1A1 MspI polymorphism) are significantly associated with an increased risk of CAD with respective odds ratios of 1.53703, 1.67710, and 1.35520; the genetic variant rs9579646 (ALOX5AP) is significantly associated with a decreased risk of CAD (OR 0.76163). Moreover, a significant smoking-gene interaction is determined with CYP1A1 MspI polymorphism rs4646903 and is associated with a decreased risk of CAD in current smokers (OR 0.52137).Conclusion: This study provides further evidence that genetic variation of the LT pathway, PON1, and CYP1A1 can modulate the atherogenic processes and eventually increase the risk of CAD in our study population. Moreover, it also shows the effect of smoking-gene interaction on CAD risk, where the CYP1A1 MspI polymorphism revealed a decreased risk in current smokers