Background: Although the current gold standard for diagnosing thyroid nodule malignancy is ultrasound-guided fine-needle aspiration (FNA) cytology, about 20–25% of cytological evaluations are considered indeterminate for malignancy. This limitation has led to the emergence of next-generation sequencing panels, for example, ThyroSeq v3 (TSv3), which recognize highly diagnostic genetic mutations of common thyroid carcinomas in FNA samples and classify them as test-negative or test-positive, helping optimize treatment for indeterminate thyroid nodules (ITNs). Our goals were to evaluate the benign call rate (BCR) of TSv3 and assess its diagnostic performance and clinical utility while highlighting the points of consideration for a public Canadian institution. Methods: This is a single-center study conducted at the Royal Victoria Hospital (McGill University Health Centre) in Montreal, Canada, between January and February 2019. Patients were offered TSv3 following the McGill algorithm for ITN workup, a novel protocol developed at our institution to select only diagnostic surgery candidates to minimize waste of public resources, considering the single-payer health care system. Patient demographics, cytopathology results, TSv3 data, treatment plan, and final histopathology result were reviewed. Results: A total of 50 ITNs underwent TSv3 testing; molecular analysis yielded 20 (40%) “positive” results and 24 (48%) “negative” results. Six (12%) results were classified as “currently negative” or “negative but limited.” “Currently negative” results indicate a low-risk mutation that alone is insufficient for development of a malignant lesion. “Negative but limited” results indicate a sample that is nondiagnostic for malignancy due to low cell count. BCR was calculated as (“negative” and “currently negative”)/total, resulting in a BCR of 58%. Twenty-three (46%) patients were scheduled for surgery and 27 (54%) patients continued with surveillance. Ninety-one percent (20 of 22) of the resected target nodules were malignant on final pathology. Conclusions: TSv3 proved beneficial in classifying ITNs as positive or negative, avoiding surgery in the latter cases. We found a lower reduction rate in surgery and BCR than the previously published studies, which is attributable to the criteria of the McGill algorithm. In the Canadian public health care system, preventing unnecessary surgery represents significant cost savings for the provincial government while also improving patient quality of life.

To compare the diagnostic performance of an immunoassay for plasma concentrations of phosphorylated tau (p-tau) 217 with visual assessments of fluorine-18 fluorodeoxyglucose [¹⁸F]FDG-PET in individuals who meet appropriate use criteria for Alzheimer dementia (AD) biomarker assessments. We performed a retrospective analysis of individuals with early-onset (age <65 years at onset) and/or atypical dementia (features other than memory at onset), who were evaluated at a tertiary care memory clinic. All participants underwent measurements of CSF biomarkers (Aβ42, p-tau181, and total tau levels), as well as [¹⁸F]FDG-PET scans, amyloid-PET scans, and plasma p-tau217 quantifications. To determine whether the [¹⁸F]FDG-PET images were compatible with AD, images were visually rated by 2 nuclear medicine experts. Using a contingency analysis, we evaluated the accuracy of [¹⁸F]FDG-PET scan interpretation and plasma p-tau217 for an AD biomarker profile in CSF and for amyloid-PET positivity. A total of 81 individuals with early onset and/or atypical dementia were included in this study (mean age = 65 years; 48/81 female (59%). Both [¹⁸F]FDG-PET and plasma p-tau217 showed high levels of agreement with reference standard AD biomarkers ([¹⁸F]FDG-PET area under the curve [AUC]: 71%; plasma p-tau217 AUC: 81%). Although both biomarkers had similar specificity for AD [¹⁸F]FDG-PET: 70%, CI: 0.56-0.81; plasma p-tau217: 70%, CI: 0.56-0.81), plasma p-tau217 had higher sensitivity for AD (plasma p-tau217: 97%, CI: 0.85-0.99 vs [¹⁸F]FDG-PET: 73%, CI: 0.57-0.85) (p = 0.01). Overall accuracy was also higher for plasma p-tau217 (AUC = 84%, CI: 0.75-0.93 vs 72%, CI: 0.60-0.83 of [¹⁸F]FDG-PET) (p = 0.02). The same pattern of results was observed when using amyloid-PET as the reference standard. Our study provides evidence that plasma p-tau217 has strong discriminative accuracy for AD among patients with early-onset and/or atypical dementia assessed in specialized settings. Future work should replicate these findings in secondary care settings.

Homocysteine is an amino acid that is toxic to vascular endothelial cells, and plasma elevations have been associated with venous thromboembolism. Severe hyperhomocysteinemia (>100 μmol/L) may result from mutations in the genes coding for enzymes in the trans-sulfuration or the folate/vitamin B₁₂-dependent re-methylation pathways. Here, we report the case of a young woman with severe, recurrent thrombo-embolic events associated with severe hyperhomocysteinemia (111 μmol/L). We identified a homozygous mutation in the cystathionine β -synthase gene (p.I278T) and the presence of the Factor V Leiden mutation. Family study shows segregation of elevated homocysteine in heterozygous relatives for the mutation in the cystathionine β -synthase gene. Management consisted of anticoagulation with warfarin and supplementation with folate, vitamin B₆ (pyridoxine) and vitamin B₁₂. After twelve years of follow-up, plasma homocysteine levels remain in the moderate range (~20 μmol/L, reference range 8-12 μmol/L) and no further thromboembolic events were identified.