Papillary thyroid carcinoma with tall cell features is as aggressive as tall cell variant: a meta-analysis

There are still ongoing debates as to which cut-off percentage of tall cell (TC) should be used to define tall cell variant (TCV) papillary thyroid carcinoma (PTC). In this meta-analysis, we aimed to investigate the clinicopathological significance of PTC with tall cell features (PTC-TCF, PTC with 10–50% of TCs) in comparison with classical PTC and TCVPTC (PTC with more than 50% of TCs) to clarify the controversial issue. Four electronic databases including PubMed, Web of Science, Scopus and Virtual Health Library were accessed to search for relevant articles. We extracted data from published studies and pooled into odds ratio (OR) and its corresponding 95% confidence intervals (CIs) using random-effect modeling. Nine studies comprising 403 TCVPTCs, 325 PTC-TCFs and 3552 classical PTCs were included for meta-analyses. Overall, the clinicopathological profiles of PTC-TCF including multifocality, extrathyroidal extension, lymph node metastasis, distant metastasis and patient mortality were not statistically different from those of TCVPTC. Additionally, PTC-TCF and TCVPTC were both associated with an increased risk for aggressive clinical courses as compared to classical PTC. The prevalence of BRAF mutation in PTC-TCF and TCVPTC was comparable and both were significantly higher than that in classical PTC. The present meta-analysis demonstrated that even a PTC comprising only 10% of TCs might be associated with a poor clinical outcome. Therefore, the proportions of PTC in PTC should be carefully estimated and reported even when the TC component is as little as 10%

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Fig 3 -

Kaplan-Meier curves illustrate the different survival patterns of PRAME-negative and PRAME-positive tumors in the entire cohort (A), IDH-mutant astrocytoma, grade 2 (B), IDH-mutant astrocytoma, grade 3 (C), and IDH-mutant astrocytoma, grade 4 (D), IDH-wildtype glioblastoma (E), astrocytoma, NOS, grade 2 (F), astrocytoma, NOS, grade 3 (G), astrocytoma, NOS, grade 4 (H), and oligodendroglioma (I).</p

S1 Fig -

Kaplan-Meier curves compare the survivorship of PRAME-positive and PRAME-negative tumors in IDH-mutant gliomas with (A) and without (B) 1p/19q co-deletion. (TIF)</p

Fig 1 -

(A) Histogram shows the distribution of the PRAME expression read counts (FPKM). The inset only shows the distribution of tumors with FPKM>1. (B) Principal component analysis (PCA) plot created by PC1 and PC2 of the nCounter Nanostring PanCancer Pathways gene panel. (C) The activity heatmap of cancer-related pathways illustrates the activity of each pathway in each sample. The p-values in the left column are calculated by the two-sample independent t-tests to compare the enrichment score (ES) of each pathway between PRAME-negative and PRAME-positive tumors. (D) The summary plot of upregulated and downregulated pathways in PRAME-positive gliomas. (E) The boxplot compares PRAME expression between different revised categories of the new WHO classification.</p

Fig 2 -

t-SNE dimension reduction plots show the distribution of DNA methylation landscapes of 474 tumors, characterized by PRAME expression status (A), re-classified WHO grades (B), and IDH mutation status (C).</p

Comparison of clinicopathological characteristics of <i>PRAME</i>-negative and <i>PRAME</i>-positive cohorts.

Comparison of clinicopathological characteristics of PRAME-negative and PRAME-positive cohorts.</p

The boxplots comparing activity of different immunologic cell populations between <i>PRAME</i>-negative and <i>PRAME</i>-positive gliomas.

The boxplots comparing activity of different immunologic cell populations between PRAME-negative and PRAME-positive gliomas.</p

Nanostring PanCancer pathways panel consists of 770 genes.

Nanostring PanCancer pathways panel consists of 770 genes.</p