Most previous studies of circulating tumor cells (CTCs) are based on the CellSearch platform, but CellSearch has a number of limitations. This study aimed to use the LiquidBiopsy system and immunofluorescence to test the human epidermal growth factor receptor 2 (HER2) status of CTCs in patients with breast cancer.The LiquidBiopsy system was used to detect HER2-positive (HER2+) cells in whole blood by microfluidic immunomagnetic bead screening and immunofluorescence assay, according to the manufacturer;s instructions. HER2 expression on CTCs was assessed using the Ariol system, calibrated through spiking experiments of 100 cells (BT474, SKBR3, A431, and MDA-MB-231) and 2.5 × 107 white blood cells/mL from healthy donors. Seventy-one patients with breast cancer and 107 non-cancer donors consented to provide blood.Based on breast cancer cell lines experiments, HER2+ CTCs were defined as CTCs with HER2 immunofluorescence intensity ≥ 3.5 times higher than the CD45 immunofluorescence intensity (100% sensitivity and 99.9% specificity). Among the 71 patients with breast cancer, 31 (43.7%) had HER2+ tumor. Among the HER2+ patients, 41.9% (13/31) were found to be HER2+ based on CTC ≥ 1, and 25.8% (8/31) were positive based on CTC ≥ 3. In HER2-negative patients by pathologic examination, 1 (2.5%) patient was found to have ≥ 3 HER2+ CTCs, whereas 15 (37.5%) patients had ≥ 1 HER2+ CTC. HER2+ CTCs were detected at all stages, even in early breast cancer, but the detection rate was higher in metastatic breast cancer.This proof-of-concept study strongly suggests that HER2+ CTCs can be detected using the LiquidBiopsy system.
Depression is a common psychological problem in adolescents worldwide. Although the World Health Organization recommends that members of this population engage in physical activity to reduce depressive symptoms, compliance with this recommendation is often low. Furthermore, although behavioral activation (BA) is recommended as a treatment for adolescents with depression, the reported effect size is small. Compared with traditional exercises, gamified physical activity (GPA) can be particularly appealing to adolescents because it is perceived as an enjoyable experience. In this study, we integrated BA and GPA to create behavioral activation play therapy (BAPT). We designed a clinical trial to investigate the feasibility, acceptability, and effectiveness of this treatment in adolescents with depression.
Objective: Single-dose intravenous ketamine has rapid but time-limited antidepressant effects. We aimed to examine the sustained effects of six consecutive ketamine infusions in Chinese patients with major depressive disorder. Methods: Seventy-seven patients with major depressive disorder were eligible to receive augmentation with six ketamine infusions (0.5 mg/kg over 40 min) administered over the course of 12 days (Monday–Wednesday–Friday). The coprimary outcome measures were the rates of response and remission as measured on the 10-item Montgomery-Asberg Depression Rating Scale. Psychotomimetic and dissociative symptoms were measured with the Brief Psychiatric Rating Scale-positive symptoms and the Clinician Administered Dissociative States Scale, respectively. Results: After the first ketamine infusion, only 10 (13.0%) and 6 (7.8%) patients responded and remitted, respectively; after six ketamine infusions, 52 (67.5%) patients responded and 37 (48.1%) remitted. There was a significant mean decrease in Montgomery-Asberg Depression Rating Scale score at four hours after the first ketamine infusion (7.0±7.5, p<0.001), and this decrease was maintained for the duration of the infusion period. The response to ketamine treatment was positively associated with no history of psychiatric hospitalization (odds ratio=3.56, p=0.009). Suicidal ideation rapidly decreased across the entire study sample, even among the nonresponder group. No significant differences were found regarding Brief Psychiatric Rating Scale and Clinician Administered Dissociative States Scale scores from the first infusion at baseline to four hours post-infusion. Conclusion: Six ketamine infusions increased rates of response and remission when compared to a single-dose ketamine infusion in patients with major depressive disorder. Future controlled studies are warranted to confirm and expand these findings.
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