CDKN2A somatic copy number amplification in normal tissues surrounding gastric carcinoma reduces cancer metastasis risk in droplet digital PCR analysis.

BACKGROUND: The CDKN2A gene is frequently affected by somatic copy number variations (SCNVs, including deletions and amplifications [SCNdel and SCNamp]) in the cancer genome. Using surgical gastric margin tissue samples (SMs) as the diploid reference in SCNV analysis via CDKN2A/P16-specific real-time PCR (P16-Light), we previously reported that the CDKN2A SCNdel was associated with a high risk of metastasis of gastric carcinoma (GC). However, the status of CDKN2A SCNVs in SMs and their clinical significance have not been reported. METHODS: Peripheral white blood cell (WBC) and frozen GC and SM tissue samples were collected from patients (n = 80). Droplet digital PCR (ddPCR) was used to determine the copy number (CN) of the CDKN2A gene in tissue samples using paired WBCs as the diploid reference. RESULTS: A novel P16-ddPCR system was initially established with a minimal proportion (or limit, 10%) of the detection of CDKN2A CN alterations. While CDKN2A SCNamp events were detected in both SMs and GCs, fewer CDKN2A SCNdel events were detected in SMs than in GCs (15.0% vs. 41.3%, P = 4.77E-04). Notably, significantly more SCNamp and fewer SCNdel of the CDKN2A gene were detected in SMs from GC patients without metastasis than in those from patients with lymph node metastasis by P16-ddPCR (P = 0.023). The status of CDKN2A SCNVs in SM samples was significantly associated with overall survival (P = 0.032). No cancer deaths were observed among the 11 patients with CDKN2A SCNamp. CONCLUSION: CDKN2A SCNVs in SMs identified by P16-ddPCR are prevalent and significantly associated with GC metastasis and overall survival.

Gaining insight into irrational off-label use of vidarabine through analysis of a spontaneous reporting system in China.

WHAT IS KNOWN AND OBJECTIVE: Although superseded by other antiviral agents in many Western countries, vidarabine is still widely used in some countries, including China; hence, the extent and appropriateness of vidarabine prescriptions in children require better characterization. This study examined the rationale, extent, and health risks associated with irrational off-label vidarabine use in China. METHODS: Data used in the study were extracted from a multi-provincial joint adverse drug reactions monitoring platform from 2002 to 2018. Descriptive statistics were used to analyse the characteristics of individual case safety reports (ICSRs) related to vidarabine use. RESULTS AND DISCUSSION: Among 2772 individual ICSRs related to vidarabine, 2223 (80.19%) cases occurred in patients aged 0-9. In all patients, the median age and interquartile range were 2 (0-6). Although most adverse events were mild, five deaths were recorded, all in children below 7 years of age. Paediatric use is the most prominent off-label use of vidarabine. Additionally, several other irrational off-label uses were identified, including 218 (7.86%) cases of overdosing and numerous applications beyond the approved indications, dosages, routes of administration, and solvents. WHAT IS NEW AND CONCLUSION: Data indicate that vidarabine was mainly prescribed for suspected common viral infections in paediatric patients, demonstrating serious inappropriate off-label uses. The problem was further complicated by the lack of sufficient information regarding safety, efficacy, and dosing regimens in children, as well as by several additional risk factors such as inappropriate solvents, routes of administration, and overdose. In the case of children, the physicians' lack of understanding of antiviral activities and compassionate prescriptions were mainly responsible for drug overuse. The health risks associated with the paediatric use of vidarabine in China require greater attention and further investigation.

Safety profile of traditional Chinese herbal injection: An analysis of a spontaneous reporting system in China.

PURPOSE: Although a series of serious adverse events have continually raised concerns about the potential toxicity of traditional Chinese medicine injections (TCM injections), studies on this subject are still sparse. We conducted a descriptive analysis of a spontaneous reporting system in China to describe the safety profile of TCM injections. METHODS: The safety profile of TCM injections is described by descriptive analysis of 559 066 adverse reports collected from Guangdong Provincial Center for adverse drug reaction (ADR) Monitoring in China during 2003 to 2017. RESULTS: The percentage of new or serious ADRs of TCM injections is much higher than average percentage of China's spontaneous reporting system (SRS) as a whole (48.70% vs <25%). Compared with conventional injections, TCM injections have a slightly lower percentage of serious ADRs (6.02% vs 6.72%) and much higher percentage of unknown (new) ADRs (46.74% vs 24.13%). The gender and age distribution for TCM injections are similar to conventional injections. The reporting rates of ADRs increased with age. Anaphylactic shock and anaphylactoid reaction are high-risk ADRs for TCM injections and, anaphylactic shock is ranked number 1 in causing deaths (50.00%). CONCLUSIONS: There are some differences and similarities on the safety profile between TCM injections and conventional injections. TCM injections have higher risk of adverse effects than any other dosage forms of TCM medications and higher percentage of new or serious adverse effects than conventional injections. A lot of work need to be done to clarify the huge amount of potential unknown adverse effects related to TCM injections.