Background: Squamous cell carcinoma (SCC) is the most common type of head and neck cancer, and head and neck squamous cell carcinoma (HNSCC) was proved to having a high prevalence of perineural invasion (PNI). Although some reports have revealed a relationship between PNI and the prognosis in HNSCC patients, the contribution of PNI to the prognosis remains unclear. Objectives: This study was aimed to comprehensively and quantitatively summarize the prognostic value of PNI for the survival of patients with HNSCC. Material and methods: We conducted PubMed and EMBASE to identify all relevant studies. A meta-analysis and subgroup analysis were performed to clarify the prognostic role of PNI. Results: A total of 18 studies (n = 3894) were included. 989 (25.4%) of the 3894 patients exhibited positive PNI, PNI was shown to be significantly associated with overall survival (OS) [hazard ratio (HR): 2.8, 95% confidence interval (CI): 1.88–4.16], disease-free survival (DFS) (HR = 2.42, 95% CI: 1.92–3.05) and disease-specific survival (DSS) (HR = 2.60, 95% CI: 1.86–3.63). Conclusions: The presence of PNI significantly affected OS, DFS and DSS in patients with HNSCC.

To assess the efficacy/safety of ivarmacitinib, a selective Janus kinase (JAK) 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients were randomised (1:1:1) to receive either placebo (n=188), ivarmacitinib 4 mg (n=189) or ivarmacitinib 8 mg (n=189) once daily, with background csDMARDs allowed. After 24 weeks, patients on placebo switched to ivarmacitinib 4 mg for an additional 28 weeks, while those on ivarmacitinib continued their initial dosage. The primary endpoint was the proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. At week 24, ACR20 response rates were significantly higher in the ivarmacitinib 4 mg (70.4%) and 8 mg (75.1%) groups compared with the placebo group (40.4%; both p<0.0001). Both ivarmacitinib doses achieved numerically higher Disease Activity Score 28-joint count C reactive protein of <2.6/≤3.2 response rates compared with placebo. Improvements in efficacy and patient-reported outcomes were sustained through 52 weeks and were noted in patients who switched from placebo after week 24. During the placebo-controlled period, treatment-emergent adverse events (TEAEs) occurred in 81.5% and 90.5% of patients in the ivarmacitinib 4 mg and 8 mg groups, versus 79.3% in the placebo group. Infection-related TEAEs were slightly higher in the ivarmacitinib groups. Ivarmacitinib may offer a potential therapeutic option for patients with RA who have an inadequate response to csDMARDs, with a safety profile that was generally manageable over 1 year of treatment and similar to other JAK inhibitors. NCT04333771.

Aims: CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation, and the cell-cycle regulatory proteins often change in human neoplasms. To gain insight into the role of epigenetic aberration of cell-cycle regulator genes in oesophagus squamous cell carcinoma (ESCC), the authors determined the hypermethylation profile in ESCC. Methods: The promoter methylation status of nine cell-cycle regulator genes was examined in 50 ESCC, 50 dysplastic tissues and 50 normal epithelial tissues by methylation-specific PCR. Results: The frequency of promoter methylation was 52% for p14, 44% for p15, 50% for p16, 56% for p21, 38% for p27, 8% for p53, 42% for p57, 36% for p73, and 44% for RB1 of 50 ESCC. CIMP+ was detected in 54% (27/50) of ESCC and 8% (4/50) of dysplastic tissues; no CIMP+ was present in normal epithelial tissues (p<0.001). The results show that promoter methylation of p14, p15, p16, p21, p27, p57 and p73 was far more common in ESCC samples with CIMP+ than those with CIMP−. A significant difference between CIMP status and TNM stage and metastasis was found in ESCC (p<0.05). Patients with ESCC with CIMP+ had poorer 4-year survival than those with CIMP−. Conclusions: The results suggest that CIMP of a subset of cell-cycle regulatory genes has an important role in the pathogenesis and progression of ESCC.