Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles

Background Immune checkpoint blockers (ICBs) activate CD8⁺ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear.Methods Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab—sICB) or combination (nivolumab and ipilimumab—cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8⁺ T cells was sequenced and differential gene expression according to irAE development assessed.Results 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9–33.4) versus not-reached (P = 2.8 × 10⁻⁶). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8⁺ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment.Conclusions Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.Subject terms: Immunotherapy, Melanoma     

Efficacy and safety of ND:YAG 1064 nm lasers for photoepilation: a systematic review

Lasers in Medical Science - Using light sources in phototherapy has presented promising results regarding several types of facial and body skin affections for centuries. The neodymium-doped yttrium...     

高分辨率CT对颞部疾病的检查价值

目的：探讨高分辨率CT（HRCT）对颞部疾病的检查价值。方法：对43例颞部疾病患者行常规CT和高分辨率CT（HRCT）检查所获图像对比分析，并讨论HRCT的检查技术和图像后处理。结果：HRCT对病变的显示率及病变引起骨质破坏的程度，病变边缘，轮廓的显示均明显优于常规CT，尤其能清楚显示常规CT难以显示的中耳及内耳的细微结构，结论：高分辨率CT是颞部疾病的首选检查方法，使用高分辨率CT对颞部疾病的检查给临床提供更多，更准确的诊断信息。     

Juvenile-onset acid maltase deficiency with unusual familial features

From early childhood, two brothers had mild gait difficulties due to acid maltase deficiency (AMD). Biochemical studies of family members were consistent with autosomal recessive inheritance, but the asymptomatic mother had AM activity in the homozygote range, and her parents had decreased AM activity. The asymptomatic mother may be homozygous for the adult-onset variant of AMD. Alternatively, either the mother or the children may be genetic compounds of the childhood and adult forms of AMD.     

Intratemporal vascular tumors: detection with CT and MR imaging

The diagnostic contributions of computed tomography (CT) and magnetic resonance (MR) imaging were compared in 12 patients with benign intratemporal vascular tumors (hemangioma or vascular malformation). The tumors included six in the internal acoustic canal and six in the geniculate ganglion region. Clinical and histologic correlations were made. Two of the six patients with tumors in the internal acoustic canal underwent CT, and both required gas cisternography to show the tumor. Five patients in that group underwent MR imaging, and all five studies showed the tumor. All six patients with geniculate ganglion tumors underwent CT. Results in one study were questionable, and five showed the tumor. Five patients in this group underwent MR imaging, but the MR findings were positive in only two cases. MR imaging should therefore be performed before CT in the evaluation of facial nerve dysfunction, as it demonstrated all tumors in the internal acoustic canal and some in the geniculate ganglion region. If MR findings are negative, CT should then be performed to rule out a possible geniculate ganglion lesion.