Immune signature and therapeutic approach of natural killer cell in chronic liver disease and hepatocellular carcinoma.

Natural killer (NK) cells are one of the key members of innate immunity that predominantly reside in the liver, potentiating immune responses against viral infections or malignant tumors. It has been reported that changes in cell numbers and function of NK cells are associated with the development and progression of chronic liver diseases (CLDs) including non-alcoholic fatty liver disease, alcoholic liver disease, and chronic viral hepatitis. Also, it is known that the crosstalk between NK cells and hepatic stellate cells plays an important role in liver fibrosis and cirrhosis. In particular, the impaired functions of NK cells observed in CLDs consequently contribute to occurrence and progression of hepatocellular carcinoma (HCC). Chronic infections by hepatitis B or C viruses counteract the anti-tumor immunity of the host by producing the sheddases. Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA), released from the cell surfaces by sheddases, disrupts the interaction and affects the function of NK cells. Recently, the MICA/B-NK stimulatory receptor NK group 2 member D (NKG2D) axis has been extensively studied in HCC. HCC patients with low membrane-bound MICA or high sMICA concentration have been associated with poor prognosis. Therefore, reversing the sMICA-mediated downregulation of NKG2D has been proposed as an attractive strategy to enhance both innate and adaptive immune responses against HCC. This review aims to summarize recent studies on NK cell immune signatures and its roles in CLD and hepatocellular carcinogenesis and discusses the therapeutic approaches of MICA/B-NKG2D-based or NK cell-based immunotherapy for HCC.

The Effect of the COVID-19 Pandemic on Early Adolescent Fractures in the Republic of Korea.

Background and Objectives: Restrictions on daily activities to slow down the propagation of COVID-19 have changed the epidemiological pattern of pediatric fractures in many countries. However, the effect of the pandemic on pediatric fractures has not been fully studied. In this study, we investigated the impact of COVID-19 on early adolescent fractures in Korea. Materials and methods: We conducted a retrospective follow-up on a nationwide cohort of Korean early adolescents born between 2006 and 2009. The prevalence and incidence of pediatric fractures and the frequency of surgical treatment were compared between two different eras. Results: The prevalence and incidence of fractures during the pandemic have both shown a significant decrease: prevalence reduced from 34,626 to 24,789 (p < 0.001), while incidence decreased from 29,804 to 18,898 (p < 0.001). Considering sex, the shift in fracture prevalence was statistically significant (p = 0.020), whereas the incidence was not (p = 0.862). The decline in both fracture prevalence and incidence exhibited significant variation across birth year groups (prevalence, p < 0.001; incidence, p < 0.001), with a more pronounced reduction observed in the older age groups. While the proportion of patients who required surgeries has increased, the mean frequency of surgical treatment per patient remained at a similar level (by prevalence, p = 0.181; by incidence, p = 0.735). The decline in both fracture prevalence and incidence has shown significant variation in relation to fracture sites (prevalence, p < 0.001; incidence, p < 0.001), with a decrease in distal limb fractures and an increase in forearm and axial body fractures. Conclusions: The pediatric fracture pattern in Korea has been notably influenced by the COVID-19 pandemic, warranting further investigation into causal factors. Our findings should help predict epidemiology in the post-pandemic period and thus aid policymaking and patient management.

Epidemiology of pediatric fractures before versus during the coronavirus disease 2019 pandemic.

Several studies have reported changes in the prevalence of childhood fractures between the prepandemic and coronavirus disease 2019 pandemic periods considering the overall decrease in activity during the latter. This review aimed to organize and summarize the global trends in pediatric fracture incidence. Our findings should help predict fracture patterns in the postpandemic period by identifying changes in the past and present, thus aiding patient management.