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Thyroid eye disease (TED) is the major extrathyroidal manifesta tion of Graves’ disease (GD). Treatment choice is based on clinical activity and severi ty of TED, as evaluated with clinical activity score (CAS) and magnetic resonance (MR) imagi ng. We aimed to determine the relationship between neutrophil-to-lymphocyte ratio (NLR), a readily available indicator of systemic inflammation, and clinical and MR imaging parameters in TED patients. Eighty-seven consecutive TED patients were included. The average signa l intensity ratio (SIR), average extraocular muscle (EOM) diameter, and proptosis of the study eye were extracted from MR images. A baseline NLR ≥ 2.0 was recorded in 37 (42.5%) patients and NLR < 2.0 in 50 (57.5%) patients. TED patients with NLR ≥ 2.0 were older, had a higher CAS, average SIR, average EOM diameter and proptosis, and a lower serum thyrotrop hin receptor antibody level than patients with NLR < 2.0 (all P < 0.05). All MR parameters showed significant correlation with CAS (P < 0.05). NLR correlated significantly with CAS (P = 0.001), average SIR (P = 0.004), average EOM diameter (P = 0.007), and proptosis (P = 0.007). Multiple regression revealed a significant correlation between NLR and CAS (P = 0.001), average SIR (P = 0.029), and proptosis (P = 0.037). Cox regression analysis showed that a high NLR at baseline was associated with a worse clinical outcome of TED (hazard rat io 3.7, 95% CI 1.22–11.2, P = 0.02), at a median follow-up of 25 months. In conclusion, NLR was correlated with CAS and MR imaging parameters and was associated with a worse clini cal outcome of TED at follow-up in patients with TED. Additional prospective studies are needed to validate our findings.

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and challenging management. The present study aimed to investigate the expression of programmed death ligand-1 (PD-L1) and V-domain Ig-containing suppressor of T cell activation (VISTA) in ACC and their associations with clinicopathological features and survival outcomes. Immunohistochemistry was performed on formalin-fixed paraffin-embedded specimens from 54 ACC patients. Chi-square/Fisher's exact tests or independent samples t/Mann--Whitney U tests were performed to assess correlations between immunoscores and clinicopathological parameters. The Kaplan--Meier method and Cox regression were conducted for survival analysis and to identify independent predictors of overall (OS) and disease-free (DFS) survival. Results showed that VISTA was expressed in tumor cells (TCs) and tumor-infiltrating immune cells (TICs) in 81.5% (44/54) and 40.7% (22/54) of the patients, respectively. PD-L1 positivity was found in either TCs or TICs in 11.1% (6/54) of the patients. Patients with positive VI STA expression in TCs had a higher tumor stage (56.9% vs 20%, P = 0.036) and Ki-67 index (30.50 ± 23.51% vs 14.76 ± 11.75%, P = 0.006). However, PD-L1 positivity in either TCs or TICs had no association with patient clinicopathological features. A higher VISTA expression intensity, a larger area and a higher immunoscore were associated with increased risks of disease progression and overall mortality, but PD-L1 expression in TCs or TICs was not associated with OS or DFS. In conclusion, positive TC VISTA expression was correlated with pathological parameters related to malignancy in ACC patients. This finding provides novel evidence of the value of VISTA, in addition to PD-L1, as an immunotherapeutic target in ACC. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is difficult to manage due to the lack of effective treatments. Increased oxygen consumption caused by ove rnutrition, along with reduced oxygen delivery to liver cells induces hepatic steatosi s. Here, we investigated the efficacy of oxygen therapy (OT) to alleviate hepatic steatosi s. The effect of OT on hepatic steatosis was evaluated in high-fat-diet (HFD)-fed mice and palmitic acid (PA)- treated primary hepatocytes. Liver biopsy tissue samples were u sed to determine the relationship between the expression of hypoxia-inducible fa ctor-2α (HIF-2α) and the progression of NAFLD. The role of HIF-2α in the OT group was determined based on the overexpression of HIF-2α in vitro. OT safely alleviated hepatic hypoxia and improved hepatic steatosis by inhibiting hepatic de novo lipogenesis in HFD-fed mice and PA-treated primary hepatocytes, and this was accompanied by red uced expression of HIF-2α and hepatic de novo lipogenesis. The analysis of liver tissues from individuals wi th or without NAFLD revealed a positive correlation between hepati c HIF-2α expression and NAFLD progression. Overexpression of HIF-2α in vitro inhibited the beneficial effect of OT against hepatic lipogenesis and steatosis. OT might be a via ble treatment option for NAFLD and functions by alleviating hypoxia and inhibiting the l iver HIF-2α signaling pathway. [ABSTRACT FROM AUTHOR]