We elucidated the clinical and immunologic implications of serum IL-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev). We prospectively enrolled 165 patients with unresectable HCC (discovery cohort: 84 patients from three centres; validation cohort: 81 patients from one centre). Baseline blood samples were analysed using a flow cytometric bead array. The tumour immune microenvironment was analysed using RNA sequencing. In the discovery cohort, clinical benefit 6 months (CB_6m) was defined as complete or partial response, or stable disease for ≥6 months. Among various blood-based biomarkers, serum IL-6 levels were significantly higher in participants without CB_6m than in those with CB_6m (mean 11.56 vs. 5.05 pg/ml, p = 0.02). Using maximally selected rank statistics, the optimal cut-off value for high IL-6 was determined as 18.49 pg/ml, and 15.2% of participants were found to have high IL-6 levels at baseline. In both the discovery and validation cohorts, participants with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev treatment compared with those with low baseline IL-6 levels. In multivariable Cox regression analysis, the clinical implications of high IL-6 levels persisted, even after adjusting for various confounding factors. Participants with high IL-6 levels showed reduced interferon-γ and tumour necrosis factor-α secretion from CD8⁺ T cells. Moreover, excess IL-6 suppressed cytokine production and proliferation of CD8⁺ T cells. Finally, participants with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumour microenvironment. High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment. Although patients with hepatocellular carcinoma who respond to treatment with atezolizumab and bevacizumab exhibit favourable clinical outcomes, a fraction of these still experience primary resistance. We found that high baseline serum levels of IL-6 correlate with poor clinical outcomes and impaired T-cell response in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Objective: This study aimed to evaluate glymphatic system function in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS) in comparison to healthy controls, using diffusion tensor imaging (DTI)‐analysis along the perivascular space (ALPS) method. We hypothesized that there is glymphatic system dysfunction in TLE patients with HS.Methods: We retrospectively enrolled 25 TLE patients with HS and 26 age‐ and sex‐matched healthy controls. All participants underwent DTI with the same 3T magnetic resonance imaging scanner, and the DTI‐ALPS index was calculated. We evaluated the differences in the DTI‐ALPS index between TLE patients with HS and healthy controls. Moreover, we evaluated the correlation between the DTI‐ALPS index and clinical characteristics of epilepsy, including age, age at seizure onset, duration of epilepsy, and number of anti‐seizure medications (ASMs).Results: There was a difference in the DTI‐ALPS index between TLE patients with HS and healthy controls. The DTI‐ALPS index in TLE patients with HS was lower than that in healthy controls (1.497 vs. 1.668, P = .015). However, there was no difference in the DTI‐ALPS index between the newly diagnosed TLE patients with HS and the chronic TLE patients with HS. The DTI‐ALPS index was negatively correlated with age (r = −0.420, P = .036). However, the DTI‐ALPS index was not correlated with other clinical characteristics, including age at seizure onset, duration of epilepsy, and number of ASMs.Significance: Our findings showed that the DTI‐ALPS index was significantly lower in TLE patients with HS than in healthy controls, indicating the presence of glymphatic system dysfunction in TLE patients with HS. Our study also suggests that the DTI‐ALPS method may be useful for evaluating glymphatic system function in epilepsy.

Objective: This study aimed to investigate the differences in brain morphology according to handedness.Materials and Methods: Forty‐two healthy subjects were enrolled (21 right‐handers and 21 nonright‐handers). The two groups were classified according to the Edinburgh Handedness Inventory. Measures of cortical morphology, such as thickness, surface area, volume, and curvature, and the volumes of subcortical structures, such as the amygdala, caudate, hippocampus, globus pallidus, putamen, and thalamus, were compared between the groups according to handedness using whole‐brain 3D T1‐weighted MRI. In addition, we investigated the white matter differences between the groups using diffusion tensor imaging. Moreover, we quantified correlations between the handedness scales of the Edinburgh Handedness Inventory and each measure of different brain morphologies.Results: The volumes of the right putamen and left globus pallidus in nonright‐handed participants were significantly larger than those who were right‐handed (0.3559 vs. 0.3155%, p = .0028; 0.1101 vs. 0.0975%, p = .0025; respectively). Moreover, the volumes of the right putamen and left globus pallidus were negatively correlated with the handedness scales of the Edinburgh Handedness Inventory (r = −.392, p = .0101; r = −.361, p = .0189; respectively). However, the cortex morphology and the other subcortical volumes were not significantly different between the two groups. In addition, we did not find any white matter differences between the groups.Conclusions: We demonstrated that there were significant differences in brain morphology between right‐handers and nonright‐handers, especially in the basal ganglia, which could produce differences in motor control according to handedness.