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Supplemental Digital Content is Available in the Text. Background: For patients with multiple sclerosis (MS), both structure and microvasculature alterations in the inner retina have been investigated in several studies. However, little is known about the alterations in the outer retina and choroid. Hence, this study aimed to assess the outer retinal and choroidal changes in patients with MS with no history of optic neuritis (ON). Methods: Patients with MS and healthy control participants were enrolled in this cross-sectional study. Quantitative analyses were performed using swept source optical coherence tomography and swept source optical coherence tomography angiography images to assess outer retina thickness (ORT) and choroid thickness (CT), vessel density (VD) of choriocapillaris, and choroidal vascularity index (CVI), which were then compared between the groups. Results: A total of 37 participants with MS (72 eyes) and 74 healthy control participants (148 eyes) were included in this study. Compared with healthy controls, patients with MS with no history of ON showed reduced VD of the choriocapillaris and CVI. There was no significant difference in ORT and CT between 2 groups. Meanwhile, in patients with MS, no correlation between OCTA parameters and expanded disability status scale score were found in this study. Conclusions: Our study indicates that patients with MS with no history of optical neuritis have reduced choriocapillaris vessel density and decreased choroidal vascularity index without detectable alteration in outer retina thickness and choroid thickness. The findings complement the outer retinal and choroidal component of MS, providing deeper insight into the pathophysiology of MS. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing–remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS. Methods: Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively. Results: Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed distinct trajectory from clonal expansion. In addition, T-bet acted as a key transcriptional factor that elicited GzmB expression in CD8 + TEMRA cells of patients with SPMS. Finally, the expression of GzmB in CD8 + T cells was positively correlated with disability and progression of MS, and could effectively distinguish SPMS from RRMS with a high accuracy. Conclusions: Our study mapped peripheral immune cells of RRMS and SPMS patients and provided an evidence for the involvement of GzmB + CD8 + TEMRA cells in the progression of MS, which could be used as a diagnostic biomarker for distinguishing SPMS from RRMS. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the correlations between estimated small dense low-density lipoprotein-cholesterol (esd-LDL-c) and the development of end-stage kidney disease (ESKD), cardiovascular mortality, and all-cause mortality in individuals with diabetic kidney disease (DKD) or diabetes mellitus (DM) concomitant chronic kidney disease (CKD)., Methods: We analyzed the data from a biopsy-proven DKD cohort conducted at West China Hospital of Sichuan University between 2009 and 2021 (the DKD cohort) and participants with DM and CKD in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 (the NHANES DM-CKD cohort). Cox regression analysis was also used to estimate associations between esd-LDL-c and the incidence of ESKD, cardiovascular mortality, and all-cause mortality., Results: There were 175 ESKD events among 338 participants in the DKD cohort. Patients were divided into three groups based on esd-LDL-c tertiles (T1 < 33.7 mg/dL, T2 ≥ 33.7 mg/dL to <45.9 mg/dL, T3 ≥ 45.9 mg/dL). The highest tertile of esd-LDL-c was associated with ESKD (adjusted HR 2.016, 95% CI 1.144-3.554, p  = .015). Furthermore, there were 99 deaths (39 cardiovascular) among 293 participants in the NHANES DM-CKD cohort. Participants were classified into three groups in line with the tertile values of esd-LDL-c in the DKD cohort. The highest tertile of esd-LDL-c was associated with cardiovascular mortality (adjusted HR 3.95, 95% CI 1.3-12, p  = .016) and all-cause mortality (adjusted HR 2.37, 95% CI 1.06-5.32, p  = .036)., Conclusions: Higher esd-LDL-c was associated with increased risk of ESKD in people with biopsy-proven DKD, and higher cardiovascular and all-cause mortality risk among those with DM-CKD.