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Lower extremity arteriosclerosis obliterans (LEASO) is a vascular disease that may result in adult limb loss worldwide. CD4+T cell-mediated immunity plays a significant role in LEASO. The T cell immunoglobulin and mucin domain 3 (Tim-3) and inhibitory receptor programmed cell death-1 (PD-1) are well-known immune checkpoints that play crucial roles in regulating CD4+T cell activation or tolerance. In this study, blood mononuclear cells were isolated from the blood samples of healthy controls and patients who were diagnosed with LEASO for the first time [stage III or IV according to the Fontaine classification system and had not received drugs (except for heparin) or surgery treatment]. We concluded the higher proportion of Tim-3+PD-1+CD4+T cells in human higher stage LEASO, and oxidized low-density lipoprotein increased Tim-3 and PD-1 co-expression by activating CD4+T cells in a dose- dependent manner. Tim-3+PD-1+CD4+T cells displayed a more active status and produced more anti-atherogenic cytokines compared to Tim-3-PD-1-CD4+T cells. Apart from the increased frequency, the altered function of Tim-3+PD-1+CD4+T cells was also observed in LEASO compared to those from healthy controls. These in vitro results indicated that Tim-3 and PD-1 might be promising early warning targets of higher stage LEASO. In addition, the blockade of Tim-3 and PD-1 signaling pathways aggravated the pro-atherogenic Th1 responses in LEASO, further suggesting that the cardiovascular safety must be a criterion considered in using immune checkpoint inhibitors to reverse T cell exhaustion during tumors and chronic viral infections. [ABSTRACT FROM AUTHOR]

Background: Patients aged 40-60 years who require total hip arthroplasty (THA) often first receive unindicated hip arthroscopy or magnetic resonance imaging (MRI). Our objective was to identify potentially inappropriate resource utilization before THA, specifically reporting on the proportion of patients aged 40-60 years who underwent hip arthroscopy or MRI in the year before THA., Methods: We conducted a retrospective, population-based study at the provincial level. We retrieved data from the Canadian Institute for Health Information (CIHI). We included all Ontario residents who underwent an elective, primary THA for osteoarthritis between Apr. 1, 2004, and Mar. 31, 2016. We identified the rates and timing of patients who underwent an MRI or hip arthroscopy before their index THA., Results: The percentage of patients who underwent an MRI before THA increased significantly over the study period, from 8.7% in 2004 to 23.8% in 2015. There was also a significant but variable trend in the percentage of patients who underwent a hip arthroscopy before THA., Conclusion: Our results demonstrate a high, gradually increasing proportion of patients who received a hip MRI and a low but increasing proportion of patients who received hip arthroscopy in close proximity to THA. Multidisciplinary collaboration may improve knowledge translation and help reduce the rate of clinically unnecessary diagnostic and therapeutic interventions in this population of patients who require THA., Competing Interests: Competing interests:: None declared., (© 2024 CMA Impact Inc. or its licensors.)

Lower extremity arteriosclerosis obliterans (LEASO) is a vascular disease that may result in adult limb loss worldwide. CD4 + T cell-mediated immunity plays a significant role in LEASO. The T cell immunoglobulin and mucin domain 3 (Tim-3) and inhibitory receptor programmed cell death-1 (PD-1) are well-known immune checkpoints that play crucial roles in regulating CD4 + T cell activation or tolerance. In this study, blood mononuclear cells were isolated from the blood samples of healthy controls and patients who were diagnosed with LEASO for the first time [stage III or IV according to the Fontaine classification system and had not received drugs (except for heparin) or surgery treatment]. We concluded the higher proportion of Tim-3 + PD-1 + CD4 + T cells in human higher stage LEASO, and oxidized low-density lipoprotein increased Tim-3 and PD-1 co-expression by activating CD4 + T cells in a dose- dependent manner. Tim-3 + PD-1 + CD4 + T cells displayed a more active status and produced more anti-atherogenic cytokines compared to Tim-3 - PD-1 - CD4 + T cells. Apart from the increased frequency, the altered function of Tim-3 + PD-1 + CD4 + T cells was also observed in LEASO compared to those from healthy controls. These in vitro results indicated that Tim-3 and PD-1 might be promising early warning targets of higher stage LEASO. In addition, the blockade of Tim-3 and PD-1 signaling pathways aggravated the pro-atherogenic Th1 responses in LEASO, further suggesting that the cardiovascular safety must be a criterion considered in using immune checkpoint inhibitors to reverse T cell exhaustion during tumors and chronic viral infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cui, Chen, Dai, Ou, Qiu and Wang.)