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BACKGROUNDSARS-CoV-2 causes COVID-19 through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns (DAMPs) and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) is able to blunt the broad inflammatory response induced by DAMPs in multiple models. A recent randomized phase III trial evaluating the impact of CD24Fc in patients with severe COVID-19 demonstrated encouraging clinical efficacy. METHODSWe studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial (NCT04317040) collected before and after treatment with CD24Fc or placebo. We performed high dimensional spectral flow cytometry analysis of peripheral blood mononuclear cells and measured the levels of a broad array of cytokines and chemokines. A systems analytical approach was used to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. FINDINGSTwenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found systemic hyper-activation of multiple cellular compartments in the placebo group, including CD8+ T cells, CD4+ T cells, and CD56+ NK cells. By contrast, CD24Fc-treated patients demonstrated blunted systemic inflammation, with a return to homeostasis in both NK and T cells within days without compromising the ability of patients to mount an effective anti-Spike protein antibody response. A single dose of CD24Fc significantly attenuated induction of the systemic cytokine response, including expression of IL-10 and IL-15, and diminished the coexpression and network connectivity among extensive circulating inflammatory cytokines, the parameters associated with COVID-19 disease severity. INTERPRETATIONOur data demonstrates that CD24Fc treatment rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19. FUNDINGNIH
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Objective To compare intramedullary nailing assisted by minimally invasive cerclage with simple intramedullary nailing in the treatment of femoral long oblique subtrochanteric fractures.Methods From April 2010 to September 2015,our department treated 39 patients with femoral long oblique subtrochanteric fracture.Of them,16 were treated by cephalomedullary nailing combined with minimally invasive cerclage (observation group of 11 males and 5 females with an average age of 42.8 ± 13.2 years) and 23 by simple cephalomedullary nailing (control group of 17 males and 6 females with an average age of 46.2 ± 10.1 years).Their operation time,intraoperative blood loss,radiologic results (union time and alignment) and functional results [Visual Analog Scale (VAS) and Harris hip score] were compared between the 2 groups.Results The 39 patients were followed up from 12 to 30 months (average,15 months).For the observation group,the varus angle (2.2°± 1.4°) was significantly smaller than for the control group(4.1°±2.2°),the VAS scores at 1 and 3 months postoperatively (3.43 ± 1.54,1.13 ± 1.20) were significantly lower than for the control group (5.61 ± 1.41,3.34 ± 1.82),and the clinical union ratio at 3 months postoperatively(87.5％,14/16) significantly higher than for the control group (47.8％,11/23) (P ＜ 0.05).There were no significant differences between the 2 groups in terms of operation time,intraoperative blood loss,Harris hip score at one year postoperatively,VAS score at 6 months postoperatively,or clinical union ratio at 6 or 12 months postoperatively(P ＞ 0.05).Conclusions Cephalomedullary nailing is effective for the treatment of femoral long oblique subtrochanteric fractures no matter it is assisted by minimally invasive cerclage or not.However,since minimally invasive cerclage has the advantage of improving reduction and mechanical stability,combination of minimally invasive cerclage and cephalomedullary nailing may be more advantageous in early pain-relieving and functional recovery.
