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Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis
Qin R, He L, Yang Z, Jia N, Chen R, Xie J, Fu W, Chen H, Lin X, Huang R, et al
Clinical reviews in allergy & immunology. 2022;:1-33
Abstract
Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4(+) T/CD8(+) T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3(+) T,CD4(+)T and CD8(+)T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4(+) and CD8(+) T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.
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Effectiveness and tolerability of different therapies in preventive treatment of MOG-IgG-associated disorder: A network meta-analysis
Wang X, Kong L, Zhao Z, Shi Z, Chen H, Lang Y, Lin X, Du Q, Zhou H
Frontiers in immunology. 2022;13:953993
Abstract
BACKGROUND Immunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of specific treatments remains unclear. AIM: To identify the efficacy and tolerability of different treatments for MOG-AD. METHODS Systematic search in Pubmed, Embase, Web of Science, and Cochrane Library databases from inception to March 1, 2021, were performed. Published articles including patients with MOG-AD and reporting the efficacy or tolerability of two or more types of treatment in preventing relapses were included. Reported outcomes including incidence of relapse, annualized relapse rate (ARR), and side effects were extracted. Network meta-analysis with a random-effect model within a Bayesian framework was conducted. Between group comparisons were estimated using Odds ratio (OR) or mean difference (MD) with 95% credible intervals (CrI). RESULTS Twelve studies that compared the efficacy of 10 different treatments in preventing MOG-AD relapse, including 735 patients, were analyzed. In terms of incidence of relapse, intravenous immunoglobulins (IVIG), oral corticosteroids (OC), mycophenolate mofetil (MMF), azathioprine (AZA), and rituximab (RTX) were all significantly more effective than no treatment (ORs ranged from 0.075 to 0.34). On the contrary, disease-modifying therapy (DMT) (OR=1.3, 95% CrI: 0.31 to 5.0) and tacrolimus (TAC) (OR=5.9, 95% CrI: 0.19 to 310) would increase the incidence of relapse. Compared with DMT, IVIG significantly reduced the ARR (MD=-0.85, 95% CrI: -1.7 to -0.098). AZA, MMF, OC and RTX showed a trend to decrease ARR, but those results did not reach significant differences. The combined results for relapse rate and adverse events, as well as ARR and adverse events showed that IVIG and OC were the most effective and tolerable therapies. CONCLUSIONS Whilst DMT should be avoided, IVIG and OC may be suited as first-line therapies for patients with MOG-AD. RTX, MMF, and AZA present suitable alternatives.
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Efficacy and incidence of treatment related adverse events of thrombopoietin receptor agonists in adults with immune thrombocytopenia: a systematic review and network meta-analysis of randomized controlled study
Liu Y, Zhang HX, Su J, Geng QC, Lin X, Feng CX
Acta haematologica. 2022
Abstract
INTRODUCTION To conduct a network meta-analysis to assess the efficacy and incidence of treatment related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO) and hetrombopag for adult immune thrombocytopenia (ITP). METHODS Randomized controlled trails (RCTs) of the five therapies from inception to June 1, 2022 were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 x 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were caculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome. RESULTS In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI, 1.74-31.69) and rhTPO (OR, 3.86; 95%CI, 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0. CONCLUSIONS These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy of adult ITP.
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Application of postoperative autotransfusion in total joint arthroplasty reduces allogeneic blood requirements: a meta-analysis of randomized controlled trials
Ji W, Lin X, Zhang R, Tang P, Mo J, Teng X, Fan Q, Wang B, Fan S, Zhang J, et al
Bmc Musculoskeletal Disorders. 2017;18((1)):378.
Abstract
BACKGROUND Total joint arthroplasty is associated with significant blood loss and often requires blood transfusion. However, allogeneic blood transfusion (ABT) may lead to severe problems, such as immunoreaction and infection. Postoperative autotransfusion, an alternative to ABT, is controversial. We conducted a meta-analysis to evaluate the ability of postoperative autotransfusion to reduce the need for ABT following total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS Systematic literature searches for randomized controlled trials were performed using PubMed, Embase, and the Cochrane Library until February 2016. Relative risks (RRs) and weighted mean differences with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect models; we also evaluated publication bias and heterogeneity. RESULTS Seventeen trials with a total of 2314 patients were included in the meta-analysis. The pooled RRs of ABT rate between autotransfusion and the regular drainage/no drainage groups for TKA and THA were 0.446 (95% CI = 0.287, 0.693; p < 0.001) and 0.757 (95% CI = 0.599, 0.958; p = 0.020), respectively. In the subgroup analysis performed in TKA patients according to control interventions, the pooled RRs were 0.377 (95% CI = 0.224, 0.634; p < 0.001) (compared with regular drainage) and 0.804 (95% CI = 0.453, 1.426, p = 0.456) (compared with no drainage). In the subgroup analysis performed for THA, the pooled RRs were 0.536 (95% CI = 0.379, 0.757, p < 0.001) (compared with regular drainage) and 1.020 (95% CI = 0.740, 1.405, p = 0.904) (compared with no drainage). CONCLUSIONS Compared to regular drainage, autotransfusion reduces the need for ABT following TKA and THA. This reduction is not present when comparing autotransfusion to no drainage. However, the reliability of the meta-analytic results concerning TKA was limited by significant heterogeneity in methods among the included studies.
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Meta-analysis of predictors of early severe bleeding in patients who underwent transcatheter aortic valve implantation
Sun Y, Liu X, Chen Z, Fan J, Jiang J, He Y, Zhu Q, Hu P, Wang L, Xu Q, et al
The American Journal of Cardiology. 2017;120((4):):655-661
Abstract
Severe bleeding (SB) in patients who underwent transcatheter aortic valve implantation (TAVI) could be fatal. Although multiple independent predictors of bleeding post-TAVI have been identified, the definitions of bleeding and predictors vary across studies. This study aimed to provide summary effect estimates for predictors of SB within 30 days post-TAVI. A systematic review of studies that reported the incidence of bleeding post-TAVI with raw data for predictors of interest was performed. Data on characteristics of study, patient, and procedure were extracted. Crude risk ratios (RRs) and 95% confidence intervals were calculated using random-effect model. Fifteen predictors on 65,209 patients from 47 studies were analyzed. The median rate of SB was 11% across studies. Seven factors (3 patient related and 4 procedure related) were recognized as predictors of early SB post-TAVI. Age ≥90 years (RR 1.17; p = 0.008), female (RR 1.13; p = 0.01), and sheath diameter >19 Fr (RR 1.19; p = 0.04) were weak predictors. Chronic kidney disease (RR 1.94; p <0.001) and transapical (TA) (RR 1.82; p <0.001) were moderate predictors that were almost associated with twofold risk. Vascular complication (RR 2.97; p <0.001) and circulatory support (RR 3.39; p <0.001) were strong predictors that were nearly associated with threefold risk. In conclusion, age, gender, chronic kidney disease, TA, sheath diameter, vascular complication, and circulatory support were all predictors of early SB post-TAVI in this meta-analysis, which provided possible guidance for prevention and management of SB related to TAVI.