Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis
Clinical reviews in allergy & immunology. 2022;:1-33
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.
Association of iron supplementation with risk of transfusion, hospital length of stay, and mortality in geriatric patients undergoing hip fracture surgeries: a meta-analysis
European geriatric medicine. 2021;12(1):5-15
AIMS: To assess the efficacy and safety of iron supplementation for perioperative anemia in geriatric patients with hip fracture. METHODS A systematic search was conducted for studies published using PubMed, EMBASE and Cochrane Library Databases that compared iron supplementation with placebo in patients undergoing hip fracture surgery. The outcomes were blood transfusion rate and volume, length of stay, infection and mortality (last follow-up). Sub-group and sensitivity analyses were performed in cases of substantial heterogeneity. RESULTS The meta-analysis (6 studies: 1201 patients) indicated that iron supplements were not associated with reducing blood transfusion rate (OR 0.92, 95% CI 0.60-1.41; P = 0.69), but high heterogeneity (I(2) = 61%) was detected and a significant association was found in sensitivity analysis of four studies (n = 637; OR 0.68, 95% CI 0.49-0.95; P = 0.02). A significant reduction was detected in transfusion volume (two studies: n = 234; MD - 0.45 units/patient, 95% CI - 0.74 to - 0.16; P = 0.002), hospital stay (five studies: n = 998; MD - 1.42, 95% CI - 2.18 to - 0.67; P = 0.0002) and caused no increased risk of mortality (five studies: n = 937; OR 0.94, 95% CI 0.65-1.36; P = 0.76) and infection (four studies: n = 701; OR 0.58, 95% CI 0.38-0.90; P = 0.01). Sub-group analyses of four studies showed that the preoperative intravenous use of iron at 200-300 mg (two studies) may be the beneficial option for hip fractures patients. CONCLUSIONS Iron supplementation, especially preoperative intravenous use of 200-300 mg iron, is safe and associated with reducing transfusion requirement and hospital stay. Unfortunately, data were too limited to draw a definite conclusion. Further evaluation is required before recommending iron supplementation for older patients with hip fracture surgeries.
Risk factors for mortality of diffuse alveolar hemorrhage in systemic lupus erythematosus: a systematic review and meta-analysis
Arthritis research & therapy. 2021;23(1):57
BACKGROUND Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). The current knowledge of the prognostic factors for SLE-associated DAH is controversial. This meta-analysis was undertaken to investigate the relevant risk factors for mortality in SLE-associated DAH. METHODS Studies were searched from PubMed, EMBASE, and Web of Science databases published up to May 27, 2020, and were selected or removed according to the inclusion and exclusion criteria. Two reviewers extracted data independently from the enrolled studies, and the odds ratios (OR) or the standardized mean difference (SMD) was utilized to identify and describe the prognostic factors for mortality. RESULTS Eight studies encompassing 251 patients with SLE-associated DAH were included in the meta-analysis. No significant publication bias was shown. Age at the diagnosis of DAH (SMD = 0.35, 95% confidence interval (CI) (0.08, 0.61), P = 0.01, I(2) = 0.0%) was found to be an independent risk factor of mortality. Longer lupus disease duration (SMD = 0.28, 95% CI (0.01, 0.55), P = 0.042, I(2) = 0.0%), concurrent infection (OR = 2.77, 95% CI (1.55, 4.95), P = 0.001, I(2) = 37.5%), plasmapheresis treatment (OR = 1.96, 95% CI (1.04, 3.70), P = 0.038, I(2) = 14.6%), and mechanical ventilation (OR = 6.11, 95% CI (3.27, 11.39), P < 0.0001, I(2) = 23.3%) were also related to poor survival, whereas no noticeable relationships were revealed between survival and concurrent lupus nephritis (OR = 5.45, 95% CI (0.52, 56.95), P = 0.16, I(2) = 58.4%) or treatment of cyclophosphamide (CTX) (OR = 0.74, 95% CI (0.16, 3.41), P = 0.70, I(2) = 75.5%). CONCLUSIONS Older age at the diagnosis of DAH, longer disease duration of SLE, concurrent infection, plasmapheresis treatment, and mechanical ventilation were found related to increased mortality in patients with SLE-associated DAH according to our meta-analysis. However, due to limited studies with heterogeneity, these results should be interpreted cautiously. Notably, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.
The efficacy and safety of epsilon-aminocaproic acid for blood loss and transfusions in spinal deformity surgery: A meta-analysis
World neurosurgery. 2019
OBJECTIVE To assess the efficacy and safety of epsilon-aminocaproic acid (EACA) in reducing the blood loss and transfusion volume during open spinal deformity surgery. METHODS A systematic search was conducted for all studies written in English published on or before October 2018 in PubMed, EMBASE and the Cochrane Library that compared antifibrinolytic agents with placebos for open spinal deformity surgeries. The primary outcomes included the total blood loss, intraoperative, and postoperative blood loss, transfusions volume and complication rate. RESULTS Seven studies that included 525 patients who were diagnosed with spinal deformity. Compared with placebo, the patients who received EACA showed a reduction in the postoperative blood loss (95% confidence interval (CI), [MD = -249.80 (-375.65, -123.95); P = 0.0001], and total blood loss (95% CI, [MD = -670.30 (-1142.63, -197.98); P = 0.005]. Furthermore, the patients treated with EACA received approximately 1.67 fewer units of blood (95% CI, [MD = -1.67 (-3.10, -0.24); P = 0.02]. However, in this cohort, no statistically significant difference were observed in the intraoperative blood loss (95% CI, [MD = -452.19 (-1082.21, 177.83); P = 0.16], and complication rate (95% CI, [OR = 0.73 (0.16, 3.24); P = 0.68]. CONCLUSION This meta-analysis demonstrated that EACA could be safe and potentially efficacious for reducing blood loss and transfusions volume in patients with spinal deformity surgeries when compared with placebo. In light of the significant heterogeneity, the findings of this meta-analysis should be confirmed in methodologically rigorous and adequately powered clinical trials.