Abstract

AIMS: Previous studies have reported inconsistent findings on the efficacy of platelet-rich plasma (PRP) therapy in women with implantation failure. The objective of this review was to evaluate whether PRP administration could improve pregnancy outcomes in women with implantation failure undergoing in vitro fertilization. METHODS Electronic databases were searched for studies that explored the effects of PRP for patients with implantation failure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Based on the available data, we performed subgroup analyses and sensitivity analyses. RESULTS Eight studies were included. PRP treatment improved pregnancy outcomes for all women compared with no treatment or placebo (clinical pregnancy rate: OR 2.24, 95% CI 1.41-3.54; live birth rate: OR 5.76, 95% CI 1.55-21.44; miscarriage rate: OR 0.18, 95% CI 0.05-0.63), especially in randomized controlled trials. No significant differences were detected in multiple pregnancy rates (OR 2.54, 95% CI 0.67-9.67). Furthermore, subgroup analysis based on the number of previous implantation failures showed that PRP treatment improved pregnancy outcomes in women with recurrent implantation failure (clinical pregnancy rate: OR 2.55, 95% CI 1.49-4.38; live birth rate: OR 5.07, 95% CI 1.15-22.34; miscarriage rate: OR 0.20, 95% CI 0.05-0.78). CONCLUSION PRP administration could improve pregnancy outcomes in women with recurrent implantation failure. Due to the limited evidence available, the efficacy of PRP in women with recurrent implantation failure needs to be further verified in high-quality studies with larger sample sizes.

Abstract

BACKGROUND Hyperinflammation and coagulopathy are hallmarks of COVID-19 and synergistically contribute to illness progression. Antiplatelet agents have been proposed as candidate drugs for COVID-19 treatment on the basis of their antithrombotic and anti-inflammatory properties. A systematic review and meta-analysis that included early observational studies and recent randomized controlled trials (RCTs) was performed to summarize and compare evidence on this issue. METHODS PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify studies published up to Nov 7, 2021, and the results of registered clinical trials were followed up to Mar 30, 2022. We included RCTs and observational studies assessing the effect of antiplatelet therapy in adult patients with COVID-19. Data on baseline patient characteristics, interventions, controls, and outcomes were extracted by two independent reviewers. The primary outcome was mortality. Data were pooled using a random-effects model. RESULTS Twenty-seven studies were included, of which 23 observational studies were pooled in a meta-analysis, and the remaining four RCTs (ACTIV-4B, RECOVERY, ACTIV-4a, and REMAP-CAP) were narratively synthesized. Based on 23 observational studies of 87,824 COVID-19 patients, antiplatelet treatment favors a lower risk of mortality [odds ratio (OR) 0.72, 95% confidence interval (CI) 0.61-0.85; I (2) = 87.0%, P < 0.01]. The narrative synthesis of RCTs showed conflicting evidence, which did not support adding antiplatelet therapy to the standard care, regardless of the baseline illness severity and concomitant anticoagulation intensity. CONCLUSION While the rationale for using antiplatelet treatment in COVID-19 patients is compelling and was supported by the combined result of early observational studies, evidence from RCTs did not confirm this approach. Several factors that could explain this inconsistency were highlighted alongside perspectives on future research directions.

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.

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.

Abstract

OBJECTIVE There were limited randomized controlled trials (RCTs) of epsilon-aminocaproic acid (EACA) versus tranexamic acid (TXA) in total knee arthroplasty (TKA). The aim of the study was to compare the efficacy and safety of TXA and EACA in the combination of intravenous (IV) and intra-articular (IA) administration on reducing blood loss in patients following primary TKA. METHODS From January 2020 to January 2021, a total of 181 patients undergoing a primary unilateral TKA were enrolled in this prospective randomized controlled trial. Patients in the TXA group (n = 90) received 20 mg/kg of intravenous TXA preoperatively, 1 g of intra-articular TXA intraoperatively, and three doses of 20 mg/kg intravenous TXA at 0, 3, 6 h postoperatively. Patients in the EACA group (n = 91) received 120 mg/kg of intravenous EACA preoperatively, 2 g of intra-articular EACA intraoperatively, and three doses of 40 mg/kg intravenous EACA at 0, 3, 6 h postoperatively. The primary outcomes were total blood loss (TBL), transfusion rates and drop of hemoglobin (HB) level. The secondary outcomes included postoperative hospital stays and postoperative complications. The chi-square tests and Fisher's exact tests were utilized to compare categorical variables, while the independent-samples t-tests and Mann-Whitney tests were used to compare continuous variables. RESULTS The patients who received TXA averaged less TBL than the patients who received EACA (831.83 ml vs 1065.49 ml, P = 0.015), and HB drop in TXA group was generally less than that of EACA group on postoperative day 1 and 3 (20.84 ± 9.48 g/L vs 24.99 ± 9.40 g/L, P = 0.004; 31.28 ± 11.19 vs 35.46 ± 12.26 g/L, P = 0.047). The length of postoperative stays in EACA group was 3.66 ± 0.81 day, which is longer than 2.62 ± 0.68 day in TXA group (P < 0.001). No transfusions were required in either group. The risk of nausea and vomiting in TXA group was significantly higher than that in EACA group (11/90 vs 0/91, P < 0.01). CONCLUSION Although the TBL and HB drop were slightly greater in EACA group, these results were not clinically important, given that no transfusions were required. EACA could be an alternative to TXA, especially for patients with severe nausea and vomiting after using TXA postoperatively. Further studies are needed to adjust dosage of EACA to make better comparison of the two drugs.

Abstract

OBJECTIVES We aimed to evaluate the optimal regimen, efficacy and safety of tranexamic acid (TXA) and aminocaproic acid (EACA) for patients after total hip arthroplasty (THA). METHODS The network meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. The outcomes were total blood loss, transfusion rates, hemoglobin (HB) drop, and risk for pulmonary embolism (PE) or deep vein thrombosis (DVT). Subgroup analyses were performed among most effective regimens to determine the influences of timing and number of doses. RESULTS A total of 56 eligible RCTs with different regimens were assessed. For reducing total blood loss, all high doses of TXA and EACA except high dose of intra-articular (IA) TXA, as well as medium dose of combination of intravenous and intra-articular (combined IV/IA) TXA were most effective. All high doses of TXA, as well as medium dose of combined IV/IA TXA did not show inferiority in reducing transfusion rates and HB drop compared with other regimens. No regimens showed higher risk for PE or DVT compared with placebo, and no statistical differences were seen among most effective regimens in subgroup analyses. CONCLUSIONS As effective as high doses of EACA and TXA, medium dose (20-40 mg/kg or 1.5-3.0 g) of combined IV/IA TXA was enough to control bleeding for patients after THA without increasing risk for PE/DVT. TXA was at least 5 times more potent than EACA. Timing and number of doses had few influences on blood conserving efficacy. LEVEL OF EVIDENCE Level I.

Abstract

BACKGROUND Nafamostat mesilate (NM), a broad-spectrum and potent serine protease inhibitor, can be used as an anticoagulant during extracorporeal circulation, as well as a promising drug effective against coronavirus disease 2019 (COVID-19). We conducted a systematic meta-analysis to evaluate the safety and efficacy of NM administration in critically ill patients who underwent blood purification therapy (BPT). METHODS The Cochrane Library, Web of Science and PubMed were comprehensively searched from inception to August 20, 2021, for potential studies. RESULTS Four randomized controlled trials (RCTs) and seven observational studies with 2723 patients met the inclusion criteria. The meta-analysis demonstrated that conventional therapy (CT) significantly increased hospital mortality compared with NM administration (RR = 1.25, p = 0.0007). In subgroup analyses, the in-hospital mortality of the NM group was significantly lower than that of the anticoagulant-free (NA) group (RR = 1.31, p = 0.002). The CT interventions markedly elevated the risk ratio of bleeding complications by 45% (RR = 1.45, p = 0.010) compared with NM interventions. In another subgroup analysis, NM used exhibited a significantly lower risk of bleeding complications than those of the low-molecular-weight heparin (LMWH) used (RR = 4.58, p = 0.020). The filter lifespan was decreased significantly (MD = -10.59, p < 0.0001) in the NA groups compared with the NM groups. Due to the poor quality of the included RCTs, these results should be interpreted with caution. CONCLUSION Given the better survival outcomes, lower risk of bleeding, NM anticoagulation seems to be a safe and efficient approach for BPT patients and could yield a favorable filter lifespan. More multi-center RCTs with large samples are required for further validation of this study.

Abstract

BACKGROUND The aim of this meta-analysis was to evaluate the efficacy and safety of peri-articular injection of tranexamic acid (TXA) during total knee arthroplasty (TKA) from clinical controlled trials. METHOD Eligible scientific articles published prior to October 2021 were retrieved from the PubMed, Springer, ScienceDirect and Cochrane Library databases. The statistical analysis was performed with RevMan 5.1. RESULT 2 RCTs and 3 non-RCTs met the inclusion criteria. Meta-analysis showed significant differences in terms of hemoglobin reduction (MD = -1.04, 95% CI: -1.33 to -.76, P < .00001), total blood loss (MD = -342.80.70, 95% CI: -437.52 to -248.08, P < .00001), drainage volume (MD = -297.24, 95% CI: -497.26 to -97.23, P = .004) and blood transfusion rate (OR = .30, 95% CI: .14 to .62, P = .001) were found in the control group. No postoperative infection and deep venous thrombosis were found between 2 groups. CONCLUSION Peri-articular injection of TXA can effectively decrease perioperative blood loss and blood transfusion rate without increasing the incidence of postoperative complications during TKA.

Abstract

PURPOSE To investigate whether local administration of epsilon-aminocaproic acid (EACA) is effective and safe in reducing the post-operative blood loss in surgery for Sanders III-IV calcaneal fractures. METHODS Patients with Sanders III-IV calcaneal fractures who were hospitalized in our hospital from January 2016 to February 2021 and underwent open reduction internal fixation (ORIF) via lateral approach with an L-shaped incision were included in the current study. Eighty five patients were randomly divided into two groups, EACA group (43) and control group (42). Twenty milliliters of 5% EACA solution or normal saline was perfused into the incision of patients in EACA group and control group, respectively. The volume of post-operative drainage was investigated as the primary outcome. Post-operative blood test, coagulation test, and wound complications were analyzed as the secondary outcomes. RESULTS The volume of post-operative drainage at 24 and 48 h was 164.8 ± 51.4 ml, 18.9 ± 3.8 ml for patients in EACA group, and 373.0 ± 88.1 ml, 21.2 ± 4.4 ml for patients in the control group, respectively. EACA greatly reduced the post-operative blood loss compared to the control (normal saline). The difference between the two groups was statistically significant. No statistically significant difference was found between EACA group and control group with regard to the pre-operative, baseline characteristics. Post-operative blood test results demonstrated that haemoglobin and hematocrit were significantly higher in EACA compared to those of control group. No significant difference was found between EACA group and control group in terms of the platelet counts, prothrombin time (P.T.), activated partial prothrombin time (APTT), and wound complications. CONCLUSION Local administration of EACA is effective in post-operative blood loss reduction in ORIF surgeries for Sanders III-IV types of calcaneal fractures without increasing the incidence of periwound complication.

Abstract

OBJECTIVE To assess the effect of platelet-rich plasma as a conservative therapy in individuals with partial-thickness rotator cuff tears or tendinopathy on pain, and function. DATA SOURCES Embase, MEDLINE, CENTRAL, Web of Science, CINAHL, PEDro, and the grey literature (to 31 March 2021). METHODS Randomized controlled trials in English that reported short-term (6 ± 1 months), or long-term (⩾1 year) outcomes (shoulder pain or function) were conducted. Two independent reviewers screened the literature, completed the assessment of the Cochrane's risk of bias and extracted the data. Mean difference or standardized mean difference was used for continuous data. Heterogeneity was identified with I(2) test. RESULTS A total of 11 studies were eligible, and nine studies (n = 629) were included in this meta-analysis, that showed statistically significant short-term effects of platelet-rich plasma on pain relief (MD = -1.56; 95% CI -2.82 to -0.30), Constant-Murley score (MD = 16.48; 95% CI 12.57 to 20.40), and Shoulder Pain and Disability Index (MD = -18.78; 95% CI -36.55 to -1.02). Nonetheless, no long-term effect was observed on pain and function, except Constant-Murley score (MD = 24.30; 95% CI 23.27 to 25.33). The results of minimal important difference reached the minimal clinically important difference, except American Shoulder and Elbow Surgeons. For subgroup analysis, differences of pain relief were statistically significant in platelet-rich plasma-treated groups with double centrifugation, single injection, and post-injection rehabilitation. CONCLUSION Our results suggested platelet-rich plasma had positive effects on pain relief and functional improvement for partial-thickness rotator cuff tears and rotator cuff tendinopathy, although the effects may not last for a long time.