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

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.

Abstract

Objective: Intraoperative bleeding during endoscopic sinus surgery (ESS) for high-grade rhinosinusitis can be serious and can further obscure the surgical field. This study was designed to evaluate the effect of tranexamic acid (TXA) on the surgical visualization of ESS for high-grade rhinosinusitis. Methods: In total, 60 patients with high-grade chronic rhinosinusitis (Lund-Mackay score 12 or greater) treated by ESS were randomized into two groups: the control group (Group C) or the TXA group (Group T). Each group included 30 patients. Patients in Group T received intravenous TXA, and those in Group C received normal saline. The Boezaart grading scale (BS) score was assessed as the primary outcome. Total blood loss (TBL), whole blood coagulation, and fibrinolysis were assessed by Sonoclot analysis, and complications were recorded and compared between the groups. Result: A significant difference was found in the BS score between Group T and Group C [2.02 (1.88-2.05) vs. 2.27 (2.13-2.41), P = 0.011]. Increases in platelet function (PF) and fibrin degradation time (FDT) were assessed during the operation and showed significant differences between Group T and Group C (P = 0.040 for PF; P = 0.010 for FDT). No difference in complications was found between the two groups. Conclusion: A 15 mg/kg bolus of intravenous TXA before surgery can improve the surgical visualization of ESS for high-grade chronic rhinosinusitis without causing significant adverse effects. Intravenous TXA may be beneficial in ESS for high-grade chronic rhinosinusitis. Clinical Trial Registration: https://www.chictr.org.cn/edit.aspx?pid=121653&htm=4.

Abstract

BACKGROUND Anemia is a common complication for patients with kidney disease. Roxadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), which is a newly approved oral drug for anemia. We performed this study to build evidence regarding efficacy and safety of roxadustat in kidney disease patients with or without dialysis. METHODS We searched the databases of PubMed, Embase, Cochrane library and clinicaltrials.gov from the inception to July 20, 2020. The randomized controlled trials (RCTs) which compared roxadustat with placebo or other therapies in the treatment of anemia in kidney disease patients were included. Data were extracted from eligible studies and pooled in a meta-analysis model using RevMan5.3 and stata13.0 software. RESULTS Eight RCTs with 1010 patients were included in our analysis. We found that roxadustat significantly increased hemoglobin (Hb) level (1.10 g/dL, 95% CI [0.52 g/dL, 1.67 g/dL], p = 0.0002), total iron-binding capacity (TIBC) (58.71 µg/dL, 95% CI [44.10 µg/dL, 73.32 µg/dL], p < 0.00001), iron level (9.28 µg/dL, 95% CI [0.11 µg/dL, 18.45 µg/dL], p = 0.05) compared with control group in kidney disease patients. In addition, our result showed that a significant reduction in hepcidin level (- 31.96 ng/mL, 95% CI [- 35.05 ng/mL, - 28.87 ng/mL], p < 0.00001), ferritin (- 44.82 ng/mL, 95% CI [- 64.42 ng/mL, - 25.23 ng/mL], p < 0.00001) was associated with roxadustat. No difference was found between roxadustat and control group in terms of oral iron supplementation, adverse events (AEs), serious adverse events (SAEs), infection, myocardial infraction, stroke, heart failure and death. CONCLUSIONS Roxadustat has higher mean Hb level than placebo or EPO. Due to the short follow-up period and the lack of critical data, more RCTs are needed to prove long-term safety and effectiveness of roxadustat in the future.

Abstract

Pneumatic tourniquets are used in total knee arthroplasty (TKA) for surgical field visualization and improved cementation; however, their use is controversial. This study aimed to assess the effects of tourniquet application on faster recovery post-TKA. Our hypothesis was that inflammation and limb function would be similar with different tourniquet applications. A prospective randomized double-blinded trial assessed tourniquets effects on postoperative pain, swelling, and early outcome in TKA. In present study, 50 TKAs were enrolled in each group as follows: full course (FC), cementation through closure (CTC), and no tourniquet (NT), CTC as treatment group while FC and NT as control groups. Topical blood samples of 3 mL from the joint cavity and drainage bags were obtained at special time point. At last, all samples such as tumor necrosis factor-a (TNF-a), C-C motif chemokine ligand 2 (CCL2), pentraxin 3 (PTX3), prostaglandin E2 (PGE2), superoxide dismutase 1 (SOD1), and myoglobin (Mb) were detected by ELISA. Active and passive range of motion (ROM) values, pain score by the visual analog scale (VAS), change of thigh circumference were recorded at special time point as well. In topical blood, the change of inflammatory factors, such as TNF-a, PTX3, CCL2, PGE2, SOD1, and Mb, was lower in CTC and NT groups than in FC group (p < 0.01 and 0.05). Although VAS and ROM were comparable preoperatively in three groups (p > 0.05), the perimeter growth rate was lower, pain scores (VAS) were reduced, and ROM values were improved in CTC and NT groups compared with FC group at T4, T5, and T6 postoperatively (p < 0.01 and 0.05). Improved therapeutic outcome was observed in the CTC group, indicating patients should routinely undergo TKA with cementation through closure tourniquet application.

Abstract

BACKGROUND High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia. METHODS This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30 × 10(9) platelets per L or a platelet count of less than 50 × 10(9) platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30 × 10(9) platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT04217148, and is now completed. FINDINGS Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths. INTERPRETATION The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety. FUNDING The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China.

Abstract

PURPOSE Platelet-rich plasma (PRP) is a promising noninvasive technique for facial rejuvenation. This systematic literature review aims to appraise the nature and quality of published evidence evaluating the effectiveness and safety of PRP in facial rejuvenation. PATIENTS AND METHODS A systematic literature review was conducted with the search string "Platelet-rich plasma AND Facial rejuvenation" in PubMed and Embase. Clinical studies evaluating the outcomes after PRP-based facial rejuvenation either as monotherapy or in combination with other treatment modalities were included. Studies evaluating wound-healing properties of PRP were excluded. The outcomes included both patient-reported and physician-assessed outcomes. Nonstatistical synthesis of evidence was performed by qualitative assessment. The results are reported by the Synthesis Without Meta-analysis (SWiM) reporting standard. RESULTS A total of 36 studies that included a total of 3172 patients were considered for the evidence synthesis. The number of patients in the included studies ranging from 11 to 2005 with a median of 27.5 patients that reflects the challenges in clinically assessing the aesthetic outcomes after PRP-based facial rejuvenation. Among the 36 studies, 17 were observational studies and 18 were interventional studies with 1 being case report PRP was evaluated either alone or in combination with hyaluronic acid, lipofilling, micro-needling technique, and laser-based interventions. Among the studies, 1 study reported the enhanced platelet concentrate in a fibrin matrix to be relatively safe and effective with a maximum benefit observed at 12 weeks suggesting the platelet-rich fibrin matrix may provide desired aesthetic outcomes and it requires further studies to substantiate. CONCLUSION The results suggest very limited clinical evidence, and further clinical studies are warranted to establish the effectiveness of PRP in facial rejuvenation. Furthermore, a consensus for end points used for establishing clinical utility in patients requiring facial rejuvenation is warranted.

Abstract

OBJECTIVE It remains unclear whether transfusion strategies during orthopedic surgery and infection are related. The purpose of this study is to evaluate whether liberal blood transfusion strategies contribute to infection risk in orthopedic patients by analyzing randomized controlled trials (RCTs). METHODS RCTs with liberal versus restrictive red blood cell (RBC) transfusion strategies were identified by searching PubMed, Embase, the Cochrane Central Register of Controlled Trials from their inception to July 2019. Ten studies with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. RESULTS Ten trials involving 3938 participants were included in this study. The pooled risk ratio (RR) for the association between liberal transfusion strategy and infection was 1.34 (95% confidence intervals [CI], 0.94-1.90; P = .106). The sensitivity analysis indicated unstable results, and no significant publication bias was observed. CONCLUSION This pooled analysis of RCTs demonstrates that liberal transfusion strategies in orthopedic patients result in a nonsignificant increase in infections compared with more restrictive strategies. The conclusions are mainly based on retrospective studies and should not be considered as recommendation before they are supported by larger scale and well-designed RCTs.

Abstract

We performed a systematic review and meta-analysis to fully investigate the thrombocytopenia of Platelet-derived Growth Factor Receptor Kinase Inhibitors (PDGFR-TKIs) in cancer patients. Databases were searched for randomized controlled trials (RCTs) treated with PDGFR-TKIs till January 2021. The relevant RCTs in cancer patients treated with PDGFR-TKIs were retrieved and the systematic evaluation was conducted. Nineteen RCTs and 3962 patients were included. Our study suggests that PDGFR-TKIs significantly increased the risks of all-grade (RR, 5.72; 95%CI, 4.32-7.59;p<0.00001; I(2) = 32%) and high-grade (RR, 5.65; 95%CI, 3.28- 9.75; p<0.00001; I(2) = 0%) thrombocytopenia in cancer patients. Sunitinib tend to be associated with the highest risk of thrombocytopenia among the included PDGFR-TKIs. The RR of high-grade thrombocytopenia varies significantly according to treatment line and median age. The available data suggested that the use of PDGFR-TKIs were associated with a significantly increased risk of thrombocytopenia. This article is protected by copyright. All rights reserved.