Combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) in the treatment of knee osteoarthritis: a meta-analysis of randomised controlled trials
Zhao J, Liang G, Han Y, Yang W, Xu N, Luo M, Pan J, Liu J, Zeng LF
BMJ open. 2022;12(11):e061008
OBJECTIVES The purpose of this meta-analysis was to investigate the efficacy and safety of mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA). DESIGN Systematic review and meta-analysis. PARTICIPANTS Patients with KOA. INTERVENTIONS Use of MSCs+PRP. PRIMARY AND SECONDARY OUTCOMES Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and adverse reactions. DATA SOURCES PubMed, Cochrane Library, Embase and China National Knowledge Infrastructure were searched from inception to 15 July 2021. MEASURES The OR or weighted mean difference (WMD) of relevant outcome indicators was calculated. Study quality was evaluated using the risk-of-bias assessment tool version 2.0. Heterogeneity among studies was evaluated by calculating I(2). If I(2)＜50%, a fixed-effect model was applied; conversely, if I(2) ≥50%, a random-effect model was applied. RESULTS Six controlled clinical trials with 493 cases were included. The meta-analysis results showed that in terms of the VAS score 3 months after treatment, MSCs+PRP had no significant effect on the reduction of the VAS score in patients with KOA compared with the control (p=0.09), hyaluronic acid (HA) (p=0.15) or PRP alone (p=0.07). MSCs+PRP was more effective in reducing the VAS score at 6 and 12 months after treatment than the control (WMD=-0.55, 95% CI -0.87 to -0.22, p<0.001), HA (WMD=-1.20, 95% CI -2.28 to -0.13, p=0.03) or PRP alone (WMD=-0.54, 95% CI -0.89 to -0.18, p=0.003). Regarding the decrease in the total WOMAC score at 3 and 6 months after treatment, MSCs+PRP showed better clinical efficacy than the control or HA alone (p<0.01). Compared with the control, MSCs+PRP exhibited no significant difference in reducing the total WOMAC score 12 months after treatment (p=0.39). There was no significant difference between MSCs+PRP and the control in terms of improvement of the KOOS 12 months after treatment (p=0.16). Compared with MSCs alone, MSCs+PRP exhibited no significant difference in the incidence of adverse reactions (p=0.22) 12 months after treatment. CONCLUSIONS Treatment with MSCs+PRP showed good clinical efficacy in improving pain and joint function in patients with KOA. Compared with MSCs alone, there was no significant difference in the incidence of adverse reactions with MSCs+PRP. PROSPERO REGISTRATION NUMBER CRD 42021275830.
A randomised non-inferiority trial comparing the effectiveness of oral versus intravenous tranexamic acid in primary total hip and knee arthroplasty
DeFrancesco CJ, Reichel JF, Gbaje E, Popovic M, Freeman C, Wong M, DeMeo D, Liu J, Gonzalez Della Valle A, Ranawat A, et al
British journal of anaesthesia. 2022
BACKGROUND Tranexamic acid (TXA) reduces rates of blood transfusion for total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although the use of oral TXA rather than intravenous (i.v.) TXA might improve safety and reduce cost, it is not clear whether oral administration is as effective. METHODS This noninferiority trial randomly assigned consecutive patients undergoing primary THA or TKA under neuraxial anaesthesia to either one preoperative dose of oral TXA or one preoperative dose of i.v. TXA. The primary outcome was calculated blood loss on postoperative day 1. Secondary outcomes were transfusions and complications within 30 days of surgery. RESULTS Four hundred participants were randomised (200 THA and 200 TKA). The final analysis included 196 THA patients (98 oral, 98 i.v.) and 191 TKA patients (93 oral, 98 i.v.). Oral TXA was non-inferior to i.v. TXA in terms of calculated blood loss for both THA (effect size=-18.2 ml; 95% confidence interval [CI], -113 to 76.3; P<0.001) and TKA (effect size=-79.7 ml; 95% CI, -178.9 to 19.6; P<0.001). One patient in the i.v. TXA group received a postoperative transfusion. Complication rates were similar between the two groups (5/191 [2.6%] oral vs 5/196 [2.6%] i.v.; P=1.00). CONCLUSIONS Oral TXA can be administered in the preoperative setting before THA or TKA and performs similarly to i.v. TXA with respect to blood loss and transfusion rates. Switching from i.v. to oral TXA in this setting has the potential to improve patient safety and decrease costs.
The efficacy of tranexamic acid treatment with different time and doses for traumatic brain injury: a systematic review and meta-analysis
Huang H, Xin M, Wu X, Liu J, Zhang W, Yang K, Zhang J
Thrombosis journal. 2022;20(1):79
OBJECTIVE Tranexamic acid (TXA) plays a significant role in the treatment of traumatic diseases. However, its effectiveness in patients with traumatic brain injury (TBI) seems to be contradictory, according to the recent publication of several meta-analyses. We aimed to determine the efficacy of TXA treatment at different times and doses for TBI treatment. METHODS PubMed, MEDLINE, EMBASE, Cochrane Library, and Google Scholar were searched for randomized controlled trials that compared TXA and a placebo in adults and adolescents (≥ 15 years of age) with TBI up to January 31, 2022. Two authors independently abstracted the data and assessed the quality of evidence. RESULTS Of the identified 673 studies, 13 involving 18,675 patients met our inclusion criteria. TXA had no effect on mortality (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.92-1.06), adverse events (RR 0.93, 95% Cl 0.76-1.14), severe TBI (Glasgow Coma Scale score from 3 to 8) (RR 0.99, 95% Cl 0.94-1.05), unfavorable Glasgow Outcome Scale (GOS < 4) (RR 0.96, 95% Cl 0.82-1.11), neurosurgical intervention (RR 1.11, 95% Cl 0.89-1.38), or rebleeding (RR 0.97, 95% Cl 0.82-1.16). TXA might reduce the mean hemorrhage volume on subsequent imaging (standardized mean difference, -0.35; 95% CI [-0.62, -0.08]). CONCLUSION TXA at different times and doses was associated with reduced mean bleeding but not with mortality, adverse events, neurosurgical intervention, and rebleeding. More research data is needed on different detection indexes and levels of TXA in patients with TBI, as compared to those not receiving TXA; although the prognostic outcome for all harm outcomes was not affected, the potential for harm was not ruled out. TRIAL REGISTRATION The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42022300484).
Ischemic stroke and intracranial hemorrhage in extracorporeal membrane oxygenation for COVID-19: A systematic review and meta-analysis
Jin Y, Zhang Y, Liu J
PURPOSE Extracorporeal membrane oxygenation (ECMO) is employed to support critically ill COVD-19 patients. The occurrence of ischemic stroke and intracranial hemorrhage (ICH), as well as the implementation of anticoagulation strategies under the dual influence of ECMO and COVID-19 remain unclear. We conducted a systematic review and meta-analysis to describe the ischemic stroke, ICH and overall in-hospital mortality in COVID-19 patients receiving ECMO and summarize the anticoagulation regimens. METHODS EMBASE, PubMed, Cochrane, and Scopus were searched for studies examining ischemic stroke, ICH, and mortality in COVID-19 patients supported with ECMO. The outcomes were incidences of ischemic stroke, ICH, overall in-hospital mortality and anticoagulation regimens. We calculated the pooled proportions and 95% confidence intervals (CIs) to summarize the results. RESULTS We analyzed 12 peer-reviewed studies involving 6039 COVID-19 patients. The incidence of ischemic stroke had a pooled estimate of 2.2% (95% CI: 1.2%-3.2%). The pooled prevalence of ICH was 8.0% (95% CI: 6.3%-9.6%). The pooled estimate of overall in-hospital mortality was 40.3% (95% CI: 33.1%-47.5%). The occurrence of ICH was significantly higher in COVID-19 patients supported with ECMO than in other respiratory ECMO [relative risk=1.75 (95% CI: 1.00-3.07)]. Unfractionated heparin was the most commonly used anticoagulant, and anticoagulation monitoring practice varied among centers. CONCLUSIONS Ischemic stroke and ICH were common under the double "hit" of COVID-19 and ECMO. The prevalence of ICH was significantly higher in COVID-19 patients supported with ECMO than non-COVID-19 patients requiring ECMO. Individualized anticoagulation regimens may be a good choice to balance thrombosis and bleeding. More detailed research and further exploration are needed to clarify the underlying mechanism and clinical management decisions.
LNG-IUS vs. medical treatments for women with heavy menstrual bleeding: A systematic review and meta-analysis
Chen S, Liu J, Peng S, Zheng Y
Frontiers in medicine. 2022;9:948709
INTRODUCTION To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with medical treatments for women with heavy menstrual bleeding. MATERIALS AND METHODS We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant randomized controlled trials (RCTs) in November 2021. All meta-analyses were performed using the random-effects model. PROSPERO registration number: CRD42021295379. RESULTS A total of trials (with 14 references) reporting on 1,677 women were included in this systematic review. The majority of the included RCTs were rated with low-to-unclear risk of bias in selection, detection, attrition, reporting, and other bias. All RCTs were rated as high risk in performance bias because blinding was difficult to ensure in the compared groups. Results of meta-analyses revealed that the number of clinical responders was greater in the LNG-IUS group than that in the medical treatments group at both 6-month (steroidal: five RCTs; n = 490; risk ratio [RR]: 1.72 [1.13, 2.62]; I (2) = 92%; nonsteroidal: one RCT; n = 42; RR: 2.34 [1.31, 4.19]) and 12-month (steroidal: three RCTs; n = 261; RR: 1.31 [1.01, 1.71]; I (2) = 74%) endpoints, with no clear differences on number of dropouts, and the incidence of adverse events. CONCLUSION Evidence indicates that LNG-IUS is superior to the medical treatments in short-term and medium-term clinical responses, blood loss control, compliance, and satisfaction. Meanwhile, frequency of adverse events related to LNG-IUS is acceptable. SYSTEMATIC REVIEW REGISTRATION PROSPERO, identifier CRD42021259335, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021295379.
Effect of Mirena Intrauterine Device on Endometrial Thickness, Quality of Life Score, and Curative Effect in Patients with Perimenopausal Abnormal Uterine Bleeding
Yu Y, Zhou Z, Wang L, Liu J
Computational and mathematical methods in medicine. 2022;2022:5648918
OBJECTIVE To study the effect of Mirena intrauterine device (IUD) on endometrial thickness, life quality score, and curative effect in patients with perimenopausal abnormal uterine bleeding. METHODS Eighty patients with perimenopausal abnormal uterine bleeding cured from January 2020 to December 2021 were enrolled as the object of study. According to random number table, the patients were classified into the study (n = 40) and control (n = 40) groups. The control cases were cured with medroxyprogesterone. The study cases were cured with Mirena IUD. The effective rate of clinical therapies was evaluated after 3 months of treatment. The endometrial thickness, menstrual volume score, and life quality score (WHOQOL-BREF) was measured after 1 month, 2 months, and 3 months of treatment. RESULTS The effective rate of patients with Mirena IUD for 3 months was higher compared to the control group (P < 0.05). The endometrial thickness and menstrual volume scores of study cohort after 1 month, 2 months, and 3 months following treatment were remarkably lower than those before treatment (P < 0.05) and were considerably lower than those of control cohort (P < 0.05). The hemoglobin level of the studied cases after 1 month, 2 months, and 3 months after therapy was remarkably upregulated (P < 0.05) and was greatly higher compared to the controlled cases (P < 0.05). After 3-month treatment, the WHOQOL-BREF score of the study group was higher compared to the control group (P < 0.05). CONCLUSION The Mirena IUD is far more effective in the treatment of perimenopausal abnormal uterine bleeding and is helpful in reducing the thickness of the endometrium. Patients' menstrual flow can be controlled, and anemia can be corrected; thus, patients improve their quality of life and health status and can be considered for further promotion.
Does Tranexamic Acid Reduce the Blood Loss in Various Surgeries? An Umbrella Review of State-of-the-Art Meta-Analysis
Hong P, Liu R, Rai S, Liu J, Ding Y, Li J
Frontiers in pharmacology. 2022;13:887386
Background: Tranexamic acid (TXA) has been applied in various types of surgery for hemostasis purposes. The efficacy and safety of TXA are still controversial in different surgeries. Guidelines for clinical application of TXA are needed. Materials and method: We systematically searched multiple medical databases for meta-analyses examining the efficacy and safety of TXA. Types of surgery included joint replacement surgery, other orthopedic surgeries, cardiac surgery, cerebral surgery, etc. Outcomes were blood loss, blood transfusion, adverse events, re-operation rate, operative time and length of hospital stay, hemoglobin (Hb) level, and coagulation function. Assessing the methodological quality of systematic reviews 2 (AMSTAR 2) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) were used for quality assessment of the included meta-analyses. Overlapping reviews were evaluated by calculating the corrected covered area (CCA). Result: In all, we identified 47 meta-analyses, of which 44 of them were of "high" quality. A total of 319 outcomes were evaluated, in which 58 outcomes were assessed as "high" quality. TXA demonstrates significant hemostatic effects in various surgeries, with lower rates of blood transfusion and re-operation, shorter operative time and length of stay, and higher Hb levels. Besides, TXA does not increase the risk of death and vascular adverse events, but it is a risk factor for seizure (a neurological event) in cardiac surgery. Conclusion: Our study demonstrates that TXA has a general hemostatic effect with very few adverse events, which indicates TXA is the recommended medication to prevent excessive bleeding and reduce the blood transfusion rate. We also recommend different dosages of TXA for different types of adult surgery. However, we could not recommend a unified dosage for different surgeries due to the heterogeneity of the experimental design. Systematic Review Registration: clinicaltrials.gov/, identifier CRD42021240303.
Intra-Articular Injections of Platelet-rich plasma, Adipose mesenchymal stem cells and Bone marrow mesenchymal stem cells Associated With Better Outcomes than Hyaluronic acid and Saline in Knee Osteoarthritis: A systematic review and network meta-analysis
Zhao D, Pan JK, Yang WY, Han YH, Zeng LF, Liang GH, Liu J
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 2021
PURPOSE To perform a network meta-analysis to evaluate clinical efficacy and treatment related adverse events (AEs) of intra-articular hyaluronic acid (HA), leukocyte-poor platelet-rich plasma (LP-PRP), leukocyte-rich platelet-rich plasma (LR-PRP), bone marrow mesenchymal stem cells (BM-MSCs), adipose mesenchymal stem cells (AD-MSCs) and saline (placebo) during 6 and 12 months of follow-up. METHODS Six databases were searched for randomized controlled trials. Outcome assessment included the visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscore, WOMAC score, International Knee Documentation Committee (IKDC) subjective score, and treatment-related AEs. Main inclusion criteria were at least one of the aforementioned outcome measurements, a minimum follow-up period of 5 months, and >80% patient follow-up. Treatments combined with the use of other operations or drugs were excluded. RESULTS Forty-three studies meeting the eligibility criteria were included. At 6-months, VAS scores and WOMAC pain subscores showed that AD-MSCs were the best treatment option (SUCRA=96.7%, SUCRA=85.3%, respectively). According to WOMAC scores and subjective IKDC scores, LP-PRP was the most effective treatment (SUCRA=86.0%, SUCRA=80.5%, respectively). At 12-months, only AD-MSCs were associated with improved VAS scores compared with the placebo (WMD=-20.93, 95%CrI(-41.71, -0.78)). Both LP-PRP and AD-MSCs were more beneficial than the placebo for improving WOMAC pain subscores (WMD=-30.08, 95%CrI(-53.59, -6.25); WMD=-34.85, 95%CrI(-68.03, -4.86), respectively). For WOMAC scores, LP-PRP and LR-PRP were significantly associated with improved WOMAC scores compared with the placebo after sensitivity analysis was performed (WMD=-35.26, 95%Cr(-64.99, -6.01); WMD=-38.69, 95%CrI(-76.21, -2.76)). LP-PRP exhibited relatively better efficacy in improving subjective IKDC scores than the placebo (WMD=13.67, 95%CrI(4.05, 23.39). Regarding safety, all treatments except for LP-PRP (relative risk=1.83, 95%CrI(0.89, 4.64)) increased treatment-related AEs compared with the placebo. CONCLUSIONS Based on the results of current research findings, during 6 months of follow-up, AD-MSCs relieve pain the best; LP-PRP was most effective for functional improvement. During the 12-month follow-up, both AD-MSCs and LP-PRP showed potential clinical pain relief effects; functional improvement was achieved with LP-PRP. Unfortunately, AD-MSC/LP-PRP functional comparisons were only based on WOMAC scores due to missing IKDC scores. BM-MSCs seem to have potentially beneficial effects, but the wide credibility interval make it impossible to draw a well-supported conclusion. HA viscosupplementation clinical efficacy was lower than that of biological agents during follow-up, which may be related to the properties of the drugs. Considering the evaluation of treatment-related AEs, LP-PRP is the most advisable choice; although the AEs of these treatments are not serious, they may affect treatment compliance and satisfaction. LEVEL OF EVIDENCE Level II, meta-analysis of Level I and II studies.
Primary nursing intervention can improve the prognosis and postoperative quality of life of patients with hypertensive intracerebral hemorrhage undergoing minimally invasive surgery
Wu L, Liu J, Lai J, Meng L
American journal of translational research. 2021;13(4):2955-2961
OBJECTIVE This study aimed to explore the role of primary nursing in patients with hypertensive intracerebral hemorrhage (HICH) undergoing minimally invasive surgery. METHODS We randomly assigned 106 patients with HICH treated in our hospital to receive routine nursing (54 cases, group A) or primary nursing in addition to routine nursing (52 cases, group B). The scores of negative emotions, incidence of complications, quality of life, and prognosis of all patients were recorded. RESULTS The score of negative emotions and the incidence of complications were lower in group B than in group A (P < 0.05). The scores of quality of life and prognosis were higher in group B than in group A (P < 0.05). CONCLUSION Primary nursing intervention can improve the prognosis and postoperative quality of life of patients with HICH undergoing minimally invasive surgery.
A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, et al
Journal of hematology & oncology. 2021;14(1):37
BACKGROUND Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. METHODS Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10(9)/L) after 8 weeks of treatment. RESULTS The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. CONCLUSIONS In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.