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1.
Finding the optimal regimen for short-term daily recombinant human erythropoietin treatment for blood-saving purpose in patients undergoing unilateral primary total hip arthroplasty: a double-blinded randomized placebo-controlled trial
Yuan M, Tao Q, Wang D, Wang H, Zhou Z
BMC musculoskeletal disorders. 2022;23(1):243
Abstract
PURPOSE To find the best short-term daily recombinant human erythropoietin (rhEPO)-based treatment protocols for blood-saving purpose in THA. METHOD The patients were randomized to 1 of 3 interventions: Patients in group A received 10,000 IU (150 IU/kg) of subcutaneous rhEPO (1 ml) daily from 5 days preoperatively to 3 days postoperatively (9 doses in total); Patients in group B received 1 ml of subcutaneous normal saline daily from 5 days preoperatively to 3 days preoperatively and then 10,000 IU (150 IU/kg) of subcutaneous rhEPO daily until 3 days postoperatively (6 doses in total). Patients in group C received 1 ml of subcutaneous normal saline daily from 5 days preoperatively to one day preoperatively and then 10,000 IU (150 IU/kg) of subcutaneous rhEPO daily from the day of surgery to 3 days postoperatively (4 doses in total). RESULTS One hundred eighty patients were included. On postoperative day one, patients in the group A showed significantly higher Hb level (108.4 ± 11.4 g/L) than group C (103.9 ± 8.8 g/L). Group B (107.8 ± 8.4 g/L) also showed significantly higher Hb level than group C (103.9 ± 8.8 g/L) (p < 0.05). On postoperative day 3, no significant difference was found between group B and group C in Hb level (98.7 ± 10.5 and 94.9 ± 8.7 g/L, respectively) (p = 0.094), but the Hb level in group A (103.6 ± 11.0 g/L) was still markedly higher than in group B and the Hb level in group A was also markedly higher than in group C. In terms of blood loss, no markedly difference was found in intraoperative blood loss among group A, B and C (78.3 ± 22.4, 84.6 ± 29.1, and 80.3 ± 23.9 ml, respectively) (p = 0.381), but on postoperative day one, the mean blood loss in group C (522.4 ± 189.4 ml) was significantly more than group B (371.2 ± 124.6 ml), and group B was also significantly more than group A (284.8 ± 112.9 ml) with 95% confidence interval, and group B had significantly less blood loss than group C (p < 0.001). With respect to the total blood loss, the total blood loss in group C (881.6 ± 314.9 ml) was significantly more than group B (642.6 ± 232.9 ml), and group B was also significantly more than group A (514.5 ± 204.6 ml) with 95% confidence interval (Table 2). Only 2 patients in each group received allogeneic blood transfusion and each patient received 2 units of red blood cells, so, the transfusion requirements among the three groups were comparable. CONCLUSIONS Daily small-dose of subcutaneous rhEPO administered from 5 days before THA could significantly decrease perioperative blood loss and improve postoperative Hb levels, without increasing risks of complications, when compared with the application of rhEPO from 3 days before THA or from the day of surgery. However, surgeons should choose the regimen individually according to different patients' personal circumstances.
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2.
Effect of Tranexamic Acid on Blood Management during a High Tibial Osteotomy: A Systematic Review and Meta-analysis
Fang Q, Zhang Z, Wang D, Wang L, Xiong W, Tang Y, Liu W, Wang G
Orthopaedic surgery. 2022
Abstract
This study aimed to evaluate the efficiency and safety of tranexamic acid for blood management during high tibial osteotomy (HTO). A systematic search was conducted in Medline, Embase, and the Cochrane library database. Six studies and 208 patients were included in this meta-analysis using Review Manager V.5.3 and Stata 15.1 software. For primary outcomes, tranexamic acid lowered the total blood loss (WMD = -219.47, 95% CI [-355.61, -83.33], P = 0.002). For secondary outcomes, a significant reduction was found for decreased hemoglobin (POD1: WMD = -9.86, 95% CI [-13.45, -6.28], P < 0.05; POD2: WMD = -8.41, 95% CI [-11.50, -5.32], P < 0.05; POD5: WMD = -11.48, 95% CI [-14.56, -8.39], P < 0.05) and drainage (total: WMD = -105.93, 95% CI [-187.08, -24.78], P < 0.05; POD1: WMD = -122.195, 95% CI [-168.902, -75.488], P < 0.05). The sex difference (male/female ratio) was determined (total blood loss: P = 0.025; total drainage amount: p = 0.018) using meta-regression analysis. Females benefited more from tranexamic acid in terms of total blood loss (M/F > 40%: WMD = -53.11, 95% CI [-100.16, -6.05], P = 0.03; 40% ≥ M/F ≥ 20%: WMD = -362.20, 95% CI [-423.96, -300.45], P < 0.05; M/F < 20%: WMD = -263.00, 95% CI [-277.17, -248.83], P < 0.05) and total drainage (M/F > 40%: WMD = -7.11, 95% CI [-10.75, -3.47], P < 0.05; 40% ≥ M/F ≥ 20%: WMD = -104.72, 95% CI [-155.36, -54.08], P < 0.05; M/F < 20%: WMD = -222.00, 95% CI [-297.42, -146.58], P < 0.05). No significant differences were found for drainage on POD2 and POD3, wound complications, orthromboembolic events. In conclusion, tranexamic acid is effective and safe for blood management during HTO. Females appeared to benefit more from it, and an additional postoperative dose is suggested fora better effect.
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3.
Endoscopic Delivery of Polymers Reduces Delayed Bleeding after Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis
Chen Y, Zhao X, Wang D, Liu X, Chen J, Song J, Bai T, Hou X
Polymers. 2022;14(12)
Abstract
New endoscopic approaches for the prevention of delayed bleeding (DB) after gastric endoscopic submucosal dissection (ESD) have been reported in recent years, and endoscopic delivery of biodegradable polymers for iatrogenic ulcer hemostasis and coverage has emerged as one of the most promising techniques for post-ESD management. However, the comparative efficacy of these techniques remains uncertain. We performed a systematic search of multiple databases up to May 2022 to identify studies reporting DB rates as outcomes in patients undergoing gastric ESD who were treated with subsequent endoscopic management, including endoscopic closure (clip-based methods and suturing), PGA sheet tissue shielding, and hemostatic powder/gel spray (including polymeric sealants and other adhesives). The risk ratios (RRs) of delayed bleeding in treatment groups and control groups were pooled, and the Bayesian framework was used to perform a network meta-analysis (NMA). Among these studies, 16 head-to-head comparisons that covered 2742 lesions were included in the NMA. Tissue shielding using PGA sheets significantly reduced the risk of DB by nearly two thirds in high-risk patients, while hemostatic spray systems, primarily polymer-based, reduced DB in low-risk patients nine-fold. Researchers should recognize the essential role of polymers in the management of ESD-induced ulcers, and develop and validate clinical application strategies for promising materials.
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4.
Femoral and tibial cementless fixation neither increases blood loss nor impedes early functional recovery: A randomized controlled trial
Cao J, Liao K, Li ZX, Wang D, Chen JL, Wang HY, Zhou ZK
Frontiers in surgery. 2022;9:1079120
Abstract
BACKGROUND Whether cementless fixation on femoral and tibial components increases blood loss during total knee arthroplasty (TKA) is unclear. The purpose of this randomized controlled trial was to compare blood loss and early functional recovery between patients who underwent cementless or cemented TKA. METHODS Between November 2021 and April 2022, sixty-one eligible patients at our medical center were randomized to cementless and cemented group. The primary outcome was total blood loss (TBL). Secondary outcomes were drainage, knee swelling, anemia, transfusion, hematological indicators, early functional recovery, and postoperative complications. The early functional recovery included range of motion (ROM), Hospital for Special Surgery (HSS) score, walking distance. RESULTS A total of 61 patients were analyzed, of whom 30 underwent cementless fixation. On postoperative day 1, the mean TBL was 394.39 ml (SD 182.97 ml) in the cementless group and 382.41 ml (SD 208.67 ml) in the cemented group (P = 0.863). By postoperative day 3, the corresponding mean TBL was higher at 593.48 ml (SD 230.04 ml) and 603.80 ml (SD 213.16 ml) (P = 0.751). The two groups did not differ significantly in drainage, knee swelling, anemia, levels of hemoglobin or hematocrit or platelets, ROM, HSS score, walking distance, or rates of transfusion or postoperative complications. CONCLUSIONS Cementless fixation on femoral and tibial components during TKA does not increase blood loss or impede early functional recovery, which suggests that clinicians need not worry about blood loss and early functional recovery when deciding what type of fixation to perform during TKA. TRIAL REGISTRATION Number: ChiCTR2100052857; Date: November 6, 2021.
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5.
The efficacy and safety of tranexamic acid in high tibial osteotomy: a systematic review and meta-analysis
Ma J, Lu H, Chen X, Wang D, Wang Q
Journal of orthopaedic surgery and research. 2021;16(1):373
Abstract
OBJECTIVE The present meta-analysis was conducted to evaluate the efficacy and safety of the application of tranexamic acid (TXA) in patients undergoing high tibial osteotomy (HTO). METHODS PubMed (MEDLINE), EMBASE, and Cochrane Library were systematically searched for relevant literature from inception until 1 February 2021. A combined searching strategy of subject words and random words was adopted. After testing for potential publication bias and/or heterogeneity, we aggregated variables by using the random-effect model. The primary comparison outcome measures were total blood loss, hemoglobin decrease, drain output, wound complications, thrombotic events, and blood transfusion rate of the TXA group versus control. The meta-analysis was performed using the RevMan 5.3 software. RESULTS A total of 5 studies were included involving 532 patients. The results showed that there were significant differences in the two groups concerning total blood loss (95% confidence interval [CI] - 332.74 to - 146.46, P < 0.00001), hemoglobin decrease on postoperative day (POD) 1, 2, and 5 (POD 1 95% CI - 1.34 to - 0.63, P < 0.00001; POD 2 95% CI - 1.07 to - 0.68, P < 0.00001; POD 5 95% CI - 1.46 to - 0.84, P < 0.00001), drain output (POD total 95% CI - 195.86 to - 69.41, P < 0.00001) and wound complications (RR = 0.34, 95% CI 0.12 to 0.97, P = 0.04). Nonsignificant differences were found in the incidence of thromboembolic events (RR = 0.46, 95% CI 0.09 to 2.41, P = 0.36) and blood transfusion rate (RR = 0.25, 95% CI 0.03 to 2.27, P = 0.22). CONCLUSIONS This meta-analysis of the available evidence demonstrated that TXA could reduce total blood loss, hemoglobin decrease, drain output, and wound complications without increasing the incidence of thromboembolic events in patients undergoing HTO. But there is no obvious evidence that TXA could reduce blood transfusion rates. Further studies, including more large-scale and well-designed randomized controlled trials, are warranted to assess the efficacy and safety issues of routine TXA use in HTO patients.
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The Statistical Fragility of Platelet-Rich Plasma in Rotator Cuff Surgery: A Systematic Review and Meta-analysis
Parisien RL, Ehlers C, Cusano A, Tornetta P 3rd, Li X, Wang D
The American journal of sports medicine. 2021;:363546521989976
Abstract
BACKGROUND The practice of evidence-based medicine relies on objective data to guide clinical decision-making with specific statistical thresholds conveying study significance. PURPOSE To determine the utility of applying the fragility index (FI) and the fragility quotient (FQ) analysis to randomized controlled trials (RCTs) evaluating the utilization of platelet-rich plasma (PRP) in rotator cuff repairs (RCRs). STUDY DESIGN Systematic review and meta-analysis. METHODS RCTs pertaining to the utilization of PRP in surgical RCRs published in 13 peer-reviewed journals from 2000 to 2020 were evaluated. The FI was determined by manipulating each reported outcome event until a reversal of significance was appreciated. The associated FQ was determined by dividing the FI by the sample size. RESULTS Of the 9746 studies screened, 19 RCTs were ultimately included for analysis. The overall FI incorporating all 19 RCTs was only 4, suggesting that the reversal of only 4 events is required to change study significance. The associated FQ was determined as 0.092. Of the 43 outcome events reporting lost to follow-up data, 13 (30.2%) represented lost to follow-up >4. CONCLUSION Our analysis suggests that RCTs evaluating PRP for surgical RCRs may lack statistical stability with only a few outcome events required to alter trial significance. Therefore, we recommend the reporting of an FI and an FQ in conjunction with P value analysis to carefully interpret the integrity of statistical stability in future comparative trials. CLINICAL RELEVANCE Clinical decisions are often informed by statistically significant results. Thus, a true understanding of the robustness of the statistical findings informing clinical decision-making is of critical importance.
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Synergistic Effect of a Prolonged Combination Course of Tranexamic Acid and Dexamethasone Involving High Initial Doses in Total Knee Arthroplasty: A Randomized Controlled Trial
Xu H, Xie J, Yang J, Huang Z, Wang D, Pei F
The journal of knee surgery. 2021
Abstract
The optimal regimes of tranexamic acid (TXA) and dexamethasone (DXM) in total knee arthroplasty (TKA) are still uncertain. The aim of this study was to assess the efficacy and safety of a prolonged course of intravenous TXA and DXM involving a high initial dose in TKA. Patients who underwent primary TKA at our center were randomized to receive one of four regimes: control (group A), prolonged course of TXA (B), prolonged course of DXM (C), or the combination of a prolonged course of TXA and DXM (D). The four groups were compared in primary outcomes (fibrinolytic and inflammatory markers, knee function, postoperative pain levels, and consumption of opioids) and secondary outcomes (blood loss, maximal drop in hemoglobin, coagulation, fasting blood glucose, and complications). A total of 162 patients were enrolled. On postoperative days 2 and 3, fibrinolytic markers were lower in groups B and D than in groups A and C; inflammatory markers were lower in groups C and D than in groups A and B. Inflammatory markers were lower in group B than in group A on postoperative day 3. Postoperative pain levels and oxycodone consumption were lower, and knee function was better in groups C and D. The four groups did not differ in any of the secondary outcomes. A prolonged course of intravenous TXA and DXM involving high initial doses can effectively inhibit postoperative fibrinolytic and inflammatory responses, reduce pain, and improve knee function after TKA.
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8.
[Effects of reinfusion of the remaining blood filtered by leukocyte depletion filter on postoperative cellar immune function after cardiopulmonary bypass]
Luo L, Wang D, Chen M, Li M
Zhonghua wei zhong bing ji jiu yi xue. 2019;31(8):989-993
Abstract
OBJECTIVE To evaluate effects of reinfusion of the remaining blood filtered by leukocyte depletion filter on postoperative cellular immune function after cardiopulmonary bypass (CPB). METHODS Forty patients who underwent selective cardiac valve replacement surgery with CPB in department of anesthesiology of Haikou Municipal Hospital from January to June in 2018 were enrolled. All the patients were divided into the control group and experimental group according to the random number table method, with 20 patients in each group. In the experimental group, patients received residual pump blood transfusion which had been filtered by leukocyte depletion filter and stored in sterile blood collection bags. In the control group, patients received residual pump blood transfusion which was stored in sterile blood collection bags without being filtered. The remaining blood was reinfused after CPB in two groups. Blood samples were taken before CPB (T1), 2 hours following CPB (T2), and 1, 3, 5 days after reinfusion of the remaining blood (T3, T4, T5), the levels of T lymphocyte subsets CD3(+), CD4(+), CD8(+) and natural killer cells (NK cells) were detected by flow cytometer, and CD4(+)/CD8(+) ratio was calculated. The levels of plasma tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-2, IL-6, IL-8) were measured by enzyme linked immunosorbent essay (ELISA). The duration of mechanical ventilation, the length of intensive care unit (ICU) stay, the length of hospital stay, and incidence of wound and pulmonary infection after surgery were compared between two groups. RESULTS Among 40 patients, there were 22 males and 18 females; with an age of (47.88+/-12.29) years old; and with 25 cases of American Society of Anesthesiologists (ASA) physical status II, and 15 cases of ASA III. There was no statistical difference in the volume of the remaining blood between the two groups (mL: 959.00+/-116.84 vs. 971.50+/-115.68, P > 0.05). Compared with T1, the levels of T lymphocyte subsets CD3(+), CD4(+), CD8(+), NK cells and plasma levels of IL-2 were significantly decreased from T2, the CD4(+)/CD8(+) ratio was significantly decreased from T3 in two groups, but there was no statistical difference in CD3(+), CD4(+), CD8(+), NK cells, CD4(+)/CD8(+) ratio or plasma level of IL-2 at each time between the two groups. Compared with T1, the plasma levels of TNF-alpha, IL-6 and IL-8 were significantly increased at T2 in two groups and then decreased gradually. The plasma levels of TNF-alpha, IL-6 and IL-8 from T3 in experimental group were lower than those in control group [TNF-alpha (ng/L): 28.49+/-4.66 vs. 33.82+/-4.30, IL-6 (ng/L): 25.98+/-4.51 vs. 31.38+/-5.42, IL-8 (ng/L): 38.98+/-4.67 vs. 45.76+/-5.33, all P < 0.05], they restored to the level of T1 at T5. In addition, compared with control group, the duration of mechanical ventilation, the length of ICU stay in experimental group were significantly decreased (hours: 8.07+/-1.30 vs. 9.16+/-1.52, 28.22+/-2.78 vs. 31.25+/-3.18, both P < 0.05), and there was no statistical difference in the length of hospital stay (days: 20.65+/-2.76 vs. 22.45+/-3.22), incidence of wound and pulmonary infection (25.0% vs. 15.0%, 5.0% vs. 15.0%) between the two groups (all P > 0.05). CONCLUSIONS Reinfusion of the remaining blood filtered by leukocyte depletion filtercan inhibit inflammatory responses and don't affect the function of cellular immunity, and don't increase the incidence of infection.
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9.
Intravenous and subsequent long-term oral tranexamic acid in enhanced-recovery primary total knee arthroplasty without the application of a tourniquet: a randomized placebo-controlled trial
Wang HY, Wang L, Luo ZY, Wang D, Tang X, Zhou ZK, Pei FX
BMC musculoskeletal disorders. 2019;20(1):478
Abstract
BACKGROUND To assess the efficacy and safety of intravenous and subsequent long-term oral tranexamic acid (TXA) following total knee arthroplasty (TKA) without a tourniquet. METHODS In this double-blinded trial, 118 patients undergoing primary TKA were randomized into two groups: the patients in group A received intravenous TXA at 20-mg/kg 10 min before the surgery and 3 h postoperatively, and then oral 1 g TXA from postoperative day (POD) 1 to POD 14, and the patients in group B received intravenous TXA at 20-mg/kg 10 min before surgery and 3 h postoperatively, and then oral 1 g placebo from postoperative day (POD) 1 to POD 14. The primary outcome was total blood loss. Secondary outcomes included ecchymosis area and morbidity, postoperative transfusion, postoperative laboratory values, postoperative knee function and length of hospital stay. Complications, and patient satisfaction were also recorded. RESULTS The mean total blood loss was lower in Group A than in Group B (671.7 ml vs 915.8 ml, P = 0.001). There was no significant difference in the transfusion rate between the two groups. Group A had a higher hemoglobin than Group B on POD 3 (106.0 g/L vs 99.7 g/L, P = 0.001). However, no significant difference was found for Hb or hematocrit on POD 1 or POD 14 between the two groups. Patients in Group A had less ecchymosis morbidity (7 vs 38, P = 0.001), smaller ecchymosis area (1.6 vs 3.0, P = 0.001) than Group B. The blood coagulation level as measured by fibrinolysis (D-Dimer) was lower in Group A than in Group B on POD 1 and POD 3 (4.6 mg/L vs. 8.4 mg/L, respectively, P = 0.001; 1.5 mg/L vs. 3.3 mg/L, respectively, P = 0.001). However, there was no significant difference on POD 14, and the fibrin degradation products showed the same trend. Patients in Group A had less swelling than those in Group B on POD 3 and POD 14. The circumference of the knee was 43.1 cm vs. 46.1 cm (POD 3, P = 0.001) and 41.4 cm vs. 44.9 cm (POD 14, P = 0.001) in Group A vs Group B, respectively. Nevertheless, the circumference of the knee in the two groups was similar on POD 1 and POD 3 M. No significant differences were identified in knee function, pain score, or hospital stay. No significant differences were identified in thromboembolic complications, infection, hematoma, wound healing and patients satisfaction between the two groups. CONCLUSION Intravenous and subsequent long-term oral TXA produced less blood loss and less swelling and ecchymosis compared with short-term TXA without increasing the risk of complications. TRIAL REGISTRATION The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR-IPR-17012264 ).
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10.
Effect of Multiple Doses of Oral Tranexamic Acid on Haemostasis and Inflammatory Reaction in Total Hip Arthroplasty: A Randomized Controlled Trial
Wang D, Yang Y, He C, Luo ZY, Pei FX, Li Q, Zhou ZK, Zeng WN
Thrombosis and haemostasis. 2019;119(1):92-103
Abstract
Tranexamic acid (TXA) reduces surgical blood loss and alleviates inflammatory response in total hip arthroplasty. However, studies have not identified an optimal regimen. The objective of this study was to identify the most effective regimen of multiple-dose oral TXA in achieving maximum reduction of blood loss and inflammatory response based on pharmacokinetic recommendations. We prospectively studied four multiple-dose regimens (60 patients each) with control group (group A: matching placebo). The four multiple-dose regimens included: 2-g oral TXA 2 hours pre-operatively followed by 1-g oral TXA 3 hours post-operatively (group B), 2-g oral TXA followed by 1-g oral TXA 3 and 7 hours post-operatively (group C), 2-g oral TXA followed by 1-g oral TXA 3, 7 and 11 hours post-operatively (group D) and 2-g oral TXA followed by 1-g oral TXA 3, 7, 11 and 15 hours post-operatively (group E). The primary endpoint was estimated blood loss on post-operative day (POD) 3. Secondary endpoints were thromboelastographic parameters, inflammatory components, function recovery and adverse events. Groups D and E had significantly less blood loss on POD 3, with no significant difference between the two groups. Group E had the most prolonged haemostatic effect, and all thromboelastographic parameters remained within normal ranges. Group E had the lowest levels of inflammatory cytokines and the greatest range of motion. No thromboembolic complications were observed. The post-operative four-dose regimen brings about maximum efficacy in reducing blood loss, alleviating inflammatory response and improving analgaesia and immediate recovery.