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
BMC musculoskeletal disorders. 2022;23(1):243
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.
Endoscopic Delivery of Polymers Reduces Delayed Bleeding after Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis
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.
Effect of Tranexamic Acid on Blood Management during a High Tibial Osteotomy: A Systematic Review and Meta-analysis
Orthopaedic surgery. 2022
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.
The Statistical Fragility of Platelet-Rich Plasma in Rotator Cuff Surgery: A Systematic Review and Meta-analysis
The American journal of sports medicine. 2021;:363546521989976
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.
Synergistic Effect of a Prolonged Combination Course of Tranexamic Acid and Dexamethasone Involving High Initial Doses in Total Knee Arthroplasty: A Randomized Controlled Trial
The journal of knee surgery. 2021
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.
Efficacy and safety of blood purification in the treatment of deep burns: A systematic review and meta-analysis
INTRODUCTION This meta-analysis aimed to systematically review and evaluate randomized controlled trials (RCTs) and cohort studies examining the efficacy and safety of blood purification in the treatment of patients with deep burns. METHODS The PubMed, Cochrane Library, and Embase databases and relevant references were systematically searched for RCTs and cohort studies published until the end of September 2020 to investigate the potential of blood purification in improving the prognosis of severely burned patients. The primary outcome of this systematic review was overall patient mortality; secondary outcomes included the incidence of sepsis and infection prevention (vital signs and routine blood tests). RESULTS A total of 6 RCTs and 1 cohort study were included, with a total of 538 burn patients (274 patients who received blood purification and 264 control patients). Compared with patients who received conventional treatment, those treated with blood purification displayed significant 2-day reduction in mortality and sepsis with relative risks of 0.62 and 0.41, respectively (95% confidence intervals [CIs], 0.74-0.82 and 0.25-0.67, respectively; P < .05). In terms of vital signs and blood biochemistry, the respiratory rates and blood urea nitrogen levels of patients in the blood purification group 3 days post-treatment were significantly higher than those in the control group (randomized standard deviations (SMDs), 0.78 and 0.77, respectively; 95% CIs, 0.33-1.23 and 1.22-0.31, respectively; P < .05). However, there were no significant differences between groups on day 3 with regard to temperature (P = .32), heart rate (P = .26), white blood cell count (P = .54), or neutrophil count (P = .74), potentially owing to the small sample size or the relatively short intervention time. Heterogeneous differences existed between the groups with respect to blood urea nitrogen (SMD = -1.22; 95% CI, -2.16 to -0.40; P < .00001) and Cr (SMD = -3.13; 95% CI, -4.92 to -1.33; P < .00001) on day 7. No systematic adverse events occurred. CONCLUSIONS Blood purification treatment for deep burn patients can significantly reduce the mortality rate and the incidence of complications.
Reporting in clinical studies on platelet-rich plasma therapy among all medical specialties: A systematic review of Level I and II studies
PloS one. 2021;16(4):e0250007
BACKGROUND The clinical practice of platelet-rich plasma (PRP) therapy has grown significantly in recent years in multiple medical specialties. However, comparisons of PRP studies across medical fields remain challenging because of inconsistent reporting of protocols and characterization of the PRP being administered. The purpose of this systematic review was to determine the quantity of level I/II studies within each medical specialty and compare the level of study reporting across medical fields. METHODS The Cochrane Database, PubMed, and EMBASE databases were queried for level I/II clinical studies on PRP injections across all medical specialties. From these studies, data including condition treated, PRP processing and characterization, delivery, control group, and assessed outcomes were collected. RESULTS A total of 132 studies met the inclusion and exclusion criteria and involved 28 different conditions across 8 specialties (cardiothoracic surgery, cosmetic, dermatology, musculoskeletal (MSK), neurology, oral maxillofacial surgery, ophthalmology, and plastic surgery). Studies on PRP for MSK injuries made up the majority of the studies (74%), with knee osteoarthritis and tendinopathy being most commonly studied. Of the 132 studies, only 44 (33%) characterized the composition of PRP used, and only 23 (17%) reported the leukocyte component. MSK studies were more likely to use patient-reported outcome measures to assess outcomes, while studies from other specialties were more likely to use clinician- or imaging-based objective outcomes. Overall, 61% of the studies found PRP to be favorable over control treatment, with no difference in favorable reporting between MSK and other medical specialties. CONCLUSIONS The majority of level I/II clinical studies investigating PRP therapy across all medical specialties have been conducted for MSK injuries with knee osteoarthritis and tendinopathy being the most commonly studied conditions. Inconsistent reporting of PRP composition exists among all studies in medicine. Rigorous reporting in human clinical studies across all medical specialties is crucial for evaluating the effects of PRP and moving towards disease-specific and individualized treatment.
The efficacy and safety of tranexamic acid in high tibial osteotomy: a systematic review and meta-analysis
Journal of orthopaedic surgery and research. 2021;16(1):373
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.
Malaria Chemoprevention in the Postdischarge Management of Severe Anemia
The New England journal of medicine. 2020;383(23):2242-2254
BACKGROUND Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period. METHODS We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether-lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin-piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice-Williams-Peterson total-time approach. RESULTS From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P<0.001). The lower incidence of readmission or death in the chemoprevention group than in the placebo group was restricted to the intervention period (week 3 through week 14) (hazard ratio, 0.30; 95% CI, 0.22 to 0.42) and was not sustained after that time (week 15 through week 26) (hazard ratio, 1.13; 95% CI, 0.87 to 1.47). No serious adverse events were attributed to dihydroartemisinin-piperaquine. CONCLUSIONS In areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo. (Funded by the Research Council of Norway and the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT02671175.).
[Effects of reinfusion of the remaining blood filtered by leukocyte depletion filter on postoperative cellar immune function after cardiopulmonary bypass]
Zhonghua wei zhong bing ji jiu yi xue. 2019;31(8):989-993
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.