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1.
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
Abstract
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.
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2.
Reduction of Heavy Menstrual Bleeding in Women Not Designated as Responders to Elagolix Plus Add Back Therapy for Uterine Fibroids
Stewart EA, Archer DF, Owens CD, Barnhart KT, Bradley LD, Feinberg EC, Gillispie-Bell V, Imudia AN, Liu R, Kim JH, et al
Journal of women's health (2002). 2021
Abstract
Objective: To assess outcomes of women with uterine fibroids (UFs) and heavy menstrual bleeding (HMB) treated with 300 mg elagolix twice daily plus add-back therapy (E2 1 mg/NETA 0.5 mg once daily) or placebo who were not considered responders in pooled analysis of two phase 3, 6-month randomized clinical trials (Elaris UF-1 and UF-2). Methods: Responders were defined as women who met both primary end point bleeding criteria (<80 mL menstrual blood loss [MBL] during the final month and ≥50% reduction in MBL from baseline to the final month) and either completed the study or discontinued due to predefined reasons. Thus, women termed nonresponders who were analyzed in this study who met neither or one bleeding end point or met both criteria but prematurely discontinued treatment because of adverse events, perceived lack of efficacy, or required surgical or interventional treatment for UFs were analyzed in this study. This post hoc analysis assessed mean changes from baseline in MBL, as well as adverse events. Results: Among 367 women receiving elagolix with add-back with observed data, 89 (24%) were not considered responders. Within this subset, 17 (19%) women met both bleeding criteria but prematurely discontinued treatment for the reasons mentioned above, while 23 (26%) met one bleeding criterion and 49 (55%) met neither bleeding criteria, regardless of discontinuation status. Among all nonresponders, a numerical trend toward greater mean reductions in MBL was observed in those receiving elagolix with add-back, compared with placebo group nonresponders. No differences in adverse events were observed between responders and nonresponders. Conclusion: Forty of 89 (45%) women with HMB and UFs who were classified as nonresponders in the UF-1 or UF-2 trials may have had a clinically meaningful response to elagolix with add-back therapy because they met at least one of the objective bleeding criteria. Clinical Trial Registration: Clinicaltrials.gov, NCT02654054 and NCT02691494. (NEJM 2020; 382:328-340) DOI: 10.1056/NEJMoa1904351.
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3.
Clinical Efficacy of Tonic Traditional Chinese Medicine Injection on Acute Cerebral Infarction: A Bayesian Network Meta-Analysis
Zhou D, Xie L, Wang, Y, Wu S, Liu F, Zhang S, Liu R, Zhu L
Evidence-based complementary and alternative medicine : eCAM. 2020;2020:8318792
Abstract
Western medicine (WM) has certain limitations in terms of treating acute cerebral infarction (ACI), while tonic traditional Chinese medicine injections (TCMIs) have been shown to have obvious clinical effects as an adjunct to WM for ACI. However, most randomized controlled trials (RCTs) to date have not performed direct comparisons of efficacy among tonic TCMIs. This study designed a Bayesian network meta-analysis (NMA) to explore the therapeutic effect of tonic TCMIs on ACI. A comprehensive search of RCTs of TCMIs combined with WM for ACI was conducted using electronic databases for studies dated from the start date of each database until February 2020. Stata 13.0 and ADDIS 1.16.7 software were used to plot and analyze the data. Sixty-six RCTs with a total of 5,989 patients involving 7 kinds of tonic TCMIs were included. Among TCMIs, Shenfu injection (SFI) + WM ranked first in terms of improving clinical efficacy and the activities of daily living (ADLs) rating and reducing interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels. While Ciwujia injection (CI) + WM was the best choice for reducing neurological impairment and the high-cut viscosity of whole blood (HCV). Shenmai injection (SI) + WM had the greatest effects in terms of decreasing the levels of low-cut viscosity of whole blood (LCV), fibrinogen (FIB), and plasma viscosity (PV). Based on the cluster analysis of the clinical efficacy and the neurological impairment, CI + WM and Shenqifuzheng (SQI) + WM were the best options for treating ACI. With respect to adverse drug reactions (ADRs), 35 RCTs did not monitor ADRs during treatment. In conclusion, tonic TCMIs could assist WM in benefiting patients with ACI. However, due to the limitations of the current study, strict monitoring of ADRs and data from high-quality RCTs will be required in future to verify the advantage of TCMIs.
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4.
Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids
Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Feinberg EC, Hurtado SM, Kim J, et al
The New England journal of medicine. 2020;382(4):328-340
Abstract
BACKGROUND Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. METHODS We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. RESULTS A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy. CONCLUSIONS Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).
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5.
Intra-articular vs. intravenous administration: a meta-analysis of tranexamic acid in primary total knee arthroplasty
Li J, Liu R, Rai S, Ze R, Tang X, Hong P
Journal of orthopaedic surgery and research. 2020;15(1):581
Abstract
BACKGROUND The optimal dosage and administration approach of tranexamic acid (TXA) in primary total knee arthroplasty (TKA) remains controversial. In light of recently published 14 randomized controlled trials (RCTs), the study aims to incorporate the newly found evidence and compare the efficacy and safety of intra-articular (IA) vs. intravenous (IV) application of TXA in primary TKA. METHODS PubMed, Embase, Web of Science, and Cochrane Library were searched for RCTs comparing IA with IV TXA for primary TKA. Primary outcomes included total blood loss (TBL) and drain output. Secondary outcomes included hidden blood loss (HBL), hemoglobin (Hb) fall, blood transfusion rate, perioperative complications, length of hospital stay, and tourniquet time. RESULT In all, 34 RCTs involving 3867 patients were included in our meta-analysis. Significant advantages of IA were shown on TBL (MD = 33.38, 95% CI = 19.24 to 47.51, P < 0.001), drain output (MD = 28.44, 95% CI = 2.61 to 54.27, P = 0.03), and postoperative day (POD) 3+ Hb fall (MD = 0.24, 95% CI = 0.09 to 0.39, P = 0.001) compared with IV. There existed no significant difference on HBL, POD1 and POD2 Hb fall, blood transfusion rate, perioperative complications, length of hospital stay, and tourniquet time between IA and IV. CONCLUSION Intra-articular administration of TXA is superior to intravenous in primary TKA patients regarding the performance on TBL, drain output, and POD3+ Hb fall, without increased risk of perioperative complications. Therefore, intra-articular administration is the recommended approach in clinical practice for primary TKA.
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6.
Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas
Simon JA, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Dayspring T, Feinberg EC, Gillispie V, Hurtado S, et al
Obstet Gynecol. 2020;135(6):1313-1326
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Abstract
OBJECTIVE To investigate the safety and efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy for up to 12 months in women with heavy menstrual bleeding associated with uterine leiomyomas. METHODS Elaris UF-EXTEND was a phase 3 extension study that evaluated an additional 6 months (up to 12 months total) of elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg and norethindrone acetate 0.5 mg once daily) in women who completed an initial 6 months of the same treatment in one of two preceding phase 3 studies. The primary endpoint was the percentage of women with both less than 80 mL menstrual blood loss during final month and a 50% or greater reduction in menstrual blood loss from baseline to final month. Safety evaluations included adverse events and bone mineral density changes. The planned sample size of UF-EXTEND was based on estimated rollover and discontinuation rates in the two preceding studies. RESULTS From September 2016 to March 2019, 433 women were enrolled in UF-EXTEND. Of these women, 218 received up to 12 months of elagolix with add-back therapy; the mean+/-SD age of this group was 42.4+/-5.4 years and 67.3% were black. The percentage of women who met the primary endpoint in this elagolix with add-back group was 87.9% (95% CI [83.4-92.3]). The most frequently reported adverse events with up to 12 months of elagolix plus add-back therapy were hot flush (6.9%), night sweats (3.2%), headache (5.5%), and nausea (4.1%). Mean percent decreases in bone mineral density from baseline to extension month 6 were significantly less with elagolix plus add-back therapy than with elagolix alone {between-group difference in lumbar spine: -3.3 (95% CI [-4.1 to -2.5])}. CONCLUSION Up to 12 months of elagolix with add-back therapy provided sustained reduction in menstrual blood loss in women with uterine leiomyomas, with the addition of add-back therapy attenuating the hypoestrogenic effects of elagolix alone. No new or unexpected safety concerns were associated with an additional 6 months of elagolix with addback therapy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT02925494. FUNDING SOURCE AbbVie Inc funded this study.
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Partial splenic embolization has beneficial effects for the management of gastroesophageal variceal hemorrhage
Wang P, Liu R, Tong L, Zhang Y, Yue T, Qiao H, Zhang F, Sun X
Saudi Journal of Gastroenterology : Official Journal of the Saudi Gastroenterology Association. 2016;22((6)):399-406.
Abstract
BACKGROUND/AIMS: Partial splenic embolization (PSE) is used in the management of gastroesophageal variceal hemorrhage (GEVH). However, it is uncertain whether it has beneficial effects for GEVH patients in preventing variceal recurrence and variceal hemorrhage, as well as promoting overall survival (OS), when it is combined with conventional therapies. MATERIALS AND METHODS The databases including PubMed, EMBASE, Web of Science, Google scholar, and Cochrane Central Register of Controlled Trials were searched up to 11th of November, 2015. Meta-analyses were performed by using Review Manager 5.3 software for analyzing the risk of bias, Newcastle-Ottawa Scale for assessing the bias of cohort studies, and GRADEprofiler software for assessing outcomes obtained from the meta-analyses. RESULTS A total of 1505 articles were reviewed, and 1 randomized controlled trial and 5 cohort studies with 244 participants were eligible for inclusion. The pooled hazard ratio (HR) of variceal recurrence is 0.50 (95% confidence interval (CI) 0.37, 0.68; P< 0.00001; I2 = 0%). The pooled HR of variceal hemorrhage is 0.24 (95% CI 0.15, 0.39; P< 0.00001; I2 = 0%). The pooled HR of OS is 0.50 (95% CI 0.33, 0.67; P< 0.00001; I2 = 0%). Meta-analyses demonstrated statistically significant superiority of combinational therapies over conventional therapies in preventing variceal recurrence and variceal hemorrhage and prolonging OS. The complications related to PSE were mild or moderate and nonfatal. CONCLUSIONS The results indicate that PSE has beneficial effects for GEVH patients, however, future investigation with a larger number of subjects in clinical trials is warranted.
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Cell salvage in emergency trauma surgery
Li J, Sun SL, Tian JH, Yang K, Liu R, Li J
Cochrane Database of Systematic Reviews. 2015;((1):):CD007379.
Abstract
BACKGROUND Trauma is the leading cause of death in people under the age of 45 years. Over the past 20 years, intraoperative autologous transfusions (obtained by cell salvage, also known as intraoperative blood salvage (IBS)) have been used as an alternative to blood products from other individuals during surgery because of the risk of transfusion-related infections such as hepatitis and human immunodeficiency virus (HIV). In this review, we sought to assess the effects and cost of cell salvage in individuals undergoing abdominal or thoracic surgery. OBJECTIVES To compare the effect and cost of cell salvage with those of standard care in individuals undergoing abdominal or thoracic trauma surgery. SEARCH METHODS We ran the search on 25 November 2014. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid OLDMEDLINE, EMBASE Classic + EMBASE (OvidSP), PubMed, and ISI Web of Science (SCI-Expanded & CPSI-SSH). We also screened reference lists and contacted principal investigators. SELECTION CRITERIA Randomised controlled trials comparing cell salvage with no cell salvage (standard care) in individuals undergoing abdominal or thoracic trauma surgery. DATA COLLECTION AND ANALYSIS Two authors independently extracted data from the trial reports. We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS Only one small study (n = 44) fulfilled the inclusion criteria. Results suggested that cell salvage did not affect mortality overall (death rates were 67% (14/21 participants) in the cell salvage group and 65% (15/23) in the control group) (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.31 to 3.72). For individuals with abdominal injury, mortality was also similar in both groups (OR 0.48, 95% CI 0.11 to 2.10).Less donor blood was needed for transfusion within the first 24 hours postinjury in the cell salvage group compared with the control group (mean difference (MD) -4.70 units, 95% CI -8.09 to -1.31). Adverse events, notably postoperative sepsis, did not differ between groups (OR 0.54, 95% CI 0.11 to 2.55). Cost did not notably differ between groups (MD -177.81, 95% CI -452.85 to 97.23, measured in GBP in 2002). AUTHORS' CONCLUSIONS Evidence for the use of cell salvage in individuals undergoing abdominal or thoracic trauma surgery remains equivocal. Large, multicentre, methodologically rigorous trials are needed to assess the relative efficacy, safety and cost-effectiveness of cell salvage in different surgical procedures in the emergency context.
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Retrograde autologous priming of the cardiopulmonary bypass circuit reduces blood transfusion in small adults: a prospective, randomized trial
Hou X, Yang F, Liu R, Yang J, Zhao Y, Wan C, Ni H, Gong Q, Dong P
European Journal of Anaesthesiology. 2009;26((12):):1061-6.
Abstract
BACKGROUND AND OBJECTIVE Extreme haemodilution occurring with cardiopulmonary bypass imposes a primary risk factor for blood transfusion in small adult cardiac surgical patients. Priming of the cardiopulmonary bypass circuit with patients' own blood [retrograde autologous priming (RAP)] is a technique used to limit haemodilution and reduce transfusion requirements. We designed this study to evaluate the effects of RAP on reducing perioperative blood transfusion in small adults. METHODS One hundred and twenty patients with a body surface area of less than 1. 5 m undergoing first-time, nonemergency cardiac surgery were randomized to either the standard priming group or the RAP group. All patients followed strict transfusion criteria. Homologous transfusion, haematocrit, plasma colloid osmotic pressure and postoperative clinical outcomes were evaluated perioperatively. RESULTS Patient characteristics and operative parameters were equal for patients in both groups. With autologous priming, a mean volume of 614. 8 +/- 138. 8 ml of priming solution was replaced with autologous blood. This allowed a significantly higher haematocrit value during cardiopulmonary bypass (P < 0. 05). Red blood cell transfusion was necessary in 83. 3% of patients of the standard priming group on pump, whereas only 26. 7% of patients of the RAP group required transfusion (P < 0. 01). The overall transfusion rate of the RAP group was significantly less than that in the standard priming group during the hospitalization (90. 0 vs. 50. 0%, P < 0. 01). Amongst patients who received transfusion on pump, the number of homologous units of packed red blood cells was less in the RAP group than that in the standard priming group intraoperatively and perioperatively (0. 94 +/- 0. 32 vs. 1. 48 +/- 0. 68 units, P = 0. 03; 1. 24 +/- 0. 54 vs. 1. 69 +/- 0. 69 units, P = 0. 15). Ten minutes after aortic cross-clamp, colloid osmotic pressure was reduced by 39. 7 +/- 2. 8% in the standard priming group and by 28. 6 +/- 3. 2% in the RAP group (P < 0. 05). Clinical outcomes were similar with respect to pulmonary, renal and hepatic function, length of ICU stay and hospital stay. CONCLUSION RAP resulted in a significant decrease in intraoperative haemodilution and conserved the use of blood. This technique should be considered for patients with a small body surface area (<1. 5 m) undergoing open heart surgery.