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1.
Effects of hypoxia-inducible factor prolyl hydroxylase inhibitors versus erythropoiesis-stimulating agents on iron metabolism and inflammation in patients undergoing dialysis: A systematic review and meta-analysis
Zheng Q, Zhang P, Yang H, Geng Y, Tang J, Kang Y, Qi A, Li S
Heliyon. 2023;9(4):e15310
Abstract
AIMS: This study aimed to evaluate the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism and inflammation in dialysis-dependent chronic kidney disease (DD-CKD) patients. METHODS PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov websites were searched for randomized controlled trials (RCTs) investigating HIF-PHIs versus ESAs for DD-CKD patients. KEY FINDINGS Twenty studies with 14,737 participants were included in the meta-analysis, which demonstrated no significant difference in the effect of transferrin saturation and ferritin between HIF-PHIs and the ESAs group (MD, 0.65; 95%CI, -0.45 to 1.75; very low certainty; SMD, -0.03; 95% CI, -0.13 to 0.07; low certainty). However, HIF-PHIs significantly increased the iron (MD, 2.30; 95% CI, 1.40 to 3.20; low certainty), total iron-binding capacity (SMD, 0.82; 95% CI, 0.66 to 0.98; low certainty), and transferrin (SMD, 0.90; 95%CI, 0.74 to 1.05; moderate certainty) levels when compared with the ESAs group. In contrast, the hepcidin level and dosage of intravenous iron were significantly decreased in the HIF-PHIs group compared with the ESAs group (MD, -15.06, 95%CI, -21.96 to -8.16; low certainty; MD, -18.07; 95% CI, -30.05 to -6.09; low certainty). The maintenance dose requirements of roxadustat were independent of baseline CRP or hsCRP levels with respect to the effect on inflammation. SIGNIFICANCE HIF-PHIs promote iron utilization and reduce the use of intravenous iron therapy. Furthermore, HIF-PHIs, such as roxadustat, maintain the erythropoietic response independent of the inflammatory state. Thus, HIF-PHIs may be an alternative treatment strategy for anemia in DD-CKD patients, where ESA is hyporesponsive due to iron deficiency and inflammation.
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2.
The Effect of Oxytocin plus Carboprost Methylate in Preventing Postpartum Hemorrhage in High-Risk Pregnancy and Its Effect on Blood Pressure
Wei L, Yang H, Sun X
Evidence-based complementary and alternative medicine : eCAM. 2022;2022:9878482
Abstract
Objective. This study aimed to explore and analyze the effectiveness of oxytocin plus carboprost methylate in preventing postpartum hemorrhage in high-risk pregnancies and its effect on blood pressure. A total of 60 women with high-risk pregnancies who gave birth in our hospital from January 2020 to May 2021 were recruited and assigned via random number table method (1 : 1) to receive either oxytocin (control group) or oxytocin plus carboprost methylate (observation group). Outcome measures included hemorrhage and blood pressure. The bleeding volume of the women in the observation group (210.55 ± 45.98, 45.21 ± 9.27, and 73.74 ± 12.18) was significantly less than that in the control group during delivery and 2h and 24h after the delivery (276.91 ± 49.21, 72.98 ± 19.68, and 92.61 ± 15.67) (all P < 0.05). The observation group showed a significantly lower bleeding rate (6.67%) than the control group (16.67%) (P < 0.05). The two groups showed similar diastolic and systolic blood pressures (P > 0.05). Oxytocin plus carboprost methylate suppository effectively prevents postpartum hemorrhage in high-risk pregnancies, significantly reduces the amount of postpartum hemorrhage in high-risk pregnancies, and has little effect on the blood pressure of patients. Given its favorable treatment efficiency and high safety profile, this treatment protocol shows great potential for clinical application.
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A multicenter, prospective, randomized clinical study to evaluate the efficacy and safety of fibrin sealant as an adjunct to sutured dural repair
Yu R, Zhu W, Kocharian R, Ilie B, Wang Z, Kang D, Zhao G, Yang H, Shu K, Liu X, et al
Chinese medical journal. 2022;135(20):2506-2508
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4.
Impact of the Tranexamic Acid on Bleeding Amount of Surgical Patient With Degenerative Spinal Disease: A Randomized Blinded Study
Yan L, Yang H, Jiang H, Yu M, Tan J, Su T, Xu G
Frontiers in surgery. 2021;8:655692
Abstract
Objective: This study aims to explore the effectiveness and safety of tranexamic acid (TXA) in reducing the bleeding amount of surgical patients with degenerative spinal disease in the perioperative period. Methods: A total of 80 cases of patients, who underwent elective posterior lumbar interbody fusion surgeries under general anesthesia, were enrolled in this study. The age of these patients ranged within 41-69 years old, and the surgical vertebral body segments were ≥2. The ASA classification was Level I or Level II. These patients were divided into two groups using the random number table (n = 40): TXA group and control group (S group). In the TXA group, the skin was incised after the anesthesia induction, and 20 mg/kg of TXA was immediately injected into the vein. The injection continued at a rate of 10 mg·kg(-1)·h(-1) during the surgery, until the surgery was finished. In the S group, IV and pump injection with an equal amount of normal saline (NS) were performed. Then, the RBC, Hb, HCT, AST, ALT, BUN, Cr, PT, TT, APTT, FIB, and D-dimer were measured before the surgery and at 1 day after the surgery, and the SSFQ, intraoperative bleeding amount, homologous transfusion volume, urine volume, infusion quantity, surgical duration, drainage volume at 24 h after the surgery, total bleeding amount and adverse event occurrence at 1 week after the surgery were recorded. Results: The RBC, Hb and HCT at 1 day after the surgery were higher in TXA group than in the S group (average P < 0.05). Intraoperative bleeding, drainage volume at 24 h after surgery, and total blood loss were lower in the TXA group than in the S group (average P < 0.05). The SSFQ score and length of stay were lesser in the TXA group than in the S group (average P < 0.05). The differences in AST, ALT, BUN, Cr, PT, TT, APTT, FIB, and D-dimer at 1 day after the surgery for these two groups of patients had no statistical significance (average P > 0.05). Conclusion: TXA can reduce the bleeding amount of surgical patients with degenerative spinal disease in the perioperative period and decrease the length of stay, but does not increase the occurrence rate of adverse events, thereby promoting postoperative rehabilitation. Clinical Trial Registration: www.chictr.org.cn/index.aspx, identifier: ChiCTR2000033597.
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5.
The Role of Knee Position in Blood Loss and Enhancement of Recovery after Total Knee Arthroplasty
Cao L, Yang H, Sun K, Wang H, Fan H, Cheng W
J Knee Surg. 2020
Abstract
The study aimed to investigate the effects of postoperative position of knee on blood loss and functional recovery after total knee arthroplasty (TKA). We enrolled patients who underwent TKA from 2017 to 2019 in our department with osteoarthritis of the knee in this prospective and randomized study. The patients were randomly allocated to flexion or extension group. In the flexion group, the affected leg was elevated by 30 degrees at the hip and the knee was flexed by 30-degree, postoperatively, while in the extension group, the affected knee was fully extended postoperatively. Patients' data related to postoperative blood loss, Hospital for Special Surgery scores, pain intensity, usage of analgesic drugs, circumference of knee, and range of motion (ROM) of knee were recorded to assess the influence of postoperative leg position on clinical outcomes. Although the transfusion rate was similar between the two groups (p > 0.05), other parameters related to blood loss (including total blood loss, hidden blood loss, usage of analgesic drugs, and postoperative circumference of knee) were significantly lower in the flexion group than those in the extension group (p < 0.05). After 6 weeks and 6 months of rehabilitation, patients gained a similar ROM in the affected knee in both groups (p > 0.05). The length of hospital stay and medical expenses were similar in both groups. Incidence of wound infection and other complications was also similar in both groups (p > 0.05). Elevation of the hip by knee flexion of 30 degrees is an effective and simple method to reduce blood loss after TKA, and contributes to reduction of the dosage of analgesic drugs in the early postoperative period. The routine application of the present protocol also did not increase medical costs and length of hospital stay after TKA.
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6.
Comparison of oral versus intravenous tranexamic acid in total knee and hip arthroplasty: A GRADE analysis and meta-analysis
Sun C, Zhang X, Chen L, Deng J, Ma Q, Cai X, Yang H
Medicine. 2020;99(44):e22999
Abstract
BACKGROUND The efficacy and safety of oral tranexamic acid (TXA) remain controversial because of the small number of clinical studies. The aim of the present study was to compare the efficacy and safety of oral TXA with intravenous TXA in patients undergoing total hip arthroplasty and total knee arthroplasty in a systematic review and meta-analysis. METHODS We conducted a meta-analysis to identify randomized controlled trials (RCTs) involving oral and intravenous TXA in total hip arthroplasty and total knee arthroplasty up to December 2019 by searching databases including PubMed, Web of Science, Embase, the Cochrane Controlled Trials Register, the Cochrane Library China Biology Medicine, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang. The mean difference or standard mean difference was used to assess continuous outcomes such as hemoglobin (Hb) drop, total blood loss, drain blood loss, and length of hospital stay, with a 95% confidence interval. Relative risks with a 95% confidence interval were used to assess dichotomous outcomes such as transfusion rate and the incidence of deep venous thrombosis and calf muscular vein thrombosis. Review Manager was used for the meta-analysis. RESULTS Ten RCTs containing 1080 participants met the inclusion criteria. We found no significant differences in terms of the average Hb drop (P = .60), total blood loss (P = .60), transfusion rate (P = .99), drain blood loss (P = .91), length of hospital stay (P = .95), and the incidence of deep venous thrombosis (P = .55) and calf muscular vein thrombosis (P = .19) between oral and IV TXA. CONCLUSIONS Compared with the IV TXA, oral TXA has similar effects on reducing the Hb drop, total blood loss, transfusion rate, drain blood loss, and length of hospital stay without increasing the risk of calf muscular vein thrombosis and deep venous thrombosis. Furthermore, oral TXA is easy to access and administer, which decreases the workload of nurses and even delivers cost-saving benefits to the health care system. We thus conclude that oral TXA may be an optimal approach in total joint arthroplasty. However, more high-quality and multicenter RCTs are still needed to confirm our conclusions. REGISTRATION The current meta-analysis was registered on PROSPERO (International Prospective Register of Systematic Reviews), and the registration number was CRD42018111291.
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Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis
Zheng Q, Wang Y, Yang H, Sun L, Fu X, Wei R, Liu YN, Liu WJ
Frontiers in pharmacology. 2020;11:573645
Abstract
Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group. Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.
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8.
Efficacy and safety of HIF prolyl-hydroxylase inhibitor vs epoetin and darbepoetin for anemia in chronic kidney disease patients not undergoing dialysis: a network meta-analysis
Zheng Q, Yang H, Sun L, Wei R, Fu X, Wang Y, Huang Y, Liu YN, Liu WJ
Pharmacol Res. 2020;:105020
Abstract
Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines being developed for the treatment of anemia in chronic kidney disease (CKD) patients. This study aimed to compare the efficacy and safety of HIF-PHI vs epoetin and darbepoetin in CKD patients with anemia not undergoing dialysis. The PubMed, Embase, Cochrane Library, Web of Science, and http://clinicaltrials.gov/ clinicaltrials.gov databases were searched from inception to October 2019 for randomized controlled trials investigating different agents (six HIF-PHIs, epoetin, darbepoetin, and placebo) for treating CKD patients with anemia that did not undergo dialysis. The outcomes included a change in hemoglobin (Hb) levels and all-cause mortality. A total of 19 studies were included. Compared with the placebo, except for vadadustat (mean differences: 1.12, 95% confidence interval [CI]: 0.11-2.35), the other drugs significantly increased Hb levels, with mean differences of 2.46 (95% CI: 0.933.99) for desidustat, 1.81 (0.872.75) for enarodustat, 1.68 (0.642.72) for molidustat, 1.66 (0.892.44) for epoetin, 1.63 (0.692.56) for darbepoetin, 1.61 (0.992.22) for roxadustat, and 1.55 (0.742.36) for daprodustat. No differences were found in the Hb level elevations among these eight drugs. Compared with the placebo, there also was no significant association between the drugs and all-cause mortality (molidustat of RR, 0.39 [95% CI, 0.062.59]; roxadustat, 0.40 (0.062.84); enarodustat, 0.33 (0.0116.25); desidustat, 0.34 (0.0117.00); epoetin, 0.50 (0.181.42); daprodustat, 0.54 (0.093.31); darbepoetin, 1.03 (0.651.65); and vadadustat, 1.43 (0.1513.27)). No differences were observed in the all-cause mortality among the drugs. In conclusion, these HIF-PHIs are effective and relatively tolerant for treating anemia patients with CKD not undergoing dialysis. Further research should consider the limitations of our study to evaluate the value of these HIF-PHIs in clinical settings.
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9.
Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update
Bohlius J, Bohlke K, Castelli R, Djulbegovic B, Lustberg MB, Martino M, Mountzios G, Peswani N, Porter L, Tanaka TN, et al
Blood advances. 2019;3(8):1197-1210
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Editor's Choice
Abstract
PURPOSE To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited. RECOMMENDATIONS ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to < 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines.
PICO Summary
Population
Patients with cancer or chronic kidney disease (17 studies).
Intervention
Erythropoiesis-stimulating agents (ESAs) including biosimilars.
Comparison
Addition of iron to an ESA, placebo or best standard therapy.
Outcome
A growing body of evidence suggested that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of red blood cell transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remained limited.
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Does tranexamic acid improve bleeding, transfusion, and hemoglobin level in patients undergoing multi-level spine surgery? A systematic review and meta-analysis
Zhang Y, Liu H, He F, Chen A, Yang H, Pi B
World neurosurgery. 2019
Abstract
OBJECTIVE To investigate the influence of TXA on blood loss and blood transfusion in multiple-level spine surgery and evaluate whether hemoglobin and platelet levels are altered as a result. METHOD This meta-analysis conducted an exhaustive search of literature from Pubmed, Embase, Cochrane Library, Web of Science, and CNKI databases. Stata 11.0 was used to analyze the pooled data. Mean differences (MD) of blood loss, transfusion volume, hemoglobin and platelet levels, as well as odds ratio (OR) of proportion of transfusion were extracted and compared between the TXA group and controls. Publication bias and sensitive analysis were also performed in this study. RESULT A total of 11 studies (6 RCTs and 5 retrospective studies) were enrolled in this meta-analysis according to the inclusion criteria. The data showed that administration of TXA can decrease intraoperative blood loss and perioperative blood transfusion compared to controls (SMD = -0.50; 95 % CI: -0.84, -0.16; I(2) = 52.9 %; p = 0.004) (OR = 0.48; 95 % CI: 0.29, 0.78; I(2) = 0 %; p = 0.003). Moreover, TXA can maintain a superior hemoglobin level after surgery than control group (SMD = -0.27; 95 % CI: 0.07, 0.47; I(2) = 0 %; p = 0.009). The above results were also observed and verified after accounting for publication bias and sensitive analysis. CONCLUSION The application of TXA can effectively reduce intraoperative blood loss and perioperative blood transfusion in patients undergoing multiple-level spine surgery, as well as restore hemoglobin levels after surgery.