Abstract

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. What is Known: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.

Abstract

OBJECTIVE We aimed at comparing the efficacy of intravenous and oral iron supplementations for the treatment of iron deficiency (ID) in patients with heart failure (HF). METHODS We searched the PubMed, Cochrane, and Embase databases from inception to January 15, 2022. We included randomized controlled trials enrolling patients with HF who were treated for ID with intravenous iron supplements, oral iron supplements, or placebo. The primary outcomes were all-cause death, cardiovascular mortality, and hospitalization for heart failure. The secondary outcomes were evaluated through the six-minute walking test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS The network meta-analysis included sixteen studies. Compared to placebo/control groups, intravenous iron supplements did not decrease all-cause death (0.69, 0.39-1.23) or cardiovascular mortality (0.89, 0.66-1.20). After 12 weeks, a reduced hospitalization for heart failure was associated with the administration of intravenous iron supplementations (0.58, 0.34-0.97). The most significant improvements regarding 6MWT (44.44, 6.10-82.79) and KCCQ (5.96, 3.19-8.73) were observed with intravenous iron supplements. Oral iron supplements reduced hospitalization for heart failure (0.36, 0.14-0.96) and all-cause death (0.34, 0.12-0.95), but did not influence the 6MWT (29.74, -47.36 to 106.83) and KCCQ (0.10, -10.95 to 11.15). CONCLUSIONS Administering intravenous iron supplements for ID in patients with HF improves their exercise capacity and quality of life. In order to reduce hospitalizations for heart failure, the supplementation should be administered for more than 12 weeks. Although oral iron supplements did not improve exercise capacity and quality of life, they could reduce all-cause death and hospitalizations for heart failure.

Abstract

OBJECTIVES This study aimed to investigate the effect of hemocoagulase combined with platelet-rich plasma (PRP) in total hip replacement (THR) on reducing bleeding and improving knee joint function in the patients with osteoarthritis. METHODS From February 2018 to February 2020, 80 osteoarthritis patients undergoing THR were included in the study, of which 40 cases were treated with PRP and hemocoagulase (test group) in the joint capsule in THR and the other 40 cases received saline and thrombin in the joint capsule after THR (control group). Postoperative drainage and corresponding functional exercise were performed for the two groups 12 hours after operation. The outcome measures including operation time, soft-tissue release, blood routine, drainage volume, perioperative blood loss, postoperative incision inflammation, deep vein thrombosis (DVT), and range of motion (ROM) of the joint were recorded. RESULTS The hemoglobin and hematocrit values of the test group on the second postoperative day were significantly higher than those of the control group (P < 0.05). The postoperative drainage volume and perioperative blood loss were significantly lower than those of the control group (P < 0.05). The test group was better than the control group in the ROM of the joint at 7 and 15 days after the operation (P < 0.05). A lower value of prothrombin time and activated partial thromboplastin time was revealed in the test group compared with the control group (P < 0.05). No significant difference in the operation time, intraoperative soft-tissue release, postoperative incision inflammation, incidence of DVT, incidence of deep infection, and ROM at day 90 after THR was found in the two groups (P > 0.05). CONCLUSIONS The application of hemocoagulase combined with PRP in THR can reduce perioperative blood loss, increase wound healing speed and quality, and improve coagulation and immune function. It is a safe and effective method for the patients with knee osteoarthritis who underwent THR.

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.

Abstract

BACKGROUND Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia. METHODS Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group (n = 56) and a twice or three times per week intravenous epoetin alfa group (n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis. CONCLUSION Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Abstract

BACKGROUND This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis. METHOD This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis. CONCLUSION The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Abstract

Introduction Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCT's) demonstrated faster time-to-response with adding caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. Methods In this systematic review and meta-analysis, we searched the literature for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk-of-bias using the Cochrane RoB-2 tool (RCT's) and Newcastle-Ottawa Scale (observational studies). The primary efficacy outcome was all-cause mortality, and the primary safety outcome was treatment-emergent bleeding. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time-to-response. Results We included two high-quality RCT's and three observational studies at high-risk-of-bias comprising 632 participants. Compared with SOC, caplacizumab was associated with a non-significant reduction in the RR (0.21 [CI 0.05-1.74]) of death in RCT's and observational studies (RR 0.62 [CI 0.07, 4.41]). Compared with SOC, caplacizumab was associated with an increased risk of bleeding in RCT's (RR 1.37 [CI 1.06, 1.77]). In observational studies, the risk of bleeding was not significantly increased (RR 7.10 [CI 0.90, 56.14]). Addition of caplacizumab was also associated with a significant reduction in refractory iTTP and exacerbation, increased risk of relapse, and shortened response time. Conclusion Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time-to-response, and improves exacerbation rates, at the expense of increased relapse and bleeding risk.

Abstract

Tourniquet use always carries potential risks, which can range from mild transient functional impairments of thigh pain, skin blisters to severe permanent dysfunction of limb paralysis, nerve injuries or compartment syndrome. The ideal method for minimizing intraoperative tourniquet pressure (TP) for reducing postoperative complications remains controversial. In this prospective, randomized and controlled study, we reinvestigated an estimation formula for TP based on thigh circumferences and systolic blood pressure (SBP) with two traditional methods for TP determination in total knee arthroplasty (TKA): SBP plus 100 mmHg and a fixed value of 300 mmHg. TP values and postoperative thigh pain scores were compared among three groups. The intraoperative TP value of the formula-calculated group was lower than that of the traditional groups (14.7 mmHg, P = 0.3475 and 94.7 mmHg, P < 0.0001, respectively), while no differences of hemostatic effect at the surgical fields and wound complications were detected among groups. The thigh pain scores at the tourniquet site decreased gradually over time and the estimation group had the lowest scores at each timepoint after surgery. Estimation method for TP was easy and rapid, without relying on specific equipment. It could provide a practical low TP and comparable hemostatic effect in TKA using an inflating tourniquet.

Abstract

This meta-analysis evaluated the efficacy and safety of infliximab as initial therapy for patients with Kawasaki disease (KD) and intravenous immunoglobulin (IVIG) resistant KD.Studies of infliximab in KD, published between January 2004 and December 2019, were curated from PubMed, MEDLINE, and Cochrane Library. Data were analyzed using STATA Version 12.0. Of the 8 studies considered, 4 evaluated the effect of infliximab combined with IVIG as primary therapy in KD, and the remaining investigated the effect of infliximab in IVIG resistant patients. Infliximab was more effective than the control group, with the total summary odds ratio (OR) of 0.34 (95% confidence interval (CI): 0.19-0.62). The treatment resistance of the infliximab group was lower than the IVIG group (0.36 [95% CI: 0.14-0.92]) when infliximab was combined with IVIG as the initial treatment. However, infliximab treatment for IVIG resistant KD was more effective than the IVIG group (0.28 [95% CI: 0.12-0.66]). There was no significant increase in the incidence of coronary artery lesions. The total summary OR for the incidence of coronary artery lesions and infliximab treatment was 0.88 (95% CI: 0.48-1.62). There was no statistically significant difference in adverse events (AEs) when compared between the groups (0.71 [95% CI: 0.44-1.16]).Infliximab combined with IVIG reduced treatment resistance in KD patients vs. conventional IVIG therapy. Infliximab improved clinical course in IVIG resistant KD patients. Infliximab treatment did not reduce the incidence of coronary artery lesions and did not show any significant increase in the incidence of AEs. PROSPERO REGISTRATION NUMBER CRD42020218554.

Abstract

STUDY DESIGN A prospective, randomized, double-blind, placebo-controlled study. OBJECTIVES There are few studies examining the balance between preventing venous thrombus embolism (VTE) and reducing blood loss in posterior/transforaminal lumbar interbody fusion (PLIF/TLIF) surgeries. This study aimed to evaluate the efficacy and safety of the combine application of TXA and rivaroxaban in patients undergoing PLIF/TLIF and explore relevant factors related to blood loss and VTE. METHODS Patients in group A which was the control group received 0.9% NaCl solution intravenously. Group B was treated by an intravenous injection of 2 g tranexamic acid (TXA) and the local use of 1 g intraoperatively. Group C was treated the same as group B intraoperatively, and they received 10 mg rivaroxaban qd treatment postoperatively. Eligible patients with an Autar score ≤ 10 were randomly assigned to group A or group B. Patients with an Autar score >10 were allocated into group C. RESULTS The intraoperative blood loss and postoperative drainage were lower in groups B and C than in group A (P < .001). The blood transfusion rate in group B was lower than that in group A (P < .001), while the incidence of VTE in group C was lower (P < .001). Four factors were found to be positively correlated with obvious total blood loss (P < .05). The data showed that 5 factors were correlated with the development of a thrombus (P < .1). CONCLUSIONS The combination of TXA and rivaroxaban in PLIF/TLIF patients is safe and effective in reducing D-dimer levels associated with VTE and reducing blood loss.