Abstract

BACKGROUND Over the past few years, many studies have been conducted to evaluate the effectiveness of platelet-rich plasma (PRP) in treating musculoskeletal conditions. However, there is controversy about its benefits for patients with Achilles tendinopathy. OBJECTIVE This study aimed to investigate whether platelet-rich plasma injections can improve outcomes in patients with Achilles tendinopathy. METHODS A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, China Biomedical CD-ROM, and Chinese Science and Technology Journal databases to identify randomised controlled clinical trials that compared the efficacy of PRP injection in patients with Achilles tendinopathy (AT) versus placebo, published between 1 January 1966 and 1 December 2022. Review Manager 5.4.1 software was used for the statistical analysis, and the Jadad score was used to assess the included literature. Only 8 of the 288 articles found met the inclusion criteria. RESULTS Our work suggests that: The PRP treatment group had a slightly higher VISA-A score than the placebo group at 6 weeks [MD = 1.92, 95% CI (-0.54, 4.38), I(2) = 34%], at 12 weeks [MD = 0.20, 95% CI (-2.65 3.05), I(2) = 60%], and 24 weeks [MD = 2.75, 95% CI (-2.76, 8.26), I(2) = 87%]). However, the difference was not statistically significant. The Achilles tendon thickness was higher at 12 weeks of treatment in the PRP treatment group compared to the control group [MD = 0.34, 95% CI (-0.04, 0.71), p = 0.08], but the difference was not statistically significant. The VAS-improvement results showed no significant difference at 6 and 24 weeks between the two groups, respectively (MD = 6.75, 95% CI = (-6.12, 19.62), I(2) = 69%, p = 0.30), and (MD = 10.46, 95% CI = (-2.44 to 23.37), I(2) = 69%, p = 0.11). However, at 12 weeks of treatment, the PRP injection group showed a substantial VAS improvement compared to the control group (MD = 11.30, 95% CI = (7.33 to 15.27), I(2) = 0%, p < 0.00001). The difference was statistically significant. The return to exercise rate results showed a higher return to exercise rate in the PRP treatment group than the placebo group [RR = 1.11, 95% CI (0.87, 1.42), p = 0.40]; the difference was not statistically significant. CONCLUSION There is no proof that PRP injections can enhance patient functional and clinical outcomes for Achilles tendinopathy. Augmenting the frequency of PRP injections may boost the outcomes, and additionally, more rigorous designs and standardised clinical randomised controlled trials are needed to produce more reliable and accurate results.

Abstract

BACKGROUND Spleen tyrosine kinase (Syk) inhibitor is a treatment option for primary immune thrombocytopenia. We aimed to evaluate the safety, tolerability, pharmacokinetics, preliminary activity, and recommended phase 2 dose of sovleplenib in patients with primary immune thrombocytopenia. METHODS This randomised, double-blind, placebo-controlled, phase 1b/2 study was conducted at nine hospitals in China. Eligible patients were aged 18-75 years, had an ECOG performance score of 0-1, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous first-line treatment or had poor response or postoperative relapse after a splenectomy. Dose-escalation (100 mg, 200 mg, or 300 mg given orally once a day) and dose-expansion phases (recommended phase 2 dose) each consisted of an 8-week, double-blind, placebo-controlled period in which patients were randomly assigned (3:1) to receive sovleplenib or placebo with an interactive web response system followed by a 16-week, open-label period with sovleplenib. Patients, investigators, and the sponsor were masked to treatment allocation during the first 8 weeks. The main efficacy endpoint was the proportion of patients whose platelet count reached 30 × 10(9) platelets per L or higher and was double of the baseline at two consecutive visits during 0-8 weeks without rescue therapy. Efficacy was evaluated by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT03951623. FINDINGS Between May 30, 2019, and April 22, 2021, 62 patients were assessed for eligibility and 45 (73%) were randomly assigned. Patients received at least one dose of the study drug during the 8-week double-blind period (placebo [n=11] and sovleplenib 100 mg [n=6], 200 mg [n=6], 300 mg [n=16], and 400 mg [n=6]; this group was added following the observation of no protocol-specified safety events at the previous doses). All participants were Asian; 18 (40%) of 45 were male and 27 (60%) were female. The median age was 40·0 years (IQR 33·0-50·0). Ten (29%) of 34 patients in sovleplenib groups versus five (45%) of 11 in the placebo group received concomitant anti-primary immune thrombocytopenia therapy. The recommended phase 2 dose was determined as 300 mg once a day. The proportion of patients who met the main efficacy endpoint were three (50%; 95% CI 12-88) in the 100 mg group, three (50%; 12-88) in the 200 mg group, ten (63%; 35-85) in the 300 mg group, and two (33%; 4-78) in the 400 mg group compared with one (9%; 0-41) in the placebo group. The overall response rate in the 300 mg group was 80% (16 of 20 who received continuous sovleplenib plus those who crossed over from placebo) and the durable response rate was 31% (11-59; five of 16) in the continuous sovleplenib 300 mg and 75% (19-99; three of four) crossed from placebo to sovleplenib during 0-24 weeks. During the 28-day safety evaluation period, two grade 2 or worse treatment-related treatment-emergent adverse events occurred in the sovleplenib groups (hypertriglyceridaemia and anaemia). During 0-8 weeks, the most frequent treatment-emergent adverse events were an increase in blood lactate dehydrogenase, haematuria, and urinary tract infection (seven [21%] of 34 in sovleplenib groups vs one [9%] of 11 in the placebo group); and occult blood-positive and hyperuricaemia (four [12%] vs three [27%] for each). No fatal treatment-emergent adverse events were recorded. INTERPRETATION Sovleplenib was well tolerated, and the recommended phase 2 dose showed a promising durable response in patients with primary immune thrombocytopenia, which provides evidence for future investigations. A phase 3 trial is ongoing (NCT05029635) to confirm the efficacy and safety of sovleplenib in patients with primary immune thrombocytopenia. FUNDING HUTCHMED.

Abstract

OBJECTIVE The development of red blood cell alloimmunization intensifies transfusion complication in thalassaemia patients. The purpose of this paper is to evaluate the existing evidence on the prevalence of erythrocyte alloimmunization in China by meta-analysis. We systematically searched cross-sectional studies regarding the alloimmunization of thalassaemia patients with regular blood transfusion in China from year 2000 to May 2021 in the Cochrane library, PubMed, EMBASE, Web of Science, and Chinese databases including CNKI, Wanfang Data, Vip and CBM. Data extraction and quality evaluation of the included studies were performed. Meta-analysis was performed using the DerSimonian and Laird random-effects models with inverse variance weighting. The presence of publication bias was tested by Egger's test, and the methodological quality of each included article was evaluated by the criteria specific to prevalence studies. RESULTS A total of 1874 patients and 263 alloantibodies from 11 studies were identified and included in the meta-analysis. The proportion of alloantibodies against antigens belonging to the Rh, MNSs and Kidd systems were as high as 70.3%, 17.9%, and 6.5%, respectively. Meta-analysis showed that the overall prevalence of alloimmunization among transfusion-dependent thalassaemia patients in China is 11.4% (95%CI: 7.2%∼16.3%). CONCLUSIONS The characteristics of red blood cell alloimmunization among thalassaemia patients with regular transfusion in China differ greatly from those in other countries. Therefore, transfusion strategies shall be actively adapted in line with thalassaemia patients in China to minimize the risk of alloimmunization.

Abstract

BACKGROUND This meta-analysis aimed to explore the impact of red blood cell (RBC) transfusion on mortality during extracorporeal membrane oxygenation (ECMO). Previous studies investigated the prognostic impact of RBC transfusion during ECMO on the risk of mortality, but no meta-analysis has been published before. METHODS The PubMed, Embase, and the Cochrane library were systematically searched for papers published up to 13 December 2021, using the MeSH terms "ECMO", "'Erythrocytes", and "Mortality" to identify meta-analyses. Total or daily RBC transfusion during ECMO and mortality were examined. RESULTS The random-effect model was used. Eight studies (794 patients, including 354 dead) were included. The total volume of RBC was associated with higher mortality standardized weighted difference (SWD = -0.62, 95% CI: -1.06,-0.18, p = .006; I2 = 79.7%, P(heterogeneity) = 0.001). The daily volume of RBC was associated with higher mortality (SWD = -0.77, 95% CI: -1.11,-0.42, p < .001; I2 = 65.7%, P(heterogeneity) = 0.020). The total volume of RBC was associated with mortality for venovenous (VV) (SWD = -0.72, 95% CI: -1.23, -0.20, p = .006) but not venoarterial ECMO (p = .126) or when reported together (p = .089). The daily volume of RBC was associated with mortality for VV (SWD = -0.72, 95% CI: -1.18, -0.26, p = 0.002; I2 = 0.0%, P(heterogeneity) = 0.642) and venoarterial (SWD = -0.95, 95% CI: -1.32, -0.57, p < .001) ECMO, but not when reported together (p = .067). The sensitivity analysis suggested the robustness of the results. CONCLUSION When considering the total and daily volumes of RBC transfusion during ECMO, the patients who survived received smaller total and daily volumes of RBC transfusion. This meta-analysis suggests that RBC transfusion might be associated with a higher risk of mortality during ECMO.

Abstract

OBJECTIVE The optimal red blood cell transfusion strategy for children remains unclear. We developed an individualized red blood cell transfusion strategy for children and tested the hypothesis that transfusion guided by this strategy could reduce blood exposure, without increasing perioperative complications in children. METHODS In this randomized controlled clinical trial, 99 children undergoing noncardiac surgeries who had blood loss of more than 20% total blood volume were randomly assigned to an individualized-strategy group using Pediatric Perioperative-Transfusion-Trigger Score or a control group. The amount of transfused red blood cell was counted, and patients were followed up for postoperative complications within 30 days. RESULTS Twenty-six children (53.1%) in the individualized-strategy group received transfusion perioperatively, as compared with 37 children (74%) in the control group (p < 0.05). During surgery, children in the individualized-strategy group were exposed to fewer transfusions than in the control group (0.87±1.03 vs 1.33±1.20 Red-Blood-Cell units per patient, p = 0.02). The incidence of severe complications in the individualized-strategy group had a lower trend compared to the control group (8.2% vs 18%, p = 0.160). No significant difference was found in the other outcomes. CONCLUSION This trial proved that red blood cell transfusion guided by the individualized strategy reduced perioperative blood exposure in children, without increasing the incidence of severe complications. This conclusion needs to be reaffirmed by larger-scale, multicenter clinical trials.

Abstract

OBJECTIVE COVID-19 is associated with an increased risk of venous thromboembolic events (VTE). Recent studies have characterized racial disparities in the incidence of VTE. The aim of our study was to present a systematic review and meta-analysis to assess the association between race and VTE in hospitalized COVID-19 patients. METHODS We performed a systematic literature review to evaluate the number of deep vein thrombosis (DVT) and pulmonary embolism (PE) events reported by racial groups in COVID-19 hospitalized patients. For qualitative analysis, independent reviewers extracted data from eligible studies, and we utilized the Newcastle-Ottawa Scale to assess the quality of design and content for accurate interpretation. For the quantitative analysis, we pooled the ORs with Der Simonian and Laird random effects models. RESULTS The qualitative analysis included 11 studies, and the meta-analysis had six of them. All studies were observational, retrospective cohort studies, except for one retrospective case-control study. Six studies were eligible for the meta-analysis due to high interstudy heterogeneity; thus, variable reports of racial groups reduced the cohort to Black/African American and White patients (n = 9723) in the analysis. The estimated proportion for DVT/PE for Black/African American and Whites was 0.07 (95% CI [0.00, 0.10]) and 0.04 (95% CI [0.00, 0.07]), respectively. The p value of 0.13 suggest non-significant difference in VTE rates between Black/African American and White patients. CONCLUSION In our study, the proportion of DVT/PE events between Black/African American and White COVID-19 patients were comparable. Future COVID-19 studies should include systematic racial group reporting to identify disparities in the setting of thromboembolic events.

Abstract

OBJECTIVE Although the application of venovenous extracorporeal membrane oxygenation (VV-ECMO) in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS) is accumulating, the feasibility and safety of this therapy remain controversial. We aimed to evaluate the effect of VV-ECMO in the treatment of these patients. METHODS A comprehensive literature search was performed using PubMed, Embase, the Cochrane Library, and International Clinical Trials Registry Platform databases through November 2021. According to the inclusion and exclusion criteria, the included studies were screened, and meta-analysis was performed by R software (version 4.0.2). RESULTS Forty-two studies including 2037 COVID-19 patients supported with VV-ECMO due to ARDS were identified. The pooled analysis revealed that 30-, 60-, and 90-day mortality among patients were respectively 46% (95% CI 37%-57%, I(2) = 66%), 46% (95% CI 30%-70%, I(2) = 93%), and 49% (95% CI 43%-58%, I(2) = 52%), and the pooled incidence rate of in-hospital mortality, major bleeding, hemorrhagic stroke, thrombosis, pulmonary embolism, deep venous thrombosis, and renal replacement therapy were respectively 35%, 39%, 11%, 40%, 15%, 21%, and 44%. CONCLUSION Although COVID-19 patients may have a higher risk of bleeding, hemorrhagic stroke, and acute kidney injury during ECMO therapy, the survival rate was more than half of the cases. Our data may support the application of VV-ECMO in COVID-19 patients.

Abstract

BACKGROUND Convalescent plasma treatment for severe and critically ill Corona Virus Disease 2019 (COVID-19) patients remains controversial. OBJECTIVE To evaluate the clinical improvement and mortality risk of convalescent plasma treatment in patients with severe and critically ill COVID-19 patients. METHODS A literature search was conducted in the electronic databases for the randomized controlled studies about convalescent plasma therapy in severe and critically ill COVID-19 patients. Two reviewers independently extracted relevant data. The primary outcomes were clinical improvement and mortality risk of severe and critically ill COVID-19 patients that were therapied by convalescent plasma. RESULTS A total of 14 randomized controlled trials with 4543 patients were included in this meta-analysis. Compared to control, no significant difference was observed for either clinical improvement (6 studies, RR 1.07, 95% CI 0.97 to 1.17, p = 0.16, moderate certainty) or mortality risk (14 studies, RR 0.94, 95% CI 0.85 to 1.03, p= 0.18, low certainty) in patients of convalescent plasma therapy group. CONCLUSION Convalescent plasma did not increase the clinical improvement or reduce the mortality risk in the severe and critically ill COVID-19 patients.

Abstract

OBJECTIVE This study compared the effectiveness and safety of carbetocin and oxytocin in preventing postpartum hemorrhage (PPH). METHODS A systematic literature search was performed on PubMed, Embase, and the Cochrane Library for relevant studies published up to February 2019. Next, two independent reviewers screened the studies according to the selection criteria as well as the strategies recommended by the Cochrane Collaboration. Data were then extracted and evaluated. All statistical analyses were performed using RevMan 5.1. RESULTS A total of 24 studies involving 37 383 patients were included for analysis. For cesarean section patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contraction (odds ratio [OR] = 0.48, 95% confidence interval [CI] [0.35, 0.65], p < 0.00001), PPH (OR = 0.70, 95% CI [0.51, 0.95], p = 0.02), blood loss (mean [MD] = -64.36, 95% CI [-107.78, -20.93], p = 0.004), and transfusion (OR = 0.59, 95% CI [0.42, 0.82], p = 0.002), and there was no significant difference in severe PPH (OR = 0.84, 95% CI [0.66, 1.090], p = 0.19). For vaginal delivery patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contractions (OR = 0.48, 95% CI [0.25, 0.93], p = 0.03), PPH (OR = 0.28, 95% CI [0.09, 0.91], p = 0.03), and blood loss (MD = -63.52, 95% CI [-113.43, -13.60], p = 0.01), and there were no significant differences in severe PPH (OR = 0.82, 95% CI [0.40, 1.69], p = 0.59) and transfusion (OR = 0.60, 95% CI [0.22, 1.61], p = 0.31). With regard to safety, for cesarean section patients, carbetocin was superior to oxytocin in reduction of the incidence of headache (OR = 0.72, [0.55, 0.95], p = 0.02), and there were no significant differences in nausea, vomiting, abdominal pain, flushing, tremors, itching, dizziness, and fever. For vaginal delivery patients, there were no significant differences in nausea, vomiting, headache, abdominal pain, flushing, tremors, itching, dizziness, and fever between the two drugs. CONCLUSION For patients undergoing cesarean section and vaginal delivery, carbetocin was superior to oxytocin in effectiveness and similar in safety. Therefore, carbetocin is expected to be an alternative uterine contraction agent for preventing PPH.

Abstract

BACKGROUND Hypertensive intracerebral hemorrhage (HICH) seriously endangers the quality of life of patients and can even lead to death. Craniotomy is a common treatment method for HICH. OBJECTIVE The aim of this study was to investigate the efficacy of two different sizes of craniotomy in patients with HICH, as well as to evaluate their effects on C-reactive protein (CRP) and blood lactate levels. MATERIALS AND METHODS A total of 72 patients with HICH in the basal ganglia were operated on in our hospital from February 2017 to March 2019 and randomly divided into two groups: the small bone window (SBW) group (n = 37) and the large bone flap group (n = 35). The curative effects of the two kinds of operations were evaluated by the length of operation, the days of hospitalization, the rate of hematoma clearance, the rate of rebleeding, and the incidence of complications. Additionally, the levels of CRP and lactate were compared between the two groups. RESULTS The results showed that the average intraoperative time, hospital stay, rebleeding rate, and postoperative complications of patients in the SBW group were less than those in the large bone flap group. Moreover, the number of patients in the SBW group with good postoperative recovery, including class V and class IV, was higher than that in the large bone flap group. Minimally invasive craniotomy with SBW reduced the lactic acid and CRP levels more quickly than the large bone flap group. CONCLUSIONS An SBW was superior to a large bone flap in terms of the operative effect and lactate and CRP levels. It is concluded that an SBW has significant advantages over a large bone flap.