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Therapeutic plasma exchange-free treatment for first-episode TTP: A systematic review
Wang J, Cheng F, Niu Y, Yan L, Li J, Tan B, Qin L
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103661
Abstract
OBJECTIVE Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), and therapeutic plasma exchange (TPE) is currently the standard treatment. However, TPE sometimes cannot be implemented. The aim of this study was to systematically review patients with a first TTP episode who were treated without TPE. METHOD The PubMed, Embase, Web of Science and Cochrane Library databases were searched by two investigators independently to collect case reports and clinical studies on TTP patients treated without TPE. After removing duplicate records and records that did not meet the inclusion criteria, the patients' data of eligible studies, including the basic characteristics, treatment regimens, and outcomes were extracted for further analysis. RESULTS A total of 5338 potentially relevant original studies were identified, from which 21 studies, including 14 cases, 3 case series and 4 retrospective studies, met eligibility requirements and were included. Treatment regimens in the absence of TPE were found to vary based on individual information. Most patients recovered, with normal platelet counts and ADAMT13 activity at discharge. In the meta-analysis of retrospective studies, the TPE-free group had no higher mortality than the TPE-treated group. CONCLUSION Our study shows that TPE-free treatment may not increase the mortality of TTP patients, which provides a new treatment concept for patients with first episodes of TTP. However, the current evidence is not high due to the lack of randomized controlled trials, so more well-designed prospective clinical trials are warranted to investigate the safety and efficacy of TPE-free treatment regimens in TTP patients.
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Sovleplenib (HMPL-523), a novel Syk inhibitor, for patients with primary immune thrombocytopenia in China: a randomised, double-blind, placebo-controlled, phase 1b/2 study
Liu X, Zhou H, Hu Y, Yin J, Li J, Chen W, Huang R, Gong Y, Luo C, Mei H, et al
The Lancet. Haematology. 2023
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.
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Prognostic of red blood cell transfusion during extracorporeal membrane oxygenation therapy on mortality: A meta-analysis
Li Y, Wang J, Li C, Wang L, Chen Y
Perfusion. 2023;:2676591231157234
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.
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Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial
Barrett CD, Moore HB, Moore EE, Wang J, Hajizadeh N, Biffl WL, Lottenberg L, Patel PR, Truitt MS, McIntyre RC Jr, et al
Chest. 2022;161(3):710-727
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Abstract
BACKGROUND Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao(2) to Fio(2) ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao(2) to Fio(2) ratio improvement of > 50% or Pao(2) to Fio(2) ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao(2) to Fio(2) ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao(2) to Fio(2) ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS gov.
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Efficacy and safety of vadadustat compared to darbepoetin alfa on anemia in patients with chronic kidney disease: a meta-analysis
Huang Q, Liao Z, Liu X, Xia Y, Wang J
International urology and nephrology. 2022
Abstract
OBJECTIVE As a novel oral agent in treating anemia of chronic kidney disease (CKD), several clinical trials of vadadustat have been conducted to compare with darbepoetin alfa. This study systematically reviews and investigates the efficacy and safety of vadadustat in the anemia treatment with different duration in both nondialysis-dependent CKD (NDD-CKD) and dialysis-dependent CKD (DD-CKD). METHODS Several main databases were searched for randomized controlled trials (RCTs) reporting vadadustat vs darbepoetin alfa for anemia patients with CKD. The outcome indicators were focused on hemoglobin (Hb), the percentage of patients within the target Hb, the need for RBC (Red Blood Cell) transfusions, and serious adverse events (SAEs). RESULTS Four eligible studies with 8,026 participants were included. The changes of Hb levels from the baseline in the darbepoetin alfa group were significantly higher than that in the vadadustat group with DD-CKD (mean difference (MD) - 0.19, [95% confidence interval (CI), - 0.21 to - 0.17], p < 0.0001). In NDD-CKD patients, the changes of Hb levels in the two groups are not significantly different (MD = - 0.06, [95% CI, - 0.18 to 0.05], p = 0.006), especially, during the treatment duration of 20-36 weeks (MD = 0.02, [95% CI, - 0.04 to 0.08], p = 0.51). The percentage of patients within the target Hb was significantly lower in the vadadustat group than that in the darbepoetin alfa group in DD-CKD patients (MD = 0.9, [95% CI, 0.86 to 0.94], p < 0.00001), while in NDD-CKD patients, there was no significant difference (MD = 1.05, [95% CI, 0.99 to 1.12], p < 0.00001). In terms of safety, the two agents had no significant difference in the incidence of RBC transfusions and SAEs (RR = 1.26 [95% CI, 0.99 to 1.61], p = 0.52; RR = 0.97, [95% CI, 0.94 to 1.01], p = 0.19; respectively). CONCLUSION Compared to darbepoetin alfa, vadadustat had the same effect in raising the hemoglobin level in NDD-CKD patients in the short term. Vadadustat may become an effective and safe alternative for the treatment of patients with anemia and CKD, especially in NDD-CKD patients. As the application of vadadustat is still under exploration, future research should compensate for the limitations of our study to estimate the vadadustat's value.
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The safty profile of blood salvage applied for collected blood with amniotic fluid during cesarean section
Rong X, Guo X, Zeng H, Wang J, Li M, Wang Y
BMC pregnancy and childbirth. 2022;22(1):160
Abstract
BACKGROUND The guidelines of National Health Service(NHS, the United Kingdom) recommended for use in obstetrics at increased risk of bleeding, requiring two suction devices to reduce amniotic fluid contamination, however, when comes to massive hemorrhage, it is may difficult to operate because the complex operation may delay time. The aim of the study was to detect the effect of amniotic fluid recovery on intraoperative cell salvage in obstetrics and provide evidence for clinical applications. METHOD Thirty-four patients undergoing elective cesarean section were randomly divided into two groups. In group 1, the cumulative blood from the operation field, including the amniotic fluid, was collected using a single suction device for processing. In group 2, after suctioning away the amniotic fluid using another suction device for the cumulative blood from the operation field. From each group, four samples were taken, including maternal venous blood (sample I), blood before washing (sample II), blood after washing (sample III) and blood after filtration with a leukocyte filter (sample IV), to detect serum potassium (K +), hemoglobin (Hb), white blood cell (WBC), fetal hemoglobin (HbF), alpha fetoprotein (AFP) and squamous cell (SC) levels. RESULTS The AFP, K + and WBC levels of sample III and sample IV were significantly lower than sample I in group 1 and group 2 (P < 0.05). Significantly more SCs were found in sample III than in sample I in group 1 and group 2 (P < 0.05), but SCs of sample IV had no statistical difference compared to sample I in group 1 and group 2 (P > 0.05). There was no significant difference in the K + , Hb, WBC, AFP and SC levels of sample IV between group 1 and group 2 (P > 0.05). The HbF levels of sample III and sample IV were significantly higher in group 1 than in group 2 (P < 0.05). CONCLUSION There is little or no possibility for AF contamination to enter the re-infusion system when used in conjunction with a leucodepletion filter. For maternal with Rh-negative blood, we recommend two suction devices to reduce HbF pollution. TRIAL REGISTRATION ChiCTR1800015684 , 2018.4.15.
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Effect of prophylactic central neck dissection following total thyroidectomy on surgical site wound infection, hematoma, and haemorrhage in subjects with clinically node-negative papillary thyroid carcinoma: A meta-analysis
Jin L, Liu L, Wang J, Zhang L
International wound journal. 2022
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Abstract
We performed a meta-analysis to evaluate the effect of prophylactic central neck dissection following total thyroidectomy on surgical site wound infection, hematoma, and haemorrhage in subjects with clinically node-negative papillary thyroid carcinoma. A systematic literature search up to April 2022 was performed and 3517 subjects with clinically node-negative papillary thyroid carcinoma at the baseline of the studies; 1503 of them were treated with prophylactic central neck dissection following total thyroidectomy, and 2014 were using total thyroidectomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of prophylactic central neck dissection following total thyroidectomy on surgical site wound infection, hematoma, and haemorrhage in subjects with clinically node-negative papillary thyroid carcinoma using the dichotomous method with a random or fixed-effect model. The prophylactic central neck dissection following total thyroidectomy subjects had a significantly lower surgical site wound infection (OR, 0.40; 95% CI, 0.20-0.78, P = .007) in subjects with clinically node-negative papillary thyroid carcinoma compared with total thyroidectomy. However, prophylactic central neck dissection following total thyroidectomy did not show any significant difference in hematoma (OR, 0.08; 95% CI, 0.43-2.71, P = .87), and haemorrhage (OR, 0.72; 95% CI, 0.26-1.97, P = .52) compared with total thyroidectomy in subjects with clinically node-negative papillary thyroid carcinoma. The prophylactic central neck dissection following total thyroidectomy subjects had a significantly higher surgical site wound infection, and no significant difference in hematoma, and haemorrhage compared with total thyroidectomy in subjects with clinically node-negative papillary thyroid carcinoma. The analysis of outcomes should be with caution because of the low number of studies in certain comparisons.
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Prevention of delayed post-polypectomy bleeding by prophylactic clipping after endoscopic colorectal polypectomy: a meta-analysis
Yu Z, Albéniz E, Hu J, Li P, Li Q, Hu Y, Chen J, Wang J
International journal of colorectal disease. 2022
Abstract
PURPOSE This meta-analysis aims to investigate the role of prophylactic clipping after endoscopic colorectal polypectomy or endoscopic mucosal resection (EMR) in prevention of delayed bleeding (DB) following polypectomy. METHODS We searched the PubMed, Embase, and Cochrane Library databases for randomized controlled trials comparing the effect of prophylactic clipping versus no clipping on DB since inception to 22nd April 2022. We then performed a meta-analysis using a random-effects model. RESULTS We included 8 studies with 5648 patients and 10,436 lesions. Prophylactic clipping did not reduce the overall risk of DB compared with no clipping (1.54% vs 2.05%; Log RR, -0.29; 95% confidence interval [CI], -0.59, 0.01; P = 0.06). In subgroup analyses, clipping significantly reduced DB rate in polyps ≥ 2 cm (Log RR, -0.63; 95% CI, -1.08, -0.18; P = 0.01), in non-pedunculated polyps (Log RR, -0.63; 95% CI, -1.01, -0.24; P = 0.00), and in large (≥ 2 cm) proximal polyps (Log RR, -0.81; 95% CI, -1.56, 0.05; P = 0.04), but not in polyps < 2 cm (Log RR, 0.01; 95% CI, -.40, 0.42; P = 0.95). CONCLUSION Prophylactic clipping does not prevent post-polypectomy bleeding after all EMR and should not be performed as a routine practice. Although prophylactic clipping may reduce DB rate following resection of large proximal polyps and non-pedunculated polyps, more high-quality studies are needed to determine the effects of factors such as polyp location, polyp morphology, antithrombotic drug use and complete or partial closure on the effectiveness of prophylactic clipping.
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Flapless osteotome-mediated sinus floor elevation using platelet-rich fibrin versus lateral approach using deproteinised bovine bone mineral for residual bone height of 2-6 mm: a randomised trial
Lv H, Sun X, Wang J, Wang H, Wang L, Zhou Y
Clinical oral implants research. 2022
Abstract
OBJECTIVES To evaluate patient-reported outcomes and radiographic results of simultaneous implant placement in severely atrophic maxilla using flapless endoscope-assisted osteotome sinus floor elevation with platelet-rich fibrin (PRF), also defined as PESS, and to compare the results with those of lateral sinus floor elevation (LSFE). METHODS Patients with a residual bone height (RBH) of 2-6 mm were included in a randomised controlled trial. PESS was performed with PRF as the sole grafting material. LSFE was performed using deproteinised bovine bone matrix. Patient-reported outcomes were recorded on a visual analogue scale (VAS-pain) and visual rating scale (VRS-swelling and VRS-willingness). Peri-implant bone height (PBH), bone mineral density (BMD), and sinus grafting remodelling index were measured using CBCT immediately postoperatively and 3(rd) , 6(th) and 18(th) months post-surgery. RESULTS The study population consisted of 20 patients in each group. The RBH of two groups averaged 3.35±0.79 mm and 2.92±0.63 mm with no significant difference (p > 0.05). VAS-pain was 18.0 (IR 15.0-22.5) and 35.0 (IR 32.5-37.0) in the PESS and LSFE groups, respectively (p < 0.01). VAS-pain decreased with time in both groups. VRS-swelling was lower in the PESS group than LSFE group. VRS-willingness was higher in the PESS group than LSFE group (p < 0.01). At 18 months post-surgery, the marginal bone loss was 0.60±0.25 mm and 0.69±0.35 mm in the two groups with no significant difference (p = 0.52). CONCLUSIONS Within the limitations of this study, PESS was associated with lower postoperative morbidity and was more tolerable than LSFE. PESS could be a reliable procedure for sinus floor elevation in patients with insufficient RBH.
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Convalescent plasma may not be an effective treatment for severe and critically ill covid-19 patients: A Systematic Review & Meta-Analysis of Randomized Controlled Trials
Yang P, Wang J, Zheng R, Tan R, Li X, Liu X, Li Y, Yuan Z, Wang Y, Chen Q, et al
Heart & lung : the journal of critical care. 2022;53:51-60
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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.