Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
Nature Communications. 2021;12(1):3189
In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development.
Efficacy of intrauterine Bakri balloon tamponade combined with ascending uterine artery ligation on postpartum hemorrhage
American journal of translational research. 2021;13(5):4995-5002
OBJECTIVE To observe the efficacy of intrauterine Bakri balloon tamponade (IBBT) combined with ascending uterine artery ligation (AUAL) in the treatment of postpartum hemorrhage (PPH) due to uterine inertia after cesarean section. METHODS A total of 92 patients with PPH due to uterine inertia after cesarean section were divided into a study group (n=46) and a control group (n=46) in accordance with the random number table. The control group was treated with IBBT alone, while the study group was treated with IBBT combined with AUAL. The clinical efficacies, hemorrhage, surgical duration, hospital stay, hemorrhage rate after removal of tamponade, recurrence rate of PPH, changes in coagulation function and quality of life were compared between the two groups. RESULTS The overall response rate (ORR) in the study group was 95.65%, remarkably higher than that of 80.43% in the control group (P < 0.05). The study group had a lesser amount of hemorrhage at 2 h and 24 h after surgery, a longer surgical duration, a shorter hospital stay, and lower hemorrhage rate after removal of tamponade and recurrence rate of PPH than the control group (P < 0.05). After treatment, prothrombin time, activated partial thromboplastin time and fibrinogen in the study group were markedly higher than those in the control group (P < 0.05). Compared with those before treatment, the scores of quality of life in the two groups were elevated at 3 months after treatment (P < 0.05), and the scores of quality of life in the study group were higher than those in the control group at 3 months after treatment (P < 0.05). CONCLUSION IBBT combined with AUAL can effectively alleviate hemorrhage and improve coagulation function and quality of life of patients with PPH due to uterine inertia after cesarean section, exhibiting a definite efficacy and a high safety profile.
Holmium laser enucleation of the prostate with Virtual Basket mode: faster and better control on bleeding
BMC urology. 2021;21(1):28
BACKGROUND To compare clinical intra and early postoperative outcomes between conventional Holmium laser enucleation of the prostate (HoLEP) and Holmium laser enucleation of the prostate using the Virtual Basket tool (VB-HoLEP) to treat benign prostatic hyperplasia (BPH). METHODS This prospective randomized study enrolled consecutive patients with BPH, who were assigned to undergo either HoLEP (n = 100), or VB-HoLEP (n = 100). All patients were evaluated preoperatively and postoperatively, with particular attention to catheterization time, operative time, blood loss, irrigation volume and hospital stay. We also evaluated the patients at 3 and 6 months after surgery and assessed maximum flow rate (Qmax), postvoid residual urine volume (PVR), the International Prostate Symptom Score (IPSS) and the Quality of Life score (QOLS). RESULTS No significant differences in preoperative parameters between patients in each study arm were found. Compared to HoLEP, VB-HoLEP resulted in less hemoglobin decrease (2.54 vs. 1.12 g/dl, P = 0.03) and reduced operative time (57.33 ± 29.71 vs. 42.99 ± 18.51 min, P = 0.04). HoLEP and VB-HoLEP detrmined similar catheterization time (2.2 vs. 1.9 days, P = 0.45), irrigation volume (33.3 vs. 31.7 l, P = 0.69), and hospital stay (2.8 vs. 2.7 days, P = 0.21). During the 6-month follow-up no significant differences in IPSS, Qmax, PVR, and QOLS were demonstrated. CONCLUSIONS HoLEP and VB-HoLEP are both efficient and safe procedures for relieving lower urinary tract symptoms. VB-HoLEP was statistically superior to HoLEP in blood loss and operative time. However, procedures did not differ significantly in catheterization time, hospital stay, and irrigation volume. No significant differences were demonstrated in QOLS, IPSS, Qmax and PVR throughout the 6-month follow-up. TRIAL REGISTRATION Current Controlled Trials ISRCTN72879639; date of registration: June 25th, 2015. Retrospectively registred.
A Meta-Analysis of Complications of Tranexamic Acid Use in Lower-Limb Orthopedic Surgery
AORN journal. 2021;113(6):657-660
Effect of Platelet-Rich Fibrin Application on Non-Infectious Complications after Surgical Extraction of Impacted Mandibular Third Molars
International journal of environmental research and public health. 2021;18(16)
Due to the frequent development of non-infectious complications after surgical removal of the third lower impacted tooth, many techniques are used to reduce their severity. Among them is the technique of applying platelet-rich fibrin to the post-extraction alveolus. The study included 90 consecutively enrolled patients. Eligible patients were randomly assigned to two groups: patients with and without platelet-rich fibrin introduced into the postoperative alveolus. Pain, swelling, trismus, and temperature were evaluated after the procedure. Pain intensity was significantly higher in the control group than in the study group at 6 h, 1, and 3 days after surgery. PRF application did not significantly affect the intensity of swelling. Body temperature was significantly higher in the control group than the study group on day two after surgery. The trismus was significantly higher in the control group than in the study group at one, two, and seven days after surgery. Application of the PRF allows for a faster and less traumatic treatment process. It will enable for speedier recovery and return to active life and professional duties.
Molidustat for Renal Anemia in Nondialysis Patients Previously Treated with Erythropoiesis-Stimulating Agents: A Randomized, Open-Label, Phase 3 Study
American journal of nephrology. 2021;:1-10
INTRODUCTION Erythropoiesis-stimulating agents (ESAs) are the current standard of care for anemia due to chronic kidney disease (CKD) in patients not undergoing dialysis. Molidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated as an alternative treatment for renal anemia. Molidustat was evaluated in five phase 3 studies, the molidustat once daily improves renal anemia by inducing erythropoietin (MIYABI) program. The present study investigated the safety and efficacy of molidustat in Japanese patients with renal anemia not undergoing dialysis and previously treated with ESAs. METHODS This was a 52-week, active-controlled, randomized (1:1), open-label, parallel-group, multicenter, phase 3 study in Japanese patients with anemia due to CKD (stages 3-5). Molidustat was initiated at 25 mg or 50 mg once daily according to previous ESA dose. The ESA darbepoetin alfa (darbepoetin) was initiated at a starting dose in accordance with the previous ESA dose and injected subcutaneously once every 2 or 4 weeks. Doses were regularly titrated to maintain hemoglobin (Hb) levels in the target range of 11.0-13.0 g/dL. The primary efficacy outcome was the mean Hb level and its change from baseline during the evaluation period (weeks 30-36). The safety outcomes included evaluation of all adverse events. RESULTS In total, 164 patients were randomized to receive molidustat (n = 82) or darbepoetin (n = 82). Baseline characteristics were well balanced. Mean (standard deviation) Hb levels at baseline were 11.31 (0.68) g/dL for molidustat and 11.27 (0.64) g/dL for darbepoetin. The mean (95% confidence interval [CI]) for mean Hb levels during the evaluation period for molidustat (11.67 [11.48-11.85] g/dL) and darbepoetin (11.53 [11.31-11.74] g/dL) was within the target range. Based on a noninferiority margin of 1.0 g/dL, molidustat was noninferior to darbepoetin regarding the change in mean Hb level during the evaluation period from baseline, with a least squares mean (95% CI) difference (molidustat-darbepoetin) of 0.13 (-0.15, 0.40) g/dL. The proportion of patients who reported at least 1 treatment-emergent adverse event (TEAE) was 92.7% for molidustat and 96.3% for darbepoetin. TEAEs leading to death were reported in 2 patients (2.4%) in the molidustat group and none in the darbepoetin group; serious TEAEs were reported in 32.9% and 26.8% of patients, respectively. DISCUSSION/CONCLUSION Molidustat was noninferior to darbepoetin and maintained Hb levels in the prespecified target range in patients with renal anemia not undergoing dialysis and previously treated with ESA. Molidustat was well tolerated, and no new safety signal was observed.
The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease
Crizanlizumab is a monoclonal antibody that binds to P-selectin. On October 28, 2020, a conditional marketing authorization valid through the European Union (EU) was issued for crizanlizumab for the prevention of recurrent vaso-occlusive crises (VOCs) in patients with sickle cell disease aged 16 years or older. Crizanlizumab was evaluated in a phase 2, double-blind, placebo-controlled randomized multicenter trial comparing high-dose (5 mg/kg) crizanlizumab, low-dose (2.5 mg/kg) crizanlizumab and placebo in patients with a history of 2-10 VOCs in the previous year. Patients who were receiving concomitant hydroxycarbamide (HC) as well as those not receiving HC were included in the study. The primary endpoint of the trial was the annual rate of sickle cell-related pain crises as adjudicated by a central review committee. High-dose crizanlizumab led to a 45.3% lower median annual rate of sickle cell-related pain crises compared to placebo (P = 0.010), with no statistically significant difference for the low dose. Treatment with high-dose crizanlizumab led to similar incidences of adverse events (AEs), grade 3 AEs, and serious AEs compared to placebo. Most frequently observed AEs that occurred more often in the crizanlizumab arm compared to placebo were infusion related reactions (34.8% versus 21%), arthralgia (18.2% versus 8.1%), diarrhea (10.6% versus 3.2%), and nausea (18.2% versus 11.3%). The aim of this article is to summarize the scientific review of the application leading to regulatory approval in the EU.
COVID-19 Convalescent Plasma: from donation to treatment - A Systematic Review & Single Center Experience
Missouri medicine. 2021;118(1):74-80
Convalescent plasma is an old treatment for a new disease. The coronavirus disease 2019 (COVID-19) pandemic caused the analysis of convalescent plasma to reemerge as a possible treatment. First, a systematic review summarizes the available research examining the use of convalescent plasma for the treatment of patients with COVID-19. Second, we describe our experience in establishing a single-center convalescent plasma donation program.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) in patients with major trauma and uncontrolled haemorrhagic shock: a systematic review with meta-analysis
World journal of emergency surgery : WJES. 2021;16(1):41
BACKGROUND Multiple studies regarding the use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in patients with non-compressible torso injuries and uncontrolled haemorrhagic shock were recently published. To date, the clinical evidence of the efficacy of REBOA is still debated. We aimed to conduct a systematic review assessing the clinical efficacy and safety of REBOA in patients with major trauma and uncontrolled haemorrhagic shock. METHODS We systematically searched MEDLINE (PubMed), EMBASE and CENTRAL up to June 2020. All randomized controlled trials and observational studies that investigated the use of REBOA compared to resuscitative thoracotomy (RT) with/without REBOA or no-REBOA were eligible. We followed the PRISMA and MOOSE guidelines. Two authors independently extracted data and appraised the risk of bias of included studies. Effect sizes were pooled in a meta-analysis using random-effects models. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Primary outcomes were mortality, volume of infused blood components, health-related quality of life, time to haemorrhage control and any adverse effects. Secondary outcomes were improvement in haemodynamic status and failure/success of REBOA technique. RESULTS We included 11 studies (5866 participants) ranging from fair to good quality. REBOA was associated with lower mortality when compared to RT (aOR 0.38; 95% CI 0.20-0.74), whereas no difference was observed when REBOA was compared to no-REBOA (aOR 1.40; 95% CI 0.79-2.46). No significant difference in health-related quality of life between REBOA and RT (p = 0.766). The most commonly reported complications were amputation, haematoma and pseudoaneurysm. Sparse data and heterogeneity of reporting for all other outcomes prevented any estimate. CONCLUSIONS Our findings on overall mortality suggest a positive effect of REBOA among non-compressible torso injuries when compared to RT but no differences compared to no-REBOA. Variability in indications and patient characteristics prevents any conclusion deserving further investigation. REBOA should be promoted in specific training programs in an experimental setting in order to test its effectiveness and a randomized trial should be planned.
Observation on the clinical effect of high-dose Intravenous Immunoglobulin combined with low-dose prednisone acetate in the treatment of patients with Kawasaki Disease
Pakistan journal of medical sciences. 2021;37(4):1122-1127
OBJECTIVE To evaluate the clinical effect of high-dose intravenous immunoglobulin (HDIVIG) single dose and pulse therapy combined with small-dose prednisone acetate in the treatment of patients with Kawasaki disease (KD). METHODS Eighty patients with KD from Baoding Children's Hospital, China, were randomly divided into two groups: the experimental group and the control group, each with 40 cases. Patients in the experimental group were treated with HDIVIG single dose, pulse therapy combined with low-dose prednisone acetate, while patients in the control group were treated with conventional-dose immunoglobulin. Patients in both groups were treated with aspirin orally, and given symptomatic treatment including anti-inflammatory, nutritional support, correction of water and electrolyte disturbance and acid-base balance. Peripheral venous blood samples were drawn from all patients at the time of admission, Day-1, Day-7 and Day-14 after treatment, and in the basic state of getting up in the morning, and then the levels of tumor necrosis factor (TNF-a), C-reactive protein (CRP), interleukin-6 (IL-6) and other inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The time of body temperature falling to normal, lymph node swelling recovery, hands and feet swelling, mucosal hyperemia regression after treatment in the two groups was recorded, and the treatment effect of the two groups was comprehensively evaluated. RESULTS After treatment, the levels of inflammatory factors such as TNF-a, CRP, IL-6 in the experimental group were significantly lower than those in the control group, with a statistically significant difference (P<0.05). In addition, the time of body temperature falling to normal, lymph node swelling recovery, hands and feet swelling, and mucosal hyperemia regression in the experimental group was significantly shorter than that in the control group (p=0.00). The effective rate of the experimental group was 95% and that of the control group was 80%, with a statistically significant difference (p=0.04). CONCLUSION HDIVIG single dose, pulse therapy combined with small-dose prednisone acetate has a favourable therapeutic effect in the treatment of patients with KD, by which the inflammatory factors can be significantly improved, clinical symptoms and weight can be quickly ameliorated, and therapeutic effect can be enhanced.