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A single-center experience of non-bioartificial DFAPP support systems among Chinese patients with hyperlipidemic moderate/severe acute pancreatitis
Cheng, X., Zhan, Y., Wang, Z., Wang, F., Zeng, X., Mao, Y., Liu, Y.
Scientific reports. 2024;14(1):1128
Abstract
To assess the clinical efficacy of Double Filtration Plasmapheresis (DFAPP), a novel blood purification method, in treating hyperlipidemic moderate/severe pancreatitis (HL-M/SAP). A total of 68 HL-M/SAP patients were enrolled in this study. The observation group, comprising 34 patients, received DFAPP treatment, while the control group underwent CVVH + PA treatment. We compared the efficacy changes between the two groups post-treatment. Patients treated with DFAPP showed significant improvements in clinical outcomes. After 72 h of DFAPP treatment, HL-M/SAP patients exhibited notably lower multiple organ failure scores and a reduced mortality rate compared to those in the CVVH + PA group. Triglyceride levels in HL-M/SAP patients treated with DFAPP for 48 h averaged 3.75 ± 1.95, significantly lower than the 9.57 ± 3.84 levels in the CVVH + PA group (P < 0.05). Moreover, CRP levels decreased markedly, IL-17 levels diminished, IL-10 levels increased, and the decline in IL-35 levels was significantly less pronounced compared to the CVVH + PA group. The recurrence rate of pancreatitis was also significantly lower after 6 months. The early implementation of DFAPP in HL-M/SAP patients effectively reduces triglyceride levels, suppresses pro-inflammatory factors, enhances anti-inflammatory factors, and mitigates cytokine storm-induced sepsis damage. Consequently, this leads to a decrease in the incidence of multiple organ failure, improved patient survival rates, and a reduce the recurrence rate of lipogenic pancreatitis.Trial registration: Chinese Clinical Trial Registry, ChiCTR2300076066.
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Efficacy and Economic Evaluation of Nonbiological Artificial Liver Therapy in Acute-on-chronic Hepatitis B Liver Failure
Wu C, Peng W, Cheng D, Gu H, Liu F, Peng S, Fu L
Journal of clinical and translational hepatology. 2023;11(2):433-440
Abstract
BACKGROUND AND AIMS Nonbiological artificial liver (NBAL) is frequently used as a first-line treatment for hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). This study aimed to compare the therapeutic efficacy and cost-effectiveness ratio (CER) of comprehensive medical treatment, plasma exchange (PE), and double plasma molecular adsorption system (DPMAS) plus half-dose PE (DPMAS+PE) in patients with HBV-ACLF. METHODS A total of 186 patients with HBV-ACLF randomly received comprehensive medical treatment, PE, or DPMAS+PE and were prospectively evaluated. Patients were divided into four subgroups based on the pretreatment prothrombin activity (PTA): Group I (PTA>40%), group II (PTA 30-40%), group III (PTA 20-30%), and group IV (PTA<20%). The main outcome measures were 28 day effectiveness; 90 day liver transplantation-free survival; change of biochemical parameters; and CER. RESULTS DPMAS+PE treatment was associated with significantly higher 28 day effectiveness and 90 day liver transplantation-free survival compared with PE treatment in patients with group I liver failure. Clearance of serum total bilirubin (TBIL), AST, and creatinine (Cr) were significantly higher in the DPMAS+PE group than in the PE group. For subjects with group I liver failure, DPMAS+PE treatment had advantages of lower CER values and better cost-effectiveness. CONCLUSIONS Compared with comprehensive medical treatment and PE alone, DPMAS with half-dose sequential PE treatment more effectively improved TBIL, AST, and Cr in HBV-ACLF patients, improved 28 day effectiveness and 90 day survival rates in patients with group I liver failure, and was more cost effective. DPMAS+PE is a viable NBAL approach for treatment of HBV-ACLF.
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Extracorporeal photopheresis as graft-versus-host disease prophylaxis: a randomized controlled trial
Ali MM, Gedde-Dahl T, Osnes LT, Perrier F, Veierød MB, Tjønnfjord GE, Iversen PO
Transplantation and cellular therapy. 2023
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Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for many patients diagnosed with hematological malignancies. A major obstacle is graft-versus-host disease (GvHD) causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied GvHD treatment, partly due to its favourable safety profile. In contrast, the use of ECP in preventing GvHD is sparse, and randomized controlled trials (RCTs) are lacking. OBJECTIVE We therefore conducted a RCT to assess if ECP applied post-transplant, could prevent the development of GvHD within the first year of transplantation. STUDY DESIGN We enrolled 157 patients (18-74 years) with a hematological malignancy receiving first allo-HSCT: 76 randomized to the intervention group and 81 to the control group. ECP was initiated directly upon engraftment and was planned twice weekly for two weeks, then once weekly for four weeks. GvHD, relapse, and death were analyzed with Cox regression analysis. RESULTS During the first year, 45 patients in the intervention and 52 control patients developed GvHD (HR=0.82, 95% CI 0.55-1.22, P=0.32). There were no differences in acute or chronic GvHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GvHD between the intervention (per-protocol; n=39 of 76) and the control group (n=77), 46% vs 68%, respectively, (HR 0.47, 95% CI 0.27-0.80, P=0.006). Relapse occurred in 15 patients in the intervention group and in 11 patients among the controls (HR=1.38, 95% CI 0.64-3.01, P=0.42). GvHD-free relapse-free (GRFS) survival, event-free survival, overall survival and non-relapse mortality did not differ significantly between the two study groups. No significant difference in immune reconstitution between the two study groups was revealed. CONCLUSION This first intention-to-treat RCT, investigating ECP as GvHD prophylaxis in allo-HSCT for hematological malignancy does not support the use of ECP as adjunct to standard drug-based GvHD-prophylaxis. This trial was registered at www. CLINICALTRIALS gov as #NCT03204721.
PICO Summary
Population
Adult patients with a haematological malignancy receiving first allogeneic haematopoietic stem cell transplantation (n= 157).
Intervention
Prophylactic extracorporeal photopheresis (ECP), (intervention group, n= 76).
Comparison
No ECP (control group, n= 81).
Outcome
During the first year, 45 patients in the intervention and 52 control patients developed graft-versus-host disease (GVHD), (HR= 0.82, 95% CI [0.55, 1.22]). There were no differences in acute or chronic GVHD or its organ distribution in this intention-to-treat randomised controlled trial. A per-protocol analysis revealed a significant difference in GVHD between the intervention (per-protocol; n= 39 of 76) and the control group (n= 77), 46% vs. 68%, respectively, (HR 0.47, 95% CI [0.27, 0.80]). Relapse occurred in 15 patients in the intervention group and in 11 control patients (HR= 1.38, 95% CI [0.64, 3.01]). GVHD-free relapse-free survival, event-free survival, overall survival and non-relapse mortality did not differ significantly between the two study groups. There also was no significant difference in immune reconstitution between the two groups.
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Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): statistical and qualitative analysis plan for a randomised controlled feasibility trial
Seed, P. T., Brien, S. B., Oakley, L. L., Robinson, V., Sharif, J., Thompson, H., Joseph, J., Oteng-Ntim, E.
Trials. 2023;24(1):225
Abstract
BACKGROUND There are significant knowledge gaps regarding the effectiveness of serial prophylactic exchange blood transfusion (SPEBT) for pregnant women with sickle cell disease (SCD). The protocol for the randomised feasibility trial assessing SPEBT versus usual care in women with SCD (TAPS2 trial) has previously been published. This publication outlines the statistical and qualitative analysis plan for the study. METHODS AND DESIGN TAPS2 is a randomised two-arm phase 2 feasibility trial with a nested qualitative study and health economic evaluation. Up to 50 pregnant women with SCD and a singleton pregnancy will be recruited and individually randomised to either SPEBT approximately every 6-10 weeks until delivery (intervention arm) or to usual care (control arm). Information will be collected on a range of feasibility and clinical outcomes. RESULTS Due to the impact of COVID-19 on study recruitment, the initial study period of 24 months was extended to 48 months. Other protocol updates designed to mitigate the impact of COVID-19-related disruption included allowing for remote consent and conducting all qualitative interviews by telephone. The primary outcome for the trial is the overall recruitment rate. The number of women screened, eligible, consented, randomised and withdrawn will be summarised as a CONSORT flow diagram. Differences in clinical outcomes will additionally be presented as an initial assessment of efficacy and to inform sample size calculations for a future definitive trial. Qualitative interviews with trial participants and clinicians will be analysed using reflexive thematic analysis; data from interviews with participants who declined to participate in the trial will be extracted and incorporated into summary tables to report key findings. The health economic analysis plan is not covered by this update. CONCLUSION The publication of this analysis plan is designed to aid transparency and to reduce the potential for reporting bias. TRIAL REGISTRATION NIH registry ( www. CLINICALTRIALS gov ), registration number NCT03975894 (registered 05/06/19); ISRCTN ( www.isrctn.com ), registration number ISRCTN52684446 (retrospectively registered 02/08/19).
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Efficacy of plasmapheresis in neutropenic patients suffering from cytokine storm because of severe COVID-19 infection
Sadeghi A, Sadeghi S, Peikar MS, Yazdi M, Sharifi M, Ghafel S, Khorvash F, Ataei B, Safavi MR, Nasri E
Blood research. 2023
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Editor's Choice
Abstract
BACKGROUND With the emergence of the coronavirus disease 2019 (COVID-19) and inability of healthcare systems to control the disease, various therapeutic theories with controversial responses have been proposed. Plasmapheresis was administered as a medication. However, the knowledge of its efficacy and indications is inadequate. This study evaluated the use of plasmapheresis in critically ill patients with cancer. METHODS This randomized clinical trial was conducted on 86 patients with malignancies, including a control group (N=41) and an intervention group (N=45) with severe COVID-19 during 2020-21. Both groups were treated with routine medications for COVID-19 management according to national guidelines, and plasmapheresis was applied to the intervention group. C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, hemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. Other variables included neutrophil recovery, intensive care unit admission, intubation requirements, length of hospital stay, and hospitalization outcomes. RESULTS CRP (p<0.001), D-dimer (p<0.001), ferritin (p=0.039), and hemoglobin (p=0.006) levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the case than in the control group (p<0.001). However, plasmapheresis did not affect the length of hospital stay (p=0.076), which could have significantly increased survival rates (p<0.001). CONCLUSION Based on the study findings, plasmapheresis led to a significant improvement in laboratory markers and survival rate in patients with severe COVID-19. These findings reinforce the value of plasmapheresis in cancer patients as a critical population suffering from neutropenia and insufficient immune responses.
PICO Summary
Population
Critically ill patients with cancer and severe COVID-19 (n= 86).
Intervention
Plasmapheresis in addition to routine management (intervention group, n= 45).
Comparison
Routine medications for COVID-19 management (control group, n= 41).
Outcome
C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase, haemoglobin, and white blood cell, polymorphonuclear, lymphocyte, and platelet levels were measured at admission and at the end of plasmapheresis. CRP, D-dimer, ferritin, and haemoglobin levels were significantly different between the groups after the intervention. Neutrophil recovery was remarkably higher in the intervention group than in the control group. Plasmapheresis did not affect the length of hospital stay.
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Neuroimaging analyses from a randomized, controlled study to evaluate plasma exchange with albumin replacement in mild-to-moderate Alzheimer's disease: additional results from the AMBAR study
Cuberas-Borrós G, Roca I, Castell-Conesa J, Núñez L, Boada M, López OL, Grifols C, Barceló M, Pareto D, Páez A
European journal of nuclear medicine and molecular imaging. 2022
Abstract
PURPOSE This study was designed to detect structural and functional brain changes in Alzheimer's disease (AD) patients treated with therapeutic plasma exchange (PE) with albumin replacement, as part of the recent AMBAR phase 2b/3 clinical trial. METHODS Mild-to-moderate AD patients were randomized into four arms: three arms receiving PE with albumin (one with low-dose albumin, and two with low/high doses of albumin alternated with IVIG), and a placebo (sham PE) arm. All arms underwent 6 weeks of weekly conventional PE followed by 12 months of monthly low-volume PE. Magnetic resonance imaging (MRI) volumetric analyses and regional and statistical parametric mapping (SPM) analysis on (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) were performed. RESULTS MRI analyses (n = 198 patients) of selected subcortical structures showed fewer volume changes from baseline to final visit in the high albumin + IVIG treatment group (p < 0.05 in 3 structures vs. 4 to 9 in other groups). The high albumin + IVIG group showed no statistically significant reduction of right hippocampus. SPM (18)FDG-PET analyses (n = 213 patients) showed a worsening of metabolic activity in the specific areas affected in AD (posterior cingulate, precuneus, and parieto-temporal regions). The high-albumin + IVIG treatment group showed the greatest metabolic stability over the course of the study, i.e., the smallest percent decline in metabolism (MaskAD), and least progression of defect compared to placebo. CONCLUSIONS PE with albumin replacement was associated with fewer deleterious changes in subcortical structures and less metabolic decline compared to the typical of the progression of AD. This effect was more marked in the group treated with high albumin + IVIG. TRIAL REGISTRATION (AMBAR trial registration: EudraCT#: 2011-001,598-25; ClinicalTrials.gov ID: NCT01561053).
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Efficacy of plasma exchange in children with severe hemophagocytic syndrome: a prospective randomized controlled trial
Yuan, Y. H., Zhang, H., Xiao, Z. H., Zhang, X. P., Lu, X. L., Xu, Z. Y., He, J., Zhu, L. F.
Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics. 2022;24(3):249-254
Abstract
OBJECTIVES To investigate the efficacy and application value of plasma exchange as an adjuvant therapy in children with hemophagocytic syndrome (HPS). METHODS A prospective randomized controlled trial was designed. Forty children with severe HPS were enrolled, who were treated in the pediatric intensive care unit (PICU) of Hunan Children's Hospital from October 2018 to October 2020. The children were randomly divided into a plasma exchange group and a conventional treatment group using a random number table, with 20 children in each group. The children in the conventional treatment group received etiological treatment and conventional symptomatic supportive treatment, and those in the plasma exchange group received plasma exchange in addition to the treatment in the conventional treatment group. The two groups were compared in terms of general information, clinical symptoms and signs before and after treatment, main laboratory markers, treatment outcome, and prognosis. RESULTS Before treatment, there were no significant differences between the two groups in gender, age, course of the disease before admission, etiological composition, pediatric critical illness score, involvement of organ or system functions, and laboratory markers (P>0.05). After 7 days of treatment, both groups had remission and improvement in clinical symptoms and signs. After treatment, the plasma exchange group had significantly lower levels of C-reactive protein, procalcitonin, and serum protein levels than the conventional treatment group (P<0.05). The plasma exchange group also had significantly lower levels of alanine aminotransferase and total bilirubin than the conventional treatment group (P<0.05). The length of stay in the PICU in the plasma exchange group was significantly shorter than that in the conventional treatment group (P<0.05). The plasma exchange group had a significantly higher treatment response rate than the conventional treatment group (P<0.05). There were no significant differences between the two groups in the total length of hospital stay and 3-month mortality rate (P>0.05). CONCLUSIONS Plasma exchange as an adjuvant therapy is effective for children with severe HPS. It can improve clinical symptoms and signs and some laboratory markers and shorten the length of stay in the PICU, and therefore, it may become an optional adjuvant therapy for children with severe HPS.
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Feasibility, safety, and tolerability of two modalities of plasma exchange with albumin replacement to treat elderly patients with Alzheimer's disease in the AMBAR study
Boada M, Kiprov D, Anaya F, López OL, Núñez L, Olazarán J, Lima J, Grifols C, Barceló M, Rohe R, et al
Journal of clinical apheresis. 2022
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Abstract
BACKGROUND In the Alzheimer Management by Albumin Replacement (AMBAR) study, mild-to-moderate Alzheimer's disease (AD) patients were treated with a plasma exchange (PE) program. Feasibility and safety of PE in this specific population are poorly understood and were analyzed in detail in this study. METHODS Qualified patients were treated with 6 weeks of weekly conventional therapeutic plasma exchange (TPE) with albumin replacement followed by monthly low-volume plasma exchange (LVPE) for 12 months. The patients were divided into four groups: placebo (sham PE treatment), low-albumin (20 g), low-albumin + intravenous immunoglobulin (IVIG) (10 g), and high-albumin (40 g) + IVIG (20 g). Adverse events (AEs) were recorded and analyzed for all PE treatment groups and PE modalities. RESULTS PE procedure-related AEs were more common in the active treatment groups (16.9% out of 1283 TPE and 12.5% out of 2203 LVPE were associated with at least one AE, a similar rate than in other PE indications) than in the placebo group (0.7% out of 1223 sham PE). Percentage of procedures with at least one AEs was higher with central venous access compared to peripheral venous access in all three active treatment groups (20.1% vs 13.1%, respectively). CONCLUSION The TPE and LVPE procedures used in the AMBAR study on mild-to-moderate AD population were as safe and feasible as in other therapeutic applications of PE or routine plasmapheresis.
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Comparable Triglyceride Reduction With Plasma Exchange and Insulin in Acute Pancreatitis - A Randomized Trial
Gubensek J, Andonova M, Jerman A, Persic V, Vajdic-Trampuz B, Zupunski-Cede A, Sever N, Plut S
Frontiers in medicine. 2022;9:870067
Abstract
BACKGROUND AND AIMS Both insulin and plasma exchange (PE) are used in hypertriglyceridemic acute pancreatitis (HTG-AP). Our aim was to compare the efficacy of both treatments. METHODS A randomized, parallel group study performed in a tertiary hospital in 22 HTG-AP patients with non-severe prognosis and triglycerides between 15 and 40 mmol/L. Patients were randomized to daily PE or insulin infusion until triglycerides were <10 mmol/L. Primary outcome was % reduction in triglycerides within 24 h. Secondary outcomes were days needed to lower triglycerides <10 mmol/L, highest CRP and percentage of patients with a severe course of pancreatitis. RESULTS There was a trend toward a greater decrease in triglycerides within the first 24 h in the PE group (67 ± 17% vs. 53 ± 17%, p = 0.07), but the absolute difference was modest [mean difference of 6 mmol/L (14% of initial value)]. Triglycerides fell below 10 mmol/L in a median (IQR) of 1 (1-2) and 2 (1-2) days, respectively (p = 0.25). Secondary outcomes related to disease severity were also comparable: highest CRP 229 vs. 211 mg/L (p = 0.69) and severe course of pancreatitis in 2/11 cases in both groups (p = 1.0). Regarding treatment complications, there was one mild hypoglycemia and one allergic reaction during PE. Survival was 100% in both groups. CONCLUSION There was no significant difference, but only a trend toward a greater decrease in triglycerides with PE, and the clinical course was also comparable. These results do not support universal use of PE in patients with HTG-AP. CLINICAL TRIAL REGISTRATION [ClinicalTrials.gov], identifier [NCT02622854].
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Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial
Stahl K, Wand P, Seeliger B, Wendel-Garcia PD, Schmidt JJ, Schmidt BMW, Sauer A, Lehmann F, Budde U, Busch M, et al
Critical care (London, England). 2022;26(1):134
Abstract
BACKGROUND Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy. METHODS In the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE. RESULTS A continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004). CONCLUSIONS Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints. Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994 ).