Efficacy and Safety of COVID-19 Treatment Using Convalescent Plasma Transfusion: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
Lee HJ, Lee JH, Cho Y, Ngoc LTN, Lee YC
International journal of environmental research and public health. 2022;19(17)
This study investigated the efficacy and safety of convalescent plasma (CP) transfusion against the coronavirus disease 2019 (COVID-19) via a systematic review and meta-analysis of randomized controlled trials (RCTs). A total of 5467 articles obtained from electronic databases were assessed; however, only 34 RCTs were eligible after manually screening and eliminating unnecessary studies. The beneficial effect was addressed by assessing the risk ratio (RR) and standardized mean differences (SMDs) of the meta-analysis. It was demonstrated that CP therapy is not effective in improving clinical outcomes, including reducing mortality with an RR of 0.88 [0.76; 1.03] (I(2) = 68% and p = 0.10) and length of hospitalization with SMD of -0.47 [-0.95; 0.00] (I(2) = 99% and p = 0.05). Subgroup analysis provided strong evidence that CP transfusion does not significantly reduce all-cause mortality compared to standard of care (SOC) with an RR of 1.01 [0.99; 1.03] (I(2) = 70% and p = 0.33). In addition, CP was found to be safe for and well-tolerated by COVID-19 patients as was the SOC in healthcare settings. Overall, the results suggest that CP should not be applied outside of randomized trials because of less benefit in improving clinical outcomes for COVID-19 treatment.
Treatment and mortality of hemophagocytic lymphohistiocytosis in critically ill children: A systematic review and meta-analysis
Tan CJ, Ng ZQ, Bhattacharyya R, Sultana R, Lee JH
Pediatric blood & cancer. 2022;:e30122
OBJECTIVE Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine overall mortality of critically ill children with HLH, and describes etiologies, treatment, and pediatric intensive care unit (PICU) support employed. DATA SOURCES PubMed, Embase, Web of Science, CINAHL, and Cochrane Library from inception until February 28, 2022. STUDY SELECTION Observational studies and randomized controlled trials reporting children aged 18 years or below, diagnosed with HLH and admitted to the PICU. DATA EXTRACTION Etiologies, treatment modalities, PICU therapies, and mortality outcomes were summarized. Random-effects meta-analysis was performed. DATA SYNTHESIS Total 36 studies (total patients = 493, mean age: 49.5 months [95% confidence interval (CI): 30.9-79.5]) were included. Pooled mortality rate was 32.6% (95% CI: 23.4-42.4). The most frequent etiologies for HLH were infections (53.3%) and primary HLH (12.8%), while the remaining cases were due to other causes of secondary HLH, including autoimmune diseases, malignancy, and drug-induced and idiopathic HLH. Pooled mortality rate was higher in primary than secondary HLH (72.2%, 95% CI: 57.8-84.5 vs. 23.9%, 95% CI: 14.4-35.02; p < .01). Univariate analysis found that treatment with etoposide was associated with higher mortality, while intravenous immunoglobulins (IVIGs) were associated with lower mortality. Conversely, multivariable analysis adjusted for etiology demonstrated no association between etoposide and IVIG use, and mortality. Twenty-one studies (total patients = 278) had detailed information on PICU therapies. Mechanical ventilation (MV), continuous renal replacement therapy, and inotropes were used in 107 (38.5%), 66 (23.7%), and 51 patients (18.3%), respectively. Need for MV was associated with increased risk of mortality (mean difference = 28%, 95% CI: 9-47). CONCLUSION Critically ill children with HLH have high mortality rates and require substantial PICU support. Collaborative work between multiple centers with standardized data collection can potentially provide more robust data.
Effect of flowable thrombin-containing collagen-based hemostatic matrix for preventing pancreatic fistula after pancreatectomy: A randomized clinical trial
Park Y, Ko JH, Kang DR, Lee JH, Hwang DW, Lee JH, Lee W, Kwon J, Park SN, Song KB, et al
Annals of hepato-biliary-pancreatic surgery. 2021;25(Suppl 1):S371
INTRODUCTION The aim of this study was to evaluate the safety and efficacy of a flowable hemostatic matrix, and their effect for postoperative pancreatic fistula (POPF) after pancreatectomy. METHODS This was a randomized, clinical, single-center, single-blind (participant), non-inferiority, phase IV, and parallel-group trial. The primary endpoint was the incidence of POPF. The secondary endpoints were risk factors for POPF, drain removal days, incidence of complication, 90-day mortality, and length of hospital stay. RESULTS This study evaluated a total of 54 patients, with 26 patients in the intervention group (flowable hemostatic matrix) and 27 patients in the control group (thrombin-coated collagen patch). POPF was more common in the control group than in the intervention group (59.3% vs. 30.8%, p = 0.037). Among participants who underwent distal pancreatectomy (DP), POPF (33.3% vs. 92.3%, p = 0.004) and clinically relevant POPF (8.3% vs. 46.2%, p = 0.027) were more common in the control group. A multivariate logistic regression model identified flowable hemostatic matrix use (p = 0.029) as an independent negative risk factor for POPF. CONCLUSIONS Flowable hemostatic matrix application is a simple, feasible, and effective method of preventing POPF after pancreatectomy, especially for patients with DP.
Efficacy and Safety of a Thrombin-Containing Collagen-based Haemostatic Agent in Spinal Surgery: A Randomized Clinical Trial
Park SM, Kang DR, Lee JH, Jeong YH, Shin DA, Yi S, Ha Y, Kim KN
World neurosurgery. 2021
OBJECTIVE When common haemostatic methods, such as suturing, cautery, and compression, fail to arrest bleeding during surgery, various local haemostatic agents are used. We aimed to evaluate the haemostatic efficacy and safety of CollaStat® (Dalim Tissen Co. Ltd., Korea), a novel thrombin-containing collagen-based topical haemostatic agent used in spinal surgery, by comparing it with Floseal® (Baxter Healthcare, USA). METHODS We performed a randomised controlled trial in 78 patients who underwent spinal surgery. The participants were randomly assigned to either an intervention group (use of CollaStat®) or a control group (use of Floseal®). We compared successful haemostasis rate, time to haemostasis, length of hospital stay, amount of fluid drainage, and rate of adverse events between the two groups. RESULTS The haemostasis success rate was 94.87% in the intervention group and 97.44% in the control group. The haemostatic efficacy and safety of CollaStat® were found to be non-inferior to those of Floseal® since the higher limit (11.09%) of the confidence interval (CI) for the difference with Floseal® was greater than the pre-specified non-inferiority margin of -13%. There were no statistically significant differences at the 5% level in haemostasis time, number of haemostatic agents used, hospitalisation period, and amount of drainage between the two groups. Also, there was no incidence of medical device-related serious adverse events (SAEs) or adverse events (AEs) in both groups. CONCLUSION The haemostatic efficacy and safety of CollaStat® were found to be non-inferior to those of Floseal®. Therefore, CollaStat® can be safely and effectively used in spinal surgery.
Effect of Flowable Thrombin-Containing Collagen-Based Hemostatic Matrix for Preventing Pancreatic Fistula after Pancreatectomy: A Randomized Clinical Trial
Park Y, Ko JH, Kang DR, Lee JH, Hwang DW, Lee JH, Lee W, Kwon J, Park SN, Song KB, et al
Journal of clinical medicine. 2020;9(10)
BACKGROUND The aim of this study was to evaluate the safety and efficacy of a flowable hemostatic matrix, and their effects for postoperative pancreatic fistula (POPF) after pancreatectomy. METHODS This was a randomized, clinical, single-center, single-blind (participant), non-inferiority, phase IV, and parallel-group trial. The primary endpoint was the incidence of POPF. The secondary endpoints were risk factors for POPF, drain removal days, incidence of complication, 90-day mortality, and length of hospital stay. RESULTS This study evaluated a total of 53 patients, of whom 26 patients were in the intervention group (flowable hemostatic matrix) and 27 patients were in the control group (thrombin-coated collagen patch). POPF was more common in the control group than in the intervention group (59.3% vs. 30.8%, p = 0.037). Among participants who underwent distal pancreatectomy, POPF (33.3% vs. 92.3%, p = 0.004), and clinically relevant POPF (8.3% vs. 46.2%, p = 0.027) was more common in the control group. A multivariate logistic regression model identified flowable hemostatic matrix use as an independent negative risk factor for POPF, especially in cases of distal pancreatectomy (DP) (odds ratio 17.379, 95% confidential interval 1.453-207.870, p = 0.024). CONCLUSION Flowable hemostatic matrix application is a simple, feasible, and effective method of preventing POPF after pancreatectomy, especially for patients with DP. Non-inferiority was demonstrated in the efficacy of preventing POPF in the intervention group compared to the control group.
The Effect of Fibrinogen/Thrombin-Coated Collagen Patch (TachoSil((R))) Application in Pancreaticojejunostomy for Prevention of Pancreatic Fistula After Pancreaticoduodenectomy: A Randomized Clinical Trial
Kwon J, Shin SH, Lee S, Park G, Park Y, Lee SJ, Lee W, Song KB, Hwang DW, Kim SC, et al
World journal of surgery. 2019
BACKGROUND Fibrin sealants and topical glue have been studied to reduce the incidence of postoperative pancreatic fistulas (POPF) after pancreatico-enteric anastomosis, but a definitive innovation is still needed. We aim to evaluate the effectiveness of fibrin sealant patch applied to pancreatico-enteric anastomosis to reduce postoperative complications, including POPF. METHODS This study was a single-center, prospective, randomized, phase IV trial involving three pancreaticobiliary surgeons. The primary outcome was POPF; secondary outcomes included complications, drain removal days, hospital stay, readmission rate, and cost. Risk factors for POPF were identified by logistic regression analysis. RESULTS A total of 124 patients were enrolled. Biochemical leakage (BL) or POPF occurred in 16 patients (25.8%) in the intervention group and 23 patients (37.1%) in the control group (no statistical significance). Clinically relevant POPF occurred in 4 patients (6.5%) in both the intervention and control groups (p = 1.000). Hospital stay (11.6 days vs. 12.1 days, p = 0.585) and drain removal days (5.7 days vs. 5.3 days, p = 0.281) were not statistically different between two groups. Complication rates were not different between the two groups (p = 0.506); nor were readmission rates (12.9% vs. 11.3%, p = 1.000) or cost ($13,549 vs. $15,038, p = 0.103). In multivariable analysis, age and soft pancreas texture were independent risk factors for BL or POPF in this study. Applying fibrin sealant patch is not a negative risk factor, but the p value may indicate a likelihood of reducing the incidence of BL (p = 0.084). CONCLUSIONS Fibrin sealant patches after pancreaticojejunostomy did not reduce the incidence of POPF or other postoperative complications. This study was registered at clinicaltrials.gov (NCT03269955).
Efficacy and safety of CKD-11101 (darbepoetin-alfa proposed biosimilar) compared with NESP in anaemic chronic kidney disease patients not on dialysis
Lee JH, Chung BH, Joo KW, Shin SK, Kim YL, Na KY, Do JY, Park SK, Shin BC, Lee JS, et al
Current medical research and opinion. 2018;:1-17.
OBJECTIVE To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP(R) in treatment of anaemia in patients with chronic kidney disease not on dialysis. CLINICAL TRIAL REGISTRATION NCT03431623. METHOD In this multicentre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24 weeks, during which patients were treated every 2 weeks. All patients who completed the EEP were treated with CKD-11101 every 2 weeks for the first four weeks and every 4 weeks for the safety evaluation period (SEP), which was from 24 weeks to 52 weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb. RESULTS The mean Hb level was increased in both groups during the EEP (both P < 0.001). The difference in mean Hb level change between the two groups was 0.01g/dL (95% CI -0.213, 0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was -1.40mcg (95% CI -6.859, 4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group). CONCLUSION CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.
Effect of intravenous ferric carboxymaltose on hemoglobin response among patients with acute isovolemic anemia following gastrectomy: the FAIRY randomized clinical trial
Kim YW, Bae JM, Park YK, Yang HK, Yu W, Yook JH, Noh SH, Han M, Ryu KW, Sohn TS, et al
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Importance: Acute isovolemic anemia occurs when blood loss is replaced with fluid. It is often observed after surgery and negatively influences short-term and long-term outcomes. Objective: To evaluate the efficacy and safety of ferric carboxymaltose to treat acute isovolemic anemia following gastrectomy. Design, Setting, and Participants: The FAIRY trial was a patient-blinded, randomized, phase 3, placebo-controlled, 12-week study conducted between February 4, 2013, and December 15, 2015, in 7 centers across the Republic of Korea. Patients with a serum hemoglobin level of 7 g/dL to less than 10 g/dL at 5 to 7 days following radical gastrectomy were included. Interventions: Patients were randomized to receive a 1-time or 2-time injection of 500 mg or 1000 mg of ferric carboxymaltose according to body weight (ferric carboxymaltose group, 228 patients) or normal saline (placebo group, 226 patients). Main Outcomes and Measures: The primary end point was the number of hemoglobin responders, defined as a hemoglobin increase of 2 g/dL or more from baseline, a hemoglobin level of 11 g/dL or more, or both at week 12. Secondary end points included changes in hemoglobin, ferritin, and transferrin saturation levels over time, percentage of patients requiring alternative anemia management (oral iron, transfusion, or both), and quality of life at weeks 3 and 12. Results: Among 454 patients who were randomized (mean age, 61.1 years; women, 54.8%; mean baseline hemoglobin level, 9.1 g/dL), 96.3% completed the trial. At week 12, the number of hemoglobin responders was significantly greater for ferric carboxymaltose vs placebo (92.2% [200 patients] for the ferric carboxymaltose group vs 54.0% [115 patients] for the placebo group; absolute difference, 38.2% [95% CI, 33.6%-42.8%]; P = .001). Compared with the placebo group, patients in the ferric carboxymaltose group experienced significantly greater improvements in serum ferritin level (week 12: 233.3 ng/mL for the ferric carboxymaltose group vs 53.4 ng/mL for the placebo group; absolute difference, 179.9 ng/mL [95% CI, 150.2-209.5]; P = .001) and transferrin saturation level (week 12: 35.0% for the ferric carboxymaltose group vs 19.3% for the placebo group; absolute difference, 15.7% [95% CI, 13.1%-18.3%]; P = .001); but there were no significant differences in quality of life. Patients in the ferric carboxymaltose group required less alternative anemia management than patients in the placebo group (1.4% for the ferric carboxymaltose group vs 6.9% for the placebo group; absolute difference, 5.5% [95% CI, 3.3%-7.6%]; P = .006). The total rate of adverse events was higher in the ferric carboxymaltose group (15 patients [6.8%], including injection site reactions [5 patients] and urticaria [5 patients]) than the placebo group (1 patient [0.4%]), but no severe adverse events were reported in either group. Conclusion and Relevance: Among adults with isovolemic anemia following radical gastrectomy, the use of ferric carboxymaltose compared with placebo was more likely to result in improved hemoglobin response at 12 weeks. Trial Registration: clinicaltrials.gov Identifier: NCT01725789.
The effect of 6% hydroxyethyl starch (130/0.4) on acute kidney injury in paediatric cardiac surgery: a prospective, randomised trial
Oh HW, Lee JH, Kim HC, Kim EH, Song IK, Kim HS, Kim JT
We have evaluated the effect of a colloid solution on acute kidney injury in paediatric cardiac surgery. A total of 195 patients were ramdomly divided into an hydroxyethyl starch group and a control group. In the starch group, 6% hydroxyethyl starch 130/0.4 (Volulyte(R) ) was used as the primary fluid for volume resuscitation but was limited to 30 ml.kg-1 . In the control group, only crystalloid fluid was used during the peri-operative period. The incidence of acute kidney injury, peri-operative transfusion, clinical outcomes and laboratory data were compared. The incidence of acute kidney injury determined by Paediatric Risk, Injury, Failure, Loss, End-stage renal disease (pRIFLE) and Acute Kidney Injury Network (AKIN) criteria were no different between the two groups (starch group 40.8% vs. control group 30.0%; p = 0.150 using pRIFLE; 19.6% vs. 21.1% respectively, p = 0.602 using AKIN). There were no differences in clinical outcomes such as mortality, major adverse events, intensive care unit stay or duration of mechanical ventilation. Clotting time as measured using rotational thromboelastometry (ROTEM) was prolonged, and clot firmness after 10 min and maximal clot firmness were shorter in the starch group compared with the control group after sternal closure. There was no difference in transfusion between the two groups. Patients with acute kidney injury had worse clinical courses than those without acute kidney injury. We conclude that intra-operative use of 6% hydroxyethyl starch 130/0.4 up to 30 ml.kg-1 was not associated with postoperative acute kidney injury in paediatric cardiac patients.
Erythromycin infusion prior to endoscopy for acute nonvariceal upper gastrointestinal bleeding: a pilot randomized controlled trial
Na HK, Jung HY, Seo DW, . Lim H, Ahn JY, Lee JH, Kim DH, Choi KD, Song HJ, Lee GH, et al
The Korean Journal of Internal Medicine. 2017;32((6):):1002-1009
Background/Aims: The aim of this study was to compare the effects of erythromycin infusion and gastric lavage in order to improve the quality of visualization during emergency upper endoscopy. Methods: We performed a prospective randomized pilot study. Patients presented with hematemesis or melena within 12 hours and were randomly assigned to the erythromycin group (intravenous infusion of erythromycin), gastric lavage group (nasogastric tube placement with gastric lavage), or erythromycin + gastric lavage group (both erythromycin infusion and gastric lavage). The primary outcome was satisfactory visualization. Secondary outcomes included identification of a bleeding source, the success rate of hemostasis, duration of endoscopy, complications related to erythromycin infusion or gastric lavage, number of transfused blood units, rebleeding rate, and bleeding-related mortality. Results: A total of 43 patients were randomly assigned: 14 patients in the erythromycin group; 15 patients in the gastric lavage group; and 14 patients in the erythromycin + gastric lavage group. Overall satisfactory visualization was achieved in 81% of patients: 92.8% in the erythromycin group; 60.0% in the gastric lavage group; and 92.9% in the erythromycin + gastric lavage group, respectively (p = 0.055). The identification of a bleeding source was possible in all cases. The success rate of hemostasis, duration of endoscopy, and number of transfused blood units did not significantly differ between groups. There were no complications. Rebleeding occurred in three patients (7.0%). Bleeding-related mortality was not reported. Conclusions: Intravenous erythromycin infusion prior to emergency endoscopy for acute nonvariceal upper gastrointestinal bleeding seems to provide satisfactory endoscopic visualization.