[Randomized controlled multicenter study of albumin replacement therapy in septic shock (ARISS)]
Der Anaesthesist. 2021
Pharmacometric Analysis Linking Immunoglobulin Exposure to Clinical Efficacy Outcomes in Chronic Inflammatory Demyelinating Polyneuropathy
CPT: pharmacometrics & systems pharmacology. 2021
The two main objectives of this analysis were to (i) characterise the relationship between immunoglobulin (Ig) exposure and chronic inflammatory demyelinating polyneuropathy (CIDP) disease severity using data from 171 patients with CIDP who received either subcutaneous Ig (IgPro20; Hizentra®) or placebo (PATH study), and to (ii) simulate and compare exposure coverage with various dosing approaches considering weekly dosing to be the reference dose. IgG PK parameters including those from a previous population PK model were used to predict individual IgG profile and exposure metrics. Treatment-related changes in inflammatory neuropathy cause and treatment (INCAT) scores were best described by an E(max) model as a function of ΔIgG (total serum IgG at INCAT score assessment minus baseline IgG levels before intravenous Ig restabilisation). Simulations indicate that flexible dosing from daily to biweekly (every other week) provide an exposure coverage equivalent to that of a weekly Ig dose.
A Systematic Review of Fibrin Glue as an Ideal Treatment for the Pilonidal Disease
Pilonidal sinus is an acquired condition caused by irritation to the hair follicles at the natal cleft, presenting with an abscess or chronic infection. It is prevalent in young adults affecting their productive lifestyle with morbidities. There are varieties of treatment options; however, there is no consensus yet for the ideal procedure. Less invasive procedures have evolved to replace the traditional surgical techniques, which cannot significantly reduce the risks of recurrence and wound complications despite extensive surgeries. We aimed to assess the effect of fibrin glue as a primary treatment after cleaning the sinus in pilonidal sinus disease. We searched for articles from PubMed®, Ovid MEDLINE®, Ovid EMBASE®, and Cochrane CENTRAL. Six studies that included 336 patients in total were analyzed. Fibrin glue treatment in these studies reported a quicker return to normal activities postoperatively, a low rate of infection, and an acceptable rate of recurrence. Thus, fibrin glue seems beneficial in the management of pilonidal disease. However, further high-quality studies are essential to support and confirm this evidence. Future research should also evaluate its cost and implications in the ambulatory service.
Evaluation of high-dose aspirin elimination in the treatment of Kawasaki disease in the incidence of coronary artery aneurysm
Annals of pediatric cardiology. 2021;14(2):146-151
BACKGROUND Standard first-step therapy for Kawasaki disease consists of Intravenous immunoglobulin and high dose Aspirin (80-100 mg/kg/day). The standard dose of Intravenous immunoglobulin (2gr/kg) is strongly effective in reducing the risk of coronary arteries abnormalities. So, the proper dose and efficacy of Aspirin to decrease the risk of coronary arteries abnormalities is a controversial issue. In this study, it is tried to assess the result of eliminating high-dose Aspirin in the treatment of the acute phase of Kawasaki and observe the incidence rate of coronary arteries abnormalities when only Intravenous immunoglobulin was administered. METHODS This study is a prospective randomized, open-label, blinded end-points clinical trial performed in Afzalipour hospital in Kerman University of Medical Sciences from September 2017 to September 2018 in 62 patients with typical and atypical Kawasaki disease. The study group received Intravenous immunoglobulin (2 g/kg) and the control group get the same dose of Intravenous immunoglobulin plus Aspirin with the dose of 80-100 mg/Kg/day until they were afebrile for 48 hours. Afterward, both groups received a daily single dose (3-5 mg/kg) of Aspirin for six weeks. Echocardiography was done after two weeks, six weeks, and six months. Internal diameter of the left and right main coronary arteries was measured and then the corresponding Z-score was calculated. RESULTS In the study group, coronary arteries abnormalities decreased from 38.7% in the 2nd week to 16.1% in the 6th month. In the control group, it declined from 54.8% to 22.6%. There was no statistically significant difference between the groups in term of frequency of abnormal coronary arteries at the study period (P=0.151). CONCLUSIONS We concluded that high dose Aspirin does not have a significant role in preventing coronary arteries abnormalities in Kawasaki disease and giving standard 2 gr/kg/day Intravenous immunoglobulin without high-dose Aspirin in acute-phases therapy does not increase the risk of coronary arteries abnormality.
Is Intra-Articular Administration of Fibrinogen Effective in Postoperative Total Knee Arthroplasty Blood Loss? A Randomized Clinical Trial
Anesthesiology and pain medicine. 2021;11(1):e107431
OBJECTIVES The purpose of this study was to evaluate the effect of intra-articular injection of fibrinogen on postoperative bleeding following total knee arthroplasty. METHODS A double-blind randomized clinical trial was conducted on 40 patients aged 40 - 70 years under spinal anesthesia candidate for total knee arthroplasty in Golestan hospital, Ahwaz, Iran, in 2017-2018. Patients were divided into fibrinogen intra-articular injection (n = 20) and control (n = 20) groups. The amounts of blood loss and blood transfusion requirement were recorded. Hemoglobin (Hb), hematocrit (HCT), international normalized ratio (INR), platelet (PLT), prothrombin time (PT), and partial thromboplastin time (PTT) were recorded before and after the surgery. RESULTS There was no significant difference in the average amount of intraoperative blood loss between the groups (P > 0.05). The average amount of blood loss 24 hours after the surgery was significantly lower in the fibrinogen group than in the control group (fibrinogen group 350.61 ± 120.32 cc; control group 540.00 ± 170.21 cc; P = 0.0002). There were significant differences in transfusion between the groups (fibrinogen group 250 ± 20 cc; control group 350 ± 50 cc; P < 0.0001). There was a significant difference between the two groups in 24 h postoperative Hb and HCT (P < 0.001). CONCLUSIONS Intra-articular fibrinogen administration may reduce acute bleeding and can be used as an effective intervention to prevent further bleeding and the need for transfusion in patients undergoing total knee arthroplasty.
Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery: A Randomized Pilot Trial
JAMA network open. 2021;4(4):e213936
IMPORTANCE Approximately 15% of patients undergoing cardiac surgery receive frozen plasma (FP) for bleeding. Four-factor prothrombin complex concentrates (PCCs) have logistical and safety advantages over FP and may be a suitable alternative. OBJECTIVES To determine the proportion of patients who received PCC and then required FP, explore hemostatic effects and safety, and assess the feasibility of study procedures. DESIGN, SETTING, AND PARTICIPANTS Parallel-group randomized pilot study conducted at 2 Canadian hospitals. Adult patients requiring coagulation factor replacement for bleeding during cardiac surgery (from September 23, 2019, to June 19, 2020; final 28-day follow-up visit, July 17, 2020). Data analysis was initiated on September 15, 2020. INTERVENTIONS Prothrombin complex concentrate (1500 IU for patients weighing ≤60 kg and 2000 IU for patients weighing >60 kg) or FP (3 U for patients weighing ≤60 kg and 4 U for patients weighing >60 kg), repeated once as needed within 24 hours (FP used for any subsequent doses in both groups). Patients and outcome assessors were blinded to treatment allocation. MAIN OUTCOMES AND MEASURES Hemostatic effectiveness (whether patients received any hemostatic therapies from 60 minutes to 4 and 24 hours after initiation of the intervention, amount of allogeneic blood components administered within 24 hours after start of surgery, and avoidance of red cell transfusions within 24 hours after start of surgery), protocol adherence, and adverse events. The analysis set comprised all randomized patients who had undergone cardiac surgery, received at least 1 dose of either treatment, and provided informed consent after surgery. RESULTS Of 169 screened patients, 131 were randomized, and 101 were treated (54 with PCC and 47 with FP), provided consent, and were included in the analysis (median age, 64 years; interquartile range [IQR], 54-73 years; 28 [28%] were female; 82 [81%] underwent complex operations). The PCC group received a median 24.9 IU/kg (IQR, 21.8-27.0 IU/kg) of PCC (2 patients [3.7%; 95% CI, 0.4%-12.7%] required FP). The FP group received a median 12.5 mL/kg (IQR, 10.0-15.0 mL/kg) of FP (4 patients [8.5%; 95% CI, 2.4%-20.4%] required >2 doses of FP). Hemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group (P = .25) nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group (P = .28). The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 14.0 U (IQR, 8.0-20.0 U) in the FP group (ratio, 0.58; 95% CI, 0.45-0.77; P < .001). After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U (IQR, 4.0-11.0 U) in the PCC group and 10.0 U (IQR, 6.0-16.0 U) in the FP group (ratio, 0.80; 95% CI, 0.59-1.08; P = .15). For red blood cells alone, the median numbers were 1.5 U (IQR, 0.0-4.0 U) in the PCC group and 3.0 U (IQR, 1.0-5.0 U) in the FP group (ratio, 0.69; 95% CI, 0.47-0.99; P = .05). During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells (P = .24). Adverse event profiles were similar. CONCLUSIONS AND RELEVANCE This randomized clinical trial found that the study protocols were feasible. Adequately powered randomized clinical trials are warranted to determine whether PCC is a suitable substitute for FP for mitigation of bleeding in cardiac surgery. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04114643.
Cardiac surgery patients (n= 101).
Prothrombin complex concentrate (PCC group, n= 54).
Frozen plasma (FP group, n= 47).
Haemostatic therapy was not required at the 4-hour time point for 43 patients (80%) in the PCC group and for 32 patients (68%) in the FP group, nor at the 24-hour time point for 41 patients (76%) in the PCC group and for 31 patients (66%) patients in the FP group. The median numbers of units for 24-hour cumulative allogeneic transfusions (red blood cells, platelets, and FP) were 6.0 U in the PCC group and 14.0 U in the FP group. After exclusion of FP administered as part of the investigational medicinal product, the median numbers of units were 6.0 U in the PCC group and 10.0 U in the FP group. For red blood cells alone, the median numbers were 1.5 U in the PCC group and 3.0 U in the FP group. During the first 24 hours after start of surgery, 15 patients in the PCC group (28%) and 8 patients in the FP group (17%) received no red blood cells. Adverse event profiles were similar.
Comparison of Published Guidelines for the Diagnosis and the Management of Vaccine-Induced Immune Thrombotic Thrombocytopenia
Critical care explorations. 2021;3(9):e0519
The development of thrombocytopenia and thrombosis after the administration of the AstraZeneca and Johnson & Johnson/Janssen vaccines has been recently described. This new condition has been called vaccine-induced immune thrombotic thrombocytopenia. The objective of this review is to summarize the clinical characteristics and therapeutic options of vaccine-induced immune thrombotic thrombocytopenia based on available published case series. Furthermore, we provide a comparison of the diagnostic pathway and treatment recommendations provided by six major medical societies. DATA SOURCES We searched MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases. STUDY SELECTION We included case series and case reports on patients who developed vaccine-induced immune thrombotic thrombocytopenia. We also included guidelines for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia from major medical societies. DATA EXTRACTION We examined baseline risk factors, symptoms, physical signs, laboratory and imaging findings, and treatment in patients with vaccine-induced immune thrombotic thrombocytopenia reported in the case series. We also analyzed the diagnostic and treatment recommendations provided by major societal guidelines on the management of vaccine-induced immune thrombotic thrombocytopenia. DATA SYNTHESIS Patients who developed vaccine-induced immune thrombotic thrombocytopenia were more likely to be young women (age 20-50) who were given the AstraZeneca or Johnson & Johnson/Janssen 4-28 days prior to presentation. Patients showed signs, symptoms, and imaging findings consistent with cerebral venous sinus thrombosis and splanchnic thrombosis. Laboratory findings showed thrombocytopenia, low fibrinogen, and elevate d-dimer levels, while positive platelet factor 4 antibodies were always positive. Major societal guidelines recommend avoidance of heparin and platelets. Treatment with nonheparin anticoagulants and IV immunoglobulin is also recommended. CONCLUSIONS Vaccine-induced immune thrombotic thrombocytopenia is a rare but highly morbid complication related to the administration of the AstraZeneca and Johnson & Johnson/Janssen vaccines. Clinicians should be prepared for the early identification of patients with suspicious symptoms and prompt treatment should be initiated to avoid catastrophic deterioration. Major societal guidelines provide useful recommendations for the diagnosis and management of patients with vaccine-induced immune thrombotic thrombocytopenia.
Fibrin Sealants and Axillary Lymphatic Morbidity: A Systematic Review and Meta-Analysis of 23 Clinical Randomized Trials
BACKGROUND use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenectomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. METHODS randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. RESULTS twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin's disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p < 0.0001, p < 0.005, p = 0.008). CONCLUSION fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found.
Characteristics and therapy of enteroviral encephalitis: case report and systematic literature review
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021
OBJECTIVES Enterovirus (EV) is a frequent cause of encephalitis. The optimal therapeutic approach remains a matter of debate. We present the case of an immunosuppressed patient with EV encephalitis successfully treated with IVIG and conduct a systematic review on the characteristics of EV encephalitis as well as the safety and efficacy of IVIG-therapy. METHODS We conducted a systematic review assessing PubMed, Cochrane Database, Biosis Previews and the ClinicalTrials.gov website to identify all reports on patients with EV encephalitis as of December 31, 2020. Main outcomes assessed were efficacy and safety of the respective therapeutic approach. RESULTS We included a total of 73 papers: one prospective trial, one retro- and prospective case series, one purely retrospective case series, and 70 case reports. The case reports cover a total of 101 patients. The immunosuppressed were at higher risk of contracting EV encephalitis and experiencing lethal courses. Hypogammaglobulinaemia particularly predisposes for EV disease, even with moderate reduction of serum IgG levels. IVIG therapy in the immunosuppressed may confer a survival advantage. CONCLUSIONS IVIG therapy is rarely associated with severe adverse events and may be considered in immunosuppressed patients with EV encephalitis. Future trials should investigate optimal IVIG dosing and route of application, the benefit of antibody-enriched IVIG preparations and the serum immunoglobulin level that should trigger prophylactic replacement.
Is there an association between intravenous immunoglobulin resistance and coronary artery lesion in Kawasaki disease?-Current evidence based on a meta-analysis
PloS one. 2021;16(3):e0248812
BACKGROUND Coronary artery lesion (CAL) caused by Kawasaki disease (KD) is a leading cause of acquired heart disease in children. Initial treatment of intravenous immunoglobulin (IVIG) can reduce the incidence of CAL. Although most of the current studies have shown a certain correlation between CAL and IVIG resistance, the conclusions are not completely consistent. Thus, we performed this meta-analysis to evaluate the association between IVIG resistance and CAL in KD. METHODS PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through April 21, 2020 were searched to detect relevant studies. Data analysis was performed with STATA 15.1. RESULTS A total of 53 relevant studies were eligible to this analysis, including 30312 KD patients, of which 4750 were IVIG resistance and 25562 were responders. There was a significant difference found between IVIG resistance and IVIG response groups in the incidence of CAL (P < 0.001, odds ratio (OR), 3.89; 95% confidence interval (CI) (3.18, 4.75)). The heterogeneity test results showed that the I2 value was 74.8%. The meta-regression analysis showed that the study regions might be the sources of heterogeneity. The subgroup analysis suggested that the incidence of CAL in the IVIG resistance group was still higher than that in the IVIG response group under different regions, IVIG resistance diagnostic criteria, CAL diagnostic criteria, and study types. Meanwhile, the sensitivity analysis did not find any significant impact from every single study. CONCLUSIONS This is the first meta-analysis to reveal the incidence of CAL was associated with IVIG resistance in KD patients. Further well-designed studies with uniform criteria are needed to evaluate the incidence of CAL in IVIG resistant patients.