CytoResc - "CytoSorb" Rescue for critically ill patients undergoing the COVID-19 Cytokine Storm: A structured summary of a study protocol for a randomized controlled trial.
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ABSTRACT:
SUBMITTER: Stockmann H
PROVIDER: S-EPMC7316574 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Evaluation of the functional outcomes of patients undergoing an early rehabilitation protocol for critically ill patients from admission to discharge from the intensive care unit.A retrospective cross-sectional study was conducted that included 463 adult patients with clinical and/or surgical diagnosis undergoing an early rehabilitation protocol. The overall muscle strength was evaluated at admission to the intensive care unit using the Medical Research Council scale. Patients were allocated to one of four intervention plans according to the Medical Research Council score, the suitability of the plan's parameters, and the increasing scale of the plan expressing improved functional status. Uncooperative patients were allocated to intervention plans based on their functional status. The overall muscle strength and/or functional status were reevaluated upon discharge from the intensive care unit by comparison between the Intervention Plans upon admission (Planinitial) and discharge (Planfinal). Patients were classified into three groups according to the improvement of their functional status or not: responsive 1 (Planfinal > Planinitial), responsive 2 (Planfinal = Planinitial) and unresponsive (Planfinal < Planinitial).In total, 432 (93.3%) of 463 patients undergoing the protocol responded positively to the intervention strategy, showing maintenance and/or improvement of the initial functional status. Clinical patients classified as unresponsive were older (74.3 ± 15.1 years of age; p = 0.03) and had longer lengths of intensive care unit (11.6 ± 14.2 days; p = 0.047) and hospital (34.5 ± 34.1 days; p = 0.002) stays.The maintenance and/or improvement of the admission functional status were associated with shorter lengths of intensive care unit and hospital stays. The results suggest that the type of diagnosis, clinical or surgical, fails to define the positive response to an early rehabilitation protocol.
| S-EPMC4489785 | biostudies-other
Project description:The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).
| S-EPMC9595535 | biostudies-literature
Project description: Not available
| S-EPMC7316579 | biostudies-literature
Project description:ObjectivesPrimary objective: To estimate the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization. Secondary objectives: To examine whether the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization varies between subgroups related to treatment characteristics, disease severity at the time of randomization, patient characteristics, or risk of bias. To examine the effect of corticosteroids compared with usual care or placebo on serious adverse events.Study designProspective meta-analysis of randomized controlled trials. Both placebo-controlled and open-label trials are eligible.ParticipantsHospitalised, critically ill patients with suspected or confirmed COVID-19.Intervention and comparatorIntervention groups will have received therapeutic doses of a steroid (dexamethasone, hydrocortisone or methylprednisolone) with IV or oral administration immediately after randomization. The comparator groups will have received standard of care or usual care or placebo.Main outcomeAll-cause mortality up to 28 days after randomization.Search methodsSystematic searching of clinicaltrials.gov , EudraCT, the WHO ISRCTN registry, and the Chinese clinical trials registry. Additionally, research and WHO networks will be asked for relevant trials.Risk of bias assessmentsThese will be based on the Cochrane RoB 2 tool, and will use structured information provided by the trial investigators on a form designed for this prospective meta-analysis. We will use GRADE to assess the certainty of the evidence.Statistical analysesTrial investigators will provide data on the numbers of participants who did and did not experience each outcome according to intervention group, overall and in specified subgroups. We will conduct fixed-effect (primary analysis) and random-effects (Paule-Mandel estimate of heterogeneity and Hartung-Knapp adjustment) meta-analyses. We will quantify inconsistency in effects between trials using I2 statistics. Evidence for subgroup effects will be quantified by ratios of odds ratios comparing effects in the subgroups, and corresponding interaction p-values. Comparisons between subgroups defined by trial characteristics will be made using random-effects meta-regression. Comparisons between subgroups defined by patient characteristics will be made by estimating trial-specific ratios of odds ratios comparing intervention effects between subgroups then combining these using random-effects meta-analysis. Steroid interventions will be classified as high or low dose according to whether the dose is greater or less than or equal to 400 mg hydrocortisone per day or equivalent. We will use network meta-analysis methods to make comparisons between the effects of high and low dose steroid interventions (because one trial randomized participants to both low and high dose steroid arms).Prospero registration numberCRD42020197242 FULL PROTOCOL: The full protocol for this prospective meta-analysis is attached as an additional file, accessible from the Trials website (Additional file 1). To expedite dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol for the systematic review.
| S-EPMC7443535 | biostudies-literature
Project description:BackgroundAcute respiratory distress syndrome is an important clinical presentation of respiratory complications caused by severe acute respiratory syndrome coronavirus 2, a novel coronavirus responsible for the ongoing pandemic. The disease is poorly understood, and immunopathogenesis is constantly evolving. Cytokine release syndrome remains central to pathology of coronavirus disease 2019. Antivirals, anticytokine treatment, and other pharmacological approaches have failed to treat it. CytoSorb, an extracorporeal cytokine adsorber that reduces the cytokine storm and other inflammatory mediators in the blood, seems promising in treating severely ill patients with coronavirus disease 2019.Case presentationThis article presents three cases of Asian ethnicity of severely ill adult patients with coronavirus disease 2019 admitted to intensive care unit who were treated with CytoSorb therapy. All patients used single CytoSorb device. During their clinical course, all patients were prescribed tocilizumab (an interleukin-6 receptor blocker), antivirals, hydroxychloroquine, azithromycin, and other antibiotics and general antipyretic drugs. No vasopressor treatment was required. The patients' average duration of stay in intensive care unit was 30 days; the average duration of stay in hospital was 31 days. All three patients showed significant improvement in biochemical parameters and clinical outcomes post CytoSorb therapy. C-reactive protein levels decreased by 91.5%, 97.4%, and 55.75 %, and mean arterial pressure improved by 18%, 23%, and 17 % in patient 1, 2, and 3, respectively, on day 7 post-therapy.ConclusionsAll three patients improved clinically and survived.
| S-EPMC8448661 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19. Leronlimab is a humanized IgG4, kappa monoclonal antibody that blocks C-C chemokine receptor type 5 (CCR5). It has been shown that in patients with severe COVID-19 treatment with leronlimab reduces elevated plasma IL-6 and chemokine ligand 5 (CCL5), and normalized CD4/CD8 ratios. We administered leronlimab to 4 critically ill COVID-19 patients in intensive care. All 4 of these patients improved clinically as measured by vasopressor support, and discontinuation of hemodialysis and mechanical ventilation. Following administration of leronlimab there was a statistically significant decrease in IL-6 observed in patient A (p=0.034) from day 0-7 and patient D (p=0.027) from day 0-14. This corresponds to restoration of the immune function as measured by CD4+/CD8+ T cell ratio. Although two of the patients went on to survive the other two subsequently died of surgical complications after an initial recovery from SARS-CoV-2 infection.
| S-EPMC7823045 | biostudies-literature
Project description:ObjectivesTo assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation.Trial designThis is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial.ParticipantsAll patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility.Inclusion criteriaall adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization.Exclusion criteriapregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent.Intervention and comparatorThe intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians.Main outcomesAs a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio.RandomisationAfter inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1.Blinding (masking)Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups.Numbers to be randomised (sample size)We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group).Trial statusThe local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020.Trial registrationThe protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial" in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020.Full protocolThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
| S-EPMC7476433 | biostudies-literature
Project description:Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. Blood was sampled from 167 severe blunt trauma patients under the age of 55 yr who consented to blood sampling. The first blood sample was taken within 12 h of the injury and 1, 4, 7, 14, 21, and 28 d after injury. Study subjects were treated under the guidance of standard operating procedures developed, implemented, and audited across all participating centers to minimize treatment variation. In addition, 37 healthy control subjects were sampled. Total blood leukocytes were isolated according to protocols published previously. Total cellular RNA was extracted and hybridized onto an HU133 Plus 2.0 GeneChip (Affymetrix) according to the manufacturer’s recommendations.
2012-03-26 | E-GEOD-36809 | biostudies-arrayexpress
Project description:IntroductionMortality among critically ill COVID-19 patients remains relatively high despite different potential therapeutic modalities being introduced recently. The treatment of critically ill patients is a challenging task, without identified credible predictors of mortality.MethodsWe performed an analysis of 160 consecutive patients with confirmed COVID-19 infection admitted to the Respiratory Intensive Care Unit between June 23, 2020, and October 2, 2020, in University Hospital Center Bezanijska kosa, Belgrade, Serbia. Patients on invasive, noninvasive ventilation and high flow oxygen therapy with moderate to severe ARDS, according to the Berlin definition of ARDS, were selected for the study. Demographic data, past medical history, laboratory values, and CT severity score were analyzed to identify predictors of mortality. Univariate and multivariate logistic regression models were used to assess potential predictors of mortality in critically ill COVID-19 patients.ResultsThe mean patient age was 65.6 years (range, 29-92 years), predominantly men, 68.8%. 107 (66.9%) patients were on invasive mechanical ventilation, 31 (19.3%) on noninvasive, and 22 (13.8%) on high flow oxygen therapy machine. The median total number of ICU days was 10 (25th to 75th percentile: 6-18), while the median total number of hospital stay was 18 (25th to 75th percentile: 12-28). The mortality rate was 60% (96/160). Univariate logistic regression analysis confirmed the significance of age, CRP, and lymphocytes at admission to hospital, serum albumin, D-dimer, and IL-6 at admission to ICU, and CT score. Serum albumin, D-dimer, and IL-6 at admission to ICU were independently associated with mortality in the final multivariate analysis.ConclusionIn the present study of 160 consecutive critically ill COVID-19 patients with moderate to severe ARDS, IL-6, serum albumin, and D-dimer at admission to ICU, accompanied by chest CT severity score, were marked as independent predictors of mortality.
| S-EPMC8081622 | biostudies-literature
Project description:Systemic inflammation is a key characteristic of sepsis but also also in non-infectious conditions such as post-cardiac arrest syndrome. Cytokine adsorption and extracorporeal membrane oxygenation are emerging therapies applied in these critically ill patients, but the experience with their concurrent use is limited. We evaluated cytokine adsorption in critically ill patients requiring support with either veno-venous (vv) or veno-arterial (va) extracorporeal membrane oxygenation (ECMO) support and hypothesized that adsorber incorporation into the ECMO circuit was technically feasible and not associated with imminent risk. We analyzed data from the first six cases of a prospective single-center registry of patients undergoing veno-venous (vv) or veno-arterial (va) ECMO therapy. While in most published cases cytokine adsorbers were inserted into a hemofiltration circuit, we directly incorporated the adsorber into the ECMO circuit without interruption of continuous ECMO support. We observed no relevant side effects attributable to cytokine adsorption. Thirty-day mortality was 83% (predicted mortality 87%), indicating that the decision for adding cytokine adsorption may have been considered as an ultima ratio decision in severe cases with poor prognosis. Vasopressor or inotrope use, lactate level, and fluid balance did not change significantly when comparing pre- vs. post-cytokine adsorption values. Interestingly, the real-time course of the mentioned three surrogate parameters remained unaltered in all but two cases, regardless of cytokine removal. Beneficial effects of cytokine adsorption are plausible in two va-ECMO-treated patient, where increasing lactate began to drop after initiation of cytokine adsorption. Taken together, these data suggest that incorporation of cytokine adsorption into the management of critically ill patients requiring continued ECMO support is feasible and easy to handle. Whether cytokine removal improves clinical outcome in ECMO-treated patients should now be investigated in randomized controlled trials.
| S-EPMC6593298 | biostudies-literature