Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of “long COVID-19”, and defines key cells and cytokines that delineate true and quasi-convalescent states

Detection of coagulopathy in paediatric heart surgery [DECISION study]:study protocol

BACKGROUND: Each year in the UK, ≈3000 children undergo major cardiac surgery requiring cardiopulmonary bypass. Approximately 40 % of these experience excessive bleeding necessitating red cell transfusion or treatment with other blood components. A further 40 % receive blood components because of the perception by clinicians that the risk of bleeding is high. Excessive bleeding and treatment with red cell transfusion or blood components are associated with post-operative complications such as infection and renal injury and are independently associated with increased morbidity and mortality. Abnormalities in blood coagulation are a major cause of excessive bleeding after cardiac surgery in children. However, the extent of these abnormalities varies between children and their characteristics may change rapidly during surgery. In adults undergoing cardiac surgery, rapid testing of blood coagulation using techniques such as thromboelastometry may assist the selection of appropriate blood component treatments. In some sub-groups of adults, this improves clinical outcomes. Rapid testing of blood coagulation in children undergoing cardiac surgery has not been evaluated fully. METHODS/DESIGN: The DECISION study is a prospective, single-centre, observational study that aims to assess the utility of rapid testing of blood coagulation in children undergoing cardiac surgery. This will be achieved by testing blood samples from 200 children obtained immediately before, and after cardiac surgery. The blood samples will be analysed in parallel using thromboelastometry and reference laboratory tests of blood coagulation. The primary clinical outcome will be clinical concern about bleeding, defined as a composite of either excessive blood loss or the use of a pro-haemostatic treatment outside of standard treatment protocols because of perceived high risk of excessive bleeding. The reference laboratory test results will be used to describe the patterns of abnormalities in blood coagulation in children and will be compared to the thromboelastometry test results to determine the diagnostic accuracy of the thromboelastometry tests. We will estimate how well the reference and thromboelastometry test results predict clinical concern about bleeding. DISCUSSION: The DECISION study will identify the most useful thromboeastometry tests of blood coagulation for the prediction of excessive bleeding in children after cardiac surgery and will inform the design of future randomised controlled trials. TRIAL REGISTRATION: The trail was registered as ISRCTN55439761 on 23(rd) April 2015

Population antibody responses following COVID-19 vaccination in 212,102 individuals

Abstract: Population antibody surveillance helps track immune responses to COVID-19 vaccinations at scale, and identify host factors that may affect antibody production. We analyse data from 212,102 vaccinated individuals within the REACT-2 programme in England, which uses self-administered lateral flow antibody tests in sequential cross-sectional community samples; 71,923 (33.9%) received at least one dose of BNT162b2 vaccine and 139,067 (65.6%) received ChAdOx1. For both vaccines, antibody positivity peaks 4-5 weeks after first dose and then declines. At least 21 days after second dose of BNT162b2, close to 100% of respondents test positive, while for ChAdOx1, this is significantly reduced, particularly in the oldest age groups (72.7% [70.9–74.4] at ages 75 years and above). For both vaccines, antibody positivity decreases with age, and is higher in females and those with previous infection. Antibody positivity is lower in transplant recipients, obese individuals, smokers and those with specific comorbidities. These groups will benefit from additional vaccine doses

A new combination testing methodology to identify accurate and economical point-of-care testing strategies

Background: Quick, cheap and accurate point-of-care testing is urgently needed to enable frequent, large-scale testing to contain COVID-19. Lateral flow tests for antigen and antibody detection are an obvious candidate for use in community-wide testing, because they are quick and cheap relative to lab-processed tests. However, their low accuracy has limited their adoption. We develop a new methodology to increase the diagnostic accuracy of a combination of cheap, quick and inaccurate index tests with correlated or discordant outcomes, and illustrate its performance on commercially available lateral flow immunoassays (LFIAs) for Sars-CoV-2 antibody detection. Methods and Findings: We analyze laboratory test outcomes of 300 serum samples from health care workers detected with PCR-confirmed SARS-Cov-2 infection at least 21 days prior to sample collection, and 500 pre-pandemic serum samples, from a national seroprevalence survey, tested using eight LFIAs (Abbott, Biosure/Mologic, Orientgene-Menarini, Fortress, Biopanda I, Biopanda II, SureScreen and Wondfo) and Hybrid DABA as reference test. For each of 14 two-test combinations (e.g., Abbott, Fortress) and 16 three-test combinations (e.g., Abbott, Fortress, Biosure/Mologic) used on at least 100 positive and 100 negative samples, we classify an outcome sequence – e.g., (+,–) for (Abbott, Fortress) – as positive if its combination positive predictive value (CPPV) exceeds a given threshold, set between 0 and 1. Our main outcome measures are the sensitivity and specificity of different classification rules for classifying the outcomes of a combination test. We define testing possibility frontiers which represent sensitivity and false positive rates for different thresholds. The envelope of frontiers further enables test selection. The eight index tests individually meet neither the UK Medicines and Healthcare Products Regulatory Agency’s 98% sensitivity and 98% specificity criterion, nor the US Center for Disease Control’s 99.5% specificity criterion. Among these eight tests, the highest single-test LFIA specificity is 99.4% (with a sensitivity of 65.2%) and the highest single-test LFIA sensitivity is 93.4% (with a specificity of 97.4%). Using our methodology, a two-test combination meets the UK Medicines and Healthcare Products Regulatory Agency’s criterion, achieving sensitivity of 98.4% and specificity of 98.0%. While two-test combinations meeting the US Center for Disease Control’s 99.5% specificity criterion have sensitivity below 83.6%, a three-test combination delivers a specificity of 99.6% and a sensitivity of 95.8%. Conclusions: Current CDC guidelines suggest combining tests, noting that “performance of orthogonal testing algorithms has not been systematically evaluated” and highlighting discordant outcomes. Our methodology combines available LFIAs to meet desired accuracy criteria, by identifying testing possibility frontiers which encompass benchmarks, enabling cost savings. Our methodology applies equally to antigen testing and can greatly expand testing capacity through combining less accurate tests, especially for use cases needing quick, accurate tests, e.g., entry to public spaces such as airports, nursing homes or hospitals

Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2

10.1038/s41598-023-49231-wSCIENTIFIC REPORTS13