ObjectiveTo identify research priorities that address the needs of people affected by cardiac surgery and those who support and care for them.DesignJames Lind Alliance (JLA) process—two surveys and a ...consensus workshop guided by an independent JLA adviser.SettingThe UK with international participation.ParticipantsThree stakeholder groups—heart surgery patients, carers and healthcare professionals involved in care delivery.MethodsThe initial survey was set to collect potential research questions in cardiac surgery as identified by stakeholders. Submitted questions were summarised into indicative questions. The existing evidence was searched to verify that these indicative questions had not been answered. In the second survey, stakeholders then voted for their top 10 from the list of unanswered questions. The top voted questions were taken forward for final ranking in a workshop.ResultsIn the initial survey, 629 respondents (28% patients/carers, 62% healthcare professionals) submitted 1082 potential questions. Of these, 797 in-scope questions were summarised into 49 indicative questions and of which 45 had not been answered by existing research. In the second survey, 492 respondents (43% patients/carers, 49% healthcare professionals) cast their votes with the top 12 from each of the three stakeholder groups totalling 21 questions advancing to the final priority setting workshop. The workshop attended by 25 delegates (10 patients/carers and 15 healthcare professionals) agreed on the top 10 research questions including long-term outcomes (quality of life), and aspects from preoperative personalised care (prehabilitation, frailty, comorbidities), intraoperative management (minimally invasive techniques), to prevention and management of postoperative complications (organ injury, atrial fibrillation, infection).ConclusionsThis Priority Setting Partnership (PSP) identified the priorities and unmet needs of patients and clinicians in cardiac surgery. The next step is to disseminate and implement the PSP results to ensure that these priorities shape future research and improve clinical services.
Abstract
We hypothesised that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. The study was performed in the cohort of the ...REVAKI-2 trial. Urine samples were collected before and 24 h after the procedure from 94 cardiac surgery patients. Urinary particle concentrations and size distribution were assessed using NanoSight. EV derivation and levels were measured using flow cytometry. Samples from 10 selected patients were sequenced, and verification was performed with advanced TaqMan assays in samples from all patients. Urinary particle concentrations significantly increased in patients with AKI after surgery, with the percentage of EV positive for CD105 and β1-integrin also increasing. Pre-surgery podocalyxin-positive EV were significantly lower in patients with AKI. Their levels correlated with the severity of the injury. Pre-operative miR-125a-5p was expressed at lower levels in urine from patients with AKI when adjusted for urinary creatinine. Levels of miR-10a-5p were lower after surgery in AKI patients and its levels correlated with the severity of the injury. Pre-operative levels of podocalyxin EVs, urinary particle concentrations and miR-125a-5p had moderate AKI predictive value and, in a logistic model together with ICU lactate levels, offered good (AUC = 82%) AKI prediction.
We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity ...paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-six adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28-29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI < 25, 25 ≤ BMI ≤ 32, and BMI > 32. The analysis indicated that protein translation-related pathways were downregulated in 25 ≤ BMI ≤ 32 compared with BMI < 25 patients. Muscle contraction transcripts were upregulated in 25 ≤ BMI ≤ 32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI > 32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI > 32 group and α-ketoglutarate increasing in the BMI < 25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.
Background Diseases of the thoracic aorta are characterized by a familial etiology in up to 30% of the cases. Nonsyndromic thoracic aorta diseases (NS-TADs) lack overt clinical signs and systemic ...features, which hinder early detection and prompt surgical intervention. We hypothesize that tailored genetic testing and imaging of first-degree and second-degree relatives of patients affected by NS-TADs may enable early diagnosis and allow appropriate surveillance or intervention. Methods and Results We conducted a feasibility study involving probands affected by familial or sporadic NS-TADs who had undergone surgery, which also offered screening to their relatives. Each participant underwent a combined imaging (echocardiogram and magnetic resonance imaging) and genetic (whole exome sequencing) evaluation, together with physical examination and psychological assessment. The study population included 16 probands (8 sporadic, 8 familial) and 54 relatives (41 first-degree and 13 second-degree relatives) with median age 48 years (range: 18-85 years). No syndromic physical features were observed. Imaging revealed mild-to-moderate aortic dilation in 24% of relatives. A genetic variant of uncertain significance was identified in 3 families. Imaging, further phenotyping, or a form of secondary prevention was indicated in 68% of the relatives in the familial group and 54% in the sporadic group. No participants fulfilled criteria for aortic surgery. No differences between baseline and 3-month follow-up scores for depression, anxiety, and self-reported quality of life were observed. Conclusions In NS-TADs, imaging tests, genetic counseling, and family screening yielded positive results in up to 1 out of 4 screened relatives, including those in the sporadic NS-TAD group. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03861741.
In an apparent paradox, morbidity and mortality are lower in obese patients undergoing cardiac surgery, although the nature of this association is unclear. We sought to determine whether the obesity ...paradox observed in cardiac surgery is attributable to reverse epidemiology, bias, or confounding.
Data from the National Adult Cardiac Surgery registry for all cardiac surgical procedures performed between April 2002 and March 2013 were extracted. A parallel systematic review and meta-analysis (MEDLINE, Embase, SCOPUS, Cochrane Library) through June 2015 were also accomplished. Exposure of interest was body mass index categorized into 6 groups according to the World Health Organization classification.
A total of 401 227 adult patients in the cohort study and 557 720 patients in the systematic review were included. A U-shaped association between mortality and body mass index classes was observed in both studies, with lower mortality in overweight (adjusted odds ratio, 0.79; 95% confidence interval, 0.76-0.83) and obese class I and II (odds ratio, 0.81; 95% confidence interval, 0.76-0.86; and odds ratio, 0.83; 95% confidence interval, 0.74-0.94) patients relative to normal-weight patients and increased mortality in underweight individuals (odds ratio, 1.51; 95% confidence interval, 1.41-1.62). In the cohort study, a U-shaped relationship was observed for stroke and low cardiac output syndrome but not for renal replacement therapy or deep sternal wound infection. Counter to the reverse epidemiology hypotheses, the protective effects of obesity were less in patients with severe chronic renal, lung, or cardiac disease and greater in older patients and in those with complications of obesity, including the metabolic syndrome and atherosclerosis. Adjustments for important confounders did not alter our results.
Obesity is associated with lower risks after cardiac surgery, with consistent effects noted in multiple analyses attempting to address residual confounding and reverse causation.
Background Anaemia, coagulopathic bleeding and transfusion are strongly associated with organ failure, sepsis and death following cardiac surgery. Objective To evaluate the clinical effectiveness and ...cost-effectiveness of medical devices used as diagnostic and therapeutic tools for the management of anaemia and bleeding in cardiac surgery. Methods and results Workstream 1 – in the COagulation and Platelet laboratory Testing in Cardiac surgery (COPTIC) study we demonstrated that risk assessment using baseline clinical factors predicted bleeding with a high degree of accuracy. The results from point-of-care (POC) platelet aggregometry or viscoelastometry tests or an expanded range of laboratory reference tests for coagulopathy did not improve predictive accuracy beyond that achieved with the clinical risk score alone. The routine use of POC tests was not cost-effective. A systematic review concluded that POC-based algorithms are not clinically effective. We developed two new clinical risk prediction scores for transfusion and bleeding that are available as e-calculators. Workstream 2 – in the PAtient-SPecific Oxygen monitoring to Reduce blood Transfusion during heart surgery (PASPORT) trial and a systematic review we demonstrated that personalised near-infrared spectroscopy-based algorithms for the optimisation of tissue oxygenation, or as indicators for red cell transfusion, were neither clinically effective nor cost-effective. Workstream 3 – in the REDWASH trial we failed to demonstrate a reduction in inflammation or organ injury in recipients of mechanically washed red cells compared with standard (unwashed) red cells. Limitations Existing studies evaluating the predictive accuracy or effectiveness of POC tests of coagulopathy or near-infrared spectroscopy were at high risk of bias. Interventions that alter red cell transfusion exposure, a common surrogate outcome in most trials, were not found to be clinically effective. Conclusions A systematic assessment of devices in clinical use as blood management adjuncts in cardiac surgery did not demonstrate clinical effectiveness or cost-effectiveness. The contribution of anaemia and coagulopathy to adverse clinical outcomes following cardiac surgery remains poorly understood. Further research to define the pathogenesis of these conditions may lead to more accurate diagnoses, more effective treatments and potentially improved clinical outcomes. Study registration Current Controlled Trials ISRCTN20778544 (COPTIC study) and PROSPERO CRD42016033831 (systematic review) (workstream 1); Current Controlled Trials ISRCTN23557269 (PASPORT trial) and PROSPERO CRD4201502769 (systematic review) (workstream 2); and Current Controlled Trials ISRCTN27076315 (REDWASH trial) (workstream 3). Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research ; Vol. 5, No. 17. See the NIHR Journals Library website for further project information.
Patient blood management (PBM) interventions aim to improve clinical outcomes by reducing bleeding and transfusion. We assessed whether existing evidence supports the routine use of combinations of ...these interventions during and after major surgery.
Five systematic reviews and a National Institute of Health and Care Excellence health economic review of trials of common PBM interventions enrolling participants of any age undergoing surgery were updated. The last search was on June 1, 2019. Studies in trauma, burns, gastrointestinal haemorrhage, gynaecology, dentistry, or critical care were excluded. The co-primary outcomes were: risk of receiving red cell transfusion and 30-day or hospital all-cause mortality. Treatment effects were estimated using random-effects models and risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity assessments used I2. Network meta-analyses used a frequentist approach. The protocol was registered prospectively (PROSPERO CRD42018085730).
Searches identified 393 eligible randomised controlled trials enrolling 54 917 participants. PBM interventions resulted in a reduction in exposure to red cell transfusion (RR=0.60; 95% CI 0.57, 0.63; I2=77%), but had no statistically significant treatment effect on 30-day or hospital mortality (RR=0.93; 95% CI 0.81, 1.07; I2=0%). Treatment effects were consistent across multiple secondary outcomes, sub-groups and sensitivity analyses that considered clinical setting, type of intervention, and trial quality. Network meta-analysis did not demonstrate additive benefits from the use of multiple interventions. No trial demonstrated that PBM was cost-effective.
In randomised trials, PBM interventions do not have important clinical benefits beyond reducing bleeding and transfusion in people undergoing major surgery.
Phenotyping has become the rate-limiting step in using large-scale genomic data to understand and improve agricultural crops. Here, the Bellwether Phenotyping Platform for controlled-environment ...plant growth and automated multimodal phenotyping is described. The system has capacity for 1140 plants, which pass daily through stations to record fluorescence, near-infrared, and visible images. Plant Computer Vision （PlantCV） was developed as open-source, hardware platform-independent software for quantitative image analysis. In a 4-week experiment, wild Setaria viridis and domesticated Setaria italica had fundamentally different temporal responses to water availability. While both lines produced similar levels of biomass under limited water conditions, Setaria viridis maintained the same water-use efficiency under water replete conditions, while Setaria italica shifted to less efficient growth. Overall, the Bellwether Phenotyping Platform and PlantCV software detected significant effects of genotype and environment on height, biomass, water-use efficiency, color, plant architecture, and tissue water status traits. All -79 000 images acquired during the course of the experiment are publicly available.
We evaluated the effects of two interventions that modify the red cell storage lesion on kidney and lung injury in experimental models of transfusion.
White-landrace pigs (n = 32) were allocated to ...receive sham transfusion (crystalloid), 14-day stored allogeneic red cells, 14-day red cells washed using the red cells washing/salvage system (CATS; Fresenius, Germany), or 14-day red cells rejuvenated using the inosine solution (Rejuvesol solution; Zimmer Biomet, USA) and washed using the CATS device. Functional, biochemical, and histologic markers of organ injury were assessed for up to 24 h posttransfusion.
Transfusion of 14 day red cells resulted in lung injury (lung injury score vs. sham, mean difference -0.3 (95% CI, -0.6 to -0.1; P = 0.02), pulmonary endothelial dysfunction, and tissue leukocyte sequestration. Mechanical washing reduced red cell-derived microvesicles but increased cell-free hemoglobin in 14-day red cell units. Transfusion of washed red cells reduced leukocyte sequestration but did not reduce the lung injury score (mean difference -0.2; 95% CI, -0.5 to 0.1; P = 0.19) relative to 14-day cells. Transfusion of washed red cells also increased endothelial activation and kidney injury. Rejuvenation restored adenosine triphosphate to that of fresh red cells and reduced microvesicle concentrations without increasing cell-free hemoglobin release. Transfusion of rejuvenated red cells reduced plasma cell-free hemoglobin, leukocyte sequestration, and endothelial dysfunction in recipients and reduced lung and kidney injury relative to 14-day or washed 14-day cells.
Reversal of the red cell storage lesion by rejuvenation reduces transfusion-associated organ injury in swine.
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
Primary objective:
To identify and summarise the findings of RCTs evaluating interventions that target the ...inflammatory response to cardiac surgery and measure both markers of inflammation and clinical outcomes.
Secondary objective:
To evaluate whether interventions that target different drivers of inflammation during cardiac surgery influence the nature of the inflammatory response or clinical outcomes.
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