1,720,971 research outputs found
Biomarkers of Inflammation and Lung Recovery in Extracorporeal Membrane Oxygenation Patients With Persistent Pulmonary Hypertension of the Newborn: A Feasibility Study
No full textIntravenous sildenafil citrate and post-cardiac surgery acute kidney injury: a double-blind, randomised, placebo-controlled trial
Full text linkBackgroundThis study assessed whether i.v. sildenafil citrate prevented acute kidney injury in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass.MethodsIn a double-blind RCT, adults at increased risk of acute kidney injury undergoing cardiac surgery in a single UK tertiary centre were randomised to receive sildenafil citrate 12.5 mg kg−1 i.v. over 150 min or dextrose 5% at the commencement of surgery. The primary outcome was serum creatinine measured at six post-randomisation time points. The primary analysis used a linear mixed-effects model adjusted for the stratification variables, baseline estimated glomerular filtration rate, and surgical procedure. Secondary outcomes considered clinical events and potential disease mechanisms. Effect estimates were expressed as mean differences (MDs) or odds ratios with 95% confidence intervals.ResultsThe analysis population comprised eligible randomised patients that underwent valve surgery or combined coronary artery bypass graft and valve surgery, with cardiopulmonary bypass, between May 2015 and June 2018. There were 60 subjects in the sildenafil group and 69 in the placebo control group. The difference between groups in creatinine concentration was not statistically significant (MD: 0.88 μmol L−1 [–5.82, 7.59]). There was a statistically significant increase in multiple organ dysfunction scores in the sildenafil group (MD: 0.54 [0.02, 1.07]; P=0.044). Secondary outcomes, and biomarkers of kidney injury, endothelial function, and inflammatory cell activation, were not significantly different between the groups.ConclusionsThese results do not support the use of i.v. sildenafil citrate for kidney protection in adult cardiac surgery
The clinical use of urinary mitochondrial DNA in adult surgical critical care patients with acute kidney injury
No full textRandomized trial of red cell washing for the prevention of transfusion-associated organ injury in cardiac surgery
Full text linkBackgroundExperimental studies suggest that mechanical cell washing to remove pro-inflammatory components that accumulate in the supernatant of stored donor red blood cells (RBCs) might reduce inflammation and organ injury in transfused patients.MethodsCardiac surgery patients at increased risk of large-volume RBC transfusion were eligible. Participants were randomized to receive either mechanically washed allogenic RBCs or standard care RBCs. The primary outcome was serum interleukin-8 measured at baseline and at four postsurgery time points. A mechanism substudy evaluated the effects of washing on stored RBCs in vitro and on markers of platelet, leucocyte, and endothelial activation in trial subjects.ResultsSixty adult cardiac surgery patients at three UK cardiac centres were enrolled between September 2013 and March 2015. Subjects received a median of 3.5 (interquartile range 2–5.5) RBC units, stored for a mean of 21 (sd 5.2) days, within 48 h of surgery. Mechanical washing reduced concentrations of RBC-derived microvesicles but increased cell-free haemoglobin concentrations in RBC supernatant relative to standard care RBC supernatant. There was no difference between groups with respect to perioperative serum interleukin-8 values [adjusted mean difference 0.239 (95% confidence intervals −0.231, 0.709), P=0.318] or concentrations of plasma RBC microvesicles, platelet and leucocyte activation, plasma cell-free haemoglobin, endothelial activation, or biomarkers of heart, lung, or kidney injury.ConclusionsThese results do not support a hypothesis that allogenic red blood cell washing has clinical benefits in cardiac surgery
An Observational Cohort Feasibility Study to Identify Microvesicle and Micro-RNA Biomarkers of Acute Kidney Injury Following Pediatric Cardiac Surgery
No full textA Comparison of Red Cell Rejuvenation versus Mechanical Washing for the Prevention of Transfusion-associated Organ Injury in Swine
No full textA Phase I study to determine the pharmacokinetic profile, safety and tolerability of sildenafil (Revatio®) in cardiac surgery: the REVAKI-1 study
No full textEffect of sildenafil (Revatio) on postcardiac surgery acute kidney injury: a randomised, placebo-controlled clinical trial: the REVAKI-2 trial protocol
Full text linkIntroduction Acute kidney injury (AKI) is a common and severe complication of cardiac surgery. The administration of pharmacological renoprotective agents during the perioperative period could prevent or reduce the severity of AKI and improve clinical outcomes. Experimental studies suggest that sildenafil may have therapeutic potential for the prevention of AKI. This trial will test the hypothesis that postoperative AKI will be reduced in cardiac surgery patients if they receive sildenafil compared with placebo.Methods and analysis Adult cardiac surgery patients 18 years of age or above undergoing cardiac surgery with cardiopulmonary bypass and cardioplegic arrest at a single tertiary cardiac centre in the UK will be randomised in a 1:1 ratio to receive either sildenafil or placebo. The primary outcome is serum creatinine concentration measured at preoperation and daily for up to 7 days postoperatively. Secondary outcomes will include measures of inflammation, organ injury, volumes of blood transfused and resource use. Allocation concealment, internet-based randomisation stratified by operation type, and blinding of outcome assessors will reduce the risk of bias. A sample size of 112 patients will have a 90% power to detect a mean difference of 10 μmol/L for serum creatinine values between treatment and placebo control groups with an alpha value of 0.05.Ethics and dissemination The trial protocol was approved by a UK ethics committee (reference 15/YH/0489). The trial findings will be disseminated in scientific journals and meetings.Trial registration number ISRCTN18386427
Acute kidney injury after cardiac surgery is associated with platelet activation
No full textBackground: Postcardiac surgery acute kidney injury (AKI) is common and associated with high mortality and morbidity. Its pathogenesis remains unclear.Objectives: To determine if platelet activation, extracellular vesicles (EVs), and microRNA levels are associated with postoperative AKI.Methods: Plasma samples from 95 microRNA in Post CArdiac Surgery study patients were collected before, immediately after, and 6 to 12, 24, and 48 hours after surgery. Platelet responsiveness was assessed using a Multiplate aggregometer. Flow cytometry was used to measure platelet and leukocyte activation and for EV derivation. EV size and concentration were analyzed using NanoSight. Circulating biomarkers were measured using immunoassays, and microRNA was analyzed using TaqMan arrays and validated by quantitative real-time polymerase chain reaction.Results: AKI occurred in 57% of patients. Platelet-derived EVs increased 24 hours after surgery in AKI patients. Platelets were desensitized to adenosine diphosphate at 6 to 12 hours, independent of aspirin or P2Y12 antagonist use. AKI patients had more activated platelets at 6 to 12 hours, more platelet-granulocyte aggregates before and at 6 to 12 and 24 hours after surgery, and higher soluble ICAM1 levels before and 48 hours after surgery. TaqMan arrays showed miR-668 was downregulated before and miR-92a-1, -920, -518a-3p, -133b, and -1262 were upregulated after surgery in AKI patients. Quantitative real-time polymerase chain reaction confirmed miR-1262 upregulation. Multivariate analysis showed that granulocyte-platelet aggregates were independently associated with AKI before and at 6 to 12 and 24 hours after surgery. Activated glycoprotein IIb/IIIa and adenosine diphosphate were associated with AKI at 6 to 12 and 24 hours and soluble ICAM1 at 48 hours.Conclusions: AKI is associated with platelet activation, suggesting alternative platelet inhibition may offer renoprotection. Larger studies are needed to validate these findings
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