Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid ...may have prothrombotic and proconvulsant effects.
In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery.
Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fisher's exact test).
Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639 .).
Aberrant overexpression of the long non‐coding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) has been documented in different types of solid tumours, such as lung cancer, oesophageal cancer, ...colorectal cancer and hepatocellular carcinoma, in which its high levels are associated with poor prognosis. In contrast, NEAT1 is downregulated in acute promyelocytic leukaemia where it promotes leucocyte differentiation. In this review, we provide an overview of current evidence concerning the oncogenic role and potential clinical utilities of NEAT1. Further investigations are warranted to elucidate the upstream and downstream mechanisms of NEAT1 overexpression.
Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, ...and there is concern about impaired organ perfusion.
In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death.
During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing.
Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150 .).
Purpose
The literature was reviewed to determine the risks or benefits of short-term (less than four weeks) smoking cessation on postoperative complications and to derive the minimum duration of ...preoperative abstinence from smoking required to reduce such complications in adult surgical patients.
Source
We searched MEDLINE, EMBASE, Cochrane, and other relevant databases for cohort studies and randomized controlled trials that reported postoperative complications (i.e., respiratory, cardiovascular, wound-healing) and mortality in patients who quit smoking within six months of surgery. Using a random effects model, meta-analyses were conducted to compare the relative risks of complications in ex-smokers with varying intervals of smoking cessation
vs
the risks in current smokers.
Principal findings
We included 25 studies. Compared with current smokers, the risk of respiratory complications was similar in smokers who quit less than two or two to four weeks before surgery (risk ratio RR 1.20; 95% confidence interval CI 0.96 to 1.50
vs
RR 1.14; CI 0.90 to 1.45, respectively). Smokers who quit more than four and more than eight weeks before surgery had lower risks of respiratory complications than current smokers (RR 0.77; 95% CI 0.61 to 0.96 and RR 0.53; 95% CI 0.37 to 0.76, respectively). For wound-healing complications, the risk was less in smokers who quit more than three to four weeks before surgery than in current smokers (RR 0.69; 95% CI 0.56 to 0.84). Few studies reported cardiovascular complications and there were few deaths.
Conclusion
At least four weeks of abstinence from smoking reduces respiratory complications, and abstinence of at least three to four weeks reduces wound-healing complications. Short-term (less than four weeks) smoking cessation does not appear to increase or reduce the risk of postoperative respiratory complications.
Perioperative stroke after noncardiac, nonneurosurgical procedures is more common than generally acknowledged. It is reported to have an incidence of 0.05-7% of patients. Most are thrombotic in ...origin and are noted after discharge from the postanesthetic care unit. Common predisposing factors include age, a previous stroke, atrial fibrillation, and vascular and metabolic diseases. The mortality is more than two times greater than in strokes occurring outside the hospital. Delayed diagnosis and a synergistic interaction between the inflammatory changes normally associated with stroke, and those normally occurring after surgery, may explain this increase. Intraoperative hypotension is an infrequent direct cause of stroke. Hypotension will augment the injury produced by embolism or other causes, and this may be especially important in the postoperative period, during which monitoring is not nearly as attentive as in the operating room. Increased awareness and management of predisposing risk factors with early detection should result in improved outcomes.
Long non‐coding RNAs (lncRNAs) are a group greater than 200 nucleotides in length. An increasing number of studies has shown that lncRNAs play important roles in diverse cellular processes, including ...proliferation, differentiation, apoptosis, invasion and chromatin remodelling. In this regard, deregulation of lncRNAs has been documented in human cancers. TUG1 is a recently identified oncogenic lncRNA whose aberrant upregulation has been detected in different types of cancer, including B‐cell malignancies, oesophageal squamous cell carcinoma, bladder cancer, hepatocellular carcinoma and osteosarcoma. In these malignancies, knock‐down of TUG1 has been shown to suppress cell proliferation, invasion and/or colony formation. Interestingly, TUG1 has been found to be downregulated in non‐small cell lung carcinoma, indicative of its tissue‐specific function in tumourigenesis. Pertinent to clinical practice, TUG1 may act as a prognostic biomarker for tumours. In this review, we summarize current knowledge concerning the role of TUG1 in tumour progression and discuss mechanisms associated with it.
Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS).
To determine ...the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality).
Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013.
Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement.
A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality.
Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom.
Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.
Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain.
...To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery.
Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations.
Obstructive sleep apnea was classified as mild (respiratory event index REI 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring.
The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications.
Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 SD, 9 years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio HR, 1.49 95% CI, 1.19-2.01; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 95% CI, 1.49-3.34; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 95% CI, 0.98-2.09; P = .07) or mild OSA (adjusted HR, 1.36 95% CI, 0.97-1.91; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 95% CI, 15.5-27.7 minutes) was longer than in those without (10.2 95% CI, 7.8-10.9 minutes) (P < .001). No significant interaction effects on perioperative outcomes were observed with type of anesthesia, use of postoperative opioids, and supplemental oxygen therapy.
Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.
Long non‐coding RNAs (lncRNAs) compose a group of non‐protein‐coding RNAs ‐ more than 200 nucleotides in length. Recent studies have shown that lncRNAs play important roles in different cellular ...processes, including proliferation, differentiation, migration and invasion. Deregulation of lncRNAs has been widely reported in human tumours, in which they are able to function as either oncogenes (on the one hand) or tumour suppressor genes (on the other). Deregulation of CCAT1 (colon cancer–associated transcript‐1), an oncogenic lncRNA, has been documented in different types of malignancy, such as gastric cancer, colorectal cancer and hepatocellular carcinoma. In this regard, enforced expression of CCAT1 exerts potent tumorigenic effects by promoting cell proliferation, invasion and migration. Recent evidence has also shown that CCAT1 may serve as a prognostic cancer biomarker. In this review, we provide an overview of current evidence relating to the role and biological function of CCAT1 in tumour development.
Summary Background Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether ...nitrous oxide affects perioperative cardiovascular risk. Methods We did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov , number NCT00430989. Findings Of 10 102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83–1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001). Interpretation Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection, the emetogenic effect of nitrous oxide can be controlled with antiemetic prophylaxis, and a desired effect of reduced volatile agent use was shown. Funding Australian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec, Heart and Stroke Foundation of Ontario, Canada; General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.
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