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Introduction In moderate to high-risk surgical procedures, 15–25% of patients develop a postoperative surgical site infection. Intraoperative incisional wound irrigation has the potential to reduce surgical site infections, and additional randomised controlled trials are required to provide evidence of effectiveness. Methods and analysis This protocol describes a pragmatic, adaptive, participant and adjudicator-blinded trial at 13 sites in Canada in up to 2500 participants. Participants planned for surgery with an abdominal or groin incision, who are eligible and provide verbal consent through an integrated consent model, are randomised to receive intraoperative incisional wound irrigation with povidone-iodine, saline or no irrigation. The primary outcome is surgical site infection within 30 days postoperatively. Secondary outcomes include quality of life measured 30 days postoperatively and morbidity, mortality and healthcare utilisation within 90 days postoperatively. Ethics and dissemination This trial has been approved by the research ethics board at the participating centres and stopped enrolling participants on May 23, 2025. All participants will provide verbal consent. Results will be disseminated via presentation at conferences, publication and posted on clinicaltrials.gov. Trial registration number The study is registered with http://clinicaltrial.gov ( NCT04548661 ; 14 September 2020).

ImportanceTranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear.ObjectiveTo determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection.Design, Setting, and ParticipantsMulticenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization.InterventionsTranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia.Main Outcomes and MeasuresThe primary outcome was receipt of red blood cell transfusion within 7 days of surgery.ResultsThe primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, −2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08).Conclusions and RelevanceAmong patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications.Trial RegistrationClinicalTrials.gov Identifier: NCT02261415

Background: Left atrial (LA) size increases in atrial fibrillation (AF). How changes in mitral annulus and atrial volume over time relate to severity of mitral regurgitation (MR) is unknown. Methods: This cohort study included 160 patients with a history of permanent AF who had at least 2 transthoracic echocardiograms (TTE) performed between 2005 and 2010 at Vancouver General Hospital (British Columbia, Canada). Patients with structural mitral valve disease, congenital heart disease, more than mild-moderate mitral/tricuspid regurgitation on their first TTE were excluded from analyses. LA volume was determined using biplane area-length method, averaged over 3 cardiac cycles. The mitral annulus diameter (MAD), defined as the distance between the hinge points of the anterior and posterior mitral leaflets from the apical 4-chamber view, was measured during end-systole and end-diastole. Linear mixed effects modeling was used in analyzing the above measurements for change over time. Mitral regurgitation was classified into 3 grades (mild, moderate, or severe) using standard color Doppler and PISA easurements where available. Results: Of the 160 subjects included in this analysis, 100 were men (62.5%). The mean age at study entry was 74±10 years. The median number of TTE performed was 3 (range 2 - 6). All 160 patients showed a progressive increase in MAD over time. There was a significant increase in MAD at end-systole and end-diastole over a mean follow-up of 3.2 ± 2.8 years; the increases were 0.48 mm/year (95% CI 0.124 -0.75, P=0.0037) and 0.45 mm/year (95% CI 0.102-0.716, P=0.0029) respectively. LA volume increased from a mean of 43 mL/m2 to 75 mL/m2 for the cohort, or 10 mL/m2 per year. Adjusting for age, sex, and left ventricular ejection fraction, an increase in MR severity by at least 1 grade was strongly and independently associated with an increase in MAD. A 15% increment in MAD was associated with an increase in MR severity by 1 grade. Conclusion: Permanent AF was associated with significant increases in MAD and LA volume over time. Severity of MR also significantly increased over time, and was independently related to the change in MAD. Further investigations as to whether this represents a mechanism for left heart failure in patients with permanent AF are warranted.

Abstract Cytoglobin is a highly conserved redox sensor heme protein with unknown physiological function. Unexpectedly, genetic deletion of zebrafish cytoglobin (cygb2) causes cardiac and gastro-intestinal tract laterality defects, modeling Kartagener’s syndrome, which in humans is associated with low airway epithelial nitric oxide (NO) production. Cygb2 co-localized with cilia and the NO synthase Nos2b in the Kupffer’s vesicle (KV) laterality organ and the structure and function of cilia were disrupted in cygb2 mutants, abolishing fluid flow within the KV. Abnormal ciliary function and organ laterality was phenocopied by depletion of nos2band gucy1a, the canonical NO receptor soluble guanylate cyclase (sGC) homolog in fish, and rescued by exposing cygb2 mutant embryos to an NO donor or an sGC stimulator and with over-expression of nos2b. Consistent with a conserved role in the modulation of ciliary function, cytoglobin knock out in the mouse also impaired airway epithelial ciliary structure and beat frequency. This is the first evidence that cytoglobin is essential for normal development stage-specific NO signaling, ciliogenesis and cilia motility, required for the establishment of left-right patterning.

Introduction Despite use of operative and non-operative interventions to reduce blood loss during liver resection, 20%–40% of patients receive a perioperative blood transfusion. Extensive intraoperative blood loss is a major risk factor for postoperative morbidity and mortality and receipt of blood transfusion is associated with serious risks including an association with long-term cancer recurrence and overall survival. In addition, blood products are scarce and associated with appreciable expense; decreasing blood transfusion requirements would therefore have health system benefits. Tranexamic acid (TXA), an antifibrinolytic, has been shown to reduce the probability of receiving a blood transfusion by one-third for patients undergoing cardiac or orthopaedic surgery. However, its applicability in liver resection has not been widely researched. Methods and analysis This protocol describes a prospective, blinded, randomised controlled trial being conducted at 10 sites in Canada and 1 in the USA. 1230 eligible and consenting participants will be randomised to one of two parallel groups: experimental (2 g of intravenous TXA) or placebo (saline) administered intraoperatively. The primary endpoint is receipt of blood transfusion within 7 days of surgery. Secondary outcomes include blood loss, postoperative complications, quality of life and 5-year disease-free and overall survival. Ethics and dissemination This trial has been approved by the research ethics boards at participating centres and Health Canada (parent control number 177992) and is currently enrolling participants. All participants will provide written informed consent. Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov. Trial registration number NCT02261415 .

Introduction: Accurate stroke volume (SV) calculation is critical for calculating aortic valve area by echocardiography. 2D-Doppler estimation of SV (SV 2D ) assumes uniform blood flow velocities through the left ventricular outflow tract (LVOT). Non-uniform flow through the LVOT, appreciated as spectral broadening of the LVOT Doppler signal, could result in inaccurate SV calculation. Hypothesis: Increased spectral broadening in the LVOT will result in overestimation of SV by the SV 2D method compared to 3D volumetric assessment of SV (SV 3D ). Methods: Fifty-one consecutive patients with aortic stenosis underwent comprehensive 2D-TTE and assessment of SV 3D . Patients with ≥ moderate mitral or aortic regurgitation were excluded. An LVOT pulse-wave Doppler signal with > 0.4 m/s difference between outer and inner edge of velocity spectral display (at time of peak velocity) was considered non-uniform flow (i.e., spectral broadening). Results: Spectral broadening was present in 33% of the cohort. These patients were commonly female with smaller ventricles and higher ejection fraction. Spectral broadening was associated with a significant overestimation of SV on Doppler-based measurements (101±20 ml vs 78±15 mL, SV 2D vs SV 3D , respectively; r=0.83, p<0.0001); such differences were not seen in patients with uniform flow velocities (82±15 vs 79±14 mL, r=0.83, p=0.03). Patient characteristics by spectral broadening are shown in table 1. Conclusion: In aortic stenosis patients with non-uniform flow, Doppler-based methods overestimated SV by 29.5% on average (maximum 64%) when compared to 3D methods. This results in a proportional increase in calculated valve area despite a similar mean gradient between groups. Substituting SV 3D resulted in similar SV, valve area, and mean gradient between uniform and non-uniform groups. When spectral broadening >0.40 cm/s is present, 3D volumetric assessment of SV should be considered for accurate estimation of aortic valve area.

Background— It is presumed that echocardiographic laboratory accreditation leads to improved quality, but there are few data. We sought to compare the quality of echocardiographic examinations performed at accredited versus nonaccredited laboratories for the evaluation of valvular heart disease. Methods and Results— We enrolled 335 consecutive valvular heart disease subjects who underwent echocardiography at our institution and an external accredited or nonaccredited institution within 6 months. Completeness and quality of echocardiographic reports and images were assessed by investigators blinded to the external laboratory accreditation status and echocardiographic results. Compared with nonaccredited laboratories, accredited sites more frequently reported patient sex (94% versus 78%; P <0.001), height and weight (96% versus 63%; P <0.001), blood pressure (86% versus 39%; P <0.001), left ventricular size (96% versus 83%; P <0.001), right ventricular size (94% versus 80%; P =0.001), and right ventricular function (87% versus 73%; P =0.006). Accredited laboratories had higher rates of complete and diagnostic color (58% versus 35%; P =0.002) and spectral Doppler imaging (45% versus 21%; P <0.0001). Concordance between external and internal grading of external studies was improved when diagnostic quantification was performed (85% versus 69%; P =0.003), and in patients with mitral regurgitation, reproducibility was improved with higher quality color Doppler imaging. Conclusions— Accredited echocardiographic laboratories had more complete reporting and better image quality, while echocardiographic quantification and color Doppler image quality were associated with improved concordance in grading valvular heart disease. Future quality improvement initiatives should highlight the importance of high-quality color Doppler imaging and echocardiographic quantification to improve the accuracy, reproducibility, and quality of echocardiographic studies for valvular heart disease.

Background— Quadricuspid aortic valve (QAV) is a rare congenital cardiac defect. This study sought to determine QAV frequency in a large echocardiography database, to characterize associated cardiovascular abnormalities, and to describe long-term outcomes. Methods and Results— Fifty patients (mean±SD age, 43.5±21.8 years at the time of the index diagnosis; female sex, 52%) received a diagnosis of QAV between January 1, 1975, and March 14, 2014 (frequency, 0.006%). The QAV was type A in 32% and type B in 32% (Hurwitz and Roberts classification). Aortic dilatation was present in 29% of the patients, and 26% had moderate or severe aortic valve regurgitation at the index diagnosis. Stenosis affected only 8% of the valves and was mild. Other findings, including abnormalities of other cardiac valves, septal defects, persistent left superior vena cava, and patent ductus arteriosus, were present in 32% of patients. During a mean±SD follow-up of 4.8±5.6 years, 8 patients underwent aortic valve surgery, with severe aortic valve regurgitation being the surgical indication in 7 patients. One patient with mild to moderate aortic valve regurgitation underwent aortic valve repair for obstruction of the left coronary ostium by the accessory cusp of QAV. No infective endocarditis or aortic dissection was found. Overall survival was 91.5% and 87.7% at 5 and 10 years. Conclusions— Aortic dilatation and other structural cardiac abnormalities were relatively common among patients with QAV. Aortic valve regurgitation was the predominant hemodynamic abnormality and the indication for aortic valve surgery in most patients who received surgery. Long-term survival was excellent.

Background— Low-flow, low-gradient aortic stenosis (AS), associated with a poor prognosis, can be caused by a reduced stroke volume despite a preserved ejection fraction (left ventricular ejection fraction). We hypothesized that impaired ventricular diastolic filling secondary to constrictive pericarditis (CP) could contribute to reduced transaortic gradients in patients with AS+CP. We sought to examine the characteristics and outcomes of this unique cohort. Methods and Results— We analyzed 84 patients with different degrees of AS and preserved left ventricular ejection fraction (≥50%): 28 diagnosed with concomitant CP by echocardiography and 56 patients without CP matched by age, sex, and AS severity during 1998 to 2013. Prior mediastinal radiation (32.1% versus 5.4%; P =0.0072) and cardiac surgery (50.0% versus 3.6%; P =0.0016) were more common in AS+CP patients than those with AS only. AS+CP patients had lower left ventricular stroke volume index and mean transaortic gradients. Five-year survival was 34.3% for AS+CP patients and 89.1% for those with AS only ( P <0.001). In univariate analysis, prior mediastinal radiation (hazard ratio, 8.35; 95% confidence interval, 3.38–20.62; P <0.001), reduced left ventricular stroke volume index of <35 mL/m 2 (hazard ratio, 12.52; 95% confidence interval, 3.97–39.48; P <0.001), and concomitant CP (hazard ratio, 13.65; 95% confidence interval, 4.85–38.41; P <0.001) were highly associated with increased mortality. Conclusions— Our findings highlighted the possibility of CP as a pathophysiological mechanism for low-flow, low-gradient AS. Left ventricular stroke volume index and transaortic gradients were commonly reduced in AS in the setting of CP despite a preserved left ventricular ejection fraction, which may result in underestimation of AS severity. Prior mediastinal radiation, lower left ventricular stroke volume index, and concomitant CP were associated with poorer survival in AS patients.