The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. OBJECTIVE: The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. METHODS AND DESIGN: CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DISCUSSION: Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. TRIAL REGISTRATION NUMBER: NCT04181996.

Computed tomographic coronary angiography for patients with heart failure (CTA-HF): a randomized controlled trial (IMAGE HF Project 1-C).

BACKGROUND: The prevalence of heart failure (HF) is rising in industrialized and developing countries. Though invasive coronary angiography (ICA) remains the gold standard for anatomical assessment of coronary artery disease in HF patients, alternatives are being sought. Computed tomographic coronary angiography (CTA) has emerged as an accurate non-invasive diagnostic tool for coronary artery disease (CAD) and has been demonstrated to have prognostic value. Whether or not CTA can be used in HF patients is unknown. Acknowledging the aging population, the growing prevalence of HF and the increasing financial burden of healthcare, we need to identify non-invasive diagnostic tests that are available, safe, accurate and cost-effective. METHODS/DESIGN: The proposed study aims to provide insight into the efficacy of CTA in HF patients. A multicenter randomized controlled trial will enroll 250 HF patients requiring coronary anatomical definition. Enrolled patients will be randomized to either CTA or ICA (n = 125 per group) as the first test to define coronary anatomy. The primary outcomes will be collected to determine downstream resource utilization. Secondary outcomes will include the composite clinical events and major adverse cardiac events. In addition, the accuracy of CTA for detecting coronary anatomy and obstruction will be assessed in patients who subsequently undergo both CTA and ICA. It is expected that CTA will be a more cost-effective strategy for diagnosis: yielding similar outcomes with fewer procedural risks and improved resource utilization. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01283659. Team grant #CIF 99470.

Altered myocardial glucose utilization and the reverse mismatch pattern on rubidium-82 perfusion/F-18-FDG PET during the sub-acute phase following reperfusion of acute anterior myocardial infarction.

BACKGROUND: Reperfused myocardium post-acute myocardial infarction (AMI) may have altered metabolism with implications for therapy response and function recovery. We explored glucose utilization and the "reverse mismatch" (RMM) pattern (decreased F-18-fluorodeoxyglucose (FDG) uptake relative to perfusion) in patients who underwent mechanical reperfusion with percutaneous coronary intervention (PCI) for AMI. METHODS AND RESULTS: Thirty-one patients with anterior wall AMI treated with acute reperfusion, with left ventricular ejection fraction ≤45%, underwent rest rubidium-82 (Rb-82) and FDG PET 2-10 days post-AMI. Resting echocardiograms were used to assess wall motion abnormalities. Significant RMM occurred in 15 (48%) patients and was associated with a shorter time to PCI of 2.9 hours (2.2, 13.3 hours) compared to patients without significant RMM: 11.4 hours (3.9, 22.4 hours) (P = .03). Within the peri-infarct regions, segments with significant RMM were more likely to have wall motion abnormalities (OR = 2.3 (1.1, 4.7), P = .02) compared to segments without significant RMM. CONCLUSIONS: RMM is a common pattern on perfusion/FDG PET during the sub-acute phase following reperfusion of AMI and is associated with shorter times to PCI. Within the peri-infarct region, RMM occurs frequently and is more often associated with wall motion abnormalities than segments without RMM. Whether this represents a myocardial metabolic shift during the sub-acute phase of recovery warrants further study.

Managing varicoceles in children: results with microsurgical varicocelectomy.

UNLABELLED: Authors from New York present their experience of elective varicocelectomy, using microsurgical techniques, in a large series of children. They found the procedure to be safe and effective, and gave a much lower complication rate than the published rate in open varicocelectomy. The results of urethroplasty in post-traumatic paediatric urethral strictures are presented by authors from Mansoura. They found the overall success of one-stage perineal anastomotic repair of such strictures to be excellent, with very little morbidity. OBJECTIVE: To report our experience of microsurgical subinguinal varicocelectomy in boys aged < or = 18 years. PATIENTS AND METHODS: Boys aged < or = 18 years treated with microsurgical varicocelectomy between 1996 and 2000 at one institution were retrospectively reviewed. Indications for surgery included ipsilateral testicular atrophy, large varicocele or pain. Microsurgery was assisted by an operating microscope (x10-25) allowing preservation of the lymphatics, and the testicular and cremasteric arteries. Patient age, varicocele grade, complications and follow-up interval were recorded. RESULTS: In all there were 97 microsurgical subinguinal varicocelectomies (23 bilateral) in 74 boys (mean age 14.7 years). Left-sided varicoceles were significantly larger (mean grade 2.9) than right-sided (mean grade 1.4) varicoceles. The mean follow-up was 9.6 months. There were four complications: two hydroceles, of which one resolved spontaneously after 4 months; one patient had persistent orchialgia that resolved after 8 months; and one developed hypertrophic scarring at the inguinal incision site. There were no infections, haematomas or intraoperative injuries to the vas deferens or testicular arteries. All boys were discharged home on the day of surgery. CONCLUSIONS: Microsurgical subinguinal varicocelectomy in boys is a safe, minimally invasive and effective means of treating varicoceles. Compared with published results of the retroperitoneal mass ligation technique, which has a 15% overall complication rate and a 7-9% hydrocele occurrence rate, the microsurgical subinguinal approach appears to offer less morbidity, with a 1% hydrocele rate. We consider that microsurgical subinguinal varicocelectomy offers the best results with lower morbidity than other techniques.

Nerve sparing extravesical repair of bilateral vesicoureteral reflux: description of technique and evaluation of urinary retention.

PURPOSE: Prolonged urinary retention remains a controversial and feared complication following bilateral extravesical ureteral reimplantation. We report a modified approach to limit detrusor nerve damage during extravesical correction of bilateral ureteral reflux that significantly reduces this adverse outcome. MATERIALS AND METHODS: A modified approach to the distal detrusor dissection and ureteral mobilization, along with limited periureteral dissection, was used to perform this technique. A retrospective review of 50 patients undergoing bilateral nerve sparing extravesical ureteral reimplantation (NSEVR) by a single surgeon between 1997 and 2002 was completed. Patient age, vesicoureteral reflux (VUR) grade, length of hospital stay, length of surgery and outcome were evaluated. RESULTS: The study included 36 girls and 14 boys, with an average age of 4 years 11 months (range 1 to 14 years). Average preoperative VUR grade was 2.61 (range 1 to 5). Average length of surgery when NSEVR was the only procedure performed was 105 minutes (range 54 to 185) and average length of hospital stay was 1.76 days (0 to 3). Transient urinary retention developed in 1 child on postoperative day 1, with a successful trial of voiding the next day. The rate of immediate urinary retention was 2%. There was no long-term urinary retention, voiding dysfunction or urinary tract infections. CONCLUSIONS: NSEVR for the correction of bilateral VUR is a simple modification that provides a reproducible and minimally invasive approach to treatment. We believe that limited distal ureteral dissection, preservation of the medial ureterovesical hiatus and judicious manipulation of the surrounding tissues result in elimination of long-term urinary retention.