Ventricular tachycardia characteristics and outcomes with catheter ablation vs. antiarrhythmic therapy: insights from the VANISH trial.

AIMS: Catheter ablation is superior to escalated antiarrhythmic drugs among patients with ventricular tachycardia (VT) and prior myocardial infarction (MI). However, it is uncertain whether clinical VT characteristics, should influence choice of therapy. The purpose of this study was to evaluate whether presentation with electrical storm and the clinical VT cycle length predicted response to ablation vs. escalated antiarrhythmic therapy. METHODS AND RESULTS: All patients enrolled in the Ventricular Tachycardia Ablation vs. Escalated Antiarrhythmic Drug Therapy in Ischaemic Heart Disease (VANISH) trial were included. The association between VT cycle length and presentation with electrical storm and the primary outcome of death, subsequent VT storm or appropriate ICD shock was evaluated. Among the study population of 259 patients, escalated antiarrhythmic drug therapy had worse outcomes for those presenting with a VT cycle length >400 ms [<150 b.p.m., 89/259, hazard ratio (HR) 1.7 (1.02-3.13)]. This effect was more pronounced among those taking amiodarone at baseline [HR of 2.22 (1.19-4.16)]. Presentation with VT storm (32/259) did not affect the primary outcome between groups. However, those presenting with VT storm on amiodarone had a trend towards worse outcomes with escalated antiarrhythmic therapy [HR 4.31 (0.55-33.93)]. CONCLUSION: The VT cycle length can influence response to either ablation or escalated drug therapy in patients with VT and prior MI. Those with slow VT had improved outcomes with ablation. Patients presenting with electrical storm demonstrated similar outcomes to the overall trial population, with a trend to benefit of catheter ablation, particularly in those on amiodarone.

White blood cell count trajectory and mortality in septic shock: a historical cohort study.

PURPOSE: Septic shock is associated with a mortality of 20-40%. The white blood cell count (WBC) at hospital admission correlates with prognosis in septic shock. Here, we explore whether the trajectory of WBC after admission provides further information about outcomes. We aimed to identify groups of patients with different WBC trajectories and the association of WBC trajectory with mortality. METHODS: We included adult patients with septic shock in two academic intensive care units (ICU) in Winnipeg, MB, Canada between 2006 and 2012. We used group-based trajectory analysis to group patients according to their WBC patterns over the first seven days in the ICU. Our primary analysis was the association of WBC trajectory group on 30-day mortality using multivariable Cox proportional hazards regression. RESULTS: We included 917 patients with septic shock. The final model identified seven distinct WBC trajectories. The rising WBC trajectory was independently associated with increased mortality (hazard ratio, 3.41; 95% confidence interval, 1.86 to 6.26; P < 0.001) compared with the stable WBC trajectory. CONCLUSION: In patients with septic shock, distinct and clinically relevant groups can be identified by analyzing WBC trajectories. A rising WBC trajectory was associated with higher mortality.

RéSUMé: OBJECTIF: Le choc septique est associé à une mortalité de 20 à 40 %. La numération leucocytaire à l'admission à l'hôpital est corrélée au pronostic en cas de choc septique. Dans ce manuscrit, nous tentons de déterminer si l'évolution de la numération leucocytaire après l'admission fournit plus d'informations sur les devenirs. Nous avons cherché à identifier des groupes de patients présentant différentes trajectoires d'évolution de numération leucocytaire et l'association entre l'évolution de la numération et la mortalité. MéTHODE: Nous avons inclus des patients adultes atteints d'un choc septique dans deux unités de soins intensifs (USI) universitaires à Winnipeg, Manitoba, Canada entre 2006 et 2012. Nous avons utilisé une analyse de l'évolution basée sur le groupe pour regrouper les patients en fonction du type d'évolution de la numération leucocytaire au cours des sept premiers jours à l'USI. Notre analyse principale consistait à déterminer l'association entre le groupe d'évolution de numération leucocytaire et la mortalité à 30 jours en utilisant une régression multivariable à risque proportionnel de Cox. RéSULTATS: Nous avons inclus 917 patients atteints de choc septique. Le modèle final a identifié sept types de trajectoire d'évolution de numération leucocytaire distincts. Une évolution ascendante de la numération leucocytaire était indépendamment associée à une augmentation de la mortalité (rapport de risque, 3,41; intervalle de confiance à 95 %, 1,86 à 6,26; P < 0,001) par rapport à une évolution de numération leucocytaire stable. CONCLUSION: Chez les patients atteints de choc septique, des groupes distincts et cliniquement pertinents peuvent être identifiés en analysant les trajectoires d'évolution de la numération leucocytaire. Une évolution ascendante de la numération leucocytaire était associée à une mortalité plus élevée.

Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty.

BACKGROUND: Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge. METHODS: We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome). RESULTS: A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43). CONCLUSIONS: Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Exercise training and reproductive outcomes in women with polycystic ovary syndrome: A pilot randomized controlled trial.

OBJECTIVE: Exercise is recommended for polycystic ovary syndrome (PCOS), but the most effective exercise prescription is unclear. This trial compared effects of high-intensity interval training (HIIT), continuous aerobic exercise training (CAET) and no-exercise control on reproductive, anthropometric and cardiometabolic outcomes in PCOS. DESIGN: Pilot randomized controlled trial. PARTICIPANTS: Previously inactive women aged 18-40 years with PCOS. MEASUREMENTS: Feasibility outcomes included recruitment, retention, adherence to exercise and daily ovulation prediction kit (OPK) testing. Preliminary efficacy outcomes included reproductive, anthropometric and cardiometabolic health markers. RESULTS: Forty-seven women were randomized to no-exercise control (n = 17), HIIT (n = 16), or CAET (n = 14). Forty (85%) participants completed the trial. Median exercise adherence was 68% (IQR 53%, 86%). Median daily OPK-testing adherence in the first half of the intervention was 87% (IQR 61%, 97%) compared with 65% (IQR 0%, 96%) in the second half. Body mass index decreased significantly in CAET compared with control (-1.0 kg/m2 , p = .01) and HIIT (-0.9 kg/m2 , p = .04). Mean waist circumference decreased in all groups (-7.3 cm, -6.9 cm, -4.5 cm in HIIT, CAET and control) with no significant between-group differences. Mean LDL-C was significantly reduced for HIIT compared to CAET (-0.33 mmol/L, p = .03). HDL-C increased in HIIT compared with control (0.18 mmol/L, p = .04). CONCLUSIONS: There were feasibility challenges with adherence to daily ovulation assessment limiting the ability to analyse the effect of the exercise interventions on ovulation. CAET and HIIT were both effective at improving anthropometrics and some cardiometabolic health markers. Further studies need to determine optimal and acceptable exercise prescriptions for this population.

Predicting acute kidney injury following nonemergent cardiac surgery: A preoperative scorecard.

OBJECTIVE: To determine the predictors of postoperative acute kidney injury (AKI) following nonemergent cardiac surgery among patients with variable preoperative estimated glomerular filtration rate (eGFR) levels. METHODS: A retrospective study of patients who underwent elective or in-hospital cardiac surgical procedures was performed between January 2006 and November 2015. The procedures included isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR), or combined CABG and AVR. The primary outcome AKI (any stage) following nonemergent cardiac surgery utilizing the 2012 Kidney Disease-Improving Global Outcomes (KDIGO) criteria. Patients were categorized based on the following renal outcomes: mild AKI, severe AKI (KDIGO stage 2 or 3), and postoperative dialysis. Patients with G5 preoperative kidney function (including dialysis patients) were excluded. RESULTS: A total of 6675 patients were included in our study. The mean age was 66.8 years (SD ± 10.4), with 76.3% being males. A total of 4487 patients had normal or mildly decreased eGFR (G1 or G2) preoperatively (67.2%), while 1960 patients were in the G3 category (29.4%). Only 228 patients (3.4%) had G4 renal function. A total of 1453 (21.7%) patients experienced postoperative AKI. The need for postoperative dialysis occurred in 3.2% of the AKI subgroup. In-hospital mortality was higher among the AKI subgroup (7.2% vs. 0.5%; p < .0001). In an adjusted model, a lower preoperative eGFR category was the strongest predictor of AKI. A practical scorecard for the preoperative estimation of severe AKI for nonemergent cardiac procedures incorporating these parameters was developed. CONCLUSIONS: Preoperative eGFR is the strongest predictor of postoperative AKI in individuals undergoing nonemergent cardiac surgery. A practical scorecard incorporating preoperative predictors of AKI may allow informed decision-making and predict AKI following nonemergent cardiac surgery.

The effect of revascularization on mortality and risk of ventricular arrhythmia in patients with ischemic cardiomyopathy.

BACKGROUND: There is clear evidence that patients with prior myocardial infarction and a reduced ejection fraction benefit from implantation of a cardioverter-defibrillator (ICD). It is unclear whether this benefit is altered by whether or not revascularization is performed prior to ICD implantation. METHODS: This was a retrospective cohort study following patients who underwent ICD implantation from 2002 to 2014. Patients with ischemic cardiomyopathy and either primary or secondary prevention ICDs were selected for inclusion. Using the electronic medical record, cardiac catheterization data, revascularization status (percutaneous coronary intervention or coronary bypass surgery) were recorded. The outcomes were mortality and ventricular arrhythmia. RESULTS: There were 606 patients included in the analysis. The mean age was 66.3 ± 10.1 years, 11.9% were women, and the mean LVEF was 30.5 ± 12.0, 58.9% had a primary indication for ICD, 82.0% of the cohort had undergone coronary catheterization prior to ICD implantation. In the overall cohort, there were fewer mortality and ventricular arrhythmia events in patients who had undergone prior revascularization. In patients who had an ICD for secondary prevention, revascularization was associated with a decrease in mortality (HR 0.46, 95% CI (0.24, 0.85) p = 0.015), and a trend towards fewer ventricular arrhythmia (HR 0.62, 95% CI (0.38, 1.00) p = 0.051). There was no association between death or ventricular arrhythmia with revascularization in patients with primary prevention ICDs. CONCLUSION: Revascularization may be beneficial in preventing recurrent ventricular arrhythmia, and should be considered as adjunctive therapy to ICD implantation to improve cardiovascular outcomes.

Secondary pituitary hormonal dysfunction patterns: tumor size and subtype matter.

PURPOSE: Patients with sellar masses (SM) frequently have secondary hormonal deficiency (SHD) at initial presentation. While larger SM are more likely to present with SHD, it is unclear whether SHD at presentation is influenced by the type of SM. METHODS: We conducted a retrospective analysis of patients with SM prospectively enrolled in our comprehensive provincial neuropituitary registry between November 2005 and December 2018. SM were subdivided based on size: < 1 cm, 1-1.9 cm, 2-2.9 cm, and > 3 cm. RESULTS: A total of 914 patients met the inclusion criteria, including: 346 nonfunctioning adenomas (NFA), 261 prolactinomas (PRLoma), 51 growth hormone adenomas, 36 adrenocorticotropic adenomas, 93 Rathke's cleft cysts, 70 craniopharyngiomas and 57 meningiomas. The overall rate of SHD at presentation was highest in PRLoma (62.8%) and craniopharyngiomas (64.3%) and lowest in meningiomas (14%). While larger SM were significantly more likely to have SHD, the rate of SHD within each group was significantly different despite similar size (p < 0.001). Of the two largest groups of SM (NFA and PRLoma), NFA had significantly higher odds ratio (3.34, CI 1.89-5.89) of having multiple SHDs when compare with PRLoma, even when corrected for age, gender and size of tumor (p < 0.001). CONCLUSION: Our study shows that the rate and distribution of SHD in SM vary dependent upon the size of the tumor and specific pathology; in particular, NFA are more likely to present with multiple SHDs. Our data will help clinicians in determining adequate hormonal testing strategy for different SM.

Six-year follow-up of aortic valve reoperation rates: Carpentier-Edwards Perimount versus St. Jude Medical Trifecta.

BACKGROUND: The Carpentier-Edwards Perimount valves have a proven track record in aortic valve replacement: good durability, hemodynamic performance, rates of survival, and low rates of valve-related complications and prosthesis-patient mismatch. The St. Jude Medical Trifecta is a newer valve that has shown comparable early and midterm outcomes. Studies show reoperation rates of Trifecta are comparable with Perimount valves, with a few recent studies bringing into focus early structural valve deterioration (SVD), and increased midterm SVD in younger patients. Given that midterm data for Trifecta is still sparse, we wanted to confirm the early low reoperation rates of Trifecta persist over time compared with Perimount. METHODS: The Maritime Heart Centre Database was searched for AVR between 2011 and 2016, inclusive. The primary endpoint of the study was all-cause reoperation rate. RESULTS: In total, 711 Perimount and 453 Trifecta implantations were included. The reoperation hazards were determined for age: 0.96 (0.92-0.99; p = .02), female (vs. male): 0.35 (0.08-1.53; p = .16), smoker (vs. nonsmoker): 2.44 (0.85-7.02; p = .1), and Trifecta (vs. Perimount): 2.68 (0.97-7.39; p = .06). Kaplan-Meier survival analysis in subgroups-age <60, age ≥60, male, female, smoker, and nonsmoker-showed Perimount having lower reoperation rates than Trifecta in patients younger than 60 (p = .02) and current smokers (p < .01). CONCLUSIONS: The rates of reoperation of Perimount and Trifecta were comparable, with Trifecta showing higher rates in patients younger than 60 years, and current smokers. Continued diligence and further independent reporting of midterm reoperation and SVD rates of the Trifecta, including detailed echocardiographic follow-up, are needed to confirm these findings.

A contemporary description of patients' estimated blood losses from diagnostic phlebotomy in a census of hospital episodes from a Canadian tertiary care center.

BACKGROUND: Phlebotomy for diagnostic testing is among the commonest hospital procedures, but hospital-wide surveys of all inpatients characterizing blood draw volumes have not been published. The objectives were to characterize the daily blood volumes drawn for diagnostic testing from patients discharged from a Canadian tertiary care center, describe the daily distributions of phlebotomy volumes across service locations, and describe changes in hemoglobin (Hb) and transfusion across service locations. STUDY DESIGN AND METHODS: Data were obtained on all patients discharged between 2012 and 2014 using linked discharge abstract and laboratory data. Cumulative daily blood volume and draw frequency were reported by service and days since admission. Changes in Hb and red blood cell (RBC) transfusion rates were reported for nontransfused and transfused patients. RESULTS: Data were included on 59,715 subjects. Mean daily estimated blood loss varied from 8.5 ± 6.5 mL/day onward to 27.2 ± 20.0 mL/day in the intensive care unit (ICU; p < 0.001). Phlebotomy volumes were highest on the first day of admission and declined thereafter (p < 0.001). For nontransfused individuals in the first week of admission, Hb levels decreased by the highest percentage in the ICU. The rate of RBC unit transfusion was highest in the ICU (232.4 units/1000 patient-days; 95% confidence interval, 225.8-239.2; p < 0.0001 compared with all other locations). CONCLUSION: Considerable variation was observed in estimated blood loss due to diagnostic phlebotomy across different services within one teaching hospital. Thi information is foundational for planning interventions to minimize estimated blood loss from phlebotomy.

Comparative effects of different whole grains and brans on blood lipid: a network meta-analysis.

PURPOSE: The comparative effects of different whole grains and brans on blood lipid are still not totally elucidated. We aimed to estimate and rank the effects of different whole grains and brans on the control of blood lipid. METHODS: We performed a strategic literature search of PubMed, EMBASE and the Cochrane Library for relevant trials. Both pairwise meta-analyses and network meta-analyses were conducted to compare and rank the intervention strategies of whole grains and brans for the control of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TG). RESULTS: Fifty-five eligible trials with a total of 3900 participants were included. Cumulative ranking analyses showed that oat bran was the most effective intervention strategy for TC and LDL-C improvements, with significant decreases of - 0.35 mmol/L (95% CI - 0.47, - 0.23 mmol/L) and - 0.32 mmol/L (95% CI - 0.44, - 0.19 mmol/L) in TC and LDL-C compared with control, respectively. In comparison with control, oat was associated with significant reductions in TC by - 0.26 mmol/L (95% CI - 0.36, - 0.15 mmol/L) and LDL-C by - 0.17 mmol/L (95% CI - 0.28, - 0.07 mmol/L), which was ranked as the second best treatment. Barley, brown rice, wheat and wheat bran were shown to be ineffective in improving blood lipid compared with control. CONCLUSIONS: This network meta-analysis suggests that oat bran and oat are ranked higher than any other treatments for the regulations of TC and LDL-C, indicating that increasing oat sources of whole grain may be recommended for lipid control.

Relationships Between Wheelchair Services Received and Wheelchair User Outcomes in Less-Resourced Settings: A Cross-Sectional Survey in Kenya and the Philippines.

OBJECTIVE: To explore the relationships between wheelchair services received during wheelchair provision and positive outcomes for users of wheelchairs. DESIGN: Secondary analysis of cross-sectional data. SETTING: Urban and periurban communities in Kenya and the Philippines. PARTICIPANTS: Adult basic manual wheelchair users (N=852), about half of whom reported having received some wheelchair services with the provision of their current wheelchairs. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed a survey that included questions related to demographic, clinical, and wheelchair characteristics. The survey also included questions about the past receipt of 13 wheelchair services and 4 positive outcomes for users of wheelchairs. The relationships between individual services received and positive outcomes were assessed using logistic regression analyses. In addition to assessing individual services and outcomes, we analyzed a composite service score (the total number of services received) and a composite outcome score (≥3 positive outcomes). RESULTS: The top 3 individual services from the perspective of relationships with the composite outcome score were "provider did training" (P=.0009), "provider assessed wheelchair fit while user propelled the wheelchair" (P=.002), and "peer group training received" (P=.033). The composite service score was significantly related to "daily wheelchair use" (P<.0001), "outdoor unassisted wheelchair use" (P<.0001), "high performance of activities of daily living" (P=.046) and the composite outcome score (P=.005), but not to the "absence of serious falls" (P=.73). CONCLUSIONS: The receipt of wheelchair services is associated with positive outcomes for users of wheelchairs, but such relationships do not exist for all services and outcomes. These findings are highly relevant to ongoing efforts to optimize wheelchair service delivery.

Global PD-L1 Signals and Tumor-Infiltrating Lymphocytes: Markers of Immunogenicity in Different Subsets of Merkel Cell Carcinoma and Potential Therapeutic Implications.

We previously studied the genetic and immunohistochemical profiles of subsets of Merkel cell carcinoma (MCC) stratified by morphology and Merkel cell polyomavirus (MCPyV) status. Recent advances in the immunotherapy of this disease prompted us to examine markers of immunogenicity [PD-L1 expression and tumor-infiltrating lymphocytes (TILS) in these subsets]. The observed clinical responses to checkpoint inhibition of the PD-1/PD-L1 pathway have not correlated with PD-L1 expression by MCC cells, and recent evidence suggests that functions of this pathway within the immune tumor microenvironment may be relevant. We conducted a semiquantitative (high, moderate, and minimal) immunohistochemical evaluation of the global PD-L1 signal in 52 cases of MCC, segregated in 3 subsets [pure MCPyV-positive (n = 28), pure MCPyV-negative (n = 9), and combined MCPyV-negative (n = 15)]. TILS were categorized as brisk, nonbrisk, or absent. Intersubset comparisons revealed that high global PD-L1 signals were exclusively associated with pure MCPyV-positive MCCs contrasted with virus-negative cases (P = 0.0003). Moderate signals were seen across all 3 groups. Brisk TILS were significantly associated with MCPyV-positive MCCs compared with MCPyV-negative cases (P = 0.029). Neither parameter (PD-L1 or TILS) was significantly different between the MCPyV-negative groups. Of potential clinical relevance, MCPyV seems to convey greater immunogenicity to MCCs than the high mutational burden/greater neoantigen load of MCPyV-negative cases. Interesting too is the fact that subset-related profiles of these markers mirrored those noted at genetic and immunohistochemical levels, separating pure MCPyV-positive MCCs from the virus-negative subsets.

Mexiletine or catheter ablation after amiodarone failure in the VANISH trial.

INTRODUCTION: In patients with ischemic heart disease and ventricular tachycardia (VT) refractory to high dose amiodarone, the two most common therapeutic options are adjunctive mexiletine therapy or catheter ablation. There are little existing data on the efficacy of these strategies. We examined the relative efficacy of adjunctive mexiletine and catheter ablation among patients enrolled in the VANISH trial. METHODS: All subjects enrolled in the VANISH trial who had VT refractory to high dose (≥ 300 mg daily) amiodarone at baseline were included. Per protocol, subjects randomized to escalated drug therapy received adjunctive mexiletine. RESULTS: Nineteen of the 259 patients were receiving high-dose amiodarone at baseline and 11 were randomized to escalated therapy with mexiletine and 8 to ablation. The adjunctive mexiletine group had a higher rate of the primary composite outcome (death, VT storm, or appropriate shock) in comparison to catheter ablation (HR 6.87 [2.08-22.8]). Over 90% of the patients in the adjunctive mexiletine/group experienced a primary endpoint during a median 9.2 months' follow-up. There was no difference in the rate of adverse events between the two groups. CONCLUSIONS: Mexiletine has limited efficacy in the treatment of recurrent VT despite high-dose amiodarone therapy, in patients with ischemic heart disease. Catheter ablation is a superior strategy in this population.

Quality of life with ablation or medical therapy for ventricular arrhythmias: A substudy of VANISH.

BACKGROUND/OBJECTIVE: We compared health-related quality of life (HRQoL) in patients randomized to escalated therapy and those randomized to ablation for ventricular tachycardia in the VANISH trial. METHODS: HRQoL was assessed among VANISH patients at baseline and 3-, 6-, and 12-month follow-up visits. Four validated instruments were used: the SF-36, the implanted cardioverter defibrillator (ICD) Concerns questionnaire (ICDC), the Hospital Anxiety and Depression Scale (HADS), and the EuroQol five dimensions questionnaire (EQ-5D). Linear mixed-effects modeling was used for repeated measures with SF-36, HADS, ICDC, and EQ-5D as dependent variables. In a second model, treatment was subdivided by amiodarone use prior to enrollment. RESULTS: HRQoL did not differ significantly between those randomized to ablation or escalated therapy. On subgroup analysis, improvement in SF-36 measures was seen at 6 months in the ablation group for social functioning (63.5-69.3, P = 0.03) and energy/fatigue (43.0-47.9, P = 0.01). ICDC measures showed a reduction in ICD concern in the ablation group at 6 months (10.4-8.7, P = 0.01) and a reduction in ICD concern in the escalated therapy group at 6 months (10.9-9.4, P = 0.04). EQ-5D measures showed a significant improvement in overall health in ablation patients at 6 months (63.4-67.3, P = 0.04). CONCLUSION: Patients in the VANISH study randomized to ablation did not have a significant change in quality of life outcomes compared to those randomized to escalated therapy. Some subgroup findings were significant, as those randomized to ablation showed persistent improvement in SF-36 energy/fatigue and ICD concern, and transient improvement in SF-36 social functioning and EQ-5D overall health.

Effect of coronary revascularization on long-term clinical outcomes in patients with ischemic cardiomyopathy and recurrent ventricular arrhythmia.

BACKGROUND: Patients with ventricular tachycardia (VT) postmyocardial infarction (MI) are a higher risk group with significant morbidity and mortality. We examined the impact of prior coronary revascularization on clinical outcomes in patients with ischemic cardiomyopathy and VT. METHODS: The VANISH trial randomized 259 patients with prior MI and antiarrhythmic drug-refractory VT to receive escalated medical therapy or catheter ablation. Clinical outcomes were compared according to whether patients have undergone prior revascularization procedures. The primary outcome was a composite of death, appropriate implantable cardiac defibrillator (ICD) shock, or VT storm. The secondary outcomes included elements of the primary outcome, hospitalization, and any ventricular arrhythmia. RESULTS: 190 patients (73%) had prior coronary revascularization. Revascularization group had more men (97% vs 83%; P  =  0.0003) and patients in that group were older (mean age 69.3 ± 7.6 vs 66.7 ± 9.2; P  =  0.04), had more renal insufficiency (22.6% vs 8.7%; P  =  0.01), and were more likely to have an implanted cardiac resynchronization device (23% vs 10%, P  =  0.03) as compared with the nonrevascularized patients. There were no significant differences in baseline medication use. There was a trend toward fewer hospitalizations in the revascularization group (64% vs 77%; P  =  0.07); there were no differences in the individual outcomes of mortality, VT storm, ICD shocks, recurrent MI, or cardiac failure. CONCLUSIONS: In this cohort of patients with an ischemic cause for VT, a history of prior coronary revascularization was not associated with a reduction in ventricular arrhythmia or mortality.

Changes in the Brain-Derived Neurotrophic Factor Are Associated with Improvements in Diabetes Risk Factors after Exercise Training in Adolescents with Obesity: The HEARTY Randomized Controlled Trial.

Obesity in youth increases the risk of type 2 diabetes (T2D), and both are risk factors for neurocognitive deficits. Exercise attenuates the risk of obesity and T2D while improving cognitive function. In adults, these benefits are associated with the actions of the brain-derived neurotrophic factor (BDNF), a protein critical in modulating neuroplasticity, glucose regulation, fat oxidation, and appetite regulation in adults. However, little research exists in youth. This study examined the associations between changes in diabetes risk factors and changes in BDNF levels after 6 months of exercise training in adolescents with obesity. The sample consisted of 202 postpubertal adolescents with obesity (70% females) aged 14-18 years who were randomized to 6 months of aerobic and/or resistance training or nonexercise control. All participants received a healthy eating plan designed to induce a 250/kcal deficit per day. Resting serum BDNF levels and diabetes risk factors, such as fasting glucose, insulin, homeostasis model assessment (HOMA-B-beta cell insulin secretory capacity) and (HOMA-IS-insulin sensitivity), and hemoglobin A1c (HbA1c), were measured after an overnight fast at baseline and 6 months. There were no significant intergroup differences on changes in BDNF or diabetes risk factors. In the exercise group, increases in BDNF were associated with reductions in fasting glucose (ß = -6.57, SE = 3.37, p = 0.05) and increases in HOMA-B (ß = 0.093, SE = 0.03, p = 0.004) after controlling for confounders. No associations were found between changes in diabetes risk factors and BDNF in controls. In conclusion, exercise-induced reductions in some diabetes risk factors were associated with increases in BDNF in adolescents with obesity, suggesting that exercise training may be an effective strategy to promote metabolic health and increases in BDNF, a protein favoring neuroplasticity. This trial is registered with ClinicalTrials.gov NCT00195858, September 12, 2005 (funded by the Canadian Institutes of Health Research).

CT Perfusion in Acute Stroke Predicts Final Infarct Volume- Inter-observer Study.

BACKGROUND: Computed tomography perfusion (CTP) is increasingly being used in the setting of acute ischemic stroke (AIS). The aim of the current study was to compare the prognostic utility of, and inter-observer variation between, baseline appearances on non-contrast CT (using Alberta Stroke Program Early CT score(ASPECTS)) and on CTP for predicting final infarct volume. We also assessed impact of training on interpretation of these images. METHODS: Retrospectively, plain head computed tomography (CT) and CTP images at presentation and CT or diffusion imaging on follow up of patients with AIS were analyzed. The lesion volume on different CTP parameters was then correlated with the final infarct volume. This analysis was done by a Neuroradiologist, a stroke Neurologist and a medical student. Kappa statistics and Intra-class correlation coefficients were used for agreement between readers. Pearson correlation coefficients were used. RESULTS: Thirty eight patients with AIS met all inclusion criteria. There was very good agreement among all readers for the CTP parameters. There was only fair agreement for ASPECT score. Correlation coefficient (r-square) between CTP parameters and final infarct volume showed that cerebral blood volume was the best parameter to predict the final infarct volume followed by cerebral blood flow and time to peak. The best reader to predict the final infarct volume on the initial CT perfusion study was the neuroradiologist followed by medical student and stroke neurologist. CONCLUSIONS: Cerebral blood volume defect correlated the best with the final infarct volume. There was a very good inter-observer agreement for all the CTP maps in predicting the final infarct volume despite the wide variation in the experience of the readers.

Sellar Masses: An Epidemiological Study.

BACKGROUND: Sellar masses (SM) are mostly benign growths of pituitary or nonpituitary origin that are increasingly encountered in clinical practice. To date, no comprehensive population-based study has reported the epidemiology of SM from North America. AIM: To determine the epidemiology of SM in the province of Nova Scotia, Canada. METHODS: Data from all pituitary-related referrals within the province were prospectively collected in interlinked computerized registries starting in November 2005. We conducted a retrospective analysis on all patients with SM seen within the province between November 2005 and December 2013. RESULTS: A total of 1107 patients were identified, of which 1005 were alive and residing within the province. The mean age at presentation was 44.6±18 years, with an overall female preponderance (62%) and a population prevalence rate of 0.1%. Of patients with SM, 837 (83%) had pituitary adenomas and 168 (17%) had nonpituitary lesions. The relative prevalence and standardized incidence ratio, respectively, of various SM were: nonfunctioning adenomas (38.4%; 2.34), prolactinomas (34.3%; 2.22), Rathke's cyst (6.5%; 0.5), growth hormone-secreting adenomas (6.5%; 0.3), craniopharyngiomas (4.5%; 0.2), adrenocorticotropic hormone-secreting adenomas (3.8%; 0.2), meningiomas (1.9%), and others (3.9%; 0.21). At presentation, 526 (52.3%) had masses ≥1 cm, 318 (31.6%) at <1 cm, and 11 (1.1%) had functioning pituitary adenomas without discernible tumor, whereas tumor size data were unavailable in 150 (14.9%) patients. The specific pathologies and their most common presenting features were: nonfunctioning adenoma (incidental, headaches, and vision loss), prolactinomas (galactorrhea, menstrual irregularity, and headache), growth hormone-secreting adenomas (enlarging extremities and sweating), adrenocorticotropic hormone-secreting adenoma (easy bruising, muscle wasting, and weight gain) and nonpituitary lesions (incidental, headaches, and vision problems). Secondary hormonal deficiencies were common, ranging from 19.6% to 65.7%; secondary hypogonadism, hypothyroidism, and growth hormone deficiencies constituted the majority of these abnormalities. CONCLUSIONS: This is the largest North American study to date to assess the epidemiology of SM in a large stable population. Given their significant prevalence in the general population, more studies are needed to evaluate the natural history of these masses and to help allocate appropriate resources for their management.