Citations

Background— Despite its salutary effects on health, aerobic exercise is often avoided after receipt of an implantable cardioverter defibrillator (ICD) because of fears that exercise may provoke acute arrhythmias. We prospectively evaluated the effects of a home aerobic exercise training and maintenance program (EX) on aerobic performance, ICD shocks, and hospitalizations exclusively in ICD recipients. Methods and Results— A total of 160 patients (124 men and 36 women) were randomly assigned who had an ICD for primary (43%) or secondary (57%) prevention to EX or usual care (UC). The primary outcome was peak oxygen consumption, measured with cardiopulmonary exercise testing at baseline and 8 and 24 weeks. EX consisted of 8 weeks of home walking for 1 h/d, 5 d/wk at 60% to 80% of heart rate reserve, followed by 16 weeks of maintenance home walking for 150 min/wk. Adherence to EX was determined from exercise logs, ambulatory heart rate recordings of exercise, and weekly telephone contacts. Patients assigned to UC received no exercise directives and were monitored by monthly telephone contact. Adverse events were identified by ICD interrogations, patient reports, and medical charts. ICD recipients averaged 55±12 years and mean ejection fraction of 40.6±15.7; all were taking β-blocker medications. EX significantly increased peak oxygen consumption (EX, 26.7±7.0 mL/kg per minute; UC, 23.9±6.6 mL/kg per minute; P =0.002) at 8 weeks, which persisted during maintenance exercise at 24 weeks (EX, 26.9±7.7 mL/kg per minute; UC, 23.4±6.0 mL/kg per minute; P <0.001). ICD shocks were infrequent (EX=4 versus UC=8), with no differences in hospitalizations or deaths between groups. Conclusions— Prescribed home exercise is safe and significantly improves cardiovascular performance in ICD recipients without causing shocks or hospitalizations. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00522340.

Background and aim Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any. Methods The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria. Results 112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was −13.0% for CXB+DFMO and −1.0% for CXB (p=0.69). Mean % change in adenoma burden was −40% (CXB+DFMO) vs −27% (CXB) (p=0.13). Video-based global polyp change was −0.80 for CXB+DFMO vs −0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02). Conclusions CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves. Trial registration number ClinicalTrials.gov number N01-CN95040.

In the past decade, impressive strides have been made in the diagnosis and management of atherosclerotic, aneurysmal, and thromboembolic diseases, thanks in large part to the explosive growth in both vascular biology and clinical vascular medicine. We review what we consider to be the top 12 advances in this field: the discovery of nitric oxide, the metabolic syndrome, new thrombophilic disorders, therapeutic angiogenesis, endoluminal treatment of chronic venous disease, and a variety of drugs, including sildenafil, cilostazol, low-molecular-weight heparins, oral direct thrombin inhibitors, clopidogrel, statins, and angiotensin-converting enzyme inhibitors and angiotensin-receptor blocking agents.

Purpose: To investigate the natural history of dilated common iliac arteries (CIA) exposed to pulsatile blood flow after endovascular abdominal aortic aneurysm repair (EVAR) and the suitability of ectatic iliac arteries as sealing zones using flared iliac limbs. Methods: Follow-up computed tomograms of 102 CIAs in 60 EVAR patients were investigated. Diameter changes in CIAs ≤16 mm (group 1) were compared with changes in vessels where a dilated segment >16 mm in diameter continued to be exposed to pulsatile blood flow (group 2). Within group 2, cases in which the stent terminated proximal to the dilated artery segment (2a) were compared with those that had been treated with a flared limb (2b). Results: The mean CIA diameter increased by 1.0±1.0 mm in group 1 (p<0.001 versus immediately after EVAR) and by 1.5±1.7 mm in group 2 (p<0.001 versus immediately after EVAR) within an average follow-up of 43.6±18.0 months. Diameter increase was more pronounced in dilated CIAs (p=0.048), and it was not significantly different between groups 2a and 2b (p=0.188). No late distal type I endoleak or stent-graft migration associated with CIA ectasia was observed. Conclusion: Dilatation of the CIA is significant after EVAR, and it is more pronounced in ectatic iliac arteries. Although ectatic iliac arteries appear to be suitable sealing zones in the short term, continued follow-up is mandatory.

Purpose: To analyze the 2-year outcomes of female patients after endovascular aortic aneurysm repair (EVAR) with the Zenith AAA Endovascular Graft. Methods: A retrospective analysis was conducted of data from the US Zenith multicenter trial and the Zenith female registry on 40 women (10.9%, study group) and 326 men (89.1%, control group) enrolled. All patients had completed their 2-year follow-up. Primary study endpoints were survival, aneurysm rupture, and conversion rate. Significance was assumed if p<0.05. Results: Overall rates of mortality (12.5% for women versus 13.2% for men, p=0.94) and aneurysm rupture (2.5% for women versus 0% for men, p=0.11) were comparable between groups. Conversion to open repair within 2 years was significantly more frequent in women compared to men (7.5% versus 0.6%, p=0.01). The incidence of endoleaks of any type was equivalent between groups at 2 years (13.3% for women versus 6.9% for men, p=0.30). No difference was observed in the need for secondary interventions (15% for women versus 13.5% for men, p=0.81) or aneurysm dilatation >5 mm (10.5% for women versus 2.3% for men, p=0.10). None of the patients developed device migration .10 mm or required intervention for migration. Conclusion: While women underwent conversion to open repair more frequently compared to men at 2 years post EVAR, there was no difference in survival, freedom from aneurysm rupture, or need for secondary interventions between groups. As in men, the Zenith AAA Endovascular Graft provides reliable protection from aneurysm rupture and aneurysm-related death in women in a midterm follow-up.

AbstractObjectives:Data suggest physicians poorly assess disease‐specific literacy and transition readiness in pediatric patients with inflammatory bowel disease (IBD). We piloted an electronic, interactive iPad quiz game that could be used in a clinical setting, with the aims of measuring IBD‐related knowledge, and concomitant mood and quality of life (QOL) in a pediatric population.Methods:Two pediatric IBD clinics developed and tested 2 versions of “Emma.” Patients between 10 and 18 years of age played Emma during an office visit. Each patient answered 12 randomly selected disease‐related questions and 4 mood‐related questions.Results:Sites 1 and 2 tested Emma v1 between May and August 2013. Emma v2 was tested from November 2013 to January 2014 and from September 2013 to January 2014. A total of 56 patients played Emma v1, whereas 60 played Emma v2. In Emma v2, 73.1% of questions were answered correctly. Patients recognized signs of IBD (88%), causes of diarrhea in addition to IBD (79.4%), and could define lactose intolerance (95.8%), but fewer patients understood serological testing used for disease monitoring (68%) or knew that magnetic resonance enterography did not involve radiation (22.9%). Patients tended to report good functioning in the areas of energy, mood, anxiety, and school‐related QOL. Patients with Crohn disease, however, reported higher stress levels compared with patients with ulcerative colitis; older patients reported lower energy levels, and postsurgical patients reported lower QOL.Conclusions:The Emma iPad game has the potential to evaluate gaps in IBD knowledge, assess emotional functioning, and increase patient engagement as a transition tool in the clinical setting.

Abstract Purpose: BNC105P inhibits tubulin polymerization, and preclinical studies suggest possible synergy with everolimus. In this phase I/II study, efficacy and safety of the combination were explored in patients with metastatic renal cell carcinoma (mRCC). Experimental Design: A phase I study in patients with clear cell mRCC and any prior number of therapies was conducted using a classical 3 + 3 design to evaluate standard doses of everolimus with increasing doses of BNC105P. At the recommended phase II dose (RP2D), patients with clear cell mRCC and one to two prior therapies (including ≥ 1 VEGF-TKI) were randomized to BNC105P with everolimus (arm A) or everolimus alone (arm B). The primary endpoint of the study was 6-month progression-free survival (6MPFS). Secondary endpoints included response rate, PFS, overall survival, and exploratory biomarker analyses. Results: In the phase I study (N = 15), a dose of BNC105P at 16 mg/m2 with everolimus at 10 mg daily was identified as the RP2D. In the phase II study, 139 patients were randomized, with 69 and 67 evaluable patients in arms A and B, respectively. 6MPFS was similar in the treatment arms (arm A: 33.82% vs. arm B: 30.30%, P = 0.66) and no difference in median PFS was observed (arm A: 4.7 mos vs. arm B: 4.1 mos; P = 0.49). Changes in matrix metalloproteinase-9, stem cell factor, sex hormone-binding globulin, and serum amyloid A protein were associated with clinical outcome with BNC105P. Conclusions: Although the primary endpoint was not met in an unselected population, correlative studies suggest several biomarkers that warrant further prospective evaluation. Clin Cancer Res; 21(15); 3420–7. ©2015 AACR.

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