The Return of Actionable Variants Empirical (RAVE) Study,a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results

Objectives

To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.

Retrograde Inversion Stripping as a Complication of the Clarivein? Mechanochemical Venous Ablation Procedure

The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein^® mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein^® device, without adverse sequelae.     

Admission inflammatory markers and isolation of a causative organism in patients with spontaneous spinal infection

Introduction

The purpose of this study was to investigate the significance of the inflammatory markers on admission in the isolation of a causative pathogen in patients with spinal infection. Spinal infection is treated frequently at spinal units and can encompass a broad range of clinical entities. Its diagnosis is often delayed because of the difficulty of identifying the responsible pathogen.

Methods

Patients with spinal infection treated in our institution over a period of eight years were identified and their notes studied retrospectively. Admission C-reactive protein (CRP), white cell count (WCC) as well as co-morbidities and mode of pathogen identification were recorded. Overall, 96 patients were included in the study.

Results

The CRP levels on admission were correlated significantly with the overall potential for isolation of a pathogen (p<0.0001) and positive biopsy cultures (p=0.0016). Admission WCC levels were associated significantly with the overall potential for isolation of a pathogen (p=0.0003) and positive biopsy cultures (p=0.0023). Both CRP and WCC levels were significantly negatively correlated with the duration of the preceding symptoms (p=0.0003 and p<0.0001 respectively). Delay in presentation was significantly negatively correlated with organism isolation (p=0.0001). Multivariate analyses identified the delay in presentation as the strongest independent variable for organism isolation (p=0.014) in cases of spontaneous spinal infection when compared with the admission CRP level (p=0.031) and WCC (p=0.056).

Conclusions

In spontaneous spinal infection, delay in presentation is the strongest independent variable for organism isolation. High inflammatory marker levels on admission are a useful prognostic marker for the overall potential of isolating a causative organism either by blood cultures or by biopsy in patients with negative blood cultures. Furthermore, the admission inflammatory marker levels allow for treating surgeons to counsel their patients of the likelihood of achieving a positive microbiological yield from biopsy.     

Brachial artery diameter and vasodilator response to nitroglycerine, but not flow-mediated dilatation, are associated with the presence and quantity of coronary artery calcium in asymptomatic adults

In the present study, we investigated whether measures of brachial artery reactivity were associated with the presence and extent of subclinical coronary atherosclerosis in asymptomatic adults. Electron beam computed tomography was employed to assess the presence and quantity of CAC (coronary artery calcium) in 441 participants (mean age, 61 years; 49% men) without prior history of CHD (coronary heart disease) or stroke, and CAC score was calculated using the method described by Agatston and co-workers [(1990) J. Am. Coll. Cardiol. 15, 827-832] High-resolution ultrasound was employed to measure BAD (brachial artery diameter), FMD (flow-mediated dilatation) and NMD (nitroglycerine-mediated dilatation). CAC score and FMD were log-transformed after adding 1 to reduce skewness. Multivariable logistic and linear regression models based on generalized estimating equations were used to assess whether BAD, FMD and NMD were each independently associated with the presence and quantity of CAC after adjustment for CHD risk factors and use of statin and hypertension medication. CAC was detectable in 64% of participants. After adjustment for age and sex, FMD was not correlated (r=-0.06; P=0.27), BAD was positively correlated (r=0.16; P=0.004) and NMD was inversely correlated in a borderline significant manner (r=-0.10; P=0.084) with log(CAC+1). In multivariable logistic regression analyses, FMD was not associated, whereas higher BAD (P=0.021) and lower NMD (P=0.030) were independently associated with the presence of CAC. In multivariable linear regression analyses, higher BAD (P=0.004) and lower NMD (P=0.016), but not FMD, were independently associated with log(CAC+1). We conclude that greater diameter of the brachial artery and lower vasodilator response to nitroglycerine, but not FMD, are associated with subclinical coronary atherosclerosis.     

Pelvic ultrasound findings in different forms of sexual precocity

Recently produced reference curves for various ultrasound dimensions were used to retrospectively assess 67 pelvic ultrasound scans carried out at the initial presentation in girls with sexual precocity. At presentation the group with precocious puberty had significantly increased uterine lengths and ovarian volumes compared with the normal population, and a significantly increased fundal–cervical ratio. Ovarian volume was also significantly increased in thelarche and thelarche variant. The fundal–cervical ratio was significantly increased in thelarche variant. There was considerable overlap between individuals with sexual precocity and normal subjects. The ultrasound findings that best discriminated early or precocious puberty from other forms of sexual precocity were the presence of a midline endometrial echo, and a uterine length above the 97th centile for age. An entirely normal pelvic ultrasound at presentation did not rule out the possibility of precocious puberty.     

Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date

Caloric restriction (CR) has been observed to retard aging processes and extend the maximum life span in rodents. In an effort to evaluate the effect of this nutritional intervention on physiologic variables in higher species, several nonhuman primate trials are ongoing. In particular, a study evaluating the independent effect of CR on the extent of atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys. Therefore, the trial was designed to achieve identical cholesterol intake after animals were randomized to a control group or a calorie-restricted group (30% reduction from baseline caloric intake). The animals were routinely evaluated for glycated proteins, plasma insulin and glucose levels, insulin sensitivity, and specific measures for abdominal fat distribution by CT scans over a 4-year interval. The results from 4 years of intervention demonstrate that CR improves cardiovascular risk factors (such as visceral fat accumulation) and improves insulin sensitivity. In contrast to other primate studies with normolipidemic animals, CR had no independent effects on plasma lipid levels and composition in the presence of equivalent amounts of dietary cholesterol intake. Preliminary analysis of atherosclerotic lesion extent in the abdominal aorta has failed to demonstrate differences between control animals and CR animals. Follow- up studies are being conducted to determine the effect of CR on atherosclerosis extent in coronary and carotid arteries.