Skin Cancer Risk Is Increased by Somatic Mutations Detected Noninvasively in Healthy-Appearing Sun-Exposed Skin.

Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. In this study, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk) was trained to predict personal history of skin cancer from age, family history, skin tone, and mutation count. The addition of mutation count significantly improved model performance (OR = 1.3, 95% confidence interval = 1.14-1.48; P = 5.3 × 10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known United States population prevalence, indicating that DNA-Skin Cancer Assessment of Risk was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk, and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection through adhesive patches.

Quantitation of the results of abdominal liposuction.

BACKGROUND: There are few objective techniques to accurately measure the outcome of liposuction. Consequently, there is also a paucity of data quantifying the results of this procedure. OBJECTIVES: The authors compare changes in abdominal volume and circumference with several objective measurement techniques in a relatively homogeneous group of individuals undergoing liposuction in a single, defined abdominal region. METHODS: This clinical study enrolled 23 patients with a body mass index (BMI) <25 kg/m(2) who had a localized anterior abdominal contour defect. Patients underwent standard suction-assisted tumescent liposuction. Changes in abdominal volume and circumference in the operative area (60 mm above to 80 mm below the umbilicus) preoperatively and 10 weeks postoperatively were assessed using a 3-dimensional (3D) digital photographic system and a standardized constant-tension manual tape measure procedure. RESULTS: The majority of the patients in this study were Caucasian women with a mean age of 42 years, a mean weight of 65.8 kg, and a mean BMI of 23.8 kg/m(2). In the study population, mean abdominal volume and umbilical circumference were reduced by 231.0 mL (~30% of subcutaneous fat) and 1.7 cm, respectively, at 10 weeks postoperatively as determined by 3D digital imaging. Fat volume in the surgical aspirate (mean = -183.3 mL) was a poor predictor of individual outcome, as assessed 10 weeks postoperatively by both the 3D digital imaging and multilevel constant-tension tape measure assessment tools. CONCLUSIONS: Both 3D digital photographic imaging and a standardized manual tape measurement procedure proved to be reliable tools for objectively assessing changes in abdominal circumference and volume produced by standard liposuction of a single, defined abdominal region.

Intravascular Cooling in the Treatment of Stroke (ICTuS): early clinical experience.

We sought to evaluate the safety and feasibility of mild therapeutic hypothermia using an endovascular temperature management system in awake acute ischemic stroke patients. The Intravascular Cooling in the Treatment of Stroke (ICTuS) study was an uncontrolled, multicenter development and feasibility study of conscious patients (n = 18) presenting within 12 hours of onset of an acute ischemic stroke at 5 clinical sites in the United States. Enrolled patients were to undergo core temperature management using an endovascular cooling system to induce and maintain mild, therapeutic hypothermia (target temperature of 33.0 degrees C) for a period of either 12 or 24 hours, followed by controlled rewarming to 36.5 degrees C over the subsequent 12-hour period. Nine patients underwent 12 hours of cooling followed by 12 hours of controlled rewarming, and 6 patients underwent 24 hours of cooling followed by 12 hours of controlled rewarming. Three patients underwent <1.5 hours of hypothermia due to clinical or technical issues. We also developed an antishivering regimen using buspirone and meperidine administered prophylactically to suppress shivering. The endovascular cooling catheter was well tolerated, with acceptable adverse event rates. Increasing the duration of hypothermia administration from 12 hours to 24 hours did not appear to increase the incidence or severity of adverse effects. Endovascular cooling with a proactive antishivering regimen can be accomplished in awake stroke patients. Further studies are needed to establish the safety and efficacy of this approach.

A novel system for mild hypothermia.

Mild hypothermia has been shown to provide protective effects in patients with ischemia (e.g. acute stroke and heart attack), but traditional methods for inducing, maintaining, and reversing hypothermia are slow, difficult to administer and control, and uncomfortable for patients. An innovative method produces mild, wholebody hypothermia (32 degrees C to 34 degrees C) by use of an endovascular heat exchanger placed into the inferior vena cava. A closed-loop system accurately changes core body temperature with average cool-down rates of 4.8 degrees C per hour, tight-target temperature control of +/- 0.1 degree C, and average rewarm rates of 1.9 degrees C per hour. By enhancing the mixing of blood in the vicinity of the heat exchanger, the disposable, small-diameter catheter efficiently exchanges heat between the closed-loop circulating fluid and the blood stream in response to body temperature. A control algorithm adapts to body physiology and thermal mass to mitigate temperature excursions. Flexible, bellow-shaped segments along the length of the catheter allow precise maneuvering within blood vessels. Heparin, covalently bonded to the catheter, helps control thrombogenicity. This novel design has potential clinical applications in cerebrovascular surgery, acute stroke, acute myocardial infarction, cardiac arrest, and fever control.

Ultrarapid, convection-enhanced intravascular hypothermia: a feasibility study in nonhuman primate stroke.

BACKGROUND AND PURPOSE: Hypothermia has been shown to be neuroprotective in a variety of clinical settings. Unfortunately, poor delivery techniques and insufficient data in appropriate preclinical models have hampered its development in human stroke. To address these limitations, we have devised a 10F intravascular catheter capable of rapid systemic cooling of nonhuman primates. METHODS: Placed in the inferior vena cava via a transfemoral approach, the catheter was used to induce mild systemic hypothermia 3 hours after the onset of hemispheric stroke in baboons. RESULTS: Cooling was achieved at a rate of 6.3+/-0.8 degrees C/h. Target brain temperatures (32.2+/-0.2 degrees C) were reached at the same time (47.7+/-6.32 minutes) as target esophageal temperatures (32.0+/-0.0 degrees C). Hypothermia was maintained for 6 hours in all animals. Animals did not experience the infections, coagulopathy, or cerebral edema commonly seen with surface cooling methods in human stroke. CONCLUSIONS: These data suggest that a brief episode of mild core hypothermia instituted at a clinically relevant time point can be achieved in primate stroke and that our intravascular cooling technique provides safe, rapid, and reproducible hypothermia.

Safety and performance of a novel intravascular catheter for induction and reversal of hypothermia in a porcine model.

OBJECTIVE: This study was undertaken to assess the acute safety and feasibility of rapidly inducing, maintaining, then reversing hypothermia using a novel heat transfer catheter and a closed-loop automatic feedback temperature control system to overcome limitations imposed by current clinical practices used for perioperative cooling and warming. METHODS: Six swine (mean mass, 53.8 +/- 3.6 kg) were studied. The heat transfer catheter was placed in the inferior vena cava via the femoral vein. Hypothermia to 32 degrees C was induced, maintained for 6 hours, then reversed to 36 degrees C. The time needed to induce and reverse hypothermia was recorded via continuous temperature monitoring of the lower esophagus, cerebrum, and rectum. Electrocardiography provided continuous monitoring, and blood draws were made at baseline and at 2-hour intervals. Examination of the catheter in situ was performed after the animals were killed. RESULTS: Cooling from 36.2 to 32.0 degrees C was rapid and uniform (mean, 7.3 +/- 0.7 degrees C/h), with animals reaching the target temperature within 60 minutes. Rewarming was also easily controlled, with animals' temperatures reaching 36 degrees C within 130 minutes. No arrhythmia was observed, and all hematological variables were within the normal range for swine. There was no evidence of hemolysis or platelet changes. Little to no thrombosis was observed. CONCLUSION: The data presented here suggest that rapid induction and reversal of hypothermia are technically possible using a core intravenous cooling catheter; this method would provide a safe, rapid, and exquisitely reproducible way to induce hypothermia with subsequent restoration of normothermia.