Overproduction of endothelin-1 impairs glucose tolerance but does not promote visceral adipose tissue inflammation or limit metabolic adaptations to exercise.

Endothelin-1 (ET-1) is a potent vasoconstrictor and proinflammatory peptide that is upregulated in obesity. Herein, we tested the hypothesis that ET-1 signaling promotes visceral adipose tissue (AT) inflammation and disrupts glucose homeostasis. We also tested if reduced ET-1 is a required mechanism by which exercise ameliorates AT inflammation and improves glycemic control in obesity. We found that 1) diet-induced obesity, AT inflammation, and glycemic dysregulation were not accompanied by significantly increased levels of ET-1 in AT or circulation in wild-type mice and that endothelial overexpression of ET-1 and consequently increased ET-1 levels did not cause AT inflammation yet impaired glucose tolerance; 2) reduced AT inflammation and improved glucose tolerance with voluntary wheel running was not associated with decreased levels of ET-1 in AT or circulation in obese mice nor did endothelial overexpression of ET-1 impede such exercise-induced metabolic adaptations; 3) chronic pharmacological blockade of ET-1 receptors did not suppress AT inflammation in obese mice but improved glucose tolerance; and 4) in a cohort of human subjects with a wide range of body mass indexes, ET-1 levels in AT, or circulation were not correlated with markers of inflammation in AT. In aggregate, we conclude that ET-1 signaling is not implicated in the development of visceral AT inflammation but promotes glucose intolerance, thus representing an important therapeutic target for glycemic dysregulation in conditions characterized by hyperendothelinemia. Furthermore, we show that the salutary effects of exercise on AT and systemic metabolic function are not contingent on the suppression of ET-1 signaling.

Methylene blue: a simple marker for intraoperative detection of gastroduodenal perforations during laparoscopic pyloromyotomy.

INTRODUCTION: We studied the feasibility of using methylene blue (MB) as a marker to detect mucosal perforations during laparoscopic pyloromyotomy using in vitro and in vivo animal models. MATERIALS AND METHODS: MB was initially tested in pig stomachs in vitro. Information gathered from these experiments was then used to test the marker during experimental live piglet laparoscopic surgery. RESULTS: MB stained the gastric mucosa blue; this tint could be seen through the intact mucosal layer exposed via myotomy. Dye extravasation was seen during laparoscopic surgery with mucosal perforations of 1.2 mm and greater with or without air insufflation of the stomach. Air extravasation was seen with perforations of 2.0 mm and greater. CONCLUSION: Full strength 1% MB dye instilled into the gastric lumen can potentially be used as a marker for detection of mucosal perforations of 1.2 mm or greater during laparoscopic pyloromyotomy.

Practice makes perfect: progressive improvement of laparoscopic pyloromyotomy results, with experience.

INTRODUCTION: Pyloric stenosis can now be treated effectively with laparoscopic pyloromyotomy (LP). Few large outcome studies have been published regarding the laparoscopic technique. In this paper, we describe our experience with the first 185 consecutive LPs. MATERIALS AND METHODS: An institutional review board-approved retrospective outcomes analysis was performed on our first 185 consecutive LPs. Previous publications comparing open pyloromyotomy (OP) and LP are reviewed. Our hypothesis is that, with experience, the outcome of LP will equal or surpass that of OP. RESULTS: A total 185 infants underwent LPs during the study period. The infants had median values of age: 33 days; body weight: 4 kg; surgery duration: 25 minutes; postoperative length of stay (LOS): 25.5 hours; and total LOS: 45 hours. There were 7 complications (3.78%): 4 incomplete pyloromyotomies (2.2%), 1 pyloric mucosal perforation (0.5%), 1 delayed duodenal perforation (0.5%), and 1 wound infection (0.5%). There has been a progressive reduction in the time required for surgery, from a median of 29 minutes in the first 60 cases to 21.5 in the last 65. Postoperative LOS has fallen from a median of 26 hours in the first half to 24.5 in the later half. Complications occurred primarily in the first third of our cases. CONCLUSIONS: We are able to demonstrate that, with experience, one can expect progressive improvement in the outcomes following LP in infants. Our surgery duration and complications in the last 65 cases are better than most published results for OP or LP.

Characterizing information decay in patient handoffs.

OBJECTIVE: The purpose of this study was to analyze the decay of information with multiple sequential patient handoff reports given by third-year medical students who have not had standardized patient handoff training. METHODS: We examine the information decay of quantitative parameters included in 2 different simulated patient history and physical handoffs conducted among third-year medical students. Both student self-surveys and third party observer surveys tracked accuracy of information. A total of 93 students were surveyed for the first patient scenario and 103 students were surveyed for second patient scenario. Survey data were aggregated into 2 separate spreadsheets, one for each patient scenario tested. A total of 16 data points pertaining to the checklist were analyzed for common trends in handoff accuracy and information decay. RESULTS: Quantitative analysis of information passed between handoffs showed that between the 2 case scenarios, there was a consistent loss of information between one presenter to the next. Overall, 33% of information was lost between the first and third handoffs. Within the progression of individual handoffs, a narrative decay was demonstrated. There was a regression in handoff accuracy, trending down to an average of only 45% of information being passed on successfully by the time each presenter reached the last piece of information in their patient presentation. When examining the survey data points that had greater than an 80% success rate of being included in the handoffs, there appeared to be no correlation between their inherent qualities. CONCLUSIONS: This study showed there is a significant decrease in accuracy of information during sequential patient handoff exercises. The information decay may be a result of time, memory, or relevance of the information to the student. Future studies incorporating teaching effective handoffs early in the clinical curriculum would be an area of future research.

Robot-assisted laparoscopic colectomy: 70 cases-one surgeon.

This study reviewed the use of robot-assisted laparoscopic surgery for colon resection. We described the six-year experience of one minimally invasive fellowship-trained surgeon performing 70 consecutive colectomies using the da Vinci system. Between September 2002 and 2007, data on 70 patients undergoing robotic colectomy for diverticular disease, polyps, cancer, or carcinoid tumor were collected. Operations were right colectomy and sigmoid colectomy. A total of 38 right and 32 sigmoid colectomies were performed in 32 males and 38 females. The postoperative diagnoses were diverticular disease (19), polyps (36), cancer (13), and carcinoid (2). Times for the right colectomies were: port setup time 33.6 ± 12.1 (20-64) min, robotic time 147.2 ± 44.4 (53-306) min, and total case time 221.3 ± 43.7 (150-380) min. The estimated blood loss (EBL) was 53.9 ± 78.2 (15-500) ml, the body mass index (BMI) 27.2 ± 4.2 (17-36.8) kg/m(2), and the median length of stay (LOS) 3 (2-27) days. The robotic portion represented 66.5 % of the total case time. Times for the sigmoid colectomies were: port setup time 30.0 ± 9.8 (10-57) min, robotic time 101.8 ± 25.3 (67-165) min, and total case time 228.4 ± 40.5 (147-323) min. The EBL was 71.2 ± 47.9 (15-200) ml, the BMI 27.1 ± 4.9 (17.0-40.5) kg/m(2), and the median LOS 4 (2-27) days. The robotic portion represented 44.6% of the total case time. Eight different types of complication occurred. Eight cases were converted-five to open and three to laparoscopic. Two resulted from robot malfunction. Residents participated in 40 cases (57.1%). In the years 2002-2006, respectively, 5, 12, 10, 11, and 19 robotic colectomies were performed. In the first nine months of 2007, 13 robotic colectomies were performed. These 70 consecutive cases have demonstrated robotic colectomy to be a safe and technically feasible approach. The number of robotic colectomies performed each year has steadily increased over the last six years. This series compared favorably with other robotic series in length of hospital stay, conversion rates, and total case time.