Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i) express critical S1P signaling elements, (ii) constrict in response to S1P and (iii) lose myogenic responsiveness following S1P receptor antagonism (JTE013). However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

A novel approach to assessing technical competence of colorectal surgery residents: the development and evaluation of the Colorectal Objective Structured Assessment of Technical Skill (COSATS).

OBJECTIVE: To develop and evaluate an objective method of technical skills assessment for graduating subspecialists in colorectal (CR) surgery-the Colorectal Objective Structured Assessment of Technical Skill (COSATS). BACKGROUND: It may be reasonable for the public to assume that surgeons certified as competent have had their technical skills assessed. However, technical skill, despite being the hallmark of a surgeon, is not directly assessed at the time of certification by surgical boards. METHODS: A procedure-based, multistation technical skills examination was developed to reflect a sample of the range of skills necessary for CR surgical practice. These consisted of bench, virtual reality, and cadaveric models. Reliability and construct validity were evaluated by comparing 10 graduating CR residents with 10 graduating general surgery (GS) residents from across North America. Expert CR surgeons, blinded to level of training, evaluated performance using a task-specific checklist and a global rating scale. The mean global rating score was used as the overall examination score and a passing score was set at "borderline competent for CR practice." RESULTS: The global rating scale demonstrated acceptable interstation reliability (0.69) for a homogeneous group of examinees. Both the overall checklist and global rating scores effectively discriminated between CR and GS residents (P < 0.01), with 27% of the variance attributed to level of training. Nine CR residents but only 3 GS residents were deemed competent. CONCLUSIONS: The Colorectal Objective Structured Assessment of Technical Skill effectively discriminated between CR and GS residents. With further validation, the Colorectal Objective Structured Assessment of Technical Skill could be incorporated into the colorectal board examination where it would be the first attempt of a surgical specialty to formally assess technical skill at the time of certification.

To plug or not to plug: a cost-effectiveness analysis for complex anal fistula.

BACKGROUND: Complex anal fistulas are unsuitable for fistulotomy because of the risk of fecal incontinence. The anal fistula plug (AFP) has demonstrated fistula healing without sphincter division. This study aims to evaluate the cost-effectiveness of the AFP compared to the endoanal advancement flap (EAAF) as an alternative sphincter-preserving option for complex anal fistulas. METHODS: The study included 24 patients who underwent treatment for complex anal fistulas. Healing and complication rates of a prospective cohort of AFP patients (n=12) were compared to a retrospective cohort of patients who underwent EAAF (n=12). Cost data were collected after validated healthcare reporting standards. A cost-effectiveness analysis was performed, including extensive modeling of fistula healing rates. RESULTS: Both cohorts (12 AFP patients and 12 EAAF patients) had similar patient demographics and fistula characteristics. Fistula healing was achieved in 50% (5/12) of AFP patients and 33% (4/12) of EAAF patients (P=.680). Median clinical follow-up was 28 weeks for the AFP patients and 14 weeks for the EAAF patients, whereas median recurrence time was 17.6 weeks (range, 0.4-43.9) and 12.6 weeks (range, 2-34.3), respectively. Use of the AFP instead of the EAAF saved $1,588 (95% confidence interval [CI], $1,211-$1,965; P<.0001), and 1.5 hospital days per healed fistula (P=.0002). This cost-saving effect persisted and amounted to $825 (95% CI, $133-$1,517; P=.022) when the cost estimates were adjusted for the reduction in the hospital length of stay. Extensive modeling over a large range of fistula healing rates confirmed the cost-effectiveness of the AFP. CONCLUSION: The AFP is a cost-saving procedure for complex anal fistulas compared to the EAAF.