Mesenchymal stem cell (MSC)-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin (two other components of the pathway) using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.

The anesthesiologist has been recognized as an integral member of the liver transplant team, and previous studies have demonstrated that inter-anesthesiologist variability can be a driver of outcomes for high-risk patients. We hypothesized that anesthesiologist experience, defined as the number of previous liver transplants performed at our institution, the Icahn School of Medicine at Mount Sinai, would be independently associated with outcomes for liver transplant patients. Eight hundred forty-nine liver transplants performed between January 2003 and January 2013 with a total of 22 anesthesiologists were analyzed. Each transplant was assigned an incremental case number that corresponded to the number of transplants that the attending anesthesiologist had already performed at our institution. Several perioperative covariates were controlled for in the context of a generalized linear mixed effects model to detail the influence of threshold levels of the incremental case number on the primary outcome, 30-day mortality, and a secondary outcome, 30-day graft failure. Sensitivity analyses were conducted to confirm the robustness of these findings. An incremental case number 5 was associated with a significantly greater risk of 30-day mortality (odds ratio 5 2.24, 95% confidence interval 5 1.11-4.54, P 5 0.025), and there was evidence suggestive of a greater risk of 30-day graft failure (odds ratio 5 1.93, 95% confidence interval 5 0.95-3.93, P 5 0.071). Sensitivity analyses ruled out threats to the validity of these findings, including dropout effects and time trends in the overall performance of the transplantation unit. In conclusion, this study shows that an anesthesiologist's level of experience has a significant effect on outcomes for liver transplant recipients, with increased mortality and possibly graft failure during a provider's first 5 cases. These findings may indicate the need for increased training and supervision for anesthesiologists joining the liver transplant team. Liver Transpl 21:89-95, 2015. V C 2014 AASLD.Received May 18, 2014; accepted September 14, 2014. Intraoperative anesthetic management has been increasingly identified as a driver of perioperative outcomes.1-4 Although anesthesiologists are recognized as integral members of the transplant team, [4][5][6][7] there is a paucity of data regarding the effects of intraoperative anesthetic interventions on orthotopic liver transplantation (OLT) outcomes. Furthermore, the potential effect of anesthesia practitioner experience is often not considered; most publications concentrate on the optimization of OLT recipient outcomes by appropriate risk stratification and sound surgical technique. 8,9

Background:The Snoring, Trouble Breathing, and Un-Refreshed (STBUR) questionnaire is a five-question screening tool for pediatric sleep-disordered breathing and risk for perioperative respiratory adverse events in children. The utility of this questionnaire as a preoperative risk-stratification tool has not been investigated. In view of limited availability of screening tools for preoperative pediatric sleep-disordered breathing, we evaluated the questionnaire's performance for postanesthesia adverse events that can impact postanesthesia care and disposition. Methods:The retrospective study protocol was approved by the institutional research board. The data were analyzed using two different definitions for a positive screening based on a five-point scale: low threshold (scores 1 to 5) and high threshold (score of 5). The primary outcome was based on the following criteria: (a) supplemental oxygen therapy following postanesthesia care unit (PACU) stay until hospital discharge, (b) greater than two hours during phase 1 recovery, (c) anesthesia emergency activation in the PACU, and (d) unplanned hospital admission.Results: About 6025 patients completed the questionnaire during the preoperative evaluation. And 1522 patients had a low threshold score and 270 had a high-threshold score. We found statistically significant associations in three outcomes based on the low threshold score: supplemental oxygen therapy (negative-predictive value[NPV] 0.97, 95% CI 0.97-98), PACU recovery time (NPV 0.99, 95% CI 0.99-0.99) and escalation of care (NPV 0.98, 95% CI 0.97-0.98). Positive-predictive values were statistically significant for all outcomes except anesthesia emergency in the PACU. Conclusion:The Snoring, Trouble Breathing, and Un-Refreshed questionnaire identified patients at higher risk for prolonged phase 1 recovery, oxygen therapy requirement, and escalation of care. The questionnaire's high-negative predictive value and specificity may make it useful as a screening tool to identify patients at low risk for prolonged stay in PACU.

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