The intestinal barrier is often disrupted in disease states, and intestinal barrier failure leads to sepsis. Ursodeoxycholic acid (UDCA) is a bile acid that may protect the intestinal barrier. We hypothesized that UDCA would protect the intestinal epithelium in injury models. To test this hypothesis, we utilized an in vitro wound-healing assay and a mouse model of intestinal barrier injury. We found that UDCA stimulates intestinal epithelial cell migration in vitro, and this migration was blocked by inhibition of cyclooxygenase 2 (COX-2), epidermal growth factor receptor (EGFR), or ERK. Furthermore, UDCA stimulated both COX-2 induction and EGFR phosphorylation. In vivo UDCA protected the intestinal barrier from LPS-induced injury as measured by FITC dextran leakage into the serum. Using 5-bromo-2'-deoxyuridine and 5-ethynyl-2'-deoxyuridine injections, we found that UDCA stimulated intestinal epithelial cell migration in these animals. These effects were blocked with either administration of Rofecoxib, a COX-2 inhibitor, or in EGFR-dominant negative Velvet mice, wherein UDCA had no effect on LPS-induced injury. Finally, we found increased COX-2 and phosphorylated ERK levels in LPS animals also treated with UDCA. Taken together, these data suggest that UDCA can stimulate intestinal epithelial cell migration and protect against acute intestinal injury via an EGFR- and COX-2-dependent mechanism. UDCA may be an effective treatment to prevent the early onset of gut-origin sepsis. NEW & NOTEWORTHY In this study, we show that the secondary bile acid ursodeoxycholic acid stimulates intestinal epithelial cell migration after cellular injury and also protects the intestinal barrier in an acute rodent injury model, neither of which has been previously reported. These effects are dependent on epidermal growth factor receptor activation and downstream cyclooxygenase 2 upregulation in the small intestine. This provides a potential treatment for acute, gut-origin sepsis as seen in diseases such as necrotizing enterocolitis.

No abstract

Background Utilization of ICP monitors for pediatric patients is low and varies between centers. We hypothesized that in more severely injured patients (GCS 3-4), there would be a decreased mortality associated with invasive monitoring devices. Methods The pediatric Trauma Quality Improvement Program (TQIP) was queried for patients aged ≤ 16 years meeting criteria for invasive monitors. Our primary outcome was mortality. Patients with ICP monitoring were compared to those without. A logistic regression was used to examine the risk of mortality. Results Of 3,808 patients, 685 (18.0%) underwent ICP monitoring. ICP monitors were associated with increased risk of mortality (OR 1.82, CI 1.36-2.44, p < 0.001). A secondary analysis including type of invasive ICP monitor and dividing GCS into 3 categories revealed both intraventricular drain (OR 1.89, CI 1.3-2.7, p = 0.001) and intraparenchymal pressure monitor (OR 1.86, CI 1.32-2.6, p < 0.001) to be independently associated with an increased likelihood of mortality regardless of GCS, while intraparenchymal oxygen monitoring was not (OR 0.47, CI 0.11-2.05, p = 0.316). The strongest effect was seen in those patients with a GCS of 5-6. Conclusion ICP monitors are an independent risk factor for mortality, particularly with intraventricular drains and intraparenchymal monitors in patients with a GCS 5-6.

Background: Ventilator-associated pneumonia (VAP) is a common healthcare-associated infection affecting as many as 27% of mechanically ventilated patients. Ventilator-associated pneumonia is an important source of morbidity and mortality in the surgical intensive care unit (SICU). The optimal diagnostic method for VAP has remained controversial and the role of therapeutic bronchoscopy in the clearance of pulmonary secretions with VAP, in essence source control, remains unknown. Our unit utilizes bronchoscopy inconsistently for these purposes and we chose to evaluate its effectiveness in our patient population with the hypothesis that bronchoscopic diagnosis and therapy results in lower mortality rates and faster clinical resolution. Methods: We analyzed retrospectively all patients treated for VAP in a single SICU between September 2003 and December 2011. Patients were divided into groups based upon diagnostic method and receipt of therapeutic bronchoscopy, and were analyzed for differences in time to clinical resolution and mortality. Results: A total of 360 patients were included in the study, including 493 episodes of VAP. The diagnostic bronchoscopy group had statistically higher APACHE II scores (p = 0.02) and fewer days in hospital prior to diagnosis (p = 0.02) when compared with the non-invasive diagnosis group. Diagnostic bronchoscopy was associated with shorter length of stay and shorter duration of antibiotics whereas receipt of a therapeutic bronchoscopy was associated with the opposite effects by multivariable analysis. Conclusion: Our hypothesis was disproved and our findings are similar to those found in recent publications. This study supports no definitive conclusions, but further consideration of the role of bronchoscopy is urged in both the diagnosis and treatment of VAP. In our population, bronchoscopy for diagnostic or therapeutic purposes in VAP was not associated with better outcomes. However, differences in baseline characteristics suggest a randomized trial may be needed to answer more completely this question.

Background: Management of perforated appendicitis in children remains controversial. Nonoperative (NO) and immediate operative (IO) strategies are used with varying outcomes. We hypothesized that IO intervention for patients with perforated appendicitis would be more cost-effective than NO management. Methods: A retrospective chart review of all patients with appendicitis from 2012 to 2015 was performed. Patients with perforated appendicitis were defined by evidence of perforation on imaging. We excluded patients who presented with sepsis, organ failure, and ventriculoperitoneal shunts. NO management was determined by surgeon preference. Univariate and multivariate analyses were performed. Results: IO was performed on 145 patients with perforated appendicitis, whereas 83 were treated with NO management. Compared to IO patients, NO patients incurred higher overall costs, greater length of stay, more readmissions, complications, peripherally inserted central venous catheter lines, interventional radiology drains, and unplanned clinic and emergency department visits (P < 0.0001 for all). Multivariate analysis adjusting for age, days of symptoms, admission C-reactive protein and white blood cell count revealed that NO management was independently associated with increased costs (OR 1.35, 1.12-1.62, 95% CI). Cost curves demonstrated that total cost for IO surpasses that of NO management when patients present with greater than 6.3 d of symptoms (P ¼ 0.01). Conclusions: Our data suggest that IO is more cost-effective than NO management for patients with perforated appendicitis who present with less than 6.3 d of symptoms, after which point, NO management is more cost-effective.

No abstract

No abstract

No abstract