Faculty Bibliography

In adults, hepatic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with significant morbidity and transplantation-related mortality (TRM). However, there is a paucity of parallel data on the incidence of, and risk factors for, liver injury (LI) and the impact of LI on TRM in pediatric allo-HSCT recipients. We compared total bilirubin, direct bilirubin, and alanine aminotransferase values before allo-HSCT and at 1 month, day +100, and 12 months after allo-HSCT in 248 patients who received either a myeloablative conditioning (MAC) regimen (n = 109) or a reduced-toxicity/reduced-intensity conditioning (RTC/RIC) regimen (n = 139). LI was defined as grade ≥ 2 hyperbilirubinemia according to the National Cancer Institute's Common Terminology Criteria for Adverse Events 3.0/4.0 (total bilirubin, >1.95 mg/dL, 1.5 times above the upper limit of normal for our laboratory). Univariate and multivariate logistic regression models were used to identify risk factors for LI and TRM. The incidence of LI at 1 month after allo-HSCT was 14.1%. The median bilirubin level was 3.5 mg/dL (range, 1.97 to 32.2 mg/dL). Only LI as defined by total bilirubin level, but not by direct bilirubin or alanine aminotransferase level, was found to be a significant predictor for TRM. The 1-year TRM was 60.7% (95% confidence interval, 42.6% to 78.7%) in patients with LI at 1 month after allo-HSCT, compared with 14.6% (95% confidence interval, 9.9% to 19.4%) (P < .0001) in patients those who did not have liver injury. Multivariate analysis identified age (P = .03), total body irradiation (P = .007), bacterial bloodstream infection (BBSI) (P = .001), and invasive fungal infection (IFI) (P = .002) as significant risk factors for developing LI at 1 month. On multivariate analysis for risk factors for TRM, only LI at 1 month after allo-HSCT (P < .0001), primary graft failure (P = .001), BBSI (P = .003), and systemic viral infection (P = .04) were identified as significant risk factors for TRM. LI before allo-HSCT conditioning was not associated with higher TRM. Although the incidence of LI in pediatric allo-HSCT recipients is low, LI is associated with very high TRM. BBSI and IFI are the primary risk factors for LI.

Biofilms are structured communities of bacteria that play a major role in the pathogenicity of bacteria and are the leading cause of antibiotic resistant bacterial infections on indwelling catheters and medical prosthetic devices. Failure to resolve these biofilm infections may necessitate the surgical removal of the prosthetic device which can be debilitating and costly. Recent studies have shown that application of surface acoustic waves to catheter surfaces can reduce the incidence of infections by a mechanism that has not yet been clarified. We report here the effects of surface acoustic waves (SAW) on the capacity of human neutrophils to eradicate S. epidermidis bacteria in a planktonic state and within biofilms. Utilizing a novel fibrin gel system that mimics a tissue-like environment, we show that SAW, at an intensity of 0.3 mW/cm(2), significantly enhances human neutrophil killing of S. epidermidis in a planktonic state and within biofilms by enhancing human neutrophil chemotaxis in response to chemoattractants. In addition, we show that the integrin CD18 plays a significant role in the killing enhancement observed in applying SAW. We propose from out data that this integrin may serve as mechanoreceptor for surface acoustic waves enhancing neutrophil chemotaxis and killing of bacteria.