Three-dimensional Printing in the Intestine.

Intestinal transplantation remains a life-saving option for patients with severe intestinal failure. With the advent of advanced tissue engineering techniques, great strides have been made toward manufacturing replacement tissues and organs, including the intestine, which aim to avoid transplant-related complications. The current paradigm is to seed a biocompatible support material (scaffold) with a desired cell population to generate viable replacement tissue. Although this technique has now been extended by the three-dimensional (3D) printing of geometrically complex scaffolds, the overall approach is hindered by relatively slow turnover and negative effects of residual scaffold material, which affects final clinical outcome. Methods recently developed for scaffold-free 3D bioprinting may overcome such obstacles and should allow for rapid manufacture and deployment of "bioprinted organs." Much work remains before 3D bioprinted tissues can enter clinical use. In this brief review we examine the present state and future perspectives of this nascent technology before full clinical implementation.

Aptamer-targeted antigen delivery.

Effective therapeutic vaccines often require activation of T cell-mediated immunity. Robust T cell activation, including CD8 T cell responses, can be achieved using antibodies or antibody fragments to direct antigens of interest to professional antigen presenting cells. This approach represents an important advance in enhancing vaccine efficacy. Nucleic acid aptamers present a promising alternative to protein-based targeting approaches. We have selected aptamers that specifically bind the murine receptor, DEC205, a C-type lectin expressed predominantly on the surface of CD8α(+) dendritic cells (DCs) that has been shown to be efficient at facilitating antigen crosspresentation and subsequent CD8(+) T cell activation. Using a minimized aptamer conjugated to the model antigen ovalbumin (OVA), DEC205-targeted antigen crosspresentation was verified in vitro and in vivo by proliferation and cytokine production by primary murine CD8(+) T cells expressing a T cell receptor specific for the major histocompatibility complex (MHC) I-restricted OVA257-264 peptide SIINFEKL. Compared with a nonspecific ribonucleic acid (RNA) of similar length, DEC205 aptamer-OVA-mediated antigen delivery stimulated strong proliferation and production of interferon (IFN)-γ and interleukin (IL)-2. The immune responses elicited by aptamer-OVA conjugates were sufficient to inhibit the growth of established OVA-expressing B16 tumor cells. Our results demonstrate a new application of aptamer technology for the development of effective T cell-mediated vaccines.

Rothman Index variability predicts clinical deterioration and rapid response activation.

BACKGROUND: The overall utility of the Rothman Index (RI), a global measure of inpatient acuity, for surgical patients is unclear. We evaluate whether RI variability can predict rapid response team (RRT) activation in surgical patients. METHODS: Surgical patients who underwent RRT activation from 2013 to 2015 were matched to four control cases. RI variability was gauged by maximum minus minimum RI (MMRI) and RI standard deviation (RISD) within a 24-h period before RRT. The primary outcome measured was RRT activation, and our secondary outcome was in-hospital mortality. RESULTS: Two hundred seventeen (217) patients underwent RRT. RISD (odds ratio, OR, 1.31, 95% confidence interval, CI, 1.23-1.38, P < 0.001; area under receiver operating characteristic, AUROC, curve 0.74, 95% CI 0.70-0.77) and MMRI (OR 1.10, 95% CI 1.08-1.12, P < 0.001; AUROC 0.76, 95% CI 0.72-0.79) predicted increased likelihood of RRT. CONCLUSIONS: RISD is predictive of RRT.