Initial single-center experience using Fiber Optic RealShape guidance in complex endovascular aortic repair.

OBJECTIVE: In the present study, we have described the technical success using Fiber Optic RealShape (FORS) endovascular guidance and its effects on the overall procedural time and radiation usage during complex endovascular aortic repair (EVAR). METHODS: Fenestrated and branched EVARs performed at a single center from 2017 to 2022 were prospectively studied. FORS-guided procedures were matched retrospectively 1:3 to non-FORS-guided procedures by the incorporated target arteries and body mass index. Technical success was defined as successful target vessel cannulation using FORS for the entirety of navigation (wire insertion to exchange for a stiff wire). The predictors of technical success were evaluated via logistic regression. The procedural times and radiation doses were compared between the matched cohorts using the Wilcoxon rank sum test. RESULTS: A total of 21 FORS-guided procedures were matched to 61 non-FORS-guided procedures. A total of 95 FORS cannulations were attempted (87 for the visceral target artery and 8 for the bifurcate gate). Technical success was achieved in 81 cannulations (85%); 15 (16%) were completed without the use of live fluoroscopy. The univariate predictors of FORS technical success included <50% target artery stenosis, <50% target artery calcification, and the target vessel attempted (P < .05 for each). FORS failures were attributed to device material properties in six cases, device failure in two cases, and the wire/catheter combination in six. The use of FORS guidance was associated with shorter median procedural and fluoroscopy times and a lower dose area product and air kerma (P ≤ .0001 for each). CONCLUSIONS: The results from our initial experience with FORS during complex EVAR, including our learning curve, has shown promise, with acceptable technical success and reductions in procedural times and radiation usage.

An evolving autoimmune microenvironment regulates the quality of effector T cell restimulation and function.

Defining the processes of autoimmune attack of tissues is important for inhibiting continued tissue destruction. In type 1 diabetes, it is not known how cytotoxic effector T cell responses evolve over time in the pancreatic islets targeted for destruction. We used two-photon microscopy of live, intact, individual islets to investigate how progression of islet infiltration altered the behavior of infiltrating islet-specific CD8(+) T cells. During early-islet infiltration, T-cell interactions with CD11c(+) antigen-presenting cells (APCs) were stable and real-time imaging of T cell receptor (TCR) clustering provided evidence of TCR recognition in these stable contacts. Early T cell-APC encounters supported production of IFN-γ by T effectors, and T cells at this stage also killed islet APCs. At later stages of infiltration, T-cell motility accelerated, and cytokine production was lost despite the presence of higher numbers of infiltrating APCs that were able to trigger T-cell signaling in vitro. Using timed introduction of effector T cells, we demonstrate that elements of the autoimmune-tissue microenvironment control the dynamics of autoantigen recognition by T cells and their resulting pathogenic effector functions.

Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics.

The real-time dynamics of the T cell receptor (TCR) reflect antigen detection and T cell signaling, providing valuable insight into the evolving events of the immune response. Despite considerable advances in studying TCR dynamics in simplified systems in vitro, live imaging of subcellular signaling complexes expressed at physiological densities in intact tissues has been challenging. In this study, we generated a transgenic mouse with a TCR fused to green fluorescent protein to provide insight into the early signaling events of the immune response. To enable imaging of TCR dynamics in naive T cells in the lymph node, we enhanced signal detection of the fluorescent TCR fusion protein and used volumetric masking with a second fluorophore to mark the T cells expressing the fluorescent TCR. These in vivo analyses and parallel experiments in vitro show minimal and transient incorporation of TCRs into a stable central supramolecular activating cluster (cSMAC) structure but strong evidence for rapid, antigen-dependent TCR internalization that was not contingent on T cell motility arrest or cSMAC formation. Short-lived antigen-independent TCR clustering was also occasionally observed. These in vivo observations demonstrate that varied TCR trafficking and cell arrest dynamics occur during early T cell activation.

Confinement-optimized three-dimensional T cell amoeboid motility is modulated via myosin IIA-regulated adhesions.

During trafficking through tissues, T cells fine-tune their motility to balance the extent and duration of cell-surface contacts versus the need to traverse an entire organ. Here we show that in vivo, myosin IIA-deficient T cells had a triad of defects, including overadherence to high-endothelial venules, less interstitial migration and inefficient completion of recirculation through lymph nodes. Spatiotemporal analysis of three-dimensional motility in microchannels showed that the degree of confinement and myosin IIA function, rather than integrin adhesion (as proposed by the haptokinetic model), optimized motility rate. This motility occurred via a myosin IIA-dependent rapid 'walking' mode with multiple small and simultaneous adhesions to the substrate, which prevented spurious and prolonged adhesions. Adhesion discrimination provided by myosin IIA is thus necessary for the optimization of motility through complex tissues.