Identification of a Distinct Monocyte-Driven Signature in Systemic Sclerosis Using Biophysical Phenotyping of Circulating Immune Cells.

OBJECTIVE: Pathologically activated circulating immune cells, including monocytes, play major roles in systemic sclerosis (SSc). Their functional characterization can provide crucial information with direct clinical relevance. However, tools for the evaluation of pathologic immune cell activation and, in general, of clinical outcomes in SSc are scarce. Biophysical phenotyping (including characterization of cell mechanics and morphology) provides access to a novel, mostly unexplored layer of information regarding pathophysiologic immune cell activation. We hypothesized that the biophysical phenotyping of circulating immune cells, reflecting their pathologic activation, can be used as a clinical tool for the evaluation and risk stratification of patients with SSc. METHODS: We performed biophysical phenotyping of circulating immune cells by real-time fluorescence and deformability cytometry (RT-FDC) in 63 SSc patients, 59 rheumatoid arthritis (RA) patients, 28 antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients, and 22 age- and sex-matched healthy donors. RESULTS: We identified a specific signature of biophysical properties of circulating immune cells in SSc patients that was mainly driven by monocytes. Since it is absent in RA and AAV, this signature reflects an SSc-specific monocyte activation rather than general inflammation. The biophysical properties of monocytes indicate current disease activity, the extent of skin or lung fibrosis, and the severity of manifestations of microvascular damage, as well as the risk of disease progression in SSc patients. CONCLUSION: Changes in the biophysical properties of circulating immune cells reflect their pathologic activation in SSc patients and are associated with clinical outcomes. As a high-throughput approach that requires minimal preparations, RT-FDC-based biophysical phenotyping of monocytes can serve as a tool for the evaluation and risk stratification of patients with SSc.

Long-Term Outcomes of Extra-Anatomic Femoro-Tibial Bypass Reconstructions in Chronic Limb-Threating Ischemia.

(1) Background: While tibial bypass surgery still plays a role in the treatment of patients with chronic limb-threatening ischemia and diabetic foot syndrome; only a few centers have recorded considerable numbers of these conditions. The current study aimed to determine contemporary practice with special focus on the performance of extra-anatomic grafting to the infrapopliteal arteries. (2) Methods: A retrospective, single-center study included patients with tibial bypass grafts from 1 January 2008 to 31 December 2019. Primary endpoints were complication rate, graft patency, amputation, overall survival, and major adverse cardiac (MACE) or limb event (MALE). The cohort was stratified by extra-anatomic vs. anatomic position. (3) Results: A total of 455 patients (31% female) with Rutherford stage 4 (12.5%) and 5/6 (69.5%) were included (thereof, 19.5% had high amputation risk according to the Wound Ischemia Foot Infection score). Autologous reconstruction was performed in 316 cases, and prosthetic reconstruction in 131 cases, with a total of 51 (11.2%) extra-anatomic grafts. Early occlusion rate was 9.0% with an in-hospital overall mortality of 2.8%. The in-hospital rate of MACE was 2.4% and of MALE, 1.5%. After one, three and five years, the primary patency of venous bypasses was 74.5%, 68.6% and 61.7%, respectively. For prosthetic grafts, this was 55.1%, 46.0%, and 38.3%, respectively (p < 0.001). The patency of extra-anatomic prosthetic grafts performed significantly better compared with anatomically positioned prosthetic grafts (log-rank p = 0.008). In multivariate analyses, diabetes (hazard ratio, HR 1.314, CI 1.023−1.688, p = 0.032), coronary artery disease (HR 1.343, CI 1.041−1.732, p = 0.023), and dialysis dependency (HR 2.678, CI 1.687−4.250, p < 0.001) were associated with lower odds of survival (4) Conclusion: In this large, single-center cohort, tibial bypass surgery demonstrated satisfactory results with overall low perioperative complication rates and long-term patency rates of 60% and 38%, respectively. Extra-anatomic bypasses represent a feasible alternative to venous grafts in terms of patency. A tailored, patient-centered approach considering predictors such as diabetes, dialysis dependency, and coronary artery disease along with prediction models may further improve the long-term results in the future.