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.

Incidence of metachronous contralateral breast cancer in the Canton of Zurich: a population-based study of the cancer registry.

PURPOSE: To examine the incidence and characteristics of metachronous contralateral breast cancer (CBC) among women in the Canton of Zurich, Switzerland. METHODS: For 1980-2006, patients with unilateral invasive breast cancer (UBC) were analysed for metachronous CBC. Poisson's regression was used to estimate incidence rates of metachronous CBC according to age, year of diagnosis, follow-up period since first breast cancer and morphology. RESULTS: Of 16,323 patients with UBC, 700 (4.3%) developed a second malignant tumour of the opposite breast. Median age at first breast cancer was lower in the CBC group than in the full cohort. Median interval time between first and second breast cancer was 5.5 (interquartile range 2.6-10.1) years. Incidence rate at age 20-29 was 1006 (95% confidence interval, CI, 452-2238) cases per 100,000 person-years and decreased to 299 (199-450) at 80-84. Age-adjusted incidence rates according to period of diagnosis decreased from 618 (530-721) for 1980-1984 to 329 (217-500) cases per 100,000 person-years for 2005-2006. Incidence rate ratio of CBC for lobular carcinoma was 1.28 (95% CI 0.99-1.67) adjusted by age group and period of diagnosis compared to ductal carcinoma. CONCLUSIONS: In our study, incidence rates for CBC are comparable with findings from the literature. A reduction in the incidence of metachronous CBC, thought to be due to adjuvant therapies, is seen in our data. In our cohort, younger age and lobular carcinoma were associated with an increased risk of CBC.