Calprotectin Impairs Platelet Survival in Patients With Primary Antiphospholipid Syndrome.

OBJECTIVE: While thrombosis and pregnancy loss are the best-known clinical features of antiphospholipid syndrome (APS), many patients also exhibit "extra-criteria" manifestations, such as thrombocytopenia. The mechanisms that drive APS thrombocytopenia are not completely understood, and no clinical biomarkers are available for predicting antiphospholipid antibody (aPL)-mediated thrombocytopenia. Calprotectin is a heterodimer of S100A8 and S100A9 that is abundant in the neutrophil cytoplasm and released upon proinflammatory neutrophil activation. Here, we sought to evaluate the presence, clinical associations, and potential mechanistic roles of circulating calprotectin in a cohort of primary APS and aPL-positive patients. METHODS: Levels of circulating calprotectin were determined in plasma by the QUANTA Flash chemiluminescent assay. A viability dye-based platelet assay was used to assess the potential impact of calprotectin on aPL-mediated thrombocytopenia. RESULTS: Circulating calprotectin was measured in 112 patients with primary APS and 30 aPL-positive (without APS criteria manifestations or lupus) patients as compared to patients with lupus (without APS), patients with unprovoked venous thrombosis (without aPL), and healthy controls. Levels of calprotectin were higher in patients with primary APS and aPL-positive patients compared to healthy controls. After adjustment for age and sex, calprotectin level correlated positively with absolute neutrophil count (r = 0.41, P < 0.001), positively with C-reactive protein level (r = 0.34, P = 0.002), and negatively with platelet count (r = -0.24, P = 0.004). Mechanistically, we found that calprotectin provoked aPL-mediated thrombocytopenia by engaging platelet surface toll-like receptor 4 and activating the NLRP3-inflammasome, thereby reducing platelet viability in a caspase-1-dependent manner. CONCLUSION: These data suggest that calprotectin has the potential to be a functional biomarker and a new therapeutic target for APS thrombocytopenia.

Predictors and Interrelationship of Patient-Reported Outcomes in Antiphospholipid Syndrome: A Cross-Sectional Study.

OBJECTIVE: This study assessed patient-reported outcomes (PROs) in individuals with persistently positive antiphospholipid antibodies (aPL) to better understand how living with aPL may affect their quality of life. METHODS: Patients completed Patient-Reported Outcomes Measurement Information System Physical Function (PF) and Cognitive Function (CF) Short Forms as well as the pain intensity (PI) rating (scale of 1-10). Patients were characterized for demographics, clinical manifestations of antiphospholipid syndrome (APS), cardiovascular risk factors, laboratory test results, and medication usage. Multivariate modeling was done via linear regression. RESULTS: Of 139 patients, 89 had primary APS, 21 had secondary APS, and 29 had persistent aPL without meeting clinical criteria for APS. The average T scores (±SD) for PF and CF were 45.4 ± 9.2 and 48.6 ± 11.6, respectively; the average for PI was 3.0 ± 2.6. Approximately half of the patients (47%) endorsed at least mild impairment in PF (T score < 45). Mean PF, CF, and PI did not differ between diagnostic groups. Individuals who endorsed more impairment on one measure also tended to endorse more impairment on another (Pearson r = 0.43-0.59). In the multivariate models, age, smoking, pain medications, and serotonergic medications were associated with impairment in at least one PRO domain. The Damage Index for APS was significantly correlated with both PF and CF. CONCLUSION: Individuals living with APS endorsed more impairment in PF (and potentially CF) than expected for the general population. The relationship between certain medications and PROs warrants further study, as does the longitudinal trajectory of these and other PROs.

Sustainable Urban Mobility Plans: implementation process and indicators to evaluate effects on physical activity.

BACKGROUND: Active mobility and public transport increase physical activity (PA) levels. With varying intensity and effectiveness, European cities implement Sustainable Urban Mobility Plans (SUMPs) to spur transport-related PA. Therefore, we aim to examine drivers and barriers to SUMP implementation and assess its influence on PA across European cities. METHODS: We screened policy reports to gain insights into SUMP implementation in one Danish, two German and two Polish cities. Further, we conducted semi-structured interviews with SUMP stakeholders in these cities to explore their experiences with SUMP implementation. Thematic analysis of interview transcripts was applied to identify similarities and differences across cities. To assess the effect of SUMP implementation on PA, we searched for data on indicators of transport-related PA. RESULTS: All investigated cities are committed to sustainable mobility. Nonetheless, complex institutional structures, the dominant role of motorized traffic as well as complex regional and local policy integration hamper SUMP implementation. Danish, German and Polish cities face different contexts in terms of financing, national guidelines and the prominence of sustainability as a policy objective. Each city adopts unique indicators for monitoring the effects of SUMPs on transport-related PA. The variety of indicators and limited data availability impede a comparative evaluation across cities. Constrained by this restriction, we identified motorization rate, modal split and public transport ridership as suitable indicators. CONCLUSIONS: Local idiosyncrasies need to be accounted for when assessing the implementation of SUMPs. Nonetheless, consistent indicators and data transparency are essential for comparing the effectiveness of SUMPs and their impact on PA.