Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn's Disease: A Post Hoc Analysis From the CALM Study
INFLAMMATORY BOWEL DISEASES
Authors: Reinisch, Walter; Panaccione, Remo; Bossuyt, Peter; Baert, Filip; Armuzzi, Alessandro; Hebuterne, Xavier; Travis, Simon; Danese, Silvio; Sandborn, William J.; Schreiber, Stefan; Berg, Sofie; Zhou, Qian; Kligys, Kristina; Neimark, Ezequiel; Suleiman, Ahmed A.; D'Haens, Geert; Colombel, Jean-Frederic
Background CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) <4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP <5 mg/L or >= 5 mg/L and FC <250 mu g/g or >= 250 mu g/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using chi(2) test. Results The proportion of patients who achieved the primary end point CDEIS <4 and no deep ulcers was significantly greater for those with FC <250 mu g/g (74%; P < 0.001), with an additive effect for CRP <5 mg/L. The association of FC <250 mu g/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin <250 mu g/g, CRP <5 mg/L, and CDAI <150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS <4 and no deep ulcers 48 weeks after randomization. Conclusion This post hoc analysis of CALM demonstrated that a cutoff of FC <250 mu g/g is a useful surrogate marker for mucosal healing in CD.
Mon2-monocytes and increased CD-11b expression before transcatheter aortic valve implantation are associated with earlier death
INTERNATIONAL JOURNAL OF CARDIOLOGY
Authors: Pfluecke, C.; Wydra, S.; Berndt, K.; Tarnowski, D.; Cybularz, M.; Jellinghaus, S.; Mierke, J.; Ende, G.; Poitz, D. M.; Barthel, P.; Heidrich, F. M.; Quick, S.; Sveric, K. M.; Speiser, U.; Linke, A.; Ibrahim, K.
Background: In the first three months after Transcatheter aortic valve implantation (TAVI), a remarkable number of patients have an unfavorable outcome. An inflammatory response after TAVI is suspected to have negative effects. The exact mechanisms remain unclear. We examined the influence of monocyte subpopulations on the clinical outcome, along with the degree of monocyte activation and further parameters of inflammation and platelet activation. Methods: Flow-cytometlic quantification analyses of peripheral blood were done in 120 consecutive patients who underwent TAVI (one day before TAVI and on day 1 and 7 after TAVI). Monocyte-subsets were defined by their CD14 and CD16 expression, monocyte-platelet-aggregates (MPA) by CD14/CD41 co-ex pression. The extent of monocyte activation was determined by quantification of CD11b-expression (activation epitope). Additionally, pro-inflammatoiy cytokines such as interleukin (IL)-6, IL-8, C-reactive protein were measured with the cytometric bead array method or standard laboratory tests. Results: Elevated Mon2 (CD14(-+)CD16(+)) - monocytes (38 vs. 62 cells/mu l, p < 0.001) and a high expression of CD11b prior to TAVI (MIL 50.1 vs. 84.6, p < 0.05) were independently associated with death 3 months after TAVI. Mon2 showed the highest CD11b-expression and CD11b correlated with platelet activation and markers of systemic inflammation. Even CRP and IL-8 before TAVI were associated with death after TAVI. In contrast, a systemic inflammation response shortly after TAVI was not associated with early death. Conclusions: Elevated Mon2-monocytes and a high level of monocyte activation before TAVI are associated with early mortality after TAVI. Chronic inflammation in aging patients seems to be an important risk factor after TAVI. (C) 2020 Elsevier B.V. All rights reserved.