Intravascular ultrasound findings of the Fantom sirolimus-eluting bioresorbable scaffold at six- and nine-month follow-up: The FANTOM II study

Aims: FANTOM II is a prospective multicentre trial assessing the safety and efficacy of the Fantom siroli-mus-eluting bioresorbable coronary scaffold (BRS). The present substudy focuses on the six- and nine-month IVUS findings. Methods and results: A total of 240 patients with de novo coronary artery lesions presenting with stable or unstable disease were included in two sequential cohorts (cohort A [n=117] and cohort B [n=123]) in which angiographic follow-up was performed at either six or nine months, respectively. Matched IVUS data were available for 35 paired cases in cohort A and 26 paired cases in cohort B. At six months, mean and minimum scaffold area (SA) decreased from 6.09±1.08 mm2 to 5.88±1.07 mm2, p=0.009, and 5.27±0.99 mm2 to 5.05±0.99 mm2, p=0.01, respectively. At nine months, no significant change in mean scaffold and minimum scaffold area was observed (6.46±1.11 mm2 to 6.38±0.96 mm2; p=0.35, and 5.45±1.00 mm2 to 5.36±0.86 mm2; p=0.32, respectively). Neointimal hyperplasia area was low at both six (0.11±0.12 mm2) and nine months (0.20±0.21 mm2), as was in-scaffold obstruction volume (1.94±2.25% at six months, and 3.40±4.11% at nine months). Conclusions: The use of the Fantom BRS in stable coronary artery disease was associated with low rates of neointimal hyperplasia volume and in-scaffold volume obstruction at both six and nine months

Utilizing BMP-2 muteins for treatment of multiple myeloma

Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM. Therefore three BMP2 derivatives were generated with modified binding activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing either increased or decreased BMP2 activity. In the context of MM these BMP2 muteins show two functionalities since they act as a) an anti-proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation promoting growth factor. The molecular basis of both activities was shown in two different cellular models to clearly rely on the properties of the investigated BMP2 muteins to compete for the binding of Activin A to the Activin type II receptors. The experimental outcome suggests new therapeutic strategies using BMP2 variants in the treatment of MM-related pathologies