The present study sought to determine the anti-tumor effects of OXA-11, a potent, novel small-molecule amino pyrimidine inhibitor (1.2 pM biochemical IC50) of focal adhesion kinase (FAK). In studies of cancer cell lines, OXA-11 inhibited FAK phosphorylation at phospho-tyrosine 397 with a mechanistic IC50 of 1 nM in TOV21G tumor cells, which translated into functional suppression of proliferation in 3-dimensional culture with an EC50 of 9 nM. Studies of OXA-11 activity in TOV21G tumor-cell xenografts in mice revealed a pharmacodynamic EC50 of 1.8 nM, indicative of mechanistic inhibition of pFAK [Y397] in these tumors. OXA-11 inhibited TOV21G tumor growth in a dose-dependent manner and also potentiated effects of cisplatin on tumor cell proliferation and apoptosis in vitro and on tumor growth in mice. Studies of pancreatic neuroendocrine tumors in RIP-Tag2 transgenic mice revealed OXA-11 suppression of pFAK [Y397] and pFAK [Y861] in tumors and liver. OXA-11 given daily from age 14 to 17 weeks reduced tumor vascularity, invasion, and when given together with the anti-VEGFR-2 antibody DC101 reduced the incidence, abundance, and size of liver metastases. Liver micrometastases were found in 100 % of mice treated with vehicle, 84 % of mice treated with OXA-11, and 79 % of mice treated with DC101 (19–24 mice per group). In contrast, liver micrometastases were found in only 52 % of 21 mice treated with OXA-11 plus DC101, and those present were significantly smaller and less numerous. Together, these findings indicate that OXA-11 is a potent and selective inhibitor of FAK phosphorylation in vitro and in vivo. OXA-11 slows tumor growth, potentiates the anti-tumor actions of cisplatin and—when combined with VEGFR-2 blockade—reduces metastasis of pancreatic neuroendocrine tumors in RIP-Tag2 mice.

Introduction:The use of acellular dermal matrices (ADMs) in breast reconstruction is a controversial topic. Recent literature has investigated the effects of ADM sterilization on infectious complications, although with varying conclusions. Previous work by our group showed no difference between aseptic and sterilized products immediately out of the package. In this study, we investigate the microbiologic profiles of these agents after implantation.Methods:In this prospective study, we cultured samples of ADM previously implanted during the first stage of tissue expander-based immediate breast reconstruction. A 1 cm2 sample was excised during the stage II expander–implant exchange procedure, and samples were incubated for 48 hours in tryptic soy broth. Samples with growth were further cultured on tryptic soy broth and blood agar plates. Patient records were also analyzed, to determine if ADM sterilization and microbial growth were correlated with infectious complications.Results:In total, 51 samples of ADM were collected from 32 patients. Six samples were from aseptic ADM (AlloDerm), 27 samples were from ADM sterilized to 10–3 (AlloDerm Ready-to-Use), and 18 samples were from products sterilized to 10–6 (AlloMax). No samples demonstrated bacterial growth. Only 5 patients experienced postoperative complications, of whom only 1 patient was infectious in nature. We failed to demonstrate a statistically significant correlation between sterility and postoperative complications.Conclusions:Our findings showed no difference in microbial presence and clinical outcomes when comparing ADM sterility. Furthermore, no samples demonstrated growth in culture. Our study brings into question the necessity for terminal sterilization in these products.

Objective A treat‐to‐target (TTT) approach improves outcomes in rheumatoid arthritis (RA). In prior work, we found that a learning collaborative (LC) program improved implementation of TTT. We conducted a shorter virtual LC to assess the feasibility and effectiveness of this model for quality improvement and to assess TTT during virtual visits. Methods We tested a 6‐month virtual LC in ambulatory care. The LC was conducted during the 2020–2021 COVID‐19 pandemic when many patient visits were conducted virtually. All LC meetings used videoconferencing and a website to share data. The LC comprised a 6‐hour kickoff session and 6 monthly webinars. The LC discussed TTT in RA, its rationale, and rapid cycle improvement as a method for implementing TTT. Practices provided de‐identified patient visit data. Monthly webinars reinforced topics and demonstrated data on TTT adherence. This was measured as the percentage of TTT processes completed. We compared TTT adherence between in‐person visits versus virtual visits. Results Eighteen sites participated in the LC, representing 45 rheumatology clinicians. Sites inputted data on 1,826 patient visits, 78% of which were conducted in‐person and 22% of which were held in a virtual setting. Adherence with TTT improved from a mean of 51% at baseline to 84% at month 6 (P for trend < 0.001). Each aspect of TTT also improved. Adherence with TTT during virtual visits was lower (65%) than during in‐person visits (79%) (P < 0.0001). Conclusion Implementation of TTT for RA can be improved through a relatively low‐cost virtual LC. This improvement in TTT implementation was observed despite the COVID‐19 pandemic, but we did observe differences in TTT adherence between in‐person visits and virtual visits.