Bleeding and thrombotic events in bevacizumab-treated patients with colorectal cancer on novel oral anticoagulants and antiplatelet medications.

Background: Bevacizumab is a humanized monoclonal anti-VEGF antibody often given in combination with fluorouracil-based chemotherapy as therapy for metastatic colorectal cancer (mCRC). The bleeding and thrombotic event rates in the setting of concurrent novel oral anticoagulants with and without aspirin and bevacizumab treatment in patients with mCRC remain unclear. Methods: 462 patients with mCRC at Barnes-Jewish Hospital were identified between December 1, 2016 and December 1, 2021 and screened for concurrent treatment with bevacizumab and anticoagulant or antiplatelet therapy. Demographic and clinical information was extracted by electronic chart review. Results: 21 patients were identified who received bevacizumab and either apixaban or rivaroxaban for mCRC treatment. Aspirin was prescribed in some of these patients within three years of starting apixaban or rivaroxaban. Of the 13 patients without aspirin prescription, nine were given apixaban, and four were given rivaroxaban while on bevacizumab. Four out of nine of the patients who received apixaban had epistaxis, and only one case resulted in any treatment discontinuation. Three out of four of the patients who received rivaroxaban experienced bleeding, and one of these three patients discontinued bevacizumab. We also looked at eight patients who had received aspirin. Two out of seven patients who received apixaban/bevacizumab/aspirin experienced bleeding and discontinued a medication. The patient who received rivaroxaban/bevacizumab/aspirin experienced bleeding and discontinued bevacizumab. No patient experienced adverse thrombotic events. Conclusions: Patients with mCRC treated with bevacizumab and apixaban with no history of aspirin use within three years have a relatively low risk of bleeding that warrants treatment discontinuation.

Silver nanoparticles selectively treat triple-negative breast cancer cells without affecting non-malignant breast epithelial cells in vitro and in vivo.

Silver nanoparticles (AgNPs) show promise for treatment of aggressive cancers including triple-negative breast cancer (TNBC) in preclinical cancer models. For clinical development of AgNP-based therapeutics, it will be necessary to clearly define the specific physicochemical features of the nanoparticles that will be used, and to tie these properties to biological outcomes. To fill this knowledge gap, we performed thorough structure/function, mechanistic, safety, and efficacy studies to assess the potential for AgNPs to treat TNBC. We establish that AgNPs, regardless of size, shape, or stabilizing agent, are highly cytotoxic to TNBC cells at doses that are not cytotoxic to non-malignant breast epithelial cells. In contrast, TNBC cells and non-malignant breast epithelial cells are similarly sensitive to exposure to silver cation (Ag+), indicating that the nanoparticle formulation is essential for the TNBC-specific cytotoxicity. Mechanistically, AgNPs are internalized by both TNBC and non-malignant breast cells, but are rapidly degraded only in TNBC cells. Exposure to AgNPs depletes cellular antioxidants and causes endoplasmic reticulum stress in TNBC cells without causing similar damage in non-malignant breast epithelial cells. AgNPs also cause extensive DNA damage in 3D TNBC tumor nodules in vitro, but do not disrupt the normal architecture of breast acini in 3D cell culture, nor cause DNA damage or induce apoptosis in these structures. Lastly, we show that systemically administered AgNPs are effective at non-toxic doses for reducing the growth of TNBC tumor xenografts in mice. This work provides a rationale for development of AgNPs as a safe and specific TNBC treatment.

Myopia control in children through refractive therapy gas permeable contact lenses: is it for real?

PURPOSE: To compare the safety and efficacy of orthokeratology as a nonsurgical treatment for myopia in children with alternate methods, such as soft contact lenses, rigid gas permeable lenses, and spectacles, throughout multiple studies. DESIGN: Perspective with literature review. METHODS: Analysis of recent studies to determine the safety and effectiveness of orthokeratology versus soft contact lenses, rigid gas permeable lenses, and spectacles in children. RESULTS: In all of the studies reviewed, the use of orthokeratology lenses proved to reduce myopia, to improve visual acuity, and, with the exception of the SMART study, to reduce the rate of axial elongation. Orthokeratology has been shown to be as effective as other methods in treating myopia and to be more effective at treating axial elongation. There were no major adverse events in any of the studies comparing orthokeratology with other methods of myopia treatment. CONCLUSIONS: Studies show that the use of orthokeratology is a safe and efficacious nonsurgical treatment for myopia and that it is capable of slowing axial elongation, making it an effective myopic treatment for children.