Among Japanese patients with NVAF, treatment with apixaban 5/2.5 mg BID was associated with a significantly lower risk of major bleeding and any bleeding when compared to warfarin. Treatment with dabigatran 150/110 mg BID or rivaroxaban 15/10 mg QD was associated with a significantly lower risk of major bleeding, but not any bleeding, than warfarin. The potential benefit of individual NOACs in real-world practice needs to be assessed further.
Systemic treatment patterns for advanced or recurrent NSCLC in Japan were varied. Nearly 30% of all patients and approximately half of elderly patients did not receive systemic treatment. Treatment rates declined with subsequent therapeutic lines. Generally, guidelines were followed with first-line treatment administration, but not with second-line administration. These results underscore the need for better guideline adherence and more optimal treatment in and elderly patients and in those receiving later-line treatment in Japan.
Although chemotherapeutic agents and molecular medicine are pillars of successful treatment of cancer, the recent clinical development of immunotherapies shows compelling promise in the treatment of many tumor types. In hematologic malignancies, immunotherapies centered upon cytolytic T lymphocytes as drugs, such as chimeric antigen receptor (CAR)-T cells and bispecific T-cell engagers (BiTE) or antibodies (BsAb), are central among these advances. BiTEs and BsAbs are "offthe-shelf" drug therapies that circumvent the need for timeconsuming and expensive ex vivo manipulation of patient cells. These agents often consist of monoclonal antibodies or singlechain variable fragments in the case of BiTEs, engineered with one binding site directed toward a tumor-specific antigen and another against the T-lymphocyte activating receptor CD3epsilon. BsAbs redirect T cells to kill tumors by bringing them into physical contact and activating secretion of cytotoxic molecules (1). Due to their novel mode of action, BsAb therapeutics may provide an effective option for all patients, including those with cytogenetically high-risk or heavily pretreated disease that renders them more resistant to standard-of-care therapy.
Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that play a role in immune cell signaling, activation, and survival. GITR is a therapeutic target for directly activating effector CD4 and CD8 T cells, or depleting GITR-expressing regulatory T cells (Tregs), thereby promoting anti-tumor immune responses. GITR activation through its native ligand is important for understanding immune signaling, but GITR structure has not been reported. Here we present structures of human and mouse GITR receptors bound to their cognate ligands. Both species share a receptor–ligand interface and receptor–receptor interface; the unique C-terminal receptor–receptor enables higher order structures on the membrane. Human GITR–GITRL has potential to form a hexameric network of membrane complexes, while murine GITR–GITRL complex forms a linear chain due to dimeric interactions. Mutations at the receptor–receptor interface in human GITR reduce cell signaling with in vitro ligand binding assays and minimize higher order membrane structures when bound by fluorescently labeled ligand in cell imaging experiments.
In this EMR-based clinical study, patients who switched to DOACs had both poor or inadequate PT-INR control and higher risk factors of stroke. Many patients receiving warfarin did not achieve sufficient PT-INR therapeutic range. DOACs could be recommended in Japanese patients with NVAF with inadequate PT-INR control and increased risk of stroke.
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