Outpatient Follow-up of Pulmonary Embolism: Putting It all Together.

Many patients discharged after an acute pulmonary embolism (PE) admission have inconsistent outpatient follow-up and insufficient workup for chronic complications of PE. A structured outpatient care program is lacking for the different phenotypes of chronic PE, such as chronic thromboembolic disease, chronic thromboembolic pulmonary hypertension, and post-PE syndrome. A dedicated PE follow-up clinic extends the organized, systematic care provided to patients with PE via the PERT (Pulmonary Embolism Response Team) model in the outpatient setting. Such an initiative can standardize follow-up protocols after PE, limit unnecessary testing, and ensure adequate management of chronic complications.

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery.

Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.