BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas.

Bromodomain and extraterminal proteins (BET) play key roles in regulation of gene expression, and may play a role in cancer-cell proliferation, survival, and oncogenic progression. CC-90010-ST-001 (NCT03220347) is an open-label phase I study of trotabresib, an oral BET inhibitor, in heavily pretreated patients with advanced solid tumors and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Primary endpoints were the safety, tolerability, maximum tolerated dose, and RP2D of trotabresib.

Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, "window-of-opportunity" study.

Background: The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection.

Methods: Patients received trotabresib 30 mg/day on days 1-4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery.

Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma.

Background: Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas.

Methods: In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM.

Delirium and Psychiatric Sequelae Associated to SARS-CoV-2 in Asymptomatic Patients With Psychiatric History and Mild Cognitive Impairment as Risk Factors: Three Case Reports.

Human coronaviruses have neuroinvasive and neurotropic abilities that might explain psychiatric outcomes in affected patients. We hypothesized that delirium might be the sole clinical manifestation or even the prodrome of a psychiatric episode consistent with the mental history of a few infected patients with a preexisting diagnosed cognitive impairment. We examined three patients with preexisting mild cognitive impairment and delirium at admission for suspected SARS-CoV-2 infection.

Wetting properties of porous high temperature polymer electrolyte fuel cells materials with phosphoric acid.

Wetting properties of phosphoric acid in porous materials of high temperature fuel cells (HT-PEFC), operating at around 160 °C, are important for cell performance and durability, but the underlying wetting parameters have been unknown so far. Therefore, the influence of phosphoric acid temperature and concentration on the wetting behavior of porous HT-PEFC materials is investigated. The acid filling of gas diffusion and catalyst layers as function of capillary pressure is monitored with X-ray tomographic microscopy under the well defined conditions of an ex situ set-up at temperatures up to 160 °C.