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.

The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.

Identification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated with cytogenetic risk, exceeds the threshold of 60.

Clinical utility of Rome criteria managing functional gastrointestinal disorders in pediatric primary care.

Objective: Our goals were to demonstrate that functional gastrointestinal disorders (FGIDs) can be diagnosed in a positive fashion and managed by family pediatricians (FPs); to assess the compliance of FPs with a predefined diagnostic/therapeutic protocol for managing FGIDs to evaluate efficacy of continuing medical education; and to evaluate the success of reassurance by using a biopsychosocial model in comparison to drug treatment in an open-label, nonrandomized study.

Patients And Methods: A total of 9291 patients, aged birth to 14 years, were prospectively enrolled during a 3-month period by 21 FPs. Follow-up was performed at 1-, 3-, and 12-month intervals.

Serum free light chain ratio, total kappa/lambda ratio, and immunofixation results are not prognostic factors after stem cell transplantation for newly diagnosed multiple myeloma.

Background: The prognostic value of changes in paraprotein markers after stem cell transplantation is unknown. We evaluated disease response using serum immunofixation (s-IFIX), total kappa and lambda ratio (KLR), and free light chain (FLC) ratio in myeloma patients who underwent autologous or autologous plus allogeneic stem cell transplantation.

Methods: We studied s-IFIX, KLR, and FLC ratio in sera from 203 patients, 3 months after transplantation.

The state of the clerkship: a survey of emergency medicine clerkship directors.

Objectives: An emergency medicine (EM) clerkship can provide a medical student with a unique educational experience. The authors sought to describe the current experiential curriculum of the EM clerkship, along with methods of evaluation, feedback, and grading.

Methods: A descriptive survey was utilized.

Clinical evaluation of percent free prostate-specific antigen using the AxSYM system in the best analytical scenario.

Objective: Percent free prostate-specific antigen (PSA) is a promising tool for prostate cancer (CaP) diagnosis. However, its diagnostic performances have not yet been established. The present study was carried out with the aim of evaluating percent free PSA in the most favourable analytical conditions.

Detection of different estrogen receptor forms in breast cancer cytosol by enzyme immunoassay.

Estrogen receptors (ER) are routinely measured in tissue extracts from breast cancer using a radioligand binding assay (RBA) and an enzyme immunoassay (EIA). Although good correlation was found between the two methods, they are expected to measure, at least in part, different ER amounts in individual samples, because the RBA should detect unfilled ER only, whereas EIA should recognize both unfilled receptors and those filled by endogenous estrogens. The purpose of the present investigation was to evaluate if ER-EIA mainly detects ER filled by endogenous estrogens when using an estrogen-free buffer to dilute cytosol samples.