Real-world ALK Testing Trends in Patients With Advanced Non-Small-Cell Lung Cancer in the United States.

Introduction: Patients with non-small-cell lung cancer (NSCLC) whose tumors harbor anaplastic lymphoma kinase (ALK) rearrangements can be treated with ALK tyrosine kinase inhibitors. We assessed real-world ALK biomarker testing and treatment patterns of patients with NSCLC in the United States.

Patients And Methods: Data were extracted from the Flatiron Health electronic health record-derived deidentified database for patients aged ≥18 years with stage IIIB or IV NSCLC and ≥2 clinic visits between January 2011 and December 2019.

The cost-effectiveness of brigatinib in adult patients with ALK inhibitor-naive ALK-positive non-small cell lung cancer from a US perspective.

The discovery of specific oncogenic drivers in non-small cell lung cancer (NSCLC) has led to the development of highly targeted anaplastic lymphoma kinase tyrosine kinase inhibitors (ALKis). Brigatinib is a next-generation ALKi associated with prolonged progression-free survival in patients with ALKi-naive + NSCLC. To estimate the cost-effectiveness of brigatinib compared with crizotinib and alectinib in patients with ALKi-naive + NSCLC, from a US payer perspective.

Catching the GIST: Massive Gastrointestinal Stromal Tumor Presenting as Acute Dyspnea.

We present a case of a 55-year-old woman presenting with worsening shortness of breath and constipation over the course of three days. Initial computed tomography scan showed a large, complex abdominal mass with a vascular pedicle and possible pedunculated origin along the inferior aspect of the greater curvature of the stomach. The mass was further evaluated on magnetic resonance imaging showing an active hemorrhage.

Efficacy and safety of omalizumab in patients with moderate-to-severe asthma: An analytic comparison of data from randomized controlled trials between Chinese and Caucasians.

Background: Omalizumab has > 15 years of real-world evidence of effectiveness in Caucasian patients. In August 2017, it was approved as an add-on therapy for the management of moderate-to-severe asthma in China.

Objective: To compare the efficacy and safety of omalizumab in Chinese and Caucasian patients.

Timing and Duration of Sleep in Hospitalized Children: An Observational Study.

Background And Objectives: Sleep during hospitalization is important, but data on children's sleep quality during hospitalization are lacking. We sought to document sleep duration and awakenings in hospitalized children and explore associations between sleep and chronic care complexity, home sleep quality, and late-night food consumption.

Methods: Children aged 2 to 17 years admitted to a hospitalist service for at least 24 hours were approached for participation.

Indacaterol/glycopyrronium versus salmeterol/fluticasone in Asian patients with COPD at a high risk of exacerbations: results from the FLAME study.

Background: The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting β-agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations. In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study.

Patients And Methods: Patients from Asian centers with moderate-to-very severe COPD and ≥1 exacerbation in the previous year from the 52-week, randomized FLAME study were included.

Indacaterol/glycopyrronium in symptomatic patients with COPD (GOLD B and GOLD D) versus salmeterol/fluticasone: ILLUMINATE/LANTERN pooled analysis.

Background: Indacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD. This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD.

Patients And Methods: Data from LANTERN and ILLUMINATE studies were pooled and analyzed.

Efficacy and Safety of Indacaterol/Glycopyrronium (IND/GLY) Versus Salmeterol/Fluticasone in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: The Chinese Cohort from the LANTERN Study.

Inhaled indacaterol/glycopyrronium fixed-dose combination (IND/GLY) is approved in over 80 countries, including the EU, Japan, Australia and Switzerland and the US. The LANTERN study evaluated the efficacy of IND/GLY compared with inhaled long-acting β-agonist (LABA)/inhaled corticosteroid (ICS) or salmeterol/fluticasone (SFC) in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year. Here we present the efficacy and safety of IND/GLY versus SFC in the Chinese cohort from the LANTERN study.

Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study.

Purpose: Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma.

Methods: This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age).

LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD.

Background: The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient's airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.

Methods: In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.

Efficacy and safety of once-daily glycopyrronium in predominantly Chinese patients with moderate-to-severe chronic obstructive pulmonary disease: the GLOW7 study.

Background: Glycopyrronium is a once-daily (od) long-acting muscarinic antagonist for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The GLOW7 study evaluated the efficacy and safety of od glycopyrronium 50 μg in predominantly Chinese patients with moderate-to-severe COPD.

Methods: In this 26-week, multi-center, double-blind, placebo-controlled, parallel-group study, men and women ≥40 years with moderate-to-severe COPD were randomized to glycopyrronium 50 μg od or placebo (2:1).

Single-agent inhibition of Chk1 is antiproliferative in human cancer cell lines in vitro and inhibits tumor xenograft growth in vivo.

Chk1 is a serine/threonine kinase that plays several important roles in the cellular response to genotoxic stress. Since many current standard-of-care therapies for human cancer directly damage DNA or inhibit DNA synthesis, there is interest in using small molecule inhibitors of Chk1 to potentiate their clinical activity. Additionally, Chk1 is known to be critically involved in cell cycle progression of unperturbed cells.

Regulated binding of importin-α to protein kinase Cδ in response to apoptotic signals facilitates nuclear import.

PKCδ translocates into the nucleus in response to apoptotic agents and functions as a potent cell death signal. Cytoplasmic retention of PKCδ and its transport into the nucleus are essential for cell homeostasis, but how these processes are regulated is poorly understood. We show that PKCδ resides in the cytoplasm in a conformation that precludes binding of importin-α.

Induction of apoptosis is driven by nuclear retention of protein kinase C delta.

Protein kinase C delta (PKC delta) mediates apoptosis downstream of many apoptotic stimuli. Because of its ubiquitous expression, tight regulation of the proapoptotic function of PKC delta is critical for cell survival. Full-length PKC delta is found in all cells, whereas the catalytic fragment of PKC delta, generated by caspase cleavage, is only present in cells undergoing apoptosis.

Salmeterol/Fluticasone Propionate in a Single Inhaler is Superior to Budesonide Alone in Control of Chinese Asthmatic Adults : An Open-Label, Randomised, 6-Week Study.

Objective And Design: There is comparatively little information on asthma management in China. A multicentre, randomised, open-label, parallel-group, 6-week treatment study was conducted to evaluate the efficacy and safety of salmeterol/fluticasone propionate combination treatment in Chinese adult asthmatic patients.

Setting And Patients: 398 patients with a documented history of moderate-to-severe asthma were randomised to treatment.

Suppression of apoptosis in the protein kinase Cdelta null mouse in vivo.

Protein kinase C (PKC) delta is an essential regulator of mitochondrial dependent apoptosis in epithelial cells. We have used the PKCdelta(-/-) mouse to ask if loss of PKCdelta protects salivary glands against gamma-irradiation-induced apoptosis in vivo and to explore the mechanism underlying protection from apoptosis. We show that gamma-irradiation in vivo results in a robust induction of apoptosis in the parotid glands of wild type mice, whereas apoptosis is suppressed by greater than 60% in the parotid glands of PKCdelta(-/-) mice.

Suppression of cell migration by protein kinase Cdelta.

The ability of cancer cells to migrate is strongly correlated with malignant progression and metastasis. Survival signals that suppress apoptosis have also been linked to increased cell motility. We previously reported that suppression of protein kinase Cdelta (PKCdelta) provided survival signals in a rat fibroblast model system.