Differences in the perceptions of patients with primary biliary cholangitis and physicians from various hospital departments: An online survey.

OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that affects the quality of life (QoL) of patients. This study aimed to evaluate the differences in perceptions of PBC among physicians from different hospital departments and patients with PBC. METHODS: An online survey regarding the general knowledge, diagnosis, and management of PBC was completed by physicians and patients. RESULTS: A total of 239 patients with PBC and 239 physicians from eight hospital departments (gastroenterology, infectious diseases, rheumatology, hepatobiliary surgery, pathology, clinical laboratory, ultrasound, and radiology) completed the survey. The results showed that physicians from departments other than gastroenterologists and rheumatologists lacked knowledge of PBC, and that junior gastroenterologists were uncertain about the diagnostic and treatment pathways of PBC. Importantly, the lack of knowledge significantly impacted the QoL of patients, especially the emotional scores of PBC-40 (odds ratio -2.556, 95% confidence interval -3.852 to -1.260, P < 0.001). In addition, there was a perceived knowledge gap between patients and gastroenterologists. CONCLUSIONS: Physicians must improve their awareness of PBC. Patient education and patient-physician communication are important for improving the patient's QoL.

Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial.

Background: A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC. Methods: In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964. Results: From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed. Conclusions: Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

κ-opioid receptor activation prevents against arrhythmias by preserving Cx43 protein via alleviation of intracellular calcium.

κ-opioid receptor (κ-OR) activation with U50,488H, a selective κ-OR agonist, has been previously demonstrated to prevent against cardiac arrhythmias via stabilizing the synthesis and degradation of an integral membrane protein, Cx43, in gap junctions. However, the exact prevention mechanism remains unclear. The present study tested the hypothesis that the kappa OR agonist U50,488H mediates the prevention of arrhythmia through the regulation of intracellular calcium leading to the preservation of Cx43 protein. By performing electrocardiogram monitoring and immunoblotting in isolated Langendorff-perfused rat hearts, high concentrations of calcium-perfused rat hearts exhibited increased cardiac arrhythmias. Diminished expression of Cx43 protein was observed. The utilization of a whole-cell patch clamp technique revealed that U50,488H inhibited L-type calcium current in single ventricular myocytes in a dose-dependent manner. These effects were blocked by nor-binaltorphimine, potent and selective κ-OR antagonists. Administration of U50,488H before myocardial ischemia resulted in an attenuated of total arrhythmia scores. The attenuation effect was blocked by nor-binaltorphimine. The attenuation effect was antagonized both by Bay K8644, a L-type calcium channel agonist, and also by the Cx43 uncoupler heptanol. Finally, immunoblotting data demonstrated that the preservation of Cx43 protein conferred by U50,488H was reversed in the presence of Bay K8644. In summary, the present study demonstrates κ-OR activation with U50,488H may confer antiarrhythmic effects via modulation of the calcium-Cx43 pathway.