Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer.

Background The MAPK pathway plays a central role in regulation of several cellular processes, and its dysregulation is a hallmark of biliary tract cancer (BTC). Binimetinib (MEK162), a potent, selective oral MEK1/2 inhibitor, was assessed in patients with advanced BTC. Patients and Methods An expansion cohort study in patients who received ≤1 line of therapy for advanced BTC was conducted after determination of the maximum tolerated dose in this Phase 1 trial. Patients received binimetinib 60 mg twice daily. The primary objectives were to characterize the safety profile and pharmacokinetics of binimetinib in advanced BTC. Secondary objectives included assessment of clinical efficacy, changes in weight and lean body mass, and pharmacodynamic effects. Tumor samples were assessed for mutations in relevant genes. Results Twenty-eight patients received binimetinib. Common adverse events (AEs) were mild, with rash (82%) and nausea (54%) being most common. Two patients experienced grade 4 AEs, one generalized edema and the other pulmonary embolism. The pharmacokinetics in this patient population were consistent with those previously reported (Bendell JC et al., Br J Cancer 2017;116:575-583). Twelve patients (43%) experienced stable disease and two had objective responses (1 complete response, 1 partial response) per Response Evaluation Criteria in Solid Tumors and stable metabolic disease by positron emission tomography/computed tomography. Most patients (18/25; 72%) did not have KRAS, BRAF, NRAS, PI3KCA, or PTEN mutations, nor was there correlation between mutation status and response. The average non-fluid weight gain was 1.3% for lean muscle and 4.7% for adipose tissue. Conclusion Binimetinib was well tolerated and showed promising evidence of activity in patients with BTC. Correlative studies suggested the potential for binimetinib to promote muscle gain in patients with BTC.

A cross sectional study of newborn care practices in Gilgit, Pakistan.

OBJECTIVE: The purpose of this article is to explore the traditional newborn-care beliefs and practices and to identify factors that affect newborn health, aiming to design an appropriate, culturally-sensitive and acceptable intervention to reduce neonatal morbidity and mortality. METHODS: A cross sectional study was conducted in the district of Gilgit in Pakistan. A structured questionnaire was administered to 708 mothers who gave birth to a live child in the past one year. Descriptive and inferential analysis was performed to identify socio-economic and health care factors associated with newborn care practices. RESULTS: Illiterate mothers were more likely to use harmful newborn care practices, while those seeking health care from private sector were less likely to use harmful newborn care practices. Ninety-four percent of the newborns were given a bath soon after birth, likelihood to be 2 times more amongst illiterate mothers. Cord application was a very common practice, mostly with matti (crashed apricot seed), and a majority of the mothers reported newborn massage generally with mustard oil. The administration of colostrum as the first feed was relatively common in the study area. Twenty-seven percent of mothers reported giving pre-lacteals; from which prominent feeds included salt water (44%) and cow's milk (26%). Initiation of breastfeeding within 1 hour after birth was (71%), while (29%) reported to breastfeed their newborn within 24 hours. Thirty-seven percent newborns were exclusively breastfed for six months. CONCLUSION: This study underscores the existence and predominance of risky practices in newborn care; that stresses the need for health education programs to ensure safety of the newborn.

Three-dimensional echocardiography of left atrial appendage thrombus.

Transesophageal echocardiography (TEE) is superior to transthoracic echocardiography (TTE) in evaluating the left atrial appendage (LAA) as a potential cardiac source of embolus in patients with stroke. We describe two such patients in whom a TEE and subsequently a three-dimensional (3-D) reconstruction of the LAA were performed. These case reports show that 3-D echocardiography provides better visualization of LAA anatomy, and that a 3-D description of LAA morphology may be the basis of describing normal and abnormal LAA.