Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Diagnosis and Treatment of Acute Pancreatitis

The pancreas is a glandular organ that is responsible for the proper functioning of the digestive and endocrine systems, and therefore, it affects the condition of the entire body. Consequently, it is important to effectively diagnose and treat diseases of this organ. According to clinicians, pancreatitis&mdash;a common disease affecting the pancreas&mdash;is one of the most complicated and demanding diseases of the abdomen. The classification of pancreatitis is based on clinical, morphologic, and histologic criteria. Medical doctors distinguish, inter alia, acute pancreatitis (AP), the most common causes of which are gallstone migration and alcohol abuse. Effective diagnostic methods and the correct assessment of the severity of acute pancreatitis determine the selection of an appropriate treatment strategy and the prediction of the clinical course of the disease, thus preventing life-threatening complications and organ dysfunction or failure. This review collects and organizes recommendations and guidelines for the management of patients suffering from acute pancreatitis

Result of two randomized trials comparing nolatrexed (Thymitaq (TM)) versus methotrexate in patients with recurrent head and neck cancer

We report on two randomized trials performed in the USA and Europe, which compared methotrexate and nolatrexed as treatment for patients with recurrent head and neck cancer. Eligibility criteria included: histologically confirmed squamous-cell carcinoma, measurable disease, adequate hematological, renal and hepatic functions, failure of a first-line chemotherapy, and informed consent. Methotrexate 40 mg/m(2) was weekly given by short infusion, and nolatrexed 725 mg/m(2) per day was administered as a five-day continuous infusion, every three weeks. A total of 139 patients (63 in the USA, 76 in Europe) were randomized based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate, respectively. Patient characteristics included 115 males and 24 females; median age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred: neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of overall survival, respectively. Nolatrexed has demonstrated a similar activity to methotrexate

Alternating Oligo[(2,3-O-isopropylidene-L-threitol)]-co-[(E,E)-1,4-bis(styryl)benzene]s: The Linear Chirality Transmisson Additivity Relationship in Nematic Liquid Crystals

[[abstract]]Alternating oligo[2,3-O-isopropylidene-l-threitol]-co-[(E,E)-1,4-bis(styryl)benzene]s (denoted as 2−6 in the article) show helical twisting power (HTP), in 4-pentoxyl-4′-biphenylcarbonitrile (5OCB), linearly proportional to the number of the chiral cores in the oligomers. The HTP per chiral core of −1.75 μm−1 was recorded in the correlation plot with a correlation coefficient of R = 0.99. These results suggested that the C2 chiral l-threitol cores are aligned along the same axis. The comparable linear dichroism (LD) of 0.42 ± 0.02 obtained for (rac)-2−5 at 405 nm, and of 0.52 ± 0.03 for E7, a commercially available room temperature nematic solvent, at 347 nm in a parallel rubbed cell indicated that the long axis of the bis(styryl)benzene segments is more or less parallel to the director of the E7 in the LC matrix. This observation is highly exciting because the HTP per core could still be maintained, no matter whether the cores are evenly spread in a form of monomer in the LC matrix or tightly confined in a polymer. Theoretical treatments about the conformations of the dopant in the nematic matrix are discussed.[[journaltype]]國外[[incitationindex]]SCI[[incitationindex]]EI[[booktype]]紙本[[countrycodes]]US

Talactoferrin alfa versus placebo in patients with refractory advanced non-small-cell lung cancer (FORTIS-M trial)

Background: Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC). Patients and methods: An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5 g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR). Results: Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873-1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835-1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698-1.33; P = 0.8336]. The safety profiles were comparable between arms. Conclusions: There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology All rights reserved