Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression. Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55-0.75) and OS (HR 0.83; 95%-CI, 0.76-0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41-3.58). Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs

Consumer credit in comparative perspective

We review the literature in sociology and related fields on the fast global growth of consumer credit and debt and the possible explanations for this expansion. We describe the ways people interact with the strongly segmented consumer credit system around the world—more specifically, the way they access credit and the way they are held accountable for their debt. We then report on research on two areas in which consumer credit is consequential: its effects on social relations and on physical and mental health. Throughout the article, we point out national variations and discuss explanations for these differences. We conclude with a brief discussion of the future tasks and challenges of comparative research on consumer credit.Accepted manuscrip

Hydrodeoxygenation of Isoeugenol over Ni- and Co-Supported Catalysts

Hydrodeoxygenation (HDO) of isoeugenol was investigated over several Ni (Ni/SiO2, Ni/graphite) and Co (Co/SBA-15, Co/SiO2, Co/TiO2, Co/Al2O3) catalysts at 200 and 300 degrees C under 30 bar hydrogen pressure in a batch reactor. The catalysts were prepared by an impregnation method and systematically characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy and energy dispersive analysis, organic elemental, and thermogravimetrical analysis before and after the reaction. Analysis of the liquid, solid, and gaseous products was performed to identify isoeugenol transformation pathways. The maximum yield of the desired propylcyclohexane (PCH) (63%) and the highest sum of masses of reactants and products in the liquid phase based on GC results (GCLPA) (79%) were obtained over 10 wt % Co/SBA-15. HDO of isoeugenol over 11 wt % Co/SiO2 resulted in 50% PCH yield with a rather similar GCLPA of 73%. Low yields of PCH and the liquid phase mass balance closure were obtained over highly dispersed 15 wt % Co/Al2O3 and 15 wt % Co/TiO2. PCH yield was 60% over Ni/graphite and 44% over Ni/SiO2 after 4 h with GCLPA values of 73 and 70%, correspondingly. Overall PCH yields increased in the following order: Co/TiO2 < Co/Al2O3 < Ni/SiO2 < Co/SiO2 < Ni/graphite < Co/SBA-15. Regeneration and reuse of industrially relevant 11 wt % Co/SiO2 was succesfully demonstrated

Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer

The purpose of this study was to determine whether epirubicin, cisplatin and infused 5FU (ECF) improves overall survival (OS) compared to 5FU, etoposide and leucovorin (FELV) in patients with previously untreated advanced biliary cancer in a prospective randomised study. Patients were randomly assigned to receive epirubicin, cisplatin and infused 5FU ECF or bolus 5FU etoposide and leucovorin (FELV). The primary end point was OS with secondary end points of objective response rate (ORR), failure-free survival (FFS), quality of life (QOL) and toxicity. In all, 54 patients were recruited with 27 randomly assigned to each arm. The median OS for ECF was 9.02 months (95% confidence interval (CI): 6.46–11.51) and FELV 12.03 months (95% CI: 9.3–14.7), P=0.2059. Objective response rates were similar for both arms: ECF 19.2% (95% CI: 6.55–39.3); FELV 15% (95% CI: 3.2–37.9), P=0.72. There was significantly increased grade 3/4 neutropenia with FELV vs ECF (53.8 vs 29.5%, respectively, P=0.020). Symptom resolution was impressive for both regimens. This is the largest reported randomised study to date in this setting. ECF did not improve OS compared to FELV, but was associated with less acute toxicity. These data suggest that chemotherapy can prolong OS and achieve good symptomatic relief in advanced biliary cancer

Using "ghost front" to predict the arrival time and speed of CMEs at Venus and Earth

Using in-situ measurements and remote-sensing observations, we study two Coronal Mass Ejections (CMEs) that left the Sun on 13-14 June 2012 and impacted both Venus and Earth while the planets were in close radial alignment. The two CMEs generate multiple fronts in STEREO/HI images, which can also be observed in ‘J-map’ as bifurcated features. We present the ‘ghost front’ model to combine remote observations from STEREO/SECCHI and in-situ observations from the Wind and VEX spacecraft, and to derive the kinematics and propagation directions of the CMEs. By fitting the observations of multiple fronts to a kinematically evolving flux rope (KEFR) model and assuming the CMEs undergo deceleration through frictional drag with a steady-state solar wind, we confirm that the outer and inner fronts of the CMEs as detected in HI images are consistent with peaks in Thomson scattered light returned from the flank and nose of a single front for each CME. An interaction takes place between the CME-1 and CME-2 that can be observed in the HI-1 field of view before CME-1 encounters Venus. The multi-point in-situ observations of the shock-CME interaction event serve as further evidence of the interaction between CMEs. The arrival times calculated from the ghost-front model are within 2.5 hours of those observed at VEX and Wind. Our analysis indicates that ghost fronts could provide information about the longitudinally-extended shape of the CME in the field of view of HI-1, which can be used to improve the forecast of ICME arrival time at Earth

Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, treatment options are limited and often inefficient. The aim of this study was to determine current survival rates for patients diagnosed with HCC and to identify prognostic factors, which will help in choosing optimal therapies for individual patients. A retrospective analysis of medical records was performed on 389 patients who were identified through the central tumour registry at our institution from 1998 to 2003. Clinical parameters, treatments received and survival curves from time of diagnosis were analysed. Overall median survival was 11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170 patients received transarterial chemoembolisation (TACE) and/or percutaneous ethanol injections (PEI) with a median survival rate of 16 months for patients receiving TACE, 11 months for patients receiving PEI and 24 months for patients receiving TACE followed by PEI. Independent negative prognostic parameters for survival were the presence of portal vein thrombosis, advanced liver cirrhosis (Child–Pugh score B or C) and a score of >2. This study will help to estimate survival rates for patients with HCC according to their clinical status at diagnosis and the treatments received

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Frontal sinuses and human evolution

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species? holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species. Variation in frontal sinus shape and dimensions has high potential for phylogenetic discussion when studying human evolution