Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Toughness and elasticity from phase separation

A simple one-step method that enables the random copolymerization of two monomers with different solubility in ionic liquids creates phase-separated elastic and stiff domains that result in ultra-tough and stretchable ionogels.11Nsciescopu

Flexible and biodegradable electronic implants for diagnosis and treatment of brain diseases

© 2021 The Author(s)In the diagnosis and treatment of brain diseases, implantable devices have immense potential for intracranial sensing of brain activity and application of controlled therapy for providing feedback to the sensing. Flexible materials are preferred for implantable devices, as they can minimise implanted device–brain tissue mechanical mismatch. Moreover, biodegradable implantable devices can reduce potential immunological side-effects. Biodegradability also helps avoid the burdensome secondary surgery for retrieving the implanted device. In this study, we reviewed recent advancements related to the use of flexible and biodegradable type of implantable devices for the diagnosis and treatment of brain diseases. Representative cases of intracranial sensing and feedback therapy are introduced, and then a brief discussion concludes the review.11Nsciescopu

Bioresorbable Electronic Implants: History, Materials, Fabrication, Devices, and Clinical Applications

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Medical implants, either passive implants for structural support or implantable devices with active electronics, have been widely used for the diagnosis and treatment of various diseases and clinical issues. These implants offer various functions, including mechanical support of biological structures in orthopedic and dental applications, continuous electrophysiological monitoring and feedback of electrical stimulation in neuronal and cardiac applications, and controlled drug delivery while maintaining arterial structure in drug-eluting stents. Although these implants exhibit long-term biocompatibility, surgery for their retrieval is often required, which imposes physical, biological, and economical burdens on the patients. Therefore, as an alternative to such secondary surgeries, bioresorbable implants that disappear after a certain period of time inside the body, including bioresorbable active electronics, have been highlighted recently. This review first discusses the historical background of medical implants and briefly define related terminology. Representative examples of non-degradable medical implants for passive structural support and/or for diagnosis and therapy with active electronics are also provided. Then, recent progress in bioresorbable active implants composed of biosignal sensors, actuators for therapeutics, wireless power supply components, and their integrated systems are reviewed. Finally, clinical applications of these bioresorbable electronic implants are exemplified with brief conclusion and future outlook11sci

Local Drug Delivery Strategies for Glioblastoma Treatment

Glioblastoma multiforme (GBM) is a brain tumor notorious for its malignancy. The key reason for the lim- ited efficacy of standard treatment is the high recurrence rate of GBM, even after surgical resection. Hence, intensive postsurgical chemical therapies, such as the systemic delivery of various drugs and/ or drug combinations, are typically followed after surgery. However, overcoming the blood-brain barrier by systemic administration to efficiently deliver drugs to the brain tumor remains a daunting goal. There- fore, various local drug delivery methods showing potential for improved therapeutic efficacy have been proposed. In particular, the recent application of electronic devices for the controlled delivery of che- motherapy drugs to GBM tissue has attracted attention. We herein review the recent progress of local drug delivery strategies, including electronics-assisted strategies, at the research and commercial level. We also present a brief discussion of the unsolved challenges and future research direction of localized chemotherapy methods for GBM.22Nkciothe

Materials engineering, processing, and device application of hydrogel nanocomposites

Hydrogels are widely implemented as key materials in various biomedical applications owing to their soft, flexible, hydrophilic, and quasi-solid nature. Recently, however, new material properties over those of bare hydrogels have been sought for novel applications. Accordingly, hydrogel nanocomposites, i.e., hydrogels converged with nanomaterials, have been proposed for the functional transformation of conventional hydrogels. The incorporation of suitable nanomaterials into the hydrogel matrix allows the hydrogel nanocomposite to exhibit multi-functionality in addition to the biocompatible feature of the original hydrogel. Therefore, various hydrogel composites with nanomaterials, including nanoparticles, nanowires, and nanosheets, have been developed for diverse purposes, such as catalysis, environmental purification, bio-imaging, sensing, and controlled drug delivery. Furthermore, novel technologies for the patterning of such hydrogel nanocomposites into desired shapes have been developed. The combination of such material engineering and processing technologies has enabled the hydrogel nanocomposite to become a key soft component of electronic, electrochemical, and biomedical devices. We herein review the recent research trend in the field of hydrogel nanocomposites, particularly focusing on materials engineering, processing, and device applications. Furthermore, the conclusions are presented with the scope of future research outlook, which also includes the current technical limitations

A Longitudinal Analysis of Concentration Developments for Container Terminals in Northern Vietnam

Vietnam has been one of Asia's fastest growing economies since 1990, with a steady growth of 6-8 percent. Vietnam's container port throughput volume also increases impressively year by year, at around 6-8 percent since 2002. To cope with increasing cargo volume, the development of modernized container terminals in Northern Vietnam has intensified. This longitudinal study aims to identify the development of the system and, in particular, the concentration or deconcentration tendencies, as well as the geographical patterns from 2005 to 2014. In order to achieve the study's objectives, the Herfindahl–Hirschman Index (HHI), concentration ratios (CR1, CR3), the Gini coefficient, the Lorenz curve, and shift-share analysis (SSA) were applied based on container throughput volume data from 2005 to 2014. The results demonstrate that the development of container terminals in Northern Vietnam has experienced a deconcentration trend and considerable shifting among its terminals during the period of observation. The proposed and validated research is original as it is the first study of concentration, deconcentration, and geographical patterns for container terminals in Northern Vietnam. The findings will enable port authorities, policy makers, and port operators to understand the development and changes of container terminal systems in Northern Vietnam more clearly

Advances in drug delivery technology for the treatment of glioblastoma multiforme

Glioblastoma multiforme (GBM) is a particularly aggressive and malignant type of brain tumor, notorious for its high recurrence rate and low survival rate. The treatment of GBM is challenging mainly because several issues associated with the GBM microenvironment have not yet been resolved. These obstacles originate from a variety of factors such as genetics, anatomy, and cytology, all of which collectively hinder the treatment of GBM. Recent advances in materials and device engineering have presented new perspectives with regard to unconventional drug administration methods for GBM treatment. Such novel drug delivery approaches, based on the clear understanding of the intrinsic properties of GBM, have shown promise in overcoming some of the obstacles. In this review, we first recapitulate the first-line therapy and clinical challenges in the current treatment of GBM. Afterwards, we introduce the latest technological advances in drug delivery strategies to improve the efficiency for GBM treatment, mainly focusing on materials and devices. We describe such efforts by classifying them into two categories, systemic and local drug delivery. Finally, we discuss unmet challenges and prospects for the clinical translation of these drug delivery technologies.11Nsciescopu