Latest Evidence on Sulfonylureas: What's New?
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ABSTRACT:
SUBMITTER: Leiter LA
PROVIDER: S-EPMC7261305 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:While the incidence of nephrotic syndrome (NS) is decreasing in Korea, the morbidity of difficult-to-treat NS is significant. Efforts to minimize treatment toxicity showed that prolonged treatment after an initial treatment for 2-3 months with glucocorticosteroids was not effective in reducing frequent relapses. For steroid-dependent NS, rituximab, a monoclonal antibody against the CD20 antigen on B cells, was proven to be as effective, and short-term daily low-dose steroids during upper respiratory infections reduced relapses. Steroid resistance or congenital NS are indications for genetic study and renal biopsy, since the list of genes involved in NS is lengthening.
| S-EPMC4573440 | biostudies-literature
Project description:Until recently there was no effective systemic therapy for metastatic melanoma. Increased understanding of tumor biology and immune regulation has led to the development of drugs targeting the mitogen-activated protein kinase (MAPK) pathway (BRAF inhibitors and MEK inhibitors) and T-cell regulation (CTLA4 antibodies). These drugs are the new standard of care, however barriers to better patient outcomes include limited responses and significant toxicities (CTLA4 antibodies) and lack of durability in the majority of cases (BRAF and MEK inhibitors). This review discusses the next stages of development of treatments in melanoma, including immune checkpoint blocking drugs targeting the PD-1/PD-L1 axis, and the use of BRAF and MEK inhibitors in combination. Both approaches lead to a higher proportion of durable responses coupled with less toxicity. In an effort to improve outcomes even further, clinical trials of combinations of MAPK inhibitors, immunotherapies and other signal pathway inhibitors are underway. Adjuvant studies of many of these drugs have commenced, with the hope of also improving outcomes in patients with early-stage melanoma.
| S-EPMC3752177 | biostudies-literature
Project description:The accumulated evidence from two decades of randomized controlled trials has not yet resolved the question of how best to monitor colorectal cancer (CRC) survivors for early detection of recurrent and metachronous disease or even whether doing so has its intended effect. A new wave of trial data in the coming years and an evolving knowledge of relevant biomarkers may bring us closer to understanding what surveillance strategies are most effective for a given subset of patients. To best apply these insights, a number of important research questions need to be addressed, and new decision making tools must be developed. In this review, we summarize available randomized controlled trial evidence comparing alternative surveillance testing strategies, describe ongoing trials in the area, and compare professional society recommendations for surveillance. In addition, we discuss innovations relevant to CRC surveillance and outline a research agenda which will inform a more risk-stratified and personalized approach to follow-up.
| S-EPMC3934459 | biostudies-literature
Project description:Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences. Salt-losing tubulopathies can affect all tubular segments, from the proximal tubule to the collecting duct. But the more frequently observed disorders are Bartter and Gitelman syndrome, which affect salt transport in the thick ascending limb of Henle's loop and/or the distal convoluted tubule, and these disorders generate the greatest controversies regarding management. Here, we review clinical and molecular aspects of salt-losing tubulopathies and discuss novel insights provided mainly by genetic investigations and retrospective clinical reviews. Additionally, we discuss controversial topics in the management of these disorders to highlight areas of importance for future clinical trials. International collaboration will be required to perform clinical studies to inform the treatment of these rare disorders.
| S-EPMC5827598 | biostudies-literature
Project description:Ten years ago, there was an emerging view that the molecular basis for adult mitochondrial disorders was largely known and that the clinical phenotypes had been well described. Nothing could have been further from the truth. The establishment of large cohorts of patients has revealed new aspects of the clinical presentation that were not previously appreciated. Over time, this approach is starting to provide an accurate understanding of the natural history of mitochondrial disease in adults. Advances in molecular diagnostics, underpinned by next generation sequencing technology, have identified novel molecular mechanisms. Recently described mitochondrial disease phenotypes have disparate causes, and yet share common mechanistic themes. In particular, disorders of mtDNA maintenance have emerged as a major cause of mitochondrial disease in adults. Progressive mtDNA depletion and the accumulation of mtDNA mutations explain some of the clinical features, but the genetic and cellular processes responsible for the mtDNA abnormalities are not entirely clear in each instance. Unfortunately, apart from a few specific examples, treatments for adult mitochondrial disease have not been forthcoming. However, the establishment of international consortia, and the first multinational randomised controlled trial, have paved the way for major progress in the near future, underpinned by growing interest from the pharmaceutical industry. Adult mitochondrial medicine is, therefore, in its infancy, and the challenge is to harness the new understanding of its molecular and cellular basis to develop treatments of real benefit to patients.
| S-EPMC4693502 | biostudies-literature
Project description:Diffusion MRI (dMRI) provides invaluable information for the study of tissue microstructure and brain connectivity, but suffers from a range of imaging artifacts that greatly challenge the analysis of results and their interpretability if not appropriately accounted for. This review will cover dMRI artifacts and preprocessing steps, some of which have not typically been considered in existing pipelines or reviews, or have only gained attention in recent years: brain/skull extraction, B-matrix incompatibilities w.r.t the imaging data, signal drift, Gibbs ringing, noise distribution bias, denoising, between- and within-volumes motion, eddy currents, outliers, susceptibility distortions, EPI Nyquist ghosts, gradient deviations, B1 bias fields, and spatial normalization. The focus will be on "what's new" since the notable advances prior to and brought by the Human Connectome Project (HCP), as presented in the predecessing issue on "Mapping the Connectome" in 2013. In addition to the development of novel strategies for dMRI preprocessing, exciting progress has been made in the availability of open source tools and reproducible pipelines, databases and simulation tools for the evaluation of preprocessing steps, and automated quality control frameworks, amongst others. Finally, this review will consider practical considerations and our view on "what's next" in dMRI preprocessing.
| S-EPMC9379864 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) is a type of aggressive tumor that involves the intrahepatic, perihilar and distal biliary tree, and is usually diagnosed at an advanced stage. The standard first-line systemic therapy for patients with advanced CCA is a combination of gemcitabine and cisplatin; targeted therapies and angiogenesis inhibitors are not widely used clinically at present. However, with the development of precision medicine, immunotherapy has started to play a more important role. Programmed cell death protein 1 inhibitors are now considered a good therapeutic option for CCA. Treatments using chimeric antigen receptor T cells, bispecific antibodies, oncolytic viruses and cancer vaccines have also achieved satisfactory results. In addition, combinations of immunotherapy with a variety of conventional therapies have shown some efficacy, and several studies have provided insights into their use in antitumor therapy. Although there are numerous challenges in the treatment of advanced CCA, immunotherapy remains a noteworthy breakthrough. The current evidence on the immunotherapy of CCA is discussed in the present review.
| S-EPMC7608025 | biostudies-literature
Project description:IntroductionPompe disease is an autosomal recessive disorder caused by a deficiency of acid-α-glucosidase (GAA), an enzyme responsible for hydrolyzing lysosomal glycogen. A lack of GAA leads to accumulation of glycogen in the lysosomes of cardiac, skeletal, and smooth muscle cells, as well as in the central and peripheral nervous system. Enzyme replacement therapy has been the standard of care for 15 years and slows disease progression, particularly in the heart, and improves survival. However, there are limitations of ERT success, which gene therapy can overcome.Areas coveredGene therapy offers several advantages including prolonged and consistent GAA expression and correction of skeletal muscle as well as the critical CNS pathology. We provide a systematic review of the preclinical and clinical outcomes of adeno-associated viral mediated gene therapy and alternative gene therapy strategies, highlighting what has been successful.Expert opinionAlthough the preclinical and clinical studies so far have been promising, barriers exist that need to be addressed in gene therapy for Pompe disease. New strategies including novel capsids for better targeting, optimized DNA vectors, and adjuctive therapies will allow for a lower dose, and ameliorate the immune response.
| S-EPMC10084869 | biostudies-literature
Project description: Not available
| S-EPMC9944547 | biostudies-literature
Project description:Backgroundone of the World Health Organization Millennium Development Goal is to reduce tuberculosis incidence by 2015. However, more of 8.5 million tuberculosis cases have been reported in 2011, with an increase of multidrug-resistant strains. Therefore, the World Health Organization target cannot be reach without the help of a vaccine able to limit the spread of tuberculosis. Nowadays, bacille Calmette-Guérin is the only vaccine available against tuberculosis. It prevents against meningeal and disseminated tuberculosis in children, but its effectiveness against pulmonary form in adolescents and adults is argued.Methoda systematic review was performed by searches of Pubmed, references of the relevant articles and Aeras and ClinicalTrial.gov websites.Results100 articles were included in this review. Three viral vectored booster vaccines, five protein adjuvant booster vaccines, two priming vaccines and two therapeutic vaccines have been analyzed.ConclusionsSeveral vaccines are in the pipeline, but further studies on basic research, clinical trial and mass vaccination campaigns are needed to achieve the TB eradication target by 2050.
| S-EPMC4015960 | biostudies-literature