Project description:Chronic injury results in a wound healing response that eventually leads to fibrosis. The response is generalized, with features common among multiple organ systems. In the liver, various different types of injury lead to fibrogenesis, implying a common pathogenesis. Although several specific therapies for patients who have different liver diseases have been successfully developed, including antiviral therapies for those who have hepatitis B and hepatitis C virus infection, specific and effective antifibrotic therapy remains elusive. Over the past 2 decades, great advances in the understanding of fibrosis have been made and multiple mechanisms underlying hepatic fibrogenesis uncovered. Elucidation of these mechanisms has been of fundamental importance in highlighting novel potential therapies. Preclinical studies have indicated several putative therapies that might abrogate fibrogenesis. This article emphasizes mechanisms underlying fibrogenesis and reviews available and future therapeutics.
Project description:Access to quality cancer care is often unavailable in low-income and middle-income countries, and also in rural or remote areas of high-income countries. Teleoncology-oncology applications of medical telecommunications, including pathology, radiology, and other related disciplines-has the potential to enhance access to and quality of clinical cancer care, and to improve education and training. Implementation of teleoncology in the developing world requires an approach tailored to priorities, resources, and needs. Teleoncology can best achieve its proposed goals through consistent and long-term application. We review teleoncology initiatives that have the potential to decrease cancer-care inequality between resource-poor and resource-rich institutions and offer guidelines for the development of teleoncology programmes in low-income and middle-income countries.
Project description:Treatment and management of kidney disease currently presents an enormous global burden, and the application of nanotechnology principles to renal disease therapy, although still at an early stage, has profound transformative potential. The increasing translation of nanomedicines to the clinic, alongside research efforts in tissue regeneration and organ-on-a-chip investigations, are likely to provide novel solutions to treat kidney diseases. Our understanding of renal anatomy and of how the biological and physico-chemical properties of nanomedicines (the combination of a nanocarrier and a drug) influence their interactions with renal tissues has improved dramatically. Tailoring of nanomedicines in terms of kidney retention and binding to key membranes and cell populations associated with renal diseases is now possible and greatly enhances their localization, tolerability, and efficacy. This Review outlines nanomedicine characteristics central to improved targeting of renal cells and highlights the prospects, challenges, and opportunities of nanotechnology-mediated therapies for renal diseases.
Project description:BackgroundLiver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool.PurposeTo present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions.MethodsA systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed.ResultsTwenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs.ConclusionEx vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.
Project description:The relative paucity of donor livers suitable for transplantation has sparked innovations to preserve and recondition organs to expand the pool of transplantable organs. Currently, machine perfusion techniques have led to the improvement of the quality of marginal livers and to prolonged cold ischemia time and have allowed for the prediction of graft function through the analysis of the organ during perfusion, improving the rate of organ use. In the future, the implementation of organ modulation might expand the scope of machine perfusion beyond its current usage. The aim of this review was to provide an overview of the current clinical use of machine perfusion devices in liver transplantation and to provide a perspective for future clinical use, including therapeutic interventions in perfused donor liver grafts.
Project description:The delivery of medical care services in U.S. nursing homes (NHs) is dependent on a workforce that comprises physicians, nurse practitioners, and physician assistants. Each of these disciplines operates under a unique regulatory framework while adhering to common standards of care. NH provider characteristics and their roles in NH care can illuminate potential links to clinical outcomes and overall quality of care with important policy and cost implications. This perspective provides an overview of what is currently known about medical provider practice in NH and organizational models of practice. Links to quality, both conceptual and established, are presented as is a research and policy agenda that addresses the gaps in the evidence base within the context of our ever-changing health care landscape.
Project description:Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.
Project description:Acute-on-chronic liver failure (ACLF) is a frequent complication in patients with liver cirrhosis that has high short-term mortality. It is characterized by acute decompensation (AD) of liver cirrhosis, intra- and extrahepatic organ failure, and severe systemic inflammation (SI). In the recent past, several studies have investigated the management of this group of patients. Identification and treatment of precipitants of decompensation and ACLF play an important role, and management of the respective intra- and extrahepatic organ failures is essential. However, no specific treatment for ACLF has been established to date, and the only curative treatment option currently available for these patients is liver transplantation (LT). It has been shown that ACLF patients are at severe risk of waitlist mortality, and post-LT survival rates are high, making ACLF patients suitable candidates for LT. However, only a limited number of patients are eligible for LT due to related contraindications such as uncontrolled infections. In this case, bridging strategies (e.g., extracorporeal organ support systems) are required. Further therapeutic approaches have recently been developed and evaluated. Thus, this review focuses on current management and potential future treatment options.
Project description:Although radiotherapy (RT) is used for the treatment of cancers, including liver cancer, radiation-induced liver disease (RILD) has emerged as a major limitation of RT. Radiation-induced toxicities in nontumorous liver tissues are associated with the development of numerous symptoms that may limit the course of therapy or have serious chronic side effects, including late fibrosis. Although the clinical characteristics of RILD patients have been relatively well described, the understanding of RILD pathogenesis has been hampered by a lack of reliable animal models for RILD. Despite efforts to develop suitable experimental animal models for RILD, current animal models rarely present hepatic veno-occlusive disease, the pathological hallmark of human RILD patients, resulting in highly variable results in RILD-related studies. Therefore, we introduce the concept and clinical characteristics of RILD and propose a feasible explanation for RILD pathogenesis. In addition, currently available animal models of RILD are reviewed, focusing on similarities with human RILD and clues to understanding the mechanisms of RILD progression. Based on these findings from RILD research, we present potential therapeutic strategies for RILD and prospects for future RILD studies. Therefore, this review helps broaden our understanding for developing effective treatment strategies for RILD.
Project description:Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.