Project description:Significant progress has been made in understanding the principles underlying the development of liver fibrosis. This includes appreciating its dynamic nature, the importance of active fibrolysis in fibrosis regression, and the plasticity of cell populations endowing them with fibrogenic or fibrolytic properties. This is complemented by an increasing array of therapeutic targets with known roles in the progression or regression of fibrosis. With a key role for fibrosis in determining clinical outcomes and encouraging data from recently Food and Drug Administration-approved antifibrotics for pulmonary fibrosis, the development and validation of antifibrotic therapies has taken center stage in translational hepatology. In addition to summarizing the recent progress in antifibrotic therapies, the authors discuss some of the challenges ahead, such as achieving a better understanding of the interindividual heterogeneity of the fibrotic response, how to match interventions with the ideal patient population, and the development of better noninvasive methods to assess the dynamics of fibrogenesis and fibrolysis. Together, these advances will permit a better targeting and dose titration of individualized therapies. Finally, the authors discuss combination therapy with different antifibrotics as possibly the most potent approach for treating fibrosis in the liver.
Project description:Mounting evidence suggests that gustation is important for the orosensory detection of dietary fats, and might contribute to preferences that humans, rodents, and possibly other mammals exhibit for fat-rich foods. In contrast to sweet, sour, salty, bitter, and umami, fat is not widely recognized as a primary taste quality. Recent investigations, however, provide a wealth of information that is helping to elucidate the specific molecular, cellular, and neural mechanisms required for fat detection in mammals. The latest evidence supporting a fat taste will be explored in this review, with a particular focus on recent studies that suggest a surprising role for gut-brain endocannabinoid signaling in controlling intake and preference for fats based on their proposed taste properties.
Project description:Fibrosis accumulation is a dynamic process resulting from a wound-healing response to acute or chronic liver injury of all causes. The cascade starts with hepatocyte necrosis and apoptosis, which instigate inflammatory signaling by chemokines and cytokines, recruitment of immune cell populations, and activation of fibrogenic cells, culminating in the deposition of extracellular matrix. These key elements, along with pathways of transcriptional and epigenetic regulation, represent fertile therapeutic targets. New therapies include drugs specifically designed as antifibrotics, as well as drugs already available with well-established safety profiles, whose mechanism of action may also be antifibrotic. At the same time, the development of noninvasive fibrogenic markers, and techniques (e.g. fibroscan), as well as combined scoring systems incorporating serum and clinical features will allow improved assessment of therapy response. In aggregate, the advances in the elucidation of the biology of fibrosis, combined with improved technologies for assessment will provide a comprehensive framework for design of antifibrotics and their analysis in well-designed clinical trials. These efforts may ultimately yield success in halting the progression of, or reversing, liver fibrosis.
Project description:There is an increasing awareness of the prevalence of iron deficiency (ID) in patients with heart failure (HF) and its contributory role in the morbidity and mortality of HF. It is important to note that many HF patients have ID without being anaemic, hence it is vital to screen for ID even in patients with haemoglobin within the normal laboratory range. This review summarises the pathophysiology and epidemiology of ID in HF before discussing the evidence for iron replacement therapy in HF patients. Finally, it discusses the ongoing large outcome trials evaluating iron replacement in HF.
Project description:Cirrhosis is a severe form of liver fibrosis that results in the irreversible replacement of liver tissue with scar tissue in the liver. Environmental toxicity, infections, metabolic causes, or other genetic factors including autoimmune hepatitis can lead to chronic liver injury and can result in inflammation and fibrosis. This activates myofibroblasts to secrete ECM proteins, resulting in the formation of fibrous scars on the liver. Fibrosis regression is possible through the removal of pathophysiological causes as well as the elimination of activated myofibroblasts, resulting in the reabsorption of the scar tissue. To date, a wide range of antifibrotic therapies has been tried and tested, with varying degrees of success. These therapies include the use of growth factors, cytokines, miRNAs, monoclonal antibodies, stem-cell-based approaches, and other approaches that target the ECM. The positive results of preclinical and clinical studies raise the prospect of a viable alternative to liver transplantation in the near future. The present review provides a synopsis of recent antifibrotic treatment modalities for the treatment of liver cirrhosis, as well as a brief summary of clinical trials that have been conducted to date.
Project description:Purpose of reviewMolecular matching continues to be an important topic in organ transplantation. Over the years, several studies - larger and smaller - supported correlations of molecular incompatibility loads and clinical outcomes. However, their practical utility for clinical decision making remains controversial and there is no consensus on the context in which they should be used.Recent findingsThe recent literature on molecular matching can be divided into four main areas of research: several groups present improvements of the algorithmic pipelines (1), increasing the robustness of previous findings. Further clinical evidence is reported (2) in various cohorts and other organ transplant domains, such as liver and lung transplantation. Consideration is given to the application of molecular matching in the allocation of deceased organs (3), suggesting options to improve allocation equity and utility. Furthermore, evidence is provided for personalized immunosuppression based on immunological risk (4), including infection and post graft failure management.SummaryThere is ample evidence that current molecular matching algorithms add value to immunologic risk stratification for organ transplant recipients. First studies on how to translate these insights into patient management with respect to organ allocation and personalized medicine are underway and require further support.
Project description:Cardio-oncology is an emerging field tasked with identifying and treating cancer therapy related cardiac dysfunction (e.g., cytotoxic agents, immunotherapies, radiation, and hormone therapies) and optimizing the cardiovascular health of cancer patients exposed to these agents. Novel cancer therapies have led to significant improvements in clinical outcomes for breast cancer patients. In this article, we review the current literature on assessing cardiovascular risk of breast cancer therapies and discuss strategies (including pharmacological and lifestyle interventions) to prevent cardiovascular toxicity.
Project description:ObjectivesTo assess SGO members' knowledge, attitudes, and practice patterns regarding Medical Aid In Dying (MAID).MethodsSGO members were surveyed via online survey. The survey included questions regarding demographics, knowledge, attitudes, and practice patterns relating to MAID. Descriptive statistics were calculated. Associations between sociodemographic factors and attitudes related to MAID were analyzed utilizing logistic regression.ResultsOf 1,337 invited members, 225 (17%) responded. Median age was 46. Most were female (58%), white (81%), and in academic practice (64%). Over 50% had heard the term MAID and have had a patient ask about it. Few (20%) reported living in a state where MAID is legal and 61% of these respondents provided MAID. Sixty percent lived in a state that had not legalized MAID and 18% did not know if MAID was legal in their state. 36% of respondents living in a state where MAID was illegal/unknown legality indicated they would provide MAID if it were legal in their state, 30% would not, and 34% were uncertain. The majority (69%) of respondents believed MAID should be legal. Female respondents were more likely to support legalization of MAID (OR 2.44, p=<0.05). Respondents practicing in the southern U.S. were less likely to support legalization of MAID (OR 0.42, p=<0.05). Over 75% of respondents stated an SGO position statement on MAID would be helpful.ConclusionsMAID is a highly relevant topic for gynecologic oncologists. Gaps in MAID-related knowledge exist among SGO members and there is a desire for additional education and guidance regarding MAID.
Project description:Progressive fibrosing interstitial lung disease (PF-ILD) describes a phenotypic subset of interstitial lung diseases characterized by progressive, intractable lung fibrosis. PF-ILD is separate from, but has radiographic, histopathologic, and clinical similarities to idiopathic pulmonary fibrosis. Two antifibrotic medications, nintedanib and pirfenidone, have been approved for use in patients with idiopathic pulmonary fibrosis. Recently completed randomized controlled trials have demonstrated the clinical efficacy of antifibrotic therapy in patients with PF-ILD. The validation of efficacy of antifibrotic therapy in PF-ILD has changed the treatment landscape for all of the fibrotic lung diseases, providing a new treatment pathway and opening the door for combined antifibrotic and immunosuppressant drug therapy to address both the fibrotic and inflammatory components of ILD characterized by mixed pathophysiologic pathways.