Journal of internal medicine
-
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) worldwide, contributing to a great burden across a variety of patient-reported and clinical outcomes. New interventions for DKD management have been established in recent years, unleashing a novel paradigm, in which kidney-dedicated trials yield informative and robust data to guide optimal clinical management. After unprecedented results from groundbreaking randomized controlled trials were released, a new scenario of evidence-based recommendations has evolved for the management of diabetic patients with CKD. ⋯ Specifically, we review current insights on the natural history, epidemiology, pathogenesis, and therapeutics of DKD, mapping the new scientific information into the recently released Kidney Disease - Improving Global Outcomes Guidelines translating results from major novel randomized controlled trials to the clinical practice. Additionally, we approach the landscape of new therapeutics in the field, summarizing ongoing phase IIb and III trials focused on DKD. Finally, reflecting on the past and looking into the future, we highlight unmet needs in the current DKD management based on real-world evidence and offer a nephrologist's perspective into the challenge of fostering continuous improvement on clinical and patient-reported outcomes for individuals living with DKD.
-
The rules of fair play in sport generally prohibit the use of performance-enhancing drugs (PEDs). The World Anti-Doping Agency (WADA) oversees global antidoping regulations and testing for elite athletes participating in Olympic sports. ⋯ Then, we review the major PED classes with a focus on pathophysiology, complexities of antidoping testing, and relevant toxicities. Providers from diverse practice environments are likely to care for patients using PEDs for a variety of reasons and levels of sport; these providers should be aware of common PED classes and their risks.
-
Alterations in cerebral blood flow are common in several neurological diseases among the elderly including stroke, cerebral small vessel disease, vascular dementia, and Alzheimer's disease. 4D flow magnetic resonance imaging (MRI) is a relatively new technique to investigate cerebrovascular disease, and makes it possible to obtain time-resolved blood flow measurements of the entire cerebral arterial venous vasculature and can be used to derive a repertoire of hemodynamic biomarkers indicative of cerebrovascular health. The information that can be obtained from one single 4D flow MRI scan allows both the investigation of aberrant flow patterns at a focal location in the vasculature as well as estimations of brain-wide disturbances in blood flow. ⋯ We then survey key hemodynamic biomarkers that can be reliably assessed using the technique. Finally, we highlight cerebrovascular diseases where one or multiple hemodynamic biomarkers are of central interest.
-
Non-alcoholic fatty liver disease is comprised of either simple steatosis (non-alcoholic fatty liver) or a more advanced inflammatory and fibrogenic stage (non-alcoholic steatohepatitis [NASH]). NASH affects a growing proportion of the global adult and pediatric population, leading to rising rates of liver fibrosis and hepatocellular carcinoma. NASH is a multifactorial disease that is part of a systemic metabolic disorder. ⋯ Clarification of underlying fibrogenic and inflammatory mechanisms will advance the development of novel treatment strategies as there are no approved therapies at present. We discuss emerging experimental approaches and potential novel investigational strategies derived from animal models including the inflammasome, epigenetic reprogramming, Hippo signaling, Notch signaling, engineered T cells to remove fibrogenic HSCs, and HSC-specific targeting therapies. Recently completed and ongoing clinical trials and antifibrotics are discussed, illuminating the growing expectation that one or more therapies will yield clinical benefit in NASH in the coming years.
-
Adaptive immune responses play critical roles in viral clearance and protection against re-infection, and SARS-CoV-2 is no exception. What is exceptional is the rapid characterization of the immune response to the virus performed by researchers during the first 20 months of the pandemic. This has given us a more detailed understanding of SARS-CoV-2 compared to many viruses that have been with us for a long time. ⋯ The pandemic has engaged scientists and the public alike, and terms such as seroprevalence, neutralizing antibodies, antibody escape and vaccine certificates have become familiar to a broad community. Here, we review key findings concerning B cell and antibody (Ab) responses to SARS-CoV-2, focusing on non-severe cases and anti-spike (S) Ab responses in particular, the latter being central to protective immunity induced by infection or vaccination. The emergence of viral variants that have acquired mutations in S acutely highlights the need for continued characterization of both emerging variants and Ab responses against these during the evolving pathogen-immune system arms race.