Inflammatory and fibrotic mechanisms in NAFLD—Implications for new treatment strategies

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. Here, we provide an overview of the metabolic underpinnings of NASH pathogenesis and established drivers of inflammation and fibrosis. 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.     

Interstitial granulomatous dermatitis and granulomatous arteritis in the setting of PD-1 inhibitor therapy for metastatic melanoma

Checkpoint inhibition has become an important target in the management of malignant melanoma. As anti-CTLA4 inhibitors and anti-PD1 antibodies are increasingly utilized, reports of immune-related adverse events (IRAEs) are becoming more frequent. Common noted cutaneous IRAEs are morbilliform, lichenoid, bullous, granulomatous, psoriasiform, and eczematous eruptions. We report a case of interstitial granulomatous dermatitis and granulomatous arteritis in the setting of nivolumab (anti-PD1) monotherapy for metastatic melanoma. There are many different causes for granulomatous vasculitis, such as herpes virus infection, lymphoproliferative disorders, systemic vasculitis, and inflammatory bowel disease. This report adds to the growing literature on granulomatous IRAEs due to checkpoint inhibition.     

The Race Is On: Human Embryonic Stem Cell Research Goes Global

More nations are joining the human embryonic stem cell (hESC) ??race?? by aggressively publishing in the peer-reviewed journals. Here we present data on the international use and distribution of hESC using a dataset taken from the primary research literature. We extracted these papers from a comprehensive dataset of articles using hESC and human induced pluripotent stem cells (hiPSC). We find that the rate of publication by US-based authors is slowing in comparison to international labs, and then declines over the final year of the period 2008?C2010. Non-US authors published more frequently and at a significantly higher rate, significantly increasing the number of their papers. In addition, international labs use a more diverse set of hESC lines and Obama-era additions are used more in non-US locations. Even considering the flood of new lines in the US and abroad, we see that researchers continue to rely on a few lines derived before the turn of the century. These data suggest ??embargo?? effects from restrictive policies on the US stem cell field. Over time, non-US labs have freely used lines on the US registries, while federally funded US scientists have been limited to using those lines approved by the NIH.