RSV can cause severe lower respiratory complications in older adults, resulting in respiratory failure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem to improve outcomes. The unmet need for antiviral therapy and vaccination against RSV in adults should be promptly addressed.

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Nonalcoholic fatty liver disease (NAFLD) alters drug response. We previously reported that NAFLD is associated with reduced in vivo CYP3A drug-metabolism activity and hepatic CYP3A4 expression in humans as well as mouse and human hepatoma models of the disease. Here, we investigated the role of the lipidand glucose-modulating hormone fibroblast growth factor 21 (FGF21) in the molecular mechanism regulating CYP3A4 expression in NAFLD. In human subjects, mouse and cellular NAFLD models with lower CYP3A4 expression, circulating FGF21, or hepatic FGF21 mRNA levels were elevated. Administration of recombinant FGF21 or transient hepatic overexpression of FGF21 resulted in reduced liver CYP3A4 luciferase reporter activity in mice and decreased CYP3A4 mRNA expression and activity in cultured Huh7 hepatoma cells. Blocking canonical FGF21 signaling by pharmacological inhibition of MEK1 kinase in Huh7 cells caused de-repression of CYP3A4 mRNA expression with FGF21 treatment. Mice with high-fat dietinduced simple hepatic steatosis and lipid-loaded Huh7 cells had reduced nuclear localization of the pregnane X receptor (PXR), a key transcriptional regulator of CYP3A4. Furthermore, decreased nuclear PXR was observed in mouse liver and Huh7 cells after FGF21 treatment or FGF21 overexpression. Decreased PXR binding to the CYP3A4 proximal promoter was found in FGF21-treated Huh7 cells. An FGF21-PXR signaling pathway may be involved in decreased hepatic CYP3A4 metabolic activity in NAFLD.

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Background and Aims: Open liver resection requiring an upper abdominal incision is associated with significant opioid use due to postoperative pain. We tested the hypothesis that the intraoperative combination of low dose lidocaine and ketamine would reduce opioid consumption when given in conjunction with intrathecal morphine for liver resection surgery. Methods: In this triple blind, parallel group four-arm placebo-controlled trial, we randomized 124 adult ASA 2-4 liver resection patients to receive intraoperative lidocaine 0.33 mg/kg/h (group L), ketamine 70 µg/kg/h (group K), combination of lidocaine 0.33 mg/kg/h and ketamine 70 µg/kg/h (group KL) and saline (group P). All patients received 300 µg intrathecal morphine prior to induction of anesthesia. All infusions were started immediately after intubation and continued until the end of surgery. Primary outcome measurements included opioid consumption at 24-hours. Secondary outcomes included pain scores, opioid consumption at 48 and 72-hours and side effects including nausea, vomiting, dizziness, hallucinations, headaches and signs of local anaesthetic toxicity. Patients were followed up for 12 weeks.

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BACKGROUND Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non‐Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS The Stem Cell Club is a non‐profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (http://www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor‐database. Of the recruited registrants, 58.3% were male; 60.3% of males self‐reported as non‐Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor‐database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.