Vancomycin-associated nephrotoxicity is prevalent among internal medicine patients, with 5.36-fold higher odds if piperacillin-tazobactam is concomitantly administered.

Research most strongly supports the use of aerosolized ribavirin as the treatment strategy for immunocompromised adults with RSV. Addition of an immunomodulator may provide a survival benefit over ribavirin alone. Strategies and supportive data for the prevention of RSV infection in the high-risk adult are critically needed.

Structure-based drug design was utilized to develop novel, 1-hydroxy-2-naphthoate-based small-molecule inhibitors of Mcl-1. Ligand design was driven by exploiting a salt bridge with R263 and interactions with the p2 and p3 pockets of the protein. Significantly, target molecules were accessed in just two synthetic steps, suggesting further optimization will require minimal synthetic effort. Molecular modeling using the Site-Identification by Ligand Competitive Saturation (SILCS) approach was used to qualitatively direct ligand design as well as develop quantitative models for inhibitor binding affinity to Mcl-1 and the Bcl-2 relative Bcl-xL as well as for the specificity of binding to the two proteins. Results indicated hydrophobic interactions with the p2 pockets dominate the affinity of the most favourable binding ligand (3bl: Ki = 31 nM). Compounds were up to 20-fold selective for Mcl-1 over Bcl-xL. Selectivity of the inhibitors was driven by interactions with the deeper p2 pocket in Mcl-1 versus Bcl-xL. The SILCS-based SAR of the present compounds represents the foundation for the development of Mcl-1 specific inhibitors with the potential to treat a wide range of solid tumours and hematological cancers, including acute myeloid leukaemia.

When patients with NS are admitted to the hospital, develop an acute medical illness, or acquire an additional thrombotic events risk factor such as surgery, active malignancy, or pregnancy, consideration for primary pharmacologic prophylaxis with appropriately dosed low-molecular-weight heparin or other indicated anticoagulant should include the potential for increased thrombotic events risk in this patient population. Consideration may also be given to the use of primary pharmacologic prophylaxis with low-molecular-weight heparin or oral vitamin K antagonist in patients with membranous nephropathy once the albumin level drops below 2.0-2.5 g/dL. Short-term use of pharmacologic prophylaxis during the first 6 months following diagnosis warrants further investigation.