The Human Metabolome Database (HMDB, http://www.hmdb.ca) is a richly annotated resource that is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. Since its first release in 2007, the HMDB has been used to facilitate the research for nearly 100 published studies in metabolomics, clinical biochemistry and systems biology. The most recent release of HMDB (version 2.0) has been significantly expanded and enhanced over the previous release (version 1.0). In particular, the number of fully annotated metabolite entries has grown from 2180 to more than 6800 (a 300% increase), while the number of metabolites with biofluid or tissue concentration data has grown by a factor of five (from 883 to 4413). Similarly, the number of purified compounds with reference to NMR, LC-MS and GC-MS spectra has more than doubled (from 380 to more than 790 compounds). In addition to this significant expansion in database size, many new database searching tools and new data content has been added or enhanced. These include better algorithms for spectral searching and matching, more powerful chemical substructure searches, faster text searching software, as well as dedicated pathway searching tools and customized, clickable metabolic maps. Changes to the user-interface have also been implemented to accommodate future expansion and to make database navigation much easier. These improvements should make the HMDB much more useful to a much wider community of users.

BACKGROUND Cold (4°C)‐stored platelets are currently under investigation for transfusion in bleeding patients. It is currently unknown how long cold‐stored platelets can be stored for clinical applications. STUDY DESIGN AND METHODS Twenty three subjects were recruited. Twenty‐one subjects were available for in vivo assessment and received indium‐111 radiolabeled, cold‐stored platelets. We investigated 5‐ (n = 5), 10‐ (n = 6), 15‐ (n = 5), and 20‐day–stored (n = 5) platelets and obtained samples for in vitro testing at baseline and after the designated storage time. Twenty three units were available for in vitro testing. Five‐ and 7‐day (n = 5 each), room temperature (RT)‐stored platelets served as the current clinical standard control. RESULTS In vivo, we found a continuous decline in platelet recovery from 5 to 20 days. Platelet survival reached a low nadir after 10 days of storage. Ex vivo, we observed the maximum platelet αIIbβ3 integrin response to collagen at 5 days of cold storage, and we saw a continuous decline thereafter. However, platelet integrin activation and mitochondrial membrane integrity were better preserved after 20 days at 4°C, compared to 5 days at RT. Platelet metabolic parameters suggest comparable results between 20‐day cold‐stored platelets and 5‐ or 7‐day RT‐stored platelets. CONCLUSION In summary, we performed the first studies with extended, cold‐stored, apheresis platelets in plasma for up to 20 days with a fresh comparator. Storing cold‐stored platelets up to 20 days yields better results in vitro, but further studies in actively bleeding patients are needed to determine the best compromise between hemostatic efficacy and storage prolongation.

Platelets are currently stored at room temperature before transfusion to maximize circulation time. This approach has numerous downsides, including limited storage duration, bacterial growth risk, and increased costs. Cold storage could alleviate these problems. However, the functional consequences of cold exposure for platelets are poorly understood. In the present study, we compared the function of cold-stored platelets (CSP) and room temperature-stored platelets (RSP) in vitro, in vivo, and post-transfusion. CSP formed larger aggregates under in vitro shear while generating similar contractile forces compared to RSP. We found significantly reduced GPVI levels after cold exposure of 5-7 days. After transfusion in humans, CSP were mostly equivalent to RSP yet aggregated significantly less to the GPVI agonist collagen. In a mouse model of platelet transfusion, we found a significantly lower response to the GPVI-dependent agonist convulxin and significantly lower GPVI levels on the surface of transfused platelets after cold storage. In summary, our data support an immediate but short-lived benefit of CSP and highlight the need for thorough investigations of this product. (NCT03787927)