Inflammasomes are supramolecular complexes that play key roles in immune surveillance. This is accomplished by the activation of inflammatory caspases, which leads to the proteolytic maturation of interleukin 1β (IL-1β) and pyroptosis. Here, we show that nucleotide-binding domain, leucine-rich repeat, and pyrin domain–containing protein 3 (NLRP3)- and pyrin-mediated inflammasome assembly, caspase activation, and IL-1β conversion occur at the microtubule-organizing center (MTOC). Furthermore, the dynein adapter histone deacetylase 6 (HDAC6) is indispensable for the microtubule transport and assembly of these inflammasomes both in vitro and in mice. Because HDAC6 can transport ubiquitinated pathological aggregates to the MTOC for aggresome formation and autophagosomal degradation, its role in NLRP3 and pyrin inflammasome activation also provides an inherent mechanism for the down-regulation of these inflammasomes by autophagy. This work suggests an unexpected parallel between the formation of physiological and pathological aggregates.

Uncontrolled hemorrhage is the leading cause of preventable combat-related deaths. The vast majority of these deaths occur in the field before the injured can be transported to a treatment facility. Early control of hemorrhage remains the most effective strategy for treating combat casualties. A number of hemostatic agents have recently been deployed to the warfront that can be used to arrest bleeding before surgical control of the source. The purpose of this article is to summarize the background information regarding these hemostatic agents, indications and rationale for their use, and characteristics of these products that may impact effectiveness.

A number of new hemostatic products have been developed recently for use in trauma settings of severe uncontrolled bleeding. Currently, the literature on these products is controversial, with efficacy demonstrated under some circumstances but not others. In this review, we analyze the current literature pertaining to four of the most promising products (dry fibrin sealant dressing, Rapid Deployment Hemostat, HemCon chitosan dressing, and QuikClot) that have been suggested for use in combat casualty care applications. In particular, this analysis takes into account the characteristics of the animal models used for efficacy testing of these products, the desired characteristics of hemostatic dressings, and specific safety considerations. Animal models ranged from those featuring low-pressure/low-flow bleeding to those featuring high-pressure/high-flow bleeding. When data are viewed in the context of the specific characteristics of the differing animal models used, seemingly disparate experimental results related to efficacy and safety become quite complementary and lead to recommendations for the use of different products in different injury scenarios. Mission and training requirements will dictate the use of these products by military and civilian prehospital care providers.