Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines for management and care transitions in the emergency department and hospital.

BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI), formally referred to as complicated skin and soft tissue infections, include infections with resistance to previously effective antimicrobials. Increasing dramatically in incidence, they have become a challenging medical problem associated with high direct and indirect costs to both the medical system and society. OBJECTIVES: To describe the burden of ABSSSI and to explore multidisciplinary approaches to its management and new treatments that can be initiated in the emergency department. DISCUSSION: We offer a best practice model aimed at providing risk-stratified and convenient care for ABSSSI at the lowest possible cost, while minimizing complications, readmissions, and inappropriate antibiotic use. In doing so, we focus on the care provided by emergency physicians and hospitalists and the transition of management between them for inpatient care, as well as the facilitation of observation or direct-to-outpatient care for suitable patients. CONCLUSIONS: A standard, consistent, and multidisciplinary approach to ABSSSI can streamline care, reduce admissions, support antimicrobial stewardship, and improve clinical and resource consumption outcomes.

Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system.

Short-interfering RNA (siRNA) has gained significant interest for treatment of neurological diseases by providing the capacity to achieve sustained inhibition of nearly any gene target. Yet, achieving efficacious drug delivery throughout deep brain structures of the CNS remains a considerable hurdle. We herein describe a lipid-siRNA conjugate that, following delivery into the cerebrospinal fluid (CSF), is transported effectively through perivascular spaces, enabling broad dispersion within CSF compartments and through the CNS parenchyma. We provide a detailed examination of the temporal kinetics of gene silencing, highlighting potent knockdown for up to five months from a single injection without detectable toxicity. Single-cell RNA sequencing further demonstrates gene silencing activity across diverse cell populations in the parenchyma and at brain borders, which may provide new avenues for neurological disease-modifying therapies.