The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of Neutrophil Extracellular Traps.

Neutrophils release extracellular traps (NETs) in response to planktonic C. albicans. These complexes composed of DNA, histones, and proteins inhibit Candida growth and dissemination. Considering the resilience of Candida biofilms to host defenses, we examined the neutrophil response to C. albicans during biofilm growth. In contrast to planktonic C. albicans, biofilms triggered negligible release of NETs. Time lapse imaging confirmed the impairment in NET release and revealed neutrophils adhering to hyphae and migrating on the biofilm. NET inhibition depended on an intact extracellular biofilm matrix as physical or genetic disruption of this component resulted in NET release. Biofilm inhibition of NETosis could not be overcome by protein kinase C activation via phorbol myristate acetate (PMA) and was associated with suppression of neutrophil reactive oxygen species (ROS) production. The degree of impaired NET release correlated with resistance to neutrophil attack. The clinical relevance of the role for extracellular matrix in diminishing NET production was corroborated in vivo using a rat catheter model. The C. albicans pmr1Δ/Δ, defective in production of matrix mannan, appeared to elicit a greater abundance of NETs by scanning electron microscopy imaging, which correlated with a decreased fungal burden. Together, these findings show that C. albicans biofilms impair neutrophil response through an inhibitory pathway induced by the extracellular matrix.

Enhanced Recovery After Surgery Protocols for Head and Neck Cancer: Systematic Review and Meta-analysis.

OBJECTIVE: Enhanced recovery after surgery (ERAS) protocols aim to optimize the pre-, intra-, and postoperative care of patients to improve surgery outcomes, reduce complications, decrease length of stay, and more. We aim to perform a systematic review and meta-analysis of ERAS protocols for head and neck cancer surgery with or without microvascular reconstruction. DATA SOURCES: PubMed, Embase, and Web of Science databases were queried, and abstracts were screened independently by 2 investigators. REVIEW METHODS: This review was conducted in accordance with the PRISMA guidelines. We included comparative observational studies but excluded animal studies, case reports, and case series. RESULTS: Of 557 articles initially reviewed by title and/or abstract, we identified 30 for full-text screening, and 9 met the criteria for qualitative synthesis. Meta-analysis of length of stay revealed a mean decrease of 1.37 days (95% CI, 0.77-1.96; I2 = 0%; P < .00001) with the ERAS group as compared with non-ERAS controls. The standardized mean difference of the morphine milligram equivalent was 0.72 lower (95% CI, 0.26-1.18; I2 = 82%; P = .002) in the ERAS group vs controls. The quality of studies was moderate with a median MINORS score of 18.5 (range, 13.5-21.5). CONCLUSION: Implementation of ERAS protocols can lead to decreases in length of stay and opioid drug utilization. However, further high-quality prospective studies of ERAS protocols are needed, especially with stratified analysis of outcomes based on the type of head and neck cancer surgery.