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.

Health-Related Quality of Life in Patients with Low-Risk Differentiated Thyroid Cancer: A Systematic Review Examining the Extent of Thyroidectomy.

Background: Total thyroidectomy (TT) and hemithyroidectomy (HT) are acceptable surgical options for the treatment of low-risk differentiated thyroid cancer (DTC). While previous data suggest similar disease-free and disease-specific survival regardless of initial surgical treatment, the effect of the extent of surgery on health-related quality of life (HRQOL) is less clear. This systematic review aimed to examine HRQOL in low-risk DTC survivors after TT compared with HT. Methods: A search of PubMed, CINAHL, Cochrane, PsycINFO, and Scopus databases was conducted to identify studies published between January 1, 2011, and December 31, 2022, that assessed HRQOL predominantly in patients with low-risk DTC who underwent open thyroid surgery. Covidence™ software was used to apply the inclusion criteria, and a validated instrument was used to assess study quality. Results: Sixteen of the 1402 identified studies were included: 5 prospective and 11 retrospective cohort studies. The majority of included studies were of good quality (n = 14) and were from Asia and the Middle East (n = 11). Overall, six studies concluded that HT led to a better HRQOL than TT, two concluded that HT only resulted in better HRQOL compared with TT with central neck dissection (CND), and two concluded HT resulted in better short-term HRQOL that dissipated by 6 months postoperatively. The HRQOL domains found across all studies to be most consistently improved after HT included physical health, psychological/emotional, and social function. Factors found to be associated with HRQOL in more than one study included age, stage, and marital status. Conclusion: Differences in HRQOL after HT and TT tended to favor HT particularly when measured <6 months after surgery or when compared with TT with CND. Additional prospective and ideally randomized data are needed to fully determine the impact of the extent of surgery on HRQOL in patients with low-risk thyroid cancer.