Impact of sleep deficiency on surgical performance: a prospective assessment.

STUDY OBJECTIVES: Sleep deficiency can adversely affect the performance of resident physicians, resulting in greater medical errors. However, the impact of sleep deficiency on surgical outcomes, particularly among attending surgeons, is less clear. METHODS: Sixty attending surgeons from academic and community departments of surgery or obstetrics and gynecology were studied prospectively using direct observation and self-report to explore the effect of sleep deprivation on patient safety, operating room communication, medical errors, and adverse events while operating under 2 conditions, post-call (defined as > 2 hours of nighttime clinical duties) and non-post-call. RESULTS: Each surgeon contributed up to 5 surgical procedures post-call and non-post-call, yielding 362 cases total (150 post-call and 210 non-post-call). Most common were caesarian section and herniorrhaphy. Hours of sleep on the night before the operative procedure were significantly less post-call (4.98 ± 1.41) vs non-post-call (6.68 ± 0.88, P < .01). Errors were infrequent and not related to hours of sleep or post-call status. However, Non-Technical Skills for Surgeons ratings demonstrated poorer performance while post-call for situational awareness, decision-making, and communication/teamwork. Fewer hours of sleep also were related to lower ratings for situational awareness and decision-making. Decreased self-reported alertness was observed to be associated with increased procedure time. CONCLUSIONS: Sleep deficiency in attending surgeons was not associated with greater errors during procedures performed during the next day. However, procedure time was increased, suggesting that surgeons were able to compensate for sleep loss by working more slowly. Ratings on nontechnical surgical skills were adversely affected by sleep deficiency. CITATION: Quan SF, Landrigan CP, Barger LK, et al. Impact of sleep deficiency on surgical performance: a prospective assessment. J Clin Sleep Med. 2023;19(4):673-683.

Antitumor effects of hyaluronan inhibition in desmoid tumors.

Desmoid tumors (DTs) are rare, mesenchymal tumors that exhibit features of an abundant wound healing process. Previously, we showed that mesenchymal stem cells (MSCs) are constituents of DTs and may contribute to desmoid tumorigenesis via activities associated with wound healing. Hyaluronan (HA) is a long-charged chain of repeating glucuronate and N-acetylglucosamine disaccharides that is synthesized by HA synthases (HAS) and degraded by hyaluronidases (HYAL). HA is secreted into the extracellular matrix by injured stroma and is important for normal tissue repair and neoplastic progression. Here, we investigated the presence of HA in DTs and the antitumor effects of the HA inhibitor, 4-methylumbelliferone (4-MU), on DT-derived mesenchymal cells. By immunohistochemistry and enzyme-linked immunosorbent assay, we found abundant expression of HA in 29/30 DTs as well as >5-fold increased HA levels in DT-derived cell lines relative to controls. Immunohistochemistry also demonstrated high expression of HAS2 in DTs, and quantitative PCR analysis showed increased HAS2 upregulation in frozen DTs and DT-derived cells. 4-MU treatment of DT-derived cells significantly decreased proliferation as well as HA and HAS2 levels. Fluorescent immunohistochemistry showed that MSCs in DTs coexpressed HA, HAS2, HYAL2, as well as the major HA receptor CD44 and HA coreceptor TLR4. Taken together, our results suggest that paracrine regulation of HA signaling in DTs may contribute to MSC recruitment and tumor proliferation. Future studies investigating the role of HA in tumor-stroma crosstalk and inhibition of HA-MSC interactions as a novel therapeutic target in DTs and other solid tumors are warranted.

FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain.

Neuronal specification occurs at the periventricular surface of the embryonic central nervous system. During early postnatal periods, radial glial cells in various ventricular zones of the brain differentiate into ependymal cells and astrocytes. However, mechanisms that drive this time- and cell-specific differentiation remain largely unknown. Here, we show that expression of the forkhead transcription factor FoxJ1 in mice is required for differentiation into ependymal cells and a small subset of FoxJ1(+) astrocytes in the lateral ventricles, where these cells form a postnatal neural stem cell niche. Moreover, we show that a subset of FoxJ1(+) cells harvested from the stem cell niche can self-renew and possess neurogenic potential. Using a transcriptome comparison of FoxJ1-null and wild-type microdissected tissue, we identified candidate genes regulated by FoxJ1 during early postnatal development. The list includes a significant number of microtubule-associated proteins, some of which form a protein complex that could regulate the transport of basal bodies to the ventricular surface of differentiating ependymal cells during FoxJ1-dependent ciliogenesis. Our results suggest that time- and cell-specific expression of FoxJ1 in the brain acts on an array of target genes to regulate the differentiation of ependymal cells and a small subset of astrocytes in the adult stem cell niche.