RESUMEN
OBJECTIVE: To compare free flap outcomes between those who received and did not receive vasopressors (VPs) at the time of free flap reconstruction. STUDY DESIGN: This retrospective cohort study includes patients from January 2013 to January 2023. SETTING: This multicenter cohort study utilized data from the TriNetX Research Network which includes 80 health care organizations. METHODS: Head and neck cancer patients older than 18 years who underwent free flap reconstruction were separated into those who received or did not receive VPs on the day of surgery. The primary outcomes were flap failure defined by need for secondary free flap procedures, blood vessel repair, and other flap revision procedures. RESULTS: After propensity score matching, 7446 patients were analyzed. The VP group included 3723 patients (mean age [SD], 62.9 [11.4] years; 2511 males [67.4%]). The non-VP group included 3723 patients (mean age [SD], 63.0 [11.2] years; 2479 males [66.6%]). Free flap outcomes were not statistically different between groups (secondary free flap: 166 [4.5%] VP vs 155 [4.2%] non-VP, P = .04; vessel repair: 314 [8.4%] vs 319 [8.6%], P = .06; other flap revision procedures: 416 [11.2%] vs 449 [12.1%], P = .02). Bony flaps were found to have decreased rates of vessel repair in the VP group (47 [6.1%] vs 69 [9.0%], P = .003]. For secondary outcomes, pneumonia (173 [4.6%] vs 231 [6.2%], P = .0002), urinary tract infection (34 [1.0%] vs 59 [1.6%], P = .0007), and deep vein thrombosis (93 [2.5%] vs 122 [3.3%], P = .004) were significantly different. CONCLUSION: VP use is not significantly associated with free flap complications. These results imply that VP use on the same day as surgery may be safe if clinically necessary.
RESUMEN
UTX (also known as KDM6A) encodes a histone H3K27 demethylase and is an important tumour suppressor that is frequently mutated in human cancers1. However, as the demethylase activity of UTX is often dispensable for mediating tumour suppression and developmental regulation2-8, the underlying molecular activity of UTX remains unknown. Here we show that phase separation of UTX underlies its chromatin-regulatory activity in tumour suppression. A core intrinsically disordered region (cIDR) of UTX forms phase-separated liquid condensates, and cIDR loss caused by the most frequent cancer mutation of UTX is mainly responsible for abolishing tumour suppression. Deletion, mutagenesis and replacement assays of the intrinsically disordered region demonstrate a critical role of UTX condensation in tumour suppression and embryonic stem cell differentiation. As shown by reconstitution in vitro and engineered systems in cells, UTX recruits the histone methyltransferase MLL4 (also known as KMT2D) to the same condensates and enriches the H3K4 methylation activity of MLL4. Moreover, UTX regulates genome-wide histone modifications and high-order chromatin interactions in a condensation-dependent manner. We also found that UTY, the Y chromosome homologue of UTX with weaker tumour-suppressive activity, forms condensates with reduced molecular dynamics. These studies demonstrate a crucial biological function of liquid condensates with proper material states in enabling the tumour-suppressive activity of a chromatin regulator.
