Background Perioperative aspiration, while rare, is a serious complication of anesthetic care. Consequences of aspiration may include physical obstruction, wheezing, and pneumonia, resulting in mild to severe hypoxemia and even death. Aim We used a multi‐institutional registry of pediatric patients to identify factors that influence the rate and resulting harm of perioperative pulmonary aspiration. Methods The Wake Up Safe registry was queried for all severe adverse events reported from 29 institutions from 2010 to 2017. Aspiration events were identified through the “respiratory adverse event” data entry form or through free text search. Multivariable regression was used to predict aspiration events, and contributory factors were identified by reviewing free text case comments. Results Analysis included 2 440 810 anesthetics administered involving patients ≤18 years of age. There were 135 pulmonary aspiration events, for an incidence of 0.006%. Within these 135 cases, 110 cases (82%) resulted in escalation of care and 51 (38%) resulted in patient harm, including 2 deaths (1.5%). In multivariable analysis, patients undergoing emergency surgery (OR 2.0 [1.2‐3.5]) or with higher ASA status were more likely to experience aspiration (ASA 3 (OR 5.0 [2.6‐9.1]); ASA ≥ 4 (OR 5.5 [3.8‐16.8])). Noted causes of aspiration included gastrointestinal comorbid conditions (19%), postcoughing event or laryngospasm (14%), nil per os (NPO) violation (11%), blood or secretions in the airway following or during the procedure (6%), and oral premedication reaction (3%). Conclusion Although infrequent, death was reported as a consequence of perioperative aspiration in two patients. The frequency with which NPO violations were identified as a potential cause of aspiration highlights the struggles institutions face with adherence to NPO regulations, as these cases may be preventable. Furthermore, preventive measures may be needed to address other common causes of aspiration, such as gastrointestinal comorbid conditions.
Glioblastoma (GBM) is the most common and lethal primary brain tumor and remains incurable. This is in part due to the cellular heterogeneity within these tumors, which includes a subpopulation of treatment-resistant cells called cancer stem-like cells (CSC). We previously identified that the anaphase-promoting complex/cylosome (APC/C), a key cell-cycle regulator and tumor suppressor, had attenuated ligase activity in CSCs. Here, we assessed the mechanism of reduced activity, as well as the efficacy of pharmacologically targeting the APC/C in CSCs. We identified hyperphosphorylation of CDH1, but not pseudosubstrate inhibition by early mitotic inhibitor 1 (EMI1), as a major mechanism driving attenuated APC/C CDH1 activity in the G 1 -phase of the cell cycle in CSCs. Small-molecule inhibition of the APC/C reduced viability of both CSCs and nonstem tumor cells (NSTCs), with the combination of proTAME and apcin having the biggest impact. Combinatorial drug treatment also led to the greatest mitotic arrest and chromosomal abnormalities.Implications: Our findings demonstrate how the activity of the APC/C CDH1 tumor suppressor is reduced in CSCs and also validates small-molecule inhibition of the APC/C as a promising therapeutic target for the treatment of GBM.
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