Comparison of Hemodynamics in Jet Ventilation vs. Intermittent Apnea for Airway Stenosis Surgery.

OBJECTIVE: The objective of this study is to assess the impact of two different ventilation techniques, jet ventilation and apneic anesthesia with intermittent ventilation (AAIV), on patient hemodynamics and operative time during endoscopic laryngotracheal stenosis surgery. METHODS: Retrospective chart review of patients who underwent airway dilation for laryngotracheal stenosis by a single surgeon at a single institution from October 1, 2000 through January 2, 2020. Logistic regression, Mann-Whitney U tests and chi square analysis were used to determine statistical significance. RESULTS: A total of 157 patients, 43 (27.4%) male and 114 (72.6%) female, and 605 total encounters were included for analysis. There were no significant differences in hemodynamic outcomes when comparing the AAIV and jet ventilation groups. Specifically, there was no significant difference in either peak end-tidal CO2 or nadir O2 saturation between the AAIV and jet ventilation groups (p = 0.4016) and (p = 0.1357), respectively. The patients in the AAIV group had a significantly higher median BMI 32.93 (27.40-39.40) compared with 28.80 (24.1-32.65) (p = 0.0001). Although not necessarily clinically significant, patients with higher BMI had lower median O2 nadirs (97.8%) than non-obese patients (99.2%) (p < 0.0001). The median total procedure time was equivalent when comparing the two ventilation techniques. CONCLUSION: AAIV is a safe method of ventilation for patients undergoing endoscopic laryngotracheal stenosis surgery with no significant differences in patient hemodynamics or procedure time when compared with jet ventilation. AAIV was the preferred method of ventilation for obese patients undergoing endoscopic laryngotracheal stenosis surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1343-1348, 2024.

Connexin 43 Inhibition Sensitizes Chemoresistant Glioblastoma Cells to Temozolomide.

Resistance of glioblastoma (GBM) to the front-line chemotherapeutic agent temozolomide (TMZ) continues to challenge GBM treatment efforts. The repair of TMZ-induced DNA damage by O-6-methylguanine-DNA methyltransferase (MGMT) confers one mechanism of TMZ resistance. Paradoxically, MGMT-deficient GBM patients survive longer despite still developing resistance to TMZ. Recent studies indicate that the gap junction protein connexin 43 (Cx43) renders GBM cells resistant to TMZ through its carboxyl terminus (CT). In this study, we report insights into how Cx43 promotes TMZ resistance. Cx43 levels were inversely correlated with TMZ sensitivity of GBM cells, including GBM stem cells. Moreover, Cx43 levels inversely correlated with patient survival, including as observed in MGMT-deficient GBM patients. Addition of the C-terminal peptide mimetic αCT1, a selective inhibitor of Cx43 channels, sensitized human MGMT-deficient and TMZ-resistant GBM cells to TMZ treatment. Moreover, combining αCT1 with TMZ-blocked AKT/mTOR signaling, induced autophagy and apoptosis in TMZ-resistant GBM cells. Our findings suggest that Cx43 may offer a biomarker to predict the survival of patients with MGMT-independent TMZ resistance and that combining a Cx43 inhibitor with TMZ could enhance therapeutic responses in GBM, and perhaps other TMZ-resistant cancers.

Anorexigenic effects of central adrenomedullin are associated with hypothalamic changes in juvenile Gallus gallus.

Adrenomedullin (AM), a 52 residue neuropeptide, is associated with anorexia in mammals and has a poorly understood central mechanism of action. Thus, this study focused on elucidating AM's central mechanism of action in an alternative vertebrate model, the chick (Gallus gallus). In Experiment 1, chicks centrally injected with AM dose-dependently reduced food but not water intake. In Experiment 2, those chicks that received central AM had increased c-Fos immunoreactivity in the magnocellular division of the paraventricular nucleus (PaMC), ventromedial hypothalamus (VMH) and doromedial hypothalamus (DM). The lateral hypothalamic area, parvocellular division of the paraventricular hypothalamus and the arcuate nucleus were not affected. In Experiment 3, antagonism of corticotrophin releasing factor (CRF) receptors did not affect AM-associated anorexia. In Experiment 4, a comprehensive behavior analysis was conducted and AM-treated chicks pecked less, moved more, jumped more and spent more time in deep rest. In conclusion, exogenous AM induced anorexia is associated with activation of the PaMC, VMH and DM of the hypothalamus, is not CRF dependent, and affects behaviors unrelated to food intake in chicks.