Use of VOTE score in predicting outcomes in pediatric obstructive sleep apnea.

OBJECTIVES: Obstructive Sleep Apnea (OSA) affects 1-4% of the pediatric population in the U.S. Drug-Induced Sleep Endoscopy (DISE) is widely used to localize the level(s) of obstruction. The VOTE classification system is used to grade obstructions found at the velum, oropharynx, base of tongue, and epiglottis and has been validated in adults. This study aims to determine if the VOTE score has any predictive value in pediatric OSA postoperative outcomes. METHODS: A retrospective chart review of 129 patients from January 7, 2016 to 05/30/2020 was performed. Included patients were between the ages of 2 and 17, undergoing DISE, and if they had preoperative and postoperative polysomnography (PSG) data. Excluded patients did not meet one of the above or had other comorbidities contributing to their sleep apnea. 53 patients were included. RESULTS: Pearson's Correlation tests compared intraoperative VOTE score to postoperative BMI, AHI, and O2 nadir and their relationships. We found a weakly positive correlation between the VOTE and postoperative AHI with a coefficient of 0.35 and a p-value of 0.01. We found a relationship between postoperative O2 nadir and AHI, with a coefficient of -0.627 and a p-value <0.0001. Finally, a paired, two-tailed t-test compared the mean change between preoperative and postoperative BMIs (+1.6), oAHIs (-23.5), and O2 nadirs (+14), all with p-value <0.0001. CONCLUSION: We demonstrated a correlation between VOTE and improved postoperative AHI and a relationship between improved postoperative AHI and postoperative O2 nadir. The validity of VOTE may be proven with larger sample size. Alternatively, a different scoring system may be required for pediatric OSA.

Differential requirements of protein geranylgeranylation for the virulence of human pathogenic fungi.

Protein prenylation is a crucial post-translational modification largely mediated by two heterodimeric enzyme complexes, farnesyltransferase and geranylgeranyltransferase type-I (GGTase-I), each composed of a shared α-subunit and a unique ß-subunit. GGTase-I enzymes are validated drug targets that contribute to virulence in Cryptococcus neoformans and to the yeast-to-hyphal transition in Candida albicans. Therefore, we sought to investigate the importance of the α-subunit, RamB, and the ß-subunit, Cdc43, of the A. fumigatus GGTase-I complex to hyphal growth and virulence. Deletion of cdc43 resulted in impaired hyphal morphogenesis and thermo-sensitivity, which was exacerbated during growth in rich media. The Δcdc43 mutant also displayed hypersensitivity to cell wall stress agents and to cell wall synthesis inhibitors, suggesting alterations of cell wall biosynthesis or stress signaling. In support of this, analyses of cell wall content revealed decreased amounts of ß-glucan in the Δcdc43 strain. Despite strong in vitro phenotypes, the Δcdc43 mutant was fully virulent in two models of murine invasive aspergillosis, similar to the control strain. We further found that a strain expressing the α-subunit gene, ramB, from a tetracycline-inducible promoter was inviable under non-inducing in vitro growth conditions and was virtually avirulent in both mouse models. Lastly, virulence studies using C. albicans strains with tetracycline-repressible RAM2 or CDC43 expression revealed reduced pathogenicity associated with downregulation of either gene in a murine model of disseminated infection. Together, these findings indicate a differential requirement for protein geranylgeranylation for fungal virulence, and further inform the selection of specific prenyltransferases as promising antifungal drug targets for each pathogen.