Perioperative Delta Weight and Pediatric Obstructive Sleep Apnea Resolution after Adenotonsillectomy.

OBJECTIVE(S): The first-line treatment for pediatric obstructive sleep apnea (OSA) is adenotonsillectomy. Post-operative weight gain is a well-documented phenomenon. We hypothesized that higher peri-adenotonsillectomy delta weight correlates with lower rates of OSA resolution in pediatric patients. METHODS: This was a retrospective cohort study consisting of 250 patients from 2 to 17 years of age at a tertiary academic medical center between January 2021 and December 2022. Polysomnography results and body mass index (BMI) changes were collected through the electronic health record. Univariate and multivariate logistical regression analyses were performed, adjusting for confounding factors. RESULTS: Perioperative delta weight and pre-operative baseline AHI values were significant predictors of residual OSA. For every 1-kilogram gain in weight, the odds of residual OSA (AHI >5) increase by 6.0% (OR = 1.06, 95% CI = 1.02-1.10, p < 0.002), and the odds of residual severe OSA (AHI > 10) increase by 8% (OR = 1.08, 95% CI = 1.04-1.12, p < 0.001). Increased AHI, Black/African American race, and male sex were also factors associated with incomplete OSA resolution. CONCLUSIONS: Increased peri-adenotonsillectomy delta weight is associated with higher rates of residual OSA in children. Patients and families should be counseled about appropriate weight loss and control methods before adenotonsillectomy. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Human clinical mutations in mitochondrially encoded subunits of Complex I can be successfully modeled in E. coli.

Respiratory Complex I is the site of a large fraction of the mutations that appear to cause mitochondrial disease. Seven of its subunits are mitochondrially encoded, and therefore, such mutants are particularly difficult to construct in cell-culture model systems. We have selected 13 human clinical mutations found in ND2, ND3, ND4, ND4L, ND5 and ND6 that are generally found at subunit interfaces, and not in critical residues. These mutations have been modeled in E. coli subunits of Complex I, nuoN, nuoA, nuoM, nuoK, nuoL, and nuoJ, respectively. All mutants were expressed from a plasmid encoding the entire nuo operon, and membrane vesicles were analyzed for deamino-NADH oxidase activity, and proton translocation activity. ND5 mutants were also analyzed using a time-delayed expression system, recently described by this lab. Other mutants were analyzed for the ability to associate in subcomplexes, after expression of subsets of the genes. For most mutants there was a positive correlation between those that were previously determined to be pathogenic, or likely to be pathogenic, and those that we found with compromised Complex I activity or subunit interactions in E. coli. In conclusion, this approach provides another way to explore the deleterious effects of human mitochondrial mutations, and it can contribute to molecular understanding of such mutations.

Analysis of Human Mutations in the Supernumerary Subunits of Complex I.

Complex I is the largest member of the electron transport chain in human mitochondria. It comprises 45 subunits and requires at least 15 assembly factors. The subunits can be divided into 14 "core" subunits that carry out oxidation-reduction reactions and proton translocation, as well as 31 additional supernumerary (or accessory) subunits whose functions are less well known. Diminished levels of complex I activity are seen in many mitochondrial disease states. This review seeks to tabulate mutations in the supernumerary subunits of humans that appear to cause disease. Mutations in 20 of the supernumerary subunits have been identified. The mutations were analyzed in light of the tertiary and quaternary structure of human complex I (PDB id = 5xtd). Mutations were found that might disrupt the folding of that subunit or that would weaken binding to another subunit. In some cases, it appeared that no protein was made or, at least, could not be detected. A very common outcome is the lack of assembly of complex I when supernumerary subunits are mutated or missing. We suggest that poor assembly is the result of disrupting the large network of subunit interactions that the supernumerary subunits typically engage in.