No abstract

Personalized molecular profiling has an established role in selection of treatment for metastatic disease; however, its role in improving radiosensitivity and functional imaging has not been evaluated. In the current study, we examined molecular profiling as a tool for designing personalized targeted gold nanoparticles (GNP) to serve as dual-modal tumor radiosensitizers and functional imaging enhancers. To this end, molecular profiling of a patient's salivary gland adenoid cystic carcinoma (ACC) was performed, and anaplastic lymphoma kinase (ALK) mutation was detected. The extracted tumor was subcutaneously injected into mice, which were then treated either with radiation, the specific ALK inhibitor crizotinib, or a combination of therapies. One of these combinations, namely, ALK-targeted GNP (via crizotinib coating), was found to enhance radiation treatment, as demonstrated by a significant decrease in tumor volume over 24 days. In parallel, ALK-targeted GNP substantially augmented tumor visualization via computed tomography. The mechanism of radiosensitivity enhancement was mostly related to a diminished cell repair mechanism in tumors, as demonstrated by proliferating cell nuclear antigen staining. These findings indicate that personalized molecular profiling is an effective technique for enhancing cancer theranostics.

Objectives: Review the incidence and factors associated with respiratory compromise requiring intensive care unit level interventions in children with planned admission to the pediatric intensive care unit (PICU) following tonsillectomy or adenotonsillectomy (T/AT). Study design: Retrospective cohort study. Methods: Review of all patients with PICU admissions following T/AT from 2015 to 2020 at a tertiary care pediatric hospital. Patient demographics, underlying comorbidities, operative data, and respiratory complications during PICU admission were extracted. Results: Seven hundred and seventy-two patients were admitted to the PICU following T/AT, age 6.1 ± 4.6 years. All children were diagnosed with obstructive sleep apnea or sleep-disordered breathing (mean pre-operative apnea-hypopnea index 29 ± 26.5 and O2 nadir 77.1% ± 11.1). Neuromuscular disease, enteral feed dependence, and obesity were common findings (N = 240 (31%), N = 106 (14%), and N = 209 (27%) respectively). Overall, 29 patients (3.7%) developed respiratory compromise requiring PICU-level support, defined as new-onset continuous or bilevel positive airway pressure support (n = 25) or reintubation (n = 9). Three patients were diagnosed with pulmonary edema. Multivariable regression analysis demonstrated pre-operative oxygen nadir and enteral feed dependence were associated with respiratory compromise (OR = 0.97, 95% CI 0.94-0.99, P = .04; OR = 6.3, 95% CI 2.36-52.6, P = .001 respectively). Conclusions: Our study found respiratory compromise in 3.7% of patients with planned PICU admissions following T/AT. Oxygen nadir and enteral feeds were associated with higher respiratory compromise rates. Attention should be given to these factors in planning for post-operative disposition.