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OBJECTIVE: To characterize the preoperative and intraoperative findings of symptomatic tracheal stenosis associated with COVID-19 related respiratory failure requiring tracheal resection. METHOD: We performed a retrospective review identifying all patients with a history of tracheal stenosis secondary to COVID-19 related respiratory failure who subsequently received a tracheal resection at our institution between January 2020 and June 2023. Clinical, radiological, pathological, and surgical characteristics were recorded to describe and characterize pre-operative and intraoperative findings associated with tracheal stenosis in the setting of a previous COVID-19 infection. RESULTS: We retrospectively reviewed 11 patients with COVID-19 related tracheal stenosis that required open tracheal or cricotracheal resection. The mean age was 54.1. Patients were hospitalized for a mean of 49.5 days related to COVID-19 complications. Tracheotomy was completed in 10 patients (90.9%) during their initial hospitalization with COVID-19 related respiratory failure. Patients were intubated a mean of 18.6 days prior to tracheotomy completion. Ten patients (90.9%) underwent endoscopic operative interventions for their tracheal stenosis prior to open resection. Intraoperatively, the mean stenosis length was 3.33 cm. The mean tracheal resection length was 3.96 cm. Patients were hospitalized for a mean of 8.27 days post operatively with no significant post operative complications. CONCLUSIONS: Symptomatic tracheal stenosis in the setting of prolonged intubation due to COVID-19 is an under-described etiology. This is one of the largest single institution retrospective reviews that identifies 11 patients with prolonged intubation who developed symptomatic tracheal stenosis refractory to conservative management and ultimately requiring tracheal resection.
RESUMEN
The clinical impact of tumor-specific neoantigens as both immunotherapeutic targets and biomarkers has been impeded by the lack of efficient methods for their identification and validation from routine samples. We have developed a platform that combines bioinformatic analysis of tumor exomes and transcriptional data with functional testing of autologous peripheral blood mononuclear cells (PBMCs) to simultaneously identify and validate neoantigens recognized by naturally primed CD4+ and CD8+ T cell responses across a range of tumor types and mutational burdens. The method features a human leukocyte antigen (HLA)-agnostic bioinformatic algorithm that prioritizes mutations recognized by patient PBMCs at a greater than 40% positive predictive value followed by a short-term in vitro functional assay, which allows interrogation of 50 to 75 expressed mutations from a single 50-ml blood sample. Neoantigens validated by this method include both driver and passenger mutations, and this method identified neoantigens that would not have been otherwise detected using an in silico prediction approach. These findings reveal an efficient approach to systematically validate clinically actionable neoantigens and the T cell receptors that recognize them and demonstrate that patients across a variety of human cancers have a diverse repertoire of neoantigen-specific T cells.