COVID-19 Patients Presenting with Post-Intubation Upper Airway Complications: A Parallel Epidemic?

During the current pandemic, we witnessed a rise of post-intubation tracheal stenosis (PITS) in patients intubated due to COVID-19. We prospectively analyzed data from patients referred to our institution during the last 18 months for severe symptomatic post-intubation upper airway complications. Interdisciplinary bronchoscopic and/or surgical management was offered. Twenty-three patients with PITS and/or tracheoesophageal fistulae were included. They had undergone 31.85 (±22.7) days of ICU hospitalization and 17.35 (±7.4) days of intubation. Tracheal stenoses were mostly complex, located in the subglottic or mid-tracheal area. A total of 83% of patients had fracture and distortion of the tracheal wall. Fifteen patients were initially treated with rigid bronchoscopic modalities and/or stent placement and eight patients with tracheal resection-anastomosis. Post-treatment relapse in two of the bronchoscopically treated patients required surgery, while two of the surgically treated patients required rigid bronchoscopy and stent placement. Transient, non-life-threatening post-treatment complications developed in 60% of patients and were all managed successfully. The histopathology of the resected tracheal specimens didn't reveal specific alterations in comparison to pre-COVID-era PITS cases. Prolonged intubation, pronation maneuvers, oversized tubes or cuffs, and patient- or disease-specific factors may be pathogenically implicated. An increase of post-COVID PITS is anticipated. Careful prevention, early detection and effective management of these iatrogenic complications are warranted.

Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts.

A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found in breast and pancreatic tumors and are considered to be immunosuppressive. This analysis shows that antigen-presenting fibroblasts are frequent in human lung non-small cell carcinomas, where they seem to actively promote rather than suppress MHCII immunity. Lung apCAFs directly activated the TCRs of effector CD4 T cells and at the same time produced C1q, which acted on T cell C1qbp to rescue them from apoptosis. Fibroblast-specific MHCII or C1q deletion impaired CD4 T cell immunity and accelerated tumor growth, while inducing C1qbp in adoptively transferred CD4 T cells expanded their numbers and reduced tumors. Collectively, we have characterized in the lungs a subset of antigen-presenting fibroblasts with tumor-suppressive properties and propose that cancer immunotherapies might be strongly dependent on in situ MHCII antigen presentation.

Generation of Non-Small Cell Lung Cancer Patient-Derived Xenografts to Study Intratumor Heterogeneity.

Recent advances in sequencing technologies have allowed the in-depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreciated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early-stage operable non-small cell lung cancer, we used tumor growth in patient-derived xenograft (PDX) models in mice as a fast-forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency. We found that squamous cell carcinomas grafted significantly more efficiently compared with adenocarcinomas. Advanced stage, patient age and primary tumor size were positively correlated with grafting. Additionally, we isolated and characterized circulating tumor cells (CTC) from patients' peripheral blood and found that the presence of CTCs expressing epithelial-to-mesenchymal (EMT) markers correlated with the grafting potential. Interestingly, exome sequencing of the PDX tumor identified genetic alterations in DNA repair and genome integrity genes that were under-represented in the human primary counterpart. In conclusion, through the generation of a PDX biobank of NSCLC, we identified the clinical and molecular properties of tumors that affected growth in mice.

A 63-Year-Old Woman With Pulmonary Micronodules and Chronic Cough.

CASE PRESENTATION: A 63-year-old woman presented with a 2-year history of nonproductive cough. She denied the presence of shortness of breath, chest pain, arthralgia, muscle weakness, weight loss, night sweats, and fatigue. She was a never smoker and had a history of arterial hypertension and diabetes. There was no history of asthma, allergic rhinitis, nasal polyps, or gastroesophageal reflux disease, known malignancy, or collagen tissue disease. She reported exposure to house mold. There was no family history of respiratory diseases. The patient denied alcohol consumption, illicit drug use, occupational exposures, any recent travel, or exposure to TB.

Thymoma and myasthenia gravis: clinical aspects and prognosis.

Myasthenia gravis is present in a significant proportion of patients with thymoma. We investigated particular features of the clinical behavior of thymoma and its relationship to myasthenia in a retrospective study of 79 patients who underwent thymectomy for thymoma during the last 20 years. The presence of myasthenia gravis, Masaoka stage, World Health Organization histotype, myasthenia response, and survival were analyzed. The mean age of the patients was 56.1 ± 12.4 years, and 39 had myasthenia gravis. A significantly higher proportion of patients with myasthenia was found in B2 and B3 histotypes compared to A, AB, and B1. Among myasthenic patients, 33.3% had no response, 50% had a partial response, and 16.7% achieved complete remission. During the follow-up period, 16 (21.1%) patients died. Mean survival was 4.8 ± 1.4 years for patients with no myasthenia response, whereas those with a partial or complete myasthenia response had significantly better survival.