The role of thoracic surgery in the management of complicated acute and post-acute COVID-19 pneumonia (PASC).

INTRODUCTION: COVID-19 is considered a respiratory virosis in its classic form, although it may present with heterogeneous symptoms. Thoracic complications occur in a small percentage of patients. Our objective was to evaluate existing experience with this disease and its thoracic manifestations and to determine the real-world status of care of these patients. METHODS: This study is a retrospective, single-institution analysis of a group of patients hospitalized with acute and post-acute COVID-19 pneumonia at Thomayer Hospital in Prague in the period from December 2020 to March 2022 and indicated for a thoracic surgical procedure. RESULTS: During the peak of COVID-19 pandemic, a thoracic intervention was performed in 46 admitted patients. Thoracic drainage (due to pneumothorax in 18 cases, fluidothorax in 3 cases, CT-guided lung abscess drainage in 2 cases, and CT-guided pneumatocele drainage in 2 cases) were the most common thoracic surgical procedures. Pleurectomy/decortication surgery was done in 10 cases. Additionally, 12 lung parenchyma-sparing resections were performed, while lobectomy was required in 2 cases. Resection of postintubation tracheal stenosis due to a severe course of COVID-19 pneumonia was indicated in 2 patients. CONCLUSION: Even mild COVID-19 may cause a considerable morphological a functional alteration of the respiratory system. The most common complications of COVID-19 pneumonia that require a thoracic surgical intervention include pathologies associated with an air leak and accumulation of air (pneumothorax, pneumomediastinum and subcutaneous emphysema). The development of pulmonary necrosis, symptomatic bronchiectasis, pneumatocele, and bullous-fibrotic formations may result in pneumothorax, hemothorax or thoracic empyema in sporadic cases. An early thoracic surgical intervention to treat thoracic complications of COVID-19 pneumonia can improve the survival of COVID-19 patients.

Glucocorticoid availability in colonic inflammation of rat.

Recent in vitro studies have shown the involvement of pro-inflammatory cytokines in the regulation of the local metabolism of glucocorticoids via 11beta-hydroxysteroid dehydrogenase type 1 and type 2 (11HSD1 and 11HSD2). However, direct in vivo evidence for a relationship among the local metabolism of glucocorticoids, inflammation and steroid enzymes is still lacking. We have therefore examined the changes in the local metabolism of glucocorticoids during colonic inflammation induced by TNBS and the consequences of corticosterone metabolism inhibition by carbenoxolone on 11HSD1, 11HSD2, cyclooxygenase 2 (COX-2), mucin 2 (MUC-2), tumor necrosis factor alpha (TNF-alpha), and interleukin 1beta (IL-1beta). The metabolism of glucocorticoids was measured in tissue slices in vitro and their 11HSD1, 11HSD2, COX-2, MUC-2, TNF-alpha, and IL-1beta mRNA abundances by quantitative reverse transcription-polymerase chain reaction. Colitis produced an up-regulation of colonic 11HSD1 and down-regulation of 11HSD2 in a dose-dependent manner, and these changes resulted in a decreased capacity of the inflamed tissue to inactivate tissue corticosterone. Similarly, 11HSD1 transcript was increased in colonic intraepithelial lymphocytes of TNBS-treated rats. Topical intracolonic application of carbenoxolone stimulated 11HSD1 mRNA and partially inhibited 11HSD2 mRNA and tissue corticosterone inactivation and these changes were blocked by RU-486. The administration of budesonide mimicked the effect of carbenoxolone. In contrast to the local metabolism of glucocorticoids, carbenoxolone neither potentiates nor diminishes gene expression for COX-2, TNF-alpha, and IL-1beta, despite the fact that budesonide down-regulated all of them. These data indicate that inflammation is associated with the down-regulation of tissue glucocorticoid catabolism. However, these changes in the local metabolism of glucocorticoids do not modulate the expression of COX-2, TNF-alpha, and IL-1beta in inflamed tissue.

Colitis up-regulates local glucocorticoid activation and down-regulates inactivation in colonic tissue.

BACKGROUND: Pro-inflammatory processes are counteracted by anti-inflammatory factors such as glucocorticoids. The response of target cells to glucocorticoids depends on several factors including prereceptor modulation of glucocorticoid signals via local glucocorticoid metabolism. This is determined by two isoforms of 11beta-hydroxysteroid dehydrogenase (11betaHSD); 11betaHSD1 operates in vivo as a reductase converting inactive 11-oxo glucocorticoids to active glucocorticoids cortisol or corticosterone, whereas 11betaHSD2 catalyses oxidation of active glucocorticoids to their inactive 11-oxo derivatives. The aim of this study was to investigate the changes in local metabolism of glucocorticoids and in the expression of 11betaHSD1 and 11betaHSD2 mRNA during colonic inflammation. METHODS: Acute colitis was induced by intracolonic administration of 2,4,6-trinitrobenzenesulphonic acid (TNBS) or by drinking a dextran sodium sulphate (DSS) solution. Metabolism of glucocorticoids was measured in tissue fragments in vitro and 11betaHSD1 and 11betaHSD2 mRNA abundance was quantified using real-time RT-PCR one week after administration of TNBS and 10 days after drinking the DSS solution. RESULTS: In both models of inflammatory bowel disease we observed down-regulation of corticosterone oxidation to 11-dehydrocorticosterone by 64% (TNBS) and 53% (DSS) and reciprocal stimulation of reduction of 11-dehydrocorticosterone to corticosterone by 83% and 54%, respectively. A similar pattern was observed at the level of mRNA; 11betaHSD1 mRNA was significantly higher (TNBS: increase by 660%; DSS: increase by 760%) and 11betaHSD2 mRNA lower (TNBS: decrease by 85%; DSS: decrease by 60%) during inflammation. CONCLUSIONS: Colitis induces local glucocorticoid activation from 11-oxo steroids and decreases glucocorticoid inactivation; i.e. inflammation increases local tissue ratio of active and inactive glucocorticoids. The results indicate that the changes in local metabolism of glucocorticoids could contribute to the control of an overshoot of inflammation processes in the colon.