RESUMEN
BACKGROUND: Capnodynamic lung function monitoring generates variables that may be useful for pediatric perioperative ventilation. AIMS: Establish normal values for end-expiratory lung volume CO2 in healthy children undergoing anesthesia and to compare these values to previously published values obtained with alternative end-expiratory lung volume methods. The secondary aim was to investigate the ability of end-expiratory lung volume CO2 to react to positive end-expiratory pressure-induced changes in end-expiratory lung volume. In addition, normal values for associated volumetric capnography lung function variables were examined. METHODS: Fifteen pediatric patients with healthy lungs (median age 8 months, range 1-36 months) undergoing general anesthesia were examined before start of surgery. Tested variables were recorded at baseline positive end-expiratory pressure 3 cmH2 O, 1 and 3 min after positive end-expiratory pressure 10 cmH2 O and 3 min after returning to baseline positive end-expiratory pressure 3 cmH2 O. RESULTS: Baseline end-expiratory lung volume CO2 was 32 mL kg-1 (95% CI 29-34 mL kg-1 ) which increased to 39 mL kg-1 (95% CI 35-43 mL kg-1 , p < .0001) and 37 mL kg-1 (95% CI 34-41 mL kg-1 , p = .0003) 1 and 3 min after positive end-expiratory pressure 10 cmH2 O, respectively. End-expiratory lung volume CO2 returned to baseline, 33 mL kg-1 (95% CI 29-37 mL kg-1 , p = .72) 3 min after re-establishing positive end-expiratory pressure 3 cmH2 O. Airway dead space increased from 1.1 mL kg-1 (95% CI 0.9-1.4 mL kg-1 ) to 1.4 (95% CI 1.1-1.8 mL kg-1 , p = .003) and 1.5 (95% CI 1.1-1.8 mL kg-1 , p < .0001) 1 and 3 min after positive end-expiratory pressure 10 cmH2 O, respectively, and 1.2 mL kg-1 (95% CI 0.9-1.4 mL kg-1 , p = .08) after 3 min of positive end-expiratory pressure 3 cmH2 O. Additional volumetric capnography and lung function variables showed no major changes in response to positive end-expiratory pressure variations. CONCLUSIONS: Capnodynamic noninvasive and continuous end-expiratory lung volume CO2 values assessed during anesthesia in children were in close agreement with previously reported end-expiratory lung volume values generated by alternative methods. Furthermore, positive end-expiratory pressure changes resulted in physiologically expected end-expiratory lung volume CO2 responses in a timely manner, suggesting that it can be used to trend end-expiratory lung volume changes during anesthesia.
Asunto(s)
Dióxido de Carbono , Respiración , Humanos , Niño , Lactante , Preescolar , Mediciones del Volumen Pulmonar , Respiración con Presión Positiva , Pulmón , Anestesia General , Volumen de Ventilación PulmonarRESUMEN
Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microenvironment are therefore expected to be highly warranted. In this study, intratumoral spatial cross presentation was investigated as a novel concept where immune cell composition in the tumor microenvironment was suggested to act as a proxy for immune surveillance. Double immunohistochemistry revealed a prognostic role of direct spatial interactions between CD11c+ antigen-presenting cells (APCs) and CD8+ cells in contrast to each marker alone in a soft tissue sarcoma (STS) cohort of 177 patients from the Karolinska University Hospital (MFS p = 0.048, OS p = 0.025). The survival benefit was verified in multivariable analysis (MFS p = 0.012, OS p = 0.004). Transcriptomics performed in the TCGA sarcoma cohort confirmed the prognostic value of combining CD11c with CD8 (259 patients, p = 0.005), irrespective of FOXP3 levels and in a CD274 (PD-LI)-rich tumor microenvironment. Altogether, this study presents a histopathological approach to link immune surveillance and patient survival in STS. Notably, spatial cross presentation as a prognostic marker is distinct from therapy response-predictive biomarkers such as immune checkpoint molecules of the PD-L1/PD1 pathway.