RESUMO
Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered a key pathogenic driver of these diseases, but the underlying immune states and their clinical implications remain poorly understood. Multiomic factor analysis (MOFA) allows unsupervised data exploration across multiple data types, identifying major axes of variation and associating these with underlying molecular processes. We hypothesized that applying MOFA to multiomic data obtained from blood might uncover hidden sources of variance and provide pathophysiological insights linked to clinical needs. Here we compile a longitudinal multiomic dataset of the systemic immune landscape in both ACS and CCS (n = 62 patients in total, n = 15 women and n = 47 men) and validate this in an external cohort (n = 55 patients in total, n = 11 women and n = 44 men). MOFA reveals multicellular immune signatures characterized by distinct monocyte, natural killer and T cell substates and immune-communication pathways that explain a large proportion of inter-patient variance. We also identify specific factors that reflect disease state or associate with treatment outcome in ACS as measured using left ventricular ejection fraction. Hence, this study provides proof-of-concept evidence for the ability of MOFA to uncover multicellular immune programs in cardiovascular disease, opening new directions for mechanistic, biomarker and therapeutic studies.
Assuntos
Síndrome Coronariana Aguda , Humanos , Feminino , Síndrome Coronariana Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Idoso , Doença Crônica , Monócitos/imunologia , Células Matadoras Naturais/imunologia , Linfócitos T/imunologia , Inflamação/imunologiaRESUMO
OBJECTIVE: Laryngomalacia is the most common cause of stridor in newborns and infants. The aim of the contribution was to present objectified data of the outcome of transoral CO(2) laser microsurgery in patients with laryngomalacia utilizing polysomnography (PSG). PATIENTS AND METHODS: This retrospective study comprised 21 patients who were diagnosed to suffer from laryngomalacia. Diagnosis was confirmed by pharyngo-laryngoscopy under spontaneous breathing. If there was evidence for laryngomalacia a transoral CO(2) lasersurgical intervention and/or epiglottopexy was performed in the same session. 8 patients, on whom the following should be focused, received pre- and postoperative PSG which was performed for efficiency control of the applied treatment. RESULTS: All 21 patients underwent invasive treatment for laryngomalacia (lasersurgical division of the aryepiglottic folds: n=13; epiglottopexy: n=5; combined procedure: n=3). All patients were successfully extubated after surgery. In 20/21 cases breathing improved clearly after one single intervention. Stridor disappeared completely in the further course of the disease. In the 8 patients who received pre- and postinterventional PSG, lasersurgical interventions were performed. Statistical analysis of pre- and postoperative PSG revealed that MOAI/h (mixed obstructive apnea index/hour) improved significantly (p=0.016, Wilcoxon-Signed-Rank Test). Also desaturation/hour improved in the postoperative course (p=0.11). CONCLUSION: The presented concept describes an effective and reliable approach for diagnostics and treatment for laryngomalacia. To objectify the success of supraglottoplaty in patients suffering from severe laryngomalacia a pre- and postoperative PSG seems to be useful and advisable. The present results of PSG demonstrate that children with laryngomalacia to benefit from lasersurgical division of the aryepiglottic folds and/or epiglottopexy. This fact is supported by the postoperative improved clinical aspect.