Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months resulted in improved glycemic control and insulin resistance compared with results for a control group. Clinical trial registered with www.clinicaltrials.gov (NCT01801150).
A false diagnosis of asthma (misdiagnosed asthma) in obese subjects is attributable to an increased perception of dyspnea, which, during exercise, is mainly associated with systemic inflammation and excessive ventilation for metabolic demands.
CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients’ plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y12 receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder.
Immunosurveillance is compromised in patients with obstructive sleep apnea (OSA) as reflected by overexpression of the programmed death cell receptor and its ligand (PD-1/PD-L1) coinhibitory axis. However, the contributions of intermittent hypoxia (IH) and sleep fragmentation (SF) are unclear. We therefore evaluated the expression of PD-1 and PD-L1 on immune cells from mice subjected to IH or SF, and in human cells exposed to IH, oxidative stress, or both conditions. Six-week-old male C57BL/6J mice were exposed to either IH or SF using previously established in vivo models. Moreover, human peripheral blood mononuclear cells (PBMC) were cultured overnight under normoxia, IH, hydrogen peroxide (H2O2), or both. Murine splenocytes and human PBMC were isolated, and labeled using surface-specific antibodies for flow cytometry analysis. Compared to control mice, IH induced higher expression of PD-L1 on F4/80 cells and of PD-1 on CD4+ and CD8+ T-cells, whereas no significant changes emerged after SF. In vitro models of IH and oxidative stress showed similar changes for expression of PD-L1 on human monocytes and PD-1 on CD4+ T-cells. Furthermore, H2O2 increased PD-1 expression on CD8+ T-cells, compromising their cytotoxic capacity assessed by perforin expression, similar to IH. No evidence of synergistic effects was apparent. Therefore, PD-1/PD-L1 upregulation reported in patients with OSA appears to be preferentially mediated by IH rather than SF.
Volumetric computed tomography is a reliable and accurate method to predict postoperative lung function in patients undergoing lung resection that provides better accuracy than conventional procedures. Because lung computed tomography is systematically performed in the staging of patients with suspected lung cancer, this volumetric analysis might simultaneously provide the information necessary to evaluate operability.
In patients with COPD, the AL classification based on z-score predicts worse mortality than those based on percentage of predicted. It is possible that the z-score underestimates AL severity in patients older than 60 years of age with severe functional impairment.
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