158 research outputs found
AltitudeOmics: Red Blood Cell metabolic adaptation to high altitude hypoxia
Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated. Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters. Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and maintained for 16 days at high altitude. Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory
Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis
The aim of this study was to systematically review and meta-analyze published data on the diagnostic performance of combined 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the detection of primary tumors in patients with cancer of unknown primary (CUP). A systematic search for relevant studies was performed of the PubMed/MEDLINE and Embase databases. Methodological quality of the included studies was assessed. Reported detection rates, sensitivities and specificities were meta-analyzed. Subgroup analyses were performed if results of individual studies were heterogeneous. The 11 included studies, comprising a total sample size of 433 patients with CUP, had moderate methodological quality. Overall primary tumor detection rate, pooled sensitivity and specificity of FDG-PET/CT were 37%, 84% (95% CI 78–88%) and 84% (95% CI 78–89%), respectively. Sensitivity was heterogeneous across studies (P = 0.0001), whereas specificity was homogeneous across studies (P = 0.2114). Completeness of diagnostic workup before FDG-PET/CT, location of metastases of unknown primary, administration of CT contrast agents, type of FDG-PET/CT images evaluated and way of FDG-PET/CT review did not significantly influence diagnostic performance. In conclusion, FDG-PET/CT can be a useful method for unknown primary tumor detection. Future studies are required to prove the assumed advantage of FDG-PET/CT over FDG-PET alone and to further explore causes of heterogeneity
Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control
Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe
FDG PET/CT in carcinoma of unknown primary
Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic malignancies in which a primary tumor could not be detected despite thorough diagnostic evaluation. Because of its high sensitivity for the detection of lesions, combined 18F-fluoro-2-deoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) may be an excellent alternative to CT alone and conventional magnetic resonance imaging in detecting the unknown primary tumor. This article will review the use, diagnostic performance, and utility of FDG PET/CT in CUP and will discuss challenges and future considerations in the diagnostic management of CUP
Impact of chloride and strong ion difference on ICU and hospital mortality in a mixed intensive care population
BACKGROUND: Abnormal chloride levels are commonly observed in critically ill patients, but their clinical relevance remains a matter of debate. We examined the association between abnormal chloremia and ICU and hospital mortality. To further refine findings and integrate them into the ongoing discussion on the detrimental effects of chloride-rich solutions, the impact of strong ion difference (SID) on the same end points was assessed. METHODS: Retrospective cohort study in an academic tertiary intensive care unit on 8830 adult patients who stayed at least 24 h in the ICU was carried out. Patients admitted after elective cardiac surgery were treated as a separate subgroup (n = 2350). Analyses were performed using multivariable logistic regression. All statistical models were extensively adjusted for confounders, including comorbidity, admission diagnosis, other electrolytes and acid–base parameters. RESULTS: Severe hyperchloremia (>110 mmol/L), but not low (SID) was significantly associated with increased mortality in the ICU (odds ratio vs. normochloremia 1.81; 95 % CI 1.32–2.50; p < 0.001) and the hospital (odds ratio 1.49; 95 % CI 1.14–1.96; p = 0.003). Hyperchloremia and low (SID) were encountered in the majority of patients admitted after cardiac surgery (in 86.9 and 47.2 %, respectively), but were not negatively associated with mortality. CONCLUSIONS: In the ICU, hyperchloremia at admission was associated with negative outcome. On the other hand, decreased strong ion difference did not have an impact on mortality, precluding a simple extrapolation of these findings to the ongoing discussion on the detrimental effects of chloride-rich solutions. This notion is fueled by the finding that hyperchloremia after cardiac surgery, frequently encountered and probably fluid-induced, did not seem to be deleterious. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13613-016-0193-x) contains supplementary material, which is available to authorized users
Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C
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