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- Gill, Dipender, et al.
(författare)
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ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels : a Mendelian randomization study
- 2020
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Ingår i: Royal Society Open Science. - : ROYAL SOC. - 2054-5703. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 x 10(-4)) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.
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- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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- Pugin, D, et al.
(författare)
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Resting-State Brain Activity for Early Prediction Outcome in Postanoxic Patients in a Coma with Indeterminate Clinical Prognosis.
- 2020
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Ingår i: American Journal of Neuroradiology. - : American Society of Neuroradiology (ASNR). - 0195-6108 .- 1936-959X. ; 41:6, s. 1022-1030
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Early outcome prediction of postanoxic patients in a coma after cardiac arrest proves challenging. Current prognostication relies on multimodal testing, using clinical examination, electrophysiologic testing, biomarkers, and structural MR imaging. While this multimodal prognostication is accurate for predicting poor outcome (ie, death), it is not sensitive enough to identify good outcome (ie, consciousness recovery), thus leaving many patients with indeterminate prognosis. We specifically assessed whether resting-state fMRI provides prognostic information, notably in postanoxic patients in a coma with indeterminate prognosis early after cardiac arrest, specifically for good outcome.MATERIALS AND METHODS: We used resting-state fMRI in a prospective study to compare whole-brain functional connectivity between patients with good and poor outcomes, implementing support vector machine learning. Then, we automatically predicted coma outcome using resting-state fMRI and also compared the prediction based on resting-state fMRI with the outcome prediction based on DWI.RESULTS: Of 17 eligible patients who completed the study procedure (among 351 patients screened), 9 regained consciousness and 8 remained comatose. We found higher functional connectivity in patients recovering consciousness, with greater changes occurring within and between the occipitoparietal and temporofrontal regions. Coma outcome prognostication based on resting-state fMRI machine learning was very accurate, notably for identifying patients with good outcome (accuracy, 94.4%; area under the receiver operating curve, 0.94). Outcome predictors using resting-state fMRI performed significantly better (P < .05) than DWI (accuracy, 60.0%; area under the receiver operating curve, 0.63).CONCLUSIONS: Indeterminate prognosis might lead to major clinical uncertainty and significant variations in life-sustaining treatments. Resting-state fMRI might bridge the gap left in early prognostication of postanoxic patients in a coma by identifying those with both good and poor outcomes.
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- Sallinen, Ville J., et al.
(författare)
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Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors : a multi-institutional study
- 2018
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Ingår i: HPB. - : Elsevier. - 1365-182X .- 1477-2574. ; 20:3, s. 251-259
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malignant potential of small (<= 20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs.Methods: Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni-and multivariate analyses.Results: sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized <= 10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively.Conclusions: In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.
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