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- Winkler, TW, et al.
(författare)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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- Almskog, LM, et al.
(författare)
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A retrospective register study comparing fibrinogen treated trauma patients with an injury severity score matched control group
- 2020
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Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 28:1, s. 5-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFibrinogen concentrate (FC) is frequently used to treat bleeding trauma patients, although the clinical effects are not well known. In this study we describe demographic and clinical outcome data in a cohort of trauma patients receiving FC, compared to a matched control group, who did not receive FC.MethodsThis retrospective, single-center, observational study included adult trauma patients admitted to a level 1-trauma center in Sweden between January 2013 and June 2015. The study population consisted of patients to whom FC was administrated within 24 h (n = 138, “Fib+”). Patients with Injury Severity Score (ISS) > 49 and/or deceased within 1 h from arrival were excluded (n = 30). Controls (n = 108) were matched for age, gender and ISS (“Fib-“). Primary outcome was mortality (24 h−/30 days−/1 year-), and secondary outcomes were blood transfusions, thromboembolic events and organ failure.ResultsThe Fib+ group, despite having similar ISS as Fib-, had higher prevalence of penetrating trauma and lower Glasgow Coma Scale (GCS), indicating more severe injuries. Patients receiving FC had a higher mortality after 24 h/ 30 days/ 1 year compared to controls (Fib-). However, in a propensity score matched model, the differences in mortality between Fib+ and Fib- were no longer significant. Blood transfusions were more common in the Fib+ group, but no difference was observed in thromboembolic events or organ failure. In both groups, low as well as high P-fibrinogen levels at arrival were associated with increased mortality, with the lowest mortality observed at P-fibrinogen values of 2–3 g/l.ConclusionsDespite equal ISS, patients receiving FC had a higher mortality compared to the control group, presumably associated to the fact that these patients were bleeding and physiologically deranged on arrival. When applying a propensity score matching approach, the difference in mortality between the groups was no longer significant. No differences were observed between the groups regarding thromboembolic events or organ failure, despite higher transfusion volumes in patients receiving FC.
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- Almskog, LM, et al.
(författare)
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Rotational thromboelastometry results are associated with care level in COVID-19
- 2021
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Ingår i: Journal of thrombosis and thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 51:2, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- High prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The primary aim of this study was to test whether rotational thromboelastometry (ROTEM) at admission indicates hypercoagulopathy and predicts the disease severity, assessed as care level, in COVID-19 patients. The study was designed as a prospective, observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: (1) regular wards or (2) wards with specialized ventilation support. Conventional coagulation tests, blood type and ROTEM were taken at admission. 60 patients were included; age 61 (median), 67% men, many with comorbidities (e.g. hypertension, diabetes). The ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with in healthy controls (p < 0.001) and higher in severely ill patients compared with in patients at regular wards (p < 0.05). Our results suggest that hypercoagulopathy is present early in patients with mild to moderate disease, and more pronounced in severe COVID-19 pneumonia. Non-O blood types were not overrepresented in COVID-19 positive patients. ROTEM variables showed hypercoagulopathy at admission and this pattern was more pronounced in patients with increased disease severity. If this feature is to be used to predict the risk of thromboembolic complications further studies are warranted.
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- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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