Fluid management in patients with acute kidney injury-A post-hoc analysis of the FINNAKI study

Purpose: Whether positive fluid balance among patients with acute kidney injury (AKI) stems from decreased urine output, overzealous fluid administration, or both is poorly characterized. Materials and methods: This was a post hoc analysis of the prospective multicenter observational Finnish Acute Kidney Injury study including 824 AKI and 1162 non-AKI critically ill patients. Results: We matched 616 AKI (diagnosed during the three first intensive care unit (ICU) days) and non-AKI patients using propensity score. During the three first ICU days, AKI patients received median [IQR] of 11.4 L [8.0-15.2]L fluids and non-AKI patients 10.2 L [7.5-13.7]L, p < 0.001 while the fluid output among AKI patients was 4.7 L [3.0-7.2]L and among non-AKI patients 5.8 L [4.1-8.0]L, p < 0.001. In AKI patients, the median [IQR] cumulative fluid balance was 2.5 L [-0.2-6.0]L compared to 0.9 L [-1.4-3.6]L among non-AKI patients, p < 0.001. Among the 824 AKI patients, smaller volumes of fluid input with a multivariable OR of 0.90 (0.88-0.93) and better fluid output (multivariable OR 1.12 (1.07-1.18)) associated with enhanced change of resolution of AKI. Conclusions: AKI patients received more fluids albeit having lower fluid output compared to matched critically ill non-AKI patients. Smaller volumes of fluid input and higher fluid output were associated with better AKI recovery. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Identifying Cultural and Cognitive Proximity between Managers and Customers in Tornio and Haparanda Cross Border Region

Daily intercultural interactions in cross-border regions such as those between customers and managers can be a source of knowledge and ideas. However, such interactions can pose distinctive constraints and opportunities for learning and exchange of ideas. This study adopts a relatively fine–grained quantitative approach to study elements of cognitive and cultural proximity which have a major impact on these interactions. It is based on a survey of 91 managers of small service firms and 312 customers in the twin city of Tornio and Haparanda on the border between Finland and Sweden. Seven elements of proximity were identified and measured. Six elements of perceived cognitive and cultural proximity including values, conservative values towards new ideas, knowledge and use of technology, use of a foreign language, sufficiently focusing or providing specific details and ways of solving problems were found significant in terms of shaping perceptions of Swedish and Finnish managers and customers, which shape these interactions. The results enhance our understanding of how daily cross-border intercultural can be examined in the context of cross-border regional knowledge transfer

Genetic risk factors have a substantial impact on healthy life years

The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; 'lost healthy life years'). We use genetic information from 735,748 individuals and consider 80 diseases. Rare variants had the highest effect on DALYs at the individual level. Among common variants, rs3798220 (LPA) had the strongest individual-level effect, with 1.18 DALYs from carrying 1 versus 0 copies. Being in the top 10% versus the bottom 90% of a polygenic score for multisite chronic pain had an effect of 3.63 DALYs. Some common variants had a population-level effect comparable to modifiable risk factors such as high sodium intake and low physical activity. Attributable DALYs vary between males and females for some genetic exposures. Genetic risk factors can explain a sizable number of healthy life years lost both at the individual and population level.Peer reviewe

Overlap of genetic loci for central serous chorioretinopathy with age-related macular degeneration

IMPORTANCE Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases.OBJECTIVE To identify novel genetic risk factors for CSC and compare genetic risk factors for CSC and AMD.DESIGN, SETTING, AND PARTICIPANTS Using International Classification of Diseases, Ninth (ICD-9) and Tenth (ICD-10) Revision code-based inclusion and exclusion criteria, patients with CSC and controls were identified in both the FinnGen study and the Estonian Biobank (EstBB). Also included in ameta-analysis were previously reported patients with chronic CSC and controls. Data were analyzed from March 1 to September 31, 2022.MAIN OUTCOMES AND MEASURES Genome-wide association studies (GWASs) were performed in the biobank-based cohorts followed by ameta-analysis of all cohorts. The expression of genes prioritized by the polygenic priority score and nearest-gene methods were assessed in cultured choroidal endothelial cells and public ocular single-cell RNA sequencing data sets. The predictive utility of polygenic scores (PGSs) for CSC and AMD were evaluated in the FinnGen study.RESULTS A total of 1176 patients with CSC and 526 787 controls (312 162 female [59.3%]) were included in this analysis: 552 patients with CSC and 343 461 controls were identified in the FinnGen study, 103 patients with CSC and 178 573 controls were identified in the EstBB, and 521 patients with chronic CSC and 3577 controls were included in ameta-analysis. Two previously reported CSC risk loci were replicated (near CFH and GATA5) and 3 novel loci were identified (near CD34/46, NOTCH4, and PREX1). The CFH and NOTCH4 loci were associated with AMD but in the opposite direction. Prioritized genes showed increased expression in cultured choroidal endothelial cells compared with other genes in the loci (median [IQR] of log 2 [counts per million], 7.3 [0.6] vs 4.7 [3.7]; P =.004) and were differentially expressed in choroidal vascular endothelial cells in single-cell RNA sequencing data (mean [SD] fold change, 2.05 [0.38] compared with other cell types; P < 7.1 x 10(-20)). A PGS for AMD was predictive of reduced CSC risk (odds ratio, 0.76; 95% CI, 0.70-0.83 per +1 SD in AMD-PGS; P = 7.4 x 10(-10)). This association may have been mediated by loci containing complement genes.CONCLUSIONS AND RELEVANCE In this 3-cohort genetic association study, 5 genetic risk loci for CSC were identified, highlighting a likely role for genes involved in choroidal vascular function and complement regulation. Results suggest that polygenic AMD risk was associated with reduced risk of CSC and that this genetic overlap was largely due to loci containing complement genes.Ophthalmic researc