SuPAR and PAI-1 in critically ill, mechanically ventilated patients

Purpose

SuPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1) are active in the coagulation-fibrinolysis pathway. Both have been suggested as biomarkers for disease severity. We evaluated them in prediction of mortality, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sepsis and renal replacement therapy (RRT) in operative and non-operative ventilated patients.

Methods

We conducted a prospective, multicenter, observational study. Blood samples and data of intensive care were collected. Mechanically ventilated patients with baseline suPAR and PAI-1 measurements were included in the analysis, and healthy volunteers were analysed for comparison. Receiver operating characteristics (ROC), logistic regression, likelihood ratios and Kaplan–Meier analysis were performed.

Results

Baseline suPAR was 11.6 ng/ml (quartiles Q1–Q3, 9.6–14.0), compared to healthy volunteers with suPAR of 0.6 ng/ml (0.5–11.0). PAI-1 concentrations were 2.67 ng/ml (1.53–4.69) and 0.3 ng/ml (0.3–0.4), respectively. ROC analysis for suPAR 90-day mortality areas under receiver operating characteristic curves (AUC) 0.61 (95 % confidence interval (CI): 0.55–0.67), sepsis 0.68 (0.61–0.76), ALI/ARDS 0.64 (0.56–0.73) and RRT 0.65 (0.56–0.73). Patients with the highest quartile of suPAR concentrations had an odds ratio of 2.52 (1.37–4.64, p = 0.003) for 90-day mortality and 3.16 (1.19–8.41, p = 0.02) for ALI/ARDS. In non-operative patients, the AUC’s for suPAR were 90-day mortality 0.61 (0.54–0.68), RRT 0.73 (0.64–0.83), sepsis 0.70 (0.60–0.80), ALI/ARDS 0.61 (0.51–0.71). Predictive value of PAI-1 was negligible.

Conclusions

In non-operative patients, low concentrations of suPAR were predictive for survival and high concentrations for RRT and mortality. SuPAR may be used for screening for patients with potentially good survival. The association with RRT may supply an early warning sign for acute renal failure.     

C4A deficiency in children and adolescents with recurrent respiratory infections

Increased susceptibility to recurrent viral and bacterial respiratory infections in children and young adults is not well understood. To evaluate the role of complement factor C4 in the defense against respiratory infections, we studied complement factor C4 allotypes C4A and C4B and copy numbers of C4A and C4B genes in 84 children and young adults with recurrent acute otitis media, sinusitis, or pneumonia and in 74 healthy controls. The occurrence of C4A gene deficiency was significantly higher in patients compared with controls (26% vs 14%, p = 0.048). Girls predominated in the group of patients with C4A deficiency (73% girls and 27% boys, p = 0.004). The lectin pathway of complement was more often functionally impaired in patients with C4A deficiency than in patients with no C4A deficiency (41% vs 13%, p = 0.033). Classical and alternative pathways were normal in individuals with C4 null alleles. C4A deficiency is 1 of the minor defects of the innate immunity that may predispose children and young adults to recurrent respiratory infections. C4 gene testing should be added to the list of investigations when the cause for recurrent acute otitis media, maxillary sinusitis, or pneumonia in children and young adults is sought.     

Cardiovascular disease occurrence in two close but different social environments

Background  

Cardiovascular diseases estimate to be the leading cause of death and loss of disability-adjusted life years globally. Conventional risk factors for cardiovascular diseases only partly account for the social gradient. The purpose of this study was to compare the occurrence of the most frequent cardiovascular diseases and cardiovascular mortality in two close cities, the Twin cities.     

Inheritance of intrahepatic cholestasis of pregnancy in one kindred

Hirvioja M-L, Kivinen S. Inheritance of intrahepatic cholestasis of pregnancy in one kindred
Clin Genet 1993: 43: 315–317. © Munksgaard, 1993
We report three sisters with intrahepatic cholestasis of pregnancy (ICP) and the pedigree of the family, including six: generations. ICP was observed in five successive generations; most of the patients also had cholelithiasis. The uniform expression, the complete penetrance of the trait and the direct parent-to-child transmission support the Mendelian dominant mode of inheritance. Determination of HLA A, B and C haplotype was made in five ICP patients, without any findings of HLA type common to everyone. X-linked inheritance cannot be excluded in this study.     

Association of chest radiography findings with host-related genetic factors in patients with nephropathia epidemica

Different host genetic factors causes imbalance in the immune response. The purpose of this study was to establish whether pathological findings in chest radiography are related to the various host-related immunological factors in nephropathia epidemica (NE). Chest radiography findings, human leukocyte antigen (HLA) alleles B8, DR3, B27, genotypes of the genes of tumour necrosis factor alpha (TNFalpha), interleukin -1alpha (IL-1alpha), IL1beta and IL-1 receptor antagonist (IL1RA) were analysed in 114 patients with serologically confirmed acute NE. Both the presence and severity of abnormal NE-related chest radiography findings associated with the B8, DR3 and TNF2 alleles are known to form a frequent extended HLA haplotype in European populations. Pleural effusion showed the strongest association with these genetic factors. Pathological findings in chest radiography are related to host genetic factors in NE. Pleural effusion is a sign of increased capillary permeability, an important feature in NE. Host genetic factors may contribute to increased capillary permeability observed in NE patients.