The prevalence of cardiac complications and their impact on outcomes in patients with non-traumatic subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a serious condition, and a myocardial injury or dysfunction could contribute to the outcome. We assessed the prevalence and prognostic impact of cardiac involvement in a cohort with SAH. This is a prospective observational multicenter study. We included 192 patients treated for non-traumatic subarachnoid hemorrhage. We performed ECG recordings, echocardiographic examinations, and blood sampling within 24 h of admission and on days 3 and 7 and at 90 days. The primary endpoint was the evidence of cardiac involvement at 90 days, and the secondary endpoint was to examine the prevalence of a myocardial injury or dysfunction. The median age was 54.5 (interquartile range [IQR] 48.0-64.0) years, 44.3% were male and the median World Federation of Neurological Surgeons (WFNS) score was 2 (IQR 1-4). At day 90, 22/125 patients (17.6%) had left ventricular ejection fractions ≤ 50%, and 2/121 patients (1.7%) had evidence of a diastolic dysfunction as defined by mitral peak E-wave velocity by peak e' velocity (E/e') > 14. There was no prognostic impact from echocardiographic evidence of cardiac complications on neurological outcomes. The overall prevalence of cardiac dysfunction was modest. We found no demographic or SAH-related factors associated with 90 days cardiac dysfunction

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk

Miten elinsiirtojen määrää on onnistuttu lisäämään?

Teema : elinsiirro

Synovial tissue immunohistology.

<p>The antibody staining in each panel is shown as brown color. The generic TRAcP antibody (A, B, E, F), which stains both 5A and 5B isoforms, localized mostly in the lining layer (1) cells in a similar pattern between RA and OA, but a slightly more intensive staining of the sublining layer (2) cells and stroma could be seen in OA samples. The pattern of staining within deep stroma (3), which consists mostly of dense connective tissue and fat, was also similar between the diseases. TRAcP 5A stain (C, D, G, H) localized similarly to the generic antibody, and no differences were found between staining intensities of the sample groups. This indicates that most of TRAcP in the synovial tissue is likely in the 5A form, but differences in TRAcP 5B levels within the synovial tissue are possible between OA and RA. Both TRAcP antibodies were also localized in endothelial (asterisk) and lymphatic cells within the lymphatic follicle (arrow). OPN antibody stain (J, K) localized in the extracellular matrix, with only slight intracellular staining seen. OPN staining was most intense in the sublining layer (2), while the stainings of the lining layer (1) and deep stroma were lighter. OPN antibody did not localize in the endothelial cells (asterisk) but was found within the lymph node (arrow) stroma and some cells within it. No difference was found in the pattern or intensity of staining between RA and OA samples.</p

Summary of phospho-OPN and TRAcP isoform data.

<p>The TRAcP 5B/5A ratio (A) is lowered in RF+ RA and this correlates with the level of OPN’s phosphorylation (B), since TRAcP 5B is the primary phosphatase of OPN, its phosphorylation is decreased in RA. An image of phospho-OPN staining on western blot (C) is shown to highlight the differences, the photo was cropped to allow better visualization of the bands. In conclusion, we demonstrate that OPN is significantly more phosphorylated in RA than in OA synovia, and there are no significant differences between seropositive and seronegative groups (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0182904#pone.0182904.g001" target="_blank">Fig 1A</a>). TRAcP 5B/5A ratio in synovial fluid is increased in OA, and there is a significant negative correlation between the measured ratios and phospho-OPN levels.</p

Schematic illustrations of phospho-OPN and TRAcP isoforms in synovial fluid.

<p>Relative optical densities (RODs) of western blot bands for phospho-OPN (A), summarized total OPN (B) and thrombin cleaved 32kDa phospho-OPN (C), with the measured TRAcP 5A and 5B levels (D and E) and the estimated total TRAcP (F) in synovial fluid from seropositive (RF+) and seronegative (RF-) RA and OA patients. Statistically significant differences are marked with an asterisk.</p

Patient data.

<p>Patient data.</p