Thromboelastometry in patients with advanced chronic liver disease stratified by severity of portal hypertension.

BACKGROUND: Rotational thromboelastometry (ROTEM) has been studied in patients with advanced chronic liver disease (ACLD) without considering the impact of portal hypertension. We evaluated the influence of the hepatic venous pressure gradient (HVPG) on ROTEM results in patients with ACLD. METHODS: Cross-sectional study; ACLD patients undergoing HVPG measurement within the prospective Vienna Cirrhosis Study (NCT03267615) underwent concomitant ROTEM testing. RESULTS: Among 159 patients (68% male; Child-Pugh-A: 53%, Child-Pugh-B: 34%, Child-Pugh-C: 13%), 21 patients (13%) had a HVPG between 6 and 10 mmHg, 84 patients (53%) between 10 and 19 mmHg, and 54 patients (34%) ≥ 20 mmHg. Child-Pugh-C patients (vs. Child-Pugh-A and vs. Child-Pugh-B patients, respectively) showed longer clot formation time (CFT: median 187 s vs. 122 s vs. 122 s, p = 0.007) and lower maximum clot firmness (MCF: median: 45 mm vs. 56 mm vs. 56 mm, p = 0.002) in extrinsic thromboelastometry (EXTEM), while platelet counts were similar across Child-Pugh stages. In the overall cohort, ROTEM parameters did not differ by severity of portal hypertension. However, among compensated Child-Pugh-A patients, MCF decreased with increasing portal pressure, i.e. in higher HVPG strata (HVPG 9-10 mmHg: median MCF: 59 mm vs. HVPG 10-19 mmHg: 56 mm vs HVPG ≥ 20 mmHg: 54 mm, p = 0.023). Furthermore, patients with short CFT and high MCF in EXTEM had higher levels of lipopolysaccharide-binding protein, C-reactive protein, and procalcitonin, as well as higher leukocyte counts (all p < 0.05). CONCLUSIONS: Portal hypertension seems to impact ROTEM results only in compensated Child-Pugh-A patients. Bacterial translocation and systemic inflammation may trigger a procoagulant state in patients with ACLD.

Tracheostomy is associated with decreased hospital mortality after moderate or severe isolated traumatic brain injury.

BACKGROUND: Data regarding the impact and timing of tracheostomy in patients with isolated traumatic brain injury (TBI) are ambiguous. Our goal was to evaluate the impact of tracheostomy on hospital mortality in patients with moderate or severe isolated TBI. MATERIALS AND METHODS: We performed a retrospective cohort analysis of data prospectively collected at 87 Austrian intensive care units (ICUs). All patients continuously admitted between 1998 and 2010 were evaluated for the study. In total, 4,735 patients were admitted to ICUs with isolated TBI. Of these patients, 2,156 had a moderate or severe TBI (1,603 patients were endotracheally intubated only, 553 patients underwent tracheostomy). Epidemiological data (trauma severity, treatment, and outcome) of the two groups were compared. RESULTS: Patients with moderate or severe isolated TBI undergoing tracheostomy had a similar Glasgow Coma Scale score, median (interquartile range): 6 (3-8) vs 6 (3-8); p = 0.90, and Simplified Acute Physiology Score II, 45 (37-54) vs 45 (35-56); p = 0.86, compared with intubated patients not undergoing tracheostomy. Furthermore, patients undergoing tracheostomy exhibited higher Abbreviated Injury Scale Head scores and had a longer ICU stay for survivors, 30 (22-42) vs 9 (3-17) days; p < 0.0001). In contrast, risk-adjusted mortality was lower in patients undergoing tracheostomy compared with patients who remained intubated, observed-to-expected mortality ratio (95 % confidence interval): 0.62 (0.53-0.72) vs 1.00 (0.95-1.05) respectively. CONCLUSIONS: Despite the greater severity of head injury, patients with isolated TBI who underwent tracheostomy had a lower risk-adjusted mortality than patients who remained intubated. Reasons for this difference in outcome may be multifactorial and require further investigation.

Macrophage migration inhibitory factor as a potential predictor for requirement of renal replacement therapy after orthotopic liver transplantation.

Acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is associated with a poor clinical outcome. Because there is no specific treatment for postoperative AKI, early recognition and prevention are fundamental therapeutic approaches. Concentrations of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) are elevated in patients with kidney disease. We hypothesized that plasma MIF concentrations would be greater in patients developing AKI after OLT compared with patients with normal kidney function. Twenty-eight patients undergoing OLT were included in the study. Kidney injury was classified according to AKI network criteria. Fifteen patients (54%) developed severe AKI after OLT, 11 (39%) requiring renal replacement therapy (RRT). On the first postoperative day, patients with severe AKI had greater plasma MIF concentrations (237 ± 123 ng/mL) than patients without AKI (95 ± 63 ng/mL; P < 0.001). The area under the receiver operating characteristic (ROC) curve for predicting severe AKI was 0.87 [95% confidence interval (CI), 0.69-0.97] for plasma MIF, 0.61 (95% CI, 0.40-0.79) for serum creatinine (sCr), and 0.90 (95% CI, 0.72-0.98) for delta serum creatinine (ΔsCr). Plasma MIF (P = 0.02) and ΔsCr (P = 0.01) yielded a better predictive value than sCr for the development of severe AKI. Furthermore, the area under the ROC curve to predict the requirement of RRT was 0.87 (95% CI, 0.68-0.96) for plasma MIF, 0.65 (95% CI, 0.44-0.82) for sCr, and 0.72 (95% CI, 0.52-0.88) for ΔsCr. Plasma MIF had a better predictive value than sCr for the requirement of RRT (P = 0.02). In conclusion, postoperative plasma MIF concentrations were elevated in patients who developed severe AKI after OLT. Furthermore, plasma MIF concentrations showed a good prognostic value for identifying patients developing severe AKI or requiring postoperative RRT after OLT.

Microtubular and actin cytoskeletons and ultrastructural characteristics of the potentially pathogenic basidiomycetous yeast Malassezia pachydermatis.

Microtubular and actin cytoskeletons were investigated in the lipophilic yeast Malassezia pachydermatis by fluorescence and electron microscopy. To detect microtubules by indirect immunofluorescence using monoclonal anti-tubulin antibody, a prolonged incubation with lysing enzymes was necessary due to its very thick cell wall. Cytoplasmic microtubules were detected in interphase and a spindle with astral microtubules was seen in M-phase. The disintegration of cytoplasmic microtubules and migration of the nucleus to the bud before mitosis were characteristic features of the basidiomycetous yeast Malassezia pachydermatis. The visualisation of F-actin structures (patches, cables and cytokinetic rings) by fluorescence microscopy using both monoclonal anti-actin antibody and rhodamine-phalloidin failed, but actin was detected by electron microscopy with immunogold labelling. Clusters of gold particles indicating actin structures were detected at the plasma membrane of cells with unique cortical ultrastructural features characteristic of the genus Malassezia. A possible association of these with the actin cytoskeleton is suggested.

Cytoskeletal structures, ultrastructural characteristics and the capsule of the basidiomycetous yeast Cryptococcus laurentii.

The cytoskeleton, capsule and cell ultrastructure were studied during the cell cycle of Cryptococcus laurentii. In an encapsulated strain, cytoplasmic microtubules and a mitotic spindle were detected. Mitosis was preceded by migration of the nucleus into the bud. F-actin failed to be visualised by rhodamine-phalloidin (RhPh) in encapsulated cells and therefore an acapsular strain was used. The following actin structures were found: actin dots, actin cables and cytokinetic ring. Ultrastructural studies showed the presence of a nucleus in the bud before mitosis. A collar-shaped structure was seen at the base of bud emergence. A lamellar cell wall and a rough outer surface of the cells were detected. Cytoskeletal structures found in C. laurentii are similar to those in Cryptococcus neoformans, which is a serious human pathogen.