István Pénzes

4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study

IntroductionActivation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis.MethodsWe enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death.ResultsWe found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer (p = 0.091), fewer ventilation-free days (p = 0.008) and days without septic shock (p = 0.095) were observed during the first 28 days.ConclusionsIn Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables.

Elevated serum 70 kDa heat shock protein level reflects tissue damage and disease severity in the syndrome of hemolysis, elevated liver enzymes, and low platelet count.

OBJECTIVE We have recently demonstrated that serum 70 kDa heat shock protein (Hsp70) levels are increased in the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome). The aim of the present study was to investigate in an independent, larger cohort of patients whether serum Hsp70 levels are related to laboratory markers of HELLP syndrome. STUDY DESIGN The study population included 14 patients with HELLP syndrome. Serum Hsp70 levels were measured by enzyme-linked immunosorbent assay. The relationship between serum Hsp70 levels and laboratory markers of hemolysis, hepatocellular damage, renal insufficiency, inflammation or disseminated intravascular coagulation (DIC), as well as platelet count was investigated by calculating correlation coefficients, standardized regression coefficients and by principal component analysis. RESULTS Serum Hsp70 levels showed a very strong correlation to the markers of hemolysis (plasma free hemoglobin level, serum lactate dehydrogenase activity, and total bilirubin level) and of hepatocellular injury (serum aminotransferase activities), supported also by principal component analysis. Furthermore, circulating Hsp70 concentration reflected the severity of HELLP syndrome as expressed by the significant inverse correlation to the lowest platelet count. By contrast, there was no relationship between serum Hsp70 levels and markers of inflammation, coagulation, fibrinolysis or renal insufficiency. CONCLUSION Elevated serum 70 kDa heat shock protein level seems to reflect tissue damage (hemolysis and hepatocellular injury) and disease severity in patients with HELLP syndrome. However, further investigations are needed to determine the clinical relevance of these findings.

Low-frequency assessment of airway and tissue mechanics in ventilated COPD patients

Low-frequency forced oscillations have increasingly been employed to characterize airway and tissue mechanics separately in the normal respiratory system and animal models of lung disease; however, few data are available on the use of this method in chronic obstructive pulmonary disease (COPD). We studied 30 intubated and mechanically ventilated patients (COPD, n = 9; acute exacerbation of COPD, n = 21) during short apneic intervals at different levels of positive end-expiratory pressure (PEEP), with small-amplitude forced oscillations between 0.4 and 4.8 Hz. In 16 patients, measurements were made before and after inhalation of fenoterol hydrobromide plus ipratropium bromide (Berodual). Newtonian resistance and coefficients of tissue resistance (G) and elastance (H) were estimated from the respiratory system impedance (Zrs) data by model fitting. Apart from some extremely high Zrs data obtained primarily at relatively low PEEP levels, the model yielded a reasonable partitioning of the airway and tissue parameters, and the inclusion of further parameters did not improve the model performance. With increasing PEEP, Newtonian resistance and the ratio G/H decreased, reflecting the volume dependence of the airway caliber and the improved homogeneity of the lungs, respectively. Bronchodilation after the administration of Berodual was also associated with simultaneous decreases in G and H, indicating recruitment of lung units. In conclusion, the measurement of low-frequency Zrs can be accomplished in ventilated COPD patients during short apneic periods and offers valuable information on the mechanical status of the airways and tissues.

Analysis of the 8.1 ancestral MHC haplotype in severe, pneumonia-related sepsis

The most frequent Caucasian MHC haplotype, AH8.1 - associated with numerous immunopathological differences and certain autoimmune diseases - was recently linked to the delayed onset of bacterial colonization in cystic fibrosis. Based on this observation, we hypothesized that the carriers of AH8.1 have lower risk for a worse outcome in sepsis. AH8.1 carrier state was determined in 207 Caucasian patients with severe, pneumonia-related sepsis. Our data showed that in patients without chronic obstructive pulmonary disease (COPD), septic shock - a serious consequence of the bacterial infection - occurred significantly less frequently (OR=0.3383; 95% CI=0.1141-0.995; p=0.043) in carriers of AH8.1, than in non-carriers. According to the multivariate logistic regression analysis, this haplotype had an independent protective role against septic shock in all patients (OR=0.315; 95% CI=0.100-0.992; p=0.048), particularly in COPD-free patients (OR=0.117; 95% CI=0.025-0.554; p=0.007). These results indicate that AH8.1 may confer protection against the progression of bacterial infection, and this could explain, at least partially, its high frequency in the Caucasian population.

Airway and tissue mechanics in ventilated patients with pneumonia

We applied the low-frequency forced oscillation technique (LFOT) to measure respiratory impedance (Zrs) at various positive end-expiratory pressures (PEEPs) in 14 sedated and intubated patients with pneumonia classified into a mild (Group 1) and a severe group (Group 2) based on lung injury scores. The Zrs spectra were fit with the constant-phase (CP) model including Newtonian resistance (R(N)) and tissue damping (G) and elastance (H), a distributed airway resistance (DR) and a distributed tissue elastance (DH) model. Using the CP model, all parameters revealed a negative PEEP dependence (p<0.001) in Group 2 and H was higher in Group 2 (p=0.014). The variability of H from the DH model was nearly significantly larger in Group 1 (p=0.061). Following bronchodilator inhalation, G significantly decreased (p=0.009). Thus, the CP model provides a robust partitioning of Zrs into tissue properties and R(N), a surrogate for airway resistance, while the distributed models suggest that lung heterogeneity decreases with increasing PEEP.

Plasmapheresis in the treatment of hypertriglyceridemia

The authors present the case of a 38-year-old woman with severe hypertriglyceridemia-induced acute recurrent pancreatitis (triglyceride 16 761 mg/dl, 189.4 mmol/l). According to the knowledge of the authors, such a high triglyceride has not been previously reported in Hungarian and international scientific literature. The patient received conventional treatment (fluid replacement, analgesic, antibiotics, discontinuation of oral intake) and plasmapheresis too. After two sessions of plasmapheresis with one month interval the clinical and laboratory parameters greatly improved. Severe hypertriglyceridemia (triglyceride level more than 1000 mg/dl, ≈11.3 mmol/l) is an independent risk factor for acute pancreatitis. Plasmapheresis seems to be safe and effective to rapidly decrease triglyceride levels and to remove the causative agent for pancreatitis in a patient with severe hypertriglyceridemia.

Hypertriglyceridaemia kezelése plazmaferézissel

The authors present the case of a 38-year-old woman with severe hypertriglyceridemia-induced acute recurrent pancreatitis (triglyceride 16 761 mg/dl, 189.4 mmol/l). According to the knowledge of the authors, such a high triglyceride has not been previously reported in Hungarian and international scientific literature. The patient received conventional treatment (fluid replacement, analgesic, antibiotics, discontinuation of oral intake) and plasmapheresis too. After two sessions of plasmapheresis with one month interval the clinical and laboratory parameters greatly improved. Severe hypertriglyceridemia (triglyceride level more than 1000 mg/dl, ≈11.3 mmol/l) is an independent risk factor for acute pancreatitis. Plasmapheresis seems to be safe and effective to rapidly decrease triglyceride levels and to remove the causative agent for pancreatitis in a patient with severe hypertriglyceridemia.

Hypertriglyceridaemia kezelése plazmaferézissel@@@Plasmapheresis in the treatment of hypertriglyceridemia

The authors present the case of a 38-year-old woman with severe hypertriglyceridemia-induced acute recurrent pancreatitis (triglyceride 16 761 mg/dl, 189.4 mmol/l). According to the knowledge of the authors, such a high triglyceride has not been previously reported in Hungarian and international scientific literature. The patient received conventional treatment (fluid replacement, analgesic, antibiotics, discontinuation of oral intake) and plasmapheresis too. After two sessions of plasmapheresis with one month interval the clinical and laboratory parameters greatly improved. Severe hypertriglyceridemia (triglyceride level more than 1000 mg/dl, ≈11.3 mmol/l) is an independent risk factor for acute pancreatitis. Plasmapheresis seems to be safe and effective to rapidly decrease triglyceride levels and to remove the causative agent for pancreatitis in a patient with severe hypertriglyceridemia.

Hemorrhagic complications of chronic anticoagulant treatment in a single intensive care unit

INTRODUCTION There are well defined indications in which chronic anticoagulant treatment has been widely applied. However, complications of this therapy are less discussed, although these complications may lead to serious or even fatal consequences. AIM The aim of the authors was to analyze data of patients admitted to their multidisciplinary intensive care unit for complications of chronic anticoagulant therapy between January 1, 2006 and December 31, 2011. METHOD Data of 73 patients admitted for serious hemorrhagic complications of chronic anticoagulant therapy were retrospectively analysed. RESULTS Of the 73 patients, 63 patients had intracranial bleeding, most of them with traumatic origin. A few patients with other hemorrhagic complications such as spinal hematoma, gastrointestinal bleeding, hemorrhagic cystitis, hemothorax and intraabdominal bleeding were also noted. The INR values were out of therapeutic range in 43 patients. The mortality of patients was very high in spite of complex intensive care; 49 of the 73 patients (75.5%) died due to hemorrhagic complications. CONCLUSIONS Due to the high proportion of traumatic origin, the large number of out-of-range INR, and the high mortality, the authors strongly believe that regular patient follow-up, transmission of detailed information, and time-to-time reevaluation of the indications and contraindications of chronic anticoagulant therapy could help to decrease the number of serious and fatal complications of chronic anticoagulant therapy.