Presence of hypogammaglobulinemia - a risk factor of mortality in patients with severe sepsis, septic shock, and SIRS.

In this retrospective study we assessed the frequency of hypogammaglobulinemia in 708 patients with SIRS, severe sepsis and septic shock. We evaluated the relationship between hypogammaglobulinemia IgG, IgM and 28 day mortality. Total of 708 patients and 1,513 samples were analyzed. In the three subgroups we investigated, patients met the criteria of SIRS, severe sepsis and septic shock. IgG hypogammaglobulinemia was demonstrated in 114 patients with severe sepsis (25.2%), 11 septic shock patients (24.4%), and in 29 SIRS patients (13.9%). IgM hypogammaglobulinemia was documented in 55 patients with severe sepsis (12.2%), 6 septic shock patients (13.3%), and in 17 SIRS patients (8.1%). Mortality of patients with severe sepsis and normal IgG levels was significantly lower (111 patients; 32.8%) compared with those with IgG hypogammaglobulinemia (49 patients; 43.0%; p=0.001). Mortality of patients with septic shock and IgG hypogammaglobulinemia (n=5) was significantly higher compared with those with normal IgG levels (45.5% vs. 38.2%; p=0.001). Mortality of patients with severe sepsis and IgM hypogammaglobulinemia did not differ from that of patients with normal IgM levels (37.0 vs. 41.8%). Mortality of patients with septic shock and IgM hypogammaglobulinemia was significantly higher compared with those with normal IgM levels (50% vs. 38.5%; p=0.0001). This study documented relatively high incidence of hypogammaglobulinemia IgG and IgM in patients with severe sepsis, septic shock and SIRS respectively. The presence of IgG hypogammaglobulinemia in patients with severe sepsis is independent factor of mortality.

Probiotic treatment with Probioflora in patients with predicted severe acute pancreatitis without organ failure.

BACKGROUND: We previously demonstrated that probiotic prophylaxis, in patients with predicted severe pancreatitis, did not prevent infectious complications but unexpectedly increased the risk of bowel ischemia and mortality. The suggestion that these negative findings are only observed in the presence of organ failure at the start of probiotic treatment has not been confirmed. METHODS: In a retrospective analysis, all patients with predicted severe acute pancreatitis without initial organ failure admitted to a medium care facility of a teaching hospital in Prague from January 2003 to December 2010 were included. All patients routinely received probiotic treatment with Probioflora. Total parenteral nutrition (TPN) was routinely started and shifted toward total enteral nutrition. Infectious complications, mortality and the incidence of bowel ischemia were recorded. RESULTS: 99 consecutive patients, mean age 56 years, were included. Infectious complications occurred in 42 patients (42%), consisting of bacteremia (n = 40), pneumonia (n = 11) and infected necrosis (n = 11). Bowel ischemia was detected in two patients (2%). Overall mortality was 8%. CONCLUSION: In this retrospective study no apparent positive or negative impact of probiotic treatment with Probioflora was demonstrated when administered to patients with predicted severe acute pancreatitis without initial organ failure.

TREM-1 expression on monocytes is not a parameter specific for infectious etiology of systemic inflammatory response syndrome.

UNLABELLED: Determination of mTREM-1 expression on monocytes has been investigated as a perspective diagnostic method to distinguish infectious from non-infectious etiology of the inflammation. THE AIMS OF OUR STUDY WERE: i) to investigate the expression of TREM-1 on monocytes in septic patients and in those after elective spinal surgery without infection; ii) to assess the dynamics of mTREM-1 expression on monocytes and its association with the outcome in patients with severe sepsis. Fifty two patients with severe sepsis, 20 healthy volunteers, and 20 patients after elective spinal surgery were involved in our study. TREM-1 expression on monocytes was evaluated by flow cytometry. Compared with the group of healthy adults (median 42.0, interquartile range (IQR) 30.3-76 MFI), mTREM-1 expression was increased in the group of septic patients both at entry (median 138.4, IQR 78.4-187.5 MFI) and the last examination (median 136.5, IQR 69.0-170.0 MFI) as well as in patients 24 hours after spinal surgery (median 138.5, IQR 45.3-165.5 MFI). The increase was statistically significant. mTREM-1 expression in patients undergoing spinal surgery and those with severe sepsis did not differ. TREM-1 expression on the monocytes in survivors was higher than in non-survivors (p=0.007). TREM-1 levels in septic non-surviving patients correlated weakly with TNF-α levels (r=0.38; p=0.003) and with HLA-DR/CD14 levels (r=0.38; p=0.003). Increased TREM-1 expression on monocytes is not associated exclusively with the presence of systemic infection.

Genomic polymorphism and sepsis--is there a reason for optimism?

There is no doubt that, in infectious disease, genetic predisposition plays a very important role in clinical outcome. Sepsis is a polygenic syndrome initiated by infection. A fact confounding the situation is that two factors--the macroorganism and the microorganism--are at play at the same time; hence of genotype effect must be assessed in light of their interaction. From a phylogenetic point of view, infectious disease is a companion of man throughout their life and its role in terms of function of the system of innate immunity is perceived as a beneficial one. However, the presence of a major antigen load by the infectious agent results in pathological responses at the levels of the macroorganism. Assessment of the severity of the inflammatory process on the basis of genetic predisposition is a most challenging issue. Genetic polymorphisms in the immune response to infection have been shown to be associated with clinical outcomes. The advancement of single nucleotide polymorphism (SNP) genotyping in basic genes--CD14, Toll like receptors, LBP, cytokines, cytokine receptors and coagulation factors have provided valuable information on the interaction of the macro and microorganisms. The understanding of the variation in genes and differences in response to infection may contribute to tailored diagnostic and therapeutic interventions with improved outcome in these patients.

Hemodynamic parameters in a surgical devascularization model of fulminant hepatic failure in the minipig.

Animal models of fulminant hepatic failure (FHF) are important for studying the pathophysiology of this process and for evaluation of the efficacy of artificial and bioartificial liver support systems. In experiments, hemodynamic parameters were monitored in a group of minipigs with FHF induced by surgical devascularization, and compared with those in a control group. During the experiment, animals were analgosedated and were on mechanical lung ventilation. Crystalloid and colloidal solutions were administered and norepinephrine in continuous infusion was applied if mean arterial pressure (MAP) decreased below 60 mm Hg despite adequate intravascular volumes. An increase in heart rate, and decreases in MAP and systemic vascular resistance, compared with the baseline, occurred in the FHF group from 6 h after surgery. A comparison of FHF and control groups revealed no significant differences in systemic vascular resistance and MAP until after 12 h after surgery (systemic vascular resistance index: 953 FHF vs. 1658 controls; p < 0.05; MAP: 58.1 FHF vs. 76 controls; p < 0.05). No significant differences in CI were seen between the FHF group and controls. FHF animals survived for about 13 h after surgery, i.e. a period, which we consider long enough to test a support device. The parameters are believed to be quite adequate, as we were able to maintain satisfactory hemodynamic stability in all experimental animals with induced acute hepatic failure.

[A model of acute hepatic failure in a minipig from the surgical and anesthesia point of view]. / Model akutního selhání jater u miniprasete z hlediska chirurga a anesteziologa.

AIM: The aim of this study was to create an easily reproducible model of the acute hepatic failure (ASJ) in a minipig, which may allow to test supporting eliminating systems. The aim of this report was to describe the surgical technique with the anaesthesiological procedure and to demonstrate the experimental results on a group of the laboratory animals. METHODOLOGY: The ASJ was mocked using surgical devascularization of the liver: a ligature of the a. hepatica propria and v. portae, creating a portocaval anastomosis end-to-side. The animals were analgosedated during the experiment and were on a ventilatory support. Biochemical indicators of the hepatic failure, the ICP and the haemodynamics parameters were monitored. Hypoglycaemia with levels below 3.5 mmol and any increase of the intracranial pressure (ICP) were considered the onset of the hepatic failure. MATERIAL: 20 minipigs weighing 25-30 kg and divided in 3 groups, were included in the experiment: I--10 animals were assigned to the acute hepatic failure (ASJ) group, II--5 animals with the mock acute hepatic failure (ASJ), whose ICP was monitored in conjunction with the standard monitoring and III. 5 animals without the acute hepatic failure (ASJ)--a control group. RESULTS: We proved significant differences in the AST levels (33.44 +/- 39.96 vs. 1.56 +/- 0.50 mmol/l), the lactate levels (2.97 +/- 1.16 vs. 1.18 +/- 0.61 mmol/l), and the ammonium levels (264.3 +/- 93.05 vs. 42.5 +/- 12.98 micromol/l) in the acute hepatic failure (ASJ) group compared with the control group (p < 0.01) 6 hours after the surgery and significant changes in the glycaemia levels and the intracranial pressure (ICP) measurements 4 hours after the surgical procedure. Increase in the pulse frequency, the blood pressure, decrease of the mean arterial pressure (MAP) and decrease in the systemic venous resistence index (SVRI) in the acute hepatic failure (ASJ) group was recorded 6 hours after the procedure compared with the initial findings, with significant differences between the acute hepatic failure (ASJ groups and the control group as late as during the 12th hour following the procedure (SVRI: 953 ASJ vs. 1658 control, p - 0.05, MAP: 58.1 ASJ vs. 76 control, p - 0.05). No statistically significant differences in the heart index between the acute hepatic failure (ASJ) group and the control group were recorded. The animals with the acute hepatic failure (ASJ) survived 13 hours following the surgical procedure, on average.

Devascularization surgical model of acute liver failure in minipigs.

AIM: The study was designed to develop a readily reproducible model of acute liver failure (ALF) in the minipig, to gain an 8-hour therapeutic window to mimic, as closely as possible, acute liver failure in man. METHOD: We used reversible devascularization model of ALF in the minipig involving hepatic artery ligation and establish an end-to-side portocaval anastomosis. Standard laboratory monitoring was complemented with intracranial pressure (ICP) measurement. MATERIAL: Twenty minipigs (weight 25-30 kg) were used for the experiment. The animals were divided into 3 groups: I: 10 animals in an experimental group with ALF; II: 5 animals in an experimental group with ALF and ICP measurement, and III: 5 animals in a control group without ALF. RESULTS: Laboratory testing has shown the significant changes in levels of AST (33.44 +/- 39.96 vs. 1.56 +/- 0.50 mmol/l), lactate (2.97 +/- 1.16 vs. 1.18 +/- 0.61 mmol/l), and ammonia (264.3 +/- 93.05 vs. 42.5 +/- 12.98 mmol/l) between ALF groups and controls (p < 001) 6 h after the operative procedure, and significant changes in hypoglycemia and intracranial pressure were found 4 h after the operative procedure. The difference in Quick values (67.4 +/- 17.03 vs. 75.2 +/- 2.68) was not significant. We assume that the therapeutic window starts 4 h after the beginning of the experiment. CONCLUSION: Our devascularization model of ALF is simple and readily reproducible. The therapeutic window occurring shortly after surgery and persisting for a mean 9 h is suitable to evaluate bioartificial liver devices.

[Comparison of procalcitonin, interleukin-6 and C-reactive protein in the differential diagnosis of patients with sepsis syndrome in intensive care units]. / Srovnání prokalcitoninu, interleukinu-6 a C-reaktivního proteinu v diferenciální diagnostice pacientu JIP se syndromem sepse.

UNLABELLED: One of the most difficult tasks in differential diagnosis of patients with septic syndrome at the Intensive Care Units is to differentiate between infection and non-infection etiology of this syndrome. In the last years, new parameters have played an important role in this area--C-reactive protein, Interleukin-6 and procalcitonin. THE AIM: Of the investigation was to compare these three parameters in differential diagnosis of the septic syndrome. THE COHORT AND METHODS: The authors examined 56 patients (17 women and 39 men, mean age being 43 and 51 years, respectively) hospitalized at the Intensive Care Units who corresponded to the criteria of the syndrome of inflammatory response, sepsis or septic shock. A total of 99 examinations were done. The samples were taken up to 24 hours after the beginning of clinical symptomatology and submitted to the laboratory within four hours. Immediately afterwards the determination of concentrations of all three parameters--C-reactive protein, interlaukin-6 and procalcitonin, were done. The results of the examinations were compared to each other as well as to the diagnosis of sepsis--the confirmed infection etiology. RESULTS: In all the evaluated parameters the authors detected significant differences between the values of entry examination and all measurements between the patients with the syndrome of systemic inflammatory response and septic shock as well as among patients with sepsis and the septic shock. Likewise, the authors confirmed significant differences between concentrations of all three parameters in comparing the patients with sepsis and those with the septic shock. Only in the case of procalcitonin there was a significant difference in concentration between patients with the syndrome of systemic inflammatory response of non-infectious etiology and those with sepsis. The concentration of procalcitonin was the only predictive marker of diagnosis with the correlation coefficient r = 0.7263, r2 = 0.5275, P < 0.00005. CONCLUSION: Calcitonin proved to be the most specific parameter in demonstrating infection etiology in patients with the septic syndrome, its predictive value being higher than that of C-reactive protein and Interleukin-6. Monitoring of calcitonin dynamism provides important information on efficiency of the applied antibiotic treatment. In patients with diagnostic uncertainties as far as the etiology of the septic syndrome is concerned; procalcitonin is the parameter of choice, while it may be supplemented with the examination of C-reactive protein.