Neutralizing activity of human immunoglobulin preparation against toxic shock syndrome toxin-1

Human intravenous immunoglobulin (IVIG) preparation containing a variety of antibodies is widely used against severe infectious diseases. Although IVIG is supposed to promote phagocytosis of opsonized bacteria and neutralize several bacterial toxins, it is unclear what antibodies are responsible for the effect in clinical use. In this study, we found that IVIG showed neutralizing activity against toxic shock syndrome toxin-1 (TSST-1), produced by methicillin-resistant Staphylococcus aureus (MRSA). Whereas intravenous inoculation with culture medium of MRSA 1945 strain into ICR mice causes immediate death, all of the mice survived in case of previous administration of IVIG. Such effect might be attributed to neutralization of TSST-1. Murine splenocytes incubated with TSST-1 (1.0 ng/mL) for 48 hours produced IFN-gamma. By addition of IVIG at 100 micrograms/mL into culture medium, production of IFN-gamma was completely inhibited. From IVIG, anti-TSST-1 antibody was purified by affinity chromatography as one of the effective antibodies. MRSA 1945 mixed with dextran-based microcarrier beads and injected subcutaneously into mice resulted in the formation of abscess and excretion of TSST-1 in serum for 14 days. IVIG and anti-TSST-1 antibody neutralized TSST-1 in blood 24 hours after infection, although bacterial count was kept constant. Experimental rabbit TSS model was established by synergism with lipopolysaccharide (LPS) of Escherichia coli. Anti-TSST-1 antibody protected NZW rabbits from lethal challenge with TSST-1 (1 microgram/kg, i.v.) 4 hours before LPS in a dose-dependent manner (10 micrograms/kg, i.v.), whereas all of the NZW rabbits died in the control group. Thus, IVIG may be a useful tool in the prevention and perhaps therapy of staphylococcal infections and TSS.     

Lack of benefit of intravenous immune globulin in a murine model of group A streptococcal necrotizing fasciitis

Penicillin, clindamycin, and intravenous immune globulin (Venoglobulin-S; IVIG) alone and in combination were studied in a murine model of group A streptococcal necrotizing fasciitis. As assessed by bacterial clearance, treatment with IVIG was not significantly different from no treatment. All treatment regimens that contained penicillin or clindamycin were more effective (P<.05) than no treatment or treatment with IVIG alone. No significant differences were detected among results of treatment with penicillin, penicillin/clindamycin, penicillin/IVIG, clindamycin/IVIG, or all agents combined. Clindamycin alone was less effective than penicillin/IVIG (P=.02), penicillin/clindamycin (P=.009), clindamycin/IVIG (P=.04), or all agents combined (P=.02). No antagonism was observed with the addition of clindamycin or IVIG to penicillin.     

Changing outcomes of coronary revascularization in British Columbia, 1995-2001

OBJECTIVES: To examine outcomes following all first coronary revascularization procedures, isolated coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) on British Columbia (BC) resident adults from 1995 to 2001. METHODS: CABG and PCI data were obtained from the BC Cardiac Registry, and mortality data were obtained from the BC Vital Statistics Agency. Analysis was performed by annual cohorts, and the rates reported are unadjusted. RESULTS: An increasing percentage of revascularization procedures was performed with PCI (62% in 1995 to 73% in 2001; P<0.001) due to the increased use of PCI procedures. Except in emergent cases, 30-day mortality improved after PCI (1.8% to 1.1%; P=0.02) and CABG (1.8% to 1.2%; P=0.01). Emergent cases accounted for 9.0% of PCIs and 2.7% of CABGs, the percentage treated by CABG decreasing from 14.5% in 1995 to 7.5% by 2001 (P<0.001). Mortality rates among emergent cases was higher at 30 days, with no trend in PCI mortality (12%) but a substantial reduction in 30-day mortality after CABG (28% to 10%; P=0.003). One-year survival free from repeat revascularization following PCI increased from 73% in 1995 to 83% in 2001 (P<0.001) and from 94% to 95% (P<0.005) following CABG. CONCLUSIONS: Improvements in procedure-related mortality observed in trials have extended to clinical practice. With respect to emergent cases, an increasing proportion were treated by PCI with no change in PCI mortality but associated with a drop in surgical mortality. There has been a consistent and substantial drop in the need for repeat procedures within one year for patients selected for PCI.     

Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome

PURPOSE: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are uncommon disorders that are generally fatal if left untreated. Plasma exchange therapy is associated with high response rates and improved short-term survival, but most previous studies have been limited by small numbers of patients or short duration of follow-up. METHODS: We performed a retrospective cohort analysis in 126 consecutive patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, most of whom were treated principally with plasma exchange at the Sacramento Medical Foundation Blood (Center and the University of California Davis Medical Center between 1978 and 1998. We measured the effect of therapeutic plasma exchange on 30-day mortality, response rate, and overall survival, and determined which factors were associated with 30-day mortality and relapse. RESULTS: The overall 30-day mortality was 10% of the 122 patients who received plasma exchange as their principal treatment (a median of 9 exchanges and a mean cumulative infused volume of 43 +/- 77 L fresh frozen plasma); 56% were complete responders and 21% were partial responders. The relapse rate was 13%. The estimated 2-year survival was about 60%; among patients without serious underlying comorbid conditions, the estimated 2-year survival was about 80%. Each unit increase in clinical severity score (on a 0 to 8 scale) was associated with a 2.2-fold (95% confidence interval [CI]: 1.3 to 3.9) increase in the odds of 30-day mortality. Patients who were febrile at presentation were substantially less likely to suffer a relapse (odds ratio = 0.2; 95% CI: 0.03 to 0.9). CONCLUSION: Plasma exchange therapy produced high response and survival rates in this large cohort of patients with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. The Clinical Severity Score may be useful in predicting 30-day mortality, whereas fever at onset was associated with a lesser risk of relapse. Prospective studies should stratify patients according to these prognostic factors.     

Streptococcal toxic shock syndrome due to noninvasive pharyngitis.

Serious infections due to group A beta-hemolytic streptococcus (GABHS) have been reported with increasing frequency in recent years. We report a case of toxic shock syndrome (TSS) due to GABHS pharyngitis in an otherwise healthy 14-year-old boy. The organism was found to produce toxin A. To our knowledge, this is the second reported case of streptococcal TSS associated with the production of toxin A that is not associated with an invasive disease and the first case associated with a documented rise in the level of antibody to the streptococcal toxin itself. Clinicians must be especially vigilant for this entity in patients who have streptococcal pharyngitis because early recognition and institution of aggressive supportive therapy can be lifesaving.     

P4-mediated antibody therapy in an acute model of invasive pneumococcal disease

New treatments against severe bacterial infections are needed because the response to antibiotic treatment is slow in acute settings and is becoming less effective owing to the emergence of antibiotic-resistant pathogens. P4-mediated antibody therapy offers a unique treatment strategy that combines exogenous immunoglobulin with the immunoactivating peptide P4. In an acute model of pneumococcal disease, mice were infected with Streptococcus pneumoniae and treated intravenously or intranasally with P4 and intravenous immunoglobulin (IVIG). Survival of P4-IVIG-treated mice increased from 0% to 60% among those that received intravenous treatment and from 0% to 100% among those that received intranasal treatment. Importantly, intranasal administration of P4 at an early stage of infection prevented the onset of bacteremia and sepsis. Increased survival was associated with reduced bacterial burden in affected tissues and with recruitment and activation of professional phagocytes, as manifested by increased expression of Fc-γ receptors. In vitro studies involving P4-stimulated alveolar, peritoneal, and J774.2 murine macrophages showed an increased ability of these immune cells to phagocytose pneumococci independent of capsule. The use of adjunct antibody therapies to treat infectious diseases shows promise.     

Randomized comparison of two different schedules of granulocyte colony-stimulating factor administration after allogeneic bone marrow transplantation.

We performed a randomized trial to determine whether there are differential effects of G-CSF when it is either started on the day (day 0 group) or on the 6th day of marrow infusion (day 5 group) in the allogeneic BMT setting. G-CSF 450 microg was given intravenously daily until the peripheral blood ANC was over 3000/microl. Between May 1995 and April 1998, 60 patients were enrolled (30 in each group). Median number of days of G-CSF administration was significantly longer for the day 0 group (18.5 vs 14.0 days, P < 0. 001). Median days to an ANC over 500/microl were the same in both groups (16 days). Median days to an unsupported platelet count of 20 000/microl did not show significant differences (29.5 vs 28 days, P = 0.202). The frequency of hepatic VOD was higher for the day 0 group (66.7 vs 40.0%, P = 0.038). Mean plasma antithrombin III level was significantly lower in the day 0 group on post-transplant day 7 (83.6 vs 93.9%, P = 0.009). Patients in the day 0 group showed significantly worse 100-day survival (25/30 vs 30/30 surviving respectively, P = 0.019). In conclusion, early initiation of G-CSF after allogeneic BMT did not facilitate marrow engraftment. In addition, early administration of G-CSF was associated with a higher frequency of VOD and a significant fall in plasma antithrombin III level.     

Inefficacy of intravenous immunoglobulin in patients with low-risk thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome.

OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG), in comparison with plasma exchange (PE), in the treatment of patients with thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). DESIGN: Prospective, nonrandomized comparative study. SETTING: Hematology department in a general hospital. PATIENTS: 17 consecutive adult patients, six of them pregnant, with diagnosis of TTP/HUS. Three had a severity score at diagnosis less than or equal to 4 and were treated with IVIG and 14 had a severity score of greater than or equal to 5 and/or were pregnant and received PE. The response was evaluated after 5 days of therapy. RESULTS: Complete remission was obtained in 0/3 cases treated with IVIG and 10/14 (71%) with PE (Fisher's exact test P = 0.05). Three patients died for widespread TTP-HUS, and four had persistent disease. In three of the four resistant patients, complete remission was obtained by further PE but not by further IVIG. The overall remission rate was 76% (13/17). CONCLUSIONS: Our study does not confirm the utility of IVIG in the management of TTP-HUS, as suggested by earlier single case reports.     

Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors.

Between 1972 and 1989, the incidence of viridans streptococcal bacteremia at the University of Texas M. D. Anderson Cancer Center in Houston increased from one case per 10,000 admissions to 47 cases per 10,000 admissions (P less than .0001). A shock syndrome characterized by hypotension, rash, palmar desquamation, adult respiratory distress syndrome, and occasionally death developed in 26% of cases of streptococcal septicemia but in only 4% of cases of septicemia involving other gram-positive bacteria (P = .0005). The risk of streptococcal infection increased with the prophylactic administration of trimethoprim-sulfamethoxazole or a fluoroquinolone (P less than .0001) and with profound neutropenia (P less than .0001). Treatment of chemotherapy-induced gastritis with antacids or with histamine type 2 (H2) antagonists was associated with a sevenfold increase in risk (P less than .001), while sucralfate therapy did not increase risk (P = .65). Streptococcal infection may result from gastric overgrowth of organisms resistant to trimethoprim-sulfamethoxazole in an antacid- or H2 antagonist-induced alkaline environment, with the gastrointestinal tract ulceration caused by antineoplastic therapy providing a convenient portal of entry. In patients receiving chemotherapy, replacement of antacids or H2 antagonists by an acid-sparing regimen should be considered to preserve the natural acidic barrier to infection.     

Predictors of Mortality in Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae: Importance of Combination Therapy

Background.?The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens is a major challenge for clinicians. Methods.?In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. Results.?The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P?=?.02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio [OR]: 7.17; 95% confidence interval [CI]: 1.65-31.03; P?=?.008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61-10.76; P?=?.003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02-1.07; P?相似文献   

Variations in the use of emergency PCI for the treatment of re-infarction following intravenous fibrinolytic therapy: impact on outcomes in HERO-2.

BACKGROUND: Patients who suffer re-infarction during initial hospitalization for ST-elevation myocardial infarction (STEMI) have decreased survival compared to patients without re-infarction, so treatment of re-infarction may influence survival. METHODS AND RESULTS: To determine whether the utilization of reperfusion therapies varied within 12 h of re-infarction and was associated with 30-day mortality, we studied 552 patients with re-infarction of 17,073 patients with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western Countries, Asia, and Latin America). Patients presenting within 6 h of symptom-onset were randomized to receive either bivalirudin or unfractionated heparin intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6% of bivalirudin and heparin treated patients, respectively (P = 0.004), but treatment assignment did not influence mortality after re-infarction. Patients with re-infarction had a higher 30-day mortality than those without re-infarction (24 vs. 10%; P < 0.001 by Cox model). Within 12 h of re-infarction, fibrinolytic therapy was administered to 12.0 and 8.2% underwent percutaneous coronary intervention (PCI); these two treatments were more frequently utilized in patients from Western countries (n = 112), compared to patients from other countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P < 0.001). Mortality was 15% in patients receiving reperfusion therapy for re-infarction and 27% for those with conservative management, hazard ratio (HR) 0.53 (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included adjustment for clinical variables and randomized treatment assignment, 30-day mortality after re-infarction varied by region (highest Latin America 29%, lowest Western countries 15%; P = 0.01). Other independent prognostic factors included age, time from randomization to re-infarction, and Killip class at randomization. The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0.02] in analyses which excluded deaths within 12 h. CONCLUSION: Treatment of re-infarction with reperfusion therapies was markedly under-utilized, especially in non-western countries. PCI for re-infarction, in particular, was associated with a lower 30-day mortality, which may reflect both patient selection and effects of treatment.     

Plasma diafiltration therapy in patients with postoperative liver failure

Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside of the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in biochemical examination of blood and the 28-day and 90-day survival rates of patients with postoperative liver failure (PLF). Eleven patients with PLF were studied with the therapy performed 98 times. The Model for End-Stage Liver Disease (MELD) score was categorized into three grades: 20-29, 30-39, and 40 or higher. The survival rate was assessed by the severity of MELD score. The 28-day survival rate was 45.5% and that at 90 days was 27.3%. The levels of total bilirubin, BUN, and creatinine decreased significantly after treatment. On the other hand, the levels of total protein increased after treatment and those of albumin did not change significantly. PDF may be the useful blood purification therapies for use in cases of PLF in terms of medical economics and the removal of water-soluble and albumin-bound toxins.     

Impact of bacterial pneumonia and Pneumocystis carinii pneumonia on human immunodeficiency virus disease progression. Pulmonary Complications of HIV Study Group.

The course of pneumonia caused by pyogenic bacteria and Pneumocystis carinii was examined in a multicity cohort study of HIV infection. The median duration of survival among 150 individuals following initial bacterial pneumonia was 24 months, compared with 37 months among 299 human immunodeficiency virus (HIV)-infected control subjects matched by study site and CD4 lymphocyte count (P<.001). For 152 subjects with P. carinii pneumonia, median survival was 23 months, compared with 30 months for 280 matched control subjects (P = .002). Median durations of survival associated with the two types of pneumonia differed by only 47 days, despite a higher median CD4 lymphocyte count associated with bacterial pneumonia. These results suggest that both P. carinii pneumonia and bacterial pneumonia are associated with a significantly worse subsequent HIV disease course. The similarity of prognosis after one episode of bacterial pneumonia vs. an AIDS-defining opportunistic infection and the proportion of cases occurring in association with a CD4 lymphocyte count of >200 suggest that measures to prevent bacterial pneumonia should be emphasized.     

Intravenous Immunoglobulin Therapy for Acquired Coagulation Inhibitors: A Critical Review

Intravenous immunoglobulin (IVIG) therapy has been used for autoimmune diseases and disorders involving autoantibodies, including coagulation inhibitors. In this review, we have evaluated the efficacy and safety of IVIG therapy for acquired coagulation inhibitors, including factor VIII inhibitor, and for acquired von Willebrand syndrome on the basis of 44 reports published between 1965 and 2005. Among 35 patients with factor VIII inhibitor, we estimated the efficacy of IVIG therapy alone (which includes complete remissions and partial responses with a clinical benefit) to be 30% (11 cases), whereas the response to combination therapy with IVIG plus immunosuppressive agents (eg, corticosteroid, cyclophosphamide) seemed to be better (approximately 70%, 33/45 cases) than with IVIG therapy alone. In acquired von Willebrand syndrome, the efficacy of IVIG therapy was estimated to be 30%. The response to IVIG therapy appears to occur rapidly, and coagulation inhibitors seem to be neutralized immediately. Moreover, severe complications or side effects rarely occur during IVIG treatment. IVIG therapy thus may be considered one choice for treating acquired coagulation inhibitors, although its efficacy improves when used in combination with immunosuppressive agents.     

Intravenous immunoglobulin (IVIG) treatment for modulation of immune activation in human immunodeficiency virus type 1 infected therapy-naive individuals

We evaluated the ability of intravenous immunoglobulin (IVIG) to diminish immune hyperactivation, which is considered a major cause of CD4+ T cell loss during chronic HIV-1 infection and whether this affected CD4+ T cell counts and plasma HIV-1 RNA (pVL). Therefore, we treated six chronically HIV-1-infected, antiretroviral-therapy-naive patients with IVIG (0.4 g/kg) at weeks 0 and 4, with a follow-up of 12 weeks after the second dosage during which pVL, T cell numbers, and T cell activation were measured. At baseline median CD4+ T cell counts were 300 (range 200-460) x 10(6)/liter and median pVL was 5.0 (range 3.2-5.2) log10 copies/ml. IgG plasma levels peaked during the first days after administration. We observed a decrease in the percentage of activated (CD38+ HLA-DR+) CD4+ and CD8+ T cells [3.5% (range 1-7%) and 5% (1-10%), respectively (p = 0.027)], but no effect on the fraction of proliferating CD4+ or CD8+ T cells as measured by Ki67 expression. CD4+ T cell counts were significantly increased on day 4 (median +55 cells, range 0-150, p = 0.043). pVL was significantly increased on day 1 after IVIG infusion (median +0.13 log10, range 0.01-0.55, p = 0.028). All these parameters returned to baseline levels within 1 week after infusion. In conclusion, administration of IVIG caused a temporary decrease in T cell activation and an increase in CD4+ T cell counts, despite an increase in pVL. Our results support the hypothesis that T cell activation, rather than direct HIV-1 infection, mediates the loss of CD4+ T cells and suggest that immunomodulating therapy in HIV-1 infection could indeed be effective.     

Intravenous immunoglobulin adjunctive therapy in sepsis, with special emphasis on severe invasive group A streptococcal infections

Immunotherapy targeted against microbial toxins and host mediators has been studied in many preclinical investigations and clinical trials of sepsis during the past 20 y. Intravenous immunoglobulin, including both monoclonal and polyclonal antibodies, represents one such immunotherapeutic strategy. Mononclonal antibodies directed against endotoxin or tumour necrosis factor-alpha have been tested extensively in clinical trials, but have so far failed to reveal a significant effect on mortality rates. Several studies have assessed the efficacy of polyclonal intravenous immunoglobulin (IVIG) in sepsis, with varying results. Although there are no conclusive data available to date to support the use of IVIG therapy in all sepsis cases, there are strong indications that certain defined septic subgroups, such as streptococcal toxic shock syndrome caused by group A streptococcus, will benefit from its use. This review briefly summarizes the clinical trials on IVIG therapy in sepsis, and describes in more detail the mechanistic actions of IVIG and the clinical data that support the use of IVIG as adjunctive therapy in severe invasive group A streptococcal infections.     

Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy

BACKGROUND: Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency. METHODS: We compared percentages of activated (CD38(+)HLA-DR(+)) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels. RESULTS: Although the median CD4(+) cell count in controllers was 727 cells/mm(3), 3 (10%) had CD4(+) cell counts <350 cells/mm(3) and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4(+) and CD8(+) cell activation levels (P < .001 for both) than HIV-negative subjects and higher CD8(+) cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4(+) and CD8(+) T cell activation was associated with lower CD4(+) cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P < .001), and in controllers higher LPS level was associated with higher CD8(+) T cell activation (P = .039). CONCLUSION: HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4(+) T cell loss even without measurable viremia.     

Evaluation of beta-lactamase activity and microbial interference in treatment failures of acute streptococcal tonsillitis

Out of 169 patients with streptococcal tonsillitis treated with phenoxymethylpenicillin, 13 (8%) developed a new clinical infection with the same streptococcal strain within 2 weeks of completing the therapy (clinical treatment failure) and 24 (14%) were clinically healthy but harboured the same streptococcal strain after treatment (bacterial treatment failure). Patients with clinical treatment failure showed beta-lactamase activity in their saliva pellet significantly more often than patients with bacterial treatment failure, healed streptococcal tonsillitis or non-streptococcal tonsillitis as well as healthy controls. In an interference study, clinical treatment failures were compared with healthy streptococcal carriers, i.e. persons living in the same household and harbouring the same beta-streptococcal strain. 11/12 healthy carriers had alpha-streptococci with interfering activity against their own beta-streptococcal strain, while the corresponding figure for the clinical treatment failures was 2/13. Furthermore, 6/12 healthy carriers had beta-streptococci inhibiting their own alpha-strains, while the streptococci in 11/13 clinical treatment failures had this ability. The beta-lactamase activity and the interference between alpha- and beta-streptococci may be a contributory cause to treatment failure in streptococcal tonsillitis.     

Which patients benefit from hemodialysis therapy in hepatorenal syndrome?

BACKGROUND AND AIM: Hepatorenal syndrome (HRS) occurs in patients with advanced liver cirrhosis and has a poor outcome. The aim of the present study was to investigate which patients with HRS are likely to benefit from hemodialysis. METHODS: Data were collected prospectively from 30 patients with Child-Pugh C liver cirrhosis and HRS. Patients were either treated with continuous veno-venous hemodialysis (CVVHD) if they were mechanically ventilated, or with intermittent hemodialysis (HD) if they were not mechanically ventilated. Prognosis was assessed by the Child-Pugh and by the Model for End-Stage Liver Disease (MELD) score. The primary aim of the study was the analysis of overall and 30-day patient survival during hemodialysis therapy. To identify predictive factors of survival, variables obtained before the initiation of dialysis therapy were evaluated. RESULTS: Patients' 30-day survival was 8/30 (median survival time 21 days). Among patients treated with mechanical ventilation, 30-day survival time was 0/15 while 8/15 patients without mechanical ventilation survived more than 30 days (P < 0.001). Using a multivariate model, the relative hazards for serum albumin, international normalized ratio (INR) and catecholamine therapy were not different from one another (P > 0.05), indicating that these parameters were not independent predictors of survival. Mechanical ventilation was an independent risk factor for 30-day (relative hazard 6.6 [1.6-27.7], P < 0.001) and overall survival (relative hazard 6.3 [1.5-26.5], P = 0.01). Child-Pugh (P < 0.01) and the MELD (P < 0.01) score were predictive for overall survival independent of mechanical ventilation. CONCLUSIONS: Patients with HRS without mechanical ventilation may benefit from hemodialysis, whereas hemodialysis seems to be futile in patients with mechanical ventilation.     

Role of Different Replacement Fluids During Extracorporeal Treatment in a Pig Model of Sepsis

In an extracorporeal combination therapy, the impact of different replacement fluids on survival was tested in a bacterial sepsis model in pigs. In an animal study 19 pigs, weighing 7.5–11.1 kg, were included. All groups received an intravenous lethal dose of live Staphylococcus aureus over 1 h. The animals were treated by an extracorporeal circuit consisting of online centrifugation and subsequent plasma filtration for 4 h. The extracorporeal circuit was pre‐filled with 400 mL replacement fluid. In the P0 group 100% hydroxyethyl starch 130/0.4 was used as replacement fluid; in the P30 group 30% pig plasma and 70% hydroxyethyl starch; and in the P100 group 100% pig plasma. The observation time was 7 days. All animals of the group P100 survived, while all animals of group P0 and five out of seven animals of the P30 group died during the observation time. Extracorporeal therapy consisting of online centrifugation and plasma filtration with 100% pig plasma as replacement fluid significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.