Walter Spindelboeck

Oxidative albumin damage in chronic liver failure: Relation to albumin binding capacity, liver dysfunction and survival

BACKGROUND & AIMS Impaired binding function of albumin has been demonstrated in end-stage liver disease. This and other functional disturbances of albumin may be related to oxidative stress which is believed to play an important role in the pathogenesis of liver failure as well as sepsis. The aim of the present study was to relate oxidative modification of albumin to loss of albumin binding function in advanced chronic liver failure and in sepsis. METHODS Patients with decompensated cirrhosis or sepsis and healthy controls were investigated. Three fractions of albumin were separated by chromatography according to the redox state of cysteine-34: non-oxidized human mercaptalbumin, reversibly oxidized human non-mercaptalbumin-1, and irreversibly oxidized human non-mercaptalbumin-2 (HNA2). Binding properties of albumin site II were measured using dansylsarcosine as a ligand. RESULTS Both in cirrhotic and septic patients, fractions of oxidized albumin were increased and binding capacity for dansylsarcosine was decreased. Mass spectroscopy confirmed specific oxidation of cysteine-34. In cirrhotic patients, dansylsarcosine binding correlated strongly with liver function parameters and moderately with HNA2. Baseline levels of HNA2 accurately predicted 30-day and 90-day survival in cirrhotic patients and this was confirmed in an external validation cohort. CONCLUSIONS Our results suggest that oxidative damage impairs binding properties of albumin. In advanced liver disease, reduced binding capacity of albumin site II is mainly related to impaired liver function. The plasma level of HNA2 is closely related to survival and may represent a novel biomarker for liver failure.

Increasing arterial oxygen partial pressure during cardiopulmonary resuscitation is associated with improved rates of hospital admission

AIM As recent clinical data suggest a harmful effect of arterial hyperoxia on patients after resuscitation from cardiac arrest (CA), we aimed to investigate this association during cardiopulmonary resuscitation (CPR), the earliest and one of the most crucial phases of recirculation. METHODS We analysed 1015 patients who from 2003 to 2010 underwent out-of-hospital CPR administered by emergency medical services serving 300,000 inhabitants. Inclusion criteria for further analysis were nontraumatic background of CA and patients >18 years of age. One hundred and forty-five arterial blood gas analyses including oxygen partial pressure (paO2) measurement were obtained during CPR. RESULTS We observed a highly significant increase in hospital admission rates associated with increases in paO2 in steps of 100 mmHg (13.3 kPa). Subsequently, data were clustered according to previously described cutoffs (≤ 60 mmHg [8 kPa]], 61-300 mmHg [8.1-40 kPa], >300 mmHg [>40 kPa]). Baseline variables (age, sex, initial rhythm, rate of bystander CPR and collapse-to-CPR time) of the three compared groups did not differ significantly. Rates of hospital admission after CA were 18.8%, 50.6% and 83.3%, respectively. In a multivariate analysis, logistic regression revealed significant prognostic value for paO2 and the duration of CPR. CONCLUSION This study presents novel human data on the arterial paO2 during CPR in conjunction with the rate of hospital admission. We describe a significantly increased rate of hospital admission associated with increasing paO2. We found that the previously described potentially harmful effects of hyperoxia after return of spontaneous circulation were not reproduced for paO2 measured during CPR. CLINICAL TRIAL REGISTRATION n/a.

Comparison of two molecular assays with conventional blood culture for diagnosis of sepsis.

In this small study, the LightCycler® SeptiFast, and the SepsiTest™ were compared with blood culture. The SeptiFast showed a higher sensitivity (42.9%) and specificity (88.2%) when compared to blood culture than the SepsiTest™ (28.6 and 85.3%). The SeptiFast provides more species specific results, although the identification panel is smaller.

Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute, refractory gastrointestinal graft-versus-host-disease

Acute graft- versus -host disease (aGvHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT).[1][1] Although aGvHD of any target organ represents morbidity, lower gastrointestinal (GI) tract involvement is complicated by high mortality.[2][2] Here,

Arterial blood gases during and their dynamic changes after cardiopulmonary resuscitation: A prospective clinical study

PURPOSE An arterial blood gas analysis (ABG) yields important diagnostic information in the management of cardiac arrest. This study evaluated ABG samples obtained during out-of-hospital cardiopulmonary resuscitation (OHCPR) in the setting of a prospective multicenter trial. We aimed to clarify prospectively the ABG characteristics during OHCPR, potential prognostic parameters and the ABG dynamics after return of spontaneous circulation (ROSC). METHODS ABG samples were collected and instantly processed either under ongoing OHCPR performed according to current advanced life support guidelines or immediately after ROSC and data ware entered into a case report form along with standard CPR parameters. RESULTS During a 22-month observation period, 115 patients had an ABG analysis during OHCPR. In samples obtained under ongoing CPR, an acidosis was present in 98% of all cases, but was mostly of mixed hypercapnic and metabolic origin. Hypocapnia was present in only 6% of cases. There was a trend towards higher paO2 values in patients who reached sustained ROSC, and a multivariate regression analysis revealed age, initial rhythm, time from collapse to CPR initiation and the arterio-alveolar CO2 difference (AaDCO2) to be associated with sustained ROSC. ABG samples drawn immediately after ROSC demonstrated higher paO2 and unaltered pH and base excess levels compared with samples collected during ongoing CPR. CONCLUSIONS Our findings suggest that adequate ventilation and oxygenation deserve more research and clinical attention in the management of cardiac arrest and that oxygen uptake improves within minutes after ROSC. Hyperventilation resulting in arterial hypocapnia is not a major problem during OHCPR.

Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis

Probiotics may correct intestinal dysbiosis and proinflammatory conditions in patients with liver cirrhosis.

Human Nonmercaptalbumin‐2: A Novel Prognostic Marker in Chronic Liver Failure

Albumin is the major plasma protein with several important biological functions. Various disturbances of albumin function have been demonstrated in end‐stage liver disease. These functional disturbances may be related to oxidative modifications of albumin at cysteine‐34, including the irreversibly oxidized human nonmercaptalbumin‐2 (HNA2). The aim of the present study was to relate oxidative modification of albumin to short‐term prognosis in chronic liver failure. Patients with advanced cirrhosis (N = 39), acute‐on‐chronic liver failure (N = 15), and healthy controls (N = 15) were investigated. Three fractions of albumin were separated by high performance liquid chromatography according to the redox state of cysteine‐34. The HNA2 fraction was markedly increased in cirrhotic patients vs. controls and correlated with the degree of chronic liver failure as well as laboratory parameters of liver dysfunction. The HNA2 level tended to be a better predictor of short‐term mortality than the model for end stage liver disease with respect to both 30‐day mortality (area under the receiver operating characteristic curve [AUROC] 0.87 vs. 0.81, NS) and 90‐day mortality (AUROC 0.87 vs. 0.82, NS). In multivariate analysis of prognostic variables, HNA2 was the only remaining predictor of 90‐day mortality. Our results suggest that HNA2, a marker of chronic oxidative stress, is related to liver dysfunction and mortality in cirrhosis and may represent a novel biomarker of chronic liver failure.

Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion.

Objective: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. Patients: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth. Interventions: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis. Conclusions: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition.

Effects of Vitamin D Supplementation on Serum 25-Hydroxyvitamin D Concentrations in Cirrhotic Patients: A Randomized Controlled Trial

Background: The liver is crucial for 25-hydroxyvitamin D (25(OH)D) metabolism, and vitamin D deficiency is highly prevalent in patients with cirrhosis and predicts adverse outcomes. We aimed to evaluate whether vitamin D supplementation in patients with cirrhosis is effective in increasing 25(OH)D serum concentrations. Secondary outcome measures included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), and alkaline phosphatase (AP)), albumin, International Normalized Ratio (INR), bilirubin, the liver fibrosis marker hyaluronic acid, and parameters of mineral metabolism including parathyroid hormone (PTH). Methods: This is a double-center, double-blind, placebo-controlled study conducted from December 2013 to May 2014 at the Medical University of Graz, and the hospital Hoergas-Enzenbach, Austria. We enrolled 36 consecutive patients with cirrhosis and 25(OH)D concentrations below 30 ng/mL. Study participants were randomly allocated to receive either 2800 International Units of vitamin D3 per day as oily drops (n = 18) or placebo (n = 18) for 8 weeks. Results: Thirty-three study participants (mean (SD) age: 60 (9) years; 21% females; 25(OH)D: 15.6 (7.4) ng/mL) completed the trial. The mean treatment effect (95% CI) for 25(OH)D was 15.2 (8.0 to 22.4) ng/mL (p < 0.001). There was no significant effect on any secondary outcome. Conclusions: In this randomized controlled trial, vitamin D supplementation increases 25(OH)D serum concentrations, even in cirrhotic patients.

Spontaneous tension pneumothorax and CO2 narcosis in a near fatal episode of chronic obstructive pulmonary disease exacerbation

Exacerbation of chronic obstructive pulmonary disease (COPD) is a disease pattern frequently seen in emergency medical services and intensive care units. Usually, exacerbations of COPD are of infectious origin, and an acute vital threat may take several days to develop. Tension pneumothorax in patients with COPD is a rare and often unexpected cause of acute vital threat. To the best of our knowledge, this is a unique case of CO2 narcosis after spontaneous tension pneumothorax in a patient with COPD. We describe the rapid development of respiratory insufficiency and near fatal pulmonary failure in a 65-year-old female patient with COPD due to spontaneous tension pneumothorax. The patient was in respiratory failure and comatose upon arrival of the emergency service. Before mechanical ventilation, coma could be confirmed to be due to CO2 narcosis caused by exorbitant arterial hypercapnia (PCO2, 193 mm Hg). Pneumothorax was diagnosed in the hospital by chest x-ray and resolved after pleural drainage. The patient could be extubated early and discharged without sequelae. In conclusion, we want to report the occurrence of a tension pneumothorax as an important and potentially overseen condition in patients with COPD with acute respiratory failure.