T Cell Phenotyping in Individuals Hospitalized with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic. Cytokine release syndrome occurring in a minority of SARS-CoV-2 infections is associated with severe disease and high mortality. We profiled the composition, activation, and proliferation of T cells in 20 patients with severe or critical COVID-19 and 40 matched healthy controls by flow cytometry. Unsupervised hierarchical cluster analysis based on 18 T cell subsets resulted in separation of healthy controls and COVID-19 patients. Compared to healthy controls, patients suffering from severe and critical COVID-19 had increased frequencies of activated and proliferating CD38+Ki67+ CD4+ and CD8+ T cells, suggesting active antiviral T cell defense. Frequencies of CD38+Ki67+ Th1 and CD4+ cells correlated negatively with plasma IL-6. Thus, our data suggest that patients suffering from COVID-19 have a distinct T cell composition that is potentially modulated by IL-6.

[Evidence-based recommendations for the revision of the Austrian periodic health examination]. / Evidenzbasierte Empfehlungen zur Überarbeitung der österreichischen Vorsorgeuntersuchung.

The Austrian periodic health examination (PHE) was introduced in 1974 as a health insurance benefit and was redesigned for the last time in 2005. Therefore, the aim of this work was to revise the scientific basis of the PHE using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We updated the scientific evidence of examinations and consultations that are currently part of the PHE and searched and integrated new examinations. We assessed the expectations of the population towards the PHE in three focus groups. A panel of experts developed evidence-based recommendations for the revised PHE. They formulated 26 recommendations on 20 target diseases or risk factors. In comparison to the previous PHE, the panel added screening for abdominal aortic aneurysm, osteoporotic fracture risk, and chronic kidney disease to the recommendations, while screening for asymptomatic bacteriuria, screening for iron deficiency/pernicious anaemia, and risk identification of glaucoma should no longer be included.

The effect of disease modifying therapies on CD62L expression in multiple sclerosis.

BACKGROUND: The increasing armamentarium of disease-modifying therapies in multiple sclerosis is accompanied by potentially severe adverse effects. The cell-adhesion molecule CD62L, which facilitates leukocyte extravasation, has been proposed as a predictive marker for treatment tolerability. However, pre-analytical procedures might impact test results, thereby limiting its clinical usability. Whether the immediate analysis of CD62L expression of peripheral blood mononuclear cells can aid treatment decision making is yet unclear. OBJECTIVE: To investigate the effect of various disease-modifying therapies in multiple sclerosis on CD62L expression of CD3+CD4+ peripheral blood mononuclear cells in freshly collected blood samples. METHODS: We collected peripheral blood samples from patients with clinically isolated syndrome and multiple sclerosis (baseline/follow up n = 234/n = 98) and healthy controls (n = 51). CD62L+CD3+CD4+ expression was analysed within 1 hour by fluorescence-activated cell sorting. RESULTS: CD62L+CD3+CD4+ expression was significantly decreased in patients treated with natalizumab (n = 26) and fingolimod (n = 20) and increased with dimethyl-fumarate (n = 15) compared to patients receiving interferon/glatiramer acetate (n = 90/30) or no disease-modifying therapies (n = 53) and controls (n = 51) (p<0.001). CD62L expression showed temporal stability during unchanged disease-modifying therapy usage, but increased after natalizumab withdrawal and decreased upon fingolimod introduction. CONCLUSION: CD62L+CD3+CD4+ expression is altered in patients treated with different disease-modifying therapies when measured in freshly collected samples. The clinical meaning of CD62L changes under disease-modifying therapies warrants further investigation.

How are physical activity behaviors and cardiovascular risk factors associated with characteristics of the built and social residential environment?

BACKGROUND: The aim of our study was to identify perceptions of built and social residential characteristics and their association with behaviors such as physical activity (PA), nutrition and smoking and with cardiovascular risk factors (elevated BMI and fasting blood glucose). METHODS: Among participants of a preventive medical checkup at an Austrian District Health Insurance Fund (n=904, response rate = 82.2%, 42% women, 18-91 years) self-reported and measured data were collected. RESULTS: Total PA was positively associated with the presence of trees along the streets and high levels of pro-physical activity social modeling (SM) and it was negatively related to perceived safety from crime. More leisure-time PA was associated with higher levels of cycling/walking infrastructure and high levels of SM. PA for transportation was positively related to high levels of connectivity and high levels of SM. Better behavioral cardiovascular risk factor profiles (smoking and nutrition) were associated with high levels of SM and high levels of total PA. Lower BMI values were associated with high levels of infrastructure and high levels of SM. CONCLUSIONS: Both built and social residential characteristics are important correlates of PA as well as of major cardiovascular risk factors besides PA.

Volume regulation and renal function at high altitude across gender.

AIMS: We investigated changes in volume regulating hormones and renal function at high altitudes and across gender. METHODOLOGY: Included in this study were 28 subjects (n = 20 males; n = 8 females. ages: 19 - 65 yrs), who ascended to a height of 3440m (HA1), on the 3rd day and to 5050m (HA2), on the 14th day. Plasma and urinary creatinine and urinary osmolality as well as plasma levels of plasma renin activity (PRA), Aldosterone, antidiuretic hormone (ADH), and atrial natriuretic peptide (ANP) were measured. The plasma volume loss (PVL) was estimated from plasma density and hematocrit. Glomerular filtration rate (GFR) was measured based on nocturnal (9 hour) creatinine clearance; this was compared with various methods for estimation of GFR. RESULTS: The mean 24-hour urine production increased significantly in both sexes across the expedition. But PVL reached significance only in males. No changes in Na+ in plasma, urine or its fractional excretion were seen at both altitudes. Urinary osmolality decreased upon ascent to the higher altitudes. ADH and PRA decreased significantly at both altitudes in males but only at HA2 in females. However, no changes in aldosterone were seen across the sexes and at different altitudes. ANP increased significantly only in males during the expedition. GFR, derived from 9-h creatinine clearance (CreaCl), decreased in both sexes at HA1 but remained stable at HA2. Conventional Crea[p]-based GFR estimates (eGFR) showed only poor correlation to CreaCl. CONCLUSIONS: We report details of changes in hormonal patterns across high altitude sojourn. To our knowledge we are not aware of any study that has examined these hormones in same subjects and across gender during high altitude sojourn. Our results also suggest that depending on the estimation formula used, eGFR underestimated the observed decrease in renal function measured by CreaCl, thus opening the debate regarding the use of estimated glomerular filtration rates at high altitudes.

On-line dialysate infusion to estimate absolute blood volume in dialysis patients.

It was the aim to measure the distribution volume and the elimination of ultra-pure dialysate in stable hemodialysis patients during on-line hemodiafiltration (HDF). Dialysate was automatically infused as a volume indicator using standard on-line HDF equipment. Indicator concentration was noninvasively measured in the arterial blood-line (using the blood volume monitor, Fresenius Medical Care, Bad Homburg vor der Höhe, Germany), and its time course was analyzed to obtain the elimination rate and the distribution volume V(t) at the time of dilution. Blood volume at treatment start (V0) was calculated accounting for the degree of intradialytic hemoconcentration. Five patients (two females) were studied during 15 treatments. Two to six measurements using indicator volumes ranging from 60 to 210 ml were done in each treatment. V0 was 4.59 ± 1.15 L and larger than the volume of 4.08 ± 0.48 L estimated from anthropometric relationships. The mean half-life of infused volume was 17.2 ± 29.7 min. Given predialysis volume expansion V0 was consistent with blood volume determined from anthropometric measurements. Information on blood volume could substantially improve volume management in hemodialysis patients and fluid therapy in intensive care patients undergoing extracorporeal blood treatment. The system has the potential for complete automation using proper control inputs for BVM and HDF modules of the dialysis machine.

Absolute blood volume and hepatosplanchnic blood flow measured by indocyanine green kinetics during hemodialysis.

A technique to measure absolute blood volume and hepatosplanchnic blood flow (Q(h)) during hemodialysis (HD) is explored. The dispersion and elimination of indocyanine green (ICG) were measured using a noninvasive optical device attached to the extracorporeal system and compared with transcutaneous measurements. Distribution volume (V) and elimination rate constant (k) were determined from arterial indicator concentrations assuming standard single-pool behavior. Cardiac output (Q(c)) and access flow (Q(a)) were measured by saline dilution technique. Duplicate dilutions were available in seven subjects (two female subjects, 78.0 ± 9.66 kg dry weight). k was not different between measuring techniques (0.246 ± 0.07 vs. 0.249 ± 0.064 min⁻¹, p = n.s.). V was 4.71 ± 0.75 L (60.86 ± 10.21 ml/kg dry body weight) as anticipated for anthropometric blood volume (p = n.s). Indocyanine green half-life was 3.05 ± 0.89 min and in the range of normal liver function. Therefore, ICG clearance (K = kV, 1.14 ± 0.32 L/min) was assumed to correspond to Q(h). Systemic blood flow (Q(s)) calculated as difference between Q(c) (7.11 ± 1.47 L/min) and Q(a) (1.56 ± 0.88 L/min) was 5.55 ± 1.33 L/min. Thus, during HD 21 ± 5% of Q(s) were consumed by the hepatosplanchnic circulation. The analysis of ICG distribution and elimination using available online technology for routine HD provides plausible point-of-care information, which could be of clinical interests in extracorporeal applications.

Effects of a pre-dialysis patient education program on the relative frequencies of dialysis modalities.

BACKGROUND: Pre-dialysis education can guide the choice of the dialysis modality best tailored to meet the needs and preferences of individual patients with chronic kidney disease. METHODS: In a retrospective single-center cohort study, we evaluated the impact of a pre-dialysis education program on the incidence rates of patients using hemodialysis (HD) and peritoneal dialysis (PD) in our unit. The frequency distribution of dialysis modalities between people attending our education program and people not attending the program (control group) was analyzed for the 4-year period 2004 - 2008. RESULTS: From among all the incident chronic kidney disease 5D patients presenting during the 4-year period, we analyzed 227 who started dialysis either with an arteriovenous fistula or a PD catheter. In that cohort, 70 patients (30.8%) took part in the education program, and 157 (69.2%) did not receive structured pre-dialysis counseling. In the group receiving education, 38 patients (54.3%) started with PD, and 32 (45.7%), with HD. In the standard-care group not receiving education, 44 patients (28%) started with PD, and 113 (72%), with HD (p < 0.001). CONCLUSIONS: Our multidisciplinary pre-dialysis program had a significant impact on the frequency distribution of dialysis modalities, increasing the proportion of patients initiating dialysis with PD.

Paradoxical clearance of hyaluronan fragments during haemodialysis and haemodiafiltration.

BACKGROUND: The physiological clearance of hyaluronic acid (HA), a mortality marker in end-stage kidney disease (ESKD) patients, occurs in the liver and in the kidneys and depends on its molecular mass. The aim of this study was to examine the effect of different modes of renal replacement therapy on levels of low- and high-molecular-mass HA (LMWHA and HMWHA, respectively). METHODS: Levels of total plasma HA as well as LMWHA and HMWHA fractions were measured before and after haemodialysis (HD) and haemodiafliltration (HDF) treatments and compared with those in normal controls. Plasma ß2-microglobulin was determined to be an independent inflammation marker. The isolated effect of the extracorporeal system on HMWHA fractions was investigated in a separate in vitro study. RESULTS: In 150 ESKD patients, LMWHA (135 ng/mL) and HMWHA fractions (386 ng/mL) were elevated (P < 0.01), compared with those in 80 healthy persons. The LMWHA fraction remained unchanged both during HD and HDF, whereas the fraction of HMWHA, which is incapable of passing through dialysis membranes, decreased by about 40% (P < 0.05). The concentration of plasma ß2-microglobulin correlated with the pro-inflammatory LMWHA (P < 0.0001; r = 0.67) but not with total HA. In vitro dialysis runs suggested that this decrease was not caused by degradation or adsorption of HMWHA fragments. CONCLUSIONS: Our data suggest that the decrease in the high-mass HA level during HD and HDF mirrors a physiological clearance initiated by HD and HDF rather than by physical elimination in the extracorporeal circulation.

Validity of self-reported weight and height in Austrian adults: sociodemographic determinants and consequences for the classification of BMI categories.

OBJECTIVE: Epidemiological studies have shown that adults tend to underestimate their weight and overestimate their height. This may lead to a misclassification of their BMI in studies based on self-reported data. The aim of the present study was to assess the validity of self-reported weight and height in Austrian adults. DESIGN: Data on weight, height, health behaviour and sociodemographic characteristics of adults were collected in a standardized procedure via a self-filling questionnaire and a medical examination including measurements of weight and height. SETTING: A publicly accessible out-patient clinic in southern Austria. SUBJECTS: Austrian residents (n 473) aged 18 years and older who attended a health check participated in the study. RESULTS: The mean difference between reported and measured BMI was not significant in younger adults (<35 years: mean difference -0·21 kg/m2; P < 0·08) but increased significantly with age (≥55 years: mean difference -0·68 kg/m2; P < 0·001). The prevalence of normal weight (BMI = 18·5-24·9 kg/m2) and overweight (BMI = 25·0-29·9 kg/m2) was overestimated based on the self-reported data on BMI, while that for underweight (BMI < 18·5 kg/m2) and obesity (BMI ≥ 30·0 kg/m2) was underestimated (P < 0·001). The self-reported data showed an obesity prevalence of 12·5 %, while measurement showed a prevalence of 15·4 % (P < 0·001). CONCLUSIONS: Our results indicate that prevalence rates of obesity are probably underestimated for Austrian adults when using self-reported weight and height information. The deviations from the measured data clearly increased with age. Analyses based on self-reported data should therefore be adjusted for the age dependency of the validity.

Evolution of volume sensitivity during hemodialysis and ultrafiltration.

OBJECTIVE: This study aimed at assessing the evolution of cardiovascular characteristics during hemodialysis and ultrafiltration by a perturbation accurately defined in its magnitude and directly relevant to the problem of volume adjustment in stable hemodialysis patients. METHODS: Excess fluid volume was removed by constant ultrafiltration-rate as prescribed. Hemodynamic variables were continuously measured throughout treatments using non-invasive finger plethysmography. In addition to ongoing volume reduction by ultrafiltration (long-term perturbation), well-defined magnitudes of intravascular volume were transiently and reversibly sequestered (short-term perturbation) into the extracorporeal circulation at hourly intervals. Sensitivities of hemodynamic variables and of the baroreflex to the acute change in intravascular volume (volume sensitivities) were analyzed. RESULTS: Eight stable patients were assessed during two subsequent treatments. Treatments were accompanied by a decrease in cardiac output (p<0.05) and stroke volume (p<0.01), and by an increase in peripheral resistance (p<0.05) and diastolic pressure (p<0.05). Mean arterial pressure remained unchanged for the whole group but correlated with the change in total peripheral resistance in individual treatments (p<0.01). The average volume sensitivity of mean arterial pressure was 11.9±9.9 mmHg/L and increased (p<0.01) during treatments, while the average volume sensitivity of heart rate remained unchanged at -7.9±8.58 1/(min L). The corresponding volume sensitivity of the baroreflex was -0.81±1.5 1/(min mmHg) and remained unchanged for the whole group, but the change correlated with the change in mean arterial pressure in individual treatments (p<0.05). INTERPRETATION: The changes in arterial pressures during hemodialysis appear to relate to an unbalanced response of barocontrol mechanisms characterized by a compromised chronotropy and vascular over-reactivity.

Volume regulating hormone responses to repeated head-up tilt and lower body negative pressure.

BACKGROUND: We hypothesized the existence of different hormonal response patterns to repeated lower body negative pressure (LBNP) and head-up tilt (HUT) in healthy males. We compared hormonal, cardiovascular and plasma volume changes from rest to stress within- and between-LBNP and HUT applications. Hormones investigated included adrenocorticotropic hormone (ACTH), aldosterone, plasma renin activity (PRA), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP). MATERIALS AND METHODS: Three sequential 30-min bouts of LBNP at -55mmHg (n=14) or 70° HUT (n=9) were preceded by 30-min supine rest, and a 60-min supine rest followed the 3rd stimulus. RESULTS: Plasma renin activity increases above baseline, in relation to aldosterone, were larger with LBNP than with HUT. The 3rd HUT application resulted in a greater increase in aldosterone compared to LBNP. Mean arterial blood pressure was elevated significantly during 1st and 3rd HUT application. ACTH responses were highly correlated with those of aldosterone in both LBNP and HUT (r(2) =0·96). AVP responses, in contrast to ANP, to the three consecutive stress situations were not significantly different, both with LBNP and HUT. CONCLUSIONS: We speculate that the observed differences in blood pressure and hormonal responses to LBNP and HUT are caused by divergent effects of blood pooling in the splanchnic region, despite similar reductions in splanchnic perfusion. Apparently with repeated central hypovolaemia, especially by the 3rd application of stress, plasma aldosterone levels rise (along with ACTH), conceivably increasing its volume-guarding effect.

Modulation of plasma adrenomedullin by epinephrine infusion during head up tilt.

We investigated whether head up tilt (HUT) with and without simultaneous epinephrine infusion modulate plasma adrenomedullin. We studied eight healthy male volunteers, using two 5 min 70° HUT trials: control (saline infusion) and intervention (epinephrine infusion, titrated to a dose which increased supine systolic pressure by 20% above resting values). Protocols were randomized and separated by 2 weeks. Cardiac function and systolic time intervals, recorded using a phonocardiograph microphone, included left ventricular ejection time (LVET), pre-ejection period (PEP), PEP/LVET and electromechanical systole (QS2). Compared to saline infusion, epinephrine increased supine adrenomedullin (3.2 ± 0.8 pmol/l, i.e., mean ± SEM, respectively), heart rate (HR) (+11.3 ± 2.6 bpm), systolic pressure (+18.4 ± 2.6 mmHg) but decreased supine LVET, LVET corrected for HR (LVETi) and QS2-time (all p = 0.004). Despite similar HUT induced thoracic fluid shifts, reflected by similar thoracic impedance changes, HUT-induced adrenomedullin increases were minimal in epinephrine-supplemented men in comparison to controls (+8% vs. 42%). During HUT, epinephrine infusion decreased only the LVET (p = 0.039). Our findings confirm that short-term HUT increases plasma adrenomedullin. They further suggest that with increased supine epinephrine levels (epinephrine infusion clamping systolic arterial pressure at 120% control level), supine cardiac performance rises to a level similar to that during HUT, while adrenomedullin is still elevated with HUT. This might be in accordance with a 'dampening' role of adrenomedullin during catecholaminergic cardiovascular stimulation. As epinephrine is used as a drug to treat cardiac arrest and ventricular arrhythmias, our results may have important clinical/emergency resuscitation applications.

Efficacy and safety of anticoagulation with heparin versus heparin plus epoprostenol in patients undergoing extracorporeal liver support with Prometheus.

Anticoagulation for extracorporeal liver support is delicate due to underlying coagulation disorders in patients with liver failure and to the associated elevated bleeding risk. To date, there has been no detailed report on anticoagulation issues in patients treated with Prometheus, a device based on the principle of fractionated plasma separation and adsorption. We studied 17 patients from two centers treated with Prometheus, comparing standard anticoagulation with heparin (15 treatments) and a combination of heparin and the synthetic prostacyclin epoprostenol (22 treatments). Standard coagulation tests, proteins C and S, and thrombin-antithrombin (TAT) complex were determined, and adverse events were recorded. All but two treatments could be completed as scheduled, although filter exchange due to filter clotting was required in 24% of the treatments. Three out of 17 patients developed severe bleeding complications within 24 h of treatment. There were no overt thrombotic events. Addition of epoprostenol neither reduced coagulation-related adverse events nor improved standard coagulation parameters. Protein C, but not protein S, showed a significant reduction (23 +/- 18%) after Prometheus treatments, but levels rebounded to baseline within 18 h. TAT levels--a measure for activation of coagulation--were only altered by Prometheus in patients where TAT was already elevated before treatment. In conclusion, anticoagulation of Prometheus with heparin is feasible but still associated with a relatively high frequency of filter clotting and a considerable risk of severe bleeding in this high-risk patient population. As addition of epoprostenol did not prove beneficial, other strategies, such as regional anticoagulation with citrate, should be further evaluated.

Brain natriuretic peptide at altitude: relationship to diuresis, natriuresis, and mountain sickness.

BACKGROUND: Acute mountain sickness (AMS) affects some new arrivals above an altitude of 2500 m. Hypobaric hypoxia is known to produce diuresis and has natriuretic effects due to the release of natriuretic peptides. We tested the hypothesis that increases in brain natriuretic peptide (BNP) at altitude correlates with increased urination and natriuresis as well as symptomatic AMS. METHODS: Subjects were 14 mountaineers who undertook a Himalayan expedition that began at 100 m and passed through 3440 m en route to a final altitude of 5050 m. We measured the severity of AMS (Lake Louise Score), BNP values, nocturnal urine volume, and urine sodium concentration. RESULTS: Nocturnal urine volume increased from 490 +/- 90 mi at 3440 m to 1100 +/- 104 ml at 5050 m. BNP levels at the higher altitude were 10.6 +/- 4.7 pg x ml(-1) and were correlated with the severity of AMS in all mountaineers (Lake Louise Score 4 +/- 0.5 for AMS subjects). However, AMS severity did not correlate with urine volume or urine sodium concentration. CONCLUSIONS: Our results suggest that BNP secretion is not the cause of high-altitude diuresis. Further studies are needed to evaluate the possible role of BNP in individual responses to high altitude.

Antioxidant status of patients on peritoneal dialysis: associations with inflammation and glycoxidative stress.

BACKGROUND: Patients on peritoneal dialysis (PD) frequently exhibit oxidant-antioxidant imbalance, advanced glycation end-product overload, and subclinical inflammation but the interrelations between these pathophysiological changes have not been fully elucidated. SUBJECTS AND METHODS: To study possible associations, a cross-sectional study of antioxidant status, glycoxidative stress, and inflammation, using HPLC and ELISA methods, was undertaken in 37 PD patients and age- and sex-matched healthy controls. RESULTS: Plasma ascorbate concentrations were low in patients not taking at least low-dose vitamin C supplements. In patients taking vitamin C supplements, there was a positive relation between ascorbate and pentosidine concentrations. Vitamin E and carotenoid concentrations were comparable between patients and controls, while lycopene and lutein/zeaxanthin concentrations were lower. Interleukin-6, C-reactive protein (CRP), and pentosidine concentrations were elevated in PD patients. beta-Cryptoxanthin, lycopene, and lutein/zeaxanthin concentrations were inversely related to interleukin-6 concentrations. beta-Cryptoxanthin concentrations were also inversely related to CRP concentrations. Pentosidine showed a low dialysate-to-plasma ratio, indicating low peritoneal clearance. Pentosidine concentrations increased with duration of PD therapy, while alpha- and beta-carotene concentrations decreased. Malondialdehyde concentrations were elevated compared to controls but remained within the normal range. Retinol concentrations decreased with PD therapy and were inversely related to interleukin-6 and CRP concentrations. CONCLUSIONS: Low-dose vitamin C supplements and a carotenoid-rich diet should be recommended for PD patients to maintain normal antioxidant status and efficiently counteract the chronic inflammatory response, rather than high doses of vitamin C, which could play a role as a precursor of pentosidine.

Removal of bile acids by two different extracorporeal liver support systems in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is accompanied by marked intrahepatic cholestasis leading to accumulation of cytotoxic bile acids. Extracorporeal liver support systems efficiently remove bile acids, but their effect on bile acid composition in ACLF is unknown. The aim of the present study was to compare elimination of individual plasma bile acids by albumin dialysis (Molecular Adsorbents Recirculating System, MARS) and fractionated plasma separation (Prometheus). Eight consecutive patients with ACLF underwent alternating 6-hour sessions with MARS or Prometheus in a randomized, cross-over design. Serum samples were obtained before, during, and after each treatment, and individual bile acids including cholic acid and chenodeoxycholic acid (CDCA) were measured by gas chromatography. MARS and Prometheus removed total bile acids to a similar extent (reduction ratio, 45% and 46%, respectively). Both devices cleared cholic acid more efficiently than did CDCA. The molar fraction of CDCA (fCDCA) was elevated at baseline and correlated with the degree of liver dysfunction. Prometheus but not MARS treatments further increased fCDCA. Although both devices eliminate total bile acids to a similar extent, clearance of individual bile acids is different, leading to a slight change of the bile acid profile toward hydrophobic bile acids during Prometheus treatments.

Effect of extracorporeal liver support by MARS and Prometheus on serum cytokines in acute-on-chronic liver failure.

INTRODUCTION: Cytokines are believed to play an important role in acute-on-chronic liver failure (ACLF). Extracorporeal liver support systems may exert beneficial effects in ACLF via removal of cytokines. At present, two systems are commercially available, the Molecular Adsorbent Recirculating System (MARS) and Fractionated Plasma Separation, Adsorption and Dialysis (Prometheus). The aim of this study was to compare the effects of MARS and Prometheus treatments on serum cytokine levels and their clearances. METHODS: Eight patients with ACLF underwent alternating treatments with either MARS or Prometheus in a randomized cross-over design. Thirty-four treatments (17 MARS, 17 Prometheus) were available for analysis. Serum cytokines were measured before and after each treatment, and cytokine clearance was calculated from paired arterial and venous samples and effective plasma flow one hour after the start of treatment. RESULTS: Baseline serum levels of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and soluble TNF-alpha receptor 1 were significantly elevated in patients with ACLF. Measurable plasma clearances were detected for all cytokines tested, but no significant changes in serum levels of any cytokine were found after treatments with MARS or Prometheus. In MARS treatments, IL-10 was cleared from plasma more efficiently than IL-6. Clearance of IL-10 was higher in Prometheus than in MARS treatments. CONCLUSION: Cytokines are cleared from plasma by both MARS and Prometheus, but neither system is able to change serum cytokine levels. This discrepancy is probably due to a high rate of cytokine production in patients with ACLF.