Dysbalanced sex hormone status is an independent predictor of decompensation and mortality in patients with liver cirrhosis.

AIMS: Endocrinological abnormalities, including low testosterone levels, are prevalent in cirrhosis. We assessed sexual hormone status in regard to hemodynamic abnormalities and its impact on hepatic decompensation and survival. METHODS: Males with cirrhosis were prospectively included in this study since 2010. Sexual hormones including bioavailable testosterone, total testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone-binding globulin as well as Child-Pugh score, Model for End-stage Liver Disease (MELD) score, and hepatic venous pressure gradient were recorded. Sarcopenia was also assessed in patients with available computed tomography scans. Clinical follow-up for hepatic decompensation, liver transplantation, and death was recorded until May 2017. RESULTS: One hundred fourteen male cirrhotic patients were included: age 55 ± 9.4 years, MELD 13.5 (range, 7-20.7). Etiologies were alcoholic liver disease in 61(53.5%) patients, viral in 30 (26.3%) patients, and other in 23 (20.2%). Child-Pugh scores were A in 32 (28.1%) patients, B in 48 (42.1%), and C in 34 (29.8%). Levels of bioavailable testosterone and total testosterone decreased with advanced Child-Pugh score (P < 0.001 and P < 0.001) whereas prolactin increased (P = 0.002). Median bioavailable testosterone (0.8 ng/mL [0.1-2] vs. 1.68 ng/mL [0.07-2.65]; P = 0.004) and total testosterone (2.7 ng/mL [0.23-12.34] vs. 7 ng/mL [0.25-10]; P = 0.041) levels were lower in patients with severe portal hypertension (hepatic venous pressure gradient >12 mmHg). Median bioavailable testosterone (0.25 ng/mL [0.07-1.7] vs. 0.97 ng/mL [0.15-2.74)]; P = 0.017) and total testosterone levels (1.28 ng/mL [0.25-7.32] vs. 4.32 ng/mL [0.43-13.47]; P = 0.031) were significantly lower in sarcopenic patients. Median follow-up was 13 months (0.2-75 months) and liver-related events were recorded in 46 patients (40.4%; death, 31 [27.2%]). Low total testosterone was associated with an increased risk for hepatic decompensation and/or death, even after adjusting for Child-Pugh score, MELD, and other relevant factors (Child-Pugh score model: hazard ratio 2.503, 95% confidence interval, 1.214-5.157, P = 0.013; MELD model: hazard ratio 3.065, 95% confidence interval, 1.523-6.169, P = 0.002). CONCLUSION: In parallel to increasing severity of cirrhosis, levels of testosterone decline whereas prolactin levels increase. However, low testosterone levels are independently associated with a higher risk for hepatic decompensation and mortality.

Erectile dysfunction in cirrhosis is impacted by liver dysfunction, portal hypertension, diabetes and arterial hypertension.

BACKGROUND: Although several risk factors for erectile dysfunction may be present in patients with cirrhosis, data on the actual prevalence and cause of erectile dysfunction is limited. The International Index of Erectile Function-5 (IIEF-5) is a well-validated survey to determine the presence and severity of erectile dysfunction in men. We assessed (i) the prevalence and severity of erectile dysfunction, and (ii) risk factors for erectile dysfunction in patients with cirrhosis. METHODS: In this prospective study, erectile dysfunction was defined as: absent (>21 IIEF-5-points), mild (12-21) and severe (5-11). Patients with overt hepatic encephalopathy, active alcohol abuse, extrahepatic malignancy, previous urologic surgery, previous liver transplantation and severe cardiac conditions were excluded. RESULTS: Among n = 151 screened patients, n = 41 met exclusion criteria and n = 30 were sexually inactive. Thus, a final number of n = 80 male patients with cirrhosis were included. Patient characteristics: age: 53 ± 9 years; model for end-stage liver disease score (MELD): 12.7 ± 3.9; Child-Pugh score (CPS) A: 30 (37.5%), B: 35 (43.8%), C: 15 (18.7%); alcohol: 38 (47.5%), viral: 25 (31.3%), alcohol/viral: 7 (8.8%) and others: 10 (12.5%). The presence of erectile dysfunction was found in 51 (63.8%) patients with 44 (55%) and 7 (8.8%) suffering from mild-to-moderate and moderate-to-severe erectile dysfunction. Mean MELD and hepatic venous pressure gradient (HVPG) were significantly higher in patients with erectile dysfunction (P = .021; P = .028). Child-Pugh score C, MELD, creatinine, age, arterial hypertension, diabetes, low libido, low testosterone and high HVPG were associated with the presence of erectile dysfunction. Interestingly, beta-blocker therapy was not associated with an increased risk. In multivariate models, arterial hypertension (OR: 6.36 [1.16-34.85]; P = .033), diabetes (OR: 7.40 [1.31-41.75]; P = .023), MELD (OR: 1.19 [1.03-1.36]; P = .015) and increasing HVPG (n = 48; OR: 1.11 [1.002-1.23]; P = .045) were independent risk factors for the presence of erectile dysfunction. CONCLUSION: About two-thirds of male patients with cirrhosis show erectile dysfunction. Severity of liver dysfunction, portal hypertension, arterial hypertension and diabetes were identified as risk factors for erectile dysfunction.

B-type natriuretic peptide increases cortisol and catecholamine concentrations in healthy subjects.

B-type natriuretic peptide (BNP) is a hormone released by the heart in response to volume load and exerts natriuretic properties. It is clinically used as a diagnostic and prognostic biomarker and investigated as a pharmacological agent in the therapy of heart failure. Here we investigate the changes in pituitary, adrenal, and thyroid hormones in response to BNP administration in a randomized single-blinded crossover study conducted in ten healthy men aged 21-29 yr. Participants received in two study sessions a continuous intravenous infusion during 4 h (once placebo and once 3 pmol·kg-1·min-1 BNP) and remained in supine position throughout the study. Circulating concentrations of pituitary, adrenal, and thyroid hormones, heart rate, and blood pressure were measured at baseline and hourly afterwards. BNP prevented the physiological decrease in cortisol during the late morning hours leading to elevated serum cortisol levels (P = 0.022) and increased circulating epinephrine and norepinephrine concentrations (P = 0.018 and P = 0.036, respectively). These hormone changes were accompanied by an increase in heart rate (P = 0.019) but no differences in blood pressure. Taken together, the impact of BNP on the endocrine system extends beyond the well-known inhibition of the renin-angiotensin-aldosterone system and includes increased adrenergic activity and cortisol concentrations. This neuroendocrine activation might impact the outcome of therapeutical BNP administrations and should be further investigated in conditions associated with increased BNP secretion.NEW & NOTEWORTHY The heart hormone B-type natriuretic peptide (BNP) is increased in patients with heart failure, where it is thought to have beneficial effects by reducing the preload. Here we report that intravenous administration of BNP in men leads to increases in adrenal hormones cortisol, epinephrine, and norepinephrine. Cortisol and catecholamine levels are independent predictors of increased cardiovascular mortality risk; therefore, drugs targeting the BNP system should be evaluated regarding their effects on the neuroendocrine activation accompanying heart failure.

Tumor and Patient Characteristics of Individuals with Mismatch Repair Deficient Colorectal Cancer.

AIMS: To investigate tumor and patient characteristics of individuals with mismatch repair (MMR)-deficient colorectal carcinomas. METHODS: We immunhistochemically investigated tissue samples of 307 consecutive patients with colorectal cancer for defects in DNA MMR proteins (hMLH1, hMSH2, hMSH6, hPMS2) and those with mutations further for microsatellite instability (MSI) and BRAF V600E mutations. RESULTS: 32/308 (10.4%) tumors showed MMR deficiency. Seventy five percent (n = 24) had loss of hMLH1 and hPMS2 expression, 3% (n = 1) of hPMS2 alone, 18.8% (n = 6) of hMSH6 and hMSH2, 3% (n = 1) of hMSH2 alone. All MMR-deficient tumors showed high MSI. These tumors occurred preferably in the right-sided colon, in women and showed specific histological features. We obtained the family history of 18/32 patients; 2 (11.1%) met Amsterdam Criteria, 5 (27.8%) Bethesda Guidelines and 6 (33.3%) revised Bethesda Guidelines. BRAF V600E mutations were found in 16 (67%) of hMLH1 and none of the hMSH2 deficient tumors. CONCLUSION: We suggest using immunhistochemical testing of tumor tissues with subsequent MSI analysis, which may be justified as a screening method for MMR deficiency in colorectal cancer, since it identifies patients with possibly hereditary defects and unalike response to chemotherapy.

Evaluation of a new balloon occlusion catheter specifically designed for measurement of hepatic venous pressure gradient.

BACKGROUND & AIMS: Despite the important clinical value of hepatic venous pressure gradient (HVPG) and its increasing use, no specific balloon occlusion catheters have been designed to cannulate liver veins. The aim of the study was to evaluate the clinical applicability of a novel balloon (NC) occlusion catheter specifically designed for HVPG measurement. METHODS: Comparison of a new CE-certified 7 French balloon occlusion catheter with a 150° angled tip and radiopaque markers (NC, Pejcl Medizintechnik, Austria), to a commonly used straight balloon catheter (SC; Boston Scientific, USA). Successful liver vein cannulation rate, need for extra equipment and total fluoroscopy time were recorded. Experts (>200) and novices (<20) in HVPG measurements were evaluated separately. RESULTS: 566 HVPG measurements taken by 11 investigators (five experts and six novices) were analysed. Overall, HVPG could be successfully measured in 98.7% of cases. The rate of successful liver vein cannulation at first attempt was significantly higher among experts when compared to novices (87.3% vs 67.3%, P < 0.001). Moreover, the rate of successful liver vein cannulation without need for any additional equipment was higher when using the NC, both among experts (NC:91.9% vs SC:80.6%, P = 0.03) and novices (NC:73.3% vs SC:50.7%, P = 0.001). The mean fluoroscopy time needed to cannulate the hepatic vein was significantly shorter in experts as compared to novices [2.37(0.10-26) vs 5.2(0.6-30.2] min, P < 0.0001), but not significantly different between catheters. CONCLUSIONS: Both novices and experts achieve higher liver vein cannulation rates using the new specifically designed catheter. The use of the novel catheter might increase rates of successful liver vein cannulation and reduce the need for additional equipment, especially in novices.

Lower urinary tract symptoms in patients with liver cirrhosis.

PURPOSE: To evaluate the prevalence of lower urinary tract symptoms (LUTS) in men with liver cirrhosis. METHODS: In total, 128 men with known liver cirrhosis were prospectively evaluated using the validated German version of the International Prostate Symptom Score (IPSS) questionnaire. In parallel, all men underwent a detailed examination including medical history; physical examination; Child-Pugh liver function score (CPS) assessment; and measurement of blood levels of prostate-specific antigen (PSA), total and free testosterone, sexual hormone-binding globulin (SHBG), prolactin, luteotropic hormone (LH), and follicle-stimulating hormone (FSH). RESULTS: Mean patient age and mean IPSS was 56 ± 9 years and 8 ± 6, respectively. Mild (IPSS: 1-7), moderate (IPSS: 8-19), and severe (IPSS: 20-35) LUTS were present in 60.2 % (77/128), 31.3 % (40/128), and 7.0 % (9/128) of the patients, respectively. Storage symptoms increased with the CPS (p = 0.04). Voiding symptoms and overall IPSS did not differ between the CPS groups (p = 0.93 and p = 0.67). No correlation was found between ascites volume and IPSS, storage symptoms, voiding symptoms, or quality of life (QoL) (p = 0.46, p = 0.26, p = 0.81, p = 0.87). From CPS groups A to C, mean PSA levels (p = 0.04), total and free testosterone levels (p < 0.001 and p < 0.001), and SHBG levels decreased (p = 0.03); however, prolactin levels increased (p = 0.03). LH and FSH levels did not differ between the CPS groups (p = 0.15 and p = 0.35). CONCLUSIONS: Men with liver cirrhosis commonly have LUTS, with a predominance of storage symptoms. Liver cirrhosis may also affect PSA-based prostate cancer risk assessment. Accurate diagnosis and therapy strategies are warranted to improve the QoL of these patients.

Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis.

BACKGROUND & AIMS: We evaluated the gastrointestinal permeability and bacterial translocation in cirrhotic patients with portal hypertension (PHT) prior to and after non-selective betablocker (NSBB) treatment. METHODS: Hepatic venous pressure gradient (HVPG) was measured prior to and under NSBB treatment. Gastroduodenal and intestinal permeability was assessed by the sucrose-lactulose-mannitol (SLM) test. Anti-gliadin and anti-endomysial antibodies were measured. Levels of LPS-binding protein (LBP) and interleukin-6 (IL-6) were quantified by ELISA, and NOD2 and toll-like receptor 2 (TLR2) polymorphisms were genotyped. RESULTS: Fifty cirrhotics were included (72% male, 18% ascites, 60% alcoholic etiology). Abnormal gastroduodenal and intestinal permeability was found in 72% and 59% of patients, respectively. Patients with severe portal hypertension (HVPG ≥20 mm Hg; n=35) had increased markers of gastroduodenal/intestinal permeability (urine sucrose levels p=0.049; sucrose/mannitol ratios p=0.007; intestinal permeability indices p=0.002), and bacterial translocation (LBP p=0.002; IL-6 p=0.025) than patients with HVPG <20 mm Hg. A substantial portion of patients showed elevated levels of anti-gliadin antibodies (IgA: 60%, IgG: 34%) whereas no anti-endomysial antibodies were detected. A significant correlation of portal pressure (i.e., HVPG) with all markers of gastroduodenal/intestinal permeability and with LBP and IL-6 levels was observed. NOD2 and TLR2 risk variants were associated with abnormal intestinal permeability and elevated markers of bacterial translocation. At follow-up HVPG measurements under NSBB, we found an amelioration of gastroduodenal/intestinal permeability and a decrease of bacterial translocation (LBP - 16% p=0.018; IL-6 - 41% p<0.0001) levels, which was not limited to hemodynamic responders. Abnormal SLM test results and higher LBP/IL-6 levels were associated with a higher risk of variceal bleeding during follow-up but not with mortality. CONCLUSIONS: Abnormal gastroduodenal/intestinal permeability, anti-gliadin antibodies, and bacterial translocation are common findings in cirrhotic patients and are correlated with the degree of portal hypertension. NSBB treatment ameliorates gastroduodenal/intestinal permeability and reduces bacterial translocation partially independent of their hemodynamic effects on portal pressure, which may contribute to a reduced risk of variceal bleeding.

Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.

OBJECTIVE: Non-selective ß-blockers or endoscopic band ligation (EBL) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Additional α-adrenergic blockade (as by carvedilol) may increase the number of patients with haemodynamic response (reduction in hepatic venous pressure gradient (HVPG) of ≥ 20% or to values <12 mm Hg). DESIGN: Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment (80-160 mg/day) were included. HVPG responders were kept on propranolol (PROP group), while non-responders were placed on carvedilol (6.25-50 mg/day). Carvedilol responders continued treatment (CARV group), while non-responders to carvedilol underwent EBL. The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders. RESULTS: 36% (37/104) of patients showed a HVPG response to propranolol. Among the propranolol non-responders 56% (38/67) eventually achieved a haemodynamic response with carvedilol, while 44% (29/67) patients were finally treated with EBL. The decrease in HVPG was significantly greater with carvedilol (median 12.5 mg/day) than with propranolol (median 100 mg/day): -19 ± 10% versus -12 ± 11% (p<0.001). During a 2 year follow-up bleeding rates for PROP were 11% versus CARV 5% versus EBL 25% (p=0.0429). Fewer episodes of hepatic decompensation (PROP 38%/CARV 26% vs EBL 55%; p=0.0789) and significantly lower mortality (PROP 14%/CARV 11% vs EBL 31%; p=0.0455) were observed in haemodynamic responders compared to the EBL group. CONCLUSIONS: Carvedilol leads to a significantly greater decrease in HVPG than propranolol. Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response, which is associated with improved outcome with regard to prevention of variceal bleeding, hepatic decompensation and death.

B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men.

Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.

The effect of erythropoietin on platelet and endothelial activation markers: a prospective trial in healthy volunteers.

Erythropoietin (EPO) enhances formation of red blood cells and also affects thrombopoiesis and platelet function. We hypothesized that the effect of EPO may be reflected by changes in thromboxane B2 (TXB2) and endothelial cell function. Six male and six female subjects received recombinant human epoetin alpha (Erypo®) intravenously (300 U/kg). Biomarker levels were assessed at baseline and 4, 24, 48 and 72 hours after infusion. Epoetin alpha increased TXB2 levels by 140%, which reached significance at 48 hours (6.6 ± 5 ng/ml vs. 15 ± 9 ng/ml; p = 0.044) and remained at that level at 72 hours. In line, epoetin alpha increased E-selectin levels by 25% already at 24 hours (39 ± 21 ng/ml vs. 49 ± 26 ng/ml; p < 0.001) which stayed at this level until 72 hours (p < 0.001). The raise in platelet activation markers corresponded to an 88% increase in reticulocyte count (43 ± 10 × 10(9)/l vs. 81 ± 17 × 10(9)/l; p < 0.001) and a 9% increase in platelet count at 72 hours (224 ± 45 × 10(9)/l vs. 244 ± 52 × 10(9)/l; p = 0.005). Thrombomodulin and von Willebrand factor concentrations were not significantly altered by epoetin alpha. Interestingly, gender differences in the baseline levels of E-selectin and thrombomodulin were observed. E-selectin and thrombomodulin levels were doubled in men compared to women (51 ± 24 and 28 ± 10 ng/ml; p = 0.025 and 30 ± 5 ng/ml vs. 16 ± 5 ng/ml; p = 0.002, respectively). EPO increases TXB2 serum levels and soluble E-selectin. Further studies are needed to investigate whether these markers might be useful for estimation of thromboembolic risk during EPO-therapy and whether inhibition of thromboxane formation may lower thrombotic complications during EPO treatment: NCT01392612.

Ketolides--the modern relatives of macrolides : the pharmacokinetic perspective.

As with other widely used antibacterials, the abundant use of macrolides for management of ambulant infections has promoted emergence of resistance against them. Ketolides are structurally related to macrolides and were developed to overcome macrolide resistance, while sharing pharmacodynamic and pharmacokinetic characteristics. However, until now, there have been no comprehensive reviews of the comparative pharmacokinetics of macrolides and ketolides. This article reviews the pharmacokinetic parameters in plasma and relevant tissues of telithromycin, the only approved ketolide, and cethromycin, which is currently in phase III of clinical development. For comparison, the 14-membered macrolides clarithromycin and roxithromycin and the 15-membered azalide azithromycin were chosen as representatives of their class. While telithromycin achieves higher plasma concentrations than cethromycin, both antimicrobials display comparable elimination half-lives and clearance. Repeated dosing rarely influences the pharmacokinetic parameters of ketolides. Despite substantially higher maximum plasma concentrations and area under the plasma concentration-time curve (AUC) values of telithromycin, the higher antimicrobial activity of cethromycin leads to similar ratios between the AUC from 0 to 24 hours (AUC(24)) and the minimum inhibitory concentration (MIC) for relevant pathogens, suggesting comparable antimicrobial activity of both antimicrobials in plasma. Although telithromycin and cethromycin show plasma-protein binding of 90%, they have excellent tissue penetration, as indicated by volumes of distribution of about 500 L and high intracellular concentrations. Besides enhancing killing of intracellular pathogens, the high concentrations of macrolides, azalides and ketolides in leukocytes have been associated with increased delivery of the antimicrobial agent to the site of infection. Although telithromycin has been shown to accumulate in alveolar macrophages and epithelial lining fluid by 380- and 15-fold, respectively (relative to plasma concentrations), its concentration in the interstitium of soft tissues is comparable to the free fraction in plasma. Thus the pharmacokinetics of ketolides may help to explain their good activity against a wide range of respiratory tract infections, although pharmacokinetic/pharmacodynamic calculations based on plasma pharmacokinetics would indicate only minor activity against pathogens except streptococci. In contrast, AUC(24)/MIC ratios achieved in soft tissue may be considered insufficient to kill extracellular pathogens causing soft tissue infections, except for Streptococcus pyogenes. Although ketolides and macrolides share relevant pharmacokinetic properties, the pharmacokinetics of both antimicrobial classes are not considered interchangeable. With a volume of distribution similar to that of azithromycin but plasma concentrations and an elimination half-life reflecting those of clarithromycin, the pharmacokinetics of ketolides may be considered 'intermediate' between those of macrolides and azalides. Thus the pharmacokinetics of ketolides can be considered similar but not identical to those of macrolides.

S-ibuprofen effectively inhibits thromboxane B2 levels and platelet function in an experimental model of lipopolysaccharide-stimulated and non-stimulated whole blood.

OBJECTIVE: The present study aimed at testing the effect of S- and R-ibuprofen on thromboxane B(2) (TXB(2)), collagen-epinephrine closure time (CEPI-CT) and collagen-adenosine 5'-diphosphate closure time (CADP-CT) in lipopolysaccharide (LPS)-stimulated and non-stimulated human whole blood. MATERIALS AND METHODS: Whole blood was incubated with S- or R-ibuprofen with and without prior stimulation with LPS. To verify ibuprofen's potential effects on TXB(2), varying ratios of concentrations of S- and R-ibuprofen ranging from 0 to 100% were used. TXB(2) levels were measured by ELISA. The effects of S- and R-ibuprofen enantiomers on platelet aggregability were tested utilizing a PFA-100 apparatus. RESULTS: In non-stimulated and LPS-stimulated whole blood, S-ibuprofen markedly decreased TXB(2) levels at concentrations ranging from 10 to 200 microg/ml. R-ibuprofen showed its inhibiting effect at concentrations >100 microg/ml. In inflammatory and non-inflammatory conditions, CEPI-CT was prolonged at concentrations of 12.5 and 75 microg/ml for S-ibuprofen and at a concentration of 150 microg/ml of combined R- and S-ibuprofen. S-ibuprofen was significantly more effective than R-ibuprofen (p < 0.05). The combined use of S- and R-ibuprofen did not additively or synergistically prolong CEPI-CTs. CADP-CTs remained unaffected by both enantiomers. CONCLUSIONS: S-ibuprofen was more effective than the R-ibuprofen enantiomer in inhibiting TXB(2) plasma levels and aggregability of thrombocytes in non-inflammatory and inflammatory conditions.

Late vascular complications after extracorporeal membrane oxygenation support.

BACKGROUND: Extracorporeal membrane oxygenation support through the groin vessels is an established treatment option for patients with life-threatening conditions, resistant to medical treatment. However, because of critical status and type of vascular access, late vascular complications are a potential risk. METHODS: From January 1998 through December 2004, 174 adults (mean age, 45 +/- 19 years) undergoing either cardiac surgery (n = 54, 31.4%) or lung transplantation (n = 120, 68.6%) were supported with extracorporeal membrane oxygenation. Data were prospectively collected and retrospectively analyzed. Follow-up extended up to 60 months (mean, 30 +/- 10 months). Multivariable regression analysis was used to identify predictors of late vascular complications. RESULTS: Hospital survival was 57.3%. A total of 12 hospital survivors (12.2%) experienced late vascular complications. All late vascular complications were local stenosis at the former arterial cannulation site. Treatment was done by means of femorofemoral crossover bypass (n = 3), iliofemoral bypass (n = 1), thromboendarterectomy (n = 3), and percutaneous transluminal angioplasty (n = 5). We experienced no limb loss during follow-up. Predictors for long-term vascular complications were technical problems during extracorporeal membrane oxygenation explantation (p = 0.002; odds ratio, 23.2) and history of peripheral vascular disease (p = 0.015; odds ratio, 3.1). CONCLUSIONS: Extracorporal membrane oxygenation support is associated with the development of late vascular complications at the femoral access site. In selected patients alternative cannulation sites should be considered.

Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion - results of the Austrian multi-centre randomized ReoPro-BRIDGING Study.

AIMS: The aim of the ReoPro-BRIDGING Austrian multi-centre study was to investigate the effects of abciximab (ReoPro) on early reperfusion in ST-elevation myocardial infarction prior to or during primary percutaneous coronary angioplasty (pPCI). METHODS AND RESULTS: Fifty-five patients with STEMI were randomized either to start abciximab (0.25 mg/kg bolus followed by 10 microg/min infusion) during the organization phase for pPCI (Group 1, n=28) or immediately before pPCI (Group 2, n=27). The time between first bolus of abciximab and first balloon inflation of pPCI was 83+/-18 vs 21+/-13 min in Group 1 vs 2. The pre-pPCI ST-segment resolution (55+/-21.4% vs 42.4+/-18.2%, p=0.005), TIMI flow grade 3 (29% vs 7%, p=0.042), corrected TIMI frame count (58.4+/-32.7 vs 78.9+/-28.4 frame, p=0.018) %diameter stenosis (76.3 /63.5-100/ vs 100 /73.5-100/; median /interquartile range/, p=0.023), were significantly higher in Group 1 vs Group 2. Quantitative myocardial dye intensity measurement revealed a significantly higher grade of myocardial tissue perfusion (1 /0-9.25/ vs 0 /0-3.0/ grey pixel unit, p=0.048) in Group 1 before pPCI. Rapid release of cardiac enzymes was observed in Group 1 as compared with Group 2: rate of rise of CK was 210+/-209 vs 97+/-95 U/l/h (p=0.015). QRS score indicated a smaller infarct size in Group 1 (4.8+/-3.8 vs 7.6+/-3.5, p=0.011) on day 7. CONCLUSION: The use of abciximab in the organization phase for pPCI results in signs of early recanalization of the infarct-related artery and a subsequent improved myocardial tissue reperfusion.