Objective: The Framingham Heart Study showed an increased risk of cardiovascular disease with increasing pulse pressure (PP). Elevated PP is frequently observed with increasing age and may reflect the loss of elastic properties in large arteries. We investigated the effects of the MobiusHD-device on office systolic BP (SBP) and on 24-hour ambulatory BP (ABPM) in patients with high PP. Design and method: MobiusHD is designed to passively amplify pulsatile strain at the carotid sinus and reduce BP through increased baroreceptor activation, and consequently increase sympathoinhibition. A total of 40 patients were treated with MobiusHD for therapy-resistant hypertension and had BP measured at discharge, 1, 3, and 6 months. For analyses, patients were grouped according to baseline PP (high PP:>70 mmHg, n = 25; low PP:<70 mmHg, n = 15). Responsiveness at 6 months to MobiusHD treatment was defined as decrease in SBP of more than 10 mmHg, and also as decrease in ABPM of more than 5 mmHg. Linear mixed models were used to compare mean changes in BP over time between groups, chi-square tests were used to assess responsiveness. Results: Mean ± SD age was 53 ± 12 years and 50% were female. Baseline mean SBP, PP, and ABPM were 182 ± 17 mmHg, 74 ± 16 mmHg, and 165 ± 16 mmHg, respectively. Upon implantation of MobiusHD, SBP and PP were significantly reduced at 1,3,6 months by 21,29,25 mmHg (p<0.001) and by 13,16,12 mmHg (p < 0.001) in the high PP group and by 24,16,25 mmHg (p = 0.001) and by 11,6,11 mmHg (p = 0.009) in the low PP group, respectively. ABPM was significantly reduced at 3,6 months by 15,19 mmHg (p < 0.001) in the high PP group and by 14,22 mmHg (p = 0.001) in the low PP group. There were no significant differences in overall reductions in SBP, PP, ABPM between the high and low groups (p = 0.64, p = 0.28, and p = 0.90 respectively). No significant differences in SBP responsiveness were observed between high and low baseline PP groups (68%vs.80%, p = 0.41), as well as ABPM responsiveness between high and low baseline PP groups (76%vs.73%, p = 0.85). Conclusions: The MobiusHD-device effectively reduced SBP, PP, and ABPM in patients with therapy-resistant hypertension. The SBP and ABPM responses to MobiusHD were not different between patients with high or low PP.

Objective: To evaluate the safety and performance of the MobiusHD system in patients with resistant hypertension. Design and method: This is a multi-center (9 centers) non-randomized, first-in-man assessment of a nitinol self-expanding rectangular cuboid implant (MobiusHD) designed to increase carotid sinus arterial wall strain without impacting pulsatility or laminar flow. The geometric changes of the carotid sinus enhance baroreceptor sensitivity thus decreasing sympathetic activity and lowering BP. Patients with resistant hypertension (>3 antihypertensives, of which one is a diuretic, and office SBP >160 mmHg), without obstructive carotid disease received a unilateral carotid sinus MobiusHD implant. Incidence of serious adverse events and unanticipated adverse device effects were collected along with changes in blood pressure (BP) measured during 1.5-year follow-up. Results: So far 31 patients, mean age 52 (range 21–76) years, of the anticipated 50 patients received a MobiusHD implant of which 9 patients had failed on renal denervation. Mean pretreatment office BP was 182/107 (±18/15) mmHg with a median of 4.4 prescribed antihypertensives [daily defined dose (DDD): 7.4]. During follow-up 3 patients had serious adverse events (as adjudicated by the data safety monitoring board) related to procedure or device: hypotension (n = 2) and closure device failure, requiring repair (n = 1). At 180 days, 17 of the 20 patients had a reduction in office SBP >10 mmHg and/or 24-hr SBP >5 mmHg. Eight of these 17 patients had a reduction in DDD of antihypertensive medications.Conclusions: So far, implanting the MobiusHD device in patients with resistant hypertension seems to be safe and shows promising results in BP lowering.

Objective: This is a multi-center (6 centers) non-randomized, first-in-man assessment of a nitinol self-expanding rectangular cuboid implant (MobiusHD) designed to increase carotid sinus arterial wall strain without impacting pulsatility or laminar flow. The geometric changes of the carotid sinus enhance baroreceptor sensitivity thus decreasing sympathetic activity and lowering BP. Patients with stage 2 resistant hypertension (3 or more antihypertensives, of which one is a diuretic, and office SBP 160 mmHg or higher), without obstructive carotid disease received a unilateral carotid sinus MobiusHD implant. Incidence of serious adverse events and unanticipated adverse device effects were collected along with changes in blood pressure (BP) measured during 1-year follow-up. Design and method: This is a multi-center (6 centers) non-randomized, first-in-man assessment of a nitinol self-expanding rectangular cuboid implant (MobiusHD) designed to increase carotid sinus arterial wall strain without impacting pulsatility or laminar flow. The geometric changes of the carotid sinus enhance baroreceptor sensitivity thus decreasing sympathetic activity and lowering BP. Patients with stage 2 resistant hypertension (3 or more antihypertensives, of which one is a diuretic, and office SBP 160 mmHg or higher), without obstructive carotid disease received a unilateral carotid sinus MobiusHD implant. Incidence of serious adverse events and unanticipated adverse device effects were collected along with changes in blood pressure (BP) measured during 1-year follow-up. Results: So far 15 patients, mean age 55 (39–76) years, of the anticipated 40 patients received a MobiusHD implant. Mean pretreatment office BP was 181/102 (±18/11) mmHg with a median of 4.5 prescribed antihypertensives (daily defined dose (DDD): 6.6) and 6 patients had failed on renal denervation. During follow-up 3 patients had serious adverse events related to procedure or device: hypotension (n = 2) and closure device failure requiring repair (n = 1). During follow-up eleven (11) patients showed significant BP lowering (i.e. more than 10/5 mmHg decrease in office BP) and 8 required reduction in antihypertensives. Changes in DDD and BP after MobiusHD implantConclusions: So far, implanting the MobiusHD device in patients with stage 2 resistant hypertension seems to be safe and shows promising results in BP lowering.

Renal dysfunction of acute liver failure (ALF) may have distinct pathophysiological mechanisms to hepatorenal syndrome of cirrhosis. Yet, the impact of perioperative renal function on posttransplant renal outcomes in ALF patients specifically has not been established. The aims of this study were (1) to describe the incidence and risk factors for chronic renal dysfunction following liver transplantation for ALF and (2) to compare renal outcomes with age-sex-matched patients transplanted for chronic liver disease. This was a single-center study of 101 patients transplanted for ALF. Fifty-three-and-a-half percent had pretransplant acute kidney injury and 64.9% required perioperative renal replacement therapy. After transplantation the 5-year cumulative incidence of chronic kidney disease (eGFR <60 mL/min/1.73 m²) was 41.5%. There was no association between perioperative acute kidney injury (p = 0.288) or renal replacement therapy (p = 0.134) and chronic kidney disease. Instead, the independent predictors of chronic kidney disease were older age (p = 0.019), female gender (p = 0.049), hypertension (p = 0.031), cyclosporine (p = 0.027) and nonacetaminophen-induced ALF (p = 0.039). Despite marked differences in the perioperative clinical condition and survival of patients transplanted for ALF and chronic liver disease, renal outcomes were the same. In conclusion, in patients transplanted for ALF the severity of perioperative renal injury does not predict posttransplant chronic renal dysfunction.

Background Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying indices of poor prognosis at first presentation is key to both improving clinical care and determining targets for intervention. Renal failure is a feature of severe paracetamol poisoning. The aim of this study was to investigate the relationship between renal function (serum creatinine, Cr) at first hospital presentation and time of tertiary referral to outcomes in severe paracetamol poisoning. Methods This was a retrospective cohort analysis of patients referred to the Scottish Liver Transplant Unit due to paracetamol poisoning between 1992 and 2004. The relation between degree of renal injury and outcomes, including worst prothrombin time, Kings College Hospital Criteria (KCHC) and death were examined. The effects of age, nature (single or multiple) and stated size of overdose, hepatic enzyme induction (gamma-glutamyl transpeptidase, GGT), degree of liver injury (aspartate aminotransferase, prothrombin time), blood pressure and renal injury were assessed. Results Data from 522 patients were included. Renal impairment (Cr >120 mmol/l) was present in 48.8% of patients with liver injury at time of first presentation. Creatinine at first admission predicted poorer outcome in terms of worse prothrombin time, KCHC and death ( p < 0.001). Associated risk factors for renal dysfunction included later presentation, staggered ingestion, increased age, hypotension and elevated GGT at first admission. Conclusions Creatinine at first admission appears to be a predictor of poor outcome in paracetamol overdose. A better understanding of mechanisms involved in causing renal dysfunction may offer potential therapeutic targets for improving outcome in this common poisoning.

CLINICAL S179medical therapy during 2001-2007.Demographic, clinical and laboratory parameters were recorded at the beginning and end of each treatment.Six months survival and the need for LTx were recorded.Logistic regression analysis was performed to determine factors predicting survival.Variables analyzed included demographic, clinical and treatment-related data, and laboratory parameters at baseline. Results:The study population included 113 acute (ALF), 62 acute-onchronic (AOCLF), 11 graft failure (GF), and 6 miscellaneous liver failure patients.Contraindication to Ltx existed in 35% of patients and 18 patients became untransplantable during treatment.Transplantation-free survival was 68% in ALF, 18% in AOCLF and 60% in GF.The poorest six month survival (6%) was noted in a subgroup of patients with alcohol-related AOCLF and cirrhosis.AOCLF patients with merely steatotic liver had a 55% survival.Percentage of transplanted patients was 29% in ALF, 18% in AOCLF and 55% in GF.The six month survival of transplanted patients was 94% in ALF, 73% in AOCLF and 83% in re-transplanted GF patients.The prognostic factors for survival included encephalopathy grade (P = 0.001) in paracetamol-related ALF, coagulation factor levels (P = 0.049) and encephalopathy grade (P = 0.064) in nonparacetamolrelated ALF, and alanine aminotransferase (P = 0.013) and coagulation factor V levels (P = 0.022) in unknown etiology ALF.In other subgroups prognostic factors could not be identified. Conclusion:The etiology of liver failure was the most important predictor of survival in MARS treated patients (P < 0.0001).MARS treatment seems to be futile in chronic alcohol-related AOCLF patients with cirrhosis, but some patients with merely steatotic liver may benefit even without transplantation.

Background: Although renal dysfunction is a common complication of acute liver failure (ALF) with significant prognostic implications, the pathophysiological mechanisms remain unclear. The current hypothesis suggests that the renal dysfunction may mirror the hepatorenal syndrome of cirrhosis. However, ALF has distinct clinical characteristics and the circulatory derangement may be more comparable with sepsis.Objectives: To examine the relationship between the systemic inflammatory response syndrome (SIRS) and renal dysfunction in ALF, and to identify additional risk factors for renal dysfunction.Methods: A single-centre retrospective study of 308 patients with ALF was carried out. Renal dysfunction was defined according to the RIFLE criteria for acute kidney injury.Results: 67% of patients developed renal dysfunction. On univariate analysis, renal dysfunction patients were more likely to be hypothermic (p = 0.010), had a faster heart rate (p < 0.001), a higher white cell count (p = 0.001) and a lower PaCO2 (p = 0.033). 78% of renal dysfunction patients and 53% of non-renal dysfunction patients had SIRS (p < 0.001). On multivariate analysis, the risk factors for renal dysfunction were age (p = 0.024), fulfilled Kings College Hospital prognostic criteria (p < 0.001), hypotension (p, 0.001), paracetamol-induced ALF (p < 0.001), infection (p = 0.077) and SIRS (p = 0.017). SIRS remained an independent predictor of renal dysfunction in the subgroup of patients with non-paracetamol-induced ALF (n = 91, p = 0.001). In contrast, in patients with paracetamol-induced ALF (n = 217), no relationship between SIRS and renal dysfunction was demonstrated (p = 0.373).Conclusion: SIRS is strongly associated with the development of renal dysfunction in patients with non-paracetamol-induced ALF. It is proposed that the systemic inflammatory cascade plays a key role in its pathogenesis.

Background and Aims: Renal dysfunction in acute liver failure and renal dysfunction in cirrhosis are united under the umbrella term: hepatorenal syndrome.This suggests that both conditions share the same pathophysiological mechanisms.However, acute liver failure has distinct clinical characteristics and the hyperdynamic state may be more comparable with sepsis.We hypothesise that the systemic inflammatory response to acute liver injury plays a key role in the pathogenesis of renal failure in this setting.Our aim was to examine the relationship between the systemic inflammatory response syndrome (SIRS) and renal failure in acute liver failure and, in addition, to identify risk factors for renal dysfunction.Methods: Single-centre study of 442 patients with acute liver failure.Renal failure was defined as need for renal replacement therapy (RRT).The 4 SIRS components are temperature <36 or >38ºC, heart rate >90bpm, WCC <4 or >12×10 9 /L, PaCO2 < 4.3kPa.Results: Mean age at presentation was 38.9±14.2years (M:F = 1:1.3).Causes of liver injury: paracetamol (72%), viral (12%), idiosyncratic drug reactions (6%), other (10%).230 patients developed renal failure.The 28-day survival for patients who did and did not require RRT was 15% and 58% respectively (p < 0.001).On admission, 42% of renal failure patients had 3 components of SIRS and 20% of the non-renal failure group (p < 0.001).An increasing number of components of SIRS was associated with an increased probability of renal failure; 32%, 45%, 52%, 69% and 70% of patients with 0, 1, 2, 3 and 4 components of SIRS respectively required RRT (p = 0.002).The renal failure group were more likely to be diagnosed with infection (p = 0.006).Nevertheless, in both those with (p = 0.006) and those without infection (p = 0.003) the number of SIRS components was associated with renal failure.The factors independently associated with the development of renal failure were: fulfilled Kings College Hospital prognostic criteria (OR 4.64; 95% CI 2.45-8.80,p < 0.001), paracetamol-induced liver failure (OR 2.89; 95% CI 1.43-5.87,p = 0.003), infection (OR 2.85; 95% CI 1.51-5.41,p = 0.001), hypotension (OR 5.27; 95% CI 2.88-9.63,p < 0.001), number of SIRS components (OR 1.46; 95% CI 1.10-1.95,p = 0.009).Conclusions: The systemic inflammatory response to acute liver failure is a predictor of renal failure.This suggests a pathophysiological role and further investigation is warranted.

The aim of this retrospective study is to analyse the features of a cluster of acute liver diseases that occurred during the recent epidemic of Chikungunya virus (CHIK) (an alphavirus without recognized tropism for hepatocytes) observed in Saint Benoit in 2006.From January 1st to February 28th 2006,3400 patients (pts) were evaluated at the emergency wards of the Clinique Saint Benoit (CHIK infection being clinically contemplated in 750) and serum aminotransferase (SAT) activity was measured in 895 pts, Their SAT activity was compared to that of 21 1 pts seen in the same department in January-February 2004.Chronic alcoholic intoxication (CAI) was defined by a MCV >98 ~3 and therapeutic dose of paracetamol by a daily consumption of 4 g or less of PCM.In 2006, 420 out of 895 (47%) patients had SAT higher than upper limit of normal (ULN).In 82% of the patients, AST was higher than ALT.At admission, AST values higher than 10, 20, 50, 100 ULN were found in respectively 7.3% (3 1/420), 4.0%, 2.1% and 1 .0% of the patients.Theses values were not statistically different from the percentages, 5.3% (5/94), l.l%, 0%, 0%, found in the 94 patients seen during January-February 2004.In 2006, CAI was diagnosed in 65%, 45%, 12.5% of patients with AST higher than 20 ULN, 5 ULN and <5 ULN respectively (p i 0.001).During the follow-up, SAT activity was higher than 20 ULN in 24/895 pts (2.7%).Among these 24 pts, 9/12 were found to be positive for CHTK (serum RT-PCR or IgM antibody), 80% recently ingested therapeutic doses of PCM, 3/24 had chronic cardiovascular disease, 60% were chronic alcohol drinkers, 25% (6 pts) developed acute hepatic failure (AHF) and 46% (1 1 pts) died, including 4/6 with AHF (one with cirrhosis).In January-February 2004, no patient died from liver disease.In non selected adult pts in La Reunion Island, AHF ( I ) was observed in 25% of pts with SAT activity above 20 ULN, (2) was diagnosed in alcohol abusers older than 40 years, CHIK virus infected and having ingested PCM at therapeutic doses.

Four commercial test kits for parvovirus B19 IgM were evaluated by testing 491 sera assembled into 7 panels. The serum panels were designed to assess sensitivity and specificity of the commercial assays and to reflect the various clinical settings in which acute B19 infection forms part of the differential diagnosis. A mu-capture radioimmunoassay (MACRIA) was used as the reference test. With respect to MACRIA, the commercial B19 IgM assays showed an overall sensitivity of 70.1-84.1% and specificity of 92.2 to 97.4%. Assay performance varied in different clinical situations. In sera from adults with acute B19 arthropathy, all 4 assays were 100% sensitive, but in children with fifth disease, the sensitivity ranged from 44.1 to 88.6%. The sensitivity of all 4 assays was also low when testing samples collected more than 6 weeks after onset of symptoms and in women with B19-associated embryopathy. Specificity was greater than 97% in healthy blood donors, but varied from 70.9 to 83.3% in patients acutely infected with other viruses, including rubella. Although the IgM test kits here evaluated may be usefully introduced for B19 diagnosis in certain settings, knowledge of their limitations will be important when results have been interpreted.