Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure

Abstract Hyperdynamic circulation and portal hypertension characterize acute on chronic liver failure (AoCLF), partially because of circulating mediators. Molecular Absorbents Recirculating System (MARS) may remove some of these substances. The objective of this study was to evaluate the effect of MARS on portal pressure, systemic haemodynamic and endogenous vasoactive systems. MARS treatment was performed in four patients with AoCLF (mean age 36.2 ± 3.1 years; Child–Pugh C 11 ± 1.8 points; three AAH and one NASH). Systemic and splanchnic haemodynamic measurements were performed before and after each session. Plasmatic renin activity (PRA) and NE were measured at baseline, at the end of the sessions and 10 days after MARS. All patients had severe portal hypertension (HVPG = 23 ± 7 mmHg) and pronounced hyperdynamic circulation (MAP 77.8 ± 11.7 mmHg; CO 11.2 ± 1.6 L/min; SVRI 478.5 ± 105 dyne s/cm⁵). HVPG decreased at the end of the first session in all patients (23 ± 7 mmHg vs 17.3 ± 9.9 mmHg; P = 0.05; mean decrease 32 ± 24%) because of a decrease in WHVP (40.7 ± 5.6 mmHg vs 34 ± 9.6 mmHg; P = 0.025; mean decrease 18 ± 19%). MARS significantly attenuated hyperdynamic circulation as shown by a decrease in CO (11.2 ± 1.6 L/min vs 9.4 ± 2.1 L/min; mean decrease 12.3%), with an increase in MAP (77.8 ± 11.7 mmHg vs 84.2 ± 8 mmHg; mean increase 9.2%) and in SVRI (478.5 ± 105 dyne s/cm⁵ vs 622 ± 198 dyne s/cm⁵; mean increase 41%). PRA and NE decreased significantly (14.2 ± 17.2 ng/mL/h vs 3.7 ± 3.4 ng/mL/h; 1319 ± 1002 pg/mL vs 617 ± 260 pg/mL, respectively). The NE decrease was correlated to HVPG decrease (r = 1, P = 0.01). MARS decreases portal hypertension and ameliorates hyperdynamic circulation in patients with AoCLF, probably mediated by clearance of vasoactive substances. Further studies are necessary to confirm these results.     

Predictors of Poor Outcome in ANCA-Associated Vasculitis (AAV)

It is important to recognize factors that might predict poor outcome and prognosis in patients with AAV. The predictors reported in the literature encompass genetic, histopathological, and clinical ones. Genetic studies (genetic predictors) have found genes that are associated with prediction of poor response to treatment, deterioration of renal function, and risk of mortality. Histopathological studies (histopathological predictors) have shown that sclerotic renal lesions are associated with increased risk of progression to end-stage renal disease and death. Lastly, scores (clinical predictors) obtained with tool as FFS, Maldini risk score, VDI, and emerging new biomarkers could potentially be helpful in assessment of prognosis in the future.     

Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency.

Atherosclerosis develops rapidly in patients with diabetes or renal insufficiency. Plasma lipoprotein profiles are frequently abnormal in these conditions and reflect an elevation in the level of the apoprotein B (ApoB)-containing components very low density lipoprotein (VLDL) and low density lipoprotein (LDL). High levels of circulating advanced glycation end products (AGEs) also occur in diabetes and end-stage renal disease (ESRD). These products arise from glucose-derived Amadori products and include AGE-modified peptides (AGE-peptides) which result from the catabolism of AGE-modified tissue proteins. AGE-peptides have been shown to crosslink protein amino groups and to accumulate in plasma as a consequence of renal insufficiency. To address potential mechanisms for the dyslipidemia of diabetes and ESRD, we investigated the possibility that circulating AGEs react directly with plasma lipoproteins to prevent their recognition by tissue LDL receptors. AGE-specific ELISA showed a significantly increased level of AGE-modified LDL in the plasma of diabetic or ESRD patients compared with normal controls. AGE-LDL formed readily in vitro when native LDL was incubated with either synthetic AGE-peptides or AGE-peptides isolated directly from patient plasma. LDL which had been modified by AGE-peptides in vitro to the same level of modification as that present in the plasma of diabetics with renal insufficiency exhibited markedly impaired clearance kinetics when injected into transgenic mice expressing the human LDL receptor. These data indicate that AGE modification significantly impairs LDL-receptor-mediated clearance mechanisms and may contribute to elevated LDL levels in patients with diabetes or renal insufficiency. This hypothesis was further supported by the observation that the administration of the advanced glycation inhibitor aminoguanidine to diabetic patients decreased circulating LDL levels by 28%.     

Influencia de la neoateroesclerosis en el pronóstico y la respuesta al tratamiento de los pacientes con reestenosis en el stent

Introduction and objectivesNeoatherosclerosis is one of the causes of in-stent restenosis (ISR). Our objective was to evaluate the influence of neoatherosclerosis on prognosis and treatment response in patients with ISR.MethodsThis is a pooled analysis of the optical coherence tomography (OCT)-substudies of 2 multicenter, randomized clinical trials, RIBS IV and V, comparing treatment with paclitaxel-coated balloon vs everolimus-eluting stent in patients with ISR. OCT evaluation was performed at baseline and at 6 to 9 months. Neoatherosclerosis was defined in baseline OCT as neointima with calcified or lipid content. We evaluated the angiographic and OCT results at 6 to 9 months and the occurrence of major adverse cardiovascular events at 3 years of follow-up in patients with and without neoatherosclerosis treated with paclitaxel-coated balloon or everolimus-eluting stents.ResultsSixty-four patients underwent OCT at the time of the index procedure. Neoatherosclerosis was documented in 23 (36%) lesions. Angiographic follow-up at 6 to 9 months showed no differences in restenosis [5 (24%) vs 6 (15%) P = .49], minimum lumen diameter (1.79 ± 0.7 vs 1.94 ± 0.6 mm; P = .41) or late loss (0.33 ± 0.7 vs 0.15 ± 0.5; P = .34) in patients with and without neoatherosclerosis, respectively. Follow-up OCT confirmed the absence of differences in quantitative parameters and the characteristics of tissue coverage between the 2 groups. At 3 years of follow-up, the major adverse cardiovascular events rate was 3 (13%) vs 5 (12%) in the neoatherosclerosis and nonneoatherosclerosis groups (HR, 0.94; 95%CI, 0.22-3.93; P = .93).ConclusionsIn this limited study population, OCT-defined neoatherosclerosis did not seem to influence acute and long-term outcomes in patients randomized to paclitaxel-coated balloon or everolimus-eluting stents for ISR.     

Long-term survival after post-hepatectomy liver failure for colorectal liver metastases

Background

While post-hepatectomy liver failure (PHLF) accurately predicts short-term mortality, its role in prognosticating long-term overall survival (OS) remains unclear.

Variability in postheparin hepatic lipase activity is associated with plasma adiponectin levels in African Americans.

BACKGROUND: African Americans commonly have normal high-density lipoprotein cholesterol (HDL-C) and low triglyceride levels despite having insulin resistance and obesity. The higher than expected HDL-C levels are usually attributed to low levels of hepatic triglyceride lipase (HTGL) activity. Factors that regulate HTGL in African Americans are not well delineated. METHODS: In the current study, HTGL activity was examined in relation to indices of body fat (body mass index [BMI] and waist circumference [WC]), insulin resistance (fasting plasma insulin and homeostasis model assessment of insulin resistance [HOMA-IR] index), and adipokines (adiponectin and leptin). Sixty-three African Americans (33 men, 30 women; median age 31 years, range 20-50 years; median BMI 28.6 kg/m2, range 19.7-54.7 kg/m2) had anthropometry and measurement of postheparin lipase activities (HTGL), plasma HDL-C, triglycerides, and plasma adiponectin. RESULTS: HTGL correlated strongly with HDL-C (r = -.52, p < .0001) and adiponectin (r = -.49, p < .001). HTGL increased with BMI and WC (r = .297, p = .018 and r = .301, p = .016, respectively). Adiponectin correlated strongly with HDL-C (r = .50, p < .0001) and triglycerides (r = -.493, p < .001). From multiple regression models, 28% of HTGL variability among African Americans can be explained by adiponectin levels in combination with gender and 35% of HTGL is explained with HDL-C included in the model. CONCLUSION: The data suggest that adiponectin is a significant metabolic concomitant of HTGL activity in African Americans.     

Long-term modulation of Na+ and K+ channels by TGF-��1 in neonatal rat cardiac myocytes

Previous work shows that transforming growth factor-β1 (TGF-β1) promotes several heart alterations, including atrial fibrillation (AF). In this work, we hypothesized that these effects might be associated with a potential modulation of Na(+) and K(+) channels. Atrial myocytes were cultured 1-2?days under either control conditions, or the presence of TGF-β1. Subsequently, Na(+) (I(Na)) and K(+) (I(K)) currents were investigated under whole-cell patch-clamp conditions. Three K(+) currents were isolated: inward rectifier (I(Kin)), outward transitory (I(to)), and outward sustained (I(Ksus)). Interestingly, TGF-β1 decreased (50%) the densities of I(Kin) and I(Ksus) but not of I(to). In addition, the growth factor reduced by 80% the amount of I(Na) available at -80?mV. This effect was due to a significant reduction (30%) in the maximum I(Na) recruited at very negative potentials or I(max), as well as to an increased fraction of inactivated Na(+) channels. The latter effect was, in turn, associated to a -7?mV shift in V(1/2) of inactivation. TGF-β1 also reduced by 60% the maximum amount of intramembrane charge movement of Na(+) channels or Q(max), but did not affect the corresponding voltage dependence of activation. This suggests that TGF-β1 promotes loss of Na(+) channels from the plasma membrane. Moreover, TGF-β1 also reduced (50%) the expression of the principal subunit of Na(+) channels, as indicated by western blot analysis. Thus, TGF-β1 inhibits the expression of Na(+) channels, as well as the activity of K(+) channels that give rise to I(Ksus) and I(Kin). These results may contribute to explaining the previously observed proarrhythmic effects of TGF-β1.     

Serological profile of Helicobacter pylori infection in the population of San Luis (Argentina)

We performed a seroepidemiological study of anti-Helicobacter pylori IgG by a commercial enzyme immunoassay kit (Meridian Diagnostics, USA) in 509 serum samples from 314 randomly selected asymptomatic subjects from among the population, and grouped into children (n = 124), adolescents (n = 74) and adults (n = 116), and in 195 serum samples from subjects presenting clinical gastric symptoms, grouped into children (n = 38) and adults (n = 157). The cut-off value was redefined and set at OD450 = 0.050. The percentage of seropositive individuals was not significantly different between the two groups of adults studied (75.9% and 80.2%, respectively) (p < 0.05), suggesting a high degree of contact with the microorganism in this region.