Molecular Absorbent Recirculating System therapy (MARS®) in pediatric acute liver failure: a single center experience

Background

Supportive care as a bridge to transplant or recovery remains challenging in children suffering from acute liver failure (ALF). We report our experience in children using the Molecular Absorbent Recirculating System (MARS®).

Methods

Retrospective data from children receiving therapy using MARS® from October 2009 to October 2012 were included in this single-center retrospective study. Patient characteristics, clinical presentation and complications of ALF, clinical and biological data before and after each MARS® session, technical modalities and adverse events were recorded.

Results

A total of six children underwent 17 MARS® sessions during the study period. Two adolescents were treated with the adult filter MARSFLUX® and four infants were treated with the MiniMARS® filter. The mean PEdiatric Logistic Dysfunction (PELOD) score at admission was 19 (range 11–33). All patients were mechanically ventilated, and four had acute kidney injury. The neurological course improved in one case, judged as stable in two cases and worsened in one case; data were unavailable in two cases. Mean serum ammonia levels decreased significantly following treatment with MARS® from an initial 89?±?29 to 58?±?35 mcmol/L (p?=?0.02). No other significant biological improvement was observed. Hemodynamic status improved/remained unchanged in the adolescent group, but in the infants four of the seven sessions were poorly tolerated and two sessions were aborted. Three patients died, two were successfully transplanted and one recovered without transplantation.

Conclusion

In our experience, treatment with MARS® is associated with encouraging results in adolescents, but it needs modification for very sick infants to improve tolerance.     

Adherence to transition guidelines in European paediatric nephrology units

Background

There is increasing focus on the problems involved in the transition and transfer of young adult patients from paediatric to adult renal units. This situation was addressed by the 2011 International Pediatric Nephrology Association/International Society of Nephrology (IPNA/ISN) Consensus Statement on transition.

Methods

We performed a survey of transition practices of 15 paediatric nephrology units across Europe 2 years after publication of the consensus statement.

Results

Two thirds of units were aware of the guidelines, and one third had integrated them into their transition practice. Forty-seven per cent of units transfer five or fewer patients with chronic kidney disease (CKD) stage 5 per year to a median of five adult centres, with higher numbers of CKD stages 2–4 patients. Seventy-three per cent of units were required by the hospital or government to transfer patients by a certain age. Eighty per cent of units commenced transition planning after the patient turned 15 years of age and usually within 1–2 years of the compulsory transfer age. Forty-seven per cent of units used a transition or transfer clinic. Prominent barriers to effective transition were patient and parent attachment to the paediatric unit and difficulty in allowing the young person to perform self-care.

Conclusions

Whereas awareness of the consensus statement is suboptimal, it has had some impact on practice. Adult nephrologists receive transferred patients infrequently, and the process of transition is introduced too late by paediatricians. Government- and hospital-driven age-based transfer policies distract focus from the achievement of competencies in self care. Variable use of transition clinics, written patient information and support groups is probably due to economic and human-resource limitations. The consensus statement provides a standard for evolving and evaluating transition policies jointly agreed upon by paediatric and adult units.     

Absolute CBF and CBV measurements by MRI bolus tracking before and after acetazolamide challenge: repeatabilily and comparison with PET in humans

Bolus tracking magnetic resonance imaging (MRI) is a powerful technique for assessing cerebral perfusion, but its capability to measure absolute cerebral blood flow (CBF) and volume (CBV) values is still debated. To validate the MRI technique, absolute CBF and CBV values in healthy humans obtained by echo planar gradient echo MRI were compared to H(2)(15)O and (11)CO positron emission tomography (PET) before and after acetazolamide (ACZ) (n = 8) or saline (n = 4) administration. The repeatability of CBF and CBV measurements was moderate with both methods, and slightly lower with MRI than with PET. At rest, the mean CBF values were similar with both techniques except in the cortex where they were moderately higher with MRI. CBV was higher with MRI than with PET in all areas, which may reflect an underestimation of the arterial input function (AIF). After ACZ, a significant CBF increase was observed in gray matter with both MRI and PET, suggesting that MRI might be used to assess the cerebrovascular reserve. In individual subjects, the correlation between MRI and PET measurements was good for both CBF and CBV (R(2) between 0.70 and 0.84). However, when all results were considered as a group, R(2) was lower (0.40 to 0.65), and the limits of agreement between the two methods (SD of the difference) were large. Our data suggest that physiologic CBF values and systematically overestimated CBV values may be obtained with MRI in healthy humans, but that an individual scale factor should be applied to MRI measurements to improve the agreement with PET.     

Beta-2 adrenoceptor-mediated relaxation of the isolated human saphenous vein

On isolated strips of human saphenous vein, pretreated with 5 microM phenoxybenzamine and contracted with 10 mM KCl, the beta adrenoceptor mediating the relaxant effects of isoproterenol, procaterol and norepinephrine was characterized using the selective beta-1 adrenoceptor antagonist, bisoprolol, and the selective beta-2 adrenoceptor antagonist, ICI 118,551. All three agonists produced concentration-dependent relaxations of the isolated saphenous vein with an order of potency: procaterol (pD2 value, 7.69) greater than isoproterenol (pD2 value, 7.41) much greater than norepinephrine (pD2 value, 5.30). ICI 118,551 (3 X 10(-10) to 3 X 10(-9) M) was nearly 100 times more potent than bisoprolol (10(-7) to 10(-6) M) in antagonizing the relaxant effects of isoproterenol and procaterol. The slopes of the Schild plots for the antagonistic effects of ICI 118,551 and bisoprolol against isoproterenol- and procaterol-induced relaxations were not significantly different from unity indicating interaction with a homogeneous population of beta adrenoceptors. The pA2 value for ICI 118,551 amounted to 9.11 to 9.20 and for bisoprolol to 6.50 to 6.63. In addition, the concentration-response curve for the relaxant effect of norepinephrine was significantly shifted to the right by 10(-9) M ICI 118,551, but not affected by 10(-7) M bisoprolol. These results indicate that on the isolated strips of the human saphenous vein the beta adrenoceptor mediating relaxation is of the beta-2 subtype.     

Anti-GOR in hepatitis D: specific association with hepatitis C virus superinfection

Summary A group of 113 patients with chronic hepatitis D was investigated for the presence of anti-GOR and liver kidney microsomal antibodies. Eight patients were anti-GOR positive and also positive for hepatitis C virus-infection. In sera from 16 patients liver-kidney microsomal antibodies were detectable by immunofluorescence. They were classified as LKM-3 due to their fluorescence pattern. Two of the LKM-3-positive sera were also anti-hepatitis C virus and anti-human immunodeficiency virus positive. None of these patients were positive for anti-GOR. Fourteen sera from LKM-3-positive patients reacted in Western blot with a microsomal protein at 55 kDa that differs from the 50-kDa LKM-1 (cytochrome P450IID6) antigen. Our studies demonstrate that hepatitis D virus itself does not induce an autoimmune reaction against the GOR antigen and that autoimmunity to the LKM-3 antigen induced by hepatitis D virus infection does not correlated with anti-GOR. These studies support the specificity of the anti-GOR response for hepatitis C virus infection.     

Carboplatin induces less apoptosis in the cochlea of guinea pigs than cisplatin

BACKGROUND: Cisplatin (CDDP) is known to cause inner ear damage while carboplatin (CBDCA) induces less ototoxicity than CDDP. We examined apoptotic changes in the cochlea of guinea pigs after injection of CDDP or CBDCA using immunohistochemical and electrophysiological techniques. METHODS: Three days after the injection of each solution, the cochleas were immunohistochemically examined for the presence of fragments of single-stranded DNA (ssDNA). The auditory brain stem response was recorded before and three days after the injection. RESULTS: We detected fragments of ssDNA in the stria vascularis and the spiral ligament of the CDDP-treated cochlea. In this group, the threshold of the auditory brainstem response was significantly elevated, however, in the CBDCA group, no apparent change of the threshold was detected. In the CBDCA group, fragments of ssDNA were detected in the stria vascularis and the spiral ligament. The number of cells that stained positive for ssDNA, was less than that in the CDDP group. CONCLUSIONS: Our findings indicate that CBDCA induces less apoptosis than CDDP and that this phenomenon contributes to the ototoxicity of CDDP.