A comparison between minimized extracorporeal circuits and conventional extracorporeal circuits in patients undergoing aortic valve surgery: is 'minimally invasive extracorporeal circulation' just low prime or closed loop perfusion ?

INTRODUCTION: Even though results have been encouraging, an unequivocal conclusion on the beneficial effect of minimally invasive extracorporeal circulation (MiECC) in patients undergoing aortic valve surgery cannot be derived from previous publications. Long-term outcomes are rarely reported and a significant decrease in operative mortality has not been shown. Most studies have a limited number of patients and are underpowered. They merely report on short-term results of a heterogeneous intraoperative group using different types of ECC system in aortic valve surgery. The aim of the present study was to determine whether MiECC systems are more beneficial than conventional extracorporeal systems (CECC) with regard to mortality, hospital stay and inflammation and with only haemodilution and blood-air interface as differences. METHODS: We retrospectively analysed data regarding mortality, hospital stay and inflammation in patients undergoing isolated aortic valve surgery. Forty patients were divided into two groups based on the type of extracorporeal system used; conventional (n=20) or MiECC (n=20). RESULTS: Perioperative blood product requirements were significantly lower in the MiECC group (MiECC: 0.2±0.5 units vs CECC: 0.9±1.2 units, p=0.004). No differences were seen postoperatively regarding mortality (5% vs 5%, p=0.99), total length of hospital stay (10.6±7.2 days (MiECC) vs 12.1±5.9 days (CECC), p=0.39) or inflammation markers (CRP: MiECC: 7.09±13.62 mg/L vs CECC: 3.4±3.2 mg/L, p=0.89). CONCLUSION: MiECC provides circulatory support that is equally safe and feasible as conventional extracorporeal circuits. No differences in mortality, hospital stay or inflammation markers were observed.

Reduced cortisol metabolism during critical illness.

BACKGROUND: Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. METHODS: In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. RESULTS: Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). CONCLUSIONS: During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.).

Neuronal migration depends on intact peroxisomal function in brain and in extraneuronal tissues.

Functional peroxisome deficiency, as encountered in Zellweger syndrome, causes a specific impairment of neuronal migration. Although the molecular mechanisms underlying the neuronal migration defect are at present unknown, the excess of very long chain fatty acids in brain, a consequence of peroxisomalbeta-oxidation deficiency, has often been hypothesized to play a major role. The purpose of the present study was to investigate the contribution of peroxisomal dysfunction in brain as opposed to peroxisomal dysfunction in extraneuronal tissues to the migration defect. Peroxisomes were selectively reconstituted either in brain or liver of Pex5 knock-out mice, a model for Zellweger syndrome, by tissue-selective overexpression of Pex5p. We found that both rescue strains exhibited a significant correction of the neuronal migration defect despite an incomplete reconstitution of peroxisomal function in the targeted tissue. Animals with a simultaneous rescue of peroxisomes in both tissues displayed a pattern of neuronal migration indistinguishable from that of wild-type animals on the basis of cresyl violet staining and 5',3'-bromo-2'-deoxyuridine birth-dating analysis. These data suggest that peroxisomal metabolism in brain but also in extraneuronal tissues affects the normal development of the mouse neocortex. In liver-rescued mice, the improvement of the neuronal migration was not accompanied by changes in very long chain fatty acid, docosahexaenoic acid, or plasmalogen levels in brain, indicating that other metabolic factors can influence the neuronal migration process.

D,L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase deficiency (MADD).

Cardiomyopathy and leukodystrophy are life-threatening complications of multiple acyl-CoA dehydrogenase deficiency (MADD). A 2-year-old boy with this disorder developed rapidly progressive leukodystrophy resulting in complete paralysis within 4 months. Within a week of starting sodium-D,L-3-hydroxybutyrate he had improved. After 2 years, neurological function returned, including walking independently, with progressive improvement of brain MRI. Two additional infants with MADD developed life-threatening cardiomyopathy unresponsive to conventional treatment. On sodium-D,L-3-hydroxybutyrate treatment their cardiac contractility showed progressive and sustained improvement. D,L-3-hydroxybutyrate is a therapeutic option for cerebral and cardiac complications in severe fatty acid oxidation defects.