No abstract

In this randomized clinical trial comparing micafungin 100 mg with standard-care antifungal prophylaxis (fluconazole, liposomal amphotericin B, or caspofungin) in high-risk liver transplant patients, micafungin 100 mg was noninferior and had a better kidney safety profile.

Familial amyloid polyneuropathy (FAP) is characterized by deposition of mutated transthyretin (TTR) in the peripheral nervous system. Prior to amyloid fibrils, nonfibrillar TTR aggregates are deposited inducing oxidative stress with increased nitration (3-NT). As the major source of TTR is the liver, liver transplantation (LT) is used to halt FAP. Given the shortage of liver donors, domino LT (DLT) using FAP livers is performed. The correlation between TTR deposition in the skin and nerve was tested in biopsies from normal individuals, asymptomatic carriers (FAP 0) and FAP patients; in FAP 0, nonfibrillar TTR was observed both in the skin and nerve in the same individuals; in patients, amyloid was detected in both tissues. The occurrence of amyloidosis in recipients of FAP livers was evaluated 1-7 years after DLT: TTR deposition occurred in the skin 3 years after transplantation either as amyloid or aggregates; in one of the recipients, fibrillar TTR was present in the epineurium 6 years after DLT. Deposits were scarce and 3-NT immunostaining was irrelevant. Nerve biopsies from DLT recipients had no FAP-related neuropathy. Our findings suggest that TTR amyloid formation occurs faster than predicted and that TTR of liver origin can cross the blood-nerve barrier. Recipients of FAP livers should be under surveillance for TTR deposition and tissue damage.

BackgroundAcute pancreatitis (AP) is associated with considerable morbidity and mortality. Current severity scores include multiple variables and some of them are only complete within 48 h of admission. Red cell distribution width (RDW) is a simple and routine parameter that seems to be related to inflammatory status. Our aims were to evaluate the diagnostic value of RDW in severity and mortality of AP comparing with other prognostic scoring systems.MethodsRetrospective case-control study of a total of 312 patients with AP admitted between 2014 and 2016. Patients with severe AP (cases) were compared with patients with mild AP (controls) in the 1:1 proportion. Additionally, a comparison between survivor and nonsurvivor AP patients was performed. Diagnosis and severity of AP were defined according to the revised Atlanta classification 2012. Variables evaluated included demographics, comorbidities, hospital stay, laboratorial parameters, arterial blood gas analysis, prognostic scores within 24 h of admission (Ranson, BISAP and Modified Marshall) and mortality.ResultsIncluded 91 cases of severe AP, most males (58.2% vs 51.6%; p = 0.228) with mean age of 64.8 ± 16.3 years (vs 67.9 ± 13.7; p = 0.239). RDW0h was higher in patients with severe AP (14.6 ± 1.3 vs 12.7 ± 0.5; p < 0.001), as well as RDW0h-to-serum calcium ratio (1.8 ± 0.3 vs 1.3 ± 0.1; p < 0.001). After multivariate and ROC curve analysis, RDW0h (AUROC: 0.960; p < 0.001) and RDW0h-to-serum calcium ratio (AUROC: 0.973; p < 0.001) were the major predictors of severe AP for a cut-off value of 13.0 (S: 92.7%; Sp: 84.3%) and 1.4 (S: 96.3%; Sp: 84.3%), respectively. These factors were superior to prognostic scores, such as Ranson (AUROC: 0.777; p < 0.001; cut-off: 3.0), BISAP (AUROC: 0.732; p < 0.001; cut-off: 2.0) and Modified Marshall (AUROC: 0.756; p < 0.001; cut-off: 1.0). The mortality rate was 8.8% (16/182), all cases associated with severe AP (17.6%; 16/91). RDW0h and RDW0h-to-serum calcium ratio were higher in nonsurvivor AP patients (15.3 ± 1.4 vs 13.5 ± 1.3; p < 0.001 and 2.0 ± 0.3 vs 1.6 ± 0.3; p < 0.001, respectively). In multivariate and ROC curve analysis, RDW0h (AUROC: 0.842; p < 0.001; cut-off: 14.0), RDW24h (AUROC: 0.848; p < 0.001; cut-off: 13.8) and RDW0h-to-serum calcium ratio (AUROC: 0.820; p < 0.001; cut-off: 1.7) were independent predictors for AP mortality, superior to conventional prognostic scoring systems Ranson (AUROC: 0.640; p = 0.003; cut-off:3.0), BISAP (AUROC: 0.693; p = 0.017; cut-off: 2.0) and Modified Marshall (AUROC: 0.806; p < 0.001; cut-off:1.0).ConclusionsRDW is a simple routine parameter, available at admission. This AP cohort showed that RDW0h > 13.0 and RDW0h-to-total serum calcium ratio > 1.4 were excellent predictors for severity and RDW0h > 14.0 and RDW0h-to-total serum calcium ratio > 1.7 were very-good predictors for mortality, being superior to conventional prognostic scoring systems.

It was demonstrated that acute L-arg infusion was beneficial in in vivo renal ischaemia while it was harmful in isolated H/R tubules. In contrast, chronic L-arg supplementation was deleterious both in in vivo and in vitro renal ischaemia, suggesting that injurious effects had overcome the beneficial effects during excess NO exposure.