MELD at POD 1 as a predictor of outcome in liver allografts with peak AST >5000 U/l

Perioperative liver graft injury is associated with elevation of aminotransferases after orthotopic liver transplantation (OLT). Values above 5000 U/l usually are regarded as extreme liver graft injury (ELGI). Some patients and organs recover from this critical condition. The aim of the study was to evaluate factors contributing to graft and patient survival after ELGI. From chart review we identified 64 of 917 OLT adult patients (median age 54.2 years; 68.8% males) transplanted between 11/2003 and 02/2012, who presented ELGI after OLT. Donor and recipient factors were analyzed and correlated with the outcome by univariable and multivariable methods. Multivariable cox proportional hazards showed that recipient's BMI (P = 0.01), model for end stage liver disease (MELD) score before OLT (P = 0.02) and laboratory MELD score 24 h after OLT (P = 0.01) were independently associated with patient survival. 30‐days and 12‐months survival in patients with a postoperative laboratory MELD higher than 31 was 21.4%, while patients with a postoperative laboratory MELD lower than 31 displayed 30‐days and 12‐months survival rates of 80% and 71.8%, respectively (P < 0.001). Retransplantation in the setting of ELGI after OLT should be based on all available data. Utilization of the postoperative labMELD enables the transplant physician within 24 h after transplantation to identify necessity of retransplantation objectively.     

Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome

Placental protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm pre-eclampsia have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13 concentration increased with gestational age in normal pregnancies (p < 0.0001), and it was significantly higher in women presenting with preterm pre-eclampsia (p = 0.02) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (p = 0.01) than in preterm controls. Conversely, placental PP13 mRNA (p = 0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p < 0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and serum concentrations of PP13 were found at term between patients with pre-eclampsia and control women. In contrast, the immunoreactivity of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm pre-eclampsia and HELLP syndrome than in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for PP13 in pre-eclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm pre-eclampsia and HELLP syndrome.     

Autophagy Induced by Ischemic Preconditioning is Essential for Cardioprotection

Based on growing evidence linking autophagy to preconditioning, we tested the hypothesis that autophagy is necessary for cardioprotection conferred by ischemic preconditioning (IPC). We induced IPC with three cycles of 5 min regional ischemia alternating with 5 min reperfusion and assessed the induction of autophagy in mCherry-LC3 transgenic mice by imaging of fluorescent autophagosomes in cryosections. We found a rapid and significant increase in the number of autophagosomes in the risk zone of the preconditioned hearts. In Langendorff-perfused hearts subjected to an IPC protocol of 3 × 5 min ischemia, we also observed an increase in autophagy within 10 min, as assessed by Western blotting for p62 and cadaverine dye binding. To establish the role of autophagy in IPC cardioprotection, we inhibited autophagy with Tat-ATG5^K130R, a dominant negative mutation of the autophagy protein Atg5. Cardioprotection by IPC was reduced in rat hearts perfused with recombinant Tat-ATG5^K130R. To extend the potential significance of autophagy in cardioprotection, we also assessed three structurally unrelated cardioprotective agents—UTP, diazoxide, and ranolazine—for their ability to induce autophagy in HL-1 cells. We found that all three agents induced autophagy; inhibition of autophagy abolished their protective effect. Taken together, these findings establish autophagy as an end-effector in ischemic and pharmacologic preconditioning.