Thrombotic microangiopathy-like disorder after living-donor liver transplantation:A single-center experience in Japan

AIM:To investigate thrombotic microangiopathy (TMA)in liver transplantion,because TMA is an infrequent but life-threatening complication in the transplantation field. METHODS:A total of 206 patients who underwent living-donor liver transplantation (LDLT) were evaluated,and the TMA-like disorder (TMALD) occurred in seven recipients. RESULTS:These TMALD recipients showed poor outcomes in comparison with other 199 recipients. Although two TMALD recipients successfully recovered,the other five recipients finally died despite intensive treatments including repeated plasma exchange (PE) and re-transplantation. Histopathological analysis of liver biopsies after LDLT revealed obvious differences according to the outcomes. Qualitative analysis of antibodies against a disintegrin-like domain and metalloproteinase with thrombospondin type 1 motifs (ADAMTS-13) were negative in all patients. The fragmentation of red cells,the microhemorrhagic macules and the platelet counts were early markers for the suspicion of TMALD after LDLT. Although the absolute values of von Willebrand factor (vWF) and ADAMTS-13 did not necessarily reflect TMALD,the vWF/ADAMTS-13 ratio had a clear diagnostic value in all cases. The establishment of adequate treatments for TMALD,such as PE for ADAMTS-13 replenishment or treatments against inhibitory antibodies,must be decided according to each case. CONCLUSION:The optimal induction of adequate therapies based on early recognition of TMALD by the reliable markers may confer a large advantage for TMALD after LDLT.

A Genome‑Wide Association Study for Susceptibility to Axial Length in Highly Myopic Eyes

High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution.To identify novel susceptibility genes for axial length(AL)in highly myopic eyes,a genome-wide association study(GWAS)was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients.Top single nucleotide polymorphisms(SNPs)were functionally annotated.Immunofluorescence staining,quantitative polymerase chain reaction,and western blot were performed using neural retina of form-deprived myopic mice.Enrichment analyses were further performed.We identified the four top SNPs and found that ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16(ADAMTS16)and Phosphatidylinositol Glycan Anchor Biosynthesis Class Z(PIGZ)had the potential of clinical signifi-cance.Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice,especially in the ganglion cell layer.The messenger RNA(mRNA)levels of both ADAMTS16 and PIGZ were significantly higher in the neural retina of form-deprived eyes(p=0.005 and 0.007 respectively),and both proteins showed significantly upregulated expression in the neural retina of deprived eyes(p=0.004 and 0.042,respectively).Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL,and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed.In conclusion,the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes.Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest.