Search

Background: The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long‐term outcome of kidney transplantation. The CYP3A single‐nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. Methods: A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12 months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. Results: The group with high IPV had a significantly higher rate of de novo donor‐specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p =.003). The high IPV group also had a higher incidence of T‐cell‐mediated rejection (TCMR; p <.001). The high IPV had no significant influence on Epstein–Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p =.003). Overall, the graft survival rate was inferior in the high IPV group (p <.001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR‐free survival rate (p <.001). Conclusion: The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac. [ABSTRACT FROM AUTHOR]

With small kidneys, EBKTs could provide sufficient renal mass but could lead to inefficient use of resources, while SKTs could result in insufficient function due to small renal mass. We aimed to compare the outcomes of EBKT and SKT from small donors weighing ≤15 kg to pediatric recipients. We retrospectively reviewed all pediatric patients who met the inclusion criteria between January 1, 1984, and April 30, 2019, at a single institution. Of a total of 23 patients, 12 received EBKT and 11 received SKT. The median age of donors, weight of donors, and weight of recipients were comparable between the two groups. The median age of recipients and median weight of allografts were greater in the EBKT group than in the SKT group. The median follow‐up was 53.9 months. There was no significant difference in eGFR, protein creatinine ratios at 1‐year follow‐up, and overall graft survival. The size of the kidney increased by approximately 13%‐43% in the EBKT group and 40%‐60% in the SKT group. This study demonstrated that kidneys from small donors weighing 5‐15 kg could be split in pediatric recipients without compromising the outcome. [ABSTRACT FROM AUTHOR]

19F magnetic resonance (MR) based detection coupled with well‐designed inorganic systems shows promise in biological investigations. Two proof‐of‐concept inorganic probes that exploit a novel mechanism for 19F MR sensing based on converting from low‐spin (S=0) to high‐spin (S=1) Ni2+ are reported. Activation of diamagnetic NiL1 and NiL2 by light or β‐galactosidase, respectively, converts them into paramagnetic NiL0, which displays a single 19F NMR peak shifted by >35 ppm with accelerated relaxation rates. This spin‐state switch is effective for sensing light or enzyme expression in live cells using 19F MR spectroscopy and imaging that differentiate signals based on chemical shift and relaxation times. This general inorganic scaffold has potential for developing agents that can sense analytes ranging from ions to enzymes, opening up diverse possibilities for 19F MR based biosensing. [ABSTRACT FROM AUTHOR]

Fine‐needle aspiration (FNA) for serial hepatic sampling may be an efficient and less invasive alternative to core needle biopsy (CNB), the current standard for liver tissue sampling. In this randomized, open‐label trial in 31 participants with hepatitis C virus genotype 1 infection (NCT01678131/Merck protocol PN048), we evaluated the feasibility of using FNA to obtain human liver tissue samples appropriate for measuring hepatic pharmacokinetics (PK), using vaniprevir as a tool compound. The primary end point was successful retrieval of liver tissue specimens with measurable vaniprevir concentrations at two of three specified FNA time points. Twenty‐nine patients met the primary end point and, therefore, were included in the PK analyses. Hepatic vaniprevir concentrations obtained with FNA were consistent with known vaniprevir PK properties. The shape of liver FNA and CNB concentration‐time profiles were comparable. In conclusion, FNA may be effective for serial tissue sampling to assess hepatic drug exposure in patients with liver disease. [ABSTRACT FROM AUTHOR]

This study goes beyond the conventional notion of the institutional environment of emerging economies and investigates their dynamic context. It examines the complex influences of policy reforms on the characteristics and survival of foreign subsidiaries in emerging economies before and after the 1997 Asian Economic Crisis. This study proposes that FDI policy reforms during times of crisis may not only have a positive effect on institutional munificence for foreign firms, but such drastic reforms may also produce a negative effect (e.g. institutional volatility and complexity) on the environment. We consider how foreign firms effectively respond to the unfavourable forces of the post-crisis environments while taking advantage of the munificence of the policy reforms. We find that foreign subsidiaries tend to take the form of wholly-owned subsidiaries (versus joint ventures), majority joint-ventures (versus minority joint-ventures), or trading operations (versus manufacturing operations) in the post-crisis institutional environment. Consistently, foreign subsidiaries with these characteristics are more likely to survive in the post-crisis environment. [ABSTRACT FROM AUTHOR]