Hepatocellular carcinoma after kidney transplantation: analysis of Hong Kong Renal Registry.

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.

Device-assisted continuous ambulatory peritoneal dialysis: A single-centre experience.

BACKGROUND: Peritoneal dialysis (PD) patients with impaired hand-eye function require helper assistance. Our centre developed a connection device that assists patients with impaired hand-eye function to perform PD exchange themselves, but the clinical outcomes in these patients have not been investigated. METHODS: We retrospectively reviewed patients who had device-assisted continuous ambulatory peritoneal dialysis (CAPD) during 2007-2016 and compared their clinical outcomes with age- and sex-matched patients receiving helper-assisted CAPD. RESULTS: One hundred seventy-two patients (86 each in the device- and helper-assisted CAPD groups) were followed for 29.9 (19.4-43.3) months. The device- and helper-assisted groups had comparable peritonitis rates (0.489 and 0.504 episode per patient-year, respectively, p = 0.814), with no difference in the distribution of causative organisms and the organism-specific peritonitis rates. The device-assisted group showed similar peritonitis-free survival compared with the helper-assisted group (2.58 (1.85-3.31) vs. 1.78 (0.68-2.88) years, p = 0.363) and time-to-PD discontinuation (6.27 (3.65-8.90) vs. 4.35 (3.48-5.22) years, p = 0.677). The median patient survival was similar between the two groups (3.89 (2.22-5.55) vs. 3.81 (3.27-4.36) years in the device- and helper-assisted groups, respectively, p = 0.505). CONCLUSION: Device-assisted CAPD confers comparable outcomes as helper-assisted CAPD and is a viable option in PD patients with impaired hand-eye function.

Bacterial and plant ketol-acid reductoisomerases have different mechanisms of induced fit during the catalytic cycle.

Ketol-acid reductoisomerase (KARI) is the second enzyme in the branched-chain amino acid biosynthesis pathway, which is found in plants, fungi and bacteria but not in animals. This difference in metabolism between animals and microorganisms makes KARI an attractive target for the development of antimicrobial agents. Herein we report the crystal structure of Escherichia coli KARI in complex with Mg(2+) and NADPH at 2.3Å resolution. Ultracentrifugation studies confirm that the enzyme exists as a tetramer in solution, and isothermal titration calorimetry shows that the binding of Mg(2+) increases structural disorder while the binding of NADPH increases the structural rigidity of the enzyme. Comparison of the structure of the E. coli KARI-Mg(2+)-NADPH complex with that of enzyme in the absence of cofactors shows that the binding of Mg(2+) and NADPH opens the interface between the N- and C-domains, thereby allowing access for the substrates to bind: the existence of only a small opening between the domains in the crystal structure of the unliganded enzyme signifies restricted access to the active site. This observation contrasts with that in the plant enzyme, where the N-domain can rotate freely with respect to the C-domain until the binding of Mg(2+) and/or NADPH stabilizes the relative positions of these domains. Support is thereby provided for the idea that plant and bacterial KARIs have evolved different mechanisms of induced fit to prepare the active site for catalysis.