Renal failure in children with hepatic failure undergoing liver transplantation

Over a 3½ year period, 133 children with hepatic failure underwent orthotopic liver transplantation (OLT) at our center. Renal failure (creatinine clearance <20 ml/min/1.73 m(2)) was present in 19 (14.3%) of these children. In seven of the 19 children, renal failure was present before OLT, and in the other 12 after OLT. The causes of renal failure included hepatorenal syndrome in seven, postischemic acute tubular necrosis in five, severe prerenal azotemia in five, and cyclosporine nephrotoxicity in two. Eight other patients died of renal failure while awaiting emergency transplantation. Of the total of 31 deaths among 133 children who underwent OLT, nine occurred in the 19 patients with renal failure. Thus patients with OLT and renal failure had a significantly higher mortality than other patients with transplants (P <0.025). Dialysis was not associated with improved survival. The majority of deaths in patients with renal failure were related to severe hemorrhage, thromboembolic events, and systemic fungal infections. Our experience suggests that renal failure is common in children with hepatic failure and is associated with reduced patient survival after OLT

Epidermal growth factor receptor tyrosine kinase inhibition is not protective in PCK rats

Epidermal growth factor receptor tyrosine kinase inhibition is not protective in PCK rats.BackgroundAdvances in the understanding of cystogenesis, identification of the PKHD1 gene and availability of a rat model (the PCK rat) caused by a Pkhd1 mutation facilitate testing of therapies for autosomal-recessive polycystic kidney disease (ARPKD). Considerable support exists for the importance of the epidermal growth factor (EGF)/transforming growth factor-alpha (TGF-α)/EGF receptor (EGFR) axis and of the adenylyl cyclase-adenosine 3′,5′-cyclic monophosphate (cAMP) pathway in the pathogenesis of cyst formation and progressive enlargement.MethodsTo determine whether EGFR tyrosine kinase inhibition is protective in the PCK rat, male and female animals were treated with EKI-785 or EKB-569 or with vehicle alone between 3 and 10 weeks of age. Biochemical and histomorphometric analysis, immunohistochemistry, immunoblotting, enzyme immunoassay, and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to ascertain the effects of treatment.ResultsContrary to other murine models of ARPKD, overexpression and apical mislocalization of EGFR were not detected in the PCK rats. Consistent with these expression results, EKI-785 or EKB-569 administration had no effect or worsened PKD, and had no effect on the development of fibrocystic liver disease. Increased renal cAMP and vasopressin V2 receptor expression were observed in the EKI-785–treated animals.ConclusionEGFR tyrosine kinase inhibition did not protect PCK rats from the development of PKD. This may be due to effects on collecting duct cAMP that counteract possible beneficial effects on the extracellular-regulated protein kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway, particularly in the absence of EGFR overexpression or mislocalization. The relevance of these observations to the treatment of human cystic kidney diseases deserves further study

Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic

Evidence that two phenotypically distinct mouse PKD mutations, bpk and jcpk, are allelic. Numerous mouse models of polycystic kidney disease (PKD) have been described. All of these diseases are transmitted as single recessive traits and in most, the phenotypic severity is influenced by the genetic background. However, based on their genetic map positions, none of these loci appears to be allelic and none are candidate modifier loci for any other mouse PKD mutation. Previously, we have described the mouse bpk mutation, a model that closely resembles human autosomal recessive polycystic kidney disease. We now report that the bpk mutation maps to a 1.6 CM interval on mouse Chromosome 10, and that the renal cystic disease severity in our intersubspecific intercross progeny is influenced by the genetic background. Interestingly, bpk co-localizes with jcpk, a phenotyp-ically-distinct PKD mutation, and complementation testing indicates that the bpk and jcpk mutations are allelic. These data imply that distinct PKD phenotypes can result from different mutations within a single gene. In addition, based on its map position, the bpk locus is a candidate genetic modifier for jck, a third phenotypically-distinct PKD mutation

Measurement of the energy asymmetry in tt¯ j production at 13 TeV with the ATLAS experiment and interpretation in the SMEFT framework

A measurement of the energy asymmetry in jet-associated top-quark pair production is presented using 139fb-1 of data collected by the ATLAS detector at the Large Hadron Collider during pp collisions at s=13TeV. The observable measures the different probability of top and antitop quarks to have the higher energy as a function of the jet scattering angle with respect to the beam axis. The energy asymmetry is measured in the semileptonic tt¯ decay channel, and the hadronically decaying top quark must have transverse momentum above 350GeV. The results are corrected for detector effects to particle level in three bins of the scattering angle of the associated jet. The measurement agrees with the SM prediction at next-to-leading-order accuracy in quantum chromodynamics in all three bins. In the bin with the largest expected asymmetry, where the jet is emitted perpendicular to the beam, the energy asymmetry is measured to be - 0.043 ± 0.020 , in agreement with the SM prediction of - 0.037 ± 0.003. Interpreting this result in the framework of the Standard Model effective field theory (SMEFT), it is shown that the energy asymmetry is sensitive to the top-quark chirality in four-quark operators and is therefore a valuable new observable in global SMEFT fits

Measurement of the energy response of the ATLAS calorimeter to charged pions from W±→ τ±(→ π±ντ) ντ events in Run 2 data

The energy response of the ATLAS calorimeter is measured for single charged pions with transverse momentum in the range 10 < pT< 300 GeV. The measurement is performed using 139 fb - 1 of LHC proton–proton collision data at s=13 TeV taken in Run 2 by the ATLAS detector. Charged pions originating from τ-lepton decays are used to provide a sample of high-pT isolated particles, where the composition is known, to test an energy regime that has not previously been probed by in situ single-particle measurements. The calorimeter response to single-pions is observed to be overestimated by ∼ 2 % across a large part of the pT spectrum in the central region and underestimated by ∼ 4 % in the endcaps in the ATLAS simulation. The uncertainties in the measurements are ≲ 1 % for 15 < pT< 185 GeV in the central region. To investigate the source of the discrepancies, the width of the distribution of the ratio of calorimeter energy to track momentum, the energies per layer and response in the hadronic calorimeter are also compared between data and simulation