Liver Transplantation Services During the Time of COVID-19

The coronavirus disease 2019 (COVID-19) is associated with high morbidity and mortality, prompting overwhelmed hospital systems to reallocate resources to those stricken with the disease. In response, many liver transplantation programs unexpectedly came to an abrupt halt, significantly affecting the lives of living donors and recipients around the world. As the risk-benefit scale of liver transplantation has changed in the era of COVID-19, it is prudent to understand the impact of COVID-19 on those with underlying liver disease and those in need of a liver transplant. In this review, we discuss recommendations put forth by hepatology and transplant societies, summarize results from emerging studies, and propose strategies to appropriately risk stratify patients prior to transplantation.     

The relative kicking frequency of infants born full-term and preterm during learning and short-term and long-term memory periods of the mobile paradigm

BACKGROUND AND PURPOSE: Infants born preterm differ in their spontaneous kicking, as well as their learning and memory abilities in the mobile paradigm, compared with infants born full-term. In the mobile paradigm, a supine infant's ankle is tethered to a mobile so that leg kicks cause a proportional amount of mobile movement. The purpose of this study was to investigate the relative kicking frequency of the tethered (right) and nontethered (left) legs in these 2 groups of infants. SUBJECTS: Ten infants born full-term and 10 infants born preterm (<33 weeks gestational age, <2,500 g) and 10 comparison infants participated in the study. METHODS: The relative kicking frequencies of the tethered and nontethered legs were analyzed during learning and short-term and long-term memory periods of the mobile paradigm. RESULTS: Infants born full-term showed an increase in the relative kicking frequency of the tethered leg during the learning period and the short-term memory period but not for the long-term memory period. Infants born preterm did not show a change in kicking pattern for learning or memory periods, and consistently kicked both legs in relatively equal amounts. DISCUSSION AND CONCLUSION: Infants born full-term adapted their baseline kicking frequencies in a task-specific manner to move the mobile and then retained this adaptation for the short-term memory period. In contrast, infants born preterm showed no adaptation, suggesting a lack of purposeful leg control. This lack of control may reflect a general decrease in the ability of infants born preterm to use their limb movements to interact with their environment. As such, the mobile paradigm may be clinically useful in the early assessment and intervention of infants born preterm and at risk for future impairment.     

Effects of age and sex on single-dose pharmacokinetics of tigecycline in healthy subjects

The pharmacokinetics of tigecycline was evaluated in 46 healthy young and elderly men and women. Except for the volumes of distribution at steady state (approximately 350 liters in women versus 500 liters in men), there were no significant differences in tigecycline pharmacokinetic parameters. Based on pharmacokinetics, no dosage adjustment is warranted based on age or sex.     

Associations of Soluble CD14 and Endotoxin with Mortality,Cardiovascular Disease,and Progression of Kidney Disease among Patients with CKD

Background and objectives

CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD.

Design, setting, participants, & measurements

We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m² for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006.

Results

Plasma sCD14 was negatively associated with eGFR (ρ=–0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23–58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (ρ=–0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up.

Conclusions

Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.     

TET proteins and 5-methylcytosine oxidation in hematological cancers

DNA methylation has pivotal regulatory roles in mammalian development, retrotransposon silencing, genomic imprinting, and X-chromosome inactivation. Cancer cells display highly dysregulated DNA methylation profiles characterized by global hypomethylation in conjunction with hypermethylation of promoter CpG islands that presumably lead to genome instability and aberrant expression of tumor suppressor genes or oncogenes. The recent discovery of ten-eleven-translocation (TET) family dioxygenases that oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) in DNA has led to profound progress in understanding the mechanism underlying DNA demethylation. Among the three TET genes, TET2 recurrently undergoes inactivating mutations in a wide range of myeloid and lymphoid malignancies. TET2 functions as a bona fide tumor suppressor particularly in the pathogenesis of myeloid malignancies resembling chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) in human. Here we review diverse functions of TET proteins and the novel epigenetic marks that they generate in DNA methylation/demethylation dynamics and normal and malignant hematopoietic differentiation. The impact of TET2 inactivation in hematopoiesis and various mechanisms modulating the expression or activity of TET proteins are also discussed. Furthermore, we also present evidence that TET2 and TET3 collaborate to suppress aberrant hematopoiesis and hematopoietic transformation. A detailed understanding of the normal and pathological functions of TET proteins may provide new avenues to develop novel epigenetic therapies for treating hematological malignancies.