Weekend effect on early allograft outcome after kidney transplantation‐ a multi‐centre cohort study

Weekend surgery may be associated with a higher risk of early complications, but the effect of the timing of kidney transplant surgery on early allograft outcome remains uncertain. The aim of this study is to evaluate whether the association between weekend transplant surgery and allograft failure was modified by prevalent vascular disease. Using data from the Australia and New Zealand Dialysis and Transplant registry, we examined the association between weekend status and 90‐day and 1‐year allograft failure in deceased donor transplant recipients between 1994–2012. Two‐way interaction between vascular disease and weekend status was examined. Of 6622 recipients, 1868 (28.2%) received transplants during weekends. Compared with weekday transplants, weekend transplants were associated with an adjusted hazard ratio (HR) for 90‐day and 1‐year allograft failure of 0.99 (0.78–1.25; P = 0.917) and 0.93 (0.76–1.13, P = 0.468), respectively. There was a significant interaction between prevalent vascular disease and weekend status for 90‐day allograft failure (P_interaction = 0.008) but not at 1‐year, such that patients with vascular disease were more likely to experience 90‐day allograft failure if transplanted on weekend (versus weekdays), particularly failures secondary to vascular complications. Timing of transplantation does not impact on allograft outcome, although those with vascular disease may benefit from more intensive post‐transplant follow‐up for potential vascular complications.     

Tricuspid regurgitant jet velocity and myocardial tissue Doppler parameters predict mortality in a cohort of patients with sickle cell disease spanning from pediatric to adult age groups ‐ revisiting this controversial concept after 16 years of additional evidence

Sickle cell disease (SCD) is a monogenic hemoglobinopathy associated with significant morbidity and mortality. Cardiopulmonary, vascular and sudden death are the reasons for the majority of young adult mortality in SCD. To better understand the clinical importance of multi‐level vascular dysfunction, in 2009 we assessed cardiac function including tricuspid regurgitant jet velocity (TRV), tissue velocity in systole(S′) and diastole (E′), inflammatory, rheologic and hemolytic biomarkers as predictors of mortality in patients with SCD. With up to 9 years of follow up, we determined survival in 95 children, adolescents and adults with SCD. Thirty‐eight patients (40%) were less than 21 years old at initial evaluation. Survival and Cox proportional‐hazards analysis were performed. There was 19% mortality in our cohort, with median age at death of 35 years. In the pediatric subset, there was 11% mortality during the follow up period. The causes of death included cardiovascular and pulmonary complications in addition to other end‐organ failure. On Cox proportional‐hazards analysis, our model predicts that a 0.1 m/s increase in TRV increases risk of mortality 3%, 1 cm/s increase in S′ results in a 91% increase, and 1 cm/s decrease in E′ results in a 43% increase in mortality. While excluding cardiac parameters, higher plasma free hemoglobin was significantly associated with risk of mortality (p=.049). In conclusion, elevated TRV and altered markers of cardiac systolic and diastolic function predict mortality in a cohort of adolescents and young adult patients with SCD. These predictors should be considered when counseling cardiovascular risk and therapeutic optimization at transition to adult providers.     

The effect of hypotonicity, glutamine, and glycine on red cell preservation

BACKGROUND : Red cells (RBCs) stored in hypo-os-molar additive solutions with the same concentrations of adenine, dextrose, mannitol, and sodium chloride and varied amounts of ammonium, phosphate, glycerol, and glutamine were better preserved than RBCs in the standard additive solution (Adsol). Cell swelling occurred in all the experimental additives. This observation prompted the evaluation of glutamine and glycine alone, as well as a combination of glutamine and glycine, all of which have been described as producing swelling of rat liver cells. STUDY DESIGN AND METHODS : Aliquots of RBCs were stored at 4°C in Adsol or experimental additive solutions (EASs) all containing adenine, 2 mM; dextrose, 110 mM; mannitol, 55 mM; and sodium chloride, 50 mM. EAS 42 had, in addition, glutamine, 10 mM; glycine 5 mM; and phosphate, 20 mM. EAS 43 had glutamine, 10 mM; glycine, 10 mM; and phosphate 20 mM. EAS 44 had glutamine, 10 mM; EAS 45 had glutamine, 10 mM, and phosphate, 20 mM; and EAS 46 had only glycine, 10 mM. At intervals, measurements were made of mean corpuscular volume, mean corpuscular hemoglobin concentration, morphology, ATP, hemolysis, supernatant potassium, ammonia, pH, and microvesicles shed. RESULTS : The initial mean corpuscular volumes were larger in all EASs than in Adsol, but the greatest difference was between EASs 44 and 46 (108 fL) and Adsol (86 fL) (p<0.001). The morphology scores were significantly better in all the EASs (p<0.04). The ATPs were significantly greater in all the EASs (p<0.001), and highest in those with phosphate. Potassium leakage and hemolysis were less in the EASs (p<0.001). The ammonia levels were higher in all the EASs than in Adsol, with the exception of EAS 46. During storage, the extracorpuscular and intracorpuscular pH levels were essentially identical. The shedding of microvesicles was greatly reduced in all the EASs. CONCLUSION : Cell swelling induced in RBCs after collection appears to improve preservation. Ammonia and phosphate enhance RBC ATP maintenance. Glycine decreases the formation of ammonia by RBCs stored in a hypotonic medium.     

Urinary tubular biomarkers as potential early predictors of renal allograft rejection

Confirmation of kidney transplant rejection still requires a histological diagnosis on renal allograft biopsy. Research continues for new non-invasive means for early diagnosis and treatment of kidney allograft rejection. Examination of the urine in renal transplant recipients provides a logical and readily accessible non-invasive window on allograft function, reflecting the function of the kidney in its transplanted environment. Renal tubular epithelial cells (TEC) respond dynamically to the surrounding microenvironment and play an important role in allograft survival. Proteins released from TEC into the urine potentially serve as biomarkers for the early diagnosis of graft dysfunction and rejection. Activated proximal TEC express human leucocyte antigens and co-stimulatory molecules, transiently transforming into non-professional antigen-presenting cells that augment renal allograft rejection. Chemokines and chemoattractants expressed on proximal tubules may also facilitate the migration of alloreactive lymphocytes to local site of injury and stimulate cytokine release from infiltrating lymphocytes. Proximal TEC are also potential targets for circulating alloreactive antibodies and complement leading to cell damage. Changes in cell state during development, regeneration or immune response require a rapid modulation of both surface protein expression and secretion, altering the repertoire of proteins secreted or expressed at the TEC plasma membrane. Due to the proximity of TEC to the tubular lumen, these proteins are passed into the urine. In this regard, TEC possess a unique anatomic location within the transplanted organ and are therefore ideal indicators of graft function. Hence, measurement of the changes of TEC-derived molecules in the urine, in response to different challenges or modification, may predict graft outcome.     

(-)-2''-deoxy-3''-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro.

The (-)-enantiomer of 2'-deoxy-3'-thiacytidine (3TC) was found to be a potent and selective inhibitor of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) in vitro. We determined its antiviral activity against a number of laboratory strains of HIV-1 and HIV-2 in a range of CD4-bearing lymphocyte cell lines (mean 50% inhibitory concentration [IC50] range, 4 nM to 0.67 microM). 3TC was also active against a range of HIV-1 strains in peripheral blood lymphocytes (mean IC50 range, 2.5 to 90 nM). The IC50 for cytotoxicity in seven lymphocyte cell cultures, including human peripheral blood lymphocytes, ranged from 0.5 to 6 mM. 3TC had no detectable antiviral activity against a range of other viruses or in cells chronically infected with HIV-1 or HIV-2. The effects of time of addition of the compound and varying the multiplicity of infection on the antiviral activity of 3TC were determined. The results showed that 3TC is a potent and selective inhibitor of HIV-1 and HIV-2 replication in vitro.