Low-dose Thymoglobulin vs Basiliximab Induction Therapy in Low-Risk Living Related Kidney Transplant Recipients: A Prospective Randomized Trial

ContextThymoglobulin is used effectively as induction agent in kidney transplantation but the optimal dose is not well established.ObjectiveDemonstrate that low-dose thymoglobulin (3 mg/kg) has similar efficacy and safety compared to basiliximab induction in low-risk kidney transplantation under standard maintenance immunosuppressionDesign, Setting, ParticipantsProspective randomized study in kidney transplant patients (12/2016-05/2018). Inclusion criteria: Recipients > 18 years, first living donor transplant. Exclusion criteria: Second and multiorgan transplant, ABO incompatibility, positive cross-match, panel reactive antibodies (PRA) > 30%, positive donor-specific antibody, human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus positive, white blood cells < 2000 cells/mm³, platelets < 75,000 cells/mm³ and malignancy.InterventionGroup A: basiliximab (20 mg D0 and D4). Group B: thymoglobulin (3 mg/kg total). Maintenance immunosuppression: tacrolimus, mycophenolate mofetil, and steroids.Main Outcome MeasuresBiopsy-proven acute rejection (BPAR), delayed graft function, slow graft function, leukopenia, infections, adverse events, graft loss, estimated glomerular filtration rate, and death within 12 months.Results100 patients (basiliximab, n = 53) (thymoglobulin, n = 47) were included. Donor and recipient characteristics were similar except for longer dialysis (basiliximab), PRA class I (1.2% basiliximab, 4.5% thymoglobulin), HLA match (basiliximab 2.8, thymoglobulin 2.2), and cytomegalovirus status. BPAR rate was basiliximab 3.8% and thymoglobulin 6.4% (P = ns). Delayed graft function (basiliximab 3.8%; thymoglobulin 4.3%), slow graft function, and 12-month leukopenia (basiliximab 11.3%, thymoglobulin 21.3%) were similar between groups (P = ns). There was no difference in infections and adverse events between groups. Patient and graft survival were as follows: basiliximab 98.1% and 92.5%, thymoglobulin 100% and 93.6% (P = ns).ConclusionLow-dose thymoglobulin induction (3 mg/kg) can be used effectively and safely in low-risk kidney transplantation with good results during the first year post-transplant.     

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.     

Kidney recipients with allograft failure,transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.     

Testing Women’s Trust in Other Women and Same-Sex Attracted Males in Three Cultures

Heterosexual women trust mating-relevant advice received from gay men more than that received from heterosexual women. This trust is predicated on women’s perception that gay men lack ulterior sexual motives and romantically pursue other gay men. However, this trust may not hold in all cultures. For example, in both Samoa and the Istmo Zapotec of Southern Mexico, women take part in mate competition against feminine same-sex attracted males—referred to as fa’afafine and muxe, respectively—who regularly engage in sexual activity with masculine men. The present studies sought to replicate and extend research on women’s trust in males who are same-sex attracted. Experiments were conducted in Canada, Samoa, and the Istmo Zapotec, with women randomly assigned to consider the likelihood of various mate-poaching behaviors performed by either a rival woman or a same-sex attracted male. In Canada, women were more trusting of cisgender gay men than other women. Similarly, Samoan women were more trusting of fa’afafine than other women. In the Istmo Zapotec, women were equally distrustful of women and feminine muxe gunaa, whereas more masculine muxe nguiiu were rated as more trustworthy than women and muxe gunaa. These results illustrate that women’s trust in same-sex attracted males varies both between and within cultural contexts, perhaps impacted by the relative femininity of the male in question.

     

Connectivity patterns in tuberculosis and leprosy patients are indistinguishable from that of healthy donors

Connectivity, the self-defined interactions between antigen-recognising molecules in a network system can in part be assessed by measuring the reactivity of a given serum against an ordered set of immunoglobulin (Ig)G F(ab')2 fractions, separated by means of isoelectric focusing so that, the serum reactivity against the whole set of fractions defines a characteristic pattern of connectivity. Deviations from the normal condition (healthy donors) have so far been documented for two autoimmune diseases: systemic lupus erythematosus (SLE) and pemphigus vulgaris, as well as for human immunodeficiency virus (HIV)-1 infection. We tested here if bacterial infections lead to alterations in connectivity. In addition, we wanted to test if two antigenically related bacteria would produce similar or otherwise distinctive connectivity patterns. Connectivity analysis was applied on the sera from tuberculosis and leprosy patients and the sera from healthy donors were used as control. No statistically significant differences between the three groups studied were found. These results have implications for theories that set the origin of autoimmune diseases in microbial infections. To the best of our knowledge, this is the first attempt to analyze the connectivity status in bacterial infections.     

National contaminant biomonitoring program: Residues of organochlorine chemicals in U.S. Freshwater Fish, 1976–1984

The U.S. Fish and Wildlife Service periodically determines concentrations of organochlorine chemicals in freshwater fish collected from a nationwide network of stations as part of the National Contaminant Biomonitoring Program (NCBP, formerly a part of the National Pesticide Monitoring Program). From late 1984 to early 1985, a total of 321 composite fish samples were collected from 112 stations and analyzed for organochlorine chemical residues. The mean concentrations of total DDT did not change from 1980–81 to 1984, following a period of steady decline through the 1970's; however, the mean concentrations ofp,p-DDT declined significantly. The most persistent DDT homolog (p,p-DDE) was detected at 98% of the stations sampled in 1984, and constituted 73% of total DDT residues, up from 70% in 1974–79. Collectively, these findings indicate a low rate of influx and continued weathering of DDT in the environment. Residues of polychlorinated biphenyls (PCBs) also remained widespread, but a significant downward trend in total PCBs was evident, and early eluting PCB components were present at fewer stations than in the past. Mean concentrations of dieldrin have not changed since 1978–79; concentrations remained highest in Hawaii and in the Great Lakes. Toxaphene concentrations declined from 1980–81 to 1984, especially in the Great Lakes, and the incidence of toxaphene declined from 88% of the stations sampled in 1980–81 to 69% in 1984. Mean chordane concentrations did not change from 1980–81 to 1984, following a period of decline; however,trans-nonachlor replacedcis-chlordane as the most abundant component, suggesting a lower influx of chlordane to the aquatic environment. Residues of other organochlorines—mirex, pentachloroanisole (PCA), benzene hexachloride (BHC) isomers, endrin, heptachlor, hexachlorobenzene (HCB), and Dacthal^® (DCPA)—were either found at relatively few (<25%) of the stations sampled in 1984 or were characterized by relatively low concentrations. In general, organochlorine concentrations were lower in 1984 than at any time reported previously.     

Effect of SB-205384 on the decay of GABA-activated chloride currents in granule cells cultured from rat cerebellum

1. 4-Amino-7-hydroxy-2-methyl-5,6,7,8,-tetrahydrobenzo[b]thieno[2,3-b]pyridine-3-carboxylic acid, but-2-ynyl ester (SB-205384) and other γ-aminobutyric acid_A (GABA_A) receptor modulators were tested for their effects on GABA-activated chloride currents in rat cerebellar granule cells by use of the whole-cell patch clamp technique.
2. The major effect of SB-205384 on GABA_A-activated current was an increase in the half-life of decay of the response once the agonist had been removed. This is in contrast to many GABA_A receptor modulators that have previously been shown to potentiate GABA-activated currents.
3. This profile could be explained if SB-205384 stabilizes the channel in open and desensitized states so that channel closing is dramatically slowed. Such a modulatory profile may produce a novel behavioural profile in vivo.