Primary immunosuppression and outcome differences after heart transplantation: tacrolimus versus cyclosporine

Background

The superiority of tacrolimus (Tac) as primary immunosuppression for heart transplantation (HT) compared with cyclosporine (CsA) is still under debate. Outcomes of comparison studies are not consistent; the duration of these studies has been limited. The aim of this study was to evaluate long-term outcomes of patients undergoing HT based on primary immunosuppression regime.

Methods and Results

We analyzed a single-center registry of all HT patients between 1998 and 2009, comparing outcomes based on primary immunosuppressions (Tac or CsA). Patients who died before starting immunosuppression were excluded. A total of 197 patients entered the study; 103 received Tac and 94 CsA. There were no differences between groups in baseline characteristics, United Network for Organ Sharing status 1A or ventricular assist device use, except for ischemia time (195 ± 50 min in Tac group vs 182 ± 55 min in CsA; P = .08) and days on waiting list (164 ± 155 vs 100 ± 73; P < .001). After mean follow-ups of 4.5 ± 2.3 years in the Tac group and 6.3 ± 4.3 years in the CsA group, there were 19 and 36 deaths, respectively. Kaplan-Meier analysis showed increased survival for the Tac group (log rank P = .04). Tac also was significantly superior to CsA regarding mortality (relative risk 0.55; 95% confidence interval, 0.31-0.98; P = .04).

Conclusions

In our series the use of tacrolimus resulted in improved long-term survival compared with cyclosporine. At 1-year follow-up, there were no differences in acute rejection episodes or the appearance of vasculopathy.     

Austronesian genetic signature in East African Madagascar and Polynesia

The dispersal of the Austronesian language family from Southeast Asia represents the last major diaspora leading to the peopling of Oceania to the East and the Indian Ocean to the West. Several theories have been proposed to explain the current locations, and the linguistic and cultural diversity of Austronesian populations. However, the existing data do not support unequivocally any given migrational scenario. In the current study, the genetic profile of 15 autosomal STR loci is reported for the first time for two populations from opposite poles of the Austronesian range, Madagascar at the West and Tonga to the East. These collections are also compared to geographically targeted reference populations of Austronesian descent in order to investigate their current relationships and potential source population(s) within Southeast Asia. Our results indicate that while Madagascar derives 66.3% of its genetic makeup from Africa, a clear connection between the East African island and Southeast Asia can be discerned. The data suggest that although geographic location has influenced the phylogenetic relationships between Austronesian populations, a genetic connection that binds them beyond geographical divides is apparent.     

Afghanistan from a Y-chromosome perspective

Central Asia has served as a corridor for human migrations providing trading routes since ancient times. It has functioned as a conduit connecting Europe and the Middle East with South Asia and far Eastern civilizations. Therefore, the study of populations in this region is essential for a comprehensive understanding of early human dispersal on the Eurasian continent. Although Y- chromosome distributions in Central Asia have been widely surveyed, present-day Afghanistan remains poorly characterized genetically. The present study addresses this lacuna by analyzing 190 Pathan males from Afghanistan using high-resolution Y-chromosome binary markers. In addition, haplotype diversity for its most common lineages (haplogroups R1a1a*-M198 and L3-M357) was estimated using a set of 15 Y-specific STR loci. The observed haplogroup distribution suggests some degree of genetic isolation of the northern population, likely due to the Hindu Kush mountain range separating it from the southern Afghans who have had greater contact with neighboring Pathans from Pakistan and migrations from the Indian subcontinent. Our study demonstrates genetic similarities between Pathans from Afghanistan and Pakistan, both of which are characterized by the predominance of haplogroup R1a1a*-M198 (>50%) and the sharing of the same modal haplotype. Furthermore, the high frequencies of R1a1a-M198 and the presence of G2c-M377 chromosomes in Pathans might represent phylogenetic signals from Khazars, a common link between Pathans and Ashkenazi groups, whereas the absence of E1b1b1a2-V13 lineage does not support their professed Greek ancestry.