The role of platelets in coagulation dysfunction in xenotransplantation,and therapeutic options

Xenotransplantation could resolve the increasing discrepancy between the availability of deceased human donor organs and the demand for transplantation. Most advances in this field have resulted from the introduction of genetically engineered pigs, e.g., α1,3‐galactosyltransferase gene‐knockout (GTKO) pigs transgenic for one or more human complement‐regulatory proteins (e.g., CD55, CD46, CD59). Failure of these grafts has not been associated with the classical features of acute humoral xenograft rejection, but with the development of thrombotic microangiopathy in the graft and/or consumptive coagulopathy in the recipient. Although the precise mechanisms of coagulation dysregulation remain unclear, molecular incompatibilities between primate coagulation factors and pig natural anticoagulants exacerbate the thrombotic state within the xenograft vasculature. Platelets play a crucial role in thrombosis and contribute to the coagulation disorder in xenotransplantation. They are therefore important targets if this barrier is to be overcome. Further genetic manipulation of the organ‐source pigs, such as pigs that express one or more coagulation‐regulatory genes (e.g., thrombomodulin, endothelial protein C receptor, tissue factor pathway inhibitor, CD39), is anticipated to inhibit platelet activation and the generation of thrombus. In addition, adjunctive pharmacologic anti‐platelet therapy may be required. The genetic manipulations that are currently being tested are reviewed, as are the potential pharmacologic agents that may prove beneficial.     

Bone and mineral disorders after kidney transplantation: Therapeutic strategies

Mineral and bone diseases (MBD) are common in patients with chronic kidney disease who undergo kidney transplantation. The incidence, types and severity of MBD vary according to the duration of chronic kidney disease, presence of comorbid conditions and intake of certain medications. Moreover, multiple types of pathology may be responsible for MBD. After successful reversal of uremia by kidney transplantation, many bone and mineral disorders improve, while immunosuppression, other medications, and new and existing comorbidities may result in new or worsening MBD. Chronic kidney disease is also common after kidney transplantation and may impact bone and mineral disease. In this article, we reviewed the prevalence, pathophysiology, and impact of MBD on post-transplant outcomes. We also discussed the diagnostic approach; immunosuppression management and potential treatment of MBD in kidney transplant recipients.     

Socioecological and message framing factors influencing maternal influenza immunization among minority women

Objective

A suboptimal level of seasonal influenza vaccination among pregnant minority women is an intractable public health problem, requiring effective message resonance with this population. We evaluated the effects of randomized exposure to messages which emphasize positive outcomes of vaccination (“gain-frame”), or messages which emphasize negative outcomes of forgoing vaccination (“loss-frame”). We also assessed multilevel social and community factors that influence maternal immunization among racially and ethnically diverse populations.

Study design

Minority pregnant women in metropolitan Atlanta were enrolled in the longitudinal study and randomized to receive intervention or control messages. A postpartum questionnaire administered 30 days postpartum evaluated immunization outcomes following baseline message exposure among the study population. We evaluated key outcomes using bivariate and multivariate analyses.

Results

Neither gain- [OR = 0.5176, (95% CI: 0.203,1.322)] nor loss-framed [OR = 0.5000, 95% CI: (0.192,1.304)] messages were significantly associated with increased likelihood of immunization during pregnancy. Significant correlates of seasonal influenza immunization during pregnancy included healthcare provider recommendation [OR = 3.934, 95% CI: (1.331,11.627)], use of hospital-based practices as primary source of prenatal care [OR = 2.584, 95% CI: (1.091,6.122)], and perceived interpersonal support for influenza immunization [OR = 3.405, 95% CI: (1.412,8.212)].

Conclusion

Dissemination of vaccine education messages via healthcare providers, and cultivating support from social networks, will improve seasonal influenza immunization among pregnant minority women.