Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

Serine protease inhibitor-6 differentially affects the survival of effector and memory alloreactive CD8-T cells.

The clonal expansion of effector T cells and subsequent generation of memory T cells are critical in determining the outcome of transplantation. While cytotoxic T lymphocytes induce direct cytolysis of target cells through secretion of Granzyme-B (GrB), they also express cytoplasmic serine protease inhibitor-6 (Spi6) to protect themselves from GrB that has leaked from granules. Here, we studied the role of GrB/Spi6 axis in determining clonal expansion of alloreactive CD8-T cells and subsequent generation of memory CD8-T cells in transplantation. CD8-T cells from Spi6(-/-) mice underwent more GrB mediated apoptosis upon alloantigen stimulation in vitro and in vivo following adoptive transfer into an allogeneic host. Interestingly, while OT1.Spi6(-/-) CD8 T cells showed significantly lower clonal expansion following skin transplants from OVA mice, there was no difference in the size of the effector memory CD8-T cells long after transplantation. Furthermore, lack of Spi6 resulted in a decrease of short-lived-effector-CD8-cells but did not impact the pool of memory-precursor-effector-CD8-cells. Similar results were found in heart transplant models. Our findings suggest that the final alloreactive CD8-memory-pool-size is independent from the initial clonal-proliferation as memory precursors express low levels of GrB and therefore are independent of Spi6 for survival. These data advance our understanding of memory T cells generation in transplantation and provide basis for Spi6 based strategies to target effector T cells.

Aortocaval fistula after endovascular stent-grafting of abdominal aortic aneurysm.

The authors present a case report of a 79-year-old man with insufficient cardiac contractile function who underwent endovascular stent-grafting for an abdominal aortic aneurysm. Thirty months later, the aneurysm ruptured into the inferior vena cava and subsequently formed an aortocaval fistula caused by migration of the stent-graft. Urgent secondary endovascular stent-grafting successfully excluded the blood flow into the vena cava. Endovascular stent-grafting is deemed suitable for treating this serious disorder, especially in severely debilitated or compromised patients who might not withstand a standard surgical intervention. Furthermore, in patients with previous stent-grafting, since the primary stent-graft makes repair by open surgery more difficult, a secondary endovascular intervention is recommended if feasible.

[Surgical treatment of traumatic disruption of the thoracic aorta due to fall from 6 meters height tree; report of a case].

Disruption of the thoracic aorta due to blunt chest trauma is highly lethal and requires emergent operative intervention. A successful operative treatment of traumatic disruption of the thoracic aorta is reported. A 44-year-old male was admitted to our hospital following a fall from 6 m height tree. Four hours after accident, chest X-ray film demonstrated mediastinal widening. Chest helical computed tomography (CT) scanning demonstrated mediastinal hematoma, left pleural effusion and partial descending aortic dissection. Aortic disruption was diagnosed, and surgery for the thoracic aorta was performed emergently. The 2/3 of circumferentia of the aorta was found to be disrupted in the length of 2 cm, and it was replaced with a vascular prosthesis under partial cardiopulmonary bypass. We conclude that the enhanced chest helical CT scanning is helpful for diagnosis and that if other organ injuries are not critical, the emergent surgery should be required.

[Influences of serum magnesium on measurements of serum parathyroid hormone].

The amino sequence recognizable parathyroid hormones (PTH) in lower and non-lower magnesemic groups in randomized samples were measured by using various kinds of the well established PTH kits. The levels of carboxy terminal, mid-region and intact PTH in lower magnesemic group were more decreased than these in non-lower magnesemic group. It is likely that the shortage of magnesium in serum makes a suppression of PTH secretion.