Incidence and impact of anti-HLA-DP antibodies in renal transplantation.

BACKGROUND: The role of anti-HLA-DP antibodies in renal transplantation is poorly defined. This study describes the impact of donor (donor-specific antibody [DSA]) and non-donor-specific antibodies against HLA-DP antigens in renal transplant patients. METHODS: Of 195 consecutive patients transplanted between September 2009 and December 2011, 166 primary kidney recipients and their donors were typed (high-resolution) for DP antigens. Sera taken pre-transplant and at 1, 3, 6, 9, and 12 months, and annually post-transplant were retrospectively tested for anti-DP antibodies using single-antigen beads. RESULTS: In 81 (49%) patients, anti-DP antibodies were found; 64% (n=52) of patients were positive in the pre-transplant samples and 36% (n=29) were positive exclusively post-transplant. The median time from transplantation to antibody was 20.9 months. Fifty-five percent (n=16) of the de novo anti-DP antibodies were accompanied by another de novo DSA. Anti-DP antibody-positive patients had a higher rate of rejection (compared with anti-DP antibody-negative patients, P=.01). The estimated glomerular filtration rate declined more with anti-DP antibodies (-5.5% vs +26%). CONCLUSIONS: Antibodies against HLA-DP antigens are common. De novo anti-DP antibodies commonly appear after acute rejection and accompany DSA, which makes it difficult to determine whether anti-DP antibodies are the cause or the consequence of graft injury.

Neuropilin-1 modulates vascular endothelial growth factor-induced poly(ADP-ribose)-polymerase leading to reduced cerebrovascular apoptosis.

Cerebral ischemia is encompassed by cerebrovascular apoptosis, yet the mechanisms behind apoptosis regulation are not fully understood. We previously demonstrated inhibition of endothelial apoptosis by vascular endothelial growth factor (VEGF) through upregulation of poly(ADP-ribose)-polymerase (PARP) expression. However, PARP overactivation through oxidative stress can lead to necrosis. This study tested the hypothesis that neuropilin-1 (NP-1), an alternative VEGF receptor, regulates the response to cerebral ischemia by modulating PARP expression and, in turn, apoptosis inhibition by VEGF. In endothelial cell culture, NP-1 colocalized with VEGF receptor-2 (VEGFR-2) and acted as its coreceptor. This significantly enhanced VEGF-induced PARP mRNA and protein expression demonstrated by receptor-specific inhibitors and VEGF-A isoforms. NP-1 augmented the inhibitory effect of VEGF/VEGFR-2 interaction on apoptosis induced by adhesion inhibition through the αV-integrin inhibitor cRGDfV. NP-1/VEGFR-2 signal transduction involved JNK and Akt. In rat models of permanent and temporary middle cerebral artery occlusion, the ischemic cerebral hemispheres displayed endothelial and neuronal apoptosis next to increased endothelial NP-1 and VEGFR-2 expression compared to non-ischemic cerebral hemispheres, sham-operated or untreated controls. Increased vascular superoxide dismutase-1 and catalase expression as well as decreased glycogen reserves indicated oxidative stress in the ischemic brain. Of note, protein levels of intact PARP remained stable despite pro-apoptotic conditions through increased PARP mRNA production during cerebral ischemia. In conclusion, NP-1 is upregulated in conditions of imminent cerebrovascular apoptosis to reinforce apoptosis inhibition and modulate VEGF-dependent PARP expression and activation. We propose that NP-1 is a key modulator of VEGF maintaining cerebrovascular integrity during ischemia. Modulating the function of NP-1 to target PARP could help to prevent cellular damage in cerebrovascular disease.

Claudin-1 expression in cervical cancer.

Claudin-1 is a tight junction protein that has been demonstrated to be involved in tumorigenesis and tumor progression in various types of solid tumors. In the present study, the protein expression of claudin-1 in squamous cervical cancer tissues obtained from 106 patients was analyzed by immunohistochemistry. In addition, the grade of claudin-1 expression was analyzed for associations with certain clinicopathological parameters. A significant overexpression of claudin-1 was detected in the tumor cells, when compared with that in the peritumoral stroma. There was no significant association between claudin-1 expression and FIGO stage, tumor size, grading or the appearance of distant metastases. Cervical cancer patients scoring positive for claudin-1 protein expression tended to exhibit more lymph node metastasis (28.3%), compared with claudin-1-negative patients (7.1%). Regarding overall survival, the results of the present study suggest a better prognosis for claudin-1-negative patients. In order to elucidate whether claudin-1 overexpression has a significant prognostic impact on squamous cervical cancer, further studies are required.

Heart transplantation in an aging society: an analysis of 25 years of the OPTN/UNOS registry.

The annual number of adult heart transplantations in the United States is still low due to a lack of donor organs. Median long-term survival has been improved by about 1.7 years over the last 12 years. The aging of society is reflected in the United Network for Organ Sharing data, with more patients older than 70 years old receiving cardiac transplantation. The rate of acute rejection is higher in the group of younger patients, whereas older patients suffer from renal failure. They die more often from infection and malignancies, most likely due to immunosuppression. In the multivariate analysis, fewer factors are influencing their 5-year graft survival compared to that of younger patients. Increasing donor age raises their risk of death and graft failure by 1.8% per year of age. The long-term survival is significantly worse for the elderly, but the 1- and 5-year survival is acceptable. Therefore, heart transplantation in the elderly is still justified. Older patients need to be carefully selected, their immunosuppressive therapy needs to be adjusted, and they have to be monitored more closely concerning renal function, blood-levels of immunosuppressive drugs, infections, and malignancies to improve their survival.

Long-term results of endovascular aortic repair for thoracic pseudoaneurysms after previous surgical coarctation repair.

OBJECTIVES: Late aneurysm formation has been reported after every type of surgical coarctation repair in up to 10%, with rupture of such aneurysms being responsible for approximately 7% of all deaths. Secondary surgical repair carries a significant mortality (up to 15%) and morbidity rate (recurrent laryngeal nerve paralysis ∼20%, phrenic nerve injury ∼5%). According to the positive experience with endovascular therapy of atherosclerotic thoracic aortic aneurysms, it is worthwhile to evaluate the concept of minimally invasive endovascular stent grafting for secondary repair of postsurgical aneurysms. METHODS: Data were collected prospectively on consecutive patients who presented with postcoarctation false aneurysms. RESULTS: Since 1999, in a cohort of 210 endovascularly treated patients with thoracic and thoracoabdominal aortic pathologies, four patients with postcoarctation false aneurysms underwent endoluminal stent-graft placement. All of these procedures were technically successful without 30-day or one-year procedure-related mortality. After a follow-up of 71 months in median (range, 7-93 months; mean, 60.5 months), all aneurysms remain excluded without any endoleak. CONCLUSIONS: According to the current limited experience of small series, the endoluminal repair seems to be a promising alternative to redo open operations for postsurgical thoracic aneurysms associated with coarctation repair. Long-term follow-up of our small cohort confirmed the durability of the stent-graft treatment.