CT Perfusion ASPECTS in the Evaluation of Acute Ischemic Stroke: Thrombolytic Therapy Perspective

Background and Purpose: Advances in the management of acute ischemic stroke and medical imaging are creating pressure to replace the rigid one-third middle cerebral artery (MCA) and non-contrast-enhanced CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) thresholds used for the selection of patients eligible for intravenous thrombolytic therapy. The identification of potentially salvageable ischemic brain tissue lies at the core of this issue. In this study, the role of CT perfusion ASPECTS in the detection of reversible ischemia was analyzed. Materials and Methods: We retrospectively reviewed the clinical and imaging data of 92 consecutive patients who received intravenous thrombolytic therapy for acute (duration Results: A perfusion defect could be detected in 50% of the patients. ASPECTS correlated inversely with the clinical outcome in the following order: follow-up NCCT > cerebral blood volume (CBV) > mean transit time (MTT) > admission NCCT. The follow-up NCCT and the CBV displayed a statistically significant difference from the admission NCCT, while the MTT did not reach statistical significance. The threshold that best differentiated between good and bad clinical outcome on admission was CBV ASPECTS ≧7. In patients with CT perfusion ASPECTS mismatch, MTT and CBV ASPECTS essentially provided the lower and upper limits for the follow-up NCCT ASPECTS, thus defining the spectrum of possible outcomes. Furthermore, CT perfusion ASPECTS mismatch strongly correlated (r = 0.83) with the mismatch between the tissue at risk and the final infarct, i.e. the amount of salvaged tissue. This finding suggests that the CT perfusion ASPECTS mismatch adequately identifies the amount of potentially salvageable ischemic brain tissue. Conclusions: Parameters derived from the use of CT perfusion ASPECTS can detect reversible ischemia and are correlated with clinical outcome

Surgery of non-spinal skeletal metastases in renal cell carcinoma

Background and purpose - Surgery for metastases of renal cell carcinoma has increased in the last decade. It carries a risk of massive blood loss, as tumors are hypervascular and the surgery is often extensive. Preoperative embolization is believed to facilitate surgery. We evaluated the effect of preoperative embolization and resection margin on intraoperative blood loss, operation time, and survival in non-spinal skeletal metastases of renal cell carcinoma. Patients and methods - This retrospective study involved 144 patients, 56 of which were treated preoperatively with embolization. The primary outcome was intraoperative blood loss. We also identified factors affecting operating time and survival. Results - We did not find statistically significant effects on intraoperative blood loss of preoperative embolization of skeletal non-spinal metastases. Pelvic localization and large tumor size increased intraoperative blood loss. Marginal resection compared to intralesional resection, nephrectomy, level of hemoglobin, and solitary metastases were associated with better survival. Interpretation - Tumor size, but not embolization, was an independent factor for intraoperative blood loss. Marginal resection rather than intralesional resection should be the gold standard treatment for skeletal metastases in non-spinal renal cell carcinoma, especially in the case of a solitary lesion, as this improved the overall survival.Peer reviewe

Autoimmune regulator induced changes in the gene expression profile of human monocyte-dendritic cell-lineage.

The autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymic medullary epithelial cells and in the cells of the monocyte-dendritic lineage both in the thymus and in the secondary lymphoid organs. Mutations in the AIRE gene cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a recessively inherited disease characterized by loss of immunological self-tolerance to multiple endocrine organs. Recent mouse knockout studies suggest that AIRE is responsible for ectopic expression of peripheral self-antigens in the thymus. In the present study, we detected an increased level of endogenous AIRE expression during the differentiation process of the human monocyte derived dendritic cells (MoDCs). We subsequently identified candidates for AIRE-regulated genes by using cDNA microarray technology to analyse the changes in the gene expression profile brought about by overexpressing the AIRE protein in the monocytic U937 cells. The changes observed resembled those previously reported to occur during the maturation of DCs, including up-regulation of the CCL22, CD25, ICAM-1 and RelB genes. In contrast, increased expression of the steroidogenic enzymes P450c17, P450c21 and P450scc, the major autoantigens in APECED, was not found either in our cell model or in the dendritic cell cultures. We also identified the ERK signal transduction pathway as a candidate for mediating the signal that results in the altered expression profile. Our findings suggest that the role of AIRE in the DCs differs from its function in the thymus