Citations

Background— Synthetic vascular grafts cannot be used in small vessels because of graft failure caused by thrombosis and neointima formation. Rapid endothelialization may overcome this limitation. We hypothesized that a magnetic graft would be able to capture and retain endothelial cells labeled with paramagnetic particles. Methods and Results— Porcine blood derived endothelial cells were allowed to endocytose superparamagnetic iron oxide microspheres. Cell survival was assessed by trypan blue exclusion and demonstrated a dose-dependent cell survival of 75% to 95%. A flexible magnetic sheet was annealed to the external surface of a knitted Dacron graft. Labeled cells (10 6 /mL) were placed within the graft for 5 minutes. Confocal and electron microscopy confirmed uniform cell capture at the magnetized surface. The effect of shear forces on the adherent cells was evaluated in a flow chamber. The cells remained attached at rates up to 300 mL/min, with cell loss commencing at 400 mL/min. Prototype magnetic grafts were implanted in porcine carotid arteries. Labeled cells were placed within the graft for 10 minutes at the time of implantation. The grafts were evaluated after one day and uniform cell coverage was noted on the magnetized surface. In comparison, relatively few labeled cells were seen attached to a nonmagnetized surface. Conclusions— Magnetic forces can be used to rapidly cover a vascular graft with paramagnetically labeled cells. This biophysical interaction is sufficient to retain cells in the presence of blood flow. Applications of this technique may include rapid endothelialization of synthetic vascular grafts and dialysis fistulas.

Background—There are few data regarding medium-term outcome of coronary artery bypass grafting (CABG) in patients with severe left ventricular (LV) systolic dysfunction, particularly in the modern era, and even less assessing preoperative factors that might identify patients at highest risk.Methods and Results—Three hundred seventy-nine consecutive patients with LV ejection fraction ≤35%, who underwent isolated first CABG between 1995 and 1999 were studied. Potential preoperative and perioperative predictors of outcome were recorded and patients followed-up for a median of 3.8 years. The primary study end-point was all-cause mortality. The 30-day, 1-year, and 3-year survival rates were 94.5%, 88%, and 81%, respectively. The independent predictors of mortality were preoperative estimated glomerular filtration rate (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97 to 0.99 per mL/min/1.73m2;P<0.001) and age (HR, 1.03; 95% CI, 1.01 to 1.06 per year;P=0.005).Conclusions—Patients with significant LV systolic dysfunction undergoing isolated CABG using contemporary techniques have a good medium-term survival. Renal dysfunction is the strongest independent predictor of mortality.

Background— The clinical profiles and outcomes of patients treated surgically for acute type B aortic dissection (ABAD) are often reported for those in small series or for those cared for at a single institution over a long time period, during which a continuous evolution in techniques has occurred. Accordingly, we sought to evaluate the clinical features and surgical results of patients enrolled in the International Registry of Acute Aortic Dissection by identifying primary factors that influenced surgical outcome and estimating average surgical mortality for ABAD in the current era. Methods and Results— A comprehensive analysis of 290 clinical variables and their relation to surgical outcomes for 82 patients who required surgery for ABAD (from a population of 1256 patients; mean±SD age, 60.6±15.0 years; 82.9% male) and who were enrolled in the International Registry of Acute Aortic Dissection was performed. The overall in-hospital mortality was 29.3%. Factors associated with increased surgical mortality based on univariate analysis were preoperative coma or altered consciousness, partial thrombosis of the false lumen, evidence of periaortic hematoma on diagnostic imaging, descending aortic diameter >6 cm, right ventricle dysfunction at surgery, and shorter time from the onset of symptoms to surgery. Factors associated with favorable outcomes included radiating pain, normotension at surgery (systolic blood pressure 100 to 149 mm Hg), and reduced hypothermic circulatory arrest time. The 2 independent predictors of surgical mortality were age >70 years (odds ratio, 4.32; 95% confidence interval, 1.30 to 14.34) and preoperative shock/hypotension (odds ratio, 6.05; 95% confidence interval, 1.12 to 32.49). Conclusions— The present study provides insights into current-day clinical profiles and surgical outcomes of ABAD. Knowledge about different preoperative clinical conditions may help surgeons in making treatment decisions among these high-risk patients.

AbstractB-lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) ligand superfamily. Although BLyS costimulates adaptive immune cells, the ability of BLyS to stimulate innate immune cells has not been described. Here, we show that BLyS strongly induces human monocyte survival, and activation as measured by proinflammatory cytokine secretion and up-regulation of costimulatory molecule expression. In addition, monocytes cultured with BLyS differentiated into macrophage-like cells. Regarding BLyS receptor(s) expression, freshly isolated monocytes bound low levels of exogenous BLyS and expressed primarily intracellular TACI, and cell surface TACI levels increased following monocyte activation. Of interest, bone marrow monocytes from some multiple myeloma patients expressed significant levels of cell surface TACI at isolation. Our findings indicate that BLyS plays a role in activating innate immune cells. Moreover, this study may explain more clearly why high BLyS production is often correlated with certain inflammatory autoimmune diseases and B-lymphocyte malignancies.

Abstract Rationale and Hypothesis Idiopathic pulmonary fibrosis is a fatal disease with a variable rate of progression. We hypothesized that changes in distance walked and quantity of desaturation during a six-minute-walk test (6MWT) would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide. Methods One hundred ninety-seven patients with idiopathic pulmonary fibrosis were evaluated. Desaturation during the 6MWT was associated with increased mortality even if a threshold of 88% was not reached. Baseline walk distance predicted subsequent walk distance but was not a reliable predictor of subsequent mortality in multivariate survival models. The predictive ability of serial changes in physiology varied when patients were stratified by the presence/absence of desaturation ⩽ 88% during a baseline 6MWT. For patients with a baseline saturation ⩽ 88% during a 6MWT, the strongest observed predictor of mortality was serial change in diffusing capacity for carbon monoxide. For patients with saturation &gt; 88% during their baseline walk test, serial decreases in FVC and increases in desaturation area significantly predicted subsequent mortality, whereas decreases in walk distance and in diffusing capacity for carbon monoxide displayed less consistent statistical evidence of increasing mortality in our patients. Conclusion These data highlight the importance of stratifying patients by degree of desaturation during a 6MWT before attributing prognostic value to serial changes in other physiologic variables.

The effect of external force environment on the healing of a partial thickness injury to canine flexor tendon was studied. A 50% laceration was made in either the fibrocartilaginous (compressive) zone or in the tendinous (tensile) zone of canine flexor digitorum profundus tendons. After three or six weeks, the tendons were harvested. An optical method for determining zone-specific material properties showed that, in response to injury, the structural stiffness decreased in the tensile zone of the tendon but increased in the compressive zone. The mechanical properties and failure mechanism of canine tendon and their changes in response to injury vary according to tendon zone, and differences in the healing process in mechanically specialised zones of the flexor tendon are discussed.

Abstract Smoking has been consistently associated with an increased risk of colorectal adenomas and hyperplastic polyps as well as colorectal cancer. Conversely, nonsteroidal anti-inflammatory drugs (NSAID) have been associated with reduced colorectal cancer risk. We conducted a population-based case-control study to evaluate the joint association between smoking and regular NSAID use with colorectal cancer risk; we also examined these associations stratified by tumor microsatellite instability (MSI). We analyzed 1,792 incident colorectal cancer cases and 1,501 population controls in the Seattle, Washington area from 1998-2002. MSI, defined as MSI high (MSI-H) or MSI-low/microsatellite stable (MSI-L/MSS), was assessed in tumors of 1,202 cases. Compared with nonsmokers, colorectal cancer risk was modestly increased among individuals who had ever smoked. Current NSAID use was associated with a 30% lower risk compared with nonusers. There was a statistically significant interaction between smoking duration and use of NSAIDs (Pinteraction = 0.05): relative to current NSAID users who never smoked, individuals who had both smoked for &gt;40 years and had never used NSAIDs were at the highest risk for colorectal cancer (adjusted odds ratio, 2.8; 95% confidence intervals, 1.8-4.1). Compared with nonsmokers, there was a stronger association within MSI-H tumors with current smoking than there was within MSI-L/MSS tumors. Smokers of long duration were at elevated risk of MSI-H tumors even with NSAID use. The risk of MSI-L/MSS tumors was not elevated among long-duration smokers with long exposure to NSAIDs but was elevated among long-duration smokers who had never used NSAIDs. There seems to be a synergistic inverse association (implying protection) against colorectal cancer overall as a result of NSAID use and nonsmoking, but risk of MSI-H colorectal cancer remains elevated among smokers even when they have a history of NSAID use. (Cancer Res 2006; 66(13): 6877-83)