Low levels of a natural IgM antibody are associated with vein graft stenosis and failure.

BACKGROUND: All humans have natural, protective antibodies directed against phosphorylcholine (PC) epitopes, a common inflammatory danger signal appearing at sites of cell injury, oxidative stress, and on bacterial capsules. In large human cohorts, low levels of anti-PC IgM were associated with a significantly increased risk of stroke or myocardial infarction. However, it is not known if these antibodies protect against the premature closure of arterial reconstructions. METHODS: A prospective, observational study of patients undergoing elective, infrainguinal, autogenous vein bypasses for atherosclerotic occlusive disease of the legs was conducted. Clinical data were recorded prospectively, and preoperative levels of anti-PC IgM measured with the CVDefine kit from Athera Biotechnologies (Solna, Sweden). The principal clinical end point was the loss of primary patency (loss of graft flow, or any intervention for stenosis). Patients were followed regularly by duplex ultrasound at 1, 3, 6, 12, 18 months, and yearly thereafter. RESULTS: Fifty-six patients were studied, for an average of 1.3 years. Indications for surgery were claudication (33.9%), ischemic rest pain (17.9%), and ischemia with ulceration or gangrene (48.2%). Seventeen (30.4%) patients experienced loss of primary patency (10 graft occlusions, seven surgical or endovascular revisions of graft stenoses). Kaplan-Meier survival analysis showed that the quartile of patients with the lowest anti-PC IgM levels had significantly worse primary graft patency (log-rank test, P = .0085). Uni- and multivariate Cox proportional hazards analysis revealed that the preoperative anti-PC IgM level was an important predictor of graft failure. Patients with IgM values in the lowest quartile had a 3.6-fold increased risk of graft failure (95% confidence interval: 1.1-12.1), even after accounting for other significant clinical or technical factors such as indication for surgery, site of distal anastomosis, or vein graft diameter. CONCLUSIONS: A naturally occurring IgM antibody directed against the proinflammatory epitope PC may be protective against vein graft stenosis and failure, through anti-inflammatory mechanisms. Measurement of this antibody may be a useful prognostic indicator, although larger studies of more diverse populations will be needed to confirm these results. The biological actions of anti-PC IgM suggest it may be useful in developing immunotherapies to improve bypass longevity.

An experimental model for improving fat graft viability and purity.

BACKGROUND: Autologous fat is an excellent soft-tissue filler, given its abundance, ease of harvest, and natural appearance. However, graft longevity is unpredictable and is reported in the literature to be between 3 months and 8 years. METHODS: A genetically identical, age- and sex-matched mouse experiment was used to develop a model. Inguinal fat pads were subjected to different harvest and preparatory techniques. Primary endpoints-viability and purity-were assessed with the trypan blue viability assay and component counting with a hemocytometer. RESULTS: Viability and purity were highest after excisional harvest versus blunt or needle harvest, presumably secondary to differences in cellular trauma. Saline wash or centrifugation after harvest produced modest but statistically significant improvements in viability and purity. However, if grafts harvested in any fashion were treated with an initial collagenase digestion followed by an idealized centrifugation regimen and a single wash step, viability and purity were consistently 96 percent and 93 percent, respectively. CONCLUSIONS: Using an in vitro murine model, the authors have systematically developed a clinically practical model for creating a pure single-cell suspension of viable adipocytes that is reproducible, regardless of tissue harvest method.