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To better understand how different histologic patterns of allograft inflammation found on biopsies of human cardiac allografts progress to high-grade rejection, we undertook a statistical analysis of our institutional database to detect statistical patterns among different types of myocardial allograft inflammations found on sequential biopsies.Biopsies were analyzed for statistical associations between high-grade rejections (International Society of Heart and Lung Transplantation [ISHLT] grade ≥3A/4) and the type of cardiac allograft inflammation found on prior biopsies. Case cross-over and case control designs were used to compare the antecedent patterns of inflammation on biopsies with high-grade rejection compared to biopsies with low-grade rejection, all within the same subject. Quilty lesions were correlated with cyclosporine levels.Patients with Quilty B lesions or ISHLT grade 2/4 rejections show an increased risk for high-grade rejection on their next biopsies (Odds ratio 5.9 to 11.2). The presence of two pathological findings, especially Quilty B and grade 2/4 rejection, creates additional risk in excess of that found independently (Odds ratio >14). Quilty lesions are found only in cardiac allografts, and do not correlate with trough cyclosporine levels.The morphological patterns of several types of human cardiac allograft inflammation found on sequential protocol biopsies are not randomly associated. Patients with grade 2/4 rejections and Quilty B lesions show an increased risk for high-grade rejections on their next biopsies. Quilty B lesions, similar to ISHLT grade 2/4 rejections, may represent subclinical rejection. Both are more likely to progress to a high-grade rejection.