Abstract 385: Characterization of Cellular Infiltrate in Bioprosthetic Aortic and Mitral Valves
Bibliographic record
Abstract
Background: Bioprosthetic xenogeneic valves tend to deteriorate over time, termed structural valve deterioration (SVD), leading to valvular dysfunction. Several studies have hypothesized that SVD is a result of a chronic immune-mediated rejection process; however, a paucity of data exists demonstrating this conclusively. Objectives: Demonstrate that valves explanted for SVD contain a significantly greater burden of immune cellular infiltrate compared to normal human heart valves. Methods: Adult patients undergoing bioprosthetic aortic or mitral valve explantation secondary to a diagnosis of SVD were included in this study. A control arm included valves explanted from hearts without valvular disease considered for transplantation that were not utilized. Specimens underwent immunohistochemical staining using standard techniques utilizing the following primary monoclonal antibodies: anti-CD68, anti-CD20, and anti-CD3. Results: Eighteen valves explanted for SVD were analyzed along with 4 control valves. All valves were explanted from male patients with a mean age of 62-years. Overall, 12% (n=1) of patients had diabetes mellitus, 50% (n=4) had hypertension, 12% (n=1) had renal dysfunction and 38% (n=3) were on a lipid-lowering medication. Our results demonstrate that valves developing SVD have a cellular infiltrate containing significantly more immune cells than normal human valves. Specifically, there are significantly more CD3+ T-cells (p<0.05) and CD68+ macrophages (p<0.05) present in the cellular infiltrate of the SVD valves compared to the normal controls. Furthermore, while the cellular infiltrate of the SVD valves contains CD20+ B-cells, plasma cells, and neutrophils, none of these cells are present on the normal control valves (all p-values <0.05). Conclusions: Our data suggest a significantly greater immune cell infiltrate can be found in explanted bioprosthetic valves developing SVD than normal human valves, providing support for the chronic-immune mediated rejection hypothesis. This study will ultimately lead to a better understanding of the immune mechanisms responsible for SVD in bioprosthetic xenograft valves and will contribute to our goal of developing novel therapeutic techniques to mitigate development of SVD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".