Improved function of islet grafts under steroid-free immunosuppression: will grafts work forever? Response to letter by Birkeland et al.
Bibliographic record
Abstract
Birkeland et al. raise an important issue regarding potential longevity of islet grafts, and illustrate their concerns with a single patient achieving insulin independence for 15 months, returned subsequently to small doses of insulin, and remaining C-peptide positive for more than 6 years. This patient received a relatively low engraftment mass (by current standards) of 9360 islet equivalent per kg prepared from two donors (i.e., 73% of the mean islet mass in the Edmonton series). Immunosuppression with thymoglobulin induction, and maintenance cyclosporine and mycophenolate had not been tested previously in islet transplantation, but credit for initial clinical testing of a steroid-free protocol in islet transplantation should be given to Ricordi et al., who in 1992 reported insulin independence after single-donor islet infusion after cluster transplantation, with up to 50% insulin independence at 1 year in nonautoimmune surgical diabetes (1). The partial loss of islet function at 15 months in Birkeland’s patient likely reflects rejection or recurrence of autoimmunity because the combination of cyclosporine/mycophenolate is generally regarded as less immunologically potent than tacrolimus/sirolimus (2). No one knows the true longevity of islet allografts. Gradual turnover of beta cells may prevent graft attrition over time, provided rejection and autoimmunity can be adequately controlled and exposure to diabetogenic medications is minimized (3). Long-term stable islet autograft function has been reported after 13 years (4), and islet allografts have continued to secrete C-peptide for longer than 6 years in previous steroid-based protocols (5). Currently in the Edmonton series, 85% of patients remain insulin free at 1 year (11/13), 80% (4/5) are insulin free after 2 years, and 96% of grafts (22/23) continue to secrete C-peptide. Only time will tell how long these grafts will really function, but recent data continue to provide room for optimism. James Shapiro Edmond Ryan Ray Rajotte Gregory Korbutt Norman Kneteman David Bigam Breay Paty Jonathan Lakey
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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 | 0.003 | 0.016 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.002 | 0.004 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.024 | 0.035 |
| Insufficient payload (model declined to judge) | 0.004 | 0.004 |
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".