INSULIN INDEPENDENCE FOLLOWING TRANSPLANTATION OF CULTURED HUMAN ISLETS IN PATIENTS WITH TYPE 1 DIABETES: THE MIAMI EXPERIENCE
Bibliographic record
Abstract
O452* Introduction: Several clinical trials in islet transplantation are currently in progress utilizing fresh human islet allografts, including a multi-center trial. We proposed to assess the efficacy of in-vitro culture of human islets using an immunosuppression protocol similar to the one in Edmonton. Methods & Results: Fifteen consecutive patients (7 males, 8 females) with type 1 DM received human islet allografts isolated using automated method with minor modifications and cultured in Miami defined media and administered via ultrasound guided percutaneous transhepatic intraportal infusion. Immunosuppression consisted of daclizumab induction and sirolimus/tacrolimus maintenance. Fourteen patients became insulin independent (13 patients with 2 islet infusions and 1 patient with a single infusion); 1 patient was awaiting a second infusion but had to be discontinued from immunosuppression and will not be discussed below. First transplant (Tx) averaged 6919±1938 IEQ/kg (n=14; range 4592-12013) and second 7230±2031 IEQ/kg (n=13; range 3577-10306), with a total of 13633±3010 IEQ/kg (n=14; range 6250-18403). Insulin requirements pre Tx were 0.48±0.1 U/kg/day (n=13; range 0.29-0.58). At the present time 8 patients are insulin independent with stable islet allograft function and glycemic control 1009, 1008, 985*, 903*, 891, 796, 662 and 540 days post first islet infusion (*=3rd islet infusion). Four patients are currently on insulin (13±8 units or 37±26% of their pre tx requirements). Eight out of 14 patients have had deterioration of metabolic control requiring the reintroduction of insulin on post Tx day 381±110 (range 208-513). Five patients received a 3rd infusion. Two additional patients with deterioration of metabolic control were withdrawn from the trial (1 was lost to follow up and 1 discontinued immunosuppression due to intercurrent illness), There was no correlation between recurrence of autoimmunity and partial loss of graft function, but there was correlation with elevation of cytotoxic lymphocyte genes expression especially granzyme B in these patients. Conclusions: Human islet allografts cultured in Miami defined media resulted in insulin independence in 14 patients with normalization of glycemic control under steroid free immunosuppression regimen. However, there is a partial loss of islet function or islet mass as a function of time similar to what is seen with fresh islets. The mechanism(s) of this loss need(s) to be clarified. The introduction of supplemental infusions when this occurs may result again in insulin independence.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".