The Authors’ Reply: To NRP or Not to NRP, That Is the Question…
Bibliographic record
Abstract
We thank Ayorinde et al1 for their interest in our article2 and the editor for giving us the opportunity to clarify concerns. In our manuscript,2 we reported our initial experience with 46 consecutive controlled donors after circulatory death (cDCD) liver transplants (LTs) preserved with normothermic regional perfusion (NRP), presenting an 80% organ recovery rate and an outstanding low rate of complications (no cases of primary nonfunction or ischemic cholangiopathy [IC]). As the authors mentioned,1 it can be argued that the positive results could be partly justified by the short functional warm ischemia time due to premortem interventions or by a highly selected cohort. However, in the UK experience,3 they also presented excellent results with postmortem cannulation, despite a significantly longer functional warm ischemia time. Moreover, our donors cannot be considered highly selected, because our median donor age was 58 years (higher than that reported in other studies)2–4 and almost 30% were over 65 years of age. It is accepted that NRP allows a better evaluation of the graft according to liver function tests and macroscopic aspect. The authors suggest a randomized controlled trial between the rapid recovery (RR) and NRP to achieve evidence. Although it is not completely clear why NRP is beneficial, several experimental studies have demonstrated a replenishment of intracellular ATP that may help organs tolerate the subsequent cold ischemia.2,3 Moreover, RR and NRP have been recently retrospectively compared in 2 studies3,4 that demonstrate an evident benefit of NRP and even present NRP as an independent factor preventing IC. In addition, the use of NRP in Spain has significantly increased during the past years, currently being almost the only preservation system in cDCD. NRP also offers the advantage of being a relatively inexpensive technique that allows the perfusion of not only the liver but also the kidneys and pancreas and even combining with intrathoracic organ retrieval.5 Given the excellent results that we have experienced with NRP, it seems unlikely that any center would abandon NRP to perform RR and expose its recipients to a higher IC rate and graft loss. Therefore, the authors propose1 another trial comparing NRP and RR followed by ex situ machine perfusion (MP). Because NRP has shown superb results from its initial experiences,2 we do not consider NRP cDCD as marginal donors “per se,” rather donors that allow for a safe expansion of the donor pool. So, it seems to have no sense to associate MP. In our opinion, MP must still find its role in LT, although it seems to be useful in discard grafts. Our more extended experience with 83 NRP cDCD LTs has been recently presented in the International Liver Transplantation Society meeting in Toronto; primary nonfunction and IC rates remain 0% with a median follow-up of 24 months. In our opinion, although large trials would be advisable in the interest of evidence-based medicine, the results show that the benefits of NRP are so overwhelming that the adoption of the technique by worldwide active groups involved in cDCD LT is only a matter of time.
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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 | 0.005 | 0.043 |
| 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 | 0.003 | 0.004 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.021 | 0.027 |
| Insufficient payload (model declined to judge) | 0.006 | 0.006 |
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".