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End to side nerve transfers; A systematic review of preclinical data
Matthew WT Curran, MD, MSc1,2, Simon Wu, B.Sc3, Julie Shatto, B.Sc3, Mithun Rajshekar, Ph.D3 and K. Ming Chan, MD4, (1)Plastic and Reconstructive Surgery, Brisbane Hand and Upper Limb Research Institute, Spring Hill, QLD, Australia, (2)Plastic and Reconstructive Surgery, Princess Alexandra Hospital, Woolloongabba, QLD, Australia, (3)University of Alberta, Edmonton, AB, Canada, (4)Division of Physical Medicine and Rehabilitation, University of Alberta, Edmonton, AB, Canada

Introduction: End to side (ETS) neurorraphy and its related nerve transfers including reverse end to sides (RETS) neurorraphy and side to side (STS) neurorraphy are being increasingly used clinically. Although being translated to clinical practice, there are still significant basic science questions about these models. We developed a systematic review to attempt to answer some of these knowledge gaps.
Methods: A systematic review was designed according the PRISMA guidelines. MEDLINE, Web of Science, Scopus and EMBASE data bases from 1994 to 2020 were searched. Search terms included "end-to-side", "nerve transfer", "animal" and derivatives of the terms with search limits that included "animal" and "English". This pool of articles was then used as a base for which four separate arms of the study were applied, each with its own inclusion criteria. These included: 1) End to end (ETE) versus ETS transfers; 2) effect of window size and neurectomy; 3) babysitting effect and lastly; 4) reverse end to side neurorraphy (RETS). On each study, the following characteristics (animal model, nerve model, number of animals and timeline) and outcomes (histomorphometry, retrograde labelling, electrophysiology, and weight muscle weights) were extracted and analyzed.
Results: A total of 403 articles were identified. Of those that met the inclusion criteria, 39 were in the ETE versus ETS arm; 28 in the window size arm; 16 in the babysitting arm and 12 in the RETS arm. Outcomes from the studies in the ETE vs ETS arm demonstrated that ETE nerve transfers were either or no difference to ETS. Depth of the window was found to have impact depending on the outcomes used. However, studies examining neurectomy demonstrated that animals with neurectomy consistently had better outcomes compared to animals with just a window. Of the 16 articles that were adequately designed to examine the babysitting effect, 88% of studies found improved regeneration of the native axons in the injured nerve. Histomorphometry was the most frequently reported outcome in the RETS group with the RETS group having higher axon counts than ETS transfers.
Conclusions: Nerve regeneration can occur in ETS neurorraphy especially with a partial neurectomy but the outcomes are inferior to ETE neurorraphy. The babysitting effect appears effective at improving nerve regeneration. RETS nerve transfers provide better outcomes than traditional ETS nerve transfers.


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