Effect of FK506 Administration on Functional Outcomes of Peripheral Nerve Surgery: A Systematic Review and Meta-Analysis
Giulia Daneshgaran, B.S., Albert Einstein College of Medicine, Bronx, NY; Keck School of Medicine of USC, Los Angeles, CA, Daniel J Gould, MD, PhD, Keck School of Medicine of University of Southern California, Los Angeles, CA, Mitchel Seruya, MD, Children's Hospital Los Angeles, Los Angeles, CA and Ketan M. Patel, MD, Division of Plastic and Reconstructive Surgery, University of Southern California, Los Angeles, CA
Purpose: Nerve grafting is often required in the repair of peripheral nerves injured by trauma or surgery if it is not possible to re-approximate the nerve ends without tension. Autograft repair results in improved outcomes in the setting of larger nerve gaps, but in cases of limited donor site availability, allograft repair is frequently the best reconstructive alternative. The use of FK506 in the setting of peripheral nerve allograft repair has shown promising results in animal models. However, whether FK506 improves outcomes in clinical studies has not yet been elucidated. To address this knowledge gap, we conducted a systematic review and corresponding meta-analysis to determine the effect of FK506 immunosuppression on motor and sensory outcomes in peripheral nerve surgery.
Methods: A systematic review of PubMed was conducted in February 2019 to identify all published literature on outcomes of peripheral nerve surgery. Records were split into one of two groups: 1) peripheral nerve surgery with FK506 immunosuppression (IS+ group), and 2) peripheral nerve surgery without FK506 immunosuppression (IS- group). Motor and sensory recovery were the main outcomes assessed, with mean outcomes statistically analyzed using a random effects model for meta-analysis.
Results: Our search identified 409 articles of which 28 met eligibility criteria. The IS+ group included 5 articles describing 51 patients, and the IS- group included 23 articles describing 324 patients. The IS+ group was associated with significantly improved motor outcomes, with a mean of 54.5% (95% CI, 23.3%-85.6%) of cases reporting motor recovery in contrast to 12.2% (95% CI, 4.2%-20.3%) of cases in the IS- group (p=0.01). A similar result was observed when assessing sensory outcomes, with 68.6% (95% CI, 34.1%-100%) of cases in the IS+ group reporting sensory recovery as opposed to 31.9% (95% CI, 23.6%-40.1%) of cases in the IS- group (p=0.04).
Conclusion: Cases of peripheral nerve surgery performed with an FK506 immunosuppressive protocol were associated with improved motor and sensory outcomes. In our study, the IS+ group had a statistically greater mean number of cases reporting motor and sensory recovery than the IS- group, suggesting that FK506 immunosuppression has a clinically favorable effect in the repair of injured peripheral nerves. Future studies are warranted to delineate the mechanism of this effect and to establish the use of FK506 immunosuppression in peripheral nerve repair as a clinical practice guideline.
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