Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI) for pain prevention in patients with limb amputation: a protocol for a systematic review and meta-analysis

ABSTRACT Introduction Regenerative Peripheral Nerve Interface (RPNI) and Targeted Muscle Reinnervation (TMR) are two reinnervation techniques which have shown clear superiority over classical amputation. It is mainly due to a lower incidence of painful neuromas, residual limb pain and phantom limb pain associated with these new procedures. However, they have never been compared to each other. Neither has their effectiveness been evaluated based on patients demographics, age, sex, comorbidities (diabetes, coronary heart disease, peripheral arterial disease, chronic kidney disease, congestive heart failure), amputations cause, type of amputation, amputation level, previous surgeries and if there was or not previous nerve division into fascicles. Therefore, the objective of this systematic review and meta-analysis is to compile all the evidence to date and provide a comprehensive view of what each technique offers. Methods and design The review will be conducted according to this protocol, following the recommendations of the ‘Cochrane Handbook for Systematic Reviews’. A comprehensive electronic search will be performed in: Cochrane Register of Controlled Trials (CENTRAL), Web of Science, Scopus, PubMed and MedRixb. This review will include randomized, quasi-randomized, and observational studies written in any language. We will use Covidence for assessing all titles and abstracts identified during the literature search. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Ethics and dissemination The proposed systematic review will collect and analyse data from published studies; therefore, it raises no ethical issues. The results of the review will be disseminated by publication in a peer-review journal and submitted for presentations at conferences. PROSPERO registration number CRD42024617299 STRENGTHS AND LIMITATIONS OF THIS STUDY - This will be the first systematic review to include a comparison between RPNI and TMR. - Through a comprehensive search and selection of high-quality articles, the best available evidence of RPNI and TMR against classical amputation will be gathered. - Gray literature and unpublished studies will be sourced from MedRixb aiming to reduce the impact of a possible publication bias. - Exclusion of non-English/Spanish papers may lead to language bias. PICO QUESTION Population Any adults (aged over 18 years) and gender with a superior or inferior limb amputation. Intervention Prophylactic Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI). Comparators Classical amputation. TMR vs RPNI. Outcomes 1) Incidence of neuroma, 2) Incidence of residual limb pain (RLP), 3) Severity of Pain 4) Incidence of phantom limb pain (PLP), and 5) Surgical complications (dehiscence, infection, haematoma and seroma).