Healing rates and outcomes following closed transmetatarsal amputations: A systematic review and random effects meta‐analysis of proportions

Transmetatarsal amputation (TMA) is a common surgical procedure for addressing severe forefoot pathologies, such as peripheral vascular disease and diabetic foot infections. Variability in research methodologies and findings within the existing literature has hindered a comprehensive understanding of healing rates and complications following TMA. This meta‐analysis and systematic review aims to consolidate available evidence, synthesising data from multiple studies to assess healing rates and complications associated with closed TMA procedures. Following Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines, a systematic search of Medline, Embase, and Cochrane databases was conducted for articles published from January 1st, 1988, to June 1st, 2023. Inclusion criteria comprised studies reporting healing rates in non‐traumatic transmetatarsal amputation patients with more than 10 participants, excluding open TMAs. Two independent reviewers selected relevant studies, with disagreements resolved through discussion. Data extracted from eligible studies included patient demographics, healing rates, complications, and study quality. Among 22 studies encompassing 1569 transmetatarsal amputations, the pooled healing rate was 67.3%. Major amputation rates ranged from 0% to 55.6%, with a random‐effects pooled rate of 23.9%. Revision rates varied from 0% to 36.4%, resulting in a pooled rate of 14.8%. 30‐day mortality ranged from 0% to 9%, with a fixed‐effects pooled rate of 2.6%. Post‐operative infection rates ranged from 3.0% to 30.7%, yielding a random‐effects pooled rate of 16.7%. Dehiscence rates ranged from 1.7% to 60.0%, resulting in a random‐effects pooled rate of 28.8%. Future studies should aim for standardised reporting and assess the physiological and treatment factors influencing healing and complications.

Transmetatarsal amputation (TMA) is a surgical procedure commonly performed to address severe forefoot pathologies, including peripheral vascular disease and diabetic foot infections.The healing rates and associated complications following TMA are critical factors in determining the success of the procedure and the subsequent outcomes for patients.However, the existing literature on healing rates and complications following TMA is characterised by variations in methodologies, sample sizes, and inconsistent operational definitions and findings.Therefore, this meta-analysis and systematic review aims to provide a comprehensive evaluation of the available evidence, synthesising data from multiple studies to determine the healing rates and identify potential complications associated with TMA procedures.

| Data sources and searches
This systematic review and meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. 1A systematic literature search of Medline, Embase, and Cochrane was performed for articles published from database January 1st, 1988 to June 1st, 2023, using a combination and variation of the terms ('Transmetatarsal Amputation') OR ('Transmetatarsal Outcome(s)') OR ('Midfoot Amputation') OR ('TMA') AND ('Healing' OR 'Success' OR 'Healed').For each database, a specific search was generated and converted accordingly.We included only studies published in the English language.No institutional review board approval was required for the current study.

| Inclusion and exclusion criteria
We included only studies that reported healing rates in patients undergoing non-traumatic transmetatarsal amputation.Studies with less than 10 participants were excluded.Studies involving open transmetatarsal amputations or guillotine amputations were excluded.We did impose a restriction on the year of publication, we included only studies published within the last 35 years to include more recent evidence.We imposed no restrictions on publication status.Non-English language studies were excluded.Two independent reviewers (T.L.C and E.A.) selected relevant studies.Where a consensus was not reached, disagreements were resolved through discussion.

| Data analysis
Data analysis was done using R version 3.6.3(R Foundation for Statistical Computing, Vienna, Austria), using the meta and metafor package.The primary outcome (healing rate) and secondary outcomes (major amputation, revision, 30-day mortality, infection, and dehiscence) were reported with 95% confidence intervals (95% CI) and analysed using a random-effects model or fixed-effects model.The type of model chosen was dependent on the heterogeneity among studies.To quantify heterogeneity, we utilised Higgin's & Tompson's I 2 statistic. 3Low heterogeneity was defined as I 2 < 50%, moderate heterogeneity as I 2 = 50%-75%, and high heterogeneity as I 2 > 75%.
For variables with low heterogeneity, a fixed-effects model was used.
For variables with moderate or high heterogeneity, a random-effects model was chosen to account for the variability among studies.
Publication bias was evaluated using Begg's test. 4| RESULTS

| Study selection
Four-hundred and thirty-three citations were identified after the removal of duplicates.Following the title and abstract screening, 110 citations were assessed for full text eligibility.Of these, 81 studies T A B L E 1 General criteria and definitions for outcomes reported among included studies.were excluded which did not include healing rates or included open TMAs (transmetatarsal amputation).This resulted in 22 studies included in the final analysis (Figure 1). 5-26

| Study characteristics and quality
Study characteristics are summarised in Tables 2 and 3
A summary of all the results can be seen in Table 4.

| DISCUSSION
Understanding the specific complications associated with TMAs is crucial for informed consent, decision-making, optimising surgical techniques, implementing effective post-operative care protocols, and identifying unmet needs for quality improvement.Complications such as wound infection, major amputation, revision surgeries, and dehiscence can significantly impact patient recovery, quality of life and overall outcomes.Unfortunately, some of this information is not routinely reported in the literature.Only five studies reported infection or dehiscence out of the 22 included in the analysis.None reported hematoma complications.Only 14 studies reported the need for surgical revision.
T A B L E 2 Summary of included studies.F I G U R E 2 Forest plot of proportion of patients with reported healed TMA.

| Comparing transmetatarsal amputation to major amputation healing rates
Our review found a TMA healing rate of 67%.[29][30][31] 4.2 | Comparing transmetatarsal amputation and major amputation 30-day mortality Our 30-day mortality of 2.6% are similar to the findings of a recent meta-analysis of mortality following minor lower extremity amputations which found a pooled 30-day mortality rate of 3.5%. 32This mortality rate is lower than the 30-day mortality rate reported for major F I G U R E 6 Forest plot of proportion of patients with reported post-operative infections.
F I G U R E 5 Forest plot of proportion of patients with reported mortality within 30-days following TMA.

| Comparing transmetatarsal major amputation conversion and revision rates
Our findings of major amputation conversion (24%) do differ from a previous meta-analysis of transmetatarsal amputations by Thorud. 34 their meta-analysis, they reported major amputation rates of When comparing TMA-to-BKA/AKA conversion rate to the conversation rate of a BKA to an AKA, the rate appears to be similar. [38]

| Comparing transmetatarsal amputation and major amputation stump complications
We found a post-operative infection and dehiscence rate of 17% and 29%, respectively.0][41][42] However, only five studies reported infection and dehiscence rates following a TMA in this review and therefore we cannot make a fair comparison.

T A B L E 4
Outcomes of interest for transmetatarsal amputations.
Summary of reported outcomes in included studies.
Note: N, number of patients; NR, not reported; TMA, number of transmetatarsal amputations.T A B L E 3Note: N, number of patients; NR, not reported; TMA, number of transmetatarsal amputations.
Forest plot of proportion of patients with reported post-operative incision dehiscence.
a Random effects model.bFixed effects model.F I G U R E 7