Therapeutic interventions for acute complete ruptures of the ulnar collateral ligament of the thumb: a systematic review

Background: The aim of this study was to evaluate the effectiveness of interventions for acute complete rupture of the ulnar collateral ligament (UCL) of the thumb in adults. Methods: The following databases were searched: MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO, from database inception to 31 st January 2018. Inclusion criteria were: (i) randomised controlled clinical trials (RCTs) or study of intervention with a comparator; (ii) participants with diagnosis of acute complete rupture of the UCL of the thumb; (iii) participants aged 18 years of age or older at enrolment; and (iv) published in a peer-reviewed English-language journal. Results: In total, six studies were identified for inclusion after screening. All studies had a high risk of bias. Three studies were retrospective comparative case series which compared two different surgical techniques (bone anchor versus pull out suture, suture versus pull out suture, suture versus steel wire). Of these studies, three were RCTs, two of which compared different rehabilitation regimes in patients managed surgically (plaster versus early mobilization, new spica versus standard spica). The remaining RCT compared two different rehabilitation regimes in a mixed group of surgically/non-surgically treated patients. The RCT comparing a standard spica with a new spica demonstrated a statistically significant improvement in outcomes with the new spica at all time points (range of motion, Dreiser index and VAS); this was also the only study to provide sufficient outcome data for further analysis. Conclusion: There is no prospective evidence comparing surgery to non-operative treatment for acute complete ruptures of the ulnar collateral ligament of the thumb. There is weak evidence to suggest that early mobilisation may be beneficial following surgical repair. Further research is necessary to better define which patients benefit from which specific interventions.


Introduction
Acute complete ruptures of the ulnar collateral ligament (UCL) of the thumb are common injuries, accounting for around 50 in 100,000 presentations to Accident and Emergency departments. There is controversy as how to manage complete ruptures of the UCL best, although there is a degree of consensus regarding the broader treatment algorithm and general agreement that 'true' Stener lesions should be managed operatively 1,2 . The rate of the Stener lesion varies widely in the literature, perhaps reflecting the lack of reliability and accuracy of the various methods of diagnosis 3,4 .
Patients should be assessed clinically to determine the degree of instability of the metacarpophalangeal joint (MCPJ) in both extension and 30° of flexion to test both proper and accessory collateral ligaments 5 . There is some evidence to suggest that the greater the instability the higher the chances are that a Stener lesion is present 6,7 . While there is evidence to support both the use of ultrasound and MRI, the latter appears slightly superior in terms of sensitivity and specificity [8][9][10] . A recent study by Stoop et al. investigated which factors predict the chances of surgery in UCL injuries 11 . It was found that not only did patient characteristics influence the chances of surgery, but that the individual surgeon's preference was also predictive.
Our aim was to perform a systematic review of the effectiveness of available interventions for acute complete rupture of the ulnar collateral ligament of the thumb in terms of patient-reported outcome measures and to assess the rates of adverse outcomes associated with these interventions.

Methods
The systematic review was developed in accordance with the PRISMA statement (Supplementary File 1 contains a completed PRISMA checklist), using methodology decribed in the Cochrane Handbook for Systematic Reviews of Interventions. The protocol was developed prospectively and peer reviewed locally before registration on the PROSPERO database (CRD42018087656). Inclusion/exclusion criteria The inclusion and exclusion criteria were defined prospectively during the protocol stage. Any study relating to acute complete ruptures of the ulnar collateral ligament of the thumb MCPJ in adults was included. Studies had to contain an intervention and a comparator (i.e. both non-randomised controlled trials, and randomised controlled trials, including semi/quasi randomised, cluster randomised trials and comparative case series). Any therapeutic intervention or control treatments were included.

Selection of studies
Duplicates were removed and relevant studies identified from the search were imported into Covidence for screening. Studies were independently screened by title and abstract by two authors (B.J.F.D. and M.M.). This was followed by a full-text evaluation of the selected studies from the first selection step these authors. Disagreement between the two reviewers was solved by consensus involving a third author (J.C.R.W.).

Data extraction
Two reviewers (M.M. and B.J.F.D) independently extracted data. Data was extracted using a custom data extraction sheet in Covidence. Any inconsistencies between the two reviewers' forms were resolved by consensus discussion. A third review (J.C.R.W.) was available for any disagreement that could not be resolved by this initial discussion.
If data was not available from full-text articles or trial registrations, authors were contacted to provide this information. If authors were not contactable as regards additional data, then this aspect of the study was excluded from the data synthesis. If contactable authors did not respond to initial requests, they were sent two subsequent reminders over a minimum of 6 weeks. If there was still no response for the additional data, then this aspect of the study was excluded from the data synthesis.

Risk of bias assessment
Included studies were assessed for risk of bias by two independent raters (B.J.F.D. and M.M.) using the Cochrane Collaboration's tool for assessing risk of bias in randomised trials 12 . This followed the description in the Cochrane Handbook for Systematic Review of Interventions, version 5.1 (Part 2: 8.5.1) 12 . Any disagreements between ratings were resolved by discussion between the raters. A third party (J.C.R.W.) was available in any case where disagreements persisted after discussion.

Data analysis
Descriptive analysis was performed for all demographic, intervention and outcome data to facilitate narrative interpretation and comparison across studies. It was decided that a directcomparison meta-analysis would only be performed if data was available for similar time-points, outcomes and interventions across two or more studies. As this was not possible with the identified studies, we conducted a narrative synthesis of the results based on the domains of interest.

Results
A total of 158 studies were identified by the search, after duplicates were removed. After screening by full-text, six studies were identified as eligible for inclusion ( Figure 1). Of these, three were randomized controlled trials (RCTs), and three were retrospective comparative case series. The number of studies identified and excluded at each stage is detailed in Figure 1. Study characteristics of the included trials including the interventions and comparators are provided in Table 1. Of the three randomised controlled trials, two assessed the outcomes of different rehabilitation regimes in patients who had been exclusively treated with surgery 13,14 . The remaining RCT assessed the outcome in patients managed both surgically and non-surgically, who were randomised to treatment with either a plaster cast or a functional splint 15 . All three retrospective comparative case series compared different surgical techniques in patients exclusively managed surgically [16][17][18] .  there was one complication with the traditional method (broken pull-out suture at 2 weeks) and one with the new method (re-rupture at 9 months) The study by Katolik et al 16 . demonstrated a higher complication rate with pull-out suture versus bone anchor repair, but this was not statistically significant (risk ratio, 4.00; 95% CI, 0.92-17.30); all the ten complications were soft-tissue-related (five were persistent wound erythema consistent with wound infection and five were paraesthesiae, which resolved over time).

Risk of bias
All criteria were judged as low, high or unclear risk of bias.
Overall, all studies were deemed to be at a high risk of bias, particularly in terms of blinding of outcome assessment and selecting reporting. Full risk of bias assessment is available in Figure 2 and Figure 3.

Meta analysis
As a result of the degree of heterogeneity in terms of study interventions and the incomplete outcome data, it was determined that a meta-analysis of the outcomes was not possible. We carried out a meta-analysis of the complications of pull-out suture versus bone anchor, as two studies had compared these different surgical techniques 16,17 . The complication rate of pull out suture fixation was higher than that of bone anchor repair (risk ratio, 3.92; 95% CI, 1.07-14.32; P=0.04). Although suggesting a higher rate of complication, this should be interpreted with caution due to the high risk of bias in the included studes, reducing the reliability of the data and subsequent meta-analysis.

Discussion
The key finding of this systematic review is that is that no study exists comparing non-operative to surgical intervention in the treatment of complete ruptures of the UCL of the thumb. The only studies which have compared interventions are at high risk of bias, particularly in the areas of blinding of outcome assessment and selective outcome reporting. There is weak evidence to suggest that early mobilisation of the thumb MCPJ may be beneficial following surgical repair. There is weak evidence that the pull out suture fixation has a higher rate of adverse events when compared to bone anchor repair.
A systematic review by Samora et al. summarised the outcomes after both non-operative and operative treatment of complete UCL ruptures 19 . They found that the vast majority of the evidence base was low quality retrospective case series and that only a small minority of patients were treated non-operatively. It was also shown that there was no significant difference in outcome between repair of acute injury and reconstruction after chronic injury. There is a widely varying rate of Stener lesions in the literature, it being as low as 12% in the series by Pichora et al. 20 and as high as 70% in other series 21 . The reasons underlying the variability in the rate of the Stener lesion are likely multiple and complex. One aspect of this conundrum appears to be the clear problems with the reliability and accuracy of the radiological diagnosis of the Stener lesion, particularly relating to MRI 3 .  Although there are some high quality studies describing the reliability of ultrasound, there are no high quality studies relating to MRI 3 . Mahajan et al. demonstrated excellent agreement between radiologists in determining whether the UCL had completely ruptured; however, the presence or absence of a Stener lesion was not assessed radiologically 6 . Milner et al. have recently argued that any displacement of greater than 3 mm (grade 3 by their system) should be treated operatively, owing to the observed high chance that these patients will fail with non operative treatment 9 .
The recent study by Stoop et al. assessed 383 UCL injuries treated at three different hospitals in a singe American city 11 . In total, 30% of cases were avulsion fractures and 11% of cases were investigated with an MRI scan. Certain patient characteristics were associated with a higher rate of operative intervention, for example greater age and more displaced fractures. However some factors which were unrelated to patient characteristics were predictive of operative intervention, such as having an MRI and being treated by certain surgeons. It was felt that because the preoperative diagnosis of a Stener lesion has limited reliability and accuracy, the rates of surgery may vary based on surgeon beliefs, preferences and values.They also stated that "some surgeons believe some non-Stener injuries benefit from operative treatment" 11 .
This review has demonstrated that all six studies of an intervention with a comparator in UCL treatment are at high risk of bias. The blinding of participants would clearly not be possible in a trial of surgery versus non operative treatment; however, it is a recurrent theme that outcomes were assessed by non-blinded assessors (often the treating surgeon), which significantly increases the chance that detection bias will influence patient outcomes. None of the RCTs published a trial protocol with a specified primary outcome, while only the study by Rocchi et al. 14 used validated patient-reported outcome measures (Dreiser index and VAS). There was also a failure to adequately report all outcomes, with only one study reporting adequate data for all outcomes to allow further analysis. None of the three RCTs included a power calculation. While the retrospective nature of the comparative case series introduces several potential sources of bias which may have influenced these results.

Conclusions
There is no prospective randomised or observational evidence to support operative intervention compared to non-operative treatment for acute complete ruptures of the ulnar collateral ligament of the thumb. There is weak evidence to suggest that early mobilisation may be beneficial following surgical repair. Further research is necessary in order to better define which patients benefit from which specific interventions.

Data availability
All data underlying the results are available as part of the article and no additional source data are required.
1. The authors aim was to perform a systematic review of the effectiveness of available interventions for acute complete rupture of the ulnar collateral ligament of the thumb in terms of patient-reported outcome measures and to assess the rates of adverse outcomes associated with these interventions.

Open Peer Review
Their methodology appears overall sound, however I have some concerns over their request for additional data from the authors of the selected papers. If this data was not included in the original papers how can it be accepted retrospectively.
Overall the authors have achieved their aim of the systematic review however they have added a large amount of extra data particularly concerning diagnosis (MRI and US). In general I think the paper has merit to be published but in their stated aim the authors should include that they reviewed the literature concerning diagnosis as well.
11th June 2018: The status of this report has been updated from 'Approved with reservations' to 'Approved' in response to the . author comments I thank the authors for their comments and accept that no additional data was either sourced or utilised. Also, I accept their comments on the diagnostic component in the article and accept that on balance it is useful in its contribution to the overall aim.

Is the statistical analysis and its interpretation appropriate? Not applicable
Are the conclusions drawn adequately supported by the results presented in the review? Yes No competing interests were disclosed.

Competing Interests:
I have read this submission. I believe that I have an appropriate level of expertise to confirm that I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
Overall this is a well written paper, of publishable standard, describing poor quality data which is of particular value to researchers planning new studies investigating or designing new studies concerning the ulnar collateral ligament.

Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes
Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required.

Are the conclusions drawn adequately supported by the results presented in the review? Yes
No competing interests were disclosed.

Competing Interests:
I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
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