Abstract
Introduction
Robotic transanal minimally invasive surgery (R-TAMIS) was introduced in 2012 for the excision of benign rectal polyps and low grade rectal cancer. Ergonomic improvements over traditional laparoscopic TAMIS (L-TAMIS) include increased dexterity within a small operative field, with possibility of better surgical precision. We aim to collate the existing data surrounding the use of R-TAMIS to treat rectal neoplasms from cohort studies and larger case series, providing a foundation for future, large-scale, comparative studies.
Methods
Medline, EMBASE and Web of Science were searched as part of our review. Randomised controlled trials (RCTs), cohort studies or large case series (≥ 5 patients) investigating the use of R-TAMIS to resect rectal neoplasia (benign or malignant) were eligible for inclusion in our analysis. Quality assessment of included studies was performed via the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, operative details and histopathological/oncological outcomes.
Results
Eighteen studies on 317 participants were included in our analysis. The quality of studies was generally satisfactory. Overall complication rate from R-TAMIS was 9.7%. Clear margins (R0) were reported in 96.2% of patients. Local recurrence (benign or malignant) occurred in 2.2% of patients during the specified follow-up periods.
Conclusion
Our review highlights the current evidence for R-TAMIS in the local excision of rectal lesions. While R-TAMIS appears to have complication, margin negativity and recurrence rates superior to those of published L-TAMIS series, comparative studies are needed.
Supplementary Information
The online version contains supplementary material available at 10.1007/s00384-024-04645-4.
Keywords: Robotic surgery, Minimally invasive surgery, Rectal neoplasia, TAMIS
Introduction
Robotic transanal minimally invasive surgery (R-TAMIS) was introduced in 2012 for the excision of benign rectal polyps and low grade rectal cancer [1]. Robotic platforms offer the benefits of wristed articulation, 3D optics and improved ergonomics, combatting issues posed by traditional laparoscopic TAMIS (L-TAMIS) [2, 3]. Theoretical benefits of R-TAMIS include superior oncologic resections and increased dexterity, via fine motion scaling and articulated instruments respectively [4]. Similarly, the use of a robotic platform averts the need of an active surgical assistant in the already confined work space [5].
Despite promising reports in the literature, there is a void of large comparative studies, particularly comparing peri-operative and oncological outcomes between R-TAMIS and L-TAMIS [5]. In addition, most of the current literature on R-TAMIS are small series or individual case reports, limiting the power and interpretation of results [6–13]. We aim to collate the existing data surrounding the use of R-TAMIS to treat rectal neoplasms from cohort studies and larger case series, providing a foundation for future, large-scale, comparative studies.
Methods
Study design and reporting guidelines
This study is a systematic review of randomised and non-randomised trials and follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines.
Search strategy
The following databases were searched as part of the systematic review in October 2023: Medline, EMBASE and Web of Science. The terms included (R-TAMIS OR TAMIS OR Transanal OR Trans-anal) AND (Rect*). The last date of search was 1st of October 2023. The grey literature was also searched to further identify other suitable publications.
Inclusion criteria
The studies were assessed for eligibility based on the following inclusion criteria. Randomised controlled trials (RCTs), cohort studies or large case series (≥ 5 patients) investigating the use of R-TAMIS to resect rectal neoplasia (benign or malignant) were eligible for inclusion in our analysis.
Study selection, data extraction and critical appraisal
A database was created using the reference managing software EndNote X9™. Two researchers (NOS and HCT) reviewed outputs from the searches independently of each other.
Initially, duplicates were removed. The study titles were then screened and assessed for potential relevance. The abstracts of selected potential studies were then read and assessed for eligibility for inclusion, based on the inclusion/exclusion criteria detailed above. The rejected studies were grouped together in the database by their reason for exclusion. The full texts of the abstracts deemed eligible for inclusion were then further analysed using the same criteria.
In order to extract and store data efficiently, the Cochrane Collaboration screening and data extraction tool, Covidence, was used [14]. Data was collected by two reviewers (NOS and HCT) independently, using the following headings: study details, study design, population, intervention, comparison groups and outcomes. Conflicts between the two reviewers were resolved following an open discussion and a final decision by the senior author (MK).
Assessment of potential biases for the non-RCT studies was assessed using the Newcastle–Ottawa scale (NOS) risk of bias tool, and the results were tabulated. This assessment tool grades each study as being ‘satisfactory’ or ‘unsatisfactory’ across various categories. We assigned stars to evaluate study quality: 7 stars, ‘very good’; 5–6 stars, ‘good’; 3–4 stars, ‘satisfactory’; and 0–2 stars, ‘unsatisfactory’. The critical appraisal was completed by two reviewers independently (NOS and HCT), where once again a third reviewer (MK) was asked to arbitrate in cases of discrepancies in opinion.
Systematic review registration
Our systematic review was registered on PROSPERO in October 2023 (470657).
Results
Search results
The literature search described above yielded a total of 782 results (Supplementary Material S1). Following the removal of 163 duplicates, 619 studies were screened. After the initial screening, 53 abstracts were reviewed and assessed for eligibility, of which 30 were selected for full-text review. From these 30 full texts, a total of 18 studies met the inclusion criteria and were included in our analysis.
Methodological characteristics and quality of studies
Seven of the included studies were cohort studies; one prospective, six retrospective [1, 5, 15–19]. The remaining 11 studies were case series [11, 20–29]. Lee et al. provided a comparison of outcomes between L-TAMIS and R-TAMIS in their comparative study [5]. Table 1 summarises the methodological characteristics of the included studies.
Table 1.
Methodological characteristics of the included studies
| Study | Country | Journal | Impact factor | Study type |
|---|---|---|---|---|
| Atallah et al. [20] | USA | Techniques in Coloproctology | 3.5 | Case series |
| Baker et al. [15] | Australia | Colorectal Disease | 3.4 | Prospective cohort study |
| Fok et al. [21] | Australia | International Journal of Medical Robotics and Computer Assisted Surgery | 2.5 | Case series |
| Hompes et al. [22] | UK | British Journal of Surgery | 5.6 | Case series |
| Huang et al. [16] | Taiwan | Asian Journal of Surgery | 3.5 | Retrospective cohort study |
| Lee et al. [5] | USA | Surgical Endoscopy | 3.5 | Retrospective cohort study |
| Liu et al. [18] | USA | Surgical Endoscopy | 3.5 | Retrospective cohort study |
| Liu et al. [23] | USA | Techniques in Coloproctology | 3.5 | Case series |
| Liu et al. [17] | USA | Updates in Surgery | 2.7 | Retrospective cohort study |
| Lo et al. [24] | USA | Surgical Endoscopy | 2.5 | Case series |
| Marks et al. [1] | USA | Diseases of Colon and Rectum | 3.9 | Retrospective cohort study |
| Ngu et al. [25] | Taiwan | International Journal of Medical Robotics and Computer Assisted Surgery | 2.5 | Case series |
| Paull et al. [26] | USA | Journal of Robotic Surgery | 2.3 | Case series |
| Ruiz et al. [29] | Spain | Cirugia Espanola | 1.9 | Case series |
| Tomassi et al. [19] | USA | Diseases of the Colon and Rectum | 3.9 | Retrospective cohort study |
| Warren et al. [11] | Australia | Techniques in Coloproctology | 3.5 | Case series |
| Wassef et al. [27] | USA | Journal of Gastrointestinal Surgery | 3.2 | Case series |
| Yao et al. [28] | China | Surgical Innovation | 1.5 | Case series |
In regards to quality assessment, seven studies were ‘very good’, nine studies were ‘good’, two studies were ‘satisfactory’ and zero studies were ‘unsatisfactory’ when scored using the Newcastle–Ottawa Scale risk of bias tool. Supplementary Material S2 summarises the results of our risk of bias assessment.
Participant characteristics
The total number of participants from the 18 included studies was 317. The median follow-up across studies was 30 months (range 12–63). Basic participant characteristics are presented in Table 2. Indications for R-TAMIS included resection of benign neoplasia, early malignant lesions, lesions unresectable by endoscopy and select T2/T3 lesions in patients unfit for or unwilling to proceed with radical surgery.
Table 2.
Basic participant characteristics
| Study | Patients | Male:Female | Age (mean +/− SD) | BMI | Pre-operative diagnosis |
|---|---|---|---|---|---|
| Atallah et al. [20] | 9 | 4:5 | 65 | 26 | Benign neoplasia of rectum not amenable to endoscopic retrieval, selected T1 lesions, T2/T3 lesions in unfit patients |
| Baker et al. [15] | 11 | 6:5 | 70 +/− 12 | 26 |
‘Rectal lesions identified on colonoscopy’ 6 Invasive, 5 other |
| Fok et al. [21] | 5 | 5:0 | 67 | - | Benign rectal polyps or T1 tumours |
| Hompes et al. [22] | 15 | 8:8 | 65 +/− 14 | 28 +/− 5 | ‘Rectal lesions’ |
| Huang et al. [16] | 23 | 11:12 | 60 +/− 13 | 24 +/− 3 | Early rectal cancer T1 or cCR after CRTx |
| Lee et al. [5] |
40 (L-TAMIS 21, R-TAMIS 19) |
- |
L-TAMIS: 65 R-TAMIS: 67 |
L-TAMIS: 29 R-TAMIS: 30 |
Benign and malignant rectal lesions |
| Liu et al. [18] | 34 | 23:11 | 63 +/− 10 | 29 +/− 6 | Early-stage rectal neoplasm (uTis or uT1N0M0), T1 carcinoid, incomplete endoscopic resection of polyps, partial resection for palliative control of rectal bleeding in metastatic disease |
| Liu et al. [23] | 5 | 3:2 | 58 | - | Endoscopically unresectable polyps or T1 rectal cancers |
| Liu et al. [17] | 28 | 20:8 | 62 +/− 10 | 30 +/− 6 | Endoscopically unresectable polyps or low-risk malignancies (no LVI, no TB, well-moderate differentiation, favourable location) |
| Lo et al. [24] | 16 | - | 63 | - | Endoscopically unresectable tumours |
| Marks et al. [1] | 26 | 13:13 | 62 | 27 | Benign polyp, T1 cancer, selected T2 cancer after neoadjuvant therapy |
| Ngu et al. [25] | 6 | 2:4 | 62 +/− 8 | 27 | Patients with cCR after neoadjuvant therapy for rectal cancer |
| Paull et al. [26] | 21 | 13:8 |
Si: 56 +/− 13 FCD: 55 +/− 17 |
Si: 27 +/− 5 FCD: 28 +/− 7 |
T0-T1 N0 |
| Ruiz et al. [29] | 9 | 5:4 | 72 +/− 8 | - | Benign rectal lesions or T1 with good prognostic criteria |
| Tomassi et al. [19] | 58 | - | - | 28 +/− 5 | uT1N0, uT2N0, Stage 3 with cCR, polyps, carcinoids, GIST |
| Warren et al. [11] | 8 | - | - | - | - |
| Wassef et al. [27] | 19 | 11:8 | 68 +/− 10 | 31 | Incomplete endoscopic resection, not amenable neither to endoscopic resection nor conventional transanal excision |
| Yao et al. [28] | 24 | 10:14 | 59 +/− 12 | 24 | 12 AC (7cCR, 4cT1, 1cT2), 3 CIS, 2 inconclusive, 3 NE, 3 TVA, 1 endometriosis |
cCR clinical complete response, CRTx chemoradiotherapy, LVI lymphovascular invasion, GIST gastrointestinal stromal tumour, AC adenocarcinoma, CIS carcinoma in situ, NE neuroendocrine, TVA tubulovillous adenoma
Operative details
DaVinci robotic platforms (S, Si, SP or Xi) were used in all but two of the included studies reporting platform models [1, 5, 11, 15–20, 22–25, 27–29]. Fok et al. utilised the Medrobotics Flex Robotic System on their cohort, whereas Paull et al. compared outcomes between the DaVinci Si and Medrobotics Flex Robotic System in their respective studies on R-TAMIS [21, 26]. Patient positioning throughout studies included lithotomy, modified lithotomy, prone jack-knife and hockey-stick decubitus. Variable positions within individual studies were attributed to surgeon preference or tumour location (anterior, posterior, lateral). Fifteen studies reported using the Applied Medical GelPOINT Path Transanal Access Platform. Hompes et al. use a transanal glove port, generally considered a safe, inexpensive and readily available alternative tool in transanal surgery [22]. Operative details are demonstrated in Table 3. The overall mean operative time across the included studies was calculated as 110 +/− 22 min.
Table 3.
Operative details
| Study | Robotic system | Position | TAMIS port | Operative time (mean +/− SD) | Estimated blood loss |
|---|---|---|---|---|---|
| Atallah et al. [20] | DaVinci S/Si | Modified lithotomy | GelPOINT | 124 | 35 ml |
| Baker et al. [15] | DaVinci Xi | Lithotomy | GelPOINT | 67 +/− 17 | - |
| Fok et al. [21] | Medrobotics Flex System | Lithotomy | - | 142 | - |
| Hompes et al. [22] | DaVinci Si | - | Glove port | 109 +/− 40 | - |
| Huang et al. [16] | DaVinci Si/Xi | Prone jack-knife | GelPOINT | 112 +/− 59 | - |
| Lee et al. [5] | DaVinci Si/Xi | Prone jack-knife | GelPOINT |
L-TAMIS: 100 R-TAMIS: 102 |
L-TAMIS: 15 ml R-TAMIS: 5 ml |
| Liu et al. [18] | DaVinci Xi | Prone jack-knife or lithotomy | GelPOINT | 100 | - |
| Liu et al. [23] | - | Lithotomy | GelPOINT | - | - |
| Liu et al. [17] | DaVinci Xi | Lithotomy | GelPOINT | 133 +/− 47 | - |
| Lo et al. [24] | DaVinci Xi | Prone jack-knife or lithotomy | GelPOINT | 87 | 17.5 ml |
| Marks et al. [1] | DaVinci SP | Modified lithotomy | GelPOINT | 199 +/− 116 | 10 +/− 46 ml |
| Ngu et al. [25] | DaVinci Xi | Modified lithotomy | GelPOINT | 125 +/− 43 | Minimal |
| Paull et al. [26] | DaVinci Si or Medrobotics Flex System | Prone jack-knife or high lithotomy | GelPOINT |
Si: 167 +/− 84 FCD: 110 +/− 40 |
Si: 37.5 +/− 38.3 FCD: 9.5 +/− 13.6 |
| Ruiz et al. [29] | DaVinci Si | Lithotomy | GelPOINT | 76 +/− 23 | 37.4 +/− 8.6 ml |
| Tomassi et al. [19] | DaVinci Xi/Si | Hockey-stick decubitus OR prone jack-knife OR lithotomy | GelPOINT | 82 +/− 41 | - |
| Warren et al. [11] | DaVinci Xi | Prone jack-knife | GelPOINT | - | - |
| Wassef et al. [27] | - | Prone jack-knife | - | 97 +/− 17 | Minimal |
| Yao et al. [28] | DaVinci Xi/Si | Lithotomy or prone jack-knife | GelPOINT | 140 +/− 45 | Minimal |
Peri-operative outcomes
Peri-operative outcomes are illustrated in Table 4. Complications were divided into major (Clavien Dindo ≥ 3) and minor (Clavien Dindo < 3). Overall complication rate was 9.7% (n = 29/300). Minor and major complications were observed in 7% (n = 21/300) and 2.7% (n = 8/300), respectively. Of the major complications, four were bleeding requiring endoscopic intervention, one pelvic abscess requiring drainage, one poor wound healing requiring re-operative, one peritoneal violation requiring conversion and repair and one post-operative stenosis requiring dilatation.
Table 4.
Peri-operative details
| Study | Length of stay (days) | Minor complications | Major complications | Readmission | Follow-up |
|---|---|---|---|---|---|
| Atallah et al. [20] | 1.4 +/− 1.1 | - | - | - | 14 +/− 9 months |
| Baker et al. [15] | 1.8 +/− 0.9 | 0 | 1 (bleeding requiring endoscopic clipping) | 0 | 2 weeks |
| Fok et al. [21] | 0.8 +/− 0.6 | 0 | 0 | 0 | 30 days |
| Hompes et al. [22] | 1.7 +/− 1.2 | 1 | 0 | 0 | - |
| Huang et al. [16] | 4.3 +/− 2.6 | 0 | 0 | 0 | 9.6 months |
| Lee et al. [5] |
L-TAMIS: 10 h R-TAMIS: 10.5 h |
L-TAMIS: 1 R-TAMIS: 1 |
0 | 0 | - |
| Liu et al. [18] | 1 | 1 (C. Diff infection requiring antibiotics) | 0 | 0 | 188 +/− 209 days |
| Liu et al. [23] | 0 | 0 | 0 | 0 | 30 days |
| Liu et al. [17] | 82% 0 days | 1 (post-operative hypotension) | 1 (POD9 bleeding requiring endoscopy) | 1 | 24 +/− 9 months |
| Lo et al. [24] | 2.8 +/− 2.8 | 2 (stool incontinence, abscess requiring antibiotics) | 1 (poor wound healing requiring re-operation) | 1 | 80 days |
| Marks et al. [1] | 73% 0 days | 3 (wound dehiscence requiring antibiotics) | 1 (pelvic abscess requiring IR drain) | 0 | 4 +/− 4 months |
| Ngu et al. [25] | 4.2 +/− 1.3 | 0 | 0 | 0 | 21 +/− 9 months |
| Paull et at. [26] | - | - | 2 (peritoneal violation requiring conversion and repair, rectal stenosis requiring dilatations) | 0 | - |
| Ruiz et al. [29] | 2.5 +/− 1.2 | 2 (urinary retention, respiratory infection) | 0 | 0 | 19 +/− 2 months |
| Tomassi et al. [19] | 90% 0 days | 4 (2 urinary retention, nausea, suture line dehiscence requiring antibiotics) | 2 (bleeding requiring endoscopy) | - | - |
| Warren et al. [11] | - | - | - | - | - |
| Wassef et al. [27] | 79% 0 days | 6 (4 diarrhoea, pain, urgency) | 0 | - | - |
| Yao et al. [28] | 4.6 +/− 2 | 0 | 0 | 0 | 24 +/− 10 months |
Histopathological and oncological data
Tumour specifications were similar across the included studies. Specimen fragmentation occurred in only four cases. The pooled margin positivity rate across studies was 3.8% (n = 11/286). Out of the reported, the overall local recurrence (benign or malignant) occurred in 2.2% (n = 5/232) of patients within the specified follow-up period. The recurrence locations included the proctectomy scar site, anorectal junction and surgical bed. The histopathological and oncological data is demonstrated in Table 5.
Table 5.
Histopathological and oncological data
| Study | Lesion diameter (cm) | Distance to anal verge (cm) | Surface area (cm2) | Fragmentation | Positive margins | Recurrence |
|---|---|---|---|---|---|---|
| Atallah et al. [20] | 3.1 +/− 1.4 | 6.8 +/− 2.3 | - | 0 | 1/9 | 0 |
| Baker et al. [15] | 3.8 +/− 1.2 | 7.3 | - | 1/11 | 1/11 | - |
| Fok et al. [21] | 3.2 | 8.3 | - | 0 | 1/5 | - |
| Hompes et al. [22] | - | 7.3 +/− 2 | 8 +/− 5.9 | - | 2/15 | - |
| Huang et al. [16] | 2.5 | 5 +/− 1.5 | - | 0 | 2/23 | 0 |
| Lee et al. [5] | - |
L-TAMIS: 7.8 R-TAMIS: 8.2 |
L-TAMIS: 17 R-TAMIS: 17 |
- |
L-TAMIS: 2/23 R-TAMIS: 1/19 |
- |
| Liu et al. [18] | 2.6 +/− 1.1 | 8.6 +/− 3.6 | 7.7 +/− 9.8 | 0 | 0 | - |
| Liu et al. [23] | 3 | 9.7 | 8.9 | 0 | 0 | - |
| Liu et al. [17] | 4.1 +/− 3.1 | 7.8 +/− 3.9 | - | - | 1/28 | 0 |
| Lo et al. [24] | 4.1 | - | - | 0 | 0 | - |
| Marks et al. [1] | 2.8 +/− 1.3 | 3.5 +/− 7.5 | - | 0 | 0 | 0 |
| Ngu et al. [25] | 2.8 +/− 1.2 | 6.5 +/− 1.5 | - | 0 | 0 | 0 |
| Paull et al. [26] | - |
Si: 11.1 +/− 3.8 FCD: 9.6 +/− 3.6 |
- | - | 0 | 0 |
| Ruiz et al. [29] | - | 6.4 +/− 1.5 | 21.5 +/− 12.1 | 0 | 0 | 0 |
| Tomassi et al. [19] | 3.3 +/− 1.7 | 8.8 +/− 2.5 | - | 1/58 | 3/58 | 3/58 (adjacent to proctotomy scar, surgical bed, recurrent polyp) |
| Warren et al. [11] | - | - | - | 0 | - | 0 |
| Wassef et al. [27] | 2.8 +/− 0.9 | 7.5 +/− 3.5 | - | 2/19 | 0 | 1/19: site of excision |
| Yao et al. [28] | 2.8 +/− 1.1 | 6.8 +/− 2.1 | - | 0 | 0 | 1/24: anorectal junction |
Cost
Only two of the studies included in our analysis reported costs associated with R-TAMIS [5, 22]. Lee et al. reported direct costs of $3562 and $4440.92 of L-TAMIS and R-TAMIS respectively in their comparative study [5]. Hompes et al. reported a far more economical cost of €837 for a single R-TAMIS case in their institute [22]. Neither study incorporated the capital costs of robotic platforms in their calculations.
Discussion
Transanal minimally invasive local excision remains an acceptable treatment option for early-stage rectal tumours (T1, N0) within 3–8 cm of the anal verge in the absence of nodal involvement on local staging [30]. While this procedure has traditionally been performed laparoscopically, recent evidence has suggested R-TAMIS as a safe alternative, with better articulation and superior visualisation [24]. We sought to synthesise currently available data on R-TAMIS, to assess its safety and efficacy profile on cases to date.
Our review was comprised of 317 patients from 18 cohort studies or large case series (≥ 5 patients) highlighting practical aspects of R-TAMIS in addition to peri-operative and oncological outcomes. Overall complication rate from R-TAMIS was 9.7%. Clear margins (R0) were reported in 96.2% of patients. Local recurrence occurred in 2.2% of patients during the specified follow-up periods. A recent systematic review of laparoscopic TAMIS outcomes in over 1200 cases by Kim et al. found an overall complication rate of 18.4% (n = 222/1205) [31]. Margin positivity rates were also elevated at 8.6% (n = 101/1173). Finally, local recurrence was reported as 7.2% (n = 54/746). While these findings suggest a potential benefit of R-TAMIS, these studies were observational and non-comparative, making side-by-side comparison difficult and unreliable.
To date, only one study has been published directly comparing outcomes between the laparoscopic and robotic-assisted approach in patients undergoing transanal local excision of rectal lesions. In their single-centre review of 40 consecutive patients, Lee et al. compared the two approaches in terms of peri-operative outcomes, histopathological outcomes and cost [5]. Their review found no significant difference between L-TAMIS and R-TAMIS in any outcome other than cost, which was significantly higher in the R-TAMIS group (median direct cost $3562 vs. $4440.92). A breakdown of cost was not provided in this study.
Our study has several limitations. Despite only including cohort studies or large case series, the majority of included studies contained small numbers of participants, which are by default highly susceptible to potential selection bias. Similarly, a lack of comparative studies made meta-analysis of results and a statistical comparison between surgical approaches not feasible. Further studies on larger populations, ideally in the form of randomised control trials or matched cohorts, are required before conclusions can be drawn on the superiority of one modality over another. Nevertheless, R-TAMIS appears to be a safe and feasible alternative to L-TAMIS, in the transanal local excision of rectal tumours.
Conclusion
Our review highlights the current evidence for R-TAMIS in the local excision of rectal lesions. While R-TAMIS appears to have complication, margin negativity and recurrence rates superior to those of L-TAMIS published elsewhere in the literature, accurate conclusions cannot be drawn in the absence of comparative studies. Future research focusing on comparing these two approaches will shed light on best practices.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
Supported by the Joly Leadership Fund, Trinity St. James Cancer Institute.
Author contributions
Study conception and design: Niall O’Sullivan, Hugo Temperley, Satish Warrier, Michael Kelly. Data collection: Niall O’Sullivan, Hugo Temperley, John Larkin, Jacob McCormick, Emanuele Rausa, Paul McCormick. Analysis and interpretation of results: Niall O’Sullivan, Hugo Temperley, John Larkin. Draft manuscript preparation: Niall O’Sullivan, Hugo Temperley, John Larkin, Jacob McCormick, Emanuele Rausa, Paul McCormick, Alexander Heriot, Brian Mehigan, Satish Warrier, Michael Kelly. Final manuscript preparation: Niall O’Sullivan, Hugo Temperley, John Larkin, Jacob McCormick, Emanuele Rausa, Paul McCormick, Alexander Heriot, Brian Mehigan, Satish Warrier, Michael Kelly. Supervision: Alexander Heriot, Brian Mehigan, Satish Warrier, Michael Kelly.
Funding
Open Access funding provided by the IReL Consortium
Data availability
No datasets were generated or analysed during the current study.
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
No datasets were generated or analysed during the current study.