Abstract
Aim
To analyze the association between clavicular tunnel positioning and postoperative reduction loss in patients with acute acromioclavicular (AC) joint dislocation treated with anatomic coracoclavicular (CC) fixation using double clavicular tunnels.
Methods
A retrospective review of patients with AC joint dislocation, treated with anatomic CC fixation using double clavicular tunnels, was conducted. Patients with pre-operative, immediate post-operative, and final follow-up Zanca-view X-rays were included. On each X-ray, the obtained measures included: distance from lateral border of clavicle to trapezoid and conoid tunnels, distance between tunnels, clavicle length, and CC distance of affected and un-affected sides. Loss of reduction was calculated as CC distance difference between immediate and final post-operative X-rays. Association between reduction loss and tunnel positioning was analyzed.
Results
Conoid, trapezoid and tunnel ratios were 24% ± 4, 15% ± 3, and 9% ± 2, respectively. Significant reduction loss was seen in 21(45.7%) patients. Significantly higher probabilities of reduction loss were associated with trapezoid tunnels placed medial to 24 mm (30.8% vs 65.0%, OR 4.2 (IC95%: 1.2–14.4), p: 0.024) or 15% of the clavicle length (32.1% vs 66.7%, OR 4.2 (IC 95%: 1.2–14.9), p: 0.025).
Conclusions
Trapezoid tunnels placed medial to 24 mm or 15% medial to clavicle length could lead to higher probabilities of significant reduction loss. These findings support the importance of clavicular tunnels’ proper placement for decreasing significant reduction loss.
Keywords: acromioclavicular joint dislocation, coracoclavicular fixation, reduction loss, tunnel positioning, PROMs
Introduction
Acromioclavicular (AC) joint dislocations are frequent lesions representing 4%–12% of shoulder injuries.1,2 Most of these injuries occur in male patients in their second-third decades of life during sports practice.3,4 There is consensus in scientific literature that low-grade dislocations (types I and II of Rockwood5 and IIIa of International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) Consensus6) can be treated conservatively.7,8 Meanwhile, high-grade dislocations (grades IV, V, and VI of Rockwood and grade IIIb of ISAKOS consensus) benefit from surgical reduction and stabilization.9–12
Multiple techniques have been described for the surgical treatment of these injuries, all of which have the aim of facilitating anatomic reduction and AC joint stability.13–19 Anatomic coracoclavicular (CC) fixation has proven to be useful in acute AC joint dislocation (first 14–21 days).20 This technique mimics the native insertion of the trapezoid and conoid ligaments using one point of fixation on the coracoid and two points of fixation on the clavicle.13,18,21–23 Despite the publication of favorable outcomes using this technique,24 some complications have been reported, with reduction loss being one of the most important ones.21,25,26 Two studies have evaluated tunnel positioning in acute and chronic settings as an influencing factor for reduction loss,22,23 determining that the placement of conoid and trapezoid tunnels of more than 30% and 16% of the clavicle length, respectively, leads to higher rates of reduction loss.
The purpose of this study is to analyze the association between postoperative reduction loss and clavicular tunnel positioning in patients with acute high-grade AC joint dislocation treated with anatomic CC fixation using double clavicular tunnels. Our hypothesis is that there is a positive association between the medial placement of the trapezoid and conoid tunnel and significant reduction loss.
Methods
A retrospective review of patients with AC joint dislocation treated in a single clinical center between 2013 and 2019 was performed. The inclusion criteria were (i) patients with high-grade AC joint dislocations (Rockwood IV, V, and VI and ISAKOS consensus type IIIb); (ii) treated with anatomic CC fixation using double clavicular tunnels; (iii) availability of complete radiological studies (comparative preoperative and initial and final postoperative Zanca-view X-rays). The exclusion criteria were: (i) any other type of surgery for AC joint dislocation treatment, such as ligament transference (Weber-Dunn), acromioclavicular fixation, rigid CC fixation (Bosworth), single clavicle tunnel CC fixation and others; (ii) other additional surgical actions during the procedure, such as distal clavicle resection; (iii) surgery in patients more than 14 days after the injury; (iv) patients with previous surgeries on the shoulder.
Two postoperative, bilateral, comparative Zanca-view X-rays were used. The initial X-ray was taken in the first 30 postoperative days. The final X-ray was taken at least 90 days after the initial one. All X-rays were taken in the same clinical center. All X-ray measurements were performed using XERO Viewer 8.1.2 ® (Agfa HealthCare, Mortsel, Belgium). Using the same parameters measured by previous studies,22,23 the following points and lines were placed on the X-rays: the lateral clavicular point was the most lateral point, located in the middle of the clavicular thickness (Figure 1); the medial clavicular point was the most medial point, located in the middle of the clavicular thickness; the trapezoid and conoid points were placed in the middle of the lateral and medial clavicular tunnels, respectively and the superior coracoid point was the most cranial border of the coracoid on the affected and unaffected sides.
Figure 1.
The lateral clavicle point (Lat.) was the most lateral point, located in the middle of the clavicle's thickness. The medial clavicle point (Med.) was the most medial point, located in the middle of the clavicle's thickness. The trapezoid (Trap.) and conoid points (Con.) were placed in the middle of the lateral and medial clavicle tunnels, respectively. Using these points, the following distances were calculated: Clavicle length was the distance between the lateral and medial clavicle points; Trapezoid distance (Trapezoid d.) was the distance between the lateral clavicle and trapezoid points; Conoid distance (Conoid d.) was the distance between the lateral clavicle and conoid points; Tunnel distance (Tunnel d.) was the distance between the trapezoid and conoid points.
Using these points, the following distances were calculated (Figure 1):
Clavicle length: Distance between the lateral and medial clavicular points.
Trapezoid distance: Distance between the lateral clavicle and trapezoid points.
Conoid distance: Distance between the lateral clavicle and conoid points.
Tunnel distance: Distance between the trapezoid and conoid points.
Coraco-clavicular (CC) distance: The distance between the superior coracoid point and the clavicle on the affected and unaffected sides was measured perpendicular to a virtual line joining the superior coracoid points (Figure 2).
Figure 2.
The superior coracoid point was the most cranial border of the coracoid on the affected (Cor-a) and unaffected (Cor-u) side. The Coraco-clavicular distance was the distance between the superior coracoid point and the clavicle in the affected (CC-a) and unaffected (CC-u) sides, measured perpendicular to a virtual line joining the superior coracoid points.
Using these distances, the following values were calculated:
Conoid ratio: Conoid distance divided by clavicle length.
Trapezoid ratio: trapezoid distance divided by clavicle length.
Tunnel ratio: Tunnel distance divided by clavicle length.
CC ratio: difference between the CC distance of the affected and unaffected sides, divided by the CC distance of the unaffected side.
Given that there is no robust evidence correlating a specific reduction loss threshold with worst clinical outcomes, previously published definitions for significant reduction loss were used, considered as a CC distance difference between the initial and final X-rays of more than 6 mm23 or a CC ratio increase of more than 40%.21
Surgeries were performed using the same technique by three shoulder specialists (RA, AV, HC). In a beach chair position, a supraclavicular approach was performed. A 4.0-mm drill hole was made on the coracoid, and one flip-button Fliptack® (Karl Storz SE & Co. KG, Tuttlingen, Germany) together with two high-resistance sutures (Parcus suture®, Parcus Medical; Sturgeon Bay, WI, USA) were passed through the coracoid hole and flipped under the coracoid. Then, the position of the clavicular tunnels was chosen intraoperatively by the surgeons, taking into consideration the anatomic insertion of the native conoid and trapezoid ligaments and a distance of 4.5 and 2.5 cm from the lateral border of the clavicle. Two 2.5-mm drill holes were then made on the clavicle, and one of the Parcus sutures® (two tails and the loop) was passed through each clavicle hole. Reduction of the AC joint was performed, and the system was blocked using one flip button on each tunnel with a Nice knot.18
Postoperatively, patients underwent a standard rehabilitation protocol, including the use of a shoulder brace for four weeks. Elevation over 90°, weight-bearing, and extension of the shoulder at 90° in the horizontal plane were forbidden. Passive movements of the shoulder and active motions of the elbow and wrist were started on the first postoperative day. A standard physiotherapy program for shoulder started at the 4th week with (i) progressive active and passive motion of the shoulder; (ii) stretching of the glenohumeral joint; (iii) strengthening exercises for rotator cuff and periscapular muscles; (iv) proprioceptive rehabilitation. Patients were allowed to start their regular sport practices at the 12th week. Contact sports were allowed at the 16th postoperative week.
For inter-observer repeatability, all X-ray measurements were performed by three independent observers (JR, AO, JM) blinded to one-another. Each observer received specific instructions on how to perform the X-ray measurements. For intra-observer repeatability, one observer (JR) repeated the measurements 12 months after the first measurement.
Statistical analysis
A descriptive analysis of the sample was performed. A Shapiro‒Wilk test was used to assess normality for quantitative variables. Quantitative variables are expressed as means and standard deviations (SDs), and categorical variables are expressed as absolute frequencies and percentages. T tests and Wilcoxon–Mann–Whitney tests were used to compare quantitative variables according to normality distribution, and Fisher's exact test was used for categorical variables. To evaluate factors associated with significant reduction loss, the percentage of significant reduction loss was compared, using Fisher's exact test, between groups of patients defined by the categorization of the variables of interest. A receiver operating characteristic (ROC) curve was generated, and the area under the curve (AUC) was calculated for conoid and trapezoid distances and the distance between tunnels. The threshold for categorization was chosen where the highest Youden index found.27 Odds ratios were calculated, with their respective confidence intervals and hypothesis tests to assess whether these were significantly different from one (which indicates no association). Inter- and intra-observer repeatability were expressed in terms of intraclass correlation coefficients (ICC) and were calculated assuming single measurement, and using absolute agreement and a two-way random model (ICC 2,1). ICC can be interpreted as follows: <0.40 poor; 0.40–0.59 fair; 0.60–0.74 good, and 0.75–1.00 excellent.28 The analysis was performed using STATA 14.1 (STATACorp, College Station, TX, USA) with a significance level of 0.05.
Results
Radiographs of 46 patients were included in the study (mean age 36.0 ± 11.2, 45 males (97.8%), 26 right shoulders (56.5%)). The mean time to surgery was 2.8 ± 2.7 days and the mean follow up was 365.6 ± 392.4 days (Table 1). Inter- and intra-observer repeatability of measurements was excellent for all parameters (Table 2).
Table 1.
Demographic data, injury classification, clavicle measurements, and reduction losses.
| Mean ± SD | ||
|---|---|---|
| n (%) | Range | |
| Age (yrs) | 36.0 ± 11.2 | (17.0–61.0) |
| Time to surgery (days) | 2.8 ± 2.7 | (0.0–13.0) |
| Follow up (days) | 365.6 ± 392.4 | (90.0–1396.0) |
| Gender | ||
| Male | 45 (97.8%) | |
| Female | 1 (2.2%) | |
| Side | ||
| Right | 26 (56.5%) | |
| Left | 20 (43.5%) | |
| Classification (Rockwood) | ||
| 3 | 12 (26.1%) | |
| 4 | 3 (6.5%) | |
| 5 | 31 (67.4%) | |
| Age group | ||
| <40 years old | 29 (63.0%) | |
| ≥40 years old | 17 (37.0%) | |
| Time to surgery | ||
| <7 days | 44 (95.7%) | |
| ≥7 days | 2 (4.3%) | |
| Clavicle measurements | ||
| Clavicle length (cm) | 16.0 ± 1.9 | (14.1–26.4) |
| Conoid distance (mm) | 38.2 ± 5.4 | (25.6–49.5) |
| Trapezoid distance (mm) | 23.2 ± 5.1 | (12.2–33.3) |
| Tunnel distance (mm) | 15.0 ± 3.1 | (6.4–24.9) |
| Conoid ratio | 0.24 ± 0.04 | (0.12–0.33) |
| Trapezoid ratio | 0.15 ± 0.03 | (0.07–0.22) |
| Tunnel ratio | 0.09 ± 0.02 | (0.04–0.16) |
| Reduction losses | ||
| Difference CC ratio Rf-Ri (%) | 37.0 ± 23.7 | (−4.6–93.7) |
| Difference CC distance Rf-Ri (mm) | 3.7 ± 2.4 | (−1.5–8.8) |
| Significant reduction losses | ||
| Difference CC ratio Rf-Ri >40% | 20 (43.5%) | |
| Difference CC distance Rf-Ri >6 mm | 9 (19.6%) | |
| Any criteria | 21 (45.7%) | |
Abbreviations: SD, Standard Deviation; (%), percentage; yrs, years; cm, centimeters; mm, milimeters; CC, Coracoclaviclar; Rf, radiograph at final follow-up; Ri, radiograph at immediate post-operative.
Table 2.
Inter-observer and intra-observer repeatability.
| Inter-observer | Intra-observer | |||||
|---|---|---|---|---|---|---|
| Variable | ICC | 95% CI | p value | ICC | 95% CI | p value |
| CC distance unaffected side | 0.94 | (0.86–0.97) | <0 . 001 | 0.86 | (0.73–0.93) | <0.001 |
| CC distance affected side | 0.93 | (0.78–0.96) | <0.001 | 0.95 | (0.80–0.99) | <0.001 |
| Clavicle length | 0.89 | (0.71–0.93) | <0.001 | 0.91 | (0.75–0.96) | <0.001 |
| Conoid tunnel | 0.97 | (0.93–0.99) | <0.001 | 0.93 | (0.89–0.99) | <0.001 |
| Trapezoid tunnel | 0.98 | (0.97–0.99) | <0.001 | 0.95 | (0.91–0.98) | <0.001 |
Abbreviation: ICC (intraclass correlation coefficient); CI, confident interval; CC, coracoclavicular.
ICC can be interpreted as follows: <0.40 poor; 0.40–0.59 fair; 0.60–0.74 good, and 0.75–1.00 excellent.
Bold font indicates statistical significance with p value <0.05.
The clavicle length, conoid, trapezoid, and tunnel distances were 16.0 ± 1.9 cm, 38.2 ± 5.4 mm, 23.2 ± 5.1 mm, and 15.0 ± 3.1 mm, respectively. The conoid, trapezoid, and tunnel ratios were 0.24 ± 0.04, 0.15 ± 0.03, and 0.09 ± 0.02, respectively. The mean increase in the CC distance of the affected side and the CC ratio were 3.7 ± 2.4 mm and 37.0 ± 23.7%, respectively (Table 3).
Table 3.
Preoperative, initial postoperative, and final postoperative radiological evaluation.
| Preoperative | Postoperative | Final follow-up | p value* | ||||||
|---|---|---|---|---|---|---|---|---|---|
| mean ± SD | Range | mean ± SD | Range | mean ± SD | Range | Pre vs. Post | Pre vs. Final | Post vs. Final | |
| CC distance unaffected side (mm) | 8.5 ± 2.5 | (1.0–13.0) | 9.3 ± 2.2 | (3.7–14.5) | 9.6 ± 1.7 | (5.9–14.5) | 0.090 | 0.416 | 0.690 |
| CC distance affected side (mm) | 18.1 ± 5.4 | (2.0–29.7) | 7.0 ± 3.1 | (1.7–18.1) | 10.7 ± 3.3 | (4.7–17.9) | <0 . 001 | <0.001 | <0.001 |
| Displacement ratio (%) | 118.7 ± 51.2 | (11.9–304.0) | −23.7 ± 30.6 | −(77.7–83.9) | 13.3 ± 35.7 | -(45.8–92.9) | <0.001 | <0.001 | <0.001 |
| p value* (unaffected versus affected side) | <0.001 | 0.003 | 0.143 | ||||||
Abbreviations: SD, Standard Deviation; CC, coracoclavicular; (mm), millimeters; (%), percentage.
*Student T-test.
Bold font indicates statistical significance with p value <0.05.
A significant reduction loss was seen in 21 (45.7%) patients. Of these patients, 9 (19.6%) patients exhibited a CC distance increase of more than 6 mm, and 20 (43.5%) showed a CC ratio increase of more than 40% (Table 1). Compared with preoperative values, there was a significant CC distance decrease on the affected side in both initial and final postoperative X-ray measurements (18.1 mm ± 5.4 versus 10.7 mm ± 3.3, p < 0.001)(Table 3).
There was no significant difference in tunnel positioning measurements between patients with or without significant reduction loss (Table 4). The AUC of the ROC curve was 61.5%, 58.7%, and 48.0% for the trapezoid, conoid and tunnel distances, respectively. The thresholds were 24, 40, and 12 mm for the trapezoid, conoid and tunnel distances, respectively. A significantly higher probability of reduction loss was associated with trapezoid tunnels placed medial to 24 mm (p: 0.024; OR 4.2 (95% IC:1.2–14.4)) or 15% of the clavicle length (p: 0.025; OR 4.2 (95% IC: 1.2–14.9)) (Table 5). A conoid tunnel placed medial to 40 mm (p: 0.096; OR 2.8 (95% IC: 0.8–9.6)) or 27% (p: 0.154; OR 3.6 (95% IC: 0.6–20.9)) of the clavicle length was associated with a higher probability of reduction loss, but the results did not reach statistical significance.
Table 4.
Comparison between patient with and without significant reduction losses (SRL).
| Without SRL | With SRL | ||||
|---|---|---|---|---|---|
| mean ± SD | Range | mean ± SD | Range | ||
| Variable | n | % | n | % | p value* |
| Age | 35.6 ± 10.8 | (19.0–61.0) | 36.4 ± 12.0 | (17.0–58.0) | 0.806 |
| Male gender | 25 | (100.0%) | 20 | (95.2%) | 0.27œ |
| Days to surgery | 2.5 ± 2.5 | (0.0–11.0) | 3.0 ± 2.9 | (0.0–13.0) | 0.559 |
| Clavicle measurements | |||||
| Clavicle length (cm) | 16.2 ± 2.3 | (14.1–26.4) | 15.8 ± 1.0 | (14.3–18.4) | 0.991 |
| Conoid distance (mm) | 37.3 ± 5.5 | (25.6–48.2) | 39.1 ± 5.3 | (29.5–49.5) | 0.316 |
| Trapezoid distance (mm) | 22.4 ± 4.9 | (12.2–33.2) | 24.2 ± 5.2 | (16.6–33.3) | 0.182 |
| Tunnel distance (mm) | 15.0 ± 3.7 | (6.4–24.9) | 15.0 ± 2.3 | (12.0–20.0) | 0.817 |
| Conoid ratio | 0.23 ± 0.04 | (0.12–0.30) | 0.25 ± 0.03 | (0.20–0.33) | 0.360 |
| Trapezoid ratio | 0.14 ± 0.03 | (0.07–0.20) | 0.15 ± 0.03 | (0.10–0.22) | 0.168 |
| Tunnel ratio | 0.09 ± 0.03 | (0.04–0.16) | 0.09 ± 0.01 | (0.08–0.13) | 0.921 |
Abbreviations: SD, Standard Deviation; (%), percentage; (cm), centimeters; (mm), millimeters; SRL, significant reduction losses.
*Wilcoxon Mann Whitney test.
œFisher’s exact test.
Table 5.
Comparison of tunnel position between patient with and without significant reduction losses (SRL).
| Without SRL | With SRL | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Variable | n | % | n | % | AUC | OR | (IC 95%) | p value* | |
| Conoid distance (mm) | <40 mm | 18 | (72.0%) | 10 | (47.6%) | ||||
| ≥40 mm | 7 | (28.0%) | 11 | (52.4%) | 0.630 | 2.8 | (0.8–9.6) | 0.096 | |
| Conoid ratio | <0.27 | 23 | (92.0%) | 16 | (76.2%) | ||||
| ≥0.27 | 2 | (8.0%) | 5 | (23.8%) | 0.609 | 3.6 | (0.6–20.9) | 0.154 | |
| Trapezoid distance (mm) | <24 mm | 18 | (72.0%) | 8 | (38.1%) | ||||
| ≥24 mm | 7 | (28.0%) | 13 | (61.9%) | 0.674 | 4.2 | (1.2–14.4) | 0 . 024 | |
| Trapezoid ratio | <0.15 | 19 | (76.0%) | 9 | (42.9%) | ||||
| ≥0.15 | 6 | (24.0%) | 12 | (57.1%) | 0.674 | 4.2 | (1.2–14.9) | 0.025 | |
| Tunnel distance (mm) | <12 mm | 6 | (24.0%) | 1 | (4.8%) | ||||
| ≥12 mm | 19 | (76.0%) | 20 | (95.2%) | 0.565 | 6.3 | (0.7–57.5) | 0.102 | |
Abbreviations: SRL, significant reduction losses; (%), percentage; AUC: area under the curve in Receiver Operating Characteristic (ROC) curve.
*Fisher’s exact test.
Bold font indicates statistical significance with p value <0.05.
Discussion
The most important findings of this study were that a trapezoid tunnel placed medial to 24 mm or 15% of the clavicle length was associated with a higher probability of significant reduction loss. Neither conoid tunnel placement nor the distance between tunnels showed significant differences in terms of reduction loss. These findings in part confirm the hypothesis and the importance of adequate tunnel positioning in the clavicle.
There are two previous studies that specifically evaluate the association between tunnel positioning in the clavicle and reduction loss. Cook et al.23 evaluated this association in surgeries using different types of reconstructions with the use of grafts. The authors showed that medialized bone tunnels were a significant predictor of early reduction loss for both conoid (ratio of 29.2% vs. 24.8%; p = 0.012) and trapezoid tunnels (ratio of 17.1% vs. 12.8%; p = 0.004). Eisenstein et al.22 also studied tunnel positioning in patients who underwent reconstruction surgeries with and without the use of grafts. The authors showed a lower probability of reduction loss with a conoid tunnel positioning between 20% and 25% of the clavicle length and a trapezoid tunnel lateral to 16% of the clavicle length. The findings of Cook and Eisenstein et al., together with the results of the present study, suggest that either trapezoid or conoid medial placement leads to a higher probability of significant reduction loss.
Anatomic studies also show the insertion of conoid and trapezoid ligaments between these ranges. Boehm et al.29 studied 36 cadaveric clavicles and found that the average anatomic position of the conoid and trapezoid ligaments were 25% ± 0.03 and 16% ± 0.03 of the clavicle length, respectively.
The alignment of clavicle and coracoid tunnels has been studied in single tunnel technic. Seo et al.30 showed that a greater coracoclavicular tunnel angle was associated with greater reduction loss, through a windshield effect, in patients operated with a single clavicle tunnel. In double clavicle tunnel technic, Berthold et al.31 showed that a widening of the clavicle tunnel was associated with reduction loss, due to the same windshield effect. The alignment or widening of tunnels was not evaluated in the present study.
There are controversies regarding the correlation between radiographic and clinical outcomes. Breuer et al.18 showed greater CC distances were correlated with worse Constant scores, but other studies didn’t find a correlation between reduction loss and functional outcomes.32–34 Nevertheless, a better understanding of modifiable factors that could prevent reduction loss is desirable.
The findings of the present study should be interpreted in the context of the following limitations. First, this was a retrospective, case series study with a mid-term follow-up. A longer follow-up could lead to greater rates of reduction loss. Nevertheless, the highest rates of reduction loss are observed in the first three months.21 Second, we did not include postoperative stress (Alexander) X-ray projection to assess the final radiographic horizontal stability.35–37 This was because there were no conclusive data on the use of this projection at the beginning of this study. Third, a variation in the X-ray projections could lead to variability in the CC distance measurements.35 This study aimed to minimize this using comparative Zanca views in all cases, avoiding any other type of clavicle X-ray, such as unilateral AC joint projection, clavicle projection, thorax projection or others used in previous studies. Additionally, we included an inter and intra-rater reliability for each measurement. Fourth, this study didn’t evaluate other factors that could have affected the reduction loss, such as patient compliance with rehabilitation or motion-activity restrictions during the post-operative period. Additionally, other radiological characteristics associated with reduction loss, such as coracoclavicular tunnel angle30 and tunnel widening,31 were not evaluated in the present study. Fifth, even though a significant reduction loss was defined based on previously published studies, there is no robust evidence correlating a specific reduction loss threshold with worst clinical outcomes. Sixth, these results apply only to double clavicle tunnel technic, and should not be extrapolated to other single tunnel CC fixations.
Conclusions
In patients with acute high-grade AC joint dislocation treated with anatomic CC fixation using double clavicular tunnels, a medial placement of the trapezoid tunnel more than 24 mm or 15% of the clavicle length could lead to a higher probability of significant reduction loss. These findings support the importance of proper placement of clavicular tunnels to decrease the probability of significant reduction loss. Further prospective clinical studies are needed to analyzed whether tunnel positions can influence final functional outcomes.
Acknowledgements
The authors are grateful to Gabriel Mansilla for the manuscript revision and to M. Trinidad Alliende for the manuscript preparation.
Footnotes
Contributorship: Andrés Oyarzún, J Tomás Muñoz, Diego García, Andrea Canals, Alejandro Viacava, Hector Carreño, Raúl Águila. All authors reviewed and edited the manuscript and approved the final version of the manuscript.
Ethical approval: Ethical approval for this study was obtained from Santa María Clinic Scientific Ethics Committee (Resol. Ex. 012335-13-10-21)*.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Guarantor: J Tomás Rojas
ORCID iDs: J Tomás Rojas https://orcid.org/0000-0002-5929-1805
Andrés Oyarzún https://orcid.org/0000-0002-0035-8980
Alejandro Viacava https://orcid.org/0000-0002-9068-0905
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