Orthopedics

Feature Article 

Open Biceps Tenodesis: A Biomechanical Comparison of 6 Fixation Techniques

Miguel Diaz, BS; Brendan Y. Shi, BS; Matthew C. Baker, MD; Matthew T. Binkley, MD; Stephen M. Belkoff, PhD; Uma Srikumaran, MD, MBA, MPH

Abstract

Tenodesis is used to treat pathology of the long head of the biceps tendon. The authors evaluated the biomechanical properties of 6 techniques for biceps tenodesis fixation. The authors dissected 42 fresh-frozen cadaveric shoulders (mean age, 71±9.8 years; 69% male specimens), leaving the proximal humerus, proximal biceps tendon, and pectoralis major insertion. Specimens were randomized to undergo biceps tenodesis with one of the following: (1) an interference screw; (2) a cortical button; (3) a double-loaded 2.9-mm polyetheretherketone anchor (DL-2.9); (4) a double-loaded 1.9-mm all-suture anchor (DL-1.9); (5) a single-loaded 1.7-mm all-suture anchor (SL-1.7); or (6) soft tissue tenodesis. Specimens then underwent load-to-failure axial traction testing. A generalized linear and latent mixed model with a random-effects term was used to account for specimen pairing. Mean failure loads ranged from 136 N (95% confidence interval, 103–169 N) in the cortical button group to 79 N (95% confidence interval, 58–99 N) in the interference screw group. Failure occurred most often when fixation sutures pulled out of the tendon; however, 7 specimens failed elsewhere. No significant differences in ultimate failure load were found by treatment group. The interference screw group showed significantly more weakness than the cortical button and DL-2.9 groups. Tendon quality and suture parameters are likely more important than the fixation technique in determining failure load. [Orthopedics. 2020;43(2):e102–e108.]

Abstract

Tenodesis is used to treat pathology of the long head of the biceps tendon. The authors evaluated the biomechanical properties of 6 techniques for biceps tenodesis fixation. The authors dissected 42 fresh-frozen cadaveric shoulders (mean age, 71±9.8 years; 69% male specimens), leaving the proximal humerus, proximal biceps tendon, and pectoralis major insertion. Specimens were randomized to undergo biceps tenodesis with one of the following: (1) an interference screw; (2) a cortical button; (3) a double-loaded 2.9-mm polyetheretherketone anchor (DL-2.9); (4) a double-loaded 1.9-mm all-suture anchor (DL-1.9); (5) a single-loaded 1.7-mm all-suture anchor (SL-1.7); or (6) soft tissue tenodesis. Specimens then underwent load-to-failure axial traction testing. A generalized linear and latent mixed model with a random-effects term was used to account for specimen pairing. Mean failure loads ranged from 136 N (95% confidence interval, 103–169 N) in the cortical button group to 79 N (95% confidence interval, 58–99 N) in the interference screw group. Failure occurred most often when fixation sutures pulled out of the tendon; however, 7 specimens failed elsewhere. No significant differences in ultimate failure load were found by treatment group. The interference screw group showed significantly more weakness than the cortical button and DL-2.9 groups. Tendon quality and suture parameters are likely more important than the fixation technique in determining failure load. [Orthopedics. 2020;43(2):e102–e108.]

The long head of the biceps (LHB) tendon is often implicated in shoulder pain and discomfort.1–9 Injuries that produce shoulder pain related to the LHB tendon include tendinosis or partial tears of the tendon, medial subluxation of the tendon, superior labrum anterior and posterior lesions, massive rotator cuff tears with accompanying inflammation or tears of the LHB tendon, and traumatic ruptures of the LHB tendon.1,2,5–13

Techniques for biceps tenodesis differ by the exposure required, fixation construct, site of fixation, and suture parameters.2–7,11,12,14–16 The constructs available for biceps tenodesis incorporate intraosseous or extraosseous fixation and comprise an interference screw, a cortical button, suture anchors, and soft tissue tenodesis with the pectoralis major or transverse ligament.3,5,7,10–12,14,15,17 Fixation can occur intracapsularly at the bicipital groove, at the suprapectoral region of the bicipital groove, or at a subpectoral location under the pectoralis major insertion.8,12,18 The fixation techniques use suture parameters that vary according to the number of sutures, the suture configuration, and the number of tendon passes. This assortment of techniques presents variables that affect the biomechanical properties, healing capacity, and risk of complications of biceps tenodesis. Complications include persistent pain, bicipital groove pain in supra-pectoral fixation sites, tenodesis failure, nerve injury, infection, and other reactions to nonbiologic fixation components.16,17,19 The strengths and weaknesses of individual fixation techniques have been identified biomechanically and clinically, yet the optimal technique for biceps tenodesis remains unclear.

Most biomechanical studies of tenodesis fixation have suggested interference screw fixation as the optimal technique with regard to cyclic and ultimate failure load testing.1,2,6,7,11,20 Although interference screw fixation provides the most stable construct, risks include tendon rupture at the screw–bone interface and fractures or cyst formation at the site of fixation on the humerus.4,11 The ideal biceps tenodesis technique should (1) alleviate shoulder pain, (2) provide a stable construct that does not fail before healing of the tenodesis, and (3) present minimal risk of complications. Studies of the clinical outcomes of interference screw and suture anchor biceps tenodesis have reported significant postoperative improvements in pain, but a clearly superior fixation method has not been identified.5,12,16

In the current study, the authors evaluated the ultimate failure loads of 6 techniques for biceps tenodesis fixation. They compared the biomechanical properties of each technique and examined differences in anchor number (1 or 2), anchor size (2.9 mm, 1.9 mm, or 1.7 mm), suture parameters, and single- vs double-loaded anchors. The authors hypothesized that (1) the interference screw and cortical button would have the highest ultimate load to failure; (2) double-loaded single-anchor fixation and single-loaded dual-anchor fixation would have equivalent loads to failure; and (3) the site of failure for polyetheretherketone and all-suture anchors would be the suture or knot vs the tendon cutout at the distal tendon–screw interface with the interference screw.

Materials and Methods

A total of 42 fresh-frozen human cadaveric upper extremities, including the scapula and clavicle (mean age, 71±9.8 years; 69% male specimens), were disarticulated at the elbow and stored at 1o C. Dual-energy x-ray absorptiometry scans were performed at the distal radius and ulna of all specimens to evaluate bone mineral density. Cadavers were obtained from the Maryland State Anatomy Board.

The specimens were dissected free of soft tissue, leaving the proximal humerus with the biceps attachment, the conjoint tendon, and the pectoralis major insertion. No specimens showed degenerative or surgical changes, lesions of the LHB or its tendon, previous biceps tenodesis, or deformity of the proximal humerus.

A random number generator was used to assign each specimen to 1 of 6 tenodesis technique groups (7 specimens/group). Pretesting power analysis determined that 7 specimens would be required to detect significant differences between groups, with an estimated standard deviation of 30 N, a moderate effect size, an alpha level of 0.05, and a power of 80%.

The 6 tenodesis techniques were interference screw, cortical button, double-loaded 2.9-mm polyetheretherketone anchor (DL-2.9), double-loaded 1.9-mm all-suture anchor (DL-1.9), 2 single-loaded 1.7-mm all-suture anchors (SL-1.7), and soft tissue tenodesis. All procedures were performed according to the manufacturer's published surgical technique by a fellowship-trained shoulder surgeon (M.T.B, U.S.).

Interference Screw

A location within the bicipital groove between the inferior borders of the greater and lesser tubercles was marked. The transverse humeral ligament was incised, and the LHB tendon was moved medially with an 8-mm tendon fork. According to the manufacturer's guide, an 8 × 15-mm interference screw (Biceptor interference screw; Smith & Nephew, Andover, Massachusetts) was used.17 A suprapectoral location was used, as recommended by the manufacturer (Figure 1). Excess tendon (>1 cm) proximal to the tenodesis site was excised. This technique achieved fixation via interference fit alone, with no additional suture.

Photographs of suprapectoral interference screw tenodesis. The interference screw is inserted over the long head of the biceps tendon (A). Completed interference screw fixation (B).

Figure 1:

Photographs of suprapectoral interference screw tenodesis. The interference screw is inserted over the long head of the biceps tendon (A). Completed interference screw fixation (B).

Cortical Button

A location 1 cm proximal to the inferior border of the pectoralis major tendon insertion within the intertubercular groove was marked. A guide pin was placed at this location, and the near cortex was drilled with a 4.5-mm cannulated endoscopic drill. The LHB tendon was cut 3 cm proximal to the musculotendinous junction, and an interlocking Krackow stitch was placed at the proximal edge of the LHB tendon. Ultrabraid (no. 2) suture (Smith & Nephew) was used in interlocking Krackow fashion with a total of 8 locking passes, starting with 4 locking passes on the cut medial edge and returning with 4 locking passes distally to proximally on the lateral edge. The suture ends were passed through a 4 × 12-mm button (EndoButton fixation device; Smith & Nephew) (Figure 2A), and the button was introduced into the intramedullary canal. The cortical button was flipped, and the sutures were pulled to bring the proximal portion of the tendon into close proximity to the canal entrance. The sutures were tied with a surgeon's knot followed by 2 square knots (Figure 2B). Suture parameters for the fixation techniques are presented in Table 1.

Photographs of cortical button tenodesis. A Krackow stitch is seen at the distal end of the bisected long head of the biceps tendon along with the cortical button (A). Completed cortical button fixation (B).

Figure 2:

Photographs of cortical button tenodesis. A Krackow stitch is seen at the distal end of the bisected long head of the biceps tendon along with the cortical button (A). Completed cortical button fixation (B).

Suture Parameters for Biceps Tenodesis Fixation Techniques

Table 1:

Suture Parameters for Biceps Tenodesis Fixation Techniques

Anchor Tenodesis

The 3 anchor tenodesis techniques were performed in similar fashion. The pectoralis major insertion was reflected, and the inferior border was marked. Marks were made 1 and 2 cm proximal to the inferior border on the humerus.

In the single-anchor group, double-loaded anchors (Figure 3) were inserted at the 1-cm mark (Osteoraptor 2.9 Suture Anchor with 2 Ultrabraid [no. 2] sutures and Suturefix Ultra Anchor 1.9 mm with 2 Ultrabraid [no. 1] sutures [all Smith & Nephew]). In the double-anchor group, single-loaded anchors (Suturefix Ultra Anchor 1.7 mm [Smith & Nephew] with 1 Ultrabraid [no. 2] suture) were inserted at the 1-cm and 2-cm marks (Figure 4A). The sutures were passed through the LHB tendon in a lasso configuration for each suture in the single-loaded and double-loaded anchor groups. In the double-loaded groups, the sutures were first passed just proximal to the musculotendinous junction and then 1 cm proximal to this location. The suture of the distal single-loaded anchor was passed just proximal to the musculotendinous junction, whereas the suture of the proximal single-loaded anchor was passed 1 cm proximal to the previous location. The sutures were tied with a surgeon's knot followed by 2 square knots (Figure 3; Figure 4B).

Photographs of double-loaded anchor fixation. Sutures are passed through the tendon in a lasso configuration 1 cm and 2 cm proximal to the musculotendinous junction (A). Completed double-loaded anchor tenodesis with the excess tendon excised 1 cm proximal to fixation (B).

Figure 3:

Photographs of double-loaded anchor fixation. Sutures are passed through the tendon in a lasso configuration 1 cm and 2 cm proximal to the musculotendinous junction (A). Completed double-loaded anchor tenodesis with the excess tendon excised 1 cm proximal to fixation (B).

Photographs of single-loaded anchor fixation. Single-loaded anchors are placed 1 cm and 2 cm proximal to the inferior border of the pectoralis major insertion (A). Completed single-loaded all-suture anchor tenodesis with excision of the excess long head of the biceps tendon 1 cm proximal to fixation (B).

Figure 4:

Photographs of single-loaded anchor fixation. Single-loaded anchors are placed 1 cm and 2 cm proximal to the inferior border of the pectoralis major insertion (A). Completed single-loaded all-suture anchor tenodesis with excision of the excess long head of the biceps tendon 1 cm proximal to fixation (B).

Soft Tissue Tenodesis

The pectoralis major insertion was reflected laterally, and the inferior border of the pectoralis major tendon was marked. Two marks were made 1 and 2 cm proximal to the inferior border of the pectoralis major tendon. Ultrabraid (no. 2) suture was used to suture the LHB tendon into the pectoralis major tendon. At the 1-cm mark, the suture was passed through the LHB tendon and the pectoralis major tendon twice before being tied with a surgeon's knot followed by 2 square knots (Figure 5A). The same process was repeated at the 2-cm point (Figure 5B).

Photographs of soft tissue tenodesis. The first tendon pass through the long head of the biceps tendon with pectoralis major insertion 1 cm above the inferior border of the pectoralis major is seen (A). Finished soft tissue tenodesis with the excess tendon excised 1 cm proximal to fixation (B).

Figure 5:

Photographs of soft tissue tenodesis. The first tendon pass through the long head of the biceps tendon with pectoralis major insertion 1 cm above the inferior border of the pectoralis major is seen (A). Finished soft tissue tenodesis with the excess tendon excised 1 cm proximal to fixation (B).

Biomechanical Testing

After the tenodesis procedures, each specimen was disarticulated at the shoulder, and the distal humeral metaphysis was cut away from the specimen. The muscle belly of the LHB was folded in half, and the proximal and distal musculotendinous junctions were sutured together with a U-shaped Krackow stitch, with 6 passes on both the medial and lateral edges. The specimens were loaded onto a materials testing machine (Bioinix 858; MTS, Inc, Eden Prairie, Minnesota). A custom-made clamp held the surgical neck of the humerus in place (Figure 6). The suture ends holding the proximal and distal ends together were tied to the clevis pin of a clevis that was attached axially to the load cell on the testing machine. The LHB tendon was pulled parallel to the longitudinal axis of the humerus, similar to the in vivo direction of the force along the LHB and its tendon. Load-to-failure testing was conducted at 1 mm/sec, and failure was identified as the point of maximum load before tension decreased. All testing was performed at room temperature, and 0.9% normal saline was sprayed on tendon grafts to prevent desiccation.

Photographs of biomechanical evaluation of biceps tenodesis fixation methods. Setup of the specimen (A) and the materials testing machine (B) during load-to-failure testing.

Figure 6:

Photographs of biomechanical evaluation of biceps tenodesis fixation methods. Setup of the specimen (A) and the materials testing machine (B) during load-to-failure testing.

Data Analysis

Statistical analysis was performed with Stata software version 12 (Stata Corp LP, College Station, Texas). A generalized linear and latent mixed model with a random-effects term to account for specimen pairing on the cadaver was used to examine the effects of treatment group, age, sex, and bone mineral density on ultimate failure load.

Results

Treatment groups did not differ significantly in age, sex, or bone mineral density (all P>.05; Table 2). Covariate analysis found no significant influence on ultimate failure load by specimen sex (P=.091), age (P=.931), or bone mineral density (P=.683). Mean age across treatment groups was 71±9.8 years, and mean bone mineral density was 0.740±0.139 g/cm3. Of 42 harvested specimens, 29 were obtained from male donors. One male specimen failed at the attachment to the testing machine and was replaced randomly by a specimen from a female donor.

Demographic Data and Failure Loads by Biceps Tenodesis Treatment Group

Table 2:

Demographic Data and Failure Loads by Biceps Tenodesis Treatment Group

The highest ultimate failure load was found in the cortical button group, with a mean of 136 N (95% confidence interval, 103–169 N) (Table 2). The cortical button group was followed by the DL-2.9, SL-1.7, and DL-1.9 anchor groups. The mean failure load of the cortical button group was 38% greater than that of the soft tissue tenodesis group and 73% greater than that of the interference screw group, which had the lowest failure load, at 79 N (95% confidence interval, 58–99 N).

The LHB tendon was the site of failure in all but 7 specimens. Of these 7 specimens, 3 failed by rupture of the suture at the fixation site (2 in the DL-1.9 group and 1 in the cortical button group). The other 4 specimens failed when the anchor pulled out of the bone under direct loading (2 in the interference screw group and 1 each in the DL-2.9 and SL-1.7 groups). In addition, 35 specimens failed at the LHB tendon, with the sutures pulling out through the tendon in the cortical button, DL-2.9, DL-1.9, SL-1.7, and soft tissue tenodesis groups. In the interference screw group, failure occurred at the fixation site, with the tendon tearing and slipping out of the bone tunnel.

Discussion

Abnormality of the LHB tendon often causes shoulder pain. Although tenodesis provides clinical benefit, complications can occur, and the optimal fixation technique has not been identified. The authors evaluated the mechanical properties of 6 techniques for tenodesis fixation. Failure loads did not differ significantly by treatment group. Mean failure loads of the interference screw group and the cortical button and DL-2.9 groups did not have overlapping 95% confidence intervals (Table 2), suggesting that the interference screw technique was significantly weaker than the cortical button and DL-2.9 techniques.

The physiologic load on the LHB tendon is approximately 75 N when supporting the weight of the forearm and 112 N when holding a 1-kg weight with the elbow flexed to 90°.7,15,21,22 The cortical button, DL-2.9, and SL-1.7 groups had ultimate failure loads well above 112 N and therefore may be considered viable options for the treatment of tenodesis.

Failure of tenodesis constructs occurred most often at the tendon (35 of 42 specimens). Sutures pulled through the tendons in all groups except the interference screw group, in which the tendons tore at the bone–screw–tendon interface. Only 7 specimens failed because of construct failure: 3 as a result of suture failure and 4 as a result of anchor detachment at the anchor–bone interface under direct loading. These results indicate that suture parameters and tendon properties may be more important determinants of failure than the construct (implant) or bone quality.

Use of the Krackow or lasso loop stitch (cortical button and anchors) achieved higher failure loads than soft tissue tenodesis and the interference screw, which involve simple stitches or no suture, respectively. Krackow and lasso loop sutures cinch down on the tendon when loaded, increase the suture fiber–tendon contact area, and distribute the loading force over a larger area of tendon, thus delaying suture cutout through the tendon and achieving higher failure loads.23 Gigi et al23 showed that anchor tenodesis with a triple loop suture achieved higher failure loads than anchor tenodesis with a simple suture (122 N vs 46.1 N) and showed failure in distinct manners: suture slippage with the triple-loop suture and suture cutout with the simple suture technique. When comparing anchor vs interference screw fixation, Tashjian and Henninger24 reported similar failure loads in the 2 groups, but failure was attributed to suture pull-through in the anchor group and tearing of the tendon at the bone–screw–tendon interface in the interference screw, similar to the types of failure in the current authors' biomechanical study.

The current authors tested ultimate failure loads rather than cyclic loading for several reasons. There is no established protocol for cyclic loading, with the number of cycles used in published studies ranging from 100 to 5000.1,3,7,9,11,14 In cyclic testing of human cadaveric specimens, researchers have used maximum loads of 50 to 100 N.1,3,7,9,11,14 Cyclic loading tests might change the characteristics of the components at the fixation site, possibly compromising the integrity of the tendon, bone, and/or fixation construct, which could alter measurements of ultimate failure loads.

Moreover, the goal of cyclic loading is to reproduce the effects of repetitive movements during physical rehabilitation, but it cannot account for postoperative healing at the fixation site, which presents a complex balance between opposing processes. Biomechanical testing performed immediately after tenodesis with an interference screw in a sheep model differed significantly from testing performed 3 weeks after the procedure. This suggests that healing at the tendon–bone interface increases failure loads with an interference screw.25 In this situation, cyclic loading data yield useful information but do not completely represent postoperative events. Previous data on healing at the fixation site led the current authors to focus on ultimate failure load because it identifies the fixation technique that produces the strongest construct immediately after surgery. Reported rates of fixation failure range from 0.57%26 to more than 20%,27 and in the current authors' experience, when failure occurs, it tends to occur within the first few weeks after surgery, emphasizing the importance of initial fixation strength.28

The ultimate failure loads achieved in the current study differ from those reported by others. Several factors may account for the variation. In the current study, the cadaveric specimens had a mean age of 71 years, which is older than the specimens used in previous biomechanical studies of tenodesis.7,11,15,20 In the interference screw group, differences between the current results and those of previous studies can be attributed to the type of interference screw used. Biceptor (Smith & Nephew) screw fixation relies solely on interference fit and not on secondary fixation with a suture. Interference screws have been used widely in previous studies, achieving greater or equivalent failure loads compared with anchor techniques; in contrast, in the current study, the interference screw achieved the lowest failure loads, most likely because interference screw fixation did not rely on suture fixation.1,3,7,11,14,20,24 The use of a suprapectoral fixation site for the interference screw also may have contributed to construct weakness; Werner et al9 found that arthroscopic suprapectoral interference screw tenodesis was significantly weaker than open subpectoral biceps tenodesis with an interference screw. This difference supports the current findings, which suggest that properties of the suture and the tendon may have a greater influence on construct strength than implant choice for fixation to bone. The failure loads of the suture anchor treatment groups in this study are comparable to those of suture anchor treatment groups in other studies.1,7,22

The current study had several limitations. Tenodesis was performed on cadaveric specimens, which may not represent the in vivo strength of fixation constructs because of differences in the integrity of the LHB tendon. Mean age of the specimens was 71 years, which is older than typical patients who undergo biceps tenodesis and likely represents poorer tendon quality. Biceps tenodesis may be performed increasingly in older patients because tenodesis in patients older than 65 years has been shown to be successful, with a similar complication rate to that of patients younger than 65 years.29 Tissues were removed from the shoulder and humerus to facilitate construct placement; thus, the effects of surrounding tissues on failure load could not be ascertained. The effect of removal of surrounding soft tissue is unknown because the force vector was through the biceps muscle itself and was unlikely to be affected by surrounding tissues. Despite the authors' reasons for measuring load to failure, including consistency with published testing protocols, there are limitations associated with focusing on ultimate strength at time zero. Because the authors did not perform cyclic testing, they did not assess the effect of repetitive movements on the integrity of the constructs and did not measure creep at forces below yield strength. However, recent studies that included cyclic loading and load to failure have shown that ultimate failure load is relatively well correlated with performance in cyclic loading, suggesting that ultimate failure load may be an imperfect proxy for the performance of the construct in cyclic loading.2,30,31 Finally, the current study provides information about fixation strength immediately after the procedure but not about the changes that occur with biologic healing at the tenodesis site. Although it seems reasonable to avoid a construct (ie, interference screw without associated suture fixation) with load to failure that is less than that commonly reached during daily activities and rehabilitation, the authors cannot comment on the relative effectiveness of the other techniques.

Conclusion

The authors evaluated 6 techniques for biceps tenodesis by comparing load to failure and failure mechanism. Ultimate load to failure did not differ significantly among the techniques. Fixation failure occurred primarily at the tendon–suture interface and not through the anchor or the construct itself. Tendon quality and suture parameters were most important in determining failure load.

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Suture Parameters for Biceps Tenodesis Fixation Techniques

Fixation TechniqueNo. of SuturesNo. of Suture LimbsConfigurationNo. of Tendon Passes
Interference screw00Not applicable0
Cortical button12Krackow8
Double-loaded anchora24Lasso loop2
Single-loaded anchor24Lasso loop2
Soft tissue tenodesis24Simple4

Demographic Data and Failure Loads by Biceps Tenodesis Treatment Group

ParameterTreatment Group

Cortical Button (n=7)Double-Loaded 2.9-mm Anchor (n=7)Single-Loaded 1.7-mm Anchor (n=7)Double-Loaded 1.9-mm Anchor (n=7)Soft Tissue Tenodesis (n=7)Interference Screw (n=7)P
Age, mean±SD, y69±8.074±9.270±5.168±4.171±9.871±5.3.931
Female sex, No. (%)3 (43)2 (29)2 (29)3 (43)2 (29)1 (14).091
Apparent bone mineral density, mean±SD, g/cm20.70±0.120.70±0.120.75±0.140.74±0.080.75±0.070.80±0.09.683
Failure load, mean±SD, N136±33133±30132±37111±2198±2079±21.532
Authors

The authors are from The Johns Hopkins University School of Medicine (MD, BYS) and the Division of Shoulder Surgery (MTB, US), Department of Orthopaedic Surgery (MCB, SMB), The Johns Hopkins University, Baltimore, Maryland.

Mr Diaz, Mr Shi, Dr Baker, Dr Binkley, and Dr Belkoff have no relevant financial relationships to disclose. Dr Srikumaran is a paid consultant for Conventus, Fx Shoulder USA, Smith & Nephew, DePuy Synthes, Heron, and Pacira; has received grants from Smith & Nephew, Arthrex, DePuy Synthes, and Wright-Tornier; and holds stock in Tigon Medical and Quantum OPS.

This study was supported by a materials grant from Smith & Nephew, Andover, Massachusetts.

Correspondence should be addressed to: Uma Srikumaran, MD, MBA, MPH, Division of Shoulder Surgery, Department of Orthopaedic Surgery, The Johns Hopkins University, 601 N Caroline St, Baltimore, MD 21287 ( us@jhmi.edu).

Received: November 08, 2018
Accepted: February 04, 2019
Posted Online: January 13, 2020

10.3928/01477447-20200107-03

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