Article in The Journal of Bone and Joint Surgery · February 2018
Daniel Moya, MD, Silvia Ramon, MD, PhD, Wolfgang Schaden, MD, Ching-Jen Wang, MD, Leonardo Guiloff, MD, and Jai-Hong Cheng, MD
- Increasing evidence suggests that extracorporeal shockwave treatment (ESWT) is safe and effective for treating several musculoskeletal disorders.
- Two types of technical principles are usually included in ESWT: focused ESWT (F-ESWT) and radial pressure waves (RPW). These 2 technologies differ with respect to their generation devices, physical characteristics, and mechanism of action but share several indications.
- Strong evidence supports the use of ESWT in calcifying tendinopathy of the shoulder and plantar fasciitis.
- The best evidence for the use of ESWT was obtained with low to medium energy levels for tendon disorders as well as with a high energy level for tendon calcification and bone pathologies in a comprehensive rehabilitation framework.
Shockwave therapy was originally developed to disintegrate urinary stones 4 decades ago1. Since then, there has been remarkable progress regarding the knowledge of its biological and therapeutic effects. Its mechanism of action is based on acoustic mechanical waves that act at the molecular, cellular, and tissue levels to generate a biological response2.
Increasing evidence suggests that extracorporeal shockwave treatment (ESWT) is safe and effective for treating several musculoskeletal disorders3-5. The purpose of this article was to provide current evidence on the physical and biological principles, mechanism of action, clinical indications, and controversies of ESWT.
Physical Principles and Wave Generation
Two types of technical principles are included in ESWT—focused
ESWT (F-ESWT) and radial pressure waves (RPW), which are often referred to in the literature as radial shockwaves. These 2 technologies differ in their generation devices, physical characteristics, and mechanism of action, but they share several indications.
As shown in Figure 1, the following 3 shockwave generation principles are used for F-ESWT6,7:
1. Electrohydraulic sources (Fig. 1-A) produce a plasma bubble by high-voltage discharge between 2 electrodes in water at the focus closest to a paraellipsoidal reflector. The plasma expansion generates a shock front, which is reflected off the
reflector and focused on a second focus at the target tissue.
2. Electromagnetic sources (Fig. 1-B) with flat or cylindrical coils are also used. In the first system, a high-voltage pulse is sent through a coil, which is opposite a metallic membrane.
The coil produces a magnetic field, resulting in a sudden deflection of the membrane and generating pressure waves in a fluid. The waves are focused by a lens and steepen into a shockwave near the focus. The second electromagnetic generation source consists of a cylindrical coil and metallic membrane that is arranged inside a fluid-filled parabolic reflector. The membrane is accelerated away from the coil by a magnetic field.
An acoustic pulse emerges radially, and it is concentrated onto the focus of the system after reflection off the reflector.
Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a patent and/or copyright, planned, pending, or issued, broadly relevant to this work and “yes” to indicate that the author had other relationships or activities that could be perceived to influence, or have the potential to influence, what was written in this work (http://links.lww.com/JBJS/E569).
Copyright 2018 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
3. Piezoelectric sources (Fig. 1-C) produce shockwaves by a high-voltage discharge across a pattern of piezoelectric elements mounted on the inner surface of a spherical backing that is placed inside a fluid-filled cavity. Each element expands, generating a pressure pulse that propagates toward the center, or focal region, of the arrangement. Superposition of all pressure pulses and nonlinear effects produce a shockwave at focal region.
In RPW generators (Fig. 1-D), compressed air accelerates a projectile inside a cylindrical guiding tube. When the projectile hits an applicator at the end of the tube, a pressure wave is produced and radially expands into the target tissue. These devices do not emit shockwaves8 because the rise times of the pressure pulses are too long and the pressure outputs are too low (Fig. 2). Nevertheless, RPW may induce acoustic cavitation9.
The modes of action and the effects of RPW on living tissue may differ from those of focused shockwaves because bioeffects are related to the pressure waveform. F-ESWT and RPW may complement each other. While RPW is suitable for treating large areas, focused shockwaves can be concentrated deep inside the body.
Mechanism of Action
Despite the clinical success of the treatment, the mechanism of action of ESWT remains unknown. In 1997, Haupt proposed the following 4 possible mechanisms of reaction phases of ESWT on tissue10.
1. Physical phase: This phase indicates that the shockwave causes a positive pressure to generate absorption, reflection, refraction, and transmission of energy to tissues and cells11. Additional studies demonstrated that ESWT produces a tensile force by the negative pressure to induce the physical effects, such as cavitation, increasing the permeability of cell membranes and ionization of biological molecules. Meanwhile, many signal transduction pathways are activated, including the mechanotransduction signaling pathway, the extracellular signal-regulated kinase (ERK) signaling pathway, focal adhesion kinase (FAK) signaling pathway, and Toll-like receptor 3 (TLR3) signaling pathway, to regulate gene expressions 2,5,12-14.
Fig. 1 Figs. 1-A through 1-D Illustrations of an electrohydraulic (Fig. 1-A), an electromagnetic (Fig. 1-B), and a piezoelectric shockwave source (Fig. 1-C) and a radial pressure wave source (Fig. 1-D). The 26 dB region is defined as the volume within which the positive pressure is at least 50% of its maximum.
Fig. 2
Illustration showing the difference in pressure waveform between a shockwave and a radial pressure wave as used in medical applications.
2. Physicochemical phase: ESWT stimulates cells to release biomolecules, such as adenosine triphosphate (ATP), to activate cell signal pathways15,16.
3. Chemical phase: In this phase, shockwaves alter the functions of ion channels in the cell membrane and the calcium mobilization in cells17,18.
4. Biological phase: Previous studies have shown that ESWTmodulates angiogenesis (vWF [von Willebrand factor], vascular endothelial growth factor [VEGF], endothelial nitric oxide synthase [eNOS], and proliferating cell nuclear antigen [PCNA]), anti-inflammatory effects (soluble intercellular adhesion molecule 1 [sICAM] and soluble vascular cell adhesion molecule 1 [sVCAM]), wound-healing (Wnt3, Wnt5a, and beta-catenin), and bone-healing (bone morphogenetic protein [BMP]-2, osteocalcin, alkaline phosphatase, dickkopf-related protein 1 [DKK-1], and insulin-like growth factor [IGF]-1)18-22.
The effects of ESWT are summarized in Table I, with new functional proteins induced by ESWT promoting a chondroprotective effect, neovascularization, anti-inflammation, anti-apoptosis, and tissue and nerve regeneration2,12-14,16,19,22-52.
Furthermore, ESWT stimulates a shift in the macrophage phenotype from M1 to M2 and increases T-cell proliferation in the effect of immunomodulation27,28. ESWT activates the TLR3 signaling pathway to modulate inflammation by controlling the expression of interleukin (IL)-6 and IL-10 as well as improves the treatment of ischemic muscle12,13.
Finally, it appears that ESWT participates in mechanotransduction, producing biological responses through mechanical stimulation on tissues2,4,7,26.
Clinical Indications ESWT is indicated in chronic tendinopathies in which conventional conservative treatment is considered unsatisfactory after a rolonged and comprehensive management or as an alternative to surgery in patients with nonunion. ESWT is a noninvasive alternative in select cases when the indication for surgical treatment arises.
The International Society for Medical Shockwave Treatment (ISMST) has developed a list of approved clinical indications that are based on the strength of the supporting evidence53. The recommendations for ESWT indications and contraindications are summarized in Table II and Table III, respectively.
After ESWT, a comprehensive post-treatment schedule, individualized for each pathology and each patient’s clinical status, should be given to the patient including avoidance of the use of the anatomic structure, a specific exercise program, and instructions to avoid overload.
Shoulder Tendinopathies Calcifying Tendinopathy of the Shoulder (CTS) ESWT has emerged as an alternative therapy prior to invasive procedures when conservative treatment has failed as described
for Gartner type-I or II rotator cuff calcifications54,55 (Fig. 3).
Fig. 3
Anteroposterior radiographs of a right shoulder with a G¨artner type-II calcification of the supraspinatus before focused shockwave treatment (Fig. 3-A) and at 3 months after treatment (Fig. 3-B), showing that the calcification has disappeared.
The rate of successful reabsorption reported by different authors has a very wide range56-66.
Gerdesmeyer et al.58, in a multicenter randomized controlled trial (RCT) that included 144 patients, reported significantly better results in patients treated with F-ESWT, both low and high energy, compared with placebo, resulting in improvement with respect to pain, shoulder function, and calcium resorption in 86% in the high-energy group at 1 year compared with 37% in the low-energy group and 25% in the placebo ESWT group. Cosentino et al.59, in a single-blind trial using F-ESWT, reported a significant increase in shoulder function, a decrease in pain compared with placebo, and calcium resorption of 71% by using F-ESWT, at 6 months. Hsu et al.60, in an RCT, achieved good or excellent results in 87.9% of patients treated with high-energy F-ESWT.
Cacchio et al.57 obtained a surprisingly high rate of reabsorption using RPW (86.6% complete and 13.4% partial resorption) at the 6-month follow-up; however, most studies have considered that high-energy F-ESWT is more likely to result in better radiographic and clinical outcomes55,56,58-66.
Several systematic reviews and meta-analyses have demonstrated that high-energy F-ESWT is a safe, effective treatment for CTS61-66.
Kim et al.67 compared RPW with ultrasound-guided needling and reported that the latter treatment method was more effective in functional restoration and pain relief in the short term. However, Moya et al.68 pointed out numerous methodological flaws in that study. There was missing information about the ESWT device used (focused or radial), methodological explanations were short and imprecise, the point of maximum tenderness was treated instead of focusing on topographic anatomy or locating calcium deposits with fluoroscopy or ultrasound, and the ESWT treatment protocol was nonstandard68.
Rompe et al.69 and Rebuzzi et al.70 compared F-ESWT with open and arthroscopic surgery in CTS, respectively. They concluded that the results are comparable and that high-energy F-ESWT should be the first choice when conservative treatment has failed, because of its noninvasiveness.
In summary, given its efficacy in pain eduction55,56,58-65,69,70 and functional utcomes55,58,61-66,69,70, resorption rate55,58-61,63,64,66,69, safety55,59,60,64, noninvasiveness55,69,70, reduced recovery time55, and cost-effectiveness55, we consider that high-energy F-ESWT is the treatment of choice in CTS when conservative treatment has failed.
Noncalcifying Tendinopathy of the Shoulder
Unlike CTS, the treatment of noncalcified tendinopathies with shockwaves is controversial71. Both favorable and poorly performing studies in many cases present inadequate inclusion criteria (wide age ranges, heterogeneous populations, and insufficient diagnostic evaluations). It is inadmissible to consider “subacromial pain” 72 or “non-specific shoulder pain”73 as a diagnosis of shoulder disease if all possible differential diagnoses have not been ruled out. This confusion is reflected in the results of the meta-analyses and systematic reviews62,63,65.
Huisstede et al.63 found no strong evidence to support the efficacy of ESWT to treat noncalcific rotator cuff tendinosis beyond the applied energy level. Speed65 did not support lowdose or high-dose F-ESWT.
We are unable to recommend the use of ESWT in noncalcific tendinopathy of the shoulder because of the lack of compelling evidence.
Lateral Epicondylopathy of the Elbow There are many therapeutic options for treating lateral picondylopathy. The existing evidence does not clearly support the efficacy of any of the available treatment methods for this clinical condition74-79. ESWT is not the exception79, although it was approved by the U.S. Food and Drug Administration (FDA) for treating this disease in 200280.
Several systematic reviews and meta-analyses have shown conflicting evidence81-83. It is difficult to interpret the data because of the variety of study designs and the use of different shockwave devices84.
Pettrone and McCall85 reported a significant improvement with respect to pain and function in the active treatment group at 6 and 12 months compared with the placebo group in a study with Level-I evidence.
In a review study by Thiele et al.80, the authors stated that several clinical trials have achieved very good results with the use of ESWT for lateral epicondylopathy of the elbow. That review only included Level-I studies using focused ESWT and RPW, and the authors concluded that lateral epicondylopathy is a primary indication for ESWT.
Lee et al.86 found similar outcomes when comparing steroid injections with ESWT in lateral and medial epicondylopathy. Radwan et al.87 found no significant differences between F-ESWT and percutaneous tenotomy.
Although the strength of the supporting evidence is not strong, no method to treat lateral epicondylopathy is backed by studies with a high level of evidence. As the benefits largely exceed any potential harm, we recommend the use of radial or focused ESWT technologies when conventional rehabilitation treatment has failed.
Greater Trochanteric Pain Syndrome
There is no agreement about the optimal management for greater trochanteric pain syndrome88. Numerous conservative treatments (nonsteroidal anti- nflammatory drugs, physiotherapy, and corticosteroid injections) have been recommended88.
Two studies provided Level-II and III evidence for RPW effectiveness in 74% of patients at 15 months88 and 78.8% at 12 months89, respectively.
Rompe et al.88 compared RPW with 2 other reatment methods, steroid injection and home training exercise, in a quasiRCT. Although RPW was inferior to steroid injection at 1 month, RPW demonstrated better outcomes at 4 months compared with steroid injection and home exercise training, and it matched home training at 15 months88. Furia et al.89 compared RPW and nonoperative therapy in patients with greater trochanteric pain syndrome. The RPW group had significant improvement with respect to pain, function, and Roles and Maudsley scales than the standard treatment group at 12 months89.
Although the available evidence on ESWT in greater trochanteric pain syndrome is limited, RPW appears more effective than a home exercise program and local corticosteroid injection after short-term and mid-term follow-up (up to 15 months) of greater trochanteric pain syndrome88-90.
Patellar Tendinopathy
Patellar tendinopathy treatment represents a challenge91. There is no evidence-based protocol for the appropriate management of patellar tendinopathy90,92-95. Eccentric training appears to be the first-line treatment92-95.
New therapies, such as prolotherapy, dry-needling, platelet-rich plasma (PRP), cell therapy, or hyaluronic acid, may offer alternatives to standard treatments93,94.
Promising results have been shown with ESWT90,91,96-100.
Wang et al.96 compared F-ESWT and conservative treatment in an RCT and obtained good or excellent results in 90% of the ESWT group at the 2 to 3-year follow-up evaluation compared with 50% in the conservative treatment group. Furia et al.97 compared RPW and standard treatment in a retrospective study at 1 year and reported satisfactory results in 75.8% of patients receiving a single session of low-energy radial pressure waves compared with 17.2% in other nonoperative therapies.
By contrast, in an RCT, Zwerver et al.101 compared real and placebo piezoelectric ESWT in athletes and did not find significant differences between the groups in terms of pain and function at 22 weeks. Another recent RCT on 52 athletes diagnosed with patellar tendinopathy evaluated the effect of ESWTor sham ESWT in addition to an eccentric training program and did not find differences at 6 months of follow-up102.
However, these studies describing poor results with the use of ESWT included certain features and methodological errors such as: no complementary studies were performed to rule out calcification or partial rupture with a different prognosis101,102; applying ESWT with a piezoelectric device101,102;
adapting the ESWT intensity to patient tolerance instead of a specific therapeutic energy level101; high energy levels101; allowing for training and competition during and after ESWT treatment instead of removing the patient from sports101,102; and
ESWT as a solitary treatment not combined with exercise101.
Peers et al.99 retrospectively compared F-ESWT with surgery in 28 patients at an average of 24 months and showed excellent or good results according to the Roles and Maudsley score in 66% of the ESWT group, which was comparable with 58% in the surgery group. The authors concluded that F-ESWT in chronic patellar tendinopathy is an alternative to surgery, without resulting in incapacity, when conservative treatment fails99.
Review of the literature shows that ESWT is safe and effective in the treatment of patellar tendinopathy90,91,98. Current evidence supports the use of F-ESWTand RPW for patellar tendinopathy with moderate or low-intensity protocols, especially in patients attempting to avoid an invasive intervention.
Achilles Tendinopathy
Achilles tendinopathy affects active athletes as well as the sedentary population103. According to its anatomical location, it is classified into 2 categories, insertional and noninsertional or midportion tendinopathy.
Conservative treatment includes pain medication, heel lifts, eccentric exercises, physiotherapy, steroid and platelet-rich plasma injections, low-level laser therapy, and radiofrequency, among others104-109. Different shockwave sources and protocols have been used. A Level-I study with 48 patients compared piezoelectric F-ESWT and placebo ESWT and found better results for the ESWT group110. Furia reported good results for insertional111 and noninsertional112 Achilles tendinopathies with RPW.
In an RCT, Rompe et al.113 demonstrated that RPW is
more effective than eccentric loading exercises for insertional Achilles tendinopathy at the 15-month follow-up evaluation.
Furthermore, there is demonstrated superior efficacy of combining eccentric loading and ESWT compared with eccentric loading alone in those patients114.
Gerdesmeyer et al.108 highlighted the efficacy of both FESWTand RPW in chronic Achilles tendinopathy. On the other hand109, Costa et al. found no significant differences between the F-ESWT and control groups in terms of pain, function, and quality of life for 49 patients with Achilles tendinopathy at 3 months in a Level-I RCT109. Those authors concluded that there was no support for the use of ESWT in Achilles tendinopathy.
ESWTwas performed once a month for 3 months, instead of at weekly intervals as per the standard recommendations4,5. Two elderly patients had an Achilles rupture after ESWT, but, surprisingly, no complementary explorations were performed before treatment to rule out previous partial ruptures.
Three systematic reviews90,115,116 and 1 review117 showed satisfactory evidence of the effectiveness of low-energy ESWT in insertional and noninsertional chronic Achilles tendinopathy after failure of conservative treatment and before considering
surgery, especially in combination with eccentric loading.
Plantar Fasciitis
Plantar fasciitis is a degenerative musculoskeletal disorder118. In 2002, Buchbinder et al.119 found no evidence to support the use of ESWT in plantar fasciitis. In 2003, another RCT considered electromagnetic ESWT to be ineffective in this field120.
Since then, several studies with a high level of evidence have supported both focused121,122 and radial123,124 technologies for this disorder. Gollwitzer et al.125, in a study of the treatment of recalcitrant plantar fasciitis with an electromagnetic device, reported pain reduction in 69.2% of the patients in the ESWT group compared with 34.5% in the control group. Ogden et al.126, in an RCT, concluded that electrohydraulic F-ESWT is effective and safe and that the clinical improvement lasts beyond 1 year. In a Level-I study, Wang et al.122 compared F-ESWT with conservative treatment modalities. The shockwave group had excellent or good results in 82.7% of the patients compared with 55% in the control group at a follow-upof between 60 and 72 months; also, the shockwave group had a much lower recurrence rate.
Gerdesmeyer et al.123, in an RCT, reported an overall success rate of 61% with RPW compared with 42.2% in the placebo group at 12 weeks.
Recently, a multicenter study127 showed that the combination of a plantar fascia-specific stretching program with low-energy RPW achieves better results than RPW alone. Three meta-analyses128-130 found that ESWT is effective for treating chronic plantar
fasciitis. Aqil et al.128 recommended the use of shockwave treatment in plantar fasciitis on the basis of its efficacy and safety.
Several studies have compared F-ESWT with surgery131-134, supporting the use of shockwave treatment because of its effectiveness128,132,134 and because patients can quickly resume full activities131 and athletes have a chance to continue sports activities133.
Since 2010, the American College of Foot and Ankle
Surgeons has recommended ESWT as a treatment of choice for plantar fasciitis with or without a plantar spur when nonoperative treatment has failed135.
Bone Disorders
Haupt10, in 1997, recognized the dynamic interaction between ESWT and bone. It was initially hypothesized that shockwavescreated microlesions in treated bone. This appreciation completely changed when Wang et al.19,20 demonstrated that shockwaves generate upregulation and expression of various pro-angiogenic and pro-osteogenic growth factors, stimulating bone-healing.
Basic research has shown that because of mechanical forces delivered by shockwaves to the cells and to the extracellular matrix, messengers are liberated and activate different genes and groups of genes in the cell nucleus50,136-140. This phenomenon of biological conversion from a mechanical stimulus into electrochemical activity is called “mechanotransduction.”141
Fig. 4
Figs. 4-A, 4-B, and 4-C Anteroposterior radiographs of the right femur of a 37-year-old man who had sustained a femoral fracture in a motorcycle accident; the fracture was initially treated with an intramedullary nail, but it was revised 14 months later because of nonunion and an external fixator was applied. Fig. 4-A At 6 months after the second surgery, there were no signs of bone-healing. Fig. 4-B At 4 months after F-ESWT, a successful union of the fracture was evident. Fig. 4-C The final result after external fixator removal demonstrated complete healing.
The use of ESWT for nonhealing fractures was first reported, to our knowledge, in 1991 by Valchanou and Michailov142. Since then, several observations and trials have supported the efficacy of ESWT for nonunion and delayed fracture-healing143-157 (Table IV).
Cacchio et al.152, in a Level-I RCT, compared different ESWT high-energy levels (0.4 mJ/mm2 [Group 1] and 0.7 mJ/ mm2 [Group 2]) and surgery (Group 3) for the treatment of hypertrophic long-bone nonunions and obtained success rates of 70%, 71%, and 73%, respectively, at 6 months. No adverse effects occurred in the ESWT groups compared with a 7% rate of complications in the surgical group.
Similar results were reported by Furia et al.154, who observed that high-energy F-ESWTwas as effective as intramedullary screw fixation in the treatment of nonunion of a fracture of the fifth metatarsal; however, screw fixation was more often associated
with complications that frequently resulted in additional surgery.
Notarnicola et al.155 found that the results of ESWT were comparable with those of surgical stabilization and bone graft for the treatment of carpal scaphoid pseudarthrosis.
Kuo et al.156 reported that the success rate of ESWT was 63.6% in the treatment of atrophic nonunions of the femoral shaft and could be as high as 100% if applied within 12 months after the initial treatment. Poor results were associated with instability, a gap at the nonunion site of >5 mm, and atrophic nonunion.
As some Level-I and II evidence has demonstrated that the efficacy of ESWT is comparable with that of surgery for the treatment of nonunions152,154,155, and ESWT is practically free of adverse effects and more economic, it may progressively be considered as the first choice in the treatment of stable nonunions with a gap of <5 mm in long bones (Fig. 4). For bone treatment, the basic principles of acute fracture management should be implemented after F-ESWT (immobilization, casting, and weight-bearing restrictions).
ESWT seems to be an effective option in adult osteochondritis dissecans158-160, but further studies are required to determine long-term results.
Economic and Administrative Considerations
We acknowledge that it is currently difficult to obtain reimbursement for ESWT in the United States. We hope that heightened awareness as to the efficacy of ESWT, as well as recognition of how ESWT can be a cost-saving measure, will lead to changes in reimbursement coverage.
Shockwave treatment is indicated when standard conservative treatment has failed, so its cost should be comparedwith the cost of surgery. Dubs161 compared the efficacy and costs of ESWTwith the usual treatments for CTS. In addition to demonstrating that ESWT was more efficacious, it also allowed for an average savings of US$2,000 per patient in comparison with alternative therapies.
Haake et al.162 showed that the cost of treatment for CTS was between €2,700 and €4,300 per patient for ESWT compared with €13,400 to €23,450 for surgery and concluded that the cost of surgery was 5 to 7 times higher than ESWT. Ramon et al. ´ 163 reported, in absolute numbers, a savings of approximately €2,000 per patient for ESWT compared with surgery for the treatment of calcifying tendinopathy of the shoulder.
Overview ESWT is considered to be an alternative to surgery for several chronic tendinopathies and nonunions because of its efficacy, safety, and noninvasiveness. The best evidence supporting the use of ESWTwas obtained with low to medium levels of energy for tendon disorders as well as with a high energy level for tendon calcification and bone pathologies in a comprehensive rehabilitation framework.
Because of the variability in the treatment protocols, the methodological quality of many ESWT studies is limited.
Further research from well-designed, high-quality studies is required to standardize the treatment parameters and demonstrate the optimal ESWT approach for health-care decisionmaking.
With adequate patient selection, appropriate indications, homogeneous ESWT therapeutic protocols, and proper application, ESWT could make a paramount contribution to noninvasive treatment of certain musculoskeletal disorders.
NOTE: The authors thank Dr. Achim M. Loske Mehling for his important contribution on the subject of physical principles and wave generation, and John Furia, MD, for his kind contribution on Achilles tendinopathy and on economic and administrative considerations.2
Daniel Moya, MD1
Silvia Ramon, MD, PhD ´ 2
Wolfgang Schaden, MD3
Ching-Jen Wang, MD4
Leonardo Guiloff, MD5
Jai-Hong Cheng, MD4
1 Buenos Aires British Hospital, Buenos Aires, Argentina
2 Hospital Quiron, Barcelona, Fundacion Garcıa Cugat, Spain
3 AUVA-Head Office, Vienna, Austria
4 Chang Gung Memorial Hospital, Kaohsiung, Taiwan
5 Clınica Arauco Salud, Santiago de Chile, Chile
E-mail addresses for D. Moya: drdanielmoya@yahoo.com.ar;
drdanielmoya@gmail.com
ORCID iD for D. Moya: 0000-0003-1889-7699
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