ORIGINAL RESEARCH article

Front. Pediatr., 15 December 2023

Sec. Pediatric Surgery

Volume 11 - 2023 | https://doi.org/10.3389/fped.2023.1295212

Myositis ossificans in the pediatric population: a systematic scoping review

  • Department of Pediatric Orthopedic Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Abstract

Introduction:

Circumscribed or pseudomalignant myositis ossificans (MO) is a rare and benign condition characterized by heterotopic bone formation in soft tissues. The clinical presentation of MO, imaging investigations, histological findings, and treatment strategies are unclear, especially in the pediatric population.

Materials and methods:

A literature search was conducted in PubMed, Scopus, and Google Scholar electronic databases to identify original articles and reviews in English or French of traumatic and non-traumatic MO. Studies were selected by 2 independent reviewers following the PRISMA recommendation and descriptive data were extracted. We harvest in each case the sex, age at diagnosis, location, presence of initial trauma, pre-emptive diagnosis, modalities of imagery used, realized biopsy, treatment performed, and type of follow-up.

Results:

Sixty pediatric cases of MO were identified between 2002 and 2023. Twenty-three patients (38.3%) were diagnosed with idiopathic/pseudomalignant and 37 patients (61.7%) with circumscribed. The mean age at diagnosis was 9.5 years (range 0.2–17 years), with a male-to-female ratio of 1:1. The initial pre-emptive diagnosis was neoplasia in 13 patients (21.7%). The biopsy was percutaneous in 9 patients (15%) and incisional in 7 patients (11.7%). Histological analysis was achieved in 35 cases (57%). Surgical excision was the first line treatment in 46.7% of patients, and non-surgical in the remaining patients. The follow-up strategy was clinical in 16 patients (26.7%) or based on imaging investigation in 23 patients (38.3%).

Discussion:

Although MO in children is described as a rare pathology, identifying the benignity of the condition is essential to avoid unnecessary invasive treatment and to avoid delaying the treatment of a potentially life-threatening entity. It seems that there is no consensus established concerning the proper imaging for diagnosis. Clinicians should acknowledge that the absence of a triggering trauma tends to direct the investigation and the management toward a surgical attitude. Conservative management is key, however, surgical excision can be proposed on matured lesions on a case-by-case basis. The absence of recurrence is not excluded. Therefore, a close clinical follow-up is suggested for all cases. The true benefit of a radiological is questioned in a question known to be self-resolving.

Introduction

Historically, the term MO has been used to describe a broad spectrum of processes ranging from benign solitary lesions to progressive congenital syndromes (e.g., MO progressiva). The literal definition of the MO was challenged since 1868 which was first described by von Dusch as a benign, self-limiting ossifying tumor occurring within skeletal muscle. The most current accepted definition of the term is a self-limiting, benign ossifying lesion that can affect any type of soft tissue, including subcutaneous fat, tendons, and nerves. It is mostly found in skeletal muscle as a solitary lesion (). The pathophysiology of MO formation is incompletely understood (, ). The pathophysiologic hypothesis seems to show that it occurs through inappropriate differentiation of fibroblasts into osteogenic cells (). Several triggering factors for this differentiation have been described such as trauma and muscle overuse.

Fundamentally, three subgroups of MO may be proposed based on etiology: MO progressiva (severe generalized form); pseudomalignant MO (without a history of trauma); circumscribed MO (related to direct trauma) (, ). MO progressive has been excluded from the scope of this article for its distinct clinical features and management. MO progressiva typically presents as a more severe and generalized form of myositis ossificans, affecting a broader range of muscles and requires different treatment approaches compared to the circumscribed and pseudomalignant subtypes.

Circumscribed and pseudomalignant MO are most common in men aged from 20 to 30 years old (). They commonly involve the large muscle groups in the extremities such as the quadriceps femoris, brachialis muscle, thigh adductors, and deltoid muscle (). The early onset involves a firm and tender mass felt within the soft tissue. Restriction of motion of the adjacent joint is typically associated. Non-traumatic and traumatic MO are usually characterized by a period of painful active growth followed by spontaneous clinical improvement and resolution. Initially, the lesion may be confused with a growing malignant tumor or an infection such as abscess. The differential should also consider granulomatous infections, sarcomas, extraosseous osteochondroma, desmoid tumors, nodular fasciitis and calcifying aponeurotic fibroma.

In the pediatric population the rarity of this pathology, variability in terminology, clinical presentation, imaging characteristics, and histopathology at times makes the diagnosis of MO challenging. Not rarely these pathologies are initially misleading as malignancies or chronic osteoarticular infections which leads to an over-treatment sometimes invasive and generates a lot of anxiety within the patient and his family.

This study aims to perform a comprehensive review of MO in the pediatric population over the last 20 years. Additionally, the demographic data and management strategy between pseudomalignant MO (without a history of trauma); circumscribed MO (related to direct trauma) groups were confronted.

Materials and methods

Search strategy and selection criteria

Following the recommendations of the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) statement, a systematic review of the literature was performed with the following electronic databases: PubMed, Scopus, and Google Scholar. Keywords and index terms (MeSH headings) used were “MO” and “child”.

There were no language restrictions. We manually reviewed the reference lists of identified studies for further inclusions. Eligibility was independently assessed by two authors (IC and MM), and differences were resolved with the help of a third author (BT), and consensus obtained.

Study selection

The inclusion criteria for our studies were:

  • -

    Patients under 18 years old

  • -

    Patients diagnosed with traumatic (circumscribed) and non-traumatic (pseudomalignant) MO

  • -

    Case studies published between 2002 and 2022.

The exclusion criteria were:

  • -

    Cases of progressive generalized ossifying myositis

  • -

    Follow-up period of less than 6 months.

Data collection process

Eligibility was independently assessed by 2 authors (MM and IC), and differences were resolved with the help of a third author (BT) and consensus obtained. Full-text manuscripts were reviewed against specific inclusion criteria.

Two authors (MM and IC) independently extracted the following data: demographic characteristics (sex and age), localization of the lesion, initial pre-emptive diagnosis, imagery investigations, the need and the type of biopsy (percutaneous vs. open biopsy), treatment (conservative vs. surgical), follow-up monitoring strategy (clinical vs. radiological).

Results

Of 1593 identified articles between 2002 and 2022, 40 fulfilled the review criteria (Figure 1). All these reports had a level of evidence of IV or V. A total of 60 pediatric cases with traumatic and non-traumatic MO were identified (Table 1). The mean age of the patients at diagnosis was 9.5 years (range 0.2–17 years). The male-to-female ratio was 1:1. For further data analysis, the identified cases were respectively separated into an atraumatic group (AGMO) and a traumatic group (TGMO) (Table 2).

Figure 1

Table 1

AuthorYearSexAgeLocationTraumaInitial diagnosisImageryBiopsyTreatmentFollow-up
Yazici et al. ()2002M8 yearsParavertebralNoNeoplasiaRx, US, CTNoneExcisionClinical
Jayasekera et al. ()2005M15 yearsHandExcessive activityMORx, US, CT, MRINoneConservativeClinical
Chadha et al. ()2007M10 yearsElbow, wristYesMORxUDConservativeClinical
Cabello et al. ()2008M4 yearsArmNoNeoplasiaRx, MRI, BS, PET-CTPercutaneousExcisionClinical
Michelli et al. ()2009M11 yearsThighYesInfectionRx, US, CT, MRIIncisionalExcisionRx, CT
Leung et al. ()2010M11 yearsKneeYesUDMRINoneExcisionClinical
Utumi et al. ()2010M17 yearsCheekNoNeoplasiaRx, CTIncisionalExcisionRx, CT
Findlay et al. ()2010M8 yearsNeckYesMORx, CT, MRINoneConservativeCT
Koob et al. ()2010F10 yearsChestYesNeoplasiaRx, CT, BS, PET-CT, MRIIncisionalChemoth., conserv.CT
Davies et al. ()2011F15 yearsKneeYesMORx, US, MRINoneConservativeMRI
Jujena et al. ()2011M6 yearsBilat. tighNoInfectionRx, CTNoneConservativeRx
Man et al. ()2011F17 yearsNeckYesInfectionUS, CT, MRINoneExcisionUS
Harmon et al. ()2012F2,5 monthsNeckYesNeoplasiaRx, CT, MRIPercutaneousConservativeRx
Lau et al. ()2012F16 yearsThighNoNeoplasiaRx, US, MRIPercutaneousConservativeClinical
De Smet et al. ()2012F12 yearsHandYesMORx, US, CTNoneExcisionUD
Mani-Babu et al. ()2014M14 yearsThighYesMORx, MRINoneConservativeClinical
Masquijo et al. ()2014F16 yearsPsoasExcessive activityNeoplasiaRx MRIPercutaneousConservativeMRI
Kanthimati et al. ()2014M13 yearsElbowYesMORxNoneExcisionRx
Say et al. ()2015F10 yearsForearmNoNeoplasiaRx, MRIUDExcisionClinical
Akahane et al. ()2015F15 yearsHandNoUDRx, US, MRIIncisionalExcisionClinical
Yamaga et al. ()2015F11 yearsShoulderNoNeoplasiaCT, MRI, PET-CTIncisionalConservativeRx
Li et al. ()2016M9 yearsElbowNoInfectionRx, CTPercutaneousExcisionClinical
Lin et al. ()2016M13 yearsKneeNoNeoplasiaRx, CTNoneExcision (2x)Rx
Simmonds et al. ()2016F5 monthsNeckNoUDMRIPercutaneousExcisionClinical
Becker et al. ()2016M17 yearsCheekYesInfectionCTNoneExcisionCT
Desai et al. ()2017F12 yearsPoplitealExcessive activityMORx, MRINoneExcisionRx
Sferopoulos et al. ()2017F (11) M (9)3–14 yearsPelvis (6)
Thigh (2)
Elbow (10)
Chest (1)
Hip (1)
No (1)
Yes (19)
UD (20)Rx (20)NoneExcision (4)
Conservative (16)
Rx (1)
UD (19)
Mohamed et al. ()2018M15 yearsHipNoMORxNoneExcisionClinical
Kougias et al. ()2019F5 yearsBilat. hipNoMORx, CTNoneConservativeRx
M5 yearsBilat. hipNoMORx, CT, BSNoneConservativeRx, CT
Onen et al. ()2019F5 yearsLumbarNoMORx, CT, MRIUDExcisionRx
Dubuisson et al. ()2019M5 yearsNeckNoNeoplasiaRx, US, CT, MRI, BSIncisionalExcisionMRI
Palla et al. ()2020F7 yearsJawYesMOCTNoneExcisionClinical
Akatli et al. ()2021F13 yearsPectoralisNoInfectionUS, MRINoneExcisionClinical
Chen et al. ()2021M9 yearsElbowYesMORx, US, CT, MRINoneExcisionRx
Rehman et al. ()2021F12 yearsAxillaNoInfectionUS, MRINoneExcisionClinical
Cao et al. ()2021F8 yearsElbowYesMORxNoneConservativeRx
Dennison et al. ()2022MAt birthLegNoNeoplasiaRx, CT, MRIPercutaneousConservativeRx
Vitale et al. ()2022M14 yearsNeckNoNeoplasiaRx, US, CT, MRIPercutaneousExcisionUD
Xia et al. ()2022F8 yearsThighNoInfectionRx, US, CTIncisionalExcisionClinical
Silveri et al. ()2022M2 yearsElbowNoMORx, MRI, BSPercutaneousConservativeMRI

Demographic and clinical characteristics of included cases.

UD, undocumented; Y, year(s); M, month(s); Rx, Radiography; US, Ultrasound; CT, Computed Tomography; MRI, Magnetic Resonance Imaging; BS, Bone Scintigraphy

Table 2

All cases of MO n = 60TGMO n = 37AGMO n = 23P
Sex
 Male3017 (45.9)13 (56.5)0.42
 Female3020 (54.1)10 (43.5)0.42
History trauma
 Yes3434 (91.9)0
 Activity33 (8.1)0
 No23023 (100)
Initial diagnosis
 MO1611 (29.7)5 (21.7)0.65
 Neoplasia133 (8.1)10 (43.5)0.001
 Infection83 (8.1)5 (21.7)0.13
 Undocumented2321 (56.7)3 (13.0)
Location
 Upper limb23 (38.3)16 (43.0)7 (30.4)0.32
 Lower limb24 (40)15 (40.5)9 (39.1)0.92
 Trunk4 (8.3)1 (2.7)3 (13.0)0.12
 Head and neck9 (15.0)5 (13.5)4 (17.4)0.68
Imaging
 Radiography5232 (86.5)20 (86.7)0.96
 Ultrasound146 (16.2)8 (34.8)0.099
 CT2310 (27.0)13 (56.5)0.009
 MRI2511 (29.7)14 (60.9)0.017
 PET31 (2.7)2 (8.7)0.30
 Bone scintig.51 (2.7)4 (17.4)0.045
Biopsy
 None4132 (86.5)9 (39.1)0.0001
 Percutaneous92 (5.4)7 (30.4)0.008
 Incisional72 (5.4)5 (21.7)0.02
 Undocumented31 (2.7)2 (8.7)
Treatment
 Conservative3225 (67.6)7 (30.4)0.01
 Surgical2813 (35.1)15 (65.2)0.01
Follow-up
 Clinical165 (13.5)11 (47.8)0.01
 Radiological2312 (32.4)11 (47.8)0.39
Undocumented2120 (54.1)1 (4.3)

Clinical and management differences between in the TGMO and AGMO.

Twenty-three patients (38.3%) were diagnosed with idiopathic/pseudomalignant MO (=AGMO) and 37 patients (61.7%) with circumscribed MO (=TGMO). In the TGMO, a traumatic triggering event was recorded in 34/37 cases, while minor repetitive trauma or excessive activity was incriminated in 3/37 cases. All cases of AGMO had no triggering trauma identified upon clinical history.

In general, MO was localized in the muscle groups of the upper limb (23), the lower limb (13), the pelvis (11), the neck (6), the head (3), the chest wall (2), and the back (2). We observed a similar anatomical distribution between the AGMO and TGMO groups.

During the diagnosis process, the imaging investigations performed were 52 radiographs (86.6%), 14 ultrasounds (23.3%), 23 CTs scans (38.3%), 25 MRIs (41.6%), 5 bone scintigraphies (8.3%), and 3 PETs (5%). Based on clinical and imaging findings, the initial pre-emptive diagnosis was MO in 16/60 patients (26.7%), infection in 8/60 patients (13.3%), and neoplasia in 13/60 patients (21.7%). The remaining cases did not document this information.

Tissue samples were obtained by achieving percutaneous biopsy in 9 patients (15%), incisional biopsy in 7 patients (11.7%), and straightforward resection in 19 patients (31.7%). Biopsy was repeated in one patient due to a non-conclusive first histopathological examination. Four cases in the TGMO (10.8%) against 12 cases in the AGMO (52,2%) needed a biopsy to achieve a diagnosis.

First-line treatment was non-surgical in 32 patients (53.3%). Conservative treatment includes the use of anti-inflammatory drugs, corticosteroids, rest, or physiotherapy. Bisphosphonate injections were performed in only one case. Four children who failed conservative treatment had subsequent surgical excision. Surgical excision was the first-line treatment in 28 patients (46.7%). Detailed treatment strategies within the AGMO and TGMO subgroups are illustrated in Table 2.

The follow-up strategy was clinical in 16 patients (26.7%) or based on imaging investigation in 23 patients (38.3%) and was not documented in 21 cases (35%). The type of imaging performed for follow-up was radiography alone (20%), MRI (6.7%), CT scan alone (5%), radiography and CT combined (5%), and ultrasound (1.6%). Recurrence occurred in one case supposedly because of early surgical excision.

Discussion

Pseudo-malignant and circumscribed MO is a benign and self-limiting ossification within the soft tissue. The typical evolution of MO is the growth of a firm extraskeletal mass for several months until reaching its peak dimension and then spontaneously resolving (). The exact causes of MO are not well understood. It may be related to a single and direct trauma, recurrent minor trauma, microscopic damage due to muscle overuse, orthopedic or maxillofacial operations, or muscular bleeding in hemophilic children (, , ).

Demographics

MO in the pediatric population can occur at any age with a mean of 9.5 years old (range 0.2–17 years). In the general population, it typically involves young adults with a mean age of 36 years old (range 4–84 years). The sex ratio was balanced in our review (30♀/30♂) while previous reviews performed on the general population showed a significant masculine tendency ().

Clinical presentation

As observed in the general population, MO is mostly located in the large skeletal muscle of the extremities (76.6%). The upper and lower extremity have shown the same prevalence of 38.3% and 40% respectively. The head and neck, and the trunk are less frequent with a prevalence of 15.0% and 8.3% respectively.

Myosistis ossificans can clinically mimic extra-skeletal osteosarcoma, parosteal osteosarcoma, rhabdomyosarcoma, synovial sarcoma, and lymphoma. In this review, neoplasia was the initial pre-emptive diagnosis in at least 21.7% of the cases, illustrating an appreciable level of suspicion for this differential. We have also observed an increased level of suspicion for neoplasia when a history of trauma is absent (p = 0.001). This is, we believe, why clinicians are driven to perform further imaging and histopathological investigations ().

Imaging

Imaging findings change through the evolution of MO. At the onset, radiography is usually negative or may assess soft tissue swelling. In the presence of trauma, soft tissue swelling seen in early radiography is often mistaken for intramuscular hemorrhage (Figure 2A). Three to four weeks after the triggering event, a peripheral pattern of calcification with a low-density center starts to appear (). A similar evolution over time is observed in computed tomography and MRI (Figure 2B). Pathognomonic MRI features of advanced MO associate a well-defined heterogeneous mass with a signal intensity approaching bone marrow enhanced by contrast injection, and a rim of cortical calcification independent of the underlying bone (). MRI may show prominent lymph nodes, signaling inflammatory response, and may be confused with a metastatic process (). This hyperinflammatory state is also sensitively appreciated with an intake signal on PET CT and 99mTc diphosphonate bone scintigraphy (, ). Features in early imaging are not pathognomonic and therefore create confusion. This initial phase of uncertainty seems to drive clinicians to perform further imaging. Indeed, we have assessed a significant difference in the need for MRI and CT imaging, in favor of the AGMO, suggesting a more difficult diagnostic reflection when no triggering trauma is documented.

Figure 2

Biopsy and histological features

The typical microscopic findings observed in matured MO are described as the zonal phenomenon (Figure 3) (). The tumor presents a progressive maturation evolving in four levels from its center to its periphery. At the core, multiple immature and proliferative cells are packed. In the adjacent zone, cellular osteoids are observed and separated by a cellular stroma. In the more peripheral zone, osteoblasts and fibrous tissue are organized following a trabecular pattern. The outer layer is composed of matured bone and a fibrous capsule. Excisional and open biopsies procure sufficient tissue material to highlight the zonal phenomenon. Therefore, a fine-needle biopsy may fail to procure enough specimens to demonstrate the zonal phenomenon. A single specimen taken from the center of the lesion may be confused with the findings of a malignant process.

Figure 3

We noted the case of a 10-year-old boy with a chest mass mistakenly diagnosed as osteosarcoma on histology and therefore treated with chemotherapy. The authors of this report declare to have performed a biopsy too early in the clinical evolution leading to confusion. Conclusively, a biopsy performed in the early stage of evolution provides no specific findings, may worsen pain by exacerbating local inflammation, and can lead to diagnostic errors and subsequently to iatrogenic harm. Therefore, the timing of the biopsy should be carefully planned to perform adequate diagnosis.

In the absence of triggering trauma, a significantly greater need for biopsy was observed in this review. This sheds light on the importance of a meticulous history looking for a history of trauma or a cause of muscular micro-injuries (e.g., excessive activity). When confronted with MO in infants, the battered child syndrome must be raised and evaluated, especially in supposed non-traumatic MO.

In addition to histological features consistent with MO, two authors have assessed the presence of COL1A1-USP6 transcript at PCR analysis (, ). These were not described previously in the pediatric population. Reports on adult cases have already noticed USP6 gene rearrangement in MO (, ). The potential correlation between this genetic alteration and MO should be investigated by larger sample studies.

Treatment

Historically, surgical excision during the early inflammatory phase led to recurrence and confusion upon pathology analysis. Early supportive treatment is key, by combining anti-inflammatory drugs and muscle rest to calm soft tissue edema. Surgical excision on matured lesions can be proposed usually between the 6th and 12th months if confronted with persistent pain despite adequate analgesic, significant mobility restriction especially trismus, vascular compression, or threat to noble anatomical structure such as respiratory tract in neck involvements. Local compression and intense physiotherapy should follow surgical excision if performed (). A tendency for non-operative treatment is observed in the PGMO (p = 0.01), whereas more surgical excisions were observed in the AGMO.

Follow-up

We assessed that the follow-up strategy is not well defined. Authors have performed clinical follow-up as well as radiological follow-up in an even distribution. Ultrasonography, radiography, MRI, or even CT were the modality used in the radiological follow-up strategy. The question of unnecessary irradiation and cost should be raised in a disease known to be self-resolving. Moreover, Becker and colleagues observed the persistence of calcification on CT scan in a clinically asymptomatic patient (). Except for MO located in compromising anatomical sites, clinical follow-up with the clinical assessment of pain resolution, and mobility recovery is sufficient. Even though MO is considered a benign pathology, local recurrences following serial surgical excision have been described in a 10 years-old boy by Lin and colleagues (). True recurrence rate could not be assessed due to the short follow-up period (less than 12 months) in most reports.

Conclusion

Over the last 20 years, 60 cases of MO of which 37 circumscribed and 23 pseudo-malignant were reported in the literature, confirming the rarity of the pathology in the pediatric population. This review emphasizes the importance of a meticulous history when MO is suspected. Indeed, clinicians should acknowledge that the absence of a triggering trauma tends to direct the investigation and the management towards a surgical attitude. Furthermore, the timing of the biopsy and radiography should be carefully planned to perform to avoid diagnosis confusion and iatrogenic harm. Paradoxically, in a condition known to be self-limited, a straightforward resection was achieved in nearly one-third of cases. Conservative management is key and surgical excision may be proposed on matured lesions on a case-by-case basis. There is no consensus regarding the need for radiography upon follow-up. However, clinicians should be aware that despite the benignity of MO recurrence has been documented.

Statements

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.

Ethics statement

Ethical approval was not required for the study involving humans in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and the institutional requirements.

Author contributions

IC: Data curation, Formal Analysis, Investigation, Methodology, Resources, Writing – original draft. MM: Conceptualization, Data curation, Formal Analysis, Methodology, Validation, Writing – original draft, Investigation. ES: Investigation, Methodology, Supervision, Validation, Writing – review & editing. SM: Methodology, Validation, Writing – review & editing. P-YZ: Supervision, Validation, Writing – review & editing. BT: Conceptualization, Investigation, Methodology, Project administration, Supervision, Validation, Writing – review & editing.

Funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Summary

Keywords

biopsy, child, diagnosis, imaging, myositis ossificans

Citation

Cherry I, Mutschler M, Samara E, Merckaert S, Zambelli P-Y and Tschopp B (2023) Myositis ossificans in the pediatric population: a systematic scoping review. Front. Pediatr. 11:1295212. doi: 10.3389/fped.2023.1295212

Received

15 September 2023

Accepted

13 November 2023

Published

15 December 2023

Volume

11 - 2023

Edited by

Hiroo Uchida, Nagoya University Graduate School of Medicine, Japan

Reviewed by

Nikolaos Laliotis, Interbalkan Medical Center, Greece

Elpis Hatziagorou, Aristotle University of Thessaloniki, Greece

Updates

Copyright

*Correspondence: Ibrahim Cherry

† These authors share first authorship

Abbreviations MO, myositis ossificans; AGMO, atraumatic group of myositis ossificans; TGMO, traumatic group of myositis ossificans; CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography.

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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