An 18-Year Comprehensive Safety Study on Microfocused Ultrasound and Monopolar Radiofrequency Combined with Cosmetic Injectables in 1,040 Patients

An 18-Year Comprehensive Safety Study on Microfocused Ultrasound and Monopolar Radiofrequency Combined with Cosmetic Injectables in 1,040 Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article An 18-Year Comprehensive Safety Study on Microfocused Ultrasound and Monopolar Radiofrequency Combined with Cosmetic Injectables in 1,040 Patients Dong Hye Suh, Li-Chi Chen, Hye Jin Chung, Sang Jun Lee, Jihee Kim This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5471679/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Microfocused ultrasound (MFU) and (MRF) are non-invasive modalities widely used for skin rejuvenation and are often combined with injectables, including neuromodulators and soft tissue fillers. However, large-scale, long-term safety data on such combination therapies are lacking. To address this gap, we conducted a retrospective chart review at two private practice dermatology clinics in South Korea from June 2005 to December 2023. A total of 1,040 patients were included, comprising 515 (49.5%) and 525 (50.5%) patients undergoing MFU and MRF, respectively. Regarding combination therapy, the patients received neuromodulators (76.9%) or dermal filler injections using hyaluronic acid (HA) (17.3%) or poly-L-lactic acid (PLLA) (5.8%) in conjunction with MFU/MRF. Documented adverse events included one case of paradoxical bulging and three cases of eyelid ptosis among those treated with MFU/MRF and neuromodulators (overall incidence: 0.1% and 0.4%, respectively), two cases of surface irregularity among those treated with MFU/MRF and HA fillers (overall incidence: 1.1%), and one case of cheek asymmetry among those treated with MFU/MRF and PLLA injections (overall incidence: 1.7%). No adverse events such as necrosis, burns, filler migration, or unexpected premature loss of filler were reported. While limited by its retrospective design and the inclusion of only two dermatology clinics, which restricts the generalizability of the findings, o ur study highlights the favorable long-term safety profile of combining MFU and MRF with cosmetic injectables. Our study offers reassurance to clinicians and patients considering these approaches. microfocused ultrasound monopolar radiofrequency injectables hyaluronic acid poly-L-lactic acid fillers combination therapy cosmetics adverse event safety Figures Figure 1 Figure 2 Figure 3 Full Text Aging manifests uniquely in each individual, characterized by pronounced volume loss, dermal thinning, decreased fibroblast activity, and diminished subdermal fat. These changes affect the skin's skeletal, muscular, and subcutaneous layers. Therefore, a multifaceted treatment strategy is necessary to address the comprehensive nature of aging. Microfocused ultrasound (MFU) creates microcoagulation in the superficial dermis and subdermal connective tissue, leading to an initial contraction and denaturation of collagen fibers.[1] Monopolar radiofrequency (MRF), another non-invasive modality, thermally induces collagen contraction and denaturation in the deep dermal tissue.[2] These processes subsequently stimulate the synthesis of collagen and elastin fibers, resulting in skin tightening. MFU and MRF have been widely used for skin rejuvenation and are frequently combined with neuromodulators and soft tissue fillers such as hyaluronic acid (HA) and poly-l-lactic acid (PLLA).[3-6] They are adept at mitigating everything from fine lines to profound structural signs of aging. Combined treatments with energy-based device are highly demanded by patients, and same-day treatment has become popular. Despite their widespread adoption, research into their synergistic use, especially regarding the impact of MFU and MRF on the safety and longevity of cosmetic injectable is scant. Therefore, this study aims to comprehensively analyze the safety of combining MFU or MRF with neuromodulators and soft tissue fillers for facial rejuvenation over an 18-year period. A retrospective chart review was conducted on 1,040 patients who underwent MFU or MRF combined with neuromodulators and soft tissue filler injections from June 2005 to December 2023, in two dermatology clinics. This study received approval from the Institutional Review Board of the Korea National Institute for Bioethics Policy (P01-202312-01-006). Data were collected through observations during follow-up visits and telephone interviews conducted six months’ post-treatment. The study evaluated various aspects, including eyelid ptosis, asymmetry from neuromodulator spread, filler volume loss, necrosis, burn, and product migration, ensuring a thorough assessment of safety outcomes. A total of 1,040 patients, all classified as Fitzpatrick skin types III to V, were included. Within this cohort (Table 1), 515 patients received MFU, 400 underwent combined treatments with neuromodulators, and 115 underwent combined treatments with dermal fillers. Of the 525patients treated with MRF, 400 underwent combined treatments with neuromodulators, and 125 underwent combined treatments with dermal fillers. In the MFU group, there were 481 females and 34 males, with a mean age at treatment of 50.7 years (range: 22-75 years). For those receiving MRF, 480 were females and 45 were males, with a mean age at treatment of 51.2 years (range: 22-79 years). MFU and Neuromodulators Out of 400 patients (Figure 1), 366 patients (91.5%) received neuromodulators injection and MFU on the same day, 21 patients (5.25%) received neuromodulators after MFU, and 13 patients (3.25%) received before MFU. The most common injection site of neuromodulators was the glabella (69.5%), followed by the periorbital area (54.5%), forehead (48.5%), masseter muscle (36.5%), cheeks (20%), and nose (3.75%). The mean units of neuromodulators per treatment was 35.0 units. Documented adverse events included two cases of eyelid ptosis (incidence: 0.5%), both of which within 1 to 3 months without requiring any intervention (Table 1). MFU and Fillers Among the 115 patients who underwent MFU and filler treatments, 90 (78.3%) were administered HA filler (Figure 2A) and 25 (21.7%) received PLLA injections (Figure 2B). Of these, 86 patients (74.8%) received both filler injections and MFU on the same day, 19 patients (16.5%) received fillers post-MFU, and 10 patients (8.7%) had fillers before MFU. For the group receiving HA fillers with MFU, the nasolabial folds were treated most often (57.8%), followed by the cheeks (24.4%), tear trough (11.1%), frontal cheek (7.8%), temples (6.7%), marionette line (4.4%), and jawline (3.3%). The mean HA filler volume per treatment was 1.2 cc. In the group receiving PLLA fillers with MFU, the cheeks and temples were the most treated areas (48%), with the nasolabial folds (8%) following. The mean PLLA filler volume per treatment was 0.97 vial. Reported adverse events included one instance of surface irregularity on the nasolabial fold occurring on the same day after HA filler injections following MFU (incidence: 1.1%) and one case of cheek asymmetry occurring on the same day after PLLA injections following MFU (incidence: 4.0%) (Table 1). No cases of filler volume loss, necrosis, burns, or product migration were documented. Furthermore, there were no hospital admissions, emergency room visits, or referrals to otolaryngology or ophthalmology for additional evaluation. MRF and Neuromodulators A majority, 382 patients (95.5%), underwent neuromodulators and MRF on the same day and 12 (3.0%) received neuromodulators after MRF, and 6 (1.5%) received neuromodulators before MRF. The most common injection site was the glabella (73.0%), followed by the periorbital area (59.0%), forehead (52.5%), masseter muscle (33.5%), cheeks (24.3%), and nose (4.8%). On average, 36.9 units of neuromodulators were administered per session. There were two documented adverse events (0.5%) related to neuromodulators: one case of eyelid ptosis and one case of paradoxical bulging of the masseter muscle. In both cases, MRF preceded neuromodulator injection on the same day. These issues resolved spontaneously within 2-3 months without the need of intervention. MRF and Fillers Among this cohort, 90 (72.0%) received HA filler, and 35 (28.0%) received PLLA injections. Seventy-five patients (60.0%) received filler injections and MRF on the same day, 34 (27.2%) received filler injections after MRF, and 16 (12.8%) received filler injections before MRF. For those treated with HA filler injections combined with MRF, the cheeks (43.3%) and nasolabial folds (38.9%) were the most frequently treated areas, followed by temples (8.9%), frontal cheek (4.5%), marionette lines (4.5%), and jawline (1.1%). The mean volume of HA fillers administered per treatment was 1.4 cc. In the case of PLLA filler injections with MRF, the most targeted areas were the cheeks (97.1%), followed by temples (48.6%) and nasolabial folds (2.9%). The mean volume of PLLA fillers per treatment was 0.97 vial. Only single documented adverse event (0.8%) was noted with surface irregularity on the marionette lines in the patient treated with HA filler injections after MRF (incidence: 1.1%). Notably, there were no cases of filler volume loss among the 16 patients who received HA filler (n=10) and PLLA (n=6) injections before MRF. Moreover, there were no documented cases of product migration, necrosis, or burn. To our knowledge, this is the largest study to date with the longest follow-up period examining the safety of MFU and MRF in combination with either neuromodulators or fillers. Our findings illuminate the substantial safety of these combination treatments, with minimal adverse events paralleling those observed in treatments utilizing neuromodulators or fillers alone. The safety profile observed in our study, characterized by the low incidence of adverse effects, aligns with existing literature regarding other energy-based devices and cosmetic injectables, addressing previous concerns regarding potential adverse interactions. Of all patients receiving MFU or MRF in conjunction with neuromodulators, three cases of eyelid ptosis (overall incidence: 0.4%) and one case of paradoxical bulging of the masseter muscle (overall incidence: 0.1%) were observed. In all cases, MFU/MRF was performed prior to neuromodulator injections. All patients showed improvement within 1 to 3 months without needing any specific interventions. In the literature, the incidence of eyebrow ptosis and paradoxical bulging following neuromodulator injection alone ranges between 1.0% and 50.0% (average: 13.4%) and between 0.5% and 18.8%, respectively.[7, 8] Therefore, the combined use of MFU/MRF with neuromodulators is unlikely to increase the incidence of these adverse events. In the group of patients treated with MFU/MRF and dermal filler injections, two cases of surface irregularity were observed (overall incidence: 0.8%). The treating physician gently pressed the lumps with a cotton swab, and the irregularity subsided two weeks later. The adverse event in the MFU group occurred on the same day of HA filler injections following MFU treatment. Given the treatment sequence, it was highly unlikely that MFU affected the HA filler in these patients. Furthermore, the incidence of adverse events among our patients receiving HA filler injections combined with MFU (1.1%) or MRF (1.1%) was lower than the incidence of lump formation reported in a meta-analysis for those receiving HA filler injections alone (9.4%).[9] The other adverse event observed was cheek asymmetry following PLLA injections preceded by MFU treatment (incidence: 4%). Notably, this patient had baseline asymmetry even prior to MFU and PLLA injections, which was corrected by additional injections. Overall, our results not only reaffirm the safety of MFU and MRF technology in conjunction with injectable therapies but also set a precedent for their combined use in clinical practice. While our study contributes valuable insights, it acknowledges limitations, limited skin types assessed and the lack of a long-term follow-up period. Future research could benefit from a larger scale, multicenter approach incorporating these metrics to provide a more nuanced understanding of treatment outcomes. In conclusion, our study corroborates the safety and efficacy of combining MFU or MRF with neuromodulators and fillers, offering a viable, multifaceted approach to facial rejuvenation. The combination of these treatments utilizes the advantages of each, resulting in improved results while minimizing recovery time. This meets the increasing demand from patients for thorough and effective cosmetic procedures. Declarations Funding sources: None Conflicts of Interest: None declared. IRB approval status This study was approved by IRB committee by Korea National Institute for Bioethics Policy (P01-202312-01-006). Patient consent The authors have obtained written consent from all patients for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available. Author Contribution D.H.S., S.J.L., and J.K. conceptualized the study, curated and analyzed the data, and prepared the figures. H.J.C. validated the study design and data. D.H.S., J.K., L-C.C., and H.J.C. wrote the main manuscript text. All authors reviewed and approved the manuscript. References Friedmann DP, Fabi SG, Goldman MP (2014) Combination of intense pulsed light, Sculptra, and Ultherapy for treatment of the aging face. J Cosmet Dermatol 13(2) Weiss RA, Weiss MA, Munavalli G, Beasley KL (2006) Monopolar radiofrequency facial tightening: a retrospective analysis of efficacy and safety in over 600 treatments. J Drugs Dermatol 5(8):707 Fabi SG, Goldman MP, Mills DC, Werschler WP, Green JB, Kaufman J, Weiss RA, Hornfeldt CS (2016) Combining microfocused ultrasound with botulinum toxin and temporary and semi-permanent dermal fillers: safety and current use. Dermatol Surg 42:S168–S176 Casabona G, Michalany N (2014) Microfocused ultrasound with visualization and fillers for increased neocollagenesis: clinical and histological evaluation. Dermatol Surg 40:S194–S198 Urdiales-Gálvez F, Martín-Sánchez S, Maíz-Jiménez M, Castellano-Miralla A, Lionetti-Leone L (2019) Concomitant use of hyaluronic acid and laser in facial rejuvenation. Aesthetic Plast Surg 43:1061–1070 Cuerda-Galindo E, Palomar-Gallego MA, Linares-Garcíavaldecasas R (2015) Are combined same-day treatments the future for photorejuvenation? Review of the literature on combined treatments with lasers, intense pulsed light, radiofrequency, botulinum toxin, and fillers for rejuvenation. J Cosmet Laser Ther 17(1):49–54 Sethi N, Singh S, DeBoulle K, Rahman E (2021) A review of complications due to the use of botulinum toxin A for cosmetic indications. Aesthetic Plast Surg 45:1210–1220 Yeh YT, Peng JH, Peng HLP (2018) Literature review of the adverse events associated with botulinum toxin injection for the masseter muscle hypertrophy. J Cosmet Dermatol 17(5):675–687 Colon J, Mirkin S, Hardigan P, Elias MJ, Jacobs RJ (2023) Adverse events reported from hyaluronic acid dermal filler injections to the facial region: A systematic review and meta-analysis. Cureus 15(4) Tables Table 1. Characteristics of patients receiving combination treatment of microfocused ultrasound/monopolar radiofrequency and cosmetic injectables. (N=1,040) Microfocused ultrasound Monopolar radiofrequency Combined injectables Neuromodulators (n = 400) Dermal Fillers (n = 115) Neuromodulators (n = 400) Dermal Fillers (n = 125) Age, mean (range), y 50.9 (22-75) 50.2 (36-72) 51.2 (22-75) 51.2 (30-79) Sex, n (%) Male 26 (6.5) 8 (7.0) 36 (9.0) 9 (7.2) Female 374 (93.5) 107 (87.0) 364 (91.0) 116 (92.8) Adverse event, n (%) eyelid ptosis, 2 (0.5) HA (n=90) PLLA (n=25) eyelid ptosis, 1 (0.3); paradoxical bulging of masseter muscle, 1 (0.3) HA (n=90) PLLA (n=35) surface irregularity on the nasolabial fold, 1 (1.1) cheek asymmetry, 1 (4.0) surface irregularity on the marionette lines, 1 (1.1) no adverse events reported, 0 (0) Abbreviations: HA, hyaluronic acid; PLLA, poly-L-lactic acid. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 08 Dec, 2024 Reviews received at journal 30 Nov, 2024 Reviewers agreed at journal 27 Nov, 2024 Reviewers agreed at journal 23 Nov, 2024 Reviewers invited by journal 22 Nov, 2024 Editor assigned by journal 19 Nov, 2024 Submission checks completed at journal 19 Nov, 2024 First submitted to journal 17 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5471679","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":384507206,"identity":"c14898ef-fdb6-448b-89e3-419cae2356f6","order_by":0,"name":"Dong Hye Suh","email":"","orcid":"","institution":"Arumdaun Nara Dermatologic Clinic","correspondingAuthor":false,"prefix":"","firstName":"Dong","middleName":"Hye","lastName":"Suh","suffix":""},{"id":384507207,"identity":"f06d6c3d-1615-4b31-a1d5-cd1e215b23ba","order_by":1,"name":"Li-Chi Chen","email":"","orcid":"","institution":"University of Massachusetts Chan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Li-Chi","middleName":"","lastName":"Chen","suffix":""},{"id":384507208,"identity":"6a37ed87-7260-49ba-aed3-ad01213d2e43","order_by":2,"name":"Hye Jin Chung","email":"","orcid":"","institution":"Beth Israel Deaconess Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hye","middleName":"Jin","lastName":"Chung","suffix":""},{"id":384507209,"identity":"398987eb-fda0-4e6a-99bb-5d40f02365eb","order_by":3,"name":"Sang Jun Lee","email":"","orcid":"","institution":"Arumdaun Nara Dermatologic Clinic","correspondingAuthor":false,"prefix":"","firstName":"Sang","middleName":"Jun","lastName":"Lee","suffix":""},{"id":384507210,"identity":"ad2ff42e-03c7-409d-b93a-ecf06035f7b4","order_by":4,"name":"Jihee Kim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYBACgxvJjz//bJCzN7h//uEDBoYDhLVY3kgzOMzbwMZjcIOH2YAoLfZnzjDAtLBJEKXF7HgPQks1b9sdewb2ww/waznMw3D4J1CL/f3+Y7d5254lNvCkGRDSUnD4IdQWoJbDCQwMOfgdZnCYx+CwIVRLMVCLPQP/GyK0SDa4gbUwA7UwNkgQtIUNFMg54ECWnHPucGKbxDP8fjE4zPz4M+8fC3BUfnhTdtienz/5AX5rkAETD5BgI149EDD+IEn5KBgFo2AUjBQAANaLT0Cr3W6kAAAAAElFTkSuQmCC","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Jihee","middleName":"","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2024-11-17 22:38:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5471679/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5471679/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":71925668,"identity":"fec7be68-f1a3-4fcd-98c3-e3c5d7ca449f","added_by":"auto","created_at":"2024-12-19 18:40:25","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":800951,"visible":true,"origin":"","legend":"\u003cp\u003eThe patient received neuromodulator injections on the crow’s feet and underwent microfocused ultrasound treatment on the same day. Sequential clinical photographs showing signs of aging (A) before treatment and (B) 1 year, (C) 4 years, (D) 8 years, (E) 11 years, and (F) 13 years post-treatment. No adverse events were observed during the follow-up.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5471679/v1/3ce0ad3d1b49ec89f9b2c9ba.jpg"},{"id":71925669,"identity":"c60bd13f-ac04-4d81-beb2-819fd5b8bbde","added_by":"auto","created_at":"2024-12-19 18:40:25","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1133504,"visible":true,"origin":"","legend":"\u003cp\u003ePatient I received hyaluronic acid filler injections on the temple area and underwent microfocused ultrasound treatment on the same day. Sequential clinical photographs showing signs of aging (A) before treatment and (B) 2 years, (C) 3 years, (D) 5 years, (E) 9 years, and (F) 12 years post-treatment.\u003c/p\u003e\n\u003cp\u003ePatient II received poly-L-lactic acid injection on the cheek area and underwent microfocused ultrasound treatment on the same day (A) before treatment and (B) 1 year and (C) 3 years post-treatment. No adverse events were observed during the follow-up for either patient.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5471679/v1/158ce3f424a679c38baf2e3f.jpg"},{"id":71925667,"identity":"43e6e9f8-6829-4085-9055-1d7b1711ba41","added_by":"auto","created_at":"2024-12-19 18:40:25","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":33815,"visible":true,"origin":"","legend":"\u003cp\u003eSequential clinical photographs of a patient treated with combination monopolar radiofrequency and neuromodulator. (A) Baseline image of a 47-year-old patient showing signs of aging. (B) One year, (C) Three years, and (D) Nine years post-treatment.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5471679/v1/ddf4b51f50845a5890887eff.jpg"},{"id":71925670,"identity":"a3ccfa25-518c-4d90-96ab-8eed9359c0b1","added_by":"auto","created_at":"2024-12-19 18:40:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2337591,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5471679/v1/3d3775f5-d4c5-452a-bd69-3f21ae72ecf0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"An 18-Year Comprehensive Safety Study on Microfocused Ultrasound and Monopolar Radiofrequency Combined with Cosmetic Injectables in 1,040 Patients","fulltext":[{"header":"Full Text","content":"\u003cp\u003eAging manifests uniquely in each individual, characterized by pronounced volume loss, dermal thinning, decreased fibroblast activity, and diminished subdermal fat. These changes\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eaffect the skin\u0026apos;s skeletal, muscular, and subcutaneous layers. Therefore, a multifaceted treatment strategy is necessary to address the comprehensive nature of aging. Microfocused ultrasound (MFU) creates microcoagulation in\u0026nbsp;the superficial dermis and subdermal connective tissue,\u0026nbsp;leading to an initial contraction and denaturation of collagen fibers.[1] Monopolar radiofrequency (MRF), another non-invasive modality, thermally induces collagen contraction and denaturation in the deep dermal tissue.[2] These processes subsequently stimulate the synthesis of collagen and elastin fibers, resulting in skin tightening. MFU and MRF have been widely used for skin rejuvenation and are frequently combined with neuromodulators and soft tissue fillers such as hyaluronic acid (HA) and poly-l-lactic acid (PLLA).[3-6] They are adept at mitigating everything from fine lines to profound structural signs of aging. Combined treatments with energy-based device are highly demanded by patients, and same-day treatment has become popular. Despite their widespread adoption, research into their synergistic use, especially regarding the impact of MFU and MRF on the safety and longevity of cosmetic injectable is scant. Therefore, this study aims to comprehensively analyze the safety of combining MFU or MRF with neuromodulators and soft tissue fillers for facial rejuvenation over an 18-year period.\u003c/p\u003e\n\u003cp\u003eA retrospective chart review was conducted on 1,040 patients who underwent MFU or MRF combined with neuromodulators and soft tissue filler injections from June 2005 to December 2023, in two dermatology clinics. This study received approval from the Institutional Review Board of the Korea National Institute for Bioethics Policy (P01-202312-01-006).\u0026nbsp;Data were collected through observations during follow-up visits and telephone interviews conducted six months\u0026rsquo; post-treatment. The study evaluated various aspects, including eyelid ptosis, asymmetry from neuromodulator spread, filler volume loss, necrosis, burn, and product migration, ensuring a thorough assessment of safety outcomes.\u003c/p\u003e\n\u003cp\u003eA total of 1,040 patients, all classified as Fitzpatrick skin types III to V, were included. Within\u003c/p\u003e\n\u003cp\u003ethis cohort (Table 1), 515 patients received MFU, 400 underwent combined treatments with neuromodulators, and 115 underwent combined treatments with dermal fillers. Of the 525patients treated with MRF, 400 underwent combined treatments with neuromodulators, and 125 underwent combined treatments with dermal fillers. In the MFU group, there were 481 females and 34 males, with a mean age at treatment of 50.7 years (range: 22-75 years). For those receiving MRF, 480 were females and 45 were males, with a mean age at treatment of 51.2 years (range: 22-79 years).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMFU and Neuromodulators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of 400 patients (Figure 1), 366 patients (91.5%) received neuromodulators injection and MFU on the same day, 21 patients (5.25%) received neuromodulators after MFU, and 13 patients (3.25%) received before MFU. The most common injection site of neuromodulators was the glabella (69.5%), followed by the periorbital area (54.5%), forehead (48.5%), masseter muscle (36.5%), cheeks (20%), and nose (3.75%). The mean units of neuromodulators per treatment was 35.0 units.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDocumented adverse events included two cases of eyelid ptosis (incidence: 0.5%), both of which within 1 to 3 months without requiring any intervention (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMFU and Fillers\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 115 patients who underwent MFU and filler treatments, 90 (78.3%) were administered HA filler (Figure 2A) and 25 (21.7%) received PLLA injections (Figure 2B). Of these, 86 patients (74.8%) received both filler injections and MFU on the same day, 19 patients (16.5%) received fillers post-MFU, and 10 patients (8.7%) had fillers before MFU.\u003c/p\u003e\n\u003cp\u003eFor the group receiving HA fillers with MFU, the nasolabial folds were treated most often (57.8%), followed by the cheeks (24.4%), tear trough (11.1%), frontal cheek (7.8%), temples (6.7%), marionette line (4.4%), and jawline (3.3%). The mean HA filler volume per treatment was 1.2 cc. In the group receiving PLLA fillers with MFU, the cheeks and temples were the most treated areas (48%), with the nasolabial folds (8%) following. The mean PLLA filler volume per treatment was 0.97 vial.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eReported adverse events included one instance of surface irregularity on the nasolabial fold occurring on the same day after HA filler injections following MFU (incidence: 1.1%) and one case of cheek asymmetry occurring on the same day after PLLA injections following MFU (incidence: 4.0%) (Table 1). No cases of filler volume loss, necrosis, burns, or product migration were documented. Furthermore, there were no hospital admissions, emergency room visits, or referrals to otolaryngology or ophthalmology for additional evaluation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRF and Neuromodulators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA majority, 382 patients (95.5%), underwent neuromodulators and MRF on the same day and 12 (3.0%) received neuromodulators after MRF, and 6 (1.5%) received neuromodulators before MRF. The most common injection site was the glabella (73.0%), followed by the periorbital area (59.0%), forehead (52.5%), masseter muscle (33.5%), cheeks (24.3%), and nose (4.8%). On average, 36.9 units of neuromodulators were administered per session.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere were two documented adverse events (0.5%) related to neuromodulators: one case of eyelid ptosis and one case of paradoxical bulging of the masseter muscle. In both cases, MRF preceded neuromodulator injection on the same day. These issues resolved spontaneously within 2-3 months without the need of intervention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRF and Fillers\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong this cohort, 90 (72.0%) received HA filler, and 35 (28.0%) received PLLA injections.\u003c/p\u003e\n\u003cp\u003eSeventy-five patients (60.0%) received filler injections and MRF on the same day, 34 (27.2%) received filler injections after MRF, and 16 (12.8%) received filler injections before MRF.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor those treated with HA filler injections combined with MRF, the cheeks (43.3%) and nasolabial folds (38.9%) were the most frequently treated areas, followed by temples (8.9%), frontal cheek (4.5%), marionette lines (4.5%), and jawline (1.1%). The mean volume of HA fillers administered per treatment was 1.4 cc. In the case of PLLA filler injections with MRF, the most targeted areas were the cheeks (97.1%), followed by temples (48.6%) and nasolabial folds (2.9%). The mean volume of PLLA fillers per treatment was 0.97 vial.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOnly single documented adverse event (0.8%) was noted with surface irregularity\u003c/p\u003e\n\u003cp\u003eon the marionette lines in the patient treated with HA filler injections after MRF (incidence: 1.1%). Notably, there were no cases of filler volume loss among the 16 patients who received HA filler (n=10) and PLLA (n=6) injections before MRF. Moreover, there were no documented cases of product migration, necrosis, or burn.\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this is the largest study to date with the longest follow-up period examining the safety of MFU and MRF in combination with either neuromodulators or fillers. \u0026nbsp;Our findings illuminate the substantial safety of these combination treatments, with minimal adverse events paralleling those observed in treatments utilizing neuromodulators or fillers alone. The safety profile observed in our study, characterized by the low incidence of adverse effects, aligns with existing literature regarding other energy-based devices and cosmetic injectables, addressing previous concerns regarding potential adverse interactions. Of all patients receiving MFU or MRF in conjunction with neuromodulators, three cases of eyelid ptosis (overall incidence: 0.4%) and one case of paradoxical bulging of the masseter muscle (overall incidence: 0.1%) were observed. In all cases, MFU/MRF was performed prior to neuromodulator injections. All patients showed improvement within 1 to 3 months without needing any specific interventions. In the literature, the incidence of eyebrow ptosis and paradoxical bulging following neuromodulator injection alone ranges between 1.0% and 50.0% (average: 13.4%) and between 0.5% and 18.8%, respectively.[7, 8] Therefore, the combined use of MFU/MRF with neuromodulators is unlikely to increase the incidence of these adverse events.\u003c/p\u003e\n\u003cp\u003eIn the group of patients treated with MFU/MRF and dermal filler injections, two cases of surface irregularity were observed (overall incidence: 0.8%). The treating physician gently pressed the lumps with a cotton swab, and the irregularity subsided two weeks later. The adverse event in the MFU group occurred on the same day of HA filler injections following MFU treatment. Given the treatment sequence, it was highly unlikely that MFU affected the HA filler in these patients. Furthermore, the incidence of adverse events among our patients receiving HA filler injections combined with MFU (1.1%) or MRF (1.1%) was lower than the incidence of lump formation reported in a meta-analysis for those receiving HA filler injections alone (9.4%).[9] The other adverse event observed was cheek asymmetry following PLLA injections preceded by MFU treatment (incidence: 4%). Notably, this patient had baseline asymmetry even prior to MFU and PLLA injections, which was corrected by additional injections. Overall, our results not only reaffirm the safety of MFU and MRF technology in conjunction with injectable therapies but also set a precedent for their combined use in clinical practice.\u003c/p\u003e\n\u003cp\u003eWhile our study contributes valuable insights, it acknowledges limitations, limited skin types assessed and the lack of a long-term follow-up period. Future research could benefit from a larger scale, multicenter approach incorporating these metrics to provide a more nuanced understanding of treatment outcomes.\u003c/p\u003e\n\u003cp\u003eIn conclusion, our study corroborates the safety and efficacy of combining MFU or MRF with neuromodulators and fillers, offering a viable, multifaceted approach to facial rejuvenation.\u003c/p\u003e\n\u003cp\u003eThe combination of these treatments utilizes the advantages of each, resulting in improved results while minimizing recovery time. This meets the increasing demand from patients for thorough and effective cosmetic procedures.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding sources:\u003c/h2\u003e \u003cp\u003eNone\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e \u003cp\u003eNone declared.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eIRB approval status\u003c/strong\u003e \u003cp\u003e This study was approved by IRB committee by Korea National Institute for Bioethics Policy (P01-202312-01-006).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003ePatient consent\u003c/strong\u003e \u003cp\u003e The authors have obtained written consent from all patients for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eD.H.S., S.J.L., and J.K. conceptualized the study, curated and analyzed the data, and prepared the figures. H.J.C. validated the study design and data. D.H.S., J.K., L-C.C., and H.J.C. wrote the main manuscript text. All authors reviewed and approved the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFriedmann DP, Fabi SG, Goldman MP (2014) Combination of intense pulsed light, Sculptra, and Ultherapy for treatment of the aging face. J Cosmet Dermatol 13(2)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeiss RA, Weiss MA, Munavalli G, Beasley KL (2006) Monopolar radiofrequency facial tightening: a retrospective analysis of efficacy and safety in over 600 treatments. J Drugs Dermatol 5(8):707\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFabi SG, Goldman MP, Mills DC, Werschler WP, Green JB, Kaufman J, Weiss RA, Hornfeldt CS (2016) Combining microfocused ultrasound with botulinum toxin and temporary and semi-permanent dermal fillers: safety and current use. Dermatol Surg 42:S168\u0026ndash;S176\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasabona G, Michalany N (2014) Microfocused ultrasound with visualization and fillers for increased neocollagenesis: clinical and histological evaluation. Dermatol Surg 40:S194\u0026ndash;S198\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUrdiales-G\u0026aacute;lvez F, Mart\u0026iacute;n-S\u0026aacute;nchez S, Ma\u0026iacute;z-Jim\u0026eacute;nez M, Castellano-Miralla A, Lionetti-Leone L (2019) Concomitant use of hyaluronic acid and laser in facial rejuvenation. Aesthetic Plast Surg 43:1061\u0026ndash;1070\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCuerda-Galindo E, Palomar-Gallego MA, Linares-Garc\u0026iacute;avaldecasas R (2015) Are combined same-day treatments the future for photorejuvenation? Review of the literature on combined treatments with lasers, intense pulsed light, radiofrequency, botulinum toxin, and fillers for rejuvenation. J Cosmet Laser Ther 17(1):49\u0026ndash;54\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSethi N, Singh S, DeBoulle K, Rahman E (2021) A review of complications due to the use of botulinum toxin A for cosmetic indications. Aesthetic Plast Surg 45:1210\u0026ndash;1220\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYeh YT, Peng JH, Peng HLP (2018) Literature review of the adverse events associated with botulinum toxin injection for the masseter muscle hypertrophy. J Cosmet Dermatol 17(5):675\u0026ndash;687\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColon J, Mirkin S, Hardigan P, Elias MJ, Jacobs RJ (2023) Adverse events reported from hyaluronic acid dermal filler injections to the facial region: A systematic review and meta-analysis. Cureus 15(4)\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eCharacteristics of patients receiving combination treatment of microfocused ultrasound/monopolar radiofrequency and cosmetic injectables. (N=1,040)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 366px;\"\u003e\n \u003cp\u003eMicrofocused ultrasound\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 372px;\"\u003e\n \u003cp\u003eMonopolar radiofrequency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eCombined injectables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003eNeuromodulators\u003c/p\u003e\n \u003cp\u003e(n = 400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 246px;\"\u003e\n \u003cp\u003eDermal Fillers\u003c/p\u003e\n \u003cp\u003e(n = 115)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003eNeuromodulators\u003c/p\u003e\n \u003cp\u003e(n = 400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 245px;\"\u003e\n \u003cp\u003eDermal Fillers\u003c/p\u003e\n \u003cp\u003e(n = 125)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eAge, mean (range), y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e50.9 (22-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 246px;\"\u003e\n \u003cp\u003e50.2 (36-72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e51.2 (22-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 245px;\"\u003e\n \u003cp\u003e51.2 (30-79)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eSex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 245px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e26 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 246px;\"\u003e\n \u003cp\u003e8 (7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e36 (9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 245px;\"\u003e\n \u003cp\u003e9 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 120px;\"\u003e\n \u003cp\u003e374 (93.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 246px;\"\u003e\n \u003cp\u003e107 (87.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e364 (91.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 245px;\"\u003e\n \u003cp\u003e116 (92.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 126px;\"\u003e\n \u003cp\u003eAdverse event, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 120px;\"\u003e\n \u003cp\u003eeyelid ptosis,\u003c/p\u003e\n \u003cp\u003e2 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eHA (n=90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003ePLLA (n=25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 127px;\"\u003e\n \u003cp\u003eeyelid ptosis, 1 (0.3);\u003c/p\u003e\n \u003cp\u003eparadoxical bulging of masseter muscle, 1 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eHA (n=90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003ePLLA (n=35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003esurface irregularity on the nasolabial fold, 1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003echeek asymmetry, 1 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003esurface irregularity on the marionette lines, 1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eno adverse events reported, 0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 864px;\"\u003e\n \u003cp\u003eAbbreviations: HA, hyaluronic acid; PLLA, poly-L-lactic acid.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"microfocused ultrasound, monopolar radiofrequency, injectables, hyaluronic acid, poly-L-lactic acid, fillers, combination therapy, cosmetics, adverse event, safety","lastPublishedDoi":"10.21203/rs.3.rs-5471679/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5471679/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eMicrofocused ultrasound (MFU) and (MRF) are non-invasive modalities \u003c/strong\u003ewidely used for skin rejuvenation and are often combined with injectables, including neuromodulators and soft tissue fillers. However, large-scale, long-term safety data on such combination therapies are lacking.\u003cstrong\u003e To address this gap, we conducted a retrospective chart review at two private practice dermatology clinics in South Korea from June 2005 to December 2023. \u003c/strong\u003eA total of 1,040 patients were included, comprising 515 (49.5%) and 525 (50.5%) patients undergoing MFU and MRF, respectively. Regarding combination therapy, the patients received neuromodulators (76.9%) or dermal filler injections using hyaluronic acid (HA) (17.3%) or poly-L-lactic acid (PLLA) (5.8%) in conjunction with MFU/MRF. Documented adverse events included one case of paradoxical bulging and three cases of eyelid ptosis among those treated with MFU/MRF and neuromodulators (overall incidence: 0.1% and 0.4%, respectively), two cases of surface irregularity among those treated with MFU/MRF and HA fillers (overall incidence: 1.1%), and one case of cheek asymmetry among those treated with MFU/MRF and PLLA injections (overall incidence: 1.7%). \u003cstrong\u003eNo adverse events such as necrosis, burns, filler migration, or unexpected premature loss of filler were reported. While limited by its retrospective design and the inclusion of only two dermatology clinics, which restricts the generalizability of the findings, o\u003c/strong\u003eur study highlights the favorable long-term safety profile of combining MFU and MRF with cosmetic injectables. Our study offers reassurance to clinicians and patients considering these approaches.\u003c/p\u003e","manuscriptTitle":"An 18-Year Comprehensive Safety Study on Microfocused Ultrasound and Monopolar Radiofrequency Combined with Cosmetic Injectables in 1,040 Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-19 18:40:20","doi":"10.21203/rs.3.rs-5471679/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-08T21:11:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-30T07:33:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"98899896688684787098767339214551231623","date":"2024-11-28T02:22:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"187051012961165893490381388139450886001","date":"2024-11-23T06:11:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-22T13:09:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-19T11:09:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-19T11:08:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2024-11-17T22:23:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d4f79a7c-aa98-454f-bd4d-cd2aef2d7d56","owner":[],"postedDate":"December 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-12-20T21:53:18+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-19 18:40:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5471679","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5471679","identity":"rs-5471679","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}