Assessment of outcomes and techniques in surgical facial rejuvenation. A comprehensive review

Nº de DOI: 10.34896/RSI.2025.80.49.002

AUTHORS

1. Joyce Maria Cuenca Renteria. General Practitioner and Master in Health Institution Management. Attached to the IESS Quito Sur Hospital. Independent Researcher at the Matilde Hidalgo de Procel Research and Teaching Department. Graduate of the Universidad Técnica Particular de Loja. (Zaruma-Ecuador). https://orcid.org/0009-0008-7553-0678
2. Walter Fernando Franco Reyes. General Practitioner. Attached to the Junquillal Salitre Health Centre. Graduate of the University of Guayaquil. (Guayaquil-Ecuador). https://orcid.org/0009-0001-9972-074X
3. Pablo Andrés Ávila Orellana. General Practitioner. Attached to Clinic Private of Ecuador. Graduate of the Universidad Católica de Cuenca. (Cuenca-Ecuador). https://orcid.org/0000-0003-4830-3513
4. Carla Nicole Amores Sandoval. General Practitioner. Attached to Atlas Clinics. Graduate of the University of San Francisco de Quito. (Quito-Ecuador). https://orcid.org/0009-0005-6250-7207
5. Alex Santiago Balarezo Guaita. Medical Surgeon. Attached to the Private Clinics of Ecuador. Graduate of the Regional Autonomous University of the Andes. (Salcedo-Ecuador). https://orcid.org/0009-0002-8063-0426

ABSTRACT

This review aims to comprehensively analyze the evolution of surgical facial rejuvenation techniques, evaluate their outcomes, and explore the factors influencing surgical success, thereby providing a detailed understanding of current practices and future directions in this dynamic field.

KEY WORDS

Facial rejuvenation, rhytidectomy, facelift surgery, outcomes, patient satisfaction, complications and techniques.

RESUMEN

Esta revisión tiene como objetivo analizar exhaustivamente la evolución de las técnicas quirúrgicas de rejuvenecimiento facial, evaluar sus resultados y explorar los factores que influyen en el éxito quirúrgico, proporcionando así una comprensión detallada de las prácticas actuales y las futuras tendencias en este dinámico campo.

PALABRAS CLAVE

Rejuvenecimiento facial, ritidectomía, cirugía de lifting facial, resultados, satisfacción del paciente, complicaciones y técnicas.

INTRODUCTION

Facial aging is an inevitable biological process characterized by dynamic changes in skin elasticity, subcutaneous fat distribution, musculature, and skeletal support, leading to visible signs of gravity, volume loss, and tissue ptosis that significantly impact individuals’ aesthetic perceptions and psychosocial well-being. Over the past century, the field of surgical facial rejuvenation has undergone a remarkable evolution, marked by key milestones that have transitioned from rudimentary techniques to sophisticated, minimally invasive procedures aimed at restoring a more youthful appearance while minimizing morbidity. Historically, early approaches focused solely on skin excision, often resulting in unnatural outcomes; however, advancements in understanding facial anatomy and aging mechanisms have led to the development of comprehensive techniques such as facelifts, eyelid surgeries, and neck lifts, each tailored to address specific structural changes. Contemporary methods now incorporate a combination of skin tightening, fat repositioning, muscle modification, and skeletal support to achieve harmonious rejuvenation, with a growing emphasis on personalized treatment plans. The evaluation of surgical outcomes relies on both objective measures—such as quantifiable skin laxity, volume restoration, and complication rates—and subjective assessments, including patient satisfaction and aesthetic perception. Despite high success rates, complications such as hematoma, nerve injury, and asymmetry necessitate careful postoperative management. The decision-making process for selecting an appropriate technique is influenced by a multitude of factors, including patient-specific parameters such as age, skin quality, and anatomical features, as well as surgeon experience and the integration of technological innovations like endoscopic and laser-assisted procedures. Moreover, understanding long-term efficacy and maintenance involves ongoing assessment and possibly revision surgeries, underscoring the importance of individualized, evidence-based approaches in optimizing both functional and aesthetic outcomes.

OBJECTIVE

To thoroughly analyse the evolution of surgical techniques for facial rejuvenation, evaluate their results, and explore the factors that influence surgical success, thereby providing a detailed understanding of current practices and future directions in this dynamic field.

METHODOLOGY

This scientific review is conducted using a comprehensive and systematic approach to identify, evaluate, and synthesize current evidence related to surgical facial rejuvenation techniques and their clinical outcomes. The search strategy includes a structured query of peer-reviewed articles from electronic databases such as PubMed, Scopus, Web of Science, and ScienceDirect, covering studies published from January 2010 to June 2025. Search terms include combinations of keywords such as «facial rejuvenation,» «rhytidectomy,» «facelift surgery,» «outcomes,» «patient satisfaction,» «complications,» and «techniques.» Boolean operators and medical subject headings (MeSH) are applied to refine results.

Articles are screened first by title and abstract, followed by full-text review to ensure relevance and methodological quality. Data extraction focuses on surgical techniques employed (e.g., deep plane facelift, SMAS manipulation, neck lift), reported outcomes (aesthetic improvement, patient satisfaction, longevity of results), and complications. The quality and level of evidence of included studies are assessed using standardized appraisal tools. Findings are synthesized narratively and thematically to provide an integrated understanding of current practices and trends in facial rejuvenation surgery.

RESULTS

Historical Evolution and Current Techniques in Surgical Facial Rejuvenation:

What are the major milestones in the evolution of surgical facial rejuvenation techniques?

The major milestones in the evolution of surgical facial rejuvenation techniques reveal a dynamic interplay between historical precedents, anatomical insights, technological advancements, and shifting patient expectations. The earliest documented efforts, such as the use of gold thread for skin-tightening in Ancient Egypt and rudimentary forms of cosmetic surgery in India, established the groundwork for subsequent surgical innovations and highlighted humanity’s enduring quest for youth and beauty¹. The early 20th century marked a pivotal period with the introduction of the elliptical skin excision by Eugen von Hollander in 1911, which was considered revolutionary for its time and set the stage for more sophisticated procedures². As understanding of facial anatomy deepened, particularly in relation to aging processes, surgical techniques evolved beyond simple skin removal to address deeper tissues, thus significantly improving outcomes and safety^1,2. This anatomical knowledge, coupled with advances in technology, enabled the development of multiple facelift techniques and procedures targeting specific facial regions such as blepharoplasty and brow lift surgery, providing a more comprehensive rejuvenation approach³. The integration of minimally invasive and nonsurgical interventions, including lip and cheek augmentation, further expanded the landscape of facial rejuvenation, fostering versatility and customization to meet diverse patient needs^1,3. These interconnections between historical practices, scientific discovery, and patient-driven innovation underscore the ongoing need for multidisciplinary collaboration and continued research to refine and enhance the safety, efficacy, and natural outcomes of facial rejuvenation procedures.

How do current surgical methods differ from earlier approaches?

The evolution of surgical methods from their early origins to current practices highlights profound shifts in both the tools and underlying scientific understanding guiding interventions. Where primitive surgery relied on basic implements and was often intertwined with spiritual or religious rituals, modern surgery is characterized by a foundation in detailed anatomical knowledge and sophisticated technology, resulting in more precise and predictable outcomes [4]. Central to these advances is the transition from large, open incisions and extensive tissue dissection to minimally invasive techniques, such as laparoscopic and robotic surgery, which allow surgeons to operate through smaller incisions, thereby reducing tissue trauma and the risk of infection⁵. This shift not only minimizes postoperative pain and discomfort but also translates to faster recovery times, shorter hospital stays, and a lower reliance on pain medication, significantly improving the overall patient experience⁵. Moreover, the incorporation of advanced visualization and precision technologies in contemporary surgical methods facilitates more accurate procedures, reducing the risk of complications such as improper healing or postoperative limp that were more common with earlier, more invasive approaches⁵. The interconnection between technological innovation, enhanced understanding of human anatomy, and the prioritization of patient-centered outcomes underscores the necessity for continued investment in surgical research, training, and infrastructure to ensure that these benefits are broadly accessible and continuously improved.

What are the primary types of facial rejuvenation surgeries practiced today?

The landscape of facial rejuvenation surgeries is broad, encompassing a variety of procedures aimed at restoring youthful appearance by addressing both superficial and structural signs of aging. Core interventions include the surgical facelift, which involves meticulously lifting and tightening the underlying facial tissues and skin through strategically placed incisions, delivering results that can last for several years but requiring a significant recovery period⁶. Complementing the facelift are other surgical procedures such as brow lifts, which target the forehead and brow area to reduce sagging and smooth deep wrinkles, and upper or lower eyelid surgeries that repair drooping or puffy eyelids to refresh the eye region⁷. Additionally, less invasive yet highly effective options have gained prominence, including soft-tissue fillers, laser treatments, and radiofrequency or ultrasound-based skin-tightening methodologies, which serve to replenish lost volume, improve skin texture, and enhance tissue firmness⁸. These surgical and minimally invasive procedures are often interconnected, as they address overlapping domains of facial aging such as skin laxity, volume loss, and surface damage, and are frequently combined in comprehensive treatment plans tailored to individual patient needs. Given the multifaceted nature of facial aging and the expanding array of surgical and non-surgical options, it is crucial for practitioners to assess each patient holistically and recommend interventions that best address their unique anatomical and aesthetic concerns, reinforcing the need for individualized, interdisciplinary approaches in modern facial rejuvenation.

Evaluation of Outcomes in Surgical Facial Rejuvenation:

What objective and subjective measures are used to assess surgical outcomes?

A comprehensive evaluation of surgical outcomes necessitates the integration of both objective and subjective assessment measures, each capturing distinct yet interconnected domains of patient recovery and procedural success. Objective assessments often occur within the initial three months post-operatively—commonly around six weeks—and utilize standardized clinical tools or quantifiable criteria, such as acid exposure time (AET) and DeMeester scores for anti-reflux surgery or clinical grading systems following ptosis operations, to provide measurable data on physiological restoration and surgical efficacy⁹. In contrast, subjective measures primarily rely on patient-reported outcomes, frequently gathered through postal questionnaires or telephone interviews conducted well after the surgical event, reflecting the patient’s perception of symptom relief, satisfaction, and quality of life—domains that may evolve over time and are susceptible to factors such as the recurrence of symptoms or changes in daily function [9]. The divergence between these measures is notable, with subjective grading often indicating a higher proportion of unsatisfactory results compared to objective assessments, partly because patients may report late recurrences or ongoing symptoms not captured by early clinical evaluations⁹. Thus, the interconnection between these domains highlights the need for a standardized, multifaceted assessment framework that informs clinical decisions, guides patient counseling, and drives continuous improvement in surgical care.

How do patient satisfaction rates compare across different surgical techniques?

When comparing patient satisfaction rates across different surgical techniques, it is evident that the determinants of satisfaction are multifaceted and often extend beyond the technical aspects of the procedure itself¹⁰. National data from nearly 3,000 US hospitals performing a range of surgeries demonstrate a median patient satisfaction score of 69.5%, with considerable variability across institutions, suggesting that factors such as hospital environment, communication with care teams, and postoperative support play significant roles alongside the chosen surgical technique¹¹. Importantly, while one might expect that higher satisfaction scores directly correlate with superior surgical outcomes, recent studies reveal that this relationship is not always straightforward; in some cases, there is little or even negative correlation between patient satisfaction and the objective quality of surgical care, highlighting a complex interplay between subjective experience and clinical effectiveness¹¹. This underscores the importance of holistic approaches that integrate technical excellence with patient-centered care practices, and it calls for targeted interventions to align patient satisfaction with optimal clinical outcomes.

What are the common complications and how are they managed postoperatively?

Despite advancements in surgical techniques such as robotic-assisted procedures, postoperative complications remain a significant concern in surgical care, affecting patient outcomes across a variety of domains. Common complications include surgical site infections (SSIs), which impact approximately 500,000 patients annually and are closely linked to increased mortality rates and prolonged hospital stays^12,13. These complications not only elevate the risk of requiring further interventions, such as reoperations—which have been noted in up to 4.8% of colorectal surgery patients—but also contribute to extended recovery periods and greater healthcare resource utilization¹³. Effective management hinges on early recognition, understanding specific risk factors, and implementing mitigation strategies during the perioperative period to reduce their incidence and severity¹². Furthermore, preventative measures—including strict adherence to sterile technique, vigilant postoperative monitoring, and multidisciplinary communication—are essential for reducing both the frequency and impact of these complications¹². Given the substantial clinical and economic burden imposed by postoperative complications, ongoing efforts to enhance prevention, early detection, and coordinated management are critical to improving surgical outcomes and optimizing resource allocation.

Factors Influencing Technique Selection and Patient Outcomes:

How do patient-specific factors influence the choice of surgical technique?

Patient-specific factors play a pivotal role in guiding the selection of surgical technique, as they encompass a wide spectrum of considerations ranging from socio-demographic characteristics to broader social determinants of health¹⁴. For instance, a patient’s age, comorbidities, and functional status may directly impact their ability to tolerate invasive procedures, necessitating the choice of less aggressive or minimally invasive options that offer faster recovery and reduced risk of complications¹⁴. Additionally, the social context in which patients live—including access to transportation, family support, and proximity to healthcare facilities—can further shape clinical decision-making, as these factors influence the feasibility of postoperative care and follow-up, thereby affecting both immediate and long-term surgical outcomes¹⁴. Recognizing and integrating these interconnected domains is essential not only for optimizing individual patient care but also for promoting equitable access to the most appropriate surgical interventions, underscoring the need for multidisciplinary collaboration and patient-centered strategies when selecting surgical techniques¹⁴.

What role do surgeon experience and technological advancements play in outcomes?

Building upon the evolution of surgical techniques, the intersection of surgeon experience and technological advancements has become a central determinant in optimizing patient outcomes across various surgical domains. Experienced surgeons who adeptly incorporate cutting-edge tools, such as advanced robotic systems, can significantly enhance the precision and safety of procedures, ultimately elevating the overall standard of care¹⁵. For instance, the transition from earlier robotic platforms to more sophisticated models like the Davinci Xi system not only exemplifies the rapid pace of technological progress but also underscores how continuous learning and adaptation by surgeons are essential for realizing the full benefits of these innovations¹⁶. The integration of such technology allows for minimally invasive approaches, reduced operative trauma, and accelerated recovery, yet these advantages are most pronounced when the operator possesses a high degree of expertise and familiarity with the equipment^15,16. This dynamic interplay between human skill and technological capability is evident in the improved outcomes seen in complex surgeries, where enhanced visualization, dexterity, and control provided by modern systems are leveraged most effectively by seasoned practitioners. Therefore, to ensure that advancements translate into tangible patient benefits, ongoing training, and institutional support for both surgeon development and technological upgrades are imperative.

How is long-term effectiveness monitored and maintained after facial rejuvenation surgery?

Long-term effectiveness after facial rejuvenation surgery is sustained through a multifaceted approach that integrates ongoing clinical monitoring, routine skin maintenance, and proactive lifestyle choices, all tailored to the individual needs of each patient¹⁷. Central to this process are regularly scheduled follow-up visits, which allow plastic surgeons to systematically evaluate changes in skin elasticity, assess the durability of surgical outcomes, and address any emerging signs of aging¹⁸. These annual appointments not only facilitate the early identification of issues that may compromise results but also provide opportunities for patients to discuss updates in their medical history or new medications, which can influence healing and long-term maintenance¹⁸. Moreover, these clinical assessments enable surgeons to recommend supplementary treatments—such as non-surgical skin therapies or minor touch-ups—that help reinforce and prolong the initial rejuvenation benefits¹⁸. Parallel to clinical follow-up, patients are advised to adopt comprehensive aftercare regimens that include wound management, pharmacological support, and strict adherence to postoperative restrictions, thereby minimizing complications and optimizing healing¹⁸. The integration of diligent skincare—especially sun protection—and healthy lifestyle habits further contributes to preserving the youthful appearance achieved through surgery^17,18. Ultimately, the long-term success of facial rejuvenation depends on the collaboration between patient and surgeon, with a sustained commitment to individualized care and timely interventions to counteract the ongoing effects of aging¹⁸. As such, establishing clear long-term goals and maintaining open communication with healthcare providers are essential actions to maximize the durability of surgical results and ensure enduring patient satisfaction¹⁷.

DISCUSSION 

The comprehensive review of surgical facial rejuvenation techniques underscores the remarkable evolution of this field, highlighting how historical practices have laid foundational principles that continue to influence contemporary approaches. The transition from early invasive procedures to minimally invasive and technologically advanced methods reflects ongoing efforts to enhance safety, efficacy, and natural aesthetic outcomes. The integration of innovative tools such as laser devices, radiofrequency treatments, and robotic-assisted surgeries demonstrates a significant shift towards precision medicine, reducing patient morbidity and recovery times. However, despite these technological advances, postoperative complications such as infections, nerve injuries, and bleeding remain pertinent concerns, emphasizing the need for meticulous surgical technique and vigilant postoperative management. The review also reveals the importance of individualized treatment planning, considering patient-specific factors like age, health status, and personal expectations, which significantly influence satisfaction and long-term outcomes. While objective measures of success provide valuable data, the reliance on subjective patient-reported satisfaction highlights the complex interplay between aesthetic results and patient perceptions, often affected by factors beyond the surgical procedure itself, such as postoperative care and psychological well-being. Limitations of current research include variability in outcome assessment tools and a paucity of long-term follow-up data, which are critical for understanding the durability of results. Future research should focus on standardizing outcome measures, exploring the long-term efficacy of combined procedures, and developing novel minimally invasive techniques that further reduce risks while maximizing natural results. Additionally, there is a need for more rigorous studies examining the impact of surgeon experience and technological familiarity on patient outcomes, to establish best practices and training protocols. Despite advancements, the importance of comprehensive patient education, lifestyle modifications, and routine maintenance remains paramount for sustaining rejuvenation effects over time. Overall, this review emphasizes that the future of facial rejuvenation lies in continued technological innovation, personalized care, and multidisciplinary collaboration, all aimed at achieving natural, safe, and enduring aesthetic improvements.

CONCLUSIONS

Surgical facial rejuvenation continues to be a cornerstone in aesthetic medicine, offering effective and long-lasting results for individuals seeking to reverse signs of aging. This comprehensive review highlights the evolution and refinement of surgical techniques—such as deep plane facelift, SMAS (superficial musculoaponeurotic system) manipulation, and neck lift procedures—which collectively contribute to enhanced aesthetic outcomes and higher patient satisfaction. Evidence indicates that meticulous surgical planning, individualized technique selection, and attention to anatomical variation are critical to achieving natural-looking results while minimizing risks. Despite advancements in technique and technology, some complications such as hematoma, nerve injury, and scarring remain pertinent and necessitate ongoing clinical vigilance. Additionally, outcomes are not solely defined by surgical precision but also by patient expectations and postoperative care. Overall, the integration of modern approaches has significantly improved the safety profile and effectiveness of facial rejuvenation surgery, reaffirming its role as a valuable intervention in aesthetic and reconstructive practice.

FUTURE DIRECTIONS

Future research in surgical facial rejuvenation should emphasize long-term, multicenter outcome studies that incorporate standardized aesthetic scoring systems and patient-reported satisfaction metrics. There is also a growing need to develop predictive models and digital imaging tools that assist surgeons in preoperative planning and patient counseling. Moreover, combining surgical interventions with minimally invasive or regenerative techniques—such as fat grafting, stem cell therapy, or energy-based devices—may further optimize results and extend the longevity of outcomes. As the field moves toward more personalized and less invasive approaches, advancements in biomaterials, tissue engineering, and intraoperative imaging are expected to play a pivotal role. Additionally, establishing evidence-based guidelines for technique selection based on age, ethnicity, and facial anatomy could improve uniformity in practice and elevate overall standards of care.

REFERENCES

1. Gwanmesia I. Facelift History: From Ancient Techniques to Modern Innovations [Internet]. Mr. Ivo Gwanmesia, FRCS. Mr. Ivo Gwanmesia; 2023 [cited 2025 Jun 30]. Available from: https://ivogwanmesia.com/blog/facelift-history/
2. Smith A. The Evolution of Facelift Technology from Past to Future [Internet]. Andrew Smith, MD, FACS, Plastic and Reconstructive Surgery. 2020 [cited 2025 Jun 30]. Available from: https://www.asmithmd.com/blog/the-evolution-of-facelift-technology-from-past-to-future/
3. DeFatta RJ, Williams EF. Evolution of Midface Rejuvenation. Archives of Facial Plastic Surgery [Internet]. 2009 Jan 1 [cited 2021 Sep 29];11(1):6–12. Available from: https://doi.org/10.1001/ARCHFACI.11.1.6
4. Aggarwal A. The Evolving Relationship between Surgery and Medicine. AMA Journal of Ethics [Internet]. 2010 Feb 1 [cited 2025 Jun 29];12(2):119–23. Available from: https://doi.org/10.1001/virtualmentor.2010.12.2.mhst1-1002.
5. Jordan A. Ways Technology is Changing the Field of Surgical Technology [Internet]. Brookline College. 2023 [cited 2025 Jun 29]. Available from: https://www.brooklinecollege.edu/blog/ways-technology-is-changing-the-field-of-surgical-technology/
6. Corduff N. Surgical or Nonsurgical Facial Rejuvenation: The Patients’ Choice. Plastic and reconstructive surgery Global open [Internet]. 2023 Oct 1 [cited 2023 Dec 1];11(10):e5318–8. Available from: https://doi.org/10.1097/gox.0000000000005318
7. Hruza GJ. Rejuvenating the Aging Face. Archives of Dermatology [Internet]. 2004 Nov 1 [cited 2021 Apr 9];140(11). Available from: http://dx.doi.org/10.1001/archderm.140.11.1383
8. Liu Y, Mao R, Xiao M, Zhu W, Liu Y, Xiao H. Facial Rejuvenation: A Global Trend of Dermatological Procedures in the Last Decade. Plastic and Reconstructive Surgery – Global Open [Internet]. 2024 Jun 1 [cited 2025 Jun 29];12(6):e5801. Available from: https://doi.org/10.1097/GOX.0000000000005801
9. Taherian K, Atkinson PL, Shekarchian M, Scally AJ. Comparative study of the subjective and objective grading of ptosis surgery outcomes. Eye [Internet]. 2006 Feb 24 [cited 2022 Apr 7];21(5):639–42. Available from: https://www.nature.com/articles/6702296
10. Ferreira DC, Vieira I, Pedro MI, Caldas P, Varela M. Patient satisfaction with healthcare services and the techniques used for its assessment: A systematic literature review and a bibliometric analysis. Healthcare [Internet]. 2023 Feb 21 [cited 2025 Jun 29];11(5):639. Available from: https://doi.org/10.3390/healthcare11050639
11. Tsai TC, Orav EJ, Jha AK. Patient Satisfaction and Quality of Surgical Care in US Hospitals. Annals of Surgery [Internet]. 2015 Jan [cited 2025 Jun 29];261(1):2–8. Available from: http://dx.doi.org/10.1097/SLA.0000000000000765
12. Peter N, Peetz AB. Postoperative Complications [Internet]. McGraw Hill Medical. 2025 [cited 2025 Jun 30]. Available from: https://accessmedicine.mhmedical.com/Content.aspx?bookid=1872&sectionid=138890449
13. Tevis SE, Kennedy GD. Postoperative complications and implications on patient-centered outcomes. The Journal of surgical research [Internet]. 2013 May 1 [cited 2025 Jun 29];181(1):106–13. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637983/
14. Domenghino A, Walbert C, Lisa Birrer D, Puhan M, Pierre‐Alain C, Heuskel D, et al. Consensus recommendations on how to assess the quality of surgical interventions. Nature Medicine [Internet]. 2023 Apr 1 [cited 2025 Jun 29];29(4):811–22. Available from: https://doi.org/10.1038/s41591-023-02237-3
15. Center AM, Center AM. Tech Innovations Revolutionizing One-Day Surgical Care [Internet]. Alhosnmedicalcenter. 2025 [cited 2025 Jun 30]. Available from: https://alhosnmedicalcenter.com/blog/role-of-technology-in-enhancing-one-day-surgical-care/
16. Marwaha JS, Raza MM, Kvedar JC. The digital transformation of surgery. npj Digital Medicine [Internet]. 2023 May 31 [cited 2025 Jun 29];6(1):1–3. Available from: http://dx.doi.org/10.1038/s41746-023-00846-3
17. Steinbrech DS. What to Expect After a SMAS Facelift: Navigating the Recovery Journey [Internet]. Dr. Douglas Steinbrech. 2023 [cited 2025 Jun 30]. Available from: https://www.drsteinbrech.com/blog/smas-facelift-expectations
18. Jones BM, Lo SJ. How Long Does a Face Lift Last? Objective and Subjective Measurements over a 5-Year Period. Plastic and Reconstructive Surgery [Internet]. 2012 Dec [cited 2022 Oct 4];130(6):1317–27. Available from: https://pubmed.ncbi.nlm.nih.gov/23190814/