Macrophage Migration Inhibitory Factor-An Innovative Indicator for Free Flap Ischemia After Microsurgical Reconstruction

Overview

Journal Healthcare (Basel)

Specialty Health Services

Date 2021 Jun 2

PMID 34063809

Citations 3

Authors

Ioannis-Fivos Megas

David Simons

Bong-Sung Kim

Christian Stoppe

Andrzej Piatkowski

Panagiotis Fikatas

Paul Christian Fuchs

Jacqueline Bastiaanse

Norbert Pallua

Jurgen Bernhagen

Gerrit Grieb

Affiliations

Soon will be listed here.

Abstract

(1) Background: Nowadays, the use of microsurgical free flaps is a standard operative procedure in reconstructive surgery. Still, thrombosis of the microanastomosis is one of the most fatal postoperative complications. Clinical evaluation, different technical devices and laboratory markers are used to monitor critical flap perfusion. Macrophage migration inhibitory factor (MIF), a structurally unique cytokine with chemokine-like characteristics, could play a role in predicting vascular problems and the failure of flap perfusion. (2) Methods: In this prospective observational study, 26 subjects that underwent microsurgical reconstruction were observed. Besides clinical data, the number of blood leukocytes, CRP and MIF were monitored. (3) Results: Blood levels of MIF, C-reactive protein (CRP) and leukocytes increased directly after surgery. Subjects that needed surgical revision due to thrombosis of the microanastomosis showed significantly higher blood levels of MIF than subjects without revision. (4) Conclusion: We conclude that MIF is a potential and innovative indicator for thrombosis of the microanastomosis after free flap surgery. Since it is easy to obtain diagnostically, MIF could be an additional tool to monitor flap perfusion besides clinical and technical assessments.

Citing Articles

Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis.

Yu G, Chen Y, Yang N, Zhang H, Zhang X, Geng Y Adv Sci (Weinh). 2024; 11(24):e2307238.

PMID: 38639443 PMC: 11200024. DOI: 10.1002/advs.202307238.

The Role of Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (D-DT/MIF-2) in Infections: A Clinical Perspective.

Breidung D, Megas I, Freytag D, Bernhagen J, Grieb G Biomedicines. 2024; 12(1).

PMID: 38275363 PMC: 10813530. DOI: 10.3390/biomedicines12010002.

Free flaps monitoring by Laser-Doppler Flowmetry in head and neck surgery.

Salvatori P, Paradisi S, Zani A Acta Otorhinolaryngol Ital. 2022; 42(5):427-433.

PMID: 36541380 PMC: 9793142. DOI: 10.14639/0392-100X-N1956.

References

Fox P, Zeidler K, Carey J, Lee G . White light spectroscopy for free flap monitoring. Microsurgery. 2013; 33(3):198-202. DOI: 10.1002/micr.22069. View

Ibrahim M, Patel P, Wu Z, Chien J, Wisniewski N, Mohammed M . Detection of flap tissue ischemia in a rat model: Real-time monitoring of changes in oxygenation and perfusion through injectable biosensors. Surgery. 2020; 168(5):926-934. DOI: 10.1016/j.surg.2020.04.040. View

Frohwitter G, Nobis C, Weber M, Oetter N, Rau A, Kesting M . Thermal Imaging in a Clinically Non-assessable Free Flap Reconstruction of the Face. Plast Reconstr Surg Glob Open. 2021; 9(2):e3440. PMC: 7929496. DOI: 10.1097/GOX.0000000000003440. View

Luu Q, Farwell D . Advances in free flap monitoring: have we gone too far?. Curr Opin Otolaryngol Head Neck Surg. 2009; 17(4):267-9. DOI: 10.1097/MOO.0b013e32832cba6a. View

Kapurniotu A, Gokce O, Bernhagen J . The Multitasking Potential of Alarmins and Atypical Chemokines. Front Med (Lausanne). 2019; 6:3. PMC: 6351468. DOI: 10.3389/fmed.2019.00003. View

Grieb G, Kim B, Simons D, Bernhagen J, Pallua N . MIF and CD74 - suitability as clinical biomarkers. Mini Rev Med Chem. 2015; 14(14):1125-31. DOI: 10.2174/1389557515666150203143317. View

Bernhagen J, Krohn R, Lue H, Gregory J, Zernecke A, Koenen R . MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med. 2007; 13(5):587-96. DOI: 10.1038/nm1567. View

Flieger O, Engling A, Bucala R, Lue H, Nickel W, Bernhagen J . Regulated secretion of macrophage migration inhibitory factor is mediated by a non-classical pathway involving an ABC transporter. FEBS Lett. 2003; 551(1-3):78-86. DOI: 10.1016/s0014-5793(03)00900-1. View

Kang I, Bucala R . The immunobiology of MIF: function, genetics and prospects for precision medicine. Nat Rev Rheumatol. 2019; 15(7):427-437. DOI: 10.1038/s41584-019-0238-2. View

10.

Paprottka F, Klimas D, Krezdorn N, Schlarb D, Trevatt A, Hebebrand D . Cook-Swartz Doppler Probe Surveillance for Free Flaps-Defining Pros and Cons. Surg J (N Y). 2020; 6(1):e42-e46. PMC: 7054061. DOI: 10.1055/s-0040-1702922. View

11.

Smit J, Zeebregts C, Acosta R, Werker P . Advancements in free flap monitoring in the last decade: a critical review. Plast Reconstr Surg. 2010; 125(1):177-185. DOI: 10.1097/PRS.0b013e3181c49580. View

12.

Koga K, Kenessey A, Powell S, Sison C, Miller E, Ojamaa K . Macrophage migration inhibitory factor provides cardioprotection during ischemia/reperfusion by reducing oxidative stress. Antioxid Redox Signal. 2010; 14(7):1191-202. DOI: 10.1089/ars.2010.3163. View

13.

Shen A, Lonie S, Lim K, Farthing H, Hunter-Smith D, Rozen W . Free Flap Monitoring, Salvage, and Failure Timing: A Systematic Review. J Reconstr Microsurg. 2021; 37(3):300-308. DOI: 10.1055/s-0040-1722182. View

14.

Kim B, Breuer B, Arnke K, Ruhl T, Hofer T, Simons D . The effect of the macrophage migration inhibitory factor (MIF) on excisional wound healing . J Plast Surg Hand Surg. 2020; 54(3):137-144. DOI: 10.1080/2000656X.2019.1710710. View

15.

Schmulder A, Gur E, Zaretski A . Eight-year experience of the Cook-Swartz Doppler in free-flap operations: microsurgical and reexploration results with regard to a wide spectrum of surgeries. Microsurgery. 2010; 31(1):1-6. DOI: 10.1002/micr.20816. View

16.

Grieb G, Simons D, Piatkowski A, Bernhagen J, Steffens G, Pallua N . Macrophage migration inhibitory factor-A potential diagnostic tool in severe burn injuries?. Burns. 2009; 36(3):335-42. DOI: 10.1016/j.burns.2009.04.019. View

17.

Lin S, Nguyen M, Chen C, Colakoglu S, Curtis M, Tobias A . Tissue oximetry monitoring in microsurgical breast reconstruction decreases flap loss and improves rate of flap salvage. Plast Reconstr Surg. 2011; 127(3):1080-1085. DOI: 10.1097/PRS.0b013e31820436cb. View

18.

Du W, Wu P, Qing L, Wang C, Liang J, Yu F . Systemic and flap inflammatory response associates with thrombosis in flap venous crisis. Inflammation. 2014; 38(1):298-304. DOI: 10.1007/s10753-014-0033-9. View

19.

Hertelendy J, Reumuth G, Simons D, Stoppe C, Kim B, Stromps J . Macrophage Migration Inhibitory Factor - A Favorable Marker in Inflammatory Diseases?. Curr Med Chem. 2017; 25(5):601-605. DOI: 10.2174/0929867324666170714114200. View

20.

Salgado C, Moran S, Mardini S . Flap monitoring and patient management. Plast Reconstr Surg. 2009; 124(6 Suppl):e295-e302. DOI: 10.1097/PRS.0b013e3181bcf07b. View