PDF
Abstract
Objective: The transverse tibial transfer technique is employed primarily to treat diabetic foot ulcers (DFUs), aiming to enhance leg circulation and promote new blood vessel growth. This technique is also beneficial for various conditions associated with poor blood flow in the lower extremities. However, there is no clear molecular mechanism to explain the relationship between the transverse tibial transfer technique and angiogenesis in patients with diabetic foot. This study aims to preliminarily explore the change of IL-6 and related cytokines in promoting angiogenesis during transverse tibial transplantation, providing a direction for future research.
Methods: We retrospectively assessed a study from April 2022 to November 2023 on 76 patients with severe DFUs at Wagner stages 3–4. Flow cytometry was used to detect the levels of 12 cytokines in serum before the operation and 3, 7, 14, 21, and 35 days after the operation. Ankle-brachial index (ABI), transcutaneous oxygen tension (TcPO2), and glycosylated hemoglobin (Hba1c) were recorded at admission and discharge. We examined the variations in cytokine levels, wound healing duration, amputation rates, infection incidence, and other key outcomes.
Results: In our investigation, a total of 76 individuals participated, comprising 49 males and 27 females. These subjects had an average age of 64.7 years, with a standard deviation of 13 years. The mean ulcer healing time was 74 ± 31 days, amputation occurred in 3 patients, pin tract infection occurred in one patient (1.3%), and incision infection occurred in one patient (1.3%). By day 35 following the surgery, both the ABI and TcPO2 values showed a significant increase from their preoperative levels. HbA1c significantly improved compared with presurgery (p < 0.001), IL-6 levels were significantly increased compared with presurgery (p < 0.05), and then decreased.
Conclusion: The transverse tibial transfer (TTT) technique is safe and efficient for managing DFUs. The wound healing time in patients who smoke or consume alcohol is statistically significant compared with that of nonsmoking and nondrinking patients. IL-6 exhibited substantial changes at various postoperative time points. Future research could investigate the role of IL-6 in tibial transverse translation.
Keywords
Angiogenesis
/
Cytokines
/
Diabetic Foot Ulcers
/
Postoperative Inflammation
/
Transverse Tibial Transfer Technique
Cite this article
Download citation ▾
Daofei Xu,, Chunxia Bai,, Rong Hu,, Xiaoya Li,, Fudie Guo,, Dingwei Zhang,, Bo Shi,.
Exploring the Changes in IL-6 and Related Cytokines in Angiogenesis after Tibial Transverse Transplantation in Diabetic Foot Ulcers.
Orthopaedic Surgery, 2024, 16(9): 2181-2190 DOI:10.1111/os.14221
| [1] |
Cai F, Liu Y, Liu K. Diabetes mellitus impairs bone regeneration and biomechanics. J Orthop Surg Res. 2023; 18(1): 169.
|
| [2] |
Sun Y, Gao Y, Chen J. Evidence mapping of recommendations on diagnosis and therapeutic strategies for diabetes foot: an international review of 22 guidelines. Metabolism. 2019; 100: 153956.
|
| [3] |
Aday AW, Matsushita K. Epidemiology of peripheral artery disease and Polyvascular disease. Circ Res. 2021; 128(12): 1818–1832.
|
| [4] |
Yang Y, Li Y, Pan Q. Tibial cortex transverse transport accelerates wound healing via enhanced angiogenesis and immunomodulation. Bone Joint Res. 2022; 11(4): 189–199.
|
| [5] |
Xu J, Li S, Sun Y. Triplanar osteotomy combined with proximal tibial transverse transport to accelerate healing of recalcitrant diabetic foot ulcers. J Orthop Surg Res. 2022; 17(1): 528.
|
| [6] |
Armstrong DG, Tan TW, Boulton AJM. Diabetic foot ulcers: a review. JAMA. 2023; 330(1): 62–75.
|
| [7] |
Chen Y, Ding X, Zhu Y. Effect of tibial cortex transverse transport in patients with recalcitrant diabetic foot ulcers: a prospective multicenter cohort study. J Orthop Translat. 2022; 36: 194–204.
|
| [8] |
Zhang D, Huang J, Shi B. Analysis of complications in diabetic foot treated with tibial transverse transport. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2020; 34(8): 985–989.
|
| [9] |
Yuan Y, Ding X, Jing Z. Modified tibial transverse transport technique for the treatment of ischemic diabetic foot ulcer in patients with type 2 diabetes. J Orthop Translat. 2021; 29: 100–105.
|
| [10] |
Kang S, Kishimoto T. Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Exp Mol Med. 2021; 53(7): 1116–1123.
|
| [11] |
Saxton RA, Glassman CR, Garcia KC. Emerging principles of cytokine pharmacology and therapeutics. Nat Rev Drug Discov. 2023; 22(1): 21–37.
|
| [12] |
Jamaludeen N, Lehmann J, Beyer C. Assessment of immune status using inexpensive cytokines: a literature review and learning approaches. Sensors (Basel). 2022; 22(24): 9785.
|
| [13] |
Leonard WJ, Lin JX. Strategies to therapeutically modulate cytokine action. Nat Rev Drug Discov. 2023; 22(10): 827–854.
|
| [14] |
Chang CJ, Jou IM, Wu TT. Cigarette smoke inhalation impairs angiogenesis in early bone healing processes and delays fracture union. Bone Joint Res. 2020; 9(3): 99–107.
|
| [15] |
Pei J, Wang X, Pei Z. Glycemic control, HbA1c variability, and major cardiovascular adverse outcomes in type 2 diabetes patients with elevated cardiovascular risk: insights from the ACCORD study. Cardiovasc Diabetol. 2023; 22(1): 287.
|
| [16] |
Casadei G, Filippini M, Brognara L. Glycated hemoglobin (HbA1c) as a biomarker for diabetic foot peripheral neuropathy. Diseases. 2021; 9(1): 16.
|
| [17] |
Hu X, Xiu Z, Li G. Effectiveness of transverse tibial bone transport in treatment of diabetic foot ulcer: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023; 13: 1095361.
|
| [18] |
Eelen G, Treps L, Li X. Basic and therapeutic aspects of angiogenesis updated. Circ Res. 2020; 127(2): 310–329.
|
| [19] |
Sabi EM, Singh A, Althafar ZM. Elucidating the role of hypoxia-inducible factor in rheumatoid arthritis. Inflammopharmacology. 2022; 30(3): 737–748.
|
| [20] |
Rai V, Le H, Agrawal DK. Novel mediators regulating angiogenesis in diabetic foot ulcer healing. Can J Physiol Pharmacol. 2023; 101(10): 488–501.
|
| [21] |
Xiao J, Xie Y, Liu J. Assessing Mailuoning injection in wound healing and thrombophlebitis management: a rat model study. Int Wound J. 2024; 21(4):e14527.
|
| [22] |
Zegeye MM, Andersson B, Sirsjö A. IL-6 trans-signaling impairs sprouting angiogenesis by inhibiting migration, proliferation and tube formation of human endothelial cells. Cells. 2020; 9(6): 1414.
|
| [23] |
Seki T, Yanaihara N, Shapiro JS. Interleukin-6 as an enhancer of anti-angiogenic therapy for ovarian clear cell carcinoma. Sci Rep. 2021; 11(1): 7689.
|
| [24] |
Rapp J, Jung M, Klar RFU. STAT3 signaling induced by the IL-6 family of cytokines modulates angiogenesis. J Cell Sci. 2023; 136(1): jcs260182.
|
| [25] |
Katsura H, Kobayashi Y, Tata PR. IL-1 and TNFα contribute to the inflammatory niche to enhance alveolar regeneration. Stem Cell Rep. 2019; 12(4): 657–666.
|
| [26] |
González L, Rivera K, Andia ME. The IL-1 family and its role in atherosclerosis. Int J Mol Sci. 2022; 24(1): 17.
|
| [27] |
Giménez N, Schulz R, Higashi M. Targeting IRAK4 disrupts inflammatory pathways and delays tumor development in chronic lymphocytic leukemia. Leukemia. 2020; 34(1): 100–114.
|
| [28] |
Fahey E, Doyle SL. IL-1 family cytokine regulation of vascular permeability and angiogenesis. Front Immunol. 2019; 10: 1426.
|
| [29] |
LaMarche NM, Hegde S, Park MD. An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. Nature. 2024; 625(7993): 166–174.
|
| [30] |
Celik M, Labuz D, Keye J. IL-4 induces M2 macrophages to produce sustained analgesia via opioids. JCI. Insight. 2020; 5(4): e133093.
|
| [31] |
Keegan AD, Leonard WJ, Zhu J. Recent advances in understanding the role of IL-4 signaling. Fac Rev. 2021; 10: 71.
|
| [32] |
Louiselle AE, Niemiec SM, Zgheib C. Macrophage polarization and diabetic wound healing. Transl Res. 2021; 236: 109–116.
|
| [33] |
Allen JE. IL-4 and IL-13: regulators and effectors of wound repair. Annu Rev Immunol. 2023; 41: 229–254.
|
RIGHTS & PERMISSIONS
2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.