Purpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration. Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1 alpha, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA. Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31(+) cells (all p < 0.001) and VEGFR2(+) cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1 alpha, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1 alpha, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001). Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1 alpha-induced angiogenesis.

[目的]探讨胫骨横向骨搬移(tibial transverse transport,TTT)治疗合并脓毒症/脓毒症休克的重度糖尿病足的疗效.[方法]回顾性分析2015年4月—2020年8月本院治疗的合并脓毒症/脓毒症休克的重度糖尿病足77例患者的临床资料.首先所有患者均接受矫正休克,改善全身情况,应用敏感抗生素和局部清创等治疗;然后根据医患沟通结果,45例行TTT治疗,32例行传统治疗.比较两组临床及辅助检查结果.[结果]TTT组的住院时间[(21.8±7.6)d vs(28.6±12.0)d,P=0.007]、清创次数[(2.1±0.5)次vs(3.5±1.0)次,P＜0.001]、换药次数[(19.7±7.5)次 w(25.1±11.1)次,P=0.013]、出院时创面面积[(68.2±27.4)cm2vs(105.2±20.5)cm2,P=0.003]、住院期间截肢率[8(17.8％)vs 15(46.9％),P=0.006]和死亡率[1(2.2％)vs 7(21.9％),P=0.005]均显著低于传统组.随访时间1～72个月,平均(20.4±15.8)个月.末次随访时足保留者死亡例数TTT组为8(22.2％)例,传统组为6(60.0％)例,差异有统计学意义(P=0.022).保肢成功例数TTT组为26(72.2％)例,传统组为0(0％)例,差异有统计学意义(P＜0.001).截止末次随访时存活者 TTT 组的 PCS 评分[(43.5±3.4)vs(40.6±2.1),P=0.043]和 MCS 评分[(46.4±3.6)vs(36.5±2.4),P＜0.001]均显著优于传统组.随着时间的推移,两组的PCS评分和MCS评分均显著优于治疗前(P＜0.05).辅助检查方面,随着时间推移,两组的WBC、PCT、CRP、ESR、IL-6均显著降低(P＜0.05).出院时,TTT组保肢者的WBC、PCT、CRP、ESR、IL-6均显著低于传统组(P＜0.05).TTT组出院时的CTA血管显像显著优于传统组(P＜0.05),末次随访时TTT组的CTA血管显像显著优于出院时(P＜0.05).[结论]与传统治疗方法相比,TTT治疗合并脓毒症或脓毒症休克的重度糖尿病足可明显提高创面愈合率,降低截肢率和死亡率,缓解疼痛,改善患肢功能,提高生活质量.

背景:骨膜牵张也具有促进成骨和微血管生成作用,但能否用于治疗糖尿病足目前尚未明确.目的:对骨膜牵张促进骨和血管再生的研究进展进行综述,以明确该技术用于糖尿病足治疗的理论基础,并介绍其在治疗糖尿病足中的初步应用.方法:计算机检索万方医学网、中国知网、PubMed及Elsevier数据库收录的相关文献,中文检索词为:"牵张成组织技术、牵张成骨、胫骨横向骨搬移与糖尿病足、骨膜牵张、骨膜牵张成骨、骨膜牵张与糖尿病足";英文检索词为"Distraction histogenesis,Distraction osteogenesis,Tibia transverse transport and diabetic foot,Periosteal distraction osteogenesis,Periosteal distraction and diabetic foot".最终纳入42篇文献进行综述分析.结果 与结论:①基于Ilizarov张力-应力法则或牵张成组织原理,牵张成骨技术已用于治疗骨缺损、骨不连等疾病,而牵张成骨伴随的成血管原理催生了胫骨横向骨搬移技术,该技术已经成功应用于治疗包括糖尿病足在内的下肢难愈性溃疡,取得良好的治疗效果.②研究发现对骨膜进行持续、稳定、缓慢的牵张可以促进骨和血管再生,即骨膜牵张成骨和成血管现象,该现象的机制可能与骨膜的结构和成分有关.③目前关于骨膜牵张的研究主要聚焦于其成骨功能,且主要停留在动物实验阶段而极少用于人体.与胫骨横向骨搬移促进血管再生从而用于治疗糖尿病足类似,骨膜牵张促进血管再生也可能用于治疗糖尿病足,此即骨膜牵张用于治疗糖尿病足的理论基础.④该课题组已初步将骨膜牵张用于临床治疗糖尿病足,且治疗效果良好,该文章通过展示用于骨膜搬移的器械、手术方法及典型病例.初步结果显示,由于骨膜牵张技术不需要截骨,手术操作要比胫骨横向骨搬移更加简单,手术时间更短;因为骨膜牵张技术缺少对胫骨钻孔和骨搬移的操作,缺乏对胫骨髓腔的"开窗减压"作用及骨组织的搬移,可能促血管生成和创面愈合的效果要弱于胫骨横向骨搬.未来还需对骨膜牵张促进骨和血管再生的具体机制以及手术适应证及禁忌证等进一步研究.

Background:Management of recalcitrant diabetic foot ulcer (DFU) remains difficult. Distraction osteogenesis mediates new bone formation and angiogenesis in the bone itself and the surrounding tissues. Recently it was reported that tibial cortex transverse transport (TTT) was associated with neovascularization and increased perfusion at the foot in patients with recalcitrant DFUs and facilitated healing and limb salvage. However, the findings were from several single-center studies with relatively small populations, which need to be confirmed in multicenter cohort studies with relatively large populations. Furthermore, the effect of this technique on patient's health-related quality of life is still unclear. Methods:We treated patients with recalcitrant (University of Texas wound grading system 2-C to 3-D and not responding to prior routine conservative and surgical treatments for at least 8 weeks) DFUs from seven centers using TTT (a 5 ​cm ​× ​1.5 ​cm corticotomy followed by 4 weeks of medial and lateral distraction) between July 2016 and June 2019. We analyzed ulcer healing, major amputation, recurrence, health-related quality of life (physical and mental component summary scores), and complications in the 2-year follow-up. Foot arterial and perfusion changes were evaluated using computed tomography angiography and perfusion imaging 12 weeks postoperatively. Results:A total of 1175 patients were enrolled. Patients who died (85, 7.2%) or lost to follow-up (18, 1.7%) were excluded, leaving 1072 patients for evaluation. Most of the patients were male (752, 70.1%) and with a mean age of 60.4 ​± ​9.1 years. The mean ulcer size was 41.0 ​± ​8.5 ​cm2 and 187 (16.6%) ulcers extended above the ankle. During the follow-up, 1019 (94.9%) patients healed in a mean time of 12.4 ​± ​5.6 weeks, 53 (4.9%) had major amputations, and 33 (3.1%) experienced recurrences. Compared to preoperatively, the patients had higher physical (26.2 ​± ​8.3 versus 41.3 ​± ​10.6, p ​= ​0.008) and mental (33.6 ​± ​10.7 versus 45.4 ​± ​11.3, p ​= ​0.031) component summary scores at the 2-year follow-up. Closed tibial fracture at the corticotomy site was found in 8 (0.7%) patients and was treated using external fixation and healed uneventfully. There were 23 (2.1%) patients who had pin site infections and were treated successfully with dressing changes. Compared to preoperatively, the patients had more small arteries and higher foot blood flow (8.1 ​± ​2.2 versus 28.3 ​± ​3.9 ml/100 ​g/min, p ​= ​0.003) and volume (1.5 ​± ​0.3 versus 2.7 ​± ​0.4 ml/100 ​g, p ​= ​0.037) 12 weeks postoperatively. Conclusion:TTT promotes healing, limb salvage, and health-related quality of life in patients with recalcitrant DFUs as demonstrated in this multicenter cohort study. The surgical procedure was simple and straightforward and the complications were few and minor. The effect of this technique was associated with neovascularization and improved perfusion at the foot mediated by the cortex distraction. The findings are required to confirm in randomized controlled trials.The Translational Potential of this Article: TTT can be used as an effective treatment in patients with recalcitrant DFUs. The mechanism is associated with neovascularization and consequently increased perfusion in the foot after operation.

[目的]研究胫骨横向骨搬移(tibia transverse transport,TTT)治疗合并慢性肾病(chronic kidney disease,CKD)的糖尿病足溃疡(diabetic foot ulcer,DFU)的临床疗效.[方法]回顾性分析2015年2月-2019年8月于本科采用TTT治疗的糖尿病足病例资料,其中合并慢性肾病的67例列入肾病组,同期无肾病患者53例,列入无肾病组.比较两组临床与辅助检查结果.[结果]肾病组手术时间、住院时间、拆除外固定时间均大于无肾病组(P＜0.05).随访4～24个月,平均(14.38±4.38)个月.在随访期间肾病组患者有7例患者死亡于心脑血管疾病,无肾病组无患者死亡(P＜0.05).末次随访时两组间足部溃疡愈合率的差异无统计学意义(P＞0.05),但是肾病组溃疡愈合时间显著晚于无肾病组(P＜0.05).至末次随访时,肾病组足部溃疡复发率、截肢率均高于无肾病组,但两组间差异均无统计学意义(P＞0.05).与术前相比,术后两组血管显像均显著改善(P＜0.05);术后1个月时无肾病组的血管显像优于肾病组(P＜0.05),术后3个月时两组间血管显像的差异无统计学意义(P＞0.05).检验方面,与术前相比,术后1个月两组CRP水平、Cr及HbA1c均显著下降(P＜0.05),但Hb,Alb和Urea无显著变化(P＞0.05).相应时间点,肾病组的Hb,Alb显著低于无肾病组(P＜0.05),而Urea、Cr和CRP显著高于无肾病组(P＜0.05).[结论]TTT治疗合并慢性肾病的糖尿病足取得愈合率较高,截肢率、复发率较低的良好效果.