Treatment Of Chronic Ischemic Diseases Research Articles

Twenty Years Development of Tibial Cortex Transverse Transport Surgery in PR China.

Tibial cortex transverse transport (TTT) surgery is an extension of the Ilizarov technique. Based on the law of tension‐stress, its primary function is to rebuild microcirculation which can relieve ischemic symptoms and promote wound healing. It has received more and more scholars' attention and has experienced a series of changes for 20 years since it entered PR China. The mechanisms involved have gradually become clear, such as the reconstruction of the polarization balance of macrophages, the promotion of vascular tissue regeneration, and the mobilization and regulation of bone marrow‐derived stem cells. TTT technique is mainly used in the treatment of chronic ischemic diseases of the lower extremities. It has recently been successfully used in the treatment of primary lymphedema of the lower extremities. A series of improvements have been made in the external fixator's style, the size of skin incision and osteotomy, and distraction method. For example, the annular external fixator has been redesigned as a unilateral external fixator, and accordion technology has been introduced. For distraction methods after surgery, there was no uniform standard in the past. The technique can also be used in combination with other treatments to achieve better effects, such as interventional therapy, negative pressure sealed drainage, 3D printing technology, traditional Chinese medicine. Nevertheless, the surgery may bring some complications, such as secondary fracture, nail infection, skin necrosis at the surgical site, etc. Reports of complications and doubts about the technique have made the TTT technique controversial. In 2020, the relevant expert consensus was published with treatment and management principles, which might guide the better application and development of this technique.

Study on vascular selection and reconstruction in tibial transverse transport

To explore the vascular conditions and the necessity of vascular reconstruction in the treatment of chronic ischemic diseases of lower extremities with tibial transverse transport (TTT) from the perspective of vascular surgery. A clinical data of 59 patients with chronic ischemic disease of lower extremities treated by TTT between February 2014 and July 2019 were analyzed retrospectively. Among them, there were 41 patients with diabetic foot (DF), including Wagner grade 3-4, Texas grade 2-3, and stage B-D lesions; the disease duration ranged from 0.7 to 2.4 years, with an average of 1.5 years, and 5 cases complicated with arteriosclerosis obliteran (ASO). There were 14 patients with ASO (Fontaine stage Ⅳ and Rutherford stage Ⅲ-Ⅳ) with an average disease duration of 10.8 months (range, 1.5-23.4 months). There were 4 patients with thromboangiitis obliteran (TAO) with an average disease duration of 12.3 months (range, 2.1-18.2 months), and the clinical stages were all in the third stage. In 18 patients that ankle brachial index (ABI) of anterior or posterior tibial artery was less than 0.6 before operation, or the blood flow of the three branches of inferior anterior tibial artery did not reach the ankle by imaging examination, vascular reconstruction was performed before TTT (5 cases of DF combined with ASO, 12 of ASO, 1 of TAO). After operation, the effectiveness was evaluated by ulcer wound healing, skin temperature, pain visual analogue scale (VAS) score, ABI, and CT angiography (CTA) examination. The patients with DF were followed up 8-16 months (mean, 12.2 months); the ulcer wounds healed with a healing time of 5.1-9.2 weeks (mean, 6.8 weeks); CTA examination showed that the branches of inferior anterior tibial artery were opened in 5 patients after revascularization; and the tibial osteotomy healed for 5-14 weeks (mean, 8.3 weeks). The patients with ASO were followed up 13-25 months (mean, 16.8 months); the ulcer wounds healed with a healing time of 6.2-9.7 weeks (mean, 7.4 weeks). CTA examination showed that the branches of inferior anterior tibial artery were opened in 12 patients after revascularization; all tibial osteotomy healed, and the healing time was 4.5-14.4 weeks (mean, 10.2 weeks). The patients with TAO were followed up 12-23 months with an average of 12.3 months, and toe/limb amputation was performed after ineffective treatment. The patients were divided into two groups according to whether they were combined with revascularization or not. The ABI, VAS score, and skin temperature in the combined revascularization group significantly improved at 6 months after operation ( P<0.05); while there was no significant difference in ABI at 6 months after operation in the TTT group ( P>0.05), but the skin temperature and VAS scores significantly improved when compared with those before operation ( P<0.05). The ABI of anterior or posterior tibial artery is more than 0.6, radiological examination shows that at least one of the three branches of inferior anterior tibial artery leads to ankle artery, which is a prerequisite for successful TTT in the treatment of chronic ischemic disease of lower extremities. DF is the indication of TTT. ASO can choose TTT, and TAO should use this technique cautiously.

Research progress of tibial transverse transport in treatment of chronic ischemic diseases of the lower extremities

To summarize the research progress of tibial transverse transport (TTT) in treatment of chronic ischemic diseases of the lower extremities. The related literature was systematically searched and the mechanisms, clinical treatment methods, clinical efficacy, indications, contraindications, and complications of TTT were discussed. Based on the law of tension-stress, TTT is a new method in the treatment of chronic ischemic diseases of the lower extremities. It can relieve the ischemic symptoms, promote the wound healing, and increase the limb salvage rate. The clinical application in recent years has shown good effectiveness, and the scope of application is expanding. Due to the current limited clinical application, the sample size of the TTT for the chronic ischemic diseases of the lower extremities is relatively small, and the follow-up time is limited. So its validity, long-term effectiveness, and bone transport standards are need further research.

Application of Ilizarov transverse tibial bone transport and microcirculation reconstruction in the treatment of chronic ischemic diseases in lower limbs.

The aim of the present study is to investigate the clinical value of Ilizarov transverse tibial bone transport and microcirculation reconstruction in the treatment of chronic ischemic diseases in lower limbs. A total of 90 patients with chronic ischemic diseases in lower limbs were selected and randomly divided into two groups: The observation group (n=45) and the control group (n=45). Those patients were treated with Ilizarov transverse tibial bone transport and microcirculation reconstruction, and percutaneous balloon angioplasty (PTBA), respectively. Changes in the diameter, blood flow of lower limb arteries in the paretic side, wound healing time, disappearance time of pains, dorsal foot skin temperature, and the expression area of vascular endothelial growth factors (VEGFs) were detected in both groups. Compared with control group, the diameters and blood flows of lower limb arteries were significantly larger (P<0.05), and the dorsal foot skin temperature was significantly higher at 1 day, 1 week and 1 month after operation, respectively. Meantime, the expression area of VEGFs in the observation group was significantly larger than that in the control group at 1 day, 1 week and 1 month, respectively. Furthermore, compared with control group, wound healing time and disappearance time of pains of patients were earlier in the observation group (P<0.05). At 1 month after operation, the intermittent claudication, rest pain and lower limb ulcer or gangrene among clinical symptoms of patients in the observation group improved significantly more than those in the control group (P<0.05). In conclusion, the application of Ilizarov transverse tibial bone transport and microcirculation reconstruction could achieve better outcomes in the treatment of chronic ischemic diseases in lower limbs.

Identification of a novel angiogenic peptide from periostin.

Angiogenic peptides have therapeutic potential for the treatment of chronic ischemic diseases. Periostin, an extracellular matrix protein expressed in injured tissues, promotes angiogenesis and tissue repair. We previously reported that in vivo administration of both recombinant full-length protein and the first FAS I domain of periostin alleviated peripheral artery occlusive disease by stimulating the migration of humane endothelial colony forming cells (ECFCs) and subsequent angiogenesis. In the present study, we ascertained the peptide sequence responsible for the periostin-induced angiogenesis. By serial deletion mapping of the first FAS I domain, we identified a peptide sequence (amino acids 142–151) of periostin for stimulation of chemotactic migration, adhesion, proliferation and endothelial tube formation of human ECFCs in vitro. Chemotactic migration of ECFCs induced by the periostin peptide was blocked by pre-incubation with an anti-β5 integrin neutralizing antibody. Treatment of ECFCs with the periostin peptide led to phosphorylation of both AKT and ERK, and pretreatment of ECFCs with the MEK-ERK pathway inhibitor U0126 or the PI3K-AKT pathway inhibitors, LY294002 or Wortmannin, blocked the periostin peptide-stimulated migration of ECFCs. These results suggest that the synthetic periostin peptide can be applied for stimulating angiogenic and therapeutic potentials of ECFCs.