Combining Tibial Cortex Transverse Transport (TTT) and Endovascular Therapy (EVT) for Limb Salvage in Chronic Limb-Threatening Ischemia.

OBJECTIVE: The clinical management of patients with chronic limb-threatening ischemia (CLTI) faces great challenges. Enhancing wound healing and limb preservation rates in this cohort is a critical objective. This study investigates the effectiveness of combining tibial cortex transverse transport (TTT) and endovascular therapy (EVT) for the treatment of patients with severe CLTI. We aim to evaluate the therapeutic results of this combined approach on the specified patient group. METHODS: We conducted a retrospective study to compare EVT with the combination of TTT and EVT in patients (Rutherford category 5 and above) with CLTI at Guangxi Medical University's First Affiliated Hospital from June 2017 to June 2023. This cohort was subjected to a follow-up period ranging from a minimum of 6 months to a maximum of 12 months. The primary outcome measures included amputation-free survival (AFS) (avoidance of above-ankle amputation or death from any cause), overall mortality, limb salvage rates, wound healing efficiency, and the technical efficacy of the applied treatments. A variety of statistical analyses including chi-square tests, Fisher's exact tests, and Pearson's and Spearman's correlation analyses. RESULTS: In this study, 131 patients with CLTI were included: 76 in the control group receiving only EVT treatment and 55 in the TTT + EVT group. The two groups were matched on demographic and clinical characteristics. In the TTT + EVT group, after more than 6 months of follow-up, 85.5% of patients achieved AFS, and wound healing was observed in 54.5% (30 of 55 patients). After more than 12 months of follow-up, 81.9% achieved AFS, with wound healing in 32 patients. Furthermore, after more than 24 months, 74.2% of patients remained amputation-free, with wound healing in all surviving patients. In the control group, after more than 6 months of follow-up, 72.4% of patients achieved AFS, and wound healing was observed in 51.3% (39 of 96 patients). After more than 12 months, 48.9% achieved AFS, with wound healing in 21 patients. CONCLUSION: We found that combining therapy of TTT and EVT is safe and can be successfully administered in patients with CLTI and it enhances wound healing and AFS.

Correlation analysis of patients with diabetic foot ulcers treated with tibial cortex transverse transport surgery and platelet-to-lymphocyte ratio and monocyte-to-neutrophil ratio.

BACKGROUND: Diabetic foot ulcers (DFUs) represent one of the most severe late-stage complications of diabetes. Tibial cortex transverse transport (TTT) surgery stands as the prevailing method for addressing DFUs. This surgical intervention holds the promise of expediting DFU wound healing and diminishing the rate of amputations, with the mitigation of inflammatory responses playing a pivotal role. In this study, we aim to explore the correlation between inflammation and TTT surgery, with the overarching goal of facilitating swift prognostic assessments in clinical practice. OBJECTIVES: The correlation between the severity of DFUs and clinical test results remains ambiguous. A clinical prediction model was devised to explore the connection between DFU severity and the efficacy of TTT surgery, utilizing straightforward and efficient clinical indicators. MATERIAL AND METHODS: Clinical data and examination results were gathered by tracking hospitalized DFU patients who underwent TTT surgery at the First Affiliated Hospital of Guangxi Medical University (Nanning, China). Indicators associated with DFU severity and wound healing time post-surgery were identified through logistic regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Subsequently, a clinical prediction model was constructed. Finally, the intersection of these 2 sets of indicators revealed factors correlated with wound severity and post-operative healing duration. RESULTS: Our study was comprised of 202 patients who were categorized into 2 groups based on Wagner's grading classifications. Utilizing Student's t-tests, LASSO regression and logistic regression analyses, we identified 3 factors indicative of DFU severity: platelet-to-lymphocyte ratio (PLR), mixed lymphocyte reaction (MLR) and hemoglobin (HGB). Univariate COX regression analysis revealed 12 factors such as: white blood cells (WBC), neutrophils (NEUT), monocytes (MO), PLR, MLR, neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), age, lymphocytes (LY), monocyte-to-neutrophil ratio (MNR), uric acid (UA), and albumin (ALB) associated with the postoperative healing duration. Ultimately, we identified 2 factors, PLR and MNR, at the intersection of these 2 datasets. CONCLUSIONS: Platelet-to-lymphocyte ratio and MNR were identified as factors associated with both the severity of DFUs and the prognosis following TTT surgery.

Tibial Cortex Transverse Transport Facilitates Severe Diabetic Foot Wound Healing via HIF-1α-Induced Angiogenesis.

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-1α, 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-1α, 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-1α, 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-1α-induced angiogenesis.

Tibial cortex transverse transport promotes ischemic diabetic foot ulcer healing via enhanced angiogenesis and inflammation modulation in a novel rat model.

BACKGROUND: Tibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT. METHODS: We established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes. RESULTS: The TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity. CONCLUSION: Our innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.

Smartphone usage behaviors and their association with De Quervain's Tenosynovitis (DQT)among college students: a cross-sectional study in Guangxi, China.

BACKGROUND: The growing prevalence of smartphone use among college students in China has led to health concerns, including De Quervain's Tenosynovitis (DQT). However, the specific smartphone usage behaviors contributing to DQT remain poorly understood. This study aimed to explore the relationship between smartphone usage behaviors and DQT in college students. METHODS: A cross-sectional study was conducted with 937 students from various majors in Guangxi between September 2021 and April 2022. Participants completed an online questionnaire assessing smartphone usage behaviors and their association with DQT. The Finkelstein test was employed to diagnose DQT. RESULTS: Over half of the college students (52%) tested positive for DQT via Finkelstein's test. Higher levels of smartphone usage time (6-8 h/day: OR = 4.454, 95%CI:1.662-12.229; ≥8 h/day: OR = 4.521, 95%CI:1.596-12.811), phone games (OR = 1.997, 95%CI:1.312-3.040), social media (OR = 2.263, 95%CI:1.795-3.833), and leisure activities (OR = 1.679, 95%CI:1.140-2.475) were significantly associated with an increased risk of DQT. Two specific gestures (Bilateral thumbs, BT: OR = 1.900, 95%CI:1.281-2.817; Bilateral thumbs-horizontal screen, BT-HS: OR = 1.872, 95%CI:1.244-2.818) and two screen sizes (5.0-5.5inch: OR = 2.064, 95%CI:1.108-3.846; 6.0-6.5inch: OR = 2.413, 95%CI:1.125-4.083) also exhibited a higher risk of DQT. Bilateral DQT was observed, with Gesture-BT identified as the primary risk factor. CONCLUSION: Our findings suggest that increased smartphone usage time, phone games, social media, and leisure activities elevate the risk of DQT among college students. Furthermore, two specific gestures and two screen sizes were also linked to a heightened DQT risk. To mitigate DQT development, college students should reduce smartphone usage time and adopt appropriate gestures.

Efficacy and safety of unilateral tibial cortex transverse transport on bilateral diabetic foot ulcers: A propensity score matching study.

Background: Tibial Cortex Transverse Transport (TTT) has been demonstrated to be an effective treatment for unilateral diabetic foot ulcers (UDFUs). However, this retrospective study was designed to compare the efficacy and safety of unilateral TTT on bilateral diabetic foot ulcers (BDFUs). Methods: This retrospective study included a review of patients with TTT treated from January 2017 to August 2019, Propensity Score Matching (PSM) was performed to compare patients with BDFUs to those with UDFUs. Ulcer healing, recurrence, and major amputation rates were evaluated at 1-year follow-up. Changes in foot vessels were assessed in the BDFUs group using computed tomography angiography (CTA). Results: A total of 140 patients with DFUs (106 UDFUs and 34 BDFUs) were included in the study. UDFUs and BDFUs were matched in a 1:1 ratio (34 in each group) using PSM. No significant difference was observed at 1-year-follow-up [91.2% (31/34) vs. 76.5% (26/34), OR 0.315 (95% CI 0.08 to 1.31), P â€‹= â€‹0.10] and 6-month-follow-up [70.6% (24/34) vs. 50.0% (17/34), OR 0.85 (95% CI 0.15 to 1.13), P â€‹= â€‹0.08] in two groups. Significant differences in rates of major amputation and recurrence between the groups (P â€‹> â€‹0.05) were not observed. The BDFUs group appeared more angiogenesis of the foot by CTA after 8 weeks of operation. Conclusion: Results of this study suggest that severe BDFUs can be effectively treated by unilateral TTT. TTT is easy to operate and effective, which may be a good alternative for treating severe BDFUs. The translational potential of this article: In previous retrospective clinical studies, TTT has demonstrated promising clinical outcomes in the management of diabetic foot ulcers. In this current study, we aim to investigate the potential use of TTT in treating distant tissue defects by evaluating the limited availability and safety of TTT for the management of bilateral diabetic foot. While additional basic and clinical research is necessary to fully elucidate the underlying mechanisms, our study offers insight into the potential therapeutic use of TTT for this condition.

The epidemiological characteristics of neurogenic limb deformity disorder in China: a national-based study from Qin Sihe orthopedic center.

BACKGROUND: Neurogenic limb deformity disorder (NLDD) refers to limb deformity disorders caused by various neurogenic disorders. However, there are no studies to systematically summarize and analyze these diseases in China, and we first proposed the concept of NLDD. We describe the epidemiological characteristics of NLDD in China based on the largest case database of limb orthopedics in China. METHODS: This study analyzed parameters from the Qin Sihe Orthopedic Surgery Case Data (QSHOSCD). The database is based on the Rehabilitation Hospital affiliated to National Research Center for Rehabilitation, which has collected nearly 37,000 patients to date and includes a wide variety of limb deformities. The types of diseases are summarized and classified for all patients studied. Statistical analysis was based on the type of etiology, age, regional distribution, and historical surgical volume. Partial outcomes were statistically analyzed separately by common diseases (polio and cerebral palsy) and rare diseases (37 other diseases). RESULTS: From 1979 to 2019, 30,194 patients with NLDD were treated surgically for 39 neurogenic disorders. The male to female ratio was 1.48:1, the mean age was 19.65 years, and most patients (82.38%) were aged between 6 and 30 years. Patients included from 32 provinces and cities across China, mainly concentrated in populous central provinces and Heilongjiang Province. The peak of annual surgical procedures was from 1988 to 1994, and the number of annual surgical procedures for common diseases gradually decreased from 1994 onwards, but the trending is opposite for rare diseases. CONCLUSIONS: This study is the first to demonstrate the disease types, population characteristics and incidence trends of NLDD in China. It suggests that the prevention and treatment of NLDD should focus on the adolescent population and enhance the treatment of neurogenic diseases that cause limb deformities. The growth and adaption of the Ilizarov technique and its practice in Chinese orthopedic benefits the treatment of neurogenic limb deformity disorders.

Effect of tibial cortex transverse transport in patients with recalcitrant diabetic foot ulcers: A prospective multicenter cohort study.

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 â€‹cm â€‹× â€‹1.5 â€‹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 â€‹± â€‹9.1 years. The mean ulcer size was 41.0 â€‹± â€‹8.5 â€‹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 â€‹± â€‹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 â€‹± â€‹8.3 versus 41.3 â€‹± â€‹10.6, p â€‹= â€‹0.008) and mental (33.6 â€‹± â€‹10.7 versus 45.4 â€‹± â€‹11.3, p â€‹= â€‹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 â€‹± â€‹2.2 versus 28.3 â€‹± â€‹3.9 ml/100 â€‹g/min, p â€‹= â€‹0.003) and volume (1.5 â€‹± â€‹0.3 versus 2.7 â€‹± â€‹0.4 ml/100 â€‹g, p â€‹= â€‹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.

Knowledge Domains and Emerging Trends of Osteoblasts-Osteoclasts in Bone Disease From 2002 to 2021: A Bibliometrics Analysis and Visualization Study.

Background: Osteoblasts-Osteoclasts has been a major area in bone disease research for a long time. However, there are few systematic studies in this field using bibliometric analysis. We aimed to perform a bibliometric analysis and visualization study to determine hotspots and trends of osteoblasts-osteoclasts in bone diseases, identify collaboration and influence among authors, countries, institutions, and journals, and assess the knowledge base to develop basic and clinical research in the future. Methods: We collected articles and reviews for osteoblasts-osteoclasts in bone diseases from the Web of Science Core Collection. In addition, we utilized scientometrics software (CiteSpace5.8 and VOSviewer1.6.18) for visual analysis of countries/regions, institutions, authors, references, and keywords in the field. Results: In total, 16,832 authors from 579 institutions in 73 countries/regions have published 3,490 papers in 928 academic journals. The literature in this field is rapidly increasing, with Bone publishing the most articles, whereas Journal of Bone and Mineral Research had the most co-cited journals. These two journals mainly focused on molecular biology and the clinical medicine domain. The countries with the highest number of publications were the US and China, and the University of Arkansas for Medical Sciences was the most active institution. Regarding authors, Stavros C. Manolagas published the most articles, and Hiroshi Takayanagi had the most co-cited papers. Research in this field mainly includes molecular expression and regulatory mechanisms, differentiation, osteoprotection, inflammation, and tumors. The latest research hotspots are oxidative stress, mutation, osteocyte formation and absorption, bone metabolism, tumor therapy, and in-depth mechanisms. Conclusion: We identified the research hotspots and development process of osteoblasts-osteoclasts in bone disease using bibliometric and visual methods. Osteoblasts-osteoclasts have attracted increasing attention in bone disease. This study will provide a valuable reference for researchers concerned with osteoblasts-osteoclasts in bone diseases.

[Treatment of severe diabetic foot ulcer using tibia transverse transport combined with nose ring drain].

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) combined with nose ring drain (NRD) in the treatment of severe diabetic foot ulcer. METHODS: The clinical data of 60 patients with severe diabetic foot (Wagner grade 3 or 4) ulcer who were admitted between April 2017 and August 2020 and met the selection criteria were retrospectively analyzed. Among them, 30 cases were treated with TTT combined with NRD (TTT+NRD group), and 30 cases were treated with TTT (TTT group). There was no significant difference in gender, age, diabetes duration, preoperative glycated hemoglobin, comorbidities, wound area, and duration, side, and grade of diabetic foot ( P>0.05). The wound healing time, wound healing rate, amputation rate, recurrence rate, duration of antibiotic therapy, hospital stay, number of hospitalizations, and number of operations were recoreded and compared between the two groups. RESULTS: No obvious surgical complications occurred in the two groups. Patients in both groups were followed up 3-13 months, with an average of 5.7 months. The duration of antibiotic therapy and hospital stay in the TTT+NRD group were significantly shorter than those in the TTT group ( P<0.05). There was no significant difference in wound healing time, wound healing rate, number of hospitalizations, and number of operations between the two groups ( P>0.05). During follow-up, there was no recurrence of ulcer in the TTT+NRD group while 2 recurrent cases (6.7%) in the TTT group. The difference in recurrence rate was not significant ( P=0.492). One case (3.3%) in the TTT+NRD group underwent amputation due to acute lower extremity vascular embolism, and 1 case (3.3%) in the TTT group underwent amputation due to secondary necrosis. The difference in amputation rate was not significant between the two groups ( P=1.000). CONCLUSION: TTT combined with NRD is an effective method for the treatment of severe diabetic foot ulcers with deep infections or relatively closed cavities or sinuses. It can shorten the time of antibiotic use and the length of hospitalization; and the NRD has a good drainage effect without obvious comorbidities, procedure and the postoperative care are simple and easy to obtain materials.

Tibial cortex transverse transport facilitating healing in patients with recalcitrant non-diabetic leg ulcers.

OBJECTIVE: The treatment of recalcitrant not-diabetic leg ulcers remains challenging. Distraction osteogenesis is accompanying by angiogenesis and neovascularization in the surrounding tissues. We previously applied tibial cortex transverse transport (TTT) to patients with recalcitrant diabetic foot ulcers and found neovascularization and increased perfusion in the foot and consequently enhanced healing and limb salvage and reduced recurrence. However, the effects of TTT on recalcitrant non-diabetic leg ulcer remains largely unknown. METHODS: Consecutive patients (n â€‹= â€‹85) with recalcitrant non-diabetic leg ulcers (University of Texas Grade 2-B to 3-D, ie, wound penetrating to the tendon, capsule, bone, or joint with infection and/or ischemia) were recruited and divided into TTT (n â€‹= â€‹42) and control (n â€‹= â€‹43) groups based on the treatment they received. There were 36 (85.7%) arterial ulcers, 4 (9.5%) venous ulcers and 2 (4.8%) mixed ulcers in the TTT group and 32 (74.4%) arterial ulcers, 7 (16.7%) venous ulcers and 4 (9.3%) mixed ulcers in the control group (p â€‹> â€‹0.05). The two groups were matched on demographic and clinical characteristics. Patients in the TTT group underwent tibial corticotomy followed by 4 weeks of distraction medially then laterally, while those in the control group received conventional surgeries (debridements, revascularization, reconstruction with flaps, or skin grafts or equivalents). Ulcer healing and healing time, limb salvage, recurrence, and patient death were evaluated at a 1-year follow-up. Changes in leg small vessels were assessed in the TTT group using computed tomography angiography (CTA). RESULTS: TTT group had higher healing rates at 1-year follow-up than the control group (78.6% [33/42] vs. 58.1% [25/43], OR 2.64 [95% CI 1.10 to 6.85], p â€‹= â€‹0.04). The healing time of the TTT group was shorter than the control group (4.5 vs. 6.1 months, mean difference -1.60 [95% CI -2.93 to -0.26], p â€‹= â€‹0.02). There were no significant differences in rates of major amputation, reulceration, or mortality between the groups (p â€‹> â€‹0.05). TTT group displayed more small vessels 4 weeks postoperatively at the wound area, the foot, and the calf of the ipsilateral side in CTA. All patients in the TTT group achieved good union at the osteotomy site and had no skin or soft tissue necrosis or infection around the incision area. CONCLUSION: The findings showed that TTT facilitated the healing of recalcitrant non-diabetic leg ulcers and reduced the healing time compared with conventional surgeries. They suggest that TTT is an effective procedure to treat recalcitrant non-diabetic foot ulcers compared with standard surgical therapy. The procedure of TTT is relatively simple. Randomized controlled trials are required to confirm these findings. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: TTT can be used as an effective treatment for recalcitrant non-diabetic leg ulcers in patients. The mechanism may be associated with the neovascularization in the ulcerated foot induced by TTT and consequently increased perfusion. Together with previous findings from recalcitrant diabetic leg ulcers, the findings suggest TTT as an effective procedure to treat recalcitrant chronic leg ulcers.

[Treatment experiences of 516 cases of diabetic foot treated with tibial transverse transport].

Tibial transverse transport (TTT) was firstly applied to treat thromboangiitis obliterans successfully by Professor QU Long in China in 2000. Based on this, the team of Professor HUA Qikai in the First Affiliated Hospital of Guangxi Medical University applied this technique to treat diabetic foot since 2013, and until now, more than 500 patients underwent this treatment with excellent effectiveness including a salvage rate as high as 96.1%. Our team also improved this technique in many aspects, and developed a TTT-based classification system and treatment for diabetic foot. We also explored the underlying mechanism of TTT treatment using imaging, histology, and other basic research methods. To further promote the application of this technique in clinic, we reported the findings from our cases and reviewed our previous findings in this study.

Proximal Tibial Cortex Transverse Distraction Facilitating Healing and Limb Salvage in Severe and Recalcitrant Diabetic Foot Ulcers.

BACKGROUND: The management of severe and recalcitrant diabetic foot ulcers is challenging. Distraction osteogenesis is accompanied by vascularization and regeneration of the surrounding tissues. Longitudinal distraction of the proximal tibia stimulates increased and prolonged blood flow to the distal tibia. However, the effects of transverse distraction of the proximal tibia cortex on severe and recalcitrant diabetic foot ulcers are largely unknown. QUESTIONS/PURPOSES: (1) Does tibial cortex transverse distraction increase healing and decrease major amputation and recurrence of severe and recalcitrant diabetic foot ulcers compared with routine management (which generally included débridement, revascularization, negative pressure wound therapy, local or free flaps, or skin grafts as indicated)? (2) Does neovascularization and perfusion increase at the foot after the procedure? (3) What are the complications of tibial cortex transverse distraction in patients with severe and recalcitrant diabetic foot ulcers? METHODS: Between July 2014 and March 2017, we treated 136 patients with diabetes mellitus and University of Texas Grade 2B to 3D ulcers (wound penetrating to the tendon, capsule, bone, or joint with infection and/or ischemia). The patients had failed to respond to treatment for at least 6 months, and their ulcers had a mean ± SD area of 44 cm ± 10 cm. All 136 patients underwent tibial cortex transverse distraction (partial corticotomy of the upper tibia, which was in normal condition, followed by 4 weeks of transverse distraction medially then laterally). We compared these patients with the last 137 consecutive patients we treated with standard surgical treatment, consisting of débridement, revascularization, local or free flap or skin equivalent, or graft reconstruction along with negative-pressure wound therapy between May 2011 and June 2013; there was a 1-year period during which both treatments were in use, and we did not include patients whose procedures were performed during this time in either group. Patients in both groups received standard off-loading and wound care. The patients lost to follow-up by 2 years (0.7% of the treatment group [one of 137] and 1.4% of the control group [two of 139]; p = 0.57) were excluded. The patients in the treatment and control groups had a mean age of 61 years and 60 years, respectively, and they were predominantly men in both groups (70% [95 of 136] versus 64% [88 of 137]; p = 0.32). There were no differences with respect to parameters associated with the likelihood of ulcer healing, such as diabetes and ulcer duration, ulcer grades and area, smoking, and arterial status. We compared the groups with respect to ulcer healing (complete epithelialization without discharge, maintained for at least 2 weeks, which was determined by an assessor not involved with clinical care) in a 2-year follow-up, the proportion of ulcers that healed by 6 months, major amputation, recurrence, and complications in the 2-year follow-up. Foot arterial status and perfusion were assessed in the tibial cortex transverse distraction group using CT angiography and perfusion imaging. RESULTS: The tibial cortex transverse distraction group had a higher proportion of ulcers that healed in the 2-year follow-up than the control group (96% [131 of 136] versus 68% [98 of 137]; odds ratio 10.40 [95% confidence interval 3.96 to 27.43]; p < 0.001). By 6 months, a higher proportion of ulcers healed in the tibia cortex transverse distraction group than the control group (93% [126 of 136] versus 41% [56 of 137]; OR 18.2 [95% CI 8.80 to 37.76]; p < 0.001). Lower proportions of patients in the tibia cortex transverse distraction group underwent major amputation (2.9% [four of 136] versus 23% [31 of 137], OR 0.10 [95% CI 0.04 to 0.30]; p < 0.001) or had recurrences 2.9% (4 of 136) versus 17% (23 of 137), OR 0.20 [95% CI 0.05 to 0.45]; p < 0.001) than the control group in 2-year follow-up. In the feet of the patients in the tibial cortex transverse distraction group, there was a higher density of small vessels (19 ± 2.1/mm versus 9 ± 1.9/mm; mean difference 10/mm; p = 0.010), higher blood flow (24 ± 5 mL/100 g/min versus 8 ± 2.4 mL/100 g/min, mean difference 16 mL/100 g/min; p = 0.004) and blood volume (2.5 ± 0.29 mL/100 g versus 1.3 ± 0.33 mL/100 g, mean difference 1.2 mL/100 g; p = 0.03) 12 weeks postoperatively than preoperatively. Complications included closed fractures at the corticotomy site (in 1.5% of patients; two of 136), which were treated with closed reduction and healed, as well as pin-site infections (in 2.2% of patients; three of 136), which were treated with dressing changes and they resolved without osteomyelitis. CONCLUSIONS: Proximal tibial cortex transverse distraction substantially facilitated healing and limb salvage and decreased the recurrence of severe and recalcitrant diabetic foot ulcers. The surgical techniques were relatively straightforward although the treatment was unorthodox, and the complications were few and minor. These findings suggest that tibial cortex transverse distraction is an effective procedure to treat severe and recalcitrant diabetic foot ulcers compared with standard surgical therapy. Randomized controlled trials are required to confirm these findings. LEVEL OF EVIDENCE: Level II, therapeutic study.

Computed tomography perfusion study evaluating the curative effect of tibial transverse transport in patients with severe diabetic foot.

BACKGROUND: The clinical treatment of patients with severe diabetic foot (DF) is difficult. Recently, the First Affiliated Hospital of Guangxi Medical University began to apply tibial transverse transport (TTT) in patients with DF. This treatment has achieved significant effects, but its mechanism of action is unclear. Recently, microcirculation and the pathogenesis of diabetes have become the foci of research in this field. The evaluation of the possible mechanism of microcirculation reconstruction requires relevant indicators. The aim of this study was to investigate the value of computed tomography perfusion in evaluations of the curative effects of TTT and establish corresponding quantitative evaluation indicators. METHODS: Twelve patients with DF treated with TTT were recruited as the research participants. All diabetic feet were divided into the transport foot (TF) group and nontransport foot (NTF) group according to whether the patients underwent TTT. All patients underwent CT shuttle scanning preoperatively and 8 weeks after surgery. The shuttle scan data were transferred to Siemens VPCT body software and postprocessed with Customized Tumor2. We chose the TF posterior tibial artery from a distance of approximately 15 cm to the bifurcation of the plantar medial artery and the lateral plantar artery as the input artery. We selected the centre of the bilateral medial plantar muscle group on the coronal and axial regions of interest. We applied a deconvolution approach to obtain data from both sides of the plantar tissue perfusion. Skin temperature (ST) detection was performed with an ST gun to measure the average ST values in the dorsal and plantar areas, the first and fifth heads of the phalanges, and the medial and lateral malleolus points of both feet of patients with DF preoperatively and 8 weeks after surgery. RESULTS: The preoperative and postoperative ST values of the patients in the TF group were 30.73 ± 1.86 °C and 32.22 ± 1.51 °C, respectively. The preoperative and postoperative ST values for the patients in the NTF group were 30.93 ± 2.65 °C and 32.07 ± 2.09 °C, respectively. There were significant differences in the preoperative and postoperative data between the TF (P = 0.001) and NTF (P = 0.013) groups. In the patients with DF who underwent TTT, there were both preoperative and postoperative differences inside the medial plantar muscle group in the relative blood volume (rBV) value and relative mean transit time (rMTT) (P = 0.027, P = 0.026, respectively). The postoperative BV in the NTF group was increased compared with the preoperative BV (P = 0.006). CONCLUSION: There were significant differences in relative BV, relative mean transit time, and ST between the two groups before and after surgery, and the postoperative BV in the NTF group and ST values in the two groups were increased compared with the preoperative values. The BV in the NTF group and the ST values in the two groups were effective indicators in evaluating the changes between preoperative and postoperative perfusion. These results indicate that TTT could increase plantar tissue perfusion as assessed by BV and ST; this increase was among the reasons for the surface healing of severe DF ulcers. TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Preoperative CT perfusion evaluation can provide relevant information of blood vessels and microcirculation for clinical operation, and postoperative CT perfusion evaluation can provide postoperative efficacy evaluation for clinical operation. All patients received information about the study and signed a specific informed consent. Approval for this study was granted by the regional ethics committee [Regional Ethics Committee of the First Affiliated Hospital of Guangxi Medical University, China [(2018-(KY-E-069].

[The effectiveness of Ilizarov technique-based transverse tibial bone transport on treatment of severe diabetic foots complicated with systemic inflammation response syndrome].

Objective: To evaluate the effectiveness of Ilizarov technique-based transverse tibial bone transport on the treatment of severe diabetic foot ulcer (Wagner grades 3 to 5) complicated with systemic inflammatory response syndrome (SIRS). Methods: Between August 2014 and December 2017, 33 patients with severe diabetic foot and SIRS were treated with Ilizarov technique-based transverse tibial bone transport. There were 27 males and 6 females, with a mean age of 60.6 years (range, 34-79 years). All of them suffered from type 2 diabetes mellitus. The duration of diabetes was 1-28 years (mean, 10 years) and the duration of diabetic foot was 1-12 months (mean, 2.7 months). According to Wagner classification, there were 8 cases in grade 3, 23 cases in grade 4, and 2 cases in grade 5. The wound healing condition was observed after operation, and the limb salvage rate was calculated. The changes in body temperature, heart rate, respiratory rate, white blood cell count, erythrocyte sedimentation rate, and C-reactive protein concentration were assessed. The skin temperature of the dorsum of the foot was measured, and the visual analogue scale (VAS) score was used to evaluate the improvement of foot pain. Results: All 33 patients were followed up 3-30 months (mean, 14.1 months). All ulcers healed and the healing time was 3-12 months (mean, 5.3 months); the limb salvage rate was 100%. Postoperative body temperature, heart rate, respiratory rate, white blood cell count, erythrocyte sedimentation rate, and C-reactive protein concentration were significantly lower than those before operation ( P<0.05). The skin temperature of the dorsum of the foot was (32.64±2.17)℃ at 1 month after operation, which was significantly improved when compared with preoperative value [(31.28±1.99)℃] ( t=0.05, P=0.00); but there was no significant difference in skin temperature compared with healthy side [(32.46±2.10)℃] ( t=2.04, P=0.41). The VAS score was 2.4±0.7 at 1 month after operation, which was significantly improved when compared with preoperative score (4.3±0.8) ( t=3.10, P=0.00). Conclusion: Ilizarov technique-based transverse tibial bone transport is an effective way to treat severe diabetic foot complicated with SIRS. It can promote foot ulcer healing and avoid amputations.

Association of variants in 21q22 with ankylosing spondylitis in the Chinese Guangxi Zhuang population.

Genome-wide association study has reported a number of genes as being associated with ankylosing spondylitis (AS) in Caucasian European populations and Chinese Han population. The aim of the study was to investigate whether single nucleotide polymorphisms (SNPs) covering the 21q22 region are associated with AS in the Chinese Guangxi Zhuang population. A case-control study was performed in unrelated patients with AS (n = 315) and age-, sex-, and ethnicity-matched controls (n = 630) from Guangxi Zhuang ethnic group. All patients met the modified New York criteria for AS. TaqMan genotyping assay was used to genotype cases and controls for 17 tag SNPs covering 21q22. After multiple-testing correction, significant association with AS was not observed in all SNP, but one block haplotype was significantly associated with AS. The pairwise analysis of the rs8126528/rs2150414/rs6517532 alleles found that the G-A-A haplotype (OR 2.92, 95 % CI 1.48-3.55; p = 0.0002, permuted p = 0.0332) significantly increased the risk of AS in comparison with the G-A-G, A-A-A and G-G-A carriers. In conclusion, the study results define a novel risk haplotypes in 21q22 that was associated with AS in the Chinese Guangxi Zhuang population. The findings was consistent with previous genetic and functional studies that point at variants of the BRWD1 and/or PSMG1 loci as interesting genetic factors contributing to AS.

[Preliminary study on appropriate concentration gradient of nerve growth factor in promoting fracture healing].

OBJECTIVE: To study the effect of local application of different concentrations of nerve growth factor (NGF) on fracture healing, and to further search for the appropriate concentration gradient of NGF to promote fracture healing. METHODS: Seventy-five adult male Sprague Dawley rats, weighing (220.0 +/- 2.5) g, were made the right tibia fracture model at 1 cm distal from the tibial tubercle and randomly divided into 5 groups (groups A, B, C, D, and E, n=15). Fractures were treated with 0.3 mL normal saline containing different concentration of NGF (0.00648 x 10(-2), 0.032 40 x 10(-1), 0.16200 x 10(-2), and 0.81000 x 10(-2) microg/g) in groups A, B, C, and D, respectively, and the same amount of normal saline in group E. After 2, 4, and 6 weeks, the specimens were harvested from 5 rats of each group to perform the biochemical test and histological observation. Before the rats were sacrificed, the arteriovenous blood was taken from the eye-ball to test the alkaline phosphatase (ALP) activity. RESULTS: After 2, 4, and 6 weeks, the gross observation showed that the size and hardness of bone tissue and callus tissue growth gradually increased in groups A, B, C, and D, and group D was higher than groups A, B, C, and E. The X-ray films showed that the calcified area gradually increased in groups A, B, C, and D, and group D was higher than groups A, B, C, and E. The histological observation showed that the trabecular quality and maturity in group D were better than those in groups A, B, C, and E. Group D was significantly higher than groups A, B, C, and E (P < 0.05) in the gray values of callus tissue and the calcium content of callus tissue at 4 and 6 weeks, in the wet weight of callus tissue at 2 and 4 weeks, and in the ALP content of serum at 2 weeks. The trabecula surface index of osteoblast, the trabecular volume, and the trabecular width decreased as time in the order of groups A, B, C, and D, which were higher than those of group E; group D was the highest, showing significant differences when compared with the other groups (P < 0.05). CONCLUSION: The local application of NGF can promote fracture healing in rats. The high concentration gradient of NGF (0.81000 x 10(-2) microg/g) has an obvious promotion role on fracture healing.

[Study on effect of NGF on fracture healing].

OBJECTIVE: To investigate the effect of NGF on fracture healing, and to study the role of BMP-2 induced osteoblast. METHODS: Sixty cleaned male Kunming mice (aging 6-8 weeks and weighing 23-25 g) were made fracture models in the middle of femoral shaft and randomly divided into four groups (groups A, B, C and D, n=15). Fracture was treated with NGF/normal saline, BMP-2, BMP-2/NGF/normal saline, and normal saline in groups A, B, C and D, respectively. After 14, 21 and 28 days, the specimens were selected from 5 mice each group to do the biochemical and histological analysis. Before the mice were killed, the arteriovenous blood was taken from their eye-ball to test the ALP activity. RESULTS: After 14 days, 21 days and 28 days, the gross observation showed that the size and hardness of bone tissue, and callus tissue growth increased in groups A, B and C order and were higher than those in group D; the X-ray films showed that the calcified area increased in groups A, B and C order and were higher than those in group D; the histological observation showed that the trabecular maturity increased in groups A, B and C order and were higher than those in group D. The osteoblast area, the gray degree value of the radiographs in callus tissue, the ALP contents of serum and callus tissue, calcium content of callus tissue and net weight of callus were higher in groups A, B and C than in group D. There were significant differences (P < 0.05) in osteoblast area and gray degree values of the radiographs at 14, 21 and 28 days; in ALP contents of serum at 14 days; in ALP contents of callus tissue at 14 days and 21 days; in calcium content of callus tissue at 21 days and 28 days among 4 groups. There were significant differences in net weight of callus between groups B, C and groups A, D at 14 days (P < 0.05). At 21 days and 28 days, the trabecular surface index of osteoblast, the average trabecular volume and the mean trabecular width decreased as time went on, having an increase order of groups A, B, C and was higher in groups A, B, C than in group D, showing significant differences among 4 groups (P < 0.05). CONCLUSION: NGF promotes the healing of fractures. NGF possesses synergistic effect on ectopic bone formation induced by BMP-2.