Search

Background: We aimed to determine the relative risk of pedal vessel calcification (PVC) on major adverse foot events (MAFEs) and chronic kidney disease (CKD) stage in patients with diabetes mellitus (DM) and peripheral neuropathy (PN)., Methods: We retrospectively reviewed electronic medical records of 152 patients with diagnoses of DM, PN, and CKD stages one to five who had at least one foot radiograph obtained. PVC was scored (from 0-4) based on foot anatomic location and radiology reported MAFEs, which includes foot fracture, Charcot neuroarthropathy, foot ulcer, osteomyelitis, or minor amputation. Risk ratios (RR) with 95% confidence intervals (95% CI) and Poisson regressions were performed assessing the risk of sustaining MAFEs with number of PVCs and stage of CKD., Results: The risk of any MAFE increased as PVC score increased (RR = 1.23); the risk of any MAFE increased as CKD stage increased (RR = 1.35); and risk of any PVC increased as CKD stage increased (RR = 1.71)., Conclusions: Pedal vessel calcification on a foot radiograph increases the risk of any MAFE and increases with progressive stage of CKD. Pedal vessel calcification may serve as a gateway to prompt investigation, treatment, or referral for at-risk diabetic neuropathic, nephropathic patients.

Background: Pedal arch interrogation by ultrasound through systolic acceleration time measurement (Pedal Acceleration Time [PAT]) is a recently described technique that offers valuable insights into foot hemodynamics. Previous studies have demonstrated a correlation between PAT and the ankle-brachial index and PAT has been proposed as a prognostic tool for wound healing in patients with peripheral artery disease. This study aims to assess the correlation between PAT and Transcutaneous Pressure of Oxygen (TcPO2) in the diabetic foot population., Methods: In this single-center cross-sectional study PAT and TcPO2 were measured in diabetic patients with ischemic foot ulcers. The assessment of wound status was performed between the 12th and 16th week after the first evaluation. The primary outcome was to assess the correlation between the values obtained for PAT and TcPO2. The secondary outcome was to establish a cut-off value for wound healing., Results: Sixty limbs with ischemic foot ulcers were evaluated. The results showed a correlation between PAT and TcPO2 [F (1.52) = 16.928; R 2  = 0.246; P < 0.001]. The receiver operating characteristics curve analysis showed an optimal cut-off value at PAT >186 ms for predicting a nonhealing ulcer with a 96% specificity (area under the curve = 0.774; confidence interval 0.648-0.872; P < 0.001)., Conclusions: PAT showed a significant correlation with TcPO2 with high specificity to identify nonhealing foot ulcers due to insufficient foot perfusion with a potential prognostic value in the diabetic foot population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Diabetes Mellitus (DM) is a common chronic disease, affecting 435 million people globally. Impaired vasculature in DM patients leads to complications like lower extremity arterial disease (LEAD) and foot ulcers, often resulting in amputations. DM causes additional peripheral neuropathy leading to multifactorial wound problems. Current diagnostics often deem unreliable, but Near-Infrared Fluorescence with Indocyanine Green (ICG NIR) can be used to assess the foot perfusion. Therefore, this study explores DM's impact on foot perfusion using ICG NIR., Methods: Baseline ICG NIR fluorescence imaging was performed in LEAD patients with and without DM. Ten perfusion parameters were extracted and analyzed to assess differences in perfusion patterns., Results: Among 109 patients (122 limbs) of the included patients, 32.8 % had DM. Six of ten perfusion parameters, mainly inflow-related, differed significantly between DM and non-DM patients (p-values 0.007-0.039). Fontaine stage 4 DM patients had the highest in- and outflow values, with seven parameters significantly higher (p-values 0.004-0.035)., Conclusion: DM is associated with increased in- and outflow parameters. Patients with- and without DM should not be compared directly due to different vascular pathophysiology and multifactorial wound problems in DM patients. Quantified ICG NIR fluorescence imaging offers additional insight into the effect of DM on foot perfusion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation., Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest., Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared., Results: Diabetic patients showed significantly reduced mean BF in the neurogenic ( p = 0.044 ) and heart ( p = 0.001 ) components at the M1 and M5 regions ( p = 0.025 ) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic ( p = 0.049 ) and myogenic ( p = 0.032 ) components at the M1 region, as well as in the endothelial ( p < 0.001 ) component at the M5 region and in the myogenic component at the dorsal foot ( p = 0.007 ), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region ( p = 0.050 ) and heel area ( p = 0.041 ). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region ( p = 0.017 ) and heel area ( p = 0.028 ) in diabetic patients., Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients., (© 2024 The Authors.)

Background: Arterial perfusion is a key factor in diabetic foot ulcer (DFU) healing. Although it is associated with pedal arch patency, not all patients are amenable to pedal artery angioplasty. This study aims to determine the impact of angiographic improvement of the pedal arch quality after proximal arterial inflow revascularization (PAIR) and its association with wound healing., Methods: One hundred and fifty diabetic patients with tissue loss in 163 limbs who had digital subtraction angiography were studied. Cox regression analysis was used to determine independent predictors of wound healing. Wound healing rates in association with pedal arch patency were calculated by Kaplan-Meier analysis., Results: End-stage renal disease, minor amputation, and complete pedal arch patency were significant independent predictors of wound healing following PAIR with hazard ratios for failure: 3.02 (P = 0.008), 0.54 (P = 0.023), and 0.40 (P = 0.039), respectively. The prevalence of complete pedal arches increased by 24.1% with successful intervention (P < 0.001). The overall rates of wound healing at 6, 12, and 24 months were 36%, 64%, and 72%, respectively. The wound healing rate at 1 year in patients with a complete pedal arch was 73% compared to 45% in those with an absent pedal arch (P = 0.017)., Conclusions: PAIR increases complete pedal arch patency, a significant predictor of wound healing in DFU., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

The arterial lesions in the lower limbs of diabetic foot patients are very complex, and restoring arterial blood flow in the lower limbs is the key to improving the quality of life and limb preservation rate of diabetic foot patients. The current endovascular treatment technique is the main choice in China because of its minimally invasive nature and rapid postoperative recovery. In order to provide better and more standardized treatment for diabetic foot and benefit patients, the Diabetic Foot Sub-Committee of the China Association for the Promotion of International Exchange of Healthcare and the Diabetic Foot Committee of the Chinese Chapter Congress of the International Union of Angiology have developed this consensus based on the literature and the clinical experience of various experts, including the objectives and principles of diabetic foot treatment and the selection of endovascular treatment methods for vascular lesions.

Objective: To compare the potential healing prognosis of the different routine noninvasive techniques implemented in the International Working Group Diabetic Foot Guidelines with the novel use of hyperspectral imaging (HSI) in patients with diabetic foot ulcers (DFUs)., Methods: Twenty-one patients with active DFUs participated in this 1-year prospective study in a specialized diabetic foot unit between December 2018 and January 2020. HSI was performed at baseline to quantify tissue oxygenation and should be presented on an anatomical map by analyzing the following parameters: (1) oxygen saturation of the hemoglobin, (2) tissue hemoglobin index, (3) the near-infrared perfusion index, and (4) tissue water index. In addition, transcutaneous oxygen pressure (TcpO 2 ), systolic toe and ankle pressures, ankle-brachial index, and toe-brachial index values were calculated for the ulcerated limb. The primary outcome measure was wound healing, defined as complete epithelization without any drainage confirmed for at least 10 days after closure was first documented at 24 weeks., Results: During the follow-up period 14 patients (66.66 %) healed and 7 patients did not heal (33.3%) by 24 weeks. The TcpO 2 optimal cut-off point as determined by a balance of sensitivity and specificity of 28.5 mm Hg that yielded a sensitivity of 91% and a specificity of 100%, and area under the curve of 0.989 (P = .005; 95% confidence interval [CI], 0.945-1.000). Followed by the oxygen saturation of the hemoglobin optimal cut-off point as determined by a balance of sensitivity and specificity of 48.5 mm Hg that yielded a sensitivity of 93% and a specificity of 0.71%, and area under the curve of 0.932 (P = .013; 95% CI, 0.787-1.000). The logistic regression analyses showed that TcpO 2 was the only variable associated with wound healing at 24 weeks (P < .001; 95% CI, 0.046-0.642)., Conclusions: The HSI was shown to be effective in the prognosis of DFU healing compared with other noninvasive test; only TcpO 2 values resulted in better diagnosis potential in wound healing., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Diabetic foot disease (DFD) is a common and serious complication for diabetes and is characterized with impaired angiogenesis. In addition to the well-defined role of vascular endothelial growth factor (VEGF) -A and its defect in the pathogenesis of DFD, another VEGF family member, placental growth factor (PlGF), was also recently found to alter expression pattern in the DFD patients with undetermined mechanisms. This question was thus addressed in the current study. We detected attenuated PlGF upregulation in a mouse DFD model. In addition, the major cell types at the wound to express the unique PlGF receptor, VEGF receptor 1 (VEGFR1), were macrophages and endothelial cells. To assess how PlGF regulates DFD-associated angiogenesis, we injected recombinant PlGF and depleted VEGF1R specifically in macrophages by local injection of an adeno-associated virus (AAV) carrying siRNA for VEGFR1 under a macrophage-specific CD68 promoter. We found that the angiogenesis and recovery of the DFD were both improved by PlGF injection. The PlGF-induced improvement in angiogenesis and the recovery of skin injury were largely attenuated by macrophage-specific depletion of VEGF1R, likely resulting from reduced macrophage number and reduced M2 polarization. Together, our data suggest that reduced PlGF compromises angiogenesis in DFD at least partially through macrophages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Qian, Jiang, Yang, Duan and Xiao.)

Background: For patients with diabetic foot ulcers, offloading is one crucial aspect of treatment and aims to redistribute pressure away from the ulcer site. In addition to offloading strategies, patients are often advised to reduce their activity levels. Consequently, patients may avoid exercise altogether. However, it has been suggested that exercise induces an increase in vasodilation and tissue blood flow, which may potentially facilitate ulcer healing. The aim of this systematic review was to determine whether exercise improves healing of diabetic foot ulcers., Review: We conducted a systematic search of MEDLINE, CINAHL and EMBASE between July 6, 2009 and July 6, 2019 using the key terms and subject headings diabetes, diabetic foot, physical activity, exercise, resistance training and wound healing. Randomised controlled trials were included in this review. Three randomised controlled trials (139 participants) were included in this systematic review. All studies incorporated a form of non-weight bearing exercise as the intervention over a 12-week period. One study conducted the intervention in a supervised setting, while two studies conducted the intervention in an unsupervised setting. Two studies found greater improvement in percentage wound size reduction in the intervention group compared with the control group, with one of these studies achieving statistically significant findings (p < 0.05). The results of the third study demonstrated statistically significant findings for total wound size reduction (p < 0.05), however results were analysed within each treatment group and not between groups., Conclusion: This systematic review found there is insufficient evidence to conclusively support non-weight bearing exercise as an intervention to improve healing of diabetic foot ulcers. Regardless, the results demonstrate some degree of wound size reduction and there were no negative consequences of the intervention for the participants. Given the potential benefits of exercise on patient health and wellbeing, non-weight bearing exercise should be encouraged as part of the management plan for treatment of diabetic foot ulcers. Further research is required to better understand the relationship between exercise and healing of diabetic foot ulcers.

Aim: To compare temperature changes following a challenge of limb elevation, in 3 forefoot angiosomes between type 2 diabetes mellitus patients with and without peripheral arterial disease (PAD)., Methods: Participans were categorized in a no PAD, mild PAD or severe PAD group. All underwent thermal imaging, then successive thermal images were taken at 1 min intervals after the lower limbs were elevated for 5 min. Thereafter, the lower limbs were lowered to the original position and imaged after 1 min. Mean temperatures of the hallux, medial and lateral forefoot were analysed by the angiosome concept., Results: Forty-two limbs were analysed. Mean resting temperatures of all angiosomes of participants with PAD were higher than those with no peripheral arterial disease. A significant difference in the mean initial temperature between the groups was found in the medial and lateral forefoot angiosomes (p=0.048, p=0.049 respectively), whilst at the hallux these temperatures were not significant (p=0.165). After limb elevation, the only significant difference was seen in the lateral foot area at 1 min (p=0.021)., Conclusions: These results confirm that patients with PAD exhibit significantly higher forefoot temperatures, according to the angiosome concept. The challenge by foot elevation did not affect the thermal pattern significantly., Competing Interests: No conflict of interest has been declared by the authors., (Thieme. All rights reserved.)

Summary: The authors present indocyanine green angiography to assess the effects of hyperbaric oxygen therapy and as a potential biomarker to predict healing of chronic wounds. They hypothesize that favorable initial response to hyperbaric oxygen therapy (improved perfusion) would be an early indicator of eventual response to the treatment (wound healing). Two groups were recruited: patients with chronic wounds and unwounded healthy controls. Inclusion criteria included adults with only one active wound of Wagner grade III diabetic foot ulcer or caused by soft-tissue radionecrosis. Patients with chronic wounds underwent 30 to 40 consecutive hyperbaric oxygen therapy sessions, once per day, 5 days per week; controls underwent two consecutive sessions. Indocyanine green angiography was performed before and after the sessions, and perfusion patterns were analyzed. Healing was determined clinically and defined as full skin epithelialization with no clinical evidence of wound drainage. Fourteen chronic-wound patients and 10 controls were enrolled. Unlike unwounded healthy volunteers, a significant increase in indocyanine green angiography perfusion was found in chronic-wound patients immediately after therapy (p < 0.03). Moreover, the authors found that 100 percent of the wounds that demonstrated improved perfusion from session 1 to session 2 went on to heal within 30 days of hyperbaric oxygen therapy completion, compared with none in the subgroup that did not demonstrate improved perfusion (p < 0.01). This study demonstrates a beneficial impact of hyperbaric oxygen therapy on perfusion in chronic wounds by ameliorating hypoxia and improving angiogenesis, and also proposes a potential role for indocyanine green angiography in early identification of those who would benefit the most from hyperbaric oxygen therapy., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2020 by the American Society of Plastic Surgeons.)

Objective: To explore the clinical efficacy and advantages of five-in-one comprehensive limb salvage technologies for the treatment of severe diabetic foot ulcer (DFU). Approach: Clinical data for 120 patients with severe DFU treated between January 2012 and December 2017 were analyzed retrospectively. The control group (48 cases) was treated with traditional therapies, including controlling blood sugar, improving microcirculation, preserving nerve function, and dressing changes, whereas the experimental group (72 cases) was treated with traditional therapy combined with additional techniques, such as early and thorough debridement, negative pressure wound therapy, revascularization, and skin graft or flap. Ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO 2 ), wound healing rate, healing time, ulcer recurrence rate, and amputation rate were recorded. Results: Compared with the control group, the experimental group significantly improved wound healing rate (93.1% vs. 72.9%; p  < 0.01), decreased wound healing time (16.2 ± 5.4 days vs. 32.2 ± 7.8 days; p  < 0.05), reduced major limb amputation rate (1.4% vs. 10.4%, p  < 0.05), and ulcer recurrence rate (5.6% vs. 14.6%; p  < 0.05). There were no significant differences in amputation rate between experimental and control group (29.2% vs. 33.3%, p  = 0.628). After revascularization, the revascularization group showed significantly improved ABI (0.75 ± 0.21 vs. 0.35 ± 0.16, p  < 0.05) and TcPO 2 (36 ± 6 mmHg vs. 15 ± 4 mmHg, p  < 0.05). Innovation: We propose a five-in-one comprehensive treatment method, which provides a multidisciplinary cooperative model for comprehensive medical and surgical treatments for DFU. Conclusion: The five-in-one comprehensive limb salvage treatment technologies played a vital role in enhancing the healing rate of severe DFU, shortening the healing time, and reducing the rate of recurrence and major amputation, thus improving the overall quality of life.

Background: Charcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy., Design: Retrieval of surgical pathology midfoot specimens from Charcot patients (2012-2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (

The most frequent clinical complication is diabetes. Diabetes is characterized by elevated blood glucose levels resulting in sensory nerve damage or lesions. Diabetic foot wounds are often slow to heal and require medical attention and monitoring. This study evaluates the effect of far-infrared radiation on the microcirculation and plantar pressure in the diabetic foot. Ten diabetics and 4 nondiabetics were recruited in this study. The diabetic group was examined before and after the intervention in each month for 3 consecutive months. Four nondiabetic groups were also measured before and after the intervention for 2 weeks in each month. The surface temperature and blood flow in the diabetic foot was significantly improved (temperature: 32.1 ± 2.3°C vs 33.5 ± 2.2°C, P < .05; blood flow image: 118.3 ± 58.1 PU [perfusion unit] vs 50.4 ± 4.3 PU, P < .05). The sympathetic nerve activity index LF also increased from 40.8 ± 18.6% to 61.8 ± 13.5% ( P = .07) in the second month. Plantar pressure tended to increase in the third month. This might indicate that far-infrared radiation could affect the mechanical properties of the plantar foot soft tissue. These results indicated that the effects of far-infrared radiation would improve blood circulation and change the soft tissue properties in the diabetic foot.

Diabetes is a worldwide public health concern as it is associated with various complications. One of the major complications of diabetes is diabetic foot syndrome that results in catastrophic events such as ulceration and amputation. Therefore, the main four strategies of diabetic foot care involve risk prediction, prevention, and early diagnosis and prompt intervention. The drivers of ulceration are multifactorial, and importantly, include microcirculatory changes in the diabetic skin. Cutaneous microcirculation on the foot is greatly influenced by the small fibers which mediate thermal sensation and pain perception in addition to sympathetic activities such as thermoregulation and vasodilation. The interdependence between the neurovascular elements means with the loss of small fiber functions, the corresponding microcirculatory responses may be compromised. Thus, it can be hypothesized that the impairment of the microcirculation may follow the order of the corresponding small fiber nerve dysfunction or vice versa. In this review, select neurovascular investigations that inform the cutaneous microcirculatory and small fiber nerve function in response to pain, cold, and heat and pressure stimuli are reviewed and discussed in this order of sensory loss: the loss of pain, cold, warmth, touch and deep pressure sensation. We also discuss the neurological and vascular characteristics of each of these neurovascular responses. This review highlights the influence of small fibers on cutaneous microcirculation and the need for prospective studies that can determine the course of microcirculatory impairment over time. This, in turn, may help clarify the exact role of microcirculatory changes in the pathway of ulceration. The insights from this review can be pertinent to understand key microcirculatory disturbances and given that the microcirculatory impairment develops at an early stage, relevant interventions can be implemented to possibly reverse or regress the course of the disease. Therefore, knowledge of the neurovascular interactions aids to map the disease progression for early diagnosis and prevention of adverse complications., (Copyright © 2020 Balasubramanian, Vas, Chockalingam and Naemi.)

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.

This article summarizes surgical procedures for preservation of the foot in diabetic patients with peripheral artery disease. Distal bypass surgery performed to perigeniculate arteries and to an isolated 'blind' popliteal segment with visible collaterals can be performed with limb salvage rates close to what can be achieved with standard bypass to crural arteries. This is also the case when performing bypass to the dorsalis pedis artery. Bypass to the medial or lateral plantar artery or to the lateral tarsal artery is associated with a relatively high rate of early occlusion, but in the patients who have persistently open grafts, limb salvage is common. The use of an arteriovenous fistula as an adjunct to distal bypass surgery does not improve prognosis. Venous arterialization, either creating retrograde perfusion of the superficial or of the deep veins of the foot has been successful in several cases although it is difficult to predict which patients will benefit. Reconstructive surgery is often performed in a multidisciplinary team including plastic surgeons. In patients with need of more extensive cover of defects, the transplant of muscular or fasciocutaneous free flaps has provided good results in the few centres that have applied this technique. This procedure can be combined with a revascularization in the same session or at a later stage. A majority of the described techniques can be implemented in most vascular centres and they should be considered in complicated cases when standard methods of revascularization and reconstruction do not suffice., (© 2019 John Wiley & Sons Ltd.)

In patients with diabetes, foot ulceration and peripheral artery disease (PAD), it is often difficult to determine whether, when and how to revascularise the affected lower extremity. The presence of PAD is a major risk factor for non-healing and yet clinical outcomes of revascularisation are not necessarily related to technical success. The International Working Group of the Diabetic Foot updated systematic review on the effectiveness of revascularisation of the ulcerated foot in patients with diabetes and PAD is comprised of 64 studies describing >13 000 patients. Amongst 60 case series and 4 non-randomised controlled studies, we summarised clinically relevant outcomes and found them to be broadly similar between patients treated with open vs endovascular therapy. Following endovascular revascularisation, the 1 year and 2 year limb salvage rates were 80% (IQR 78-82%) and 78% (IQR 75-83%), whereas open therapy was associated with rates of 85% (IQR 80-90%) at 1 year and 87% (IQR 85-88%) at 2 years, however these results were based on a varying combination of studies and cannot therefore be interpreted as cumulative. Overall, wound healing was achieved in a median of 60% of patients (IQR 50-69%) at 1 year in those treated by endovascular or surgical therapy, and the major amputation rate of endovascular vs open therapy was 2% vs 5% at 30 days, 10% vs 9% at 1 year and 13% vs 9% at 2 years. For both strategies, overall mortality was found to be high, with 2% (1-6%) perioperative (or 30 day) mortality, rising sharply to 13% (9-23%) at 1 year, 29% (19-48%) at 2 years and 47% (39-71%) at 5 years. Both the angiosome concept (revascularisation directly to the area of tissue loss via its main feeding artery) or indirect revascularisation through collaterals, appear to be equally effective strategies for restoring perfusion. Overall, the available data do not allow us to recommend one method of revascularisation over the other and more studies are required to determine the best revascularisation approach in diabetic foot ulceration., (© 2020 John Wiley & Sons Ltd.)

Purpose: To assess the clinical efficacy of endovascular angiosome-oriented wound-targeted revascularization (WTR) vs indirect (wound-indifferent) revascularization (IR) in diabetic patients with neuroischemic foot ulcers. Materials and Methods: Between April 2009 and July 2017, 167 diabetic patients (mean age 72.8 years; 137 men) with chronic limb-threatening ischemia (Rutherford category 5) and foot wounds (Wagner 2-4) in 194 limbs were prospectively registered and scheduled for primary infragenicular endovascular treatment. Specific angiosome source artery reperfusion sustained by patent foot arches or arterial-arterial connections was attempted initially. If this approach failed, topographic revascularization via available collaterals (WTRc) and IR were sequentially attempted. Results: Reperfusion was successful in 176 (91%) of 194 limbs (113 with WTR, 28 with WTRc, and 35 with IR); the global angiosome-oriented technical success (WTR and WTRc) was 73% (141/194). The mean follow-up was 10.9±0.7 months (range 3-12.5). Over 1 year, 102 (58%) of the 176 successfully treated limbs experienced wound healing [79/113 (70%) in the WTR group, 15/28 (54%) in the WTRc group, and 7/35 (20%) in the IR group; p=0.011]. The mean time to healing was 6.8±0.4 months in the WTR group, 7.9±0.6 months in the WTRc group, and 9.8±0.7 months in the IR group (p=0.001). Relapses were noted in 18 (16%) WTR limbs, 5 (18%) WTRc limbs, and 6 (17%) IR limbs. Comparison between WTR and IR and WTRc vs IR showed improved cicatrization in the angiosome-oriented groups (p<0.05). Major adverse limb events (MALE) and limb salvage were different between WTR and WTRc and between WTR and IR groups (p<0.05), while WTRc vs IR was not. Amputation-free survival was not influenced by the revascularization strategy (p=0.093). Conclusion: Wound healing in diabetic patients with chronic limb-threatening ischemia appeared to be improved by intentional wound-targeted revascularization, but no uniform benefit concerning MALE or limb preservation was observed. IR still represents an alternative for limb salvage in cases in which angiosome-guided revascularization fails.

Objective: The addition of skin perfusion pressure (SPP) might enhance the predictive value of the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system. The purpose of the present study was to evaluate the SPP for each WIfI classification stage among patients with foot wounds by cross-referencing the results of prospectively monitored limb outcomes and to derive the SPP criteria that could be combined with other measurements to grade ischemia for the WIfI classification., Methods: From July 2015 to June 2017, patients with foot wounds that met the WIfI classification criteria were prospectively enrolled. We assessed the limbs using the WIfI ischemia grade without measuring the transcutaneous oxygen pressure but measured the SPP. After monitoring for 1 year, the predictability of the WIfI stages was analyzed according to whether the limbs had not healed (unchanged or worsened wounds, minor or major amputation, all-cause death) or had healed (improved or healed wounds) by comparing stages 1 and 2 with stages 3 and 4. We also statistically analyzed the SPP values that could be the boundary values between each ischemia grade and reevaluated the predictability of the WIfI stages with the boundary SPP values., Results: We enrolled a total of 91 limbs for 76 patients (mean age, 70.5 ± 12.0 years). The mean SPP values stratified by ischemia grade 0 to 3 were 52.1, 41.1, 27.1, and 18.8 mm Hg, respectively (an SPP of <30 mm Hg indicates severe ischemia). After monitoring for 1 year, 19 of 48 limbs in stage 1 and 2 and 35 of 43 in stage 3 and 4 were in the nonhealed group and 29 limbs in stage 1 and 2 and 8 limbs in stage 3 and 4 were in the healed group. The SPP boundary values between each ischemia (I) grade were calculated as 45 mm Hg for I-0/I-1, 35 for I-1/I-2, and 25 for I-2/I-3. When jointly using the boundary SPP values, the ischemia grade changed for 23 limbs, altering the distribution of the WIfI stages and limb outcomes: 11 of 38 limbs in stage 1 and 2 and 43 of 53 in stage 3 and 4 were transferred to the nonhealed group. The sensitivity, efficiency, and negative predictive value of WIfI staging improved when staging with SPP: from 65% to 80%, 70% to 77%, and 60% to 71%, respectively., Conclusions: The SPP boundary values that could be used with ischemia grade in the WIfI classification were identified as 45, 35, and 25 mm Hg. The addition of SPP could improve the accuracy of the evaluation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To assess the impact of autologous cell therapy on critical limb ischaemia in people with diabetes and diabetic kidney disease., Methods: A total of 59 people with diabetes (type 1 or type 2) and critical limb ischaemia, persisting after standard revascularization, were treated with cell therapy in our foot clinic over 7 years; this group comprised 17 people with and 42 without severe diabetic kidney disease. The control group had the same inclusion criteria, but was treated conservatively and comprised 21 people with and 23 without severe diabetic kidney disease. Severe diabetic kidney disease was defined as chronic kidney disease stages 4-5 (GFR <30 ml/min/1.73 m²). Death and amputation-free survival were assessed during the 18-month follow-up; changes in transcutaneous oxygen pressure were evaluated at 6 and 12 months after cell therapy., Results: Transcutaneous oxygen pressure increased significantly in both groups receiving cell therapy compared to baseline (both P<0.01); no significant change in either of the control groups was observed. The cell therapy severe diabetic kidney disease group had a significantly longer amputation-free survival time compared to the severe diabetic kidney disease control group (hazard ratio 0.36, 95% CI 0.14-0.91; P=0.042); there was no difference in the non-severe diabetic kidney disease groups. The severe diabetic kidney disease control group had a tendency to have higher mortality (hazard ratio 2.82, 95% CI 0.81-9.80; P=0.062) than the non-severe diabetic kidney disease control group, but there was no difference between the severe diabetic kidney disease and non-severe diabetic kidney disease cell therapy groups., Conclusions: The present study shows that autologous cell therapy in people with severe diabetic kidney disease significantly improved critical limb ischaemia and lengthened amputation-free survival in comparison with conservative treatment; however, the treatment did not influence overall survival., (© 2019 Diabetes UK.)

The accurate assessment of peripheral perfusion is a critical step in caring for a diabetic patient with active ulceration. This article guides the provider through diagnostic and therapeutic options. The perfusion assessment begins with a physical examination and augmented using noninvasive tests. Although some of these tests can be performed at the bedside, often a dedicated vascular laboratory is required. Additional cross-sectional imaging studies or formal angiography should be performed as well. These tools aid in the creation of the best therapeutic plan, which aims to restore perfusion and allow for rapid wound healing via open or endovascular means., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Lower limb arteriopathy is a frequent and potentially serious complication of diabetes. In fact, it largely explains the high incidence of lower limb amputations in diabetic patients as well as a significant impairment of quality of life in the case of intermittent claudication or decubitus pain. The severity of the disease is also based on the associated cardiovascular morbidity and mortality. The diagnosis is primarily made by the clinical examination, completed by functional hemodynamic tests (ankle/brachial index, transcutaneous oxygen pressure and toe pressure) and possibly imaging tests (arterial Doppler and arteriography of the lower limbs). The treatment of lower limbs arterial disease will depend on the vascular symptomatology, the severity of the vascular lesions evaluated by the hemodynamic tests and by the anatomical characteristics of the vascular lesions., Competing Interests: O. Bourron déclare faire ou avoir fait des interventions ponctuelles et avoir été pris en charge, à l'occasion de déplacements pour congrès, par Novo Nordisk, Sanofi, et Lilly.

Background: The treatment of diabetic foot ulcers in this case is complex and multidisciplinary, and an interdisciplinary team is extremely beneficial., Case Presentation: We performed the intervention on an old type 2 diabetes patient with poor health, whose left toes were severely necrotic. Surgery, including debridement and patella truncation, had positive effects on lower extremity circulation, infection control, cavity treatment, bone destruction, surgical debridement, recovery of foot function, and nursing. After 5 months, the patient's foot ulcer had healed, and walking function was preserved., Conclusions: Scheduling interventional surgery and debridement are the key point in a complicated diabetic foot ulcers case, and multidisciplinary collaboration in treatment of diabetic foot is significantly important.

Diabetic foot infection (DFI) should be treated by a multidisciplinary team to prevent amputation and morbid status. As physicians encountering DFI in outpatient clinic, a proper selection of antibiotic treatment and diagnostic approach for a vascular status is essential. We retrospectively investigated the patients with DFI from 2016 to 2017. All patients were examined for vascular status, wound status, and pathologic culture preceding the treatment. No statistical significance was observed between PEDIS grade 1 and 2 and 3 and 4 in culture status and culture results. Association analysis between vascular status and other variables, such as wound score and culture results, has no significant difference. Through these results, the helpful epidemiologic result of microbiology and necessity of examination for peripheral arterial disease were verified.

Background: Over 30 million people in the United States (over 9%) have been diagnosed with diabetes. About 25% of people with diabetes will experience a diabetic foot ulcer (DFU) in their lifetime. Unresolved DFUs may lead to sepsis and are the leading cause of lower-limb amputations. DFU rates can be reduced by screening patients with diabetes to enable risk-based interventions. Skin temperature assessment has been shown to reduce the risk of foot ulceration. While several tools have been developed to measure plantar temperatures, they only measure temperature once a day or are designed for clinic use only. In this report, wireless sensor-embedded socks designed for daily wear are introduced, which perform continuous temperature monitoring of the feet of persons with diabetes in the home environment. Combined with a mobile app, this wearable device informs the wearer about temperature increases in one foot relative to the other, to facilitate early detection of ulcers and timely intervention., Objective: A pilot study was conducted to assess the accuracy of sensors used in daily wear socks, obtain user feedback on how comfortable sensor-embedded socks were for home use, and examine whether observed temperatures correlated with clinical observations., Methods: Temperature accuracy of sensors was assessed both prior to incorporation in the socks, as well as in the completed design. The measured temperatures were compared to the reference standard, a high-precision thermostatic water bath in the range 20°C-40°C. A total of 35 patients, 18 years of age and older, with diabetic peripheral neuropathy were enrolled in a single-site study conducted under an Institutional Review Board-approved protocol. This study evaluated the usability of the sensor-embedded socks and correlated the observed temperatures with clinical findings., Results: The temperatures measured by the stand-alone sensors were within 0.2°C of the reference standard. In the sensor-embedded socks, across multiple measurements for each of the six sensors, a high agreement (R 2 =1) between temperatures measured and the reference standard was observed. Patients reported that the socks were easy to use and comfortable, ranking them at a median score of 9 or 10 for comfort and ease of use on a 10-point scale. Case studies are presented showing that the temperature differences observed between the feet were consistent with clinical observations., Conclusions: We report the first use of wireless continuous temperature monitoring for daily wear and home use in patients with diabetes and neuropathy. The wearers found the socks to be no different from standard socks. The temperature studies conducted show that the sensors used in the socks are reliable and accurate at detecting temperature and the findings matched clinical observations. Continuous temperature monitoring is a promising approach as an early warning system for foot ulcers, Charcot foot, and reulceration., (©Alexander M Reyzelman, Kristopher Koelewyn, Maryam Murphy, Xuening Shen, E Yu, Raji Pillai, Jie Fu, Henk Jan Scholten, Ran Ma. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 17.12.2018.)

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease, which is common but rarely diagnosed. Noninvasive biomarkers are urgently required to assist in the diagnosis of CLI. Accumulating evidence indicates that miRNAs play an important role in the development of various diseases. In this study, microarray profiling revealed 11 miRNAs with significantly altered expression in four T2DM patients with CLI compared with that in four sex- and age-matched T2DM patients without CLI. In independent cohorts, qRT-PCR validation confirmed the increased miRNA-4739 level in patients with CLI versus patients without CLI. miRNA-4739 levels increased with FPG and HbA1c (all P < 0.05). After adjusting for the risk factors, miRNA-4739 levels were found to be associated with an increased odds ratio (OR) of T2DM with CLI (OR =12.818, 95% confidence intervals (CI) 1.148 to 143.143, P = 0.038). ROC curve analysis revealed that the area under the curve (AUC) of miR-4739+confounding risk factors was 0.94 (95% CI 0.891 to 0.998, P < 0.001), which was higher than that of confounding risk factors (AUC 0.94 vs . 0.91, 95% CI -0.122 to 0.060, P > 0.05) and of miR-4739 (AUC 0.94 vs . 0.69, 95% CI -0.399 to -0.101, P < 0.001), respectively. We conclude that elevated plasma miRNA-4739 levels are independently associated with CLI in T2DM patients. miRNA-4739 is implicated as a novel diagnostic marker and a potential therapeutic target for CLI in diabetes.

Timely diagnostics of microcirculatory system abnormalities, which are the most severe diabetic complications, is one of the major problems facing modern health care. Functional abnormalities manifest themselves earlier than the structural ones, and therefore their assessment is the issue of primary importance. In this study Laser Doppler flowmetry, a noninvasive technique for the cutaneous blood flow monitoring, was utilized together with local temperature tests and wavelet analysis. The study of the blood flow in the microvascular bed of toes was carried out in the control group of 40 healthy subjects and in two groups of 17 type 1 and 23 type 2 diabetic patients. The local temperature tests demonstrated that the diabetic patients have impaired vasodilation in response to local heating. The tendency for impaired low frequency pulsations of the blood flow associated with endothelial and neurogenic activities in both diabetes groups was observed. Local thermal tests induced variations in perfusion and its spectral characteristics, which were different in the groups under study. In our opinion, the obtained preliminary results can be a basis for further research and provide a deeper understanding of pathological processes that drive microvascular abnormalities caused by diabetes mellitus., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Previous studies show conflicting results in wound healing outcomes based on angiosome direct perfusion (DP), but few have adjusted for wound characteristics in their analyses. We have previously shown that the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification correlates with wound healing in diabetic foot ulcers (DFUs) treated by a multidisciplinary team. The aim of this study was to compare WIfI classification vs DP and pedal arch patency as predictors of wound healing in patients presenting with DFU and peripheral arterial disease., Methods: We performed a retrospective review of a prospectively maintained database of all patients with peripheral arterial disease presenting to our multidisciplinary DFU clinic who underwent angiography. An angiosome was considered directly perfused if the artery feeding the angiosome was revascularized or was completely patent. Wound healing time at 1 year was compared on the basis of DP vs indirect perfusion, Rutherford pedal arch grade, and WIfI classification using univariable statistics and Cox proportional hazards models., Results: Angiography was performed on 225 wounds in 99 patients (mean age, 63.3 ± 1.2 years; 62.6% male; 53.5% black) during the entire study period. There were 33 WIfI stage 1, 33 stage 2, 51 stage 3, and 108 stage 4 wounds. DP was achieved in 154 wounds (68.4%) and indirect perfusion in 71 wounds (31.6%). On univariable analysis, WIfI classification was significantly associated with improved wound healing (57.2% for WIfI 3/4 vs 77.3% for WIfI 1/2; P = .02), whereas DP and pedal arch patency were not (both, P ≥ .08). After adjusting for baseline patient and wound characteristics, WIfI stage remained independently predictive of wound healing (WIfI 3/4: hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.67-0.88), whereas DP (HR, 0.82; 95% CI, 0.55-1.21) and pedal arch grade (HR, 0.85; 95% CI, 0.70-1.03) were not., Conclusions: In our population of patients treated by a multidisciplinary diabetic foot service, the Society for Vascular Surgery WIfI classification system was a stronger predictor of diabetic foot wound healing than DP or pedal arch patency. Our results suggest that a measure of wound severity should be included in all future studies assessing wound healing as an outcome, as differences in patients' wound characteristics may be a strong contributor to the variation of angiosome-directed perfusion results previously observed., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Foot offloading is the mainstay treatment for plantar diabetic foot ulcers (DFUs)., Objective: This multicenter, single-blinded, randomized controlled trial evaluates the efficacy of a total offloading foot brace for healing plantar DFUs., Materials and Methods: Seventeen patients were randomized to standard therapy (ie, reducing stress and pressure via mechanical offloading) or offloading foot brace. Comparison of plantar pressures was performed using digital pressure sensing films. The ulcers were assessed by physical inspection and digital planimetry of photographs., Results: Reductions in peak plantar pressures ranged from 67.3% to 89.4% (P = .09). Healing at weeks 12 to 15 had minimal differences (brace vs. control: 71.7% vs. 80.3%, respectively). Although not significant, earlier periods of the brace versus the control demonstrated faster wound healing in weeks 2 to 5 (36.0% vs. 6.8%, respectively) and weeks 6 to 9 (50.7% vs. 17.0%, respectively)., Conclusions: The total offloading foot brace minimizes plantar pressure, allowing for early healing of DFUs, and optimizations in brace design may enhance healing of plantar DFUs.

The improvement of peripheral circulation is crucial for the care of vasculopathic diabetic foot ulcer (DFU). Near-infrared spectroscopy (NIRS) was used to investigate the effects of Buerger's exercise on dorsal foot skin circulation with novel technique of measuring the absorption difference in wavelength of light between oxy-hemoglobin (HbO 2 ) and deoxy-hemoglobin (HbR). Patients with vasculopathic DFU who could tolerate Buerger's exercise three times a day at home for at least 8 weeks were enrolled (group A). They were divided into two subgroups: without previous percutaneous transluminal angioplasty (PTA) (group A1) vs. with previous PTA (group A2). Wireless NIRS were applied on patients' dorsal foot to assess the peripheral circulation in follow-up clinics. The patients' wound condition, follow-up time, and concentration of HbO 2 and total hemoglobin (HbT) before and after exercise rehabilitation program were documented. From May 2015 to February 2016, 14 patients with average age of 70.2 ± 11.2 were enrolled in this study (group A), including eight without previous PTA (group A1), and six with previous PTA (group A2). The concentration of HbO2 and HbT were significantly increased after exercise rehabilitation program training in group A (p = 0.024 in HbO 2 , p = 0.02 in HbT, n = 14) and group A2 (p = 0.021 in HbO 2 , p = 0.028 in HbT, n = 6), while the concentration in group A1 were improved with borderline significance after exercise (p = 0.055 in HbO 2 , p = 0.058 in HbT, n = 8). The majority of the ulcers were either completely healed (11/14 = 78.57%) or improving (3/14 = 21.43%). Buerger's exercise improved the peripheral circulation and wound condition in patients with vasculopathic DFU. The wireless apparatus is a novel and efficient tool to monitor rehabilitation program.

The aim of this study was to investigate the plantar blood flow response to the same accumulated pressure stimulus in diabetic patients with different peak plantar pressure (PPP), which is important for assessing the risk of diabetic foot ulcer. Eleven diabetic subjects with high PPP (PPP ≥ 207 kPa) and 8 diabetic subjects with low PPP (PPP < 207 kPa) were asked to walk naturally on a treadmill so as to induce an accumulated stimulus of 73,000 kPa·s on their first metatarsal head, which was monitored with a sensorized insole. Blood perfusion (BP) in the first metatarsal head was measured before and after walking. Results showed that blood flow after applying the same walking stimulus was significantly decreased in comparison to the basal BP before walking in both high PPP and low PPP groups (p < 0.05), but no significant differences were found between the two groups in terms of BP parameters and its percentage change (p > 0.05). Moreover, BP parameters were not significantly correlated to PPP and the pressure-time integral (PTI) of the subjects' gait (p > 0.05). This indicated that, besides PPP and PTI, the accumulated mechanical stimulus should be taken into consideration when assessing the risk of diabetic patients developing foot ulcers. Graphical abstract Plantar blood flow response to a walking stimulus.

Diabetes may cause different foot problems, which could easily lead to infection, ulcers, and increasing risk of amputation due to nerve or vascular injury. In order to reduce the risk of amputation, Buerger's exercise is frequently used for rehabilitation to improve the blood circulation in lower limbs. However, it is difficult to evaluate the rehabilitation efficiency with Buerger's exercise objectively. In this study, a novel non-invasively optical system is developed to non-invasively monitor the change of the foot blood circulation before and after long-term Buerger's exercise. Radial basis function neural network is also used for classifying the healthy and diabetic groups from the change of relative total hemoglobin (HbT) concentration and tissue oxygen saturation (StO2) and providing an index to evaluate the rehabilitation efficiency with Buerger's exercise. Finally, the experimental results show that the relative HbT concentration and StO2 in lower limbs corresponding to different groups are significantly different and could be used as the factors for the classification of healthy subjects and diabetic foot patients. Moreover, the tendency of the relative HbT concentration and StO2 rise after the long-term rehabilitation with Buerger's exercise.

The angiosome concept of foot perfusion was conceived based on anatomical studies of arterial circulation and used for planning surgical procedures, tissue reconstruction, and amputation. Its application is relevant in diabetic patients with critical limb ischemia and nonhealing foot ulcer or amputation. An understanding of foot angiosome anatomy is useful for predicting healing and planning arterial revascularization. A review of the literature, including the most recent systematic reviews and meta-analyses, indicates improved wound healing is achieved when the angiosome concept is followed. The greatest value of angiosome-based revascularization is in patients with lesion(s) limited to a single angiosome, or to achieve optimal healing of amputation sites. Future research should focus on proper identification of (imaging) modalities to determine the hemodynamic and functional changes before and after revascularization, thus identifying the "real" angiosome and directing optimal therapy., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The history of the recognition and surgical treatment of lower limb ischemia dates back to the Middle Ages. The twin Saints Comas and Damian were ascribed to have saved a gangrenous limb in the 13 th century and became patrons of future surgeons. The physicians that followed developed the theories of blood flow, anatomy of the arterial circulation, and recognition that occlusive disease was the cause of limb ischemia and gangrene. Innovative physicians developed the techniques of arterial surgery and bypass grafting to restore limb blood flow and allow healing of lesions. In the 1960s, the era of endovascular intervention by the pioneering work of Charles Dotter, who developed techniques to image diseased arteries during a recanalization procedure. The development of guide wires, angioplasty balloons, and stents quickly followed. Management of lower limb ischemia and the diabetic foot will continue to evolve, building on the history and passion of preceding physicians and surgeons., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The pathophysiology of the diabetic foot ulcer and soft-tissue infection is due to neuropathy, trauma, and, in many patients, concomitant peripheral artery occlusive disease. Diabetic neuropathy results in foot deformity, leading to increased skin pressure with walking. Once a foot ulcer develops, the limb is at high risk for invasive infection and, when combined with peripheral artery occlusive disease, the patient should be considered to have critical limb ischemia. A multidisciplinary approach to care for the diabetic foot is recommended, which includes annual (3-month intervals in high-risk patients) assessments by a primary care physician and referral to a podiatrist and vascular surgeon for diabetics with a foot ulcer for evaluation of foot arterial perfusion and off-loading therapy to reduce plantar skin pressure with walking. When invasive foot infection develops and tissue beneath the fascia is involved, inpatient care is recommended for systemic antibiotic therapy, vascular laboratory testing of artery limb perfusion, and surgical debridement of infected tissue. The goals of treatment are to achieve a healed foot and keep the patient ambulatory., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this multicenter, prospective, observer-blinded, parallel group, randomized controlled trial was to assess the safety and efficacy of EDX110, a nitric oxide generating medical device, in the treatment of diabetic foot ulcers in a patient group reflecting "real world" clinical practice compared against optimal standard care. Participants were recruited from ten hospital sites in multidisciplinary foot ulcer clinics. The ulcers were full thickness, with an area of 25-2,500 mm 2 and either a palpable pedal pulse or ankle brachial pressure index > 0.5. Infected ulcers were included. Treatment lasted 12 weeks, or until healed, with a 12-week follow-up period. Both arms were given optimal debridement, offloading and antimicrobial treatment, the only difference being the fixed used of EDX110 as the wound dressing in the EDX110 group. 135 participants were recruited with 148 ulcers (EDX110-75; Control-73), 30% of which were clinically infected at baseline. EDX110 achieved its primary endpoint by attaining a median Percentage Area Reduction of 88.6% compared to 46.9% for the control group (p = 0.016) at 12 weeks in the intention-to-treat population. There was no significant difference between wound size reduction achieved by EDX110 after 4 weeks and the wound size reduction achieved in the control group after 12 weeks. EDX110 was well tolerated. Thirty serious adverse events were reported (12 in the EDX110 group, of which 4 were related to the ulcer; 18 in the control group, of which 10 were related and 1 possibly related to the ulcer), with significant reduction in serious adverse events related to the ulcer in EDX group. There was no significant difference in adverse events. This study, in a real world clinical foot ulcer population, demonstrates the ability of EDX110 to improve healing, as measured by significantly reducing the ulcer area, compared to current best clinical practice., (© 2018 by the Wound Healing Society.)

Background: Peripheral arterial disease (PAD) is frequent among older diabetic patients, but the evidence about endovascular revascularization is very limited., Method: We retrospectively analyzed data collected from 120 diabetic patients consecutively admitted to a Diabetic Foot Clinic, including 64 patients aged 65-79 years and 56 patients aged 80 or more., Results: Percutaneous transluminal angioplasty (PTA) was followed by technical success in 82.5% of older patients and 62.5% of oldest old ones (p = 0.05). No significant difference was observed in regards to complete re-epithelization (76.6 vs 76.8%, p = 0.820), recurrent stenosis (26.6 vs 19.6%, p = 0.371), intra- or post-procedure complications (21.9 vs 10.7%, p = 0.102), and amputations (12.5 vs 5.4%, p = 0.176)., Discussion: Our findings suggest that older and oldest old patients with diabetic foot and critical ischemia could be effectively and safely treated with PTA.

Objective: To retrospectively evaluate the impact of pedal arch quality on tissue loss and time to healing in diabetic patients with foot wounds undergoing infrainguinal endovascular revascularization., Materials and Methods: Between January 2014 and June 2015, 137 consecutive diabetic patients with foot wounds underwent infrainguinal endovascular revascularization (femoro-popliteal or below-the-knee, arteries). Postprocedural angiography of the foot was used to divide the patients into the following three groups according to the pedal arch status: complete pedal arch (CPA), incomplete pedal arch (IPA), and absent pedal arch (APA). Time to healing and estimated 1-year outcomes in terms of freedom from minor amputation, limb salvage, and survival were evaluated and compared among the three groups., Results: Postprocedural angiography showed the presence of a CPA in 42 patients (30.7%), IPA in 60 patients (43.8%), and APA in 35 patients (25.5%). Healing within 3 months from the procedure was achieved in 21 patients with CPA (50%), 17 patients with IPA (28.3%), and in 7 patients with APA (20%) ( p = 0.01). There was a significant difference in terms of 1-year freedom from minor amputation among the three groups (CPA 84.1% vs. IPA 82.4% vs. APA 48.9%, p = 0.001). Estimated 1-year limb salvage was significantly better in patients with CPA (CPA 100% vs. IPA 93.8% vs. APA 70.1%, p < 0.001). Estimated 1-year survival was significantly better in patients with CPA (CPA 90% vs. IPA 80.8% vs. APA 62.7%, p = 0.004)., Conclusion: Pedal arch status has a positive impact on time to healing, limb salvage, and survival in diabetic patients with foot wounds undergoing infrainguinal endovascular revascularization.

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC., (© 2017 by the American Diabetes Association.)

The outcome of peripheral bypass surgery in patients at risk of limb loss is largely influenced by the anatomical integrity of the plantar arch. For this reason, in the last few decades, this area has been considered to be a sensitive territory, rarely approached surgically, and virtually untouchable by any endovascular activities. This hesitance was related to the possible damage to the thin dorsalis pedis, deep plantar, and lateral plantar arteries, together with the crucial metatarsal and digital branches arising from the arch. Twelve years ago, I argued that this area was anatomically very similar to the left anterior descending coronary artery and, thus, suitable for recanalization using standard endovascular coronary technique. Since its initial case, the pedal loop (PL) technique has become a very popular and glamorous procedure, likely performed in thousands of cases worldwide, additionally proving its efficacy in 2 large patient-registry retrospective analyses. Although the procedure is considered quite complex, from a technical point of view, it has almost no reliable alternatives in vascular and endovascular daily practice. However, by focusing attention on 12 well-established key points of the PL technique, it is likely that such may favor its diffusion among vascular surgeons and endovascular specialists., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Vascular assessment of the lower extremity is a critical step in any patient presenting with lower extremity chronic wounds to predict the likelihood of healing and risk of amputation. This concept is vital in patients with diabetes due to their complex vascular anatomy and disease distribution. Three arteries supply the six angiosomes of the lower extremity (i.e., three-dimensional blocks of tissue fed by a "source" artery in the foot and ankle). In diabetic patients, assessment of adequate blood flow to the lower extremities is complicated by the presence of arterial calcification, associated neuropathy, and inflammation. This review focuses on noninvasive vascular assessment methods to better understand perfusion and direct therapy to improve diabetic wound healing. Clinical examination of pulses and Ankle Brachial Index (ABI) can be supplemented by handheld Doppler assessment of direction of blood flow and pulse volume recordings to understand the site and extent of peripheral arterial disease. Duplex ultrasound has been used, but is operator dependent. CT angiogram has limitations in the presence of calcifications and renal insufficiency, prevalent in the diabetic population. Novel modalities, like hyperspectral imaging, ICG fluorescence angiography, and nuclear imaging are being studied for their potential to overcome some of these challenges, but the data is limited. At present, these newer modalities are not widely available, but once validated by robust data, they may supplant older, less reliable techniques and improve our ability to predict wound healing. This will help reduce healthcare costs and improve outcomes as wound care specialists will be able to more accurately direct patients to the best treatment plan to preserve mobility and reduce mortality.

Background: The aim of this study was to evaluate the impact of pedal arch status and direct-angiosome revascularization (DAR) on clinical outcomes in diabetic patients with foot wounds undergoing endovascular revascularization., Methods: Between January 2014 and June 2015, 93 diabetic patients with foot wounds underwent endovascular revascularization of at least one below-the-knee vessel. Patients were divided into three groups according to the pedal arch status: complete pedal arch (CPA), incomplete pedal arch (IPA) and absent pedal arch (APA). Healing within 3 months and 1-year outcomes in terms of freedom from minor amputation, limb salvage, and survival were evaluated on the basis of DAR and pedal arch status., Results: DAR did not affect healing within 3 months from the procedure (DAR, 13/55 cases, 23.6% vs. n-DAR, 9/38 cases, 23.7%; P=1), estimated 1-year freedom from minor amputation (DAR 74.4% vs. n-DAR 76.8%, P=0.80), limb salvage (DAR 88.2% vs. n-DAR 89.5%, P=0.44), and survival (DAR 83.3% vs. n-DAR 66.6%, P=0.15). Pedal arch had positive impact on wound healing within 3 months from the procedure (CPA 45.8% vs. IPA 12.5% vs. APA 20.7%, P=0.009), estimated 1-year limb salvage (CPA 100% vs. IPA 90.9% vs. APA 76.1%, P=0.02), and 1-year survival (CPA 100% vs. IPA 87.2% vs. APA 60.3%, P=0.02)., Conclusions: DAR is not a predictor of good outcomes in diabetic patients undergoing endovascular procedure. Pedal arch patency seems to be a key factor to obtain good outcomes in terms of wound healing, and limb salvage.

Background: Diabetic foot disease carries a high morbidity and is a leading cause of lower limb amputation. This may in part be due to the effect diabetes mellitus (DM) has on the microcirculation including in the skin., Method: We conducted a review of studies that have examined the relationship between microcirculatory function and wound healing in patients with DM. A search of the Medline, Embase, and Web of Science databases was performed coupled with a review of references for the period 1946 to March 2015., Results: Nineteen studies of diverse methodology and cohort selection were identified. Poor function of the microcirculation was related to poor outcome. Transcutaneous oxygen pressure (TcPO 2 ) was the most commonly used method to measure the microcirculation and thresholds for poor outcome proposed ranged from 10 mmHg to <34 mmHg. Two studies reexamined microcirculatory function following revascularization. Both found an increase in TcPO 2 , however only 1 reached statistical significance. No significant difference in the results of microcirculation tests was found between diabetic and nondiabetic patients., Conclusions: While it is not possible to draw firm conclusions from the evidence currently available there are clear areas that warrant research. Good microcirculation unsurprisingly appears to associate with better wound healing. The influence of DM is not clear, and neither is the degree of improvement required to achieve healing. Studies that examine a clearly defined cohort both with and without DM are urgently required. Accurate quantitative assessment of microcirculation will aid prediction of wound healing identifying those at greatest risk of amputation.

Background and Objectives: The majority of patients with diabetes foot ulcer have peripheral arterial disease. The technique of near infrared spectroscopy (NIRS) used to monitor the dorsal foot blood circulation condition is by measuring the absorption differences between oxy-hemoglobin and deoxy-hemoglobin., Study Designs/materials and Methods: Patients with diabetic foot ulcer (DFU) treated in our wound care center were divided into two sub-groups based on the Duplex ultrasound or angiography. Patients with peripheral arterial disease (PAD) and non-peripheral arterial disease were divided into group A1 and A2, respectively. We applied wireless NIRS on patients' dorsal foot to assess the peripheral circulation by continuously detect the signal penetrating the tissue while patients were asked to do Buerger's exercise. The same procedure was also repeated on 15 healthy participants as control group B., Results: From January to August 2015, 30 patients with DFU (Group A) were enrolled in the study, 9 patients in Group A1 and 21 patients in Group A2. Tissue concentration of oxygenated hemoglobin (HbO2) in each group varied in a similar trend among five stages of Buerger's exercise. HbO2 concentration increases at post-exercise stages in all groups (P = 0.006 in Group A1, P = 0.223 in Group A2, P = 0.03 in Group B), however, there were significant difference in both pre- and post-exercise stages (P = 0.001 and P = 0.01, respectively) between Group A and B. Moreover, significant differences (P = 0.0009) of HbO2 were also found between Group A1 and A2 in pre-exercise status, but no significant difference (P = 0.294) was found in post-exercise status. Similar results were also found in total hemoglobin (Hb) concentration analyses., Conclusions: Buerger's exercise could increase peripheral HbO2 and total Hb circulation in patients with diabetes foot ulcer. The NIRS could continuously and quantitatively monitor real-time peripheral circulation in postural changes and is novel to rehabilitation program. A larger scale study to prove the accuracy of NIRS system in detecting peripheral circulation could be worthwhile. Lasers Surg. Med. 49:652-657, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objective: Topical negative pressure (TNP) therapy is widely used in the treatment of acute wounds in vascular patients on the basis of proposed multifactorial benefits. However, numerous recent systematic reviews have concluded that there is inadequate evidence to support its benefits at a scientific level. This study evaluated the changes in wound volume, surface area, depth, collagen deposition, and tissue oxygenation when using TNP therapy compared with traditional dressings in patients with acute high-risk foot wounds., Methods: This study was performed with hospitalized vascular patients. Forty-eight patients were selected with an acute lower extremity wound after surgical débridement or minor amputation that had an adequate blood supply without requiring further surgical revascularization and were deemed suitable for TNP therapy. The 22 patients who completed the study were randomly allocated to a treatment group receiving TNP or to a control group receiving regular topical dressings. Wound volume and wound oxygenation were analyzed using a modern stereophotographic wound measurement system and a hyperspectral transcutaneous oxygenation measurement system, respectively. Laboratory analysis was conducted on wound biopsy samples to determine hydroxyproline levels, a surrogate marker to collagen., Results: Differences in clinical or demographic characteristics or in the location of the foot wounds were not significant between the two groups. All patients, with the exception of two, had diabetes. The two patients who did not have diabetes had end-stage renal failure. There was no significance in the primary outcome of wound volume reduction between TNP and control patients on day 14 (44.2% and 20.9%, respectively; P = .15). Analyses of secondary outcomes showed a significant result of better healing rates in the TNP group by demonstrating a reduction in maximum wound depth at day 14 (36.0% TNP vs 17.6% control; P = .03). No significant findings were found for the other outcomes of changes in hydroxyproline levels (58.0% TNP vs 94.5% control; P = .32) or tissue perfusion by tissue oxyhemoglobin saturation (19.4% TNP vs 12.0% control; P = .07) at day 14. At 1 year of follow-up, there were no significant outcomes in the analysis of wound failure, major amputation, and overall survival rates between the two groups., Conclusions: In this pilot study, applying TNP to acute high-risk foot wounds in patients with diabetes or end-stage renal failure improved the wound healing rate in reference to wound depth. This suggests that TNP may play a role in enhancing wound healing. This study sets the foundation for larger studies to evaluate the superiority of TNP over traditional dressings in high-risk foot wounds., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)