Feasibility and Accuracy of Measuring Carotid Plaque Volume (Burden) With Contrast-Enhanced Tomographic 3D Ultrasound and Ultrasound Image Fusion.

BACKGROUND: Stenosis severity has been the indication for carotid endarterectomy (CEA) for 4 decades, but the annual stroke risk in asymptomatic carotid stenosis >70% is under 2%. Atherosclerotic volume has emerged as a risk factor for future stroke, but needs to be measured noninvasively. Tomographic ultrasound (tUS) is a novel technology that assembles 3D images in seconds. We evaluated accuracy of measuring Carotid Plaque Volume (CPV) with tUS in patients undergoing CEA. METHOD: Consecutive patients were imaged immediately before CEA by tUS and contrast-enhanced tUS (CEtUS). CPV was measured using tUS, CEtUS, and a fused images incorporating both tUS and CEtUS by trained vascular scientists. Precise volume of the endarterectomy specimen was measured using Archimedes technique. RESULTS: Mean ± sd (range) CPV in 129 endarterectomy specimens was 0.75 ± 0.43 cm3 (0.10-2.47 cm3). Mean ± sd CPV measured by tUS (n = 114) was 0.87 ± 0.51 cm3, CEtUS (n = 104) was 0.75 ± 0.45 cm3 and with fusion (n = 95) was 0.83 ± 0.49 cm3. Differences between specimen volume and CPV measured by tUS (0.13 ± 0.24 cm3), CEtUS (-0.01 ± 0.21 cm3) or fusion (-0.08 ± 0.20) were clinically insignificant. Intra-/interobserver differences were minimal. CONCLUSIONS: tUS accurately measures CPV with excellent intra-/interobserver agreement. CEtUS improves accuracy if precise CPV measurement is needed for research but tUS alone would be sufficient for population screening.

Altered accelerator pedal control in a driving simulator in people with diabetic peripheral neuropathy.

AIM: To investigate whether the sensory-motor impairment attributable to diabetic peripheral neuropathy would affect control of the accelerator pedal during a driving simulator task. METHODS: A total of 32 active drivers, 11 with diabetic peripheral neuropathy (mean ± sd age 67±5.0 years), 10 with diabetes but no neuropathy (diabetes group; mean ± sd age 62±10 years), and 11 healthy individuals without diabetes (healthy group; mean ± sd age 60±11 years), undertook a test on a dynamometer to assess ankle plantar flexor muscle strength and ankle joint proprioception function of the right leg, in addition to a driving simulator task. The following variables were measured: maximal ankle plantar flexor muscle strength; speed of strength generation (Nm/s); and ankle joint proprioception (ankle repositioning error, degrees). In the driving simulator task, driving speed (mph), accelerator pedal signal (degrees) and the duration of specific 'loss-of-control events' (s) were measured during two drives (Drive 1, Drive 2). RESULTS: Participants with diabetic peripheral neuropathy had a lower speed of strength generation (P<0.001), lower maximal ankle plantar flexor muscle strength (P<0.001) and impaired ankle proprioception (P=0.034) compared to healthy participants. The diabetic peripheral neuropathy group drove more slowly compared with the healthy group (Drive 1 P=0.048; Drive 2 P=0.042) and showed marked differences in the use of the accelerator pedal compared to both the diabetes group (P=0.010) and the healthy group (P=0.002). Participants with diabetic peripheral neuropathy had the longest duration of loss-of-control events, but after one drive, this was greatly reduced (P=0.023). CONCLUSIONS: Muscle function, ankle proprioception and accelerator pedal control are all affected in people with diabetic peripheral neuropathy, adversely influencing driving performance, but potential for improvement with targeted practice remains possible.

Vertical displacement of the centre of mass during walking in people with diabetes and diabetic neuropathy does not explain their higher metabolic cost of walking.

People with diabetes display biomechanical gait alterations compared to controls and have a higher metabolic cost of walking (CoW), but it remains unknown whether differences in the vertical displacement of the body centre of mass (CoM) may play a role in this higher CoW. The aim of this study was to investigate vertical CoM displacement (and step length as a potential underpinning factor) as an explanatory factor in the previously observed increased CoW with diabetes. Thirty-one non-diabetic controls (Ctrl); 22 diabetic patients without peripheral neuropathy (DM) and 14 patients with moderate/severe Diabetic Peripheral Neuropathy (DPN), underwent gait analysis using a motion analysis system and force plates while walking at a range of matched speeds between 0.6 and 1.6 m/s. Vertical displacement of the CoM was measured over the gait cycle, and was not different in either diabetes patients with or without diabetic peripheral neuropathy compared to controls across the range of matched walking speeds examined (at 1 m/s: Ctrl: 5.59 (SD: 1.6), DM: 5.41 (1.63), DPN: 4.91 (1.66) cm; p > 0.05). The DPN group displayed significantly shorter steps (at 1 m/s: Ctrl: 69, DM: 67, DPN: 64 cm; p > 0.05) and higher cadence (at 1 m/s: Ctrl: 117 (SD1.12), DM: 119 (1.08), DPN: 122 (1.25) steps per minute; p > 0.05) across all walking speeds compared to controls. The vertical CoM displacement is therefore unlikely to be a factor in itself that contributes towards the higher CoW observed recently in people with diabetic neuropathy. The higher CoW in patients with diabetes may not be explained by the CoM displacement, but rather may be more related to shorter step lengths, increased cadence and the associated increased internal work and higher muscle forces developed by walking with more flexed joints.

Altered Achilles tendon function during walking in people with diabetic neuropathy: implications for metabolic energy saving.

The Achilles tendon (AT) has the capacity to store and release elastic energy during walking, contributing to metabolic energy savings. In diabetes patients, it is hypothesized that a stiffer Achilles tendon may reduce the capacity for energy saving through this mechanism, thereby contributing to an increased metabolic cost of walking (CoW). The aim of this study was to investigate the effects of diabetes and diabetic peripheral neuropathy (DPN) on the Achilles tendon and plantarflexor muscle-tendon unit behavior during walking. Twenty-three nondiabetic controls (Ctrl); 20 diabetic patients without peripheral neuropathy (DM), and 13 patients with moderate/severe DPN underwent gait analysis using a motion analysis system, force plates, and ultrasound measurements of the gastrocnemius muscle, using a muscle model to determine Achilles tendon and muscle-tendon length changes. During walking, the DM and particularly the DPN group displayed significantly less Achilles tendon elongation (Ctrl: 1.81; DM: 1.66; and DPN: 1.54 cm), higher tendon stiffness (Ctrl: 210; DM: 231; and DPN: 240 N/mm), and higher tendon hysteresis (Ctrl: 18; DM: 21; and DPN: 24%) compared with controls. The muscle fascicles of the gastrocnemius underwent very small length changes in all groups during walking (~0.43 cm), with the smallest length changes in the DPN group. Achilles tendon forces were significantly lower in the diabetes groups compared with controls (Ctrl: 2666; DM: 2609; and DPN: 2150 N). The results strongly point toward the reduced energy saving capacity of the Achilles tendon during walking in diabetes patients as an important factor contributing to the increased metabolic CoW in these patients. NEW & NOTEWORTHY From measurements taken during walking we observed that the Achilles tendon in people with diabetes and particularly people with diabetic peripheral neuropathy was stiffer, was less elongated, and was subject to lower forces compared with controls without diabetes. These altered properties of the Achilles tendon in people with diabetes reduce the tendon's energy saving capacity and contribute toward the higher metabolic energy cost of walking in these patients.

Altered walking strategy and increased unsteadiness in participants with impaired glucose tolerance and Type 2 diabetes relates to small-fibre neuropathy but not vitamin D deficiency.

AIMS: To investigate alterations in walking strategy and dynamic sway (unsteadiness) in people with impaired glucose tolerance and people with Type 2 diabetes in relation to severity of neuropathy and vitamin D levels. METHODS: A total of 20 people with Type 2 diabetes, 20 people with impaired glucose tolerance and 20 people without either Type 2 diabetes or impaired glucose tolerance (control group) underwent gait analysis using a motion analysis system and force platforms, and detailed assessment of neuropathy and serum 25 hydroxy-vitamin D levels. RESULTS: Ankle strength (P = 0.01) and power (P = 0.003) during walking and walking speed (P = 0.008) were preserved in participants with impaired glucose tolerance but significantly lower in participants with Type 2 diabetes compared with control participants; however, step width (P = 0.005) and dynamic medio-lateral sway (P = 0.007) were significantly higher and posterior maximal movement (P = 0.000) was lower in participants with impaired glucose tolerance, but preserved in those with Type 2 diabetes compared with the control group. Dynamic medio-lateral sway correlated with corneal nerve fibre length (P = 0.001) and corneal nerve branch density (P = 0.001), but not with vibration perception threshold (P = 0.19). Serum 25 hydroxy-vitamin D levels did not differ significantly among the groups (P = 0.10) and did not correlate with any walking variables or measures of dynamic sway. CONCLUSIONS: Early abnormalities in walking strategy and dynamic sway were evident in participants with impaired glucose tolerance, whilst there was a reduction in ankle strength, power and walking speed in participants with Type 2 diabetes. Unsteadiness correlated with small-, but not large-fibre neuropathy and there was no relationship between vitamin D levels and walking variables.

Distal lower limb strength is reduced in subjects with impaired glucose tolerance and is related to elevated intramuscular fat level and vitamin D deficiency.

AIM: To quantify muscle strength and size in subjects with impaired glucose tolerance (IGT) in relation to intramuscular non-contractile tissue, the severity of neuropathy and vitamin D level. METHODS: A total of 20 subjects with impaired glucose tolerance and 20 control subjects underwent assessment of strength and size of knee extensor, flexor and ankle plantar and dorsi-flexor muscles, as well as quantification of intramuscular non-contractile tissue and detailed assessment of neuropathy and serum 25-hydroxy vitamin D levels. RESULTS: In subjects with impaired glucose tolerance, proximal knee extensor strength (P = 0.17) and volume (P = 0.77), and knee flexor volume (P = 0.97) did not differ from those in control subjects. Ankle plantar flexor strength was significantly lower (P = 0.04) in the subjects with impaired glucose tolerance, with no difference in ankle plantar flexor (P = 0.62) or dorsiflexor volume (P = 0.06) between groups. Intramuscular non-contractile tissue level was significantly higher in the ankle plantar flexors and dorsiflexors (P = 0.03) of subjects with impaired glucose tolerance compared with control subjects, and it correlated with the severity of neuropathy. Ankle plantar flexor muscle strength correlated significantly with corneal nerve fibre density (r = 0.53; P = 0.01), a sensitive measure of small fibre neuropathy, and was significantly lower in subjects with vitamin D deficiency (P = 0.02). CONCLUSIONS: People with impaired glucose tolerance have a significant reduction in distal but not proximal leg muscle strength, which is not associated with muscle atrophy, but with increased distal intramuscular non-contractile tissue, small fibre neuropathy and vitamin D deficiency.

Is the metabolic cost of walking higher in people with diabetes?

People with diabetes walk slower and display biomechanical gait alterations compared with controls, but it remains unknown whether the metabolic cost of walking (CoW) is elevated. The aim of this study was to investigate the CoW and the lower limb concentric joint work as a major determinant of the CoW, in patients with diabetes and diabetic peripheral neuropathy (DPN). Thirty-one nondiabetic controls (Ctrl), 22 diabetic patients without peripheral neuropathy (DM), and 14 patients with moderate/severe DPN underwent gait analysis using a motion analysis system and force plates and treadmill walking using a gas analyzer to measure oxygen uptake. The CoW was significantly higher particularly in the DPN group compared with controls and also in the DM group (at selected speeds only) compared with controls, across a range of matched walking speeds. Despite the higher CoW in patients with diabetes, concentric lower limb joint work was significantly lower in DM and DPN groups compared with controls. The higher CoW is likely due to energetic inefficiencies associated with diabetes and DPN reflecting physiological and biomechanical characteristics. The lower concentric joint work in patients with diabetes might be a consequence of kinematic gait alterations and may represent a natural strategy aimed at minimizing the CoW.

The diabetic foot in 2015: an overview.

In 2015, it can be said that the diabetic foot is no longer the Cinderella of diabetic complications. Thirty years ago there was little evidence-based research taking place on the diabetic foot, and there were no international meetings addressing this topic. Since then, the biennial Malvern Diabetic Foot meetings started in 1986, the American Diabetes Association founded their Foot Council in 1987, and the European Association for the Study of Diabetes established a Foot Study Group in 1998. The first International Symposium on the Diabetic Foot in The Netherlands was convened in 1991, and this was soon followed by the establishment of the International Working Group on the Diabetic Foot that has produced useful guidelines in several areas of investigation and the management of diabetic foot problems. There has been an exponential rise in publications on diabetic foot problems in high impact factor journals, and a comprehensive evidence-base now exists for many areas of treatment. Despite the extensive evidence available, it, unfortunately, remains difficult to demonstrate that most types of education are efficient in reducing the incidence of foot ulcers. However, there is evidence that education as part of a multi-disciplinary approach to diabetic foot ulceration plays a pivotal role in incidence reduction. With respect to treatment, strong evidence exists that offloading is the best modality for healing plantar neuropathic foot ulcers, and there is also evidence from two randomized controlled trials to support the use of negative-pressure wound therapy in complex post-surgical diabetic foot wounds. Hyperbaric oxygen therapy exhibits the same evidence level and strength of recommendation. International guidelines exist on the management of infection in the diabetic foot. Many randomized trials have been performed, and these have shown that the agents studied generally produced comparable results, with the exception of one study in which tigecycline was shown to be clinically inferior to ertapenem ± vancomycin. Similarly, there are numerous types of wound dressings that might be used in treatment and which have shown efficacy, but no single type (or brand) has shown superiority over others. Peripheral artery disease is another major contributory factor in the development of ulceration, and its presence is a strong predictor of non-healing and amputation. Despite the proliferation of endovascular procedures in addition to open revascularization, many patients continue to suffer from severely impaired perfusion and exhaust all treatment options. Finally, the question of the true aetiopathogenesis of Charcot neuroarthropathy remains enigmatic, although much work is currently being undertaken in this area. In this area, it is most important to remember that a clinically uninfected, warm, insensate foot in a diabetic patient should be considered as a Charcot foot until proven otherwise, and, as such, treated with offloading, preferably in a cast.

People with diabetic peripheral neuropathy display a decreased stepping accuracy during walking: potential implications for risk of tripping.

AIM: To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. METHODS: Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non-diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. RESULTS: Patients in the diabetic peripheral neuropathy group, and patients in the diabetes-alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. CONCLUSIONS: Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking.

Resistance exercise training increases lower limb speed of strength generation during stair ascent and descent in people with diabetic peripheral neuropathy.

AIM: To examine the effects of a 16-week resistance exercise training intervention on the speed of ankle and knee strength generation during stair ascent and descent, in people with neuropathy. METHODS: A total of 43 people: nine with diabetic peripheral neuropathy, 13 with diabetes but no neuropathy and 21 healthy control subjects ascended and descended a custom-built staircase. The speed at which ankle and knee strength were generated, and muscle activation patterns of the ankle and knee extensor muscles were analysed before and after a 16-week intervention period. RESULTS: Ankle and knee strength generation during both stair ascent and descent were significantly higher after the intervention than before the intervention in the people with diabetes who undertook the resistance exercise intervention (P < 0.05). Although muscle activations were altered by the intervention, there were no observable patterns that underpinned the observed changes. CONCLUSIONS: The increased speed of ankle and knee strength generation observed after the intervention would be expected to improve stability during the crucial weight acceptance phase of stair ascent and descent, and ultimately contribute towards reducing the risk of falling. Improvements in muscle strength as a result of the resistance exercise training intervention are likely to be the most influential factor for increasing the speed of strength generation. It is recommended that these exercises could be incorporated into a multi-faceted exercise programme to improve safety in people with diabetes and neuropathy.

Pedal osteomyelitis in patients with diabetes: a retrospective audit from Saudi Arabia.

OBJECTIVE: To examine the characteristics of patients presenting to the emergency room and the specialist diabetes foot clinic with pedal osteomyelitis (PO). METHOD: A retrospective study was conducted at a regional hospital. The charts of patients with suspected PO who presented during the period 1 January to 31 December 2011 were analysed. Demographics, biochemistry and microbiological data were obtained. Bone biopsies were performed by the attending clinician either during surgical removal of infected bone, or percutaneously under guided fluoroscopy through non-infected tissue. RESULTS: Sixty-six cases of osteomyelitis affecting 102 joints were noted. The study population consisted of 44 men, mean age 62.9 +/- 1.3 years, and 22 women, mean age of 57.6 +/- 10.6 years. Gram-positive bacteria were the predominating pathogens (p < 0.05). Staphylococcus aureus was cultured in 36% of all bone biopsy cases. A predictive trend in HbA1c was observed,where every increase of 1% from the recommended level of 7% was associated with a 10% increase in the likelihood of receiving surgical intervention. CONCLUSION: S. aureus infection is a major cause of osteomyelitis in interphalangeal joints of the feet of diabetic patients.There is an apparent association with patients who present with diabetic foot osteomyelitis and sub-optimal glycaemic control, requiring surgical intervention.

Deep wound cultures correlate well with bone biopsy culture in diabetic foot osteomyelitis.

BACKGROUND: Osteomyelitis is a major complication in patients with diabetic foot ulceration. Accurate pathogenic identification of organisms can aid the clinician to a specific antibiotic therapy thereby preventing the need for amputation. METHODS: All diabetic patients with bone biopsy-confirmed osteomyelitis were included into the study: biopsies were performed either during surgical removal of infected bone or percutaneously under guided fluoroscopy through non-infected tissue. The depth and extent of the ulcer was assessed using a sterile blunt metal probe. Deep wound cultures were taken from the wound base after sharp debridement. RESULTS: Of 66 cases of suspected osteomyelitis in 102 joints, 34 patients had both bone biopsies and deep wound cultures over the study period. Thirty two of 34 (94%), had a history of preceding foot ulceration, and in 25 of the cases a positive probe to bone test was recorded. In a high proportion of patients, at least one similar organism was isolated from both the deep wound culture and bone biopsy procedures (25 of 34 cases, 73.5%, p<0.001). When organisms were isolated from both wound cultures and bone biopsies, the identical strain was identified in both procedures in a significant proportion of cases (16 of 25 cases, 64%, p<0.001, total sample analysis in 16 of 34 cases, 47%). CONCLUSIONS: Deep wound cultures correlate well with osseous cultures and provide a sensitive method in assessing and targeting likely pathogens that cause osseous infections. This will help aid the clinician in guiding antibiotic therapy in centers where bone biopsies may not be readily available.

A pocket-sized disposable device for testing the integrity of sensation in the outpatient setting.

AIMS: To compare the Ipswich Touch Test and the VibraTip with the Neuropathy Disability Score and the vibration perception threshold for detecting the 'at-risk' foot. METHODS: We directly compared the Ipswich Touch Test and the VibraTip with both the Neuropathy Disability Score ≥ 6 and the vibration perception threshold ≥ 25 V indicating 'at-risk' feet in 83 individuals. RESULTS: The vibration perception threshold and Neuropathy Disability Score tests exhibited almost perfect agreement with each other (P < 0.001). The VibraTip and Ipswich Touch Test results were identical (P < 0.001). The VibraTip and Ipswich Touch Test results also exhibited almost perfect agreement with the vibration perception threshold (P < 0.001) and the Neuropathy Disability Score (P < 0.001). CONCLUSIONS: These two simple and efficient tests are easy to teach, reliable and can be used in any setting, and neither requires an external power source. We conclude that both the VibraTip and the Ipswich Touch Test are reliable and sensitive tests for identifying the 'high-risk' foot.

An extensive primary nodular melanoma of the foot with associated distant metastases: a case report.

A Nodular Melanoma of the foot is a relatively uncommon disease, which accounts for the dearth of literature. The anatomical location of a primary malignant melanoma is of prognostic importance as primary lesions of the foot and ankle have poorer prognostic outcomes. This single case reports a life-threatening presentation, of a primary nodular melanoma of the foot with associated distant metastases of the skeletal system, organs and lymph nodes.

An assessment of the accuracy and usability of a novel optical wound measurement system.

AIMS: Measurement of wound size can predict healing and provide information to guide treatment. This study assesses a novel optical wound imaging system that creates a three-dimensional image of the ulcer. METHODS: Using a new camera-based digital system and traditional elliptical wound measurements, 36 foot ulcers from 31 patients (aged 44-94 years, median 70 years) were examined during a 12-week period at two centres. Median diabetes duration was 18 years (range 6-56 years). Seventeen percent had Type 1 diabetes, 93% had peripheral neuropathy and 57% had peripheral artery disease. Twenty-five were reviewed consecutively, resulting in 76 ulcer examinations. Median ulcer size was 94 mm(2), with size ranging from 3.1 to 2195 mm(2). RESULTS: Pearson, Spearman and Kendall rank coefficients showed a strong correlation (in all cases P < 0.001) between digital measurements of wounds against traditional hand-measured estimates. Intra-observer variation of wound length using digital elliptical measurement (DEM) gave a coefficient of variation of < 3.0%. Interobserver variation of wound length using DEM was < 6.5%. Variation from a standard known-size wound area was < 8.0% across 30 trials. CONCLUSIONS: This study shows a strong correlation between digital and traditional measurement techniques. The system can be easily deployed in routine clinical practice, providing an objective visual record, allowing remote in-depth analysis.