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Introduction: There is an absence in the application of standardised epidemiological principles when calculating and reporting on lower extremity amputation (LEA) rates [1]. The rates of minor LEAs in the diabetic population range from 1.2-362.9 per 100,000 and in the population without diabetes 0.9-109.4 per 100,000. The reported rates of major lower limb amputations vary from 5.6-600 per 100,000 in the diabetic population and 3.6-58.7 per 100,000 in the total population [1]. The variation in methodology does not facilitate comparison across populations and time. All studies published using the population from England, UK, describing minor amputations were systematically reviewed and rates and methodologies compared., Method: A systematic search was carried out using (PRISMA) guidelines [2] to reveal primary data of minor lower extremity amputation rates in England between 1988-2018. This was carried out using electronic databases, grey literature and reference list searching. The search yielded eleven studies that were eligible for review., Results: Significant variation in the reporting of minor lower extremity amputation rates across regional and gender groups in England was found. Rates in the diabetic and non-diabetic population varied from 1.2 to 362.9 per 100,000 and 0.9 to 109.4 per 100,000 respectively. This was predominately a result of poorly describing numerator and denominator populations and defining minor amputations differently. As a result, there was an inability to confidently establish regional, gender and time trends., Conclusion: The inconsistent nature of reporting minor amputations makes drawing conclusions on temporal and population change difficult. Future studies should describe and present basic numerator and denominator population characteristics e.g. number, age and sex and use the standard definition of minor amputation as one that is at or below the ankle., 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. Published by Elsevier Ltd.)

Objective: This study investigated the effects of vibrating insoles on dynamic balance and gait quality during level and stair walking and explored the influence of vibration type and frequency in individuals with diabetic peripheral neuropathy (DPN)., Research Design and Methods: Twenty-two men with DPN were assessed for gait quality and postural and dynamic balance during walking and stair negotiation using a motion capture system and force plates across seven vibratory insole conditions (Vcs) versus a control (Ctrl) condition (insole without vibration). Vibration was applied during standing and walking tasks, and 15-min rest-stop periods without vibration were interposed between conditions. Repeated measures test conditions were randomized. The primary outcomes were gait speed and dynamic balance., Results: Gait speed during walking significantly improved in all Vcs compared with Ctrl (P < 0.005), with Vc2, Vc4, and Vc6 identified as the most effective. Gait speed increased (reflecting faster walking) during stair ascent and descent in Vc2 (Ctrl vs. Vc2 for ascent 0.447 ± 0.180 vs. 0.517 ± 0.127 m/s; P = 0.037 and descent 0.394 ± 0.170 vs. 0.487 ± 0.125 m/s; P = 0.016), Vc4 (Ctrl vs. Vc4 for ascent 0.447 ± 0.180 vs. 0.482 ± 0.197 m/s; P = 0.047 and descent 0.394 ± 0.170 vs. 0.438 ± 0.181 m/s; P = 0.017), and Vc6 (Ctrl vs. Vc6 for ascent 0.447 ± 0.180 vs. 0.506 ± 0.179 m/s; P = 0.043 and descent 0.394 ± 0.170 vs. 0.463 ± 0.159 m/s; P = 0.026). Postural balance improved during quiet standing with eyes closed in Vc2, Vc4, Vc6, and Vc7 (P < 0.005)., Conclusions: Vibrating insoles are an effective acute strategy for improving postural balance and gait quality during level walking and stair descent in individuals with DPN. These benefits are particularly evident when the entire plantar foot surface is stimulated., (© 2024 by the American Diabetes Association.)

Background: The global number of people with diabetes is estimated to reach 643 million by 2030 of whom 19-34% will present with diabetic foot ulceration. Insoles which offload high-risk ulcerative regions on the foot, by removing insole material, are the main contemporary conservative treatment to maintain mobility and reduce the likelihood of ulceration. However, their effect on the rest of the foot and relationship with key gait propulsive and balance kinematics and kinetics has not been well researched., Purpose: The aim of this study is to investigate the effect of offloading insoles on gait kinematics, kinetics, and plantar pressure throughout the gait cycle., Methods: 10 healthy subjects were recruited for this experiment to walk in 6 different insole conditions. Subjects walked at three speeds on a treadmill for 10 minutes while both plantar pressure and gait kinematics, kinetics were measured using an in-shoe pressure measurement insole and motion capture system/force plates. Average peak plantar pressure, pressure time integrals, gait kinematics and centre of force were analysed., Results: The average peak plantar pressure and pressure time integrals changed by -30% (-68% to 3%) and -36% (-75% to -1%) at the region of interest when applying offloading insoles, whereas the heel strike and toe-off velocity changed by 15% (-6% to 32%) and 12% (-2% to 19%) whilst walking at three speeds., Conclusion: The study found that offloading insoles reduced plantar pressure in the region of interest with loading transferred to surrounding regions increasing the risk of higher pressure time integrals in these locations. Heel strike and toe-off velocities were increased under certain configurations of offloading insoles which may explain the higher plantar pressures and supporting the potential of integrating kinematic gait variables within a more optimal therapeutic approach. However, there was inter-individual variability in responses for all variables measured supporting individualised prescription., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shuang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Popliteal artery entrapment syndrome (PAES) is a rare condition where musculoskeletal structures compress the popliteal artery (POPA) leading to vascular compromise. This study investigates the effect of dynamic plantar- and dorsi-flexion loading on POPA hemodynamic parameters to develop a robust diagnostic ultrasound-based protocol for diagnosing functional PAES., Methods: Healthy individuals (n = 20), recreational athletes (n = 20), and symptomatic (n = 20) PAES patients were consented. Triplex ultrasound imaging of lower limb arteries was performed (n = 120 limbs). Proximal and distal POPA's in dorsi-/plantar-flexion, in prone and erect positions, were imaged at rest and flexion. Peak systolic velocities (cm/s) and vessel diameter (antero-posterior, cm) was measured., Results: Distal vessel occlusion was noted across all three groups whilst prone during plantar-flexion (62.7%). POPA occlusion was only noted in the proximal vessel within the patient group (15.8%). When prone, 50% of control (n = 40 limbs), 70% of athletes (n = 40 limbs), and 65% of patients (n = 40 limbs) had distal POPA occlusion in plantar-flexion. When prone, recreational athletes (5%), and patients (12.5%) had distal POPA compression under dorsi-flexion. POPA occlusions with the patient in erect position were only noted in the symptomatic patient group under both dorsi-flexion (15.8%) and plantar-flexion (23.7%)., Conclusion: Compression of the POPA on ultrasound should not be the sole diagnostic criteria for PAES. POPA compression exists in asymptomatic individuals, primarily under prone plantar-flexion. To reduce false positives, ultrasound-based protocols should focus on scanning patients in the erect position only to diagnose PAES, rather than asymptomatic POPA compression. A distinction should be made between the two., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background: Carotid plaque volume (CPV) can be measured by 3D ultrasound and may be a better predictor of stroke than stenosis, but analysis time limits clinical utility. This study tested the accuracy, reproducibility, and time saved of using an artificial intelligence (AI) derived semiautomatic software to measure CPV ("auto-CPV")., Methods: Three-dimensional (3D) ultrasound images for 121 individuals were analyzed by 2 blinded operators to measure auto-CPV. Corresponding endarterectomy specimen volumes were calculated by the validated saline suspension technique. Inter-rater and intrarater agreement plus accuracy compared with the volume of the endarterectomized plaque were calculated. Measurement times were compared with previous manual CPV measurement., Results: The mean difference between auto-CPV and surgical volume was small at (±s.d.) [95% confidence interval [CI]] 0.06 (0.24) [-0.41 to 0.54] cm 3 . The intraclass correlation (ICC) was strong at 0.91; 95% CI 0.86-0.94. Interobserver and intraobserver error was low with mean difference (±s.d.) [95%CI] 0.01 (0.26) [-0.5 to 0.5] cm 3 and 0.03 (0.19) [-0.35 to 0.40] cm 3 respectively. Both showed excellent ICC with narrow confidence intervals, ICC = 0.90; 95% CI (0.85-0.94) and ICC = 0.95; 95% CI (0.92-0.96). Auto-CPV measurement took 43% the time of manual planimetry; median (IQR) 05:39 (01:58) minutes compared to 13:05 (04:15) minutes, Wilcoxon rank-sum test, P < 0.01., Conclusions: Auto-CPV assessment is accurate, reproducible, and significantly faster than manual planimetry. Improved feasibility means that the utility of CPV can be assessed in large population studies to stratify risk in asymptomatic carotid disease or assess response to medical treatment., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Background: This retrospective Romanian study aimed to calculate the rate of, and comparison between, amputation and revascularisation for patients with either cardiovascular or diabetic comorbidities. (2) Materials: In our hospital-based database, we analysed patient-level data from a series of 61 hospitals for 2019, which covers 44.9% of the amputation patients for that year. The national database is compiled by the national houses of insurance and was used to follow amputations and revascularisations between 2016 and 2021. (3) Results: During the six-year period, the mean number of amputations and revascularisations was 72.4 per 100,000 inhabitants per year for both groups. In this period, a decline in open-surgical revascularisation was observed from 58.3% to 47.5% in all interventions but was not statistically significant (r = -0.20, p = 0.70). The mean age of patients with amputation (hospital-based database) was 67 years. Of these patients, only 5.1% underwent revascularisation in the same hospital prior to amputation. The most common comorbidities in those undergoing amputations were peripheral arterial disease (76.8%), diabetes (60.8%), and arterial hypertension (53.5%). Most amputations were undertaken by general surgeons (73.0%) and only a small number of patients were treated by vascular surgeons (17.4%). (4) Conclusions: The signal from our data indicates that Romanian patients probably have a high risk of amputation > 5 years earlier than Western European countries, such as Denmark, Finland, and Germany. The prevalence of revascularisations in Romania is 64% lower than in the Western European countries.

Diabetic foot ulcer non-reimbursed treatment depends on multiple factors, including the patient's buying behaviors. Factors affecting buying behaviors for the removable off-loading devices are not completely understood. The aim of this study was to investigate the patients' buying behaviors of the removable off-loading devices and their influence on the DFU treatment outcomes remotely monitored during the COVID-19 pandemic. In this prospective observational study, 45 patients affected by diabetic peripheral neuropathy, with/without peripheral arterial disease, with foot ulcers treated with removable devices were remotely monitored. Prefabricated removable cast walkers, insoles, and therapeutic footwear were the proposed off-loading methods. Patients affected by high blood pressure ( p = 0.018), peripheral arterial disease ( p = 0.029), past amputations ( p = 0.018), and ulcer on the left foot ( p = 0.007) bought removable cast walkers. Rural provenience ( p = 0.011) and male ( p = 0.034) did not buy a removable walker. The healing rate was 69.4%, while the median healing time was 20 weeks. High blood pressure negatively influenced healing time ( p = 0.020). Patients who bought the most efficient treatment method for DFUs were females from urban provenience, with amputation in the past, with peripheral arterial disease, and with high blood pressure.

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 cm 3 (0.10-2.47 cm 3 ). Mean ± sd CPV measured by tUS (n = 114) was 0.87 ± 0.51 cm 3 , CEtUS (n = 104) was 0.75 ± 0.45 cm 3 and with fusion (n = 95) was 0.83 ± 0.49 cm 3 . Differences between specimen volume and CPV measured by tUS (0.13 ± 0.24 cm 3 ), CEtUS (-0.01 ± 0.21 cm 3 ) 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., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Lower extremity amputations (LEAs) are a feared complication of diabetes mellitus (DM). Here we evaluated the recent trends in DM-related LEAs in Romania. We collected data from a national database regarding minor and major LEAs performed between 2015 and 2019 in patients with DM admitted to a public hospital. Absolute numbers of LEAs were presented by year, diabetes type, sex and age; incidence rates of LEAs in the general population were also calculated. Over the study period, 40,499 LEAs were recorded nationwide (83.16% in persons with type 2 DM [T2DM]); on average, the number of LEAs increased by 5.7%/year. This trend was driven by an increased number of LEAs in patients with T2DM; in patients with type 1 DM (T1DM), LEAs decreased over the study period. In patients with T2DM, the increase in minor LEAs was more pronounced than that in major LEAs. The overall number of LEAs showed an increasing trend with age (r = 0.72), which was most pronounced in patients aged ≥70 years. Men had a higher frequency of LEAs than women, regardless of DM type. These data support renewed efforts to prevent and decrease the burden of amputations among patients with DM.

Diabetic autonomic neuropathy is probably the most undiagnosed but serious complication of diabetes. The main objectives were to assess the prevalence of peripheral and autonomic neuropathy in a population of diabetic patients, analyze it in a real-life outpatient unit scenario and determine the feasibility of performing SUDOSCAN tests together with widely used tests for neuropathy. A total of 33 patients were included in the study. Different scoring systems (the Toronto Clinical Neuropathy Score-TCNS; the Neuropathy Disability Score-NDS; and the Neuropathy Symptom Score-NSS) were applied to record diabetic neuropathy (DN), while the SUDOSCAN medical device was used to assess sudomotor function, detect diabetic autonomic neuropathy and screen for cardiac autonomic neuropathy (CAN). Fifteen (45.5%) patients had sudomotor dysfunction. The SUDOSCAN CAN risk score was positively correlated with the hands' electrochemical sweat conductance (ESC), diastolic blood pressure (DBP), the level of the glycated hemoglobin, as well as with the TCNS, NDS and NSS. Performing SUDOSCAN tests together with other tests for DN proved to be a feasible approach that could be used in daily clinical practice in order to screen for DN, as well as for the early screening of CAN, before more complex and time-consuming tests.

Portable, custom-made electronic dynamometry for the foot and ankle is a promising assessment method that enables foot and ankle muscle function to be established in healthy participants and those affected by chronic conditions. Diabetic peripheral neuropathy (DPN) can alter foot and ankle muscle function. This study assessed ankle toque in participants with diabetic peripheral neuropathy and healthy participants, with the aim of developing an algorithm for optimizing the precision of data processing and interpretation of the results and to define a reference frame for ankle torque measurement in both healthy participants and those affected by DPN. This paper discloses the software chain and the signal processing methods used for voltage-torque conversion, filtering, offset detection and the muscle effort type identification, which further allowed for a primary statistical report. The full description of the signal processing methods will make our research reproducible. The applied algorithm for signal processing is proposed as a reference frame for ankle torque assessment when using a custom-made electronic dynamometer. While evaluating multiple measurements, our algorithm permits for a more detailed parametrization of the ankle torque results in healthy participants and those affected by DPN.

Inactivity negatively influences general health, and sedentary behaviour is known to impact the musculoskeletal system. The aim of the study was to assess the impact of time spent in active and sedentary behaviour on foot muscle strength. In this observational study, we compared the acute effects of one day of prolonged sitting and one day of low-to-moderate level of activity on ankle torque in one group of eight healthy participants. Peak ankle torque was measured using a portable custom-made electronic dynamometer. Three consecutive maximal voluntary isometric contractions for bilateral plantar flexor and dorsiflexor muscles were captured at different moments in time. The average peak torque significant statistically decreased at 6 h (p = 0.019) in both static and active behaviours, with a higher average peak torque in the active behaviour (p < 0.001). Age, gender, body mass index and average steps did not have any significant influence on the average value of maximal voluntary isometric contraction. The more time participants maintained either static or active behaviour, the less force was observed during ankle torque testation. The static behaviour represented by the sitting position was associated with a higher reduction in the average peak ankle torque during a maximal voluntary isometric contraction when compared to the active behaviour.

The negative effects of SARS-CoV-2 infection on the musculoskeletal system include symptoms of fatigue and sarcopenia. The aim of this study is to assess the impact of COVID-19 on foot muscle strength and evaluate the reproducibility of peak ankle torque measurements in time by using a custom-made electronic dynamometer. In this observational cohort study, we compare two groups of four participants, one exposed to COVID-19 throughout measurements and one unexposed. Peak ankle torque was measured using a portable custom-made electronic dynamometer. Ankle plantar flexor and dorsiflexor muscle strength was captured for both feet at different ankle angles prior and post COVID-19. Average peak torque demonstrated no significant statistical differences between initial and final moment for both groups (p = 0.945). An increase of 4.8%, p = 0.746 was obtained in the group with COVID-19 and a decrease of 1.3%, p = 0.953 was obtained in the group without COVID-19. Multivariate analysis demonstrated no significant differences between the two groups (p = 0.797). There was a very good test−retest reproducibility between the measurements in initial and final moments (ICC = 0.78, p < 0.001). In conclusion, peak torque variability is similar in both COVID-19 and non-COVID-19 groups and the custom-made electronic dynamometer is a reproducible method for repetitive ankle peak torque measurements.

Background and Objectives: Barefoot peak plantar pressures (PPPs) are elevated in diabetes patients with neuropathic foot ulcer (DFU) history; however, there is limited reported evidence for a causative link between high barefoot PPP and DFU risk. We aimed to determine, using a simple mat-based methodology, the site-specific, barefoot PPP critical threshold that will identify a plantar site with a previous DFU. Materials and Methods: In a cross-sectional study, barefoot, site-specific PPPs were measured with normal gait for patients with DFU history ( n = 21) and healthy controls ( n = 12), using a validated carbon footprint system. For each participant, PPP was recorded at twelve distinct plantar sites (1st-5th toes, 1st-5th metatarsal heads (MTHs), midfoot and heel), per right and left foot, resulting in the analysis of n = 504 distinct plantar sites in the diabetes group, and n = 288 sites in the control group. Receiver operator characteristic curve analysis determined the optimal critical threshold for sites with DFU history. Results: Median PPPs for the groups were: diabetes sites with DFU history ( n = 32) = 5.0 (3.25-7.5) kg/cm 2 , diabetes sites without DFU history ( n = 472) = 3.25 (2.0-5.0) kg/cm 2 , control sites ( n = 288) = 2.0 (2.0-3.25) kg/cm 2 ; ( p < 0.0001). Diabetes sites with elevated PPP (>6 kg/cm 2 ) were six times more likely to have had DFU than diabetes sites with PPP ≤ 6 kg/cm 2 (OR = 6.4 (2.8-14.6, 95% CI), p < 0.0001). PPP > 4.1 kg/cm 2 was determined as the optimal critical threshold for identifying DFU at a specific plantar site, with sensitivity/specificity = 100%/79% at midfoot; 80%/65% at 5th metatarsal head; 73%/62% at combined midfoot/metatarsal head areas. Conclusions: We have demonstrated, for the first time, a strong, site-specific relationship between elevated barefoot PPP and previous DFU. We have determined a critical, highly-sensitive, barefoot PPP threshold value of >4.1 kg/cm 2 , which may be easily used to identify sites of previous DFU occurrence and, therefore, increased risk of re-ulceration. This site-specific approach may have implications for how high PPPs should be investigated in future trials.

Custom-made dynamometry was shown to objectively analyze human muscle strength around the ankle joint with accuracy, easy portability and low costs. This paper describes the full method of calibration and measurement setup and the measurement procedure when capturing ankle torque for establishing reliability of a portable custom-built electronic dynamometer. After considering the load cell offset voltage, the pivotal position was determined, and calibration with loads followed. Linear regression was used for calculating the proportionality constant between torque and measured voltage. Digital means were used for data collection and processing. Four healthy consenting participants were enrolled in the study. Three consecutive maximum voluntary isometric contractions of five seconds each were registered for both feet during plantar flexion/dorsiflexion, and ankle torque was then calculated for three ankle inclinations. A calibration procedure resulted, comprising determination of the pivotal axis and pedal constant. Using the obtained data, a measurement procedure was proposed. Obtained contraction time graphs led to easier filtering of the results. When calculating the interclass correlation, the portable apparatus demonstrated to be reliable when measuring ankle torque. When a custom-made dynamometer was used for capturing ankle torque, accuracy of the method was assured by a rigorous calibration and measurement protocol elaboration.

Aims: High plantar pressure is a major risk factor in the development of diabetic foot ulcers (DFUs) and recent evidence shows plantar pressure feedback reduces DFU recurrence. This study investigated whether continued use of an intelligent insole system by patients at high-risk of DFUs causes a reduction in plantar pressures., Methods: Forty-six patients with diabetic peripheral neuropathy and previous DFU were randomised to intervention (IG) or control groups (CG). Patients received an intelligent insole system, consisting of pressure-sensing insoles and digital watch. Patients wore the device during all daily activity for 18-months or until ulceration, and integrated pressure was recorded continuously. The device provided high-pressure feedback to IG only via audio-visual-vibrational alerts. High-pressure parameters at the whole foot, forefoot and rearfoot were compared between groups, with multilevel binary logistic regression analysis., Results: CG experienced more high-pressure bouts over time than IG across all areas of the foot (P < 0.05). Differences between groups became apparent >16 weeks of wearing the device., Conclusions: Continuous plantar pressure feedback via an intelligent insole system reduces number of bouts of high-pressure in patients at high-risk of DFU. These findings suggest that patients were learning which activities generated high-pressure, and pre-emptively offloading to avoid further alerts., 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 © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

A prospective, single arm feasibility study was conducted to evaluate healing outcomes of DFUs treated with autologous skin cell suspension (ASCS) in combination with standard therapy. Wounds up to 100 cm 2 in size that failed to heal with conventional therapy were included and wound healing, pain, exudate scores, Quality of Life, satisfaction scores, and safety outcomes were evaluated over a period of 26 weeks. Sixteen subjects were enrolled having a mean DFU duration of 60.4 weeks. All ulcers in this study had a positive healing trajectory, with a mean reepithelialization of 84.9% and 12.2 cm 2 reduction in ulcer area. For ulcers that did not acquire a soft tissue infection post-treatment, all either healed or achieved ≥95% reepithelialization including some with exposed tendon. Improvements were observed in all aspects of the health-related Quality of Life questionnaire and subjects and clinicians were highly satisfied across all postoperative visits. This preliminary study suggests ASCS is a well-tolerated and promising therapy for the treatment of DFUs as all ulcers evaluated experienced positive healing results regardless of size, depth, and wound duration. Future studies are warranted to investigate ASCS compared to standard of care for all diabetic foot ulcers, inclusive of the evaluation of treatment algorithms and combination products., (© 2020 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

Of all the late complications of diabetes, those involving the foot have traditionally required more face-to-face patient visits to clinics to treat wounds by debridement, offloading, and many other treatment modalities. The advent of the coronavirus disease 2019 (COVID-19) pandemic has resulted not only in the closing of most outpatient clinics for face-to-face consultations but also in the inability to perform most laboratory and imaging investigations. This has resulted in a paradigm shift in the delivery of care for those with diabetic foot ulcers. The approaches to this challenge in two centers with an interest in diabetic foot disease, including virtual consultations using physician-to-patient and physician-to-home nurse telemedicine as well as home podiatry visits, are described in this review and are illustrated by several case vignettes. The outcomes from these two centers suggest that we may be witnessing new possibilities in models of care for the diabetic foot., (© 2020 by the American Diabetes Association.)

The predominant risk factor of diabetic foot ulcers (DFU), peripheral neuropathy, results in loss of protective sensation and is associated with abnormally high plantar pressures. DFU prevention strategies strive to reduce these high plantar pressures. Nevertheless, several constraints should be acknowledged regarding the research supporting the link between plantar pressure and DFUs, which may explain the low prediction ability reported in prospective studies. The majority of studies assess vertical, rather than shear, barefoot plantar pressure in laboratory-based environments, rather than during daily activity. Few studies investigated previous DFU location-specific pressure. Previous studies focus predominantly on walking, although studies monitoring activity suggest that more time is spent on other weight-bearing activities, where a lower "peak" plantar pressure might be applied over a longer duration. Although further research is needed, this may indicate that an expression of cumulative pressure applied over time could be a more relevant parameter than peak pressure. Studies indicated that providing pressure feedback might reduce plantar pressures, with an emerging potential use of smart technology, however, further research is required. Further pressure analyses, across all weight-bearing activities, referring to location-specific pressures are required to improve our understanding of pressures resulting in DFUs and improve effectiveness of interventions., (© 2019 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Diabetic foot ulcers can become chronic and non-healing despite systemic antibiotic treatment. The penetration of systematically-administered antibiotics to the site of infection is uncertain, as is the effectiveness of such levels against polymicrobial biofilms. We have developed an in vitro model to study the effectiveness of different treatments for infected diabetic foot ulcers in a wound-like environment and compared the activity of systemic levels of antibiotics with that for topically applied antibiotics released from calcium sulfate beads. This is the first study that has harvested bacteria from diabetic foot infections and recreated similar polymicrobial biofilms to those present in vivo for individual subjects. After treatment with levels of gentamicin attained in serum after systemic administration (higher than corresponding tissues concentrations) we measured a 0-2 log reduction in bacterial viability of P. aeruginosa, S. aureus or a polymicrobial biofilm. Conversely, addition of gentamicin loaded calcium sulfate beads resulted in 5-9 log reductions in P. aeruginosa, S aureus and polymicrobial biofilms derived from three subjects. We conclude that systemically administered antibiotics are likely to be inadequate for successfully treating these infections, especially given the vastly increased concentrations required to inhibit cells in a biofilm, and that topical antibiotics provide a more effective alternative., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aim: 3D wound imaging has provided clinicians with even greater wound measurement options. No data is available to guide clinicians as to which 3D measurements may yield the most reflective marker of wound progression to healing., Method: A prospective pilot study was undertaken to assess the accuracy of five 3D wound measurements that best reflect metrics of interest to clinicians. Twenty-one diabetic foot ulcers were enrolled from initial ulcer presentation, through to healing. The relationship between mean wound healing measurement variables was examined using linear regression and Pearsons correlation coefficient, in addition to assessing clinician inter-rater reliability of measurements using Intra-class correlation coefficients (ICC)., Results: Statistical analysis demonstrated a linear healing slope for each wound measurement as having a value greater than R 0.70 and a statistical significance of p = 0.0001. This suggests that all five wound measurements are useful prognostic markers of wound progression to healing. Low variability of measurements between users indicates good inter-observer reliability., Conclusion: 3D wound measurements demonstrate a linear correlation between the measurement and time to healing. This suggests they could be effective prognostic markers of a wounds progression to healing and closure. It may also provide important early identification of wounds not responding to standard care. Larger studies are required to validate our results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Controlled inflammatory responses of myeloid cells recruited to wounds are essential for effective repair. In diabetes, the inflammatory response is prolonged and augmented over time, with increased myeloid cells present in the wound that fail to switch from a pro-inflammatory phenotype to a pro-healing phenotype. These defects lead to delayed angiogenesis and tissue repair and regeneration, and contribute to chronic wound formation. In mouse models of diabetes, this aberrant phenotype is partially mediated by stable intrinsic changes to the developing myeloid cells in the bone marrow, affecting their maturation and polarization potential. Previous studies have shown that freshly isolated peripheral blood mononuclear cells from diabetic patients are more inflammatory than non-diabetic counterparts. However, the phenotype of macrophages from human diabetic patients has not been well characterized. Here we show that diabetic-derived human macrophages cultured for 6 days in vitro maintain a pro-inflammatory priming and hyperpolarize to a pro-inflammatory phenotype when stimulated with LPS and INF-ɣ or TNF. In addition, diabetic-derived macrophages show maturation defects associated with reduced expression of the RUNX1 transcription factor that promotes myeloid cell development. Targeting intrinsic defects in myeloid cells by protein transduction of the Hoxa3 transcription factor can rescue some inflammation and maturation defects in human macrophages from diabetic patients via upregulation of Runx1. In addition, Hoxa3 can modulate the levels of p65/NF-κB and histone acetyltransferase and deacetylase activity, as well as inhibit acetylation of the TNF promoter. Altogether, these results show a link between myeloid cell maturation and inflammatory responses, and that diabetes induces intrinsic changes to human myeloid cells that are maintained over time, as well as potentially therapeutic Hoxa3-mediated mechanisms of controlling the inflammatory response in diabetes., Competing Interests: This work was partially funded by Johnson and Johnson. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors declare no financial interests.

Introduction: Patients with diabetes and diabetic peripheral neuropathy (DPN) place their feet with less accuracy whilst walking, which may contribute to the increased falls-risk. This study examines the effects of a multi-faceted intervention on stepping accuracy, in patients with diabetes and DPN., Methods: Forty participants began the study, of which 29 completed both the pre and post-intervention tests, 8 patients with DPN, 11 patients with diabetes but no neuropathy (D) and 10 healthy controls (C). Accuracy of stepping was measured pre- and post-intervention as participants walked along an irregularly arranged stepping walkway. Participants attended a one-hour session, once a week, for sixteen weeks, involving high-load resistance exercise and visual-motor training., Results: Patients who took part in the intervention improved stepping accuracy (DPN: +45%; D: +36%) (p < 0.05). The diabetic non-intervention (D-NI) group did not display any significant differences in stepping accuracy pre- to post- the intervention period (-7%)., Discussion: The improved stepping accuracy observed in patients with diabetes and DPN as a result of this novel intervention, may contribute towards reducing falls-risk. This multi-faceted intervention presents promise for improving the general mobility and safety of patients during walking and could be considered for inclusion as part of clinical treatment programmes., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prevention of diabetic foot ulcer recurrence in high risk patients, using current standard of care methods, remains a challenge. We hypothesised that an innovative intelligent insole system would be effective in reducing diabetic foot ulcer recurrence in such patients., Methods: In this prospective, randomised, proof-of-concept study, patients with diabetes, and with peripheral neuropathy and a recent history of plantar foot ulceration were recruited from two multidisciplinary outpatient diabetic foot clinics in the UK, and were randomly assigned to either intervention or control. All patients received an insole system, which measured plantar pressure continuously during daily life. The intervention group received audiovisual alerts via a smartwatch linked to the insole system and offloading instructions when aberrant pressures were detected; the control group did not receive any alerts. The primary outcome was plantar foot ulcer occurrence within 18 months. This trial is registered with ISRCTN, ISRCTN05585501, and is closed to accrual and complete., Findings: Between March 18, 2014, and Dec 20, 2016, 90 patients were recruited and consented to the study, and 58 completed the study. At follow-up, ten ulcers from 8638 person-days were recorded in the control group and four ulcers from 11 835 person-days in the intervention group: a 71% reduction in ulcer incidence in the intervention group compared with the control group (incidence rate ratio 0·29, 95% CI, 0·09-0·93; p=0·037). The number of patients who ulcerated was similar between groups (six of 26 [control group] vs four of 32 [intervention group]; p=0·29); however, individual plantar sites ulcerated more often in the control group (ten of 416) than in the intervention group (four of 512; p=0·047). In an exploratory analysis of good compliers (n=40), ulcer incidence was reduced by 86% in the intervention group versus control group (incidence rate ratio 0·14, 95% CI 0·03-0·63; p=0·011). In the exploratory analysis, plantar callus severity (change from baseline to 6 months) was greater in re-ulcerating patients (6·5, IQR 4·0-8·3) than non-re-ulcerating patients (2·0, 0·0-4·8; p=0·040)., Interpretation: To our knowledge, this study is the first to show that continuous plantar pressure monitoring and dynamic offloading guidance, provided by an innovative intelligent insole system, can lead to a reduction in diabetic foot ulcer site recurrence., Funding: Diabetes UK and Orpyx Medical Technologies., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Doctoral-level study is increasingly popular for clinicians who wish to advance their clinical, research and academic career pathways. A range of alternatives to the traditional PhD are now well-established. This article aims to outline the different approaches and discuss some advantages and drawbacks of doctoral-level postgraduate study. By comparing the various doctoral programmes, the authors seek to clarify the issues for clinicians who may wish to embark on a future doctorate. Primary clinical or medical degrees are not discussed.

The excess risk of amputation in the diabetic population is well documented. However, approximately half of all amputations in England are in people that do not have diabetes - the remainder being mainly peripheral arterial disease. Whilst the prevalence of foot ulcers in the population without diabetes is significantly lower than their diabetic counterparts, the actual number of people with ulcers, and, therefore, the burden on services, is, the same. In addition to this inequality, the prevalence of amputation is greater in men than women and in the North of England compared with the South. We suggest that whilst diabetes is an important inequality to continue addressing, it is not the only one.

Chronic wounds such as venous leg ulcers invariably heal slowly and recur. In the case of venous leg ulcers, poor healing of chronic wounds is variously attributed to ambulatory hypertension, impaired perfusion and diffusion, presence of chronic inflammation at wound sites, lipodermatosclerosis, and senescence. The aim of this study was to investigate whether a new technique, optical coherence tomography (OCT), which permits imaging of blood capillaries in the peri-wound skin, can provide new insights into the pathology. OCT and its recent variant, dynamic OCT, permit rapid noninvasive depth-resolved imaging of the capillaries in the superficial dermis via a handheld probe, showing the morphology and density of vessels down to 20 µm in diameter. We used dynamic OCT to investigate 15 chronic wounds and assess characteristics of the vessels at the 4 poles around the wounds, the wound bed, adjacent dermatosclerosis, and unaffected skin. The results of the study show that both vessel morphology and density in the wound edges are dramatically different from that in healthy skin, showing clusters of glomuleri-like vessels (knot-like forms or clumps) and an absence of linear branching vessels, and also greater blood perfusion. Such vessel shapes are reported to be associated with tissue growth. The OCT imaging procedure was rapid and well tolerated by patients and provided new information not available from other devices. Thus, OCT appears to have great promise as a tool for the evaluation and study of chronic ulcers.

Endothelial colony forming progenitor cell (ECFC) function is compromised in diabetes, leading to poor vascular endothelial repair, which contributes to impaired diabetic foot ulcer healing. We have generated novel glycomimetic drugs with protective effects against endothelial dysfunction. We investigated the effect of glycomimetic C3 on the functional capacity of diabetic ECFCs. ECFCs were isolated from healthy controls and patients with diabetes with neuroischaemic (NI) or neuropathic (NP) foot ulcers. Functionally, diabetic ECFCs demonstrated delayed colony formation (p < 0.02), differential proliferative capacity (p < 0.001) and reduced NO bioavailability (NI ECFCs; p < 0.05). Chemokinetic migration and angiogenesis were also reduced in diabetic ECFCs (p < 0.01 and p < 0.001), and defects in wound closure and tube formation were apparent in NP ECFCs (p < 0.01). Differential patterns in mitochondrial activity were pronounced, with raised activity in NI and depressed activity in NP cells (p < 0.05). The application of glycomimetic improved scratch wound closure in vitro in patient ECFCs (p < 0.01), most significantly in NI cells (p < 0.001), where tube formation (p < 0.05) was also improved. We demonstrate restoration of the deficits in NI cells but not NP cells, using a novel glycomimetic agent, which may be advantageous for therapeutic cell transplantation or as a localised treatment for NI but not NP patients.

Pregabalin is a first-line treatment in all major international guidelines on the management of painful diabetic neuropathy (pDPN). Treatment with pregabalin leads to a clinically meaningful improvement in pain scores, offers consistent relief of pain and has an acceptable tolerance level. Despite its efficacy in relieving neuropathic pain, more robust methods and comprehensive studies are required to evaluate its effects in relation to co-morbid anxiety and sleep interference in pDPN. The sustained benefits of modulating pain have prompted further exploration of other potential target sites and the development of alternative GABAergic agents such as mirogabalin. This review evaluates the role of pregabalin in the management of pDPN as well as its potential adverse effects, such as somnolence and dizziness, which can lead to withdrawal in ~ 30% of long-term use. Recent concern about misuse and an increase in deaths linked to its use has led to demands for reclassification of pregabalin as a class C controlled substance in the UK. We believe these demands need to be tempered in relation to the difficulties it would create for repeat prescriptions for the many millions of patients with pDPN for whom pregabalin provides benefit.Plain Language Summary: Plain language summary available for this article.

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., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The number of people in the world with diabetes has nearly quadrupled in the past 40 years. Current data show that 25% of these diabetics will develop a foot ulcer in their lifetime and that the cost of care for a diabetic foot ulcer (DFU) is over twice that of any other chronic ulcer aetiology. Microbial biofilm has been linked to both wound chronicity and infection. Close to 1 in 2 diabetics with a DFU are predicted to go on to develop a diabetic foot infection (DFI). The majority of these DFIs have been found to evolve even before the diabetic individual has received an initial referral for expert DFU management. Of these infected DFUs, less than half have been shown to heal over the next year; many of these individuals will require costly hospitalisation, and current data show that far too many DFIs will require extremity amputation to achieve infection resolution. The development of an infection in a DFU is critical at least in part because paradigms of infection prevention and management are evolving. The effectiveness of our current practice standards is being challenged by a growing body of research related to the prevalence and recalcitrance of the microbes in biofilm to topical and systemic antimicrobials. This article will review the magnitude of current challenges related to DFI prevention and management along with what is currently considered to be standard of care. These ideas will be compared and contrasted with what is known about the biofilm phenotype; then, considerations to support progress towards the development of more cost-effective protocols of care are highlighted., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

High plantar pressure as a result of diabetic peripheral neuropathy is often reported as a major risk factor for ulceration. However, previous studies are confined to laboratories with equipment limited by cables, reducing the validity of measurements to daily life. The participant concerned in this case report was wearing an innovative plantar pressure feedback system as part of a wider study. The system allows for continuous plantar pressure monitoring and provides feedback throughout all activities of daily living. The participant concerned was a 59-year-old male with type 2 diabetes who presented with severe peripheral neuropathy. In addition, the right ankle had previously undergone fusion. Between monthly study appointments, the participant unknowingly had a screw embedded in his right shoe, while pressure was being recorded. Although no significant differences in pressure were present for the right foot with the embedded screw, the contralateral foot showed significantly higher pressure when the screw was embedded, compared with pre and post time periods. The increase in pressure on the contralateral foot is expected to result from the protrusion of the screw in the right shoe, causing a perturbation to balance and a shift in the center of pressure toward the contralateral side. This compensatory effect is likely to have been magnified by the limited mobility of the fused right ankle. These findings highlight the importance of checking both feet for ulcer risk, in the event of receiving high-pressure feedback. This innovative technology may improve our understanding of diabetic plantar foot ulcer development.

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.

Foot infections are common among diabetic patients with peripheral neuropathy and/or peripheral arterial disease, and it can be the pivotal event leading to a minor or major amputation of the lower extremity. Treatment of diabetic foot infections, especially deep-seated ones, remains challenging, in part because impaired blood perfusion and the presence of biofilms can impair the effectiveness of systemic antibiotics. The local application of antibiotics is an emerging field in the treatment of diabetic foot infections, with demonstrable advantages. These include delivery of high concentrations of antibiotics in the affected area, limited systemic absorption, and thus negligible side effects. Biodegradable vehicles, such as calcium sulfate beads, are the prototypical system, providing a good elution profile and the ability to be impregnated with a variety of antibiotics. These have largely superseded the nonbiodegradable vehicles, but the strongest evidence available is for calcium bead implantation for osteomyelitis management. Natural polymers, such as collagen sponge, are an emerging class of delivery systems, although thus far, data on diabetic foot infections are limited. There is recent interest in the novel antimicrobial peptide pexiganan in the form of cream, which is active against most of the microorganisms isolated in diabetic foot infections. These are promising developments, but randomized trials are required to ascertain the efficacy of these systems and to define the indications for their use. Currently, the role of topical antibiotic agents in treating diabetic foot infections is limited and outside of routine practice.

Background: We describe the development of a new mobile app called "FootSnap," to standardize photographs of diabetic feet and test its reliability on different occasions and between different operators., Methods: FootSnap was developed by a multidisciplinary team for use with the iPad. The plantar surface of 30 diabetic feet and 30 nondiabetic control feet were imaged using FootSnap on two separate occasions by two different operators. Reproducibility of foot images was determined using the Jaccard similarity index (JSI)., Results: High intra- and interoperator reliability was demonstrated with JSI values of 0.89-0.91 for diabetic feet and 0.93-0.94 for control feet., Conclusions: Similarly high reliability between groups indicates FootSnap is appropriate for longitudinal follow-ups in diabetic feet, with potential for monitoring pathology.

Diabetes patients display gait alterations compared to controls including a higher metabolic cost of walking. This study aimed to investigate whether differences in external moment arm (ExtMA) and effective mechanical advantage (EMA) at the ankle in diabetes patients could partly explain the increased cost of walking compared to controls. Thirty one non-diabetic controls (Ctrl); 22 diabetes 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. The internal Achilles tendon moment arm length was determined using magnetic resonance imaging during weight-bearing and ExtMA was calculated using gait analysis. A greater value (P<0.01) for the EMA at the ankle was found in the DPN (0.488) and DM (0.46) groups compared to Ctrl (0.448). The increased EMA was mainly caused by a smaller ExtMA in the DPN (9.63cm; P<0.01) and DM (10.31cm) groups compared to Ctrl (10.42cm) These findings indicate that the ankle plantarflexor muscles would need to generate lower forces to overcome the external resistance during walking compared to controls. Our findings do not explain the previously observedhigher metabolic cost of walking in the DM and DPN groups, but uncover a new mechanism through which patients with diabetes and particularly those with DPN reduce the joint moment at the ankle during walking: by applying the ground reaction force more proximally on the foot, or at an angle directed more towards the ankle, thereby increasing the EMA and reducing the ankle joint moment., (Copyright © 2017. Published by Elsevier B.V.)

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., (© 2017 Diabetes UK.)

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., (© 2016 Diabetes UK.)

Diabetes has major implications for public health, with diabetic foot ulcers (DFUs) being responsible for significant morbidity and mortality. A key factor in the development of nonhealing ulcers is infection, which often leads to the development of biofilm, gangrene, and amputation. A novel approach to treating DFUs is the local release of antibiotics from calcium sulfate beads. We have developed a novel model system to study and compare the release and efficacy of antibiotics released locally, using collagen as a substrate for biofilm growth and incorporating serum to mimic the biochemical complexity of the wound environment. We found that our soft-tissue model supports the growth of a robust Pseudomonas aeruginosa biofilm, and that this was completely eradicated by the introduction of calcium sulfate beads loaded with tobramycin or gentamicin. The model also enabled us to measure the concentration of these antibiotics at different distances from the beads and in simulated wound fluid bathing the collagen matrix. We additionally found that a multidrug-resistant Staphylococcus aureus biofilm, nonsusceptible to antibiotics, nonetheless showed an almost 1-log drop in viable counts when exposed to calcium sulfate beads combined with antibiotics. Together, these data suggest that locally applied antibiotics combined with calcium sulfate provide surprising efficacy in diabetic foot infections and offer an effective alternative approach to infection management. Our study additionally establishes our new system as a biochemically and histologically relevant model that may be used to study the effectiveness of a range of therapies locally or systemically for infected DFUs., (Copyright © 2016 Price et al.)

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., (© 2015 Diabetes UK.)

Aim: To investigate lower limb biomechanical strategy during stair walking in patients with diabetes and patients with diabetic peripheral neuropathy, a population known to exhibit lower limb muscular weakness., Methods: The peak lower limb joint moments of twenty-two patients with diabetic peripheral neuropathy and thirty-nine patients with diabetes and no neuropathy were compared during ascent and descent of a staircase to thirty-two healthy controls. Fifty-nine of the ninety-four participants also performed assessment of their maximum isokinetic ankle and knee joint moment (muscle strength) to assess the level of peak joint moments during the stair task relative to their maximal joint moment-generating capabilities (operating strengths)., Results: Both patient groups ascended and descended stairs slower than controls (p<0.05). Peak joint moments in patients with diabetic peripheral neuropathy were lower (p<0.05) at the ankle and knee during stair ascent, and knee only during stair descent compared to controls. Ankle and knee muscle strength values were lower (p<0.05) in patients with diabetic peripheral neuropathy compared to controls, and lower at knee only in patients without neuropathy. Operating strengths were higher (p<0.05) at the ankle and knee in patients with neuropathy during stair descent compared to the controls, but not during stair ascent., Conclusion: Patients with diabetic peripheral neuropathy walk slower to alter gait strategy during stair walking and account for lower-limb muscular weakness, but still exhibit heightened operating strengths during stair descent, which may impact upon fatigue and the ability to recover a safe stance following postural instability., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Muscle weakness and atrophy of the lower limbs may develop in patients with diabetes, increasing their risk of falls. The underlying basis of these abnormalities has not been fully explained. The aim of this study was to objectively quantify muscle strength and size in patients with type 2 diabetes mellitus (T2DM) in relation to the severity of neuropathy, intramuscular noncontractile tissue (IMNCT), and vitamin D deficiency., Research Design and Methods: Twenty patients with T2DM and 20 healthy control subjects were matched by age, sex, and BMI. Strength and size of knee extensor, flexor, and ankle plantar and dorsiflexor muscles were assessed in relation to the severity of diabetic sensorimotor polyneuropathy (DSPN), amount of IMNCT, and serum 25-hydroxyvitamin D (25OHD) levels., Results: Compared with control subjects, patients with T2DM had significantly reduced knee extensor strength (P = 0.003) and reduced muscle volume of both knee extensors (P = 0.045) and flexors (P = 0.019). Ankle plantar flexor strength was also significantly reduced (P = 0.001) but without a reduction in ankle plantar flexor (P = 0.23) and dorsiflexor (P = 0.45) muscle volumes. IMNCT was significantly increased in the ankle plantar (P = 0.006) and dorsiflexors (P = 0.005). Patients with DSPN had significantly less knee extensor strength than those without (P = 0.02) but showed no difference in knee extensor volume (P = 0.38) and ankle plantar flexor strength (P = 0.21) or volume (P = 0.96). In patients with <25 nmol/L versus >25 nmol/L 25OHD, no significant differences were found for knee extensor strength and volume (P = 0.32 vs. 0.18) and ankle plantar flexors (P = 0.58 vs. 0.12)., Conclusions: Patients with T2DM have a significant reduction in proximal and distal leg muscle strength and a proximal but not distal reduction in muscle volume possibly due to greater intramuscular fat accumulation in distal muscles. Proximal but not distal muscle strength is related to the severity of peripheral neuropathy but not IMNCT or 25OHD level., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

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., (Copyright © 2016 John Wiley & Sons, Ltd.)

Patients with diabetes and ankle equinus are at particularly high risk for forefoot ulceration because of the development of high forefoot pressures. Stiffness in the triceps surae muscles and tendons are thought to be largely responsible for equinus in patients with diabetes and underpins the surgical rationale for Achilles tendon lengthening (ATL) procedures to alleviate this deformity and reduce ulcer risk. The established/traditional surgical approach is the triple hemisection along the length of the Achilles tendon. Although the percutaneous approach has been successful in achieving increases in ankle dorsiflexion >30°, the tendon rupture risk has led to some surgeons looking at alternative approaches. The gastrocnemius aponeurosis may be considered as an alternative because of the Achilles tendon's poor blood supply. ATL procedures are a balance between achieving adequate tendon lengthening and minimizing tendon rupture risk during or after surgery. After ATL surgery, the first 7 days should involve reduced loading and protected range of motion to avoid rupture, after which gradual reintroduction to loading should be encouraged to increase tendon strength. In summary, there is a moderate level of evidence to support surgical intervention for ankle joint equinus in patients with diabetes and forefoot ulceration that is non-responsive to other conservative treatments. Areas of caution for ATL procedures include the risk for overcorrection, tendon rupture and the tendon's poor blood supply. Further prospective randomized control trials are required to confirm the benefits of ATL procedures over conservative care and the most optimal anatomical sites for surgical intervention., (Copyright © 2016 John Wiley & Sons, Ltd.)

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., (Copyright © 2016 the American Physiological Society.)