Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This is the first guideline on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes published by the IWGDF. We followed the GRADE Methodology to devise clinical questions in the PACO (Population, Assessment, Comparison, Outcome) and PICO (Population, Intervention, Comparison, Outcome) format, conducted a systematic review of the medical literature, and developed recommendations with the rationale. The recommendations are based on the evidence from our systematic review, expert opinion when evidence was not available, and also taking into account weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to an intervention. We here present the 2023 Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus and also suggest key future topics of research.

Diagnosis and treatment of active charcot neuro-osteoarthropathy in persons with diabetes mellitus: A systematic review.

BACKGROUND: There are uncertainties regarding the diagnostic criteria, optimal treatment methods, interventions, monitoring and determination of remission of Charcot neuro-osteoarthropathy (CNO) of the foot and ankle in people with diabetes mellitus (DM). The aims of this systematic review are to investigate the evidence for the diagnosis and subsequent treatment, to clarify the objective methods for determining remission and to evaluate the evidence for the prevention of re-activation in people with CNO, DM and intact skin. METHODS: We performed a systematic review based on clinical questions in the following categories: Diagnosis, Treatment, Identification of Remission and Prevention of Re-Activation in people with CNO, DM and intact skin. Included controlled studies were assessed for methodological quality and key data from all studies were extracted. RESULTS: We identified 37 studies for inclusion in this systematic review. Fourteen retrospective and observational studies relevant to the diagnosis of active CNO with respect to clinical examination, imaging and blood laboratory tests in patients with DM and intact skin were included. We identified 18 studies relevant to the treatment of active CNO. These studies included those focused on offloading (total contact cast, removable/non-removable knee high devices), medical treatment and surgical treatment in the setting of active CNO. Five observational studies were identified regarding the identification of remission in patients who had been treated for active CNO. We did not identify any studies that met our inclusion criteria for the prevention of re-activation in patients with DM and intact skin who had been previously treated for active CNO and were in remission. CONCLUSIONS: There is a paucity of high-quality data on the diagnosis, treatment, and prognosis of active CNO in people with DM and intact skin. Further research is warranted to address the issues surrounding this complex disease.

Achilles tendon assessment on quantitative MRI: Sources of variability and relationships to tendinopathy.

Quantitative MRI (qMRI) measures are useful in assessing musculoskeletal tissues, but application to tendon has been limited. The purposes of this study were to optimize, identify sources of variability, and establish reproducibility of qMRI to assess Achilles tendon. Additionally, preliminarily estimates of effect of tendon pathology on qMRI metrics and structure-function relationships between qMRI measures and ankle performance were examined. T1, T1ρ, T2, and T2* maps of the Achilles tendon were obtained using a 3T MRI scanner. In participants with asymptomatic tendons (n = 21), MRI procedures were repeated twice, and region of interest selection was performed by three raters. Variance decomposition and reproducibility statistics were completed. To estimate the effect of pathology, qMRI measures from individuals with asymptomatic tendons were compared to qMRI measures from a pilot group of individuals with Achilles tendinopathy (n = 7). Relationships between qMRI and ankle performance measures were assessed. Between-participant variation accounted for the majority of variability (46.7%-64.0%) in all qMRI measures except T2*. ICCs met or exceeded 0.7 for all qMRI measures when averaged across raters or scans. Relaxation times were significantly longer in tendinopathic tendons (mean (SD) T1: 977.8 (208.6) ms, T1ρ: 35.4 (7.1) ms, T2: 42.8 (7.9) ms, T2*: 14.1 (7.6) ms, n = 7) compared to asymptomatic control tendons (T1: 691.7 (32.4) ms, T1ρ: 24.0 (3.6) ms, T2: 24.4 (7.5) ms, T2*: 9.5 (3.4) ms, n = 21) (p < 0.011 for all comparisons). T1 related to functional performance measures in symptomatic and asymptomatic groups. Study findings suggest that qMRI is reliable to assess the Achilles tendon. qMRI quantitatively assesses the presence of tendon pathology and relates to functional performance outcomes, supporting the utility of incorporating qMRI in research and clinic.

Quantitative Assessment of Peripheral Oxidative Metabolism With a New Dynamic 1 H MRI Technique: A Pilot Study in People With and Without Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is linked to impaired mitochondrial function. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a gadolinium-contrast-free 1 H method to assess mitochondrial function by measuring low-concentration metabolites. A CEST MRI-based technique may serve as a non-invasive proxy for assessing mitochondrial health. HYPOTHESIS: A 1 H CEST MRI technique may detect significant differences in in vivo skeletal muscle phosphocreatine (SMPCr) kinetics between healthy volunteers and T2DM patients undergoing standardized isometric exercise. STUDY TYPE: Cross-sectional study. SUBJECTS: Seven subjects without T2DM (T2DM-) and seven age, sex, and BMI-matched subjects with T2DM (T2DM+). FIELD STRENGTH/SEQUENCE: Single-shot rapid acquisition with refocusing echoes (RARE) and single-shot gradient-echo sequences, 3 T. ASSESSMENT: Subjects underwent a rest-exercise-recovery imaging protocol to dynamically acquire SMPCr maps in calf musculature. Medial gastrocnemius (MG) and soleus SMPCr concentrations were plotted over time, and SMPCr recovery time, τ $$ \tau $$ , was determined. Mitochondrial function index was calculated as the ratio of resting SMPCr to τ $$ \tau $$ . Participants underwent a second exercise protocol for imaging of skeletal muscle blood flow (SMBF), and its association with SMPCr was assessed. STATISTICAL TESTS: Unpaired t-tests and Pearson correlation coefficient. A P value <0.05 was considered statistically significant. RESULTS: SMPCr concentrations in MG and soleus displayed expected declines during exercise and returns to baseline during recovery. τ $$ \tau $$ was significantly longer in the T2DM+ cohort (MG 83.5 ± 25.8 vs. 54.0 ± 21.1, soleus 90.5 ± 18.9 vs. 51.2 ± 14.5). The mitochondrial function index in the soleus was significantly lower in the T2DM+ cohort (0.33 ± 0.08 vs. 0.66 ± 0.19). SMBF was moderately correlated with the SMPCr in T2DM-; this correlation was not significant in T2DM+ (r = -0.23, P = 0.269). CONCLUSION: The CEST MRI method is feasible for quantifying SMPCr in peripheral muscle tissue. T2DM+ individuals had significantly lower oxidative capacities than T2DM- individuals. In T2DM, skeletal muscle metabolism appeared to be decoupled from perfusion. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Regional skeletal muscle perfusion distribution in diabetic feet may differentiate short-term healed foot ulcers from non-healed ulcers.

OBJECTIVES: The purpose of this study was to leverage a magnetic resonance imaging (MRI) approach to characterize foot perfusion distribution in patients with diabetes, with or without foot ulcers, and determine the ability of the regional perfusion measurements to identify ulcer-healing status. METHODS: Three groups of participants (n = 15 / group) were recruited: controls (without diabetes), type II diabetes, and type II diabetes with foot ulcers. All participants underwent MRI evaluating foot perfusion in three muscle layers (from plantar to dorsal) at rest and during a standardized toe-flexion exercise. The exercise perfusion and perfusion reserve values were analyzed around and away from ulcers. Participants with foot ulcers were followed up 3 months after the MRI exams to determine the foot healing status. RESULTS: Foot plantar muscle perfusion reserves were progressively lower from controls to diabetes, and to diabetes with foot ulcers (e.g., 2.58 ± 0.67, 1.48 ± 0.71, 1.12 ± 0.35, p < 0.001). In controls, the plantar layer had significantly higher perfusion reserve than the dorsal layer, whereas in either diabetes group, there was no significant difference in perfusion reserve among muscle layers. Using the ratio of total exercise perfusion around ulcers to that away from ulcers, the sensitivity and specificity to differentiate healing from non-healed ulcers were 100% and 86%, respectively. CONCLUSIONS: Our study reveals significantly different foot perfusion distribution among controls, diabetes, and diabetes with foot ulcers. The prognostic value of MRI regional perfusion assessments has the potential to monitor interventions to improve ulcer healing outcomes. KEY POINTS: • Contrast-free MRI permits quantitative assessment of regional foot muscle perfusion at rest and during isometric exercise. • Patients with diabetes and foot ulcers, without clinical evidence of peripheral arterial disease, had significantly impaired foot muscle perfusion and perfusion reserve. • Regional foot perfusion distribution may be used to predict the short-term healing status of foot ulcers in diabetes.

Computed Tomography and Magnetic Resonance Correlation and Agreement for Foot Muscle and Adipose Tissue Measurements.

BACKGROUND: Volumetric measures of intrinsic foot muscle and intermuscular adipose tissue (IMAT) infiltration are important in understanding foot injury and disease. We questioned whether measures of muscle and fat derived from computed tomography (CT) and magnetic resonance (MR) would be comparable. METHODS: This study determined the correlation and level of agreement between CT and MR measurements of foot muscle and IMAT from 32 subjects with diabetes and peripheral neuropathy. Volumetric CT and DIXON 3T MR scans were obtained. Intermuscular adipose tissue and muscle volumes used to create the IMAT to muscle ratio were obtained by segmenting the forefoot muscle compartment from each modality. RESULTS: Computed tomography IMAT ratios were significantly correlated (r = 0.85, P < 0.0001) with MR IMAT ratios. Computed tomography and MR IMAT ratio mean difference between CT and MR was small (0.044 unit, Bland-Altman plots). CONCLUSIONS: The CT and MR IMAT ratio measurements were highly correlated, indicating both modalities represent tissue quantification similarly.Level of Evidence: 2Technical Efficacy: 1.

Pilot study of contrast-free MRI reveals significantly impaired calf skeletal muscle perfusion in diabetes with incompressible peripheral arteries.

Patients with diabetes mellitus (DM) are more likely to have densely calcified lesions in the below-the-knee tibial arteries. However, the relationship between peripheral arterial calcification and local skeletal muscle perfusion has not been explored. Thirty subjects were prospectively recruited into three groups in this pilot study: (1) Non-DM: 10 people without DM; (2) DM, ABI < 1.3: 10 people with DM and normal ankle-brachial index (ABI) (0.9-1.3); and (3) DM, ABI ⩾ 1.3: 10 people with DM and ABI ⩾ 1.3. All subjects underwent calf perfusion measurements at rest and during an isometric plantarflexion contraction exercise within the magnetic resonance imaging (MRI) system. The noncontrast MRI techniques were applied to quantitatively assess skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in medial gastrocnemius and soleus muscles. Both SMBF and SMOEF reserves were calculated as the ratio of the exercise value to the resting value. Exercise SMBF and SMOEF values in the medial gastrocnemius muscle were lower in the two DM groups than in the non-DM group (p < 0.05). The SMBF reserve in medial gastrocnemius was significantly lower in the DM, ABI ⩾ 1.3 group compared to the DM, ABI < 1.3 group (p < 0.05). This study demonstrates that people with DM and calcified arteries had lower perfusion in gastrocnemius muscle compared to those without DM and those with DM and a normal ABI.

Static Ankle Dorsiflexion and Hip and Pelvis Kinematics During Forward Step-Down in Patients With Hip-Related Groin Pain.

CONTEXT: The authors hypothesized that in people with hip-related groin pain, less static ankle dorsiflexion could lead to compensatory hip adduction and contralateral pelvic drop during step-down. Ankle dorsiflexion may be a modifiable factor to improve ability in those with hip-related groin pain to decrease hip/pelvic motion during functional tasks and improve function. OBJECTIVE: To determine whether smaller static ankle dorsiflexion angles were associated with altered ankle, hip, and pelvis kinematics during step-down in people with hip-related groin pain. DESIGN: Cross-sectional Setting: Academic medical center. PATIENTS: A total of 30 people with hip-related groin pain (12 males and 18 females; 28.7 [5.3] y) participated. INTERVENTION: None. MAIN OUTCOME MEASURES: Weight-bearing static ankle dorsiflexion with knee flexed and knee extended were measured via digital inclinometer. Pelvis, hip, and ankle kinematics during forward step-down were measured via 3D motion capture. Static ankle dorsiflexion and kinematics were compared with bivariate correlations. RESULTS: Smaller static ankle dorsiflexion angles were associated with smaller ankle dorsiflexion angles during the step-down for both the knee flexed and knee extended static measures. Among the total sample, smaller static ankle dorsiflexion angle with knee flexed was associated with greater anterior pelvic tilt and greater contralateral pelvic drop during the step-down. Among only those who did not require a lowered step for safety, smaller static ankle dorsiflexion angles with knee flexed and knee extended were associated with greater anterior pelvic tilt, greater contralateral pelvic drop, and greater hip flexion. CONCLUSIONS: Among those with hip-related groin pain, smaller static ankle dorsiflexion angles are associated with less ankle dorsiflexion motion and altered pelvis and hip kinematics during a step-down. Future research is needed to assess the effect of treating restricted ankle dorsiflexion on quality of motion and symptoms in patients with hip-related groin pain.

Diffusion Tensor Imaging of the Calf Muscles in Subjects With and Without Diabetes Mellitus.

BACKGROUND: Diffusion tensor imaging (DTI) has been used to characterize calf skeletal muscle architecture. PURPOSE: To assess the diffusional properties of the calf muscles of subjects with and without diabetes, at rest and during isometric plantarflexion exercise. STUDY TYPE: Prospective. SUBJECTS: Twenty-six subjects in two groups: 13 healthy and 13 subjects with type 2 diabetes (DM); each group consisted of seven females and six males. FIELD STRENGTH/SEQUENCE: 3T/2D single-shot spin echo planar imaging. ASSESSMENT: Fractional anisotropy (FA), mean diffusivity (MD), diffusion eigenvalues, and fiber tracking indices were obtained from the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL) muscles of the calf at rest and during isometric plantarflexion exercise. STATISTICAL TESTS: We used a combination of nonparametric (Wilcoxon) and parametric (t-test) statistical assessments. RESULTS: The medial gastrocnemius muscle had more indices with significant differences between the two groups (six indices with P < 0.05) than did the lateral gastrocnemius (three indices with P < 0.05) and soleus muscles (only one index with P < 0.05). While the healthy group showed elevated MD values from rest to exercise (MG = 5.83%, LG = 13.45%, and SOL = 11.68%), the diabetic MD showed higher increases (MG = 19.74%, LG = 29.31%, and SOL = 20.84%) that were different between groups (MG: P = 0.009, LG: P = 0.037, and SOL: P = 0.049). DATA CONCLUSION: Our results indicate considerable diffusional changes between healthy subjects and subjects with diabetes at rest and during isometric plantarflexion exercise in the calf muscles. The medial gastrocnemius muscle displayed the most diffusion sensitivity to diabetes-related microstructural changes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1285-1295.

Intravenous contrast-free standardized exercise perfusion imaging in diabetic feet with ulcers.

BACKGROUND: Impaired foot perfusion is a primary contributor to foot ulcer formation. There is no existing device nor method that can be used to measure local foot perfusion during standardized foot muscle exercise in an MRI environment. PURPOSE: To develop a new MRI-compatible foot dynamometer and MRI methods to characterize local perfusion in diabetic feet with ulcers. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Seven participants without diabetes and 10 participants with diabetic foot ulcers. FIELD STRENGTH/SEQUENCE: 3.0T, arterial spin labeling (ASL). ASSESSMENTS: Using a new MRI-compatible foot dynamometer, all participants underwent MRI ASL perfusion assessment at rest and during a standardized toe-flexion exercise. The participants without diabetes were scanned twice to assess the reproducibility of perfusion measurements. The absolute perfusion and perfusion reserve values were compared between two groups and between regions near ulcers (peri-ulcer) and away from ulcers (away-ulcer). STATISTICAL TESTS: Bland-Altman methods for the calculation of coefficient of repeatability (CR) and two-sided and unpaired Student's t-test to compare multiple differences. RESULTS: The perfusion reserves measured had the best reproducibility (CR in medial region: 1.6, lateral region: 0.9). The foot perfusion reserve was significantly lower in the participants with diabetes compared with the participants without diabetes (1.34 ± 0.32, 95% confidence interval [CI]: 1.1, 1.58 vs. 1.76 ± 0.31, 95% CI: 1.53, 1.98, P = 0.02). Both peri-ulcer exercise perfusion (8.7 ± 3.9 ml/min/100g) and perfusion reserve (1.07 ± 0.39, 95% CI: 0.78, 1.35) were significantly lower than away-ulcer exercise perfusion (12.7 ± 3.8 ml/min/100g, P = 0.02) and perfusion reserve (1.39 ± 0.37, 95% CI: 1.11, 1.66, P = 0.03), respectively. DATA CONCLUSION: This study demonstrates intravenous contrast-free methods for local perfusion in feet with ulcers by standardized exercise-based MRI. Ischemia regions around foot ulcers can be quantitatively distinguished from normal perfused muscle regions. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:474-480.

Oximetric angiosome imaging in diabetic feet.

PURPOSE: To develop a noncontrast oximetric angiosome imaging approach to assess skeletal muscle oxygenation in diabetic feet. MATERIALS AND METHODS: In four healthy and five subjects with diabetes, the feasibility of foot oximetry was examined using a 3T clinical magnetic resonance imaging (MRI) scanner. The subjects' feet were scanned at rest and during a toe-flexion isometric exercise. The oxygen extraction fraction of skeletal muscle was measured using a susceptibility-based MRI method. Our newly developed MR foot oximetric angiosome model was compared with the traditional angiosome model in the assessment of the distribution of oxygen extraction fraction. RESULTS: Using the traditional angiosome during the toe-flexion exercise, the oxygen extraction fraction in the medial foot of healthy subjects increased (4.9 ± 3%) and decreased (-2.7 ± 4.4%) in subjects with diabetes (difference = 7.6%; 95% confidence interval = -13.7 ± 1.4; P = 0.02). Using the oximetric angiosome, the percent difference in the areas of oxygen extraction fraction within the 0.7-1.0 range (expected oxygen extraction fraction during exercise) between rest and exercise was higher in healthy subjects (8 ± 4%) than in subjects with diabetes (4 ± 4%; P = 0.02). CONCLUSION: This study demonstrates the feasibility of measuring skeletal muscle oxygen extraction fraction in the foot muscle during a toe-flexion isometric exercise. Instead of assessing oxygen extraction fraction in a foot muscle region linked to a supplying artery (traditional angiosome), the foot oximetric angiosome model assesses oxygen extraction fraction by its different levels in all foot muscle regions and thus may be more appropriate for assessing local ischemia in ulcerated diabetic feet. J. Magn. Reson. Imaging 2016. J. MAGN. RESON. IMAGING 2016;44:940-946.

A Case of a Methicillin-Resistant Staphylococcus Aureus Retropharyngeal Abscess With Mediastinal Extension in an 11-Month-Old Girl.

We present the case of an 11-month-old girl with Mycoplasma pneumoniae-associated pneumonia who was subsequently diagnosed with a methicillin-resistant Staphylococcus aureus retropharyngeal abscess with mediastinal extension.

Non-contrast MRI perfusion angiosome in diabetic feet.

OBJECTIVE: The purpose of this study is to develop a non-contrast magnetic resonance imaging (MRI) approach to evaluate skeletal muscle perfusion in the diabetic foot based on the concept of angiosomes of the foot. METHODS: Five healthy volunteers and five participants with diabetes (HbA1c = 7.2 ± 1.8%) without a history of peripheral artery disease were examined. The non-contrast perfusion measurements were performed during a toe flexion challenge. Absolute perfusion maps were created and two regions (medial and lateral) on the maps were segmented based on angiosomes. RESULT: Regional difference in the perfusion of foot muscle was readily visualized in the MRI perfusion angiosomes during the challenge. In the participants with diabetes, the perfusion during toe flexion challenge was significantly lower than in healthy volunteers (P < 0.01). The average perfusion for the medial plantar region of the right foot was lower in subjects with diabetes (38 ± 9 ml/min/100 g) than in healthy subjects (93 ± 33 ml/min/100 g). CONCLUSIONS: Non-contrast MRI perfusion angiosome maps demonstrate the feasibility of determining regional perfusion in foot muscles during toe challenge and may facilitate evaluation of muscle perfusion in diabetic feet. KEY POINTS: • Non-contrast MRI perfusion angiosome maps measure regional perfusion in foot muscles non-invasively. • Foot perfusion response to challenge is reduced in persons with diabetes. • MRI perfusion angiosome maps may help evaluation of regional foot muscle perfusion.

Use of computed tomography to identify muscle quality subgroups, spatial mapping, and preliminary relationships to function in those with diabetic peripheral neuropathy.

BACKGROUND: Decreased muscle volume and increased muscle-associated adipose tissue (MAAT, sum of intra and inter-muscular adipose tissue) of the foot intrinsic muscle compartment are associated with deformity, decreased function, and increased risk of ulceration and amputation in those with diabetic peripheral neuropathy (DPN). RESEARCH QUESTION: What is the muscle quality (normal, abnormal muscle, and adipose volumes) of the DPN foot intrinsic compartment, how does it change over time, and is muscle quality related to gait and foot function? METHODS: Computed tomography was performed on the intrinsic foot muscle compartment of 45 subjects with DPN (mean age: 67.2 ± 6.4 years) at baseline and 3.6 years. Images were processed to obtain volumes of MAAT, highly abnormal, mildly abnormal, and normal muscle. For each category, annual rates of change were calculated. Paired t-tests compared baseline and follow-up. Foot function during gait was assessed using 3D motion analysis and the Foot and Ankle Ability Measure. Correlations between muscle compartment and foot function during gait were analyzed using Pearson's correlations. RESULTS: Total muscle volume decreased, driven by a loss of normal muscle and mildly abnormal muscle (p<0.05). MAAT and the adipose-muscle ratio increased. At baseline, 51.5% of the compartment was abnormal muscle or MAAT, increasing to 55.0% at follow-up. Decreased total muscle volume correlated with greater midfoot collapse during gait (r = -0.40, p = 0.02). Greater volumes of highly abnormal muscle correlated with a lower FAAM score (r = -0.33, p = 0.03). SIGNIFICANCE: Muscle volume loss may progress in parallel with MAAT accumulation, impacting contractile performance in individuals with DPN. Only 48.5% of the DPN intrinsic foot muscle compartment consists of normal muscle and greater abnormal muscle is associated with worse foot function. These changes identify an important target for rehabilitative intervention to slow or prevent muscle deterioration and poor foot outcomes.

Reliability and validity of a MR-based volumetric analysis of the intrinsic foot muscles.

PURPOSE: To describe a semi-automated program that will segment subcutaneous fat, muscle, and adipose tissue in the foot using MR imaging, determine the reliability of the program between and within raters, and determine the validity of the program using MR phantoms. MATERIALS AND METHODS: MR images were acquired from 19 subjects with and without diabetes and peripheral neuropathy. Two raters segmented and measured volumes from single MR slices at the forefoot, midfoot, and hindfoot at two different times. Intra- and inter-rater correlation coefficients were determined. Muscle and fat MR phantoms of known volumes were measured by the program. RESULTS: Most ICC reliability values were over 0.950. Validity estimates comparing MR estimates and known volumes resulted in r(2) values above 0.970 for all phantoms. The root mean square error was less than 5% for all phantoms. CONCLUSION: Subcutaneous fat, lean muscle, and adipose tissue volumes in the foot can be quantified in a reliable and valid way. This program can be applied in future studies investigating the relationship of these foot structures to functions in important pathologies, including the neuropathic foot or other musculoskeletal problems.

Weight-bearing versus nonweight-bearing exercise for persons with diabetes and peripheral neuropathy: a randomized controlled trial.

OBJECTIVE: To determine the effects of weight-bearing (WB) versus nonweight-bearing (NWB) exercise for persons with diabetes mellitus (DM) and peripheral neuropathy (PN). DESIGN: Randomized controlled trial with evaluations at baseline and after intervention. SETTING: University-based physical therapy research clinic. PARTICIPANTS: Participants with DM and PN (N=29) (mean age ± SD, 64.5±12.5y; mean body mass index [kg/m(2)] ± SD, 35.5±7.3) were randomly assigned to WB (n=15) and NWB (n=14) exercise groups. All participants (100%) completed the intervention and follow-up evaluations. INTERVENTIONS: Group-specific progressive balance, flexibility, strengthening, and aerobic exercise conducted sitting or lying (NWB) or standing and walking (WB) occurred 3 times a week for 12 weeks. MAIN OUTCOME MEASURES: Measures included the 6-minute walk distance (6MWD) and daily step counts. Secondary outcome measures represented domains across the International Classification of Functioning, Disability and Health. RESULTS: The WB group showed greater gains than the NWB group over time on the 6MWD and average daily step count (P<.05). The mean and 95% confidence intervals (CIs) between-group difference over time was 29m (95% CI, 6-51) for the 6MWD and 1178 (95% CI, 150-2205) steps for the average daily step count. The NWB group showed greater improvements than the WB group over time in hemoglobin A1c values (P<.05). CONCLUSIONS: The results of this study indicate the ability of this population with chronic disease to increase 6MWD and daily step count with a WB exercise program compared with an NWB exercise program.

Remote Research: Resources, Intervention Needs, and Methods in People with Diabetes and Peripheral Neuropathy.

BACKGROUND: Stay-at-home orders associated with the SARS-CoV-2 (COVID-19) pandemic were particularly important for older adults with type 2 diabetes, at risk for severe COVID-19 complications. In response, research shifted to remote telehealth methodology. Study participant interests, equipment needs, and ability to adapt methods to the remote/telehealth environment were unknown. Study purposes to assess (1) resource needs (internet/devices accessibility), (2) future telehealth interests, and (3) ability to adapt common research and clinical measures of glycemic control, physical function, activity measures, and quality of life outcomes to a telehealth setting. METHOD: Twenty-one participants with type 2 diabetes and peripheral neuropathy were recruited from a longitudinal study (11 female; age: 66.3 ± 8.3 years; DM: 15.1 ± 8.7 years). Technology needs and future telehealth interests were assessed. A glycemic measure (HbA1c), a five-times chair rise, a one-week activity monitor, and surveys (self-efficacy, depression, and balance) were collected. All aspects of the study were completed remotely over email and video/phone call. RESULTS: Twelve participants used computers; nine used phones for study completion. Participants had the following resource needs: connectivity (n = 3), devices (n = 6), and technical support (n = 12). Twenty people expressed interest in participating in future telehealth studies related to balance, exercise, and diabetes management. Methodological considerations were primarily the need for assistance for participants to complete the home HbA1c test, five-time chair rise, wearable activity monitoring, and surveys. CONCLUSIONS: Older adults with type 2 diabetes and peripheral neuropathy would need technological and personal assistance (connection, device, guidance) to complete a long-term telehealth intervention. Despite technology needs, participants were interested in telehealth interventions. CLINICAL TRIAL: Parent study, "Metatarsal Phalangeal Joint Deformity Progression-R01 (NCT02616263) is registered at https://clinicaltrials.gov/.

Quantative MRI predicts tendon mechanical behavior, collagen composition, and organization.

Quantitative magnetic resonance imaging (qMRI) measures have provided insights into the composition, quality, and structure-function of musculoskeletal tissues. Low signal-to-noise ratio has limited application to tendon. Advances in scanning sequences and sample positioning have improved signal from tendon allowing for evaluation of structure and function. The purpose of this study was to elucidate relationships between tendon qMRI metrics (T1, T2, T1ρ and diffusion tensor imaging [DTI] metrics) with tendon tissue mechanics, collagen concentration and organization. Sixteen human Achilles tendon specimens were collected, imaged with qMRI, and subjected to mechanical testing with quantitative polarized light imaging. T2 values were related to tendon mechanics [peak stress (rsp = 0.51, p = 0.044), equilibrium stress (rsp = 0.54, p = 0.033), percent relaxation (rsp = -0.55, p = 0.027), hysteresis (rsp = -0.64, p = 0.007), linear modulus (rsp = 0.67, p = 0.009)]. T1ρ had a statistically significant relationship with percent relaxation (r = 0.50, p = 0.048). Collagen content was significantly related to DTI measures (range of r = 0.56-0.62). T2 values from a single slice of the midportion of human Achilles tendons were strongest predictors of tendon tensile mechanical metrics. DTI diffusivity indices (mean diffusivity, axial diffusivity, radial diffusivity) were strongly correlated with collagen content. These findings build on a growing body of literature supporting the feasibility of qMRI to characterize tendon tissue and noninvasively measure tendon structure and function. Statement of Clinical Significance: Quantitative MRI can be applied to characterize tendon tissue and is a noninvasive measure that relates to tendon composition and mechanical behavior.

Rate of tarsal and metatarsal bone mineral density change in adults with diabetes mellitus and peripheral neuropathy: a longitudinal study.

BACKGROUND: In people with diabetes (DM) and peripheral neuropathy (PN), loss of bone mineral density (BMD) in the tarsals and metatarsals contribute to foot complications; however, changes in BMD of the calcaneal bone is most commonly reported. This study reports rate of change in BMD of all the individual bones in the foot, in participants with DM and PN. Our aim was to investigate whether the rate of BMD change is similar across all the bones of the foot. METHODS: Participants with DM and PN (n = 60) were included in this longitudinal cohort study. Rate of BMD change of individual bones was monitored using computed tomography at baseline and 6 months, 18 months, and 3-4 years from baseline. Personal factors (age, sex, medication use, step count, sedentary time, and PN severity) were assessed. A random coefficient model estimated rate of change of BMD in all bones and Pearson correlation tested relationships between personal factor variables and rate of BMD change. RESULTS: Mean and calcaneal BMD decreased over the study period (p < 0.05). Individual tarsal and metatarsal bones present a range of rate of BMD change (-0.3 to -0.9%/year) but were not significantly different than calcaneal BMD change. Only age showed significant correlation with BMD and rate of BMD change. CONCLUSION: The rate of BMD change did not significantly differ across different foot bones at the group level in people with DM and PN without foot deformity. Asymmetric BMD loss between individual bones of the foot and aging may be indicators of pathologic changes and require further investigation. TRIAL REGISTRATION: Metatarsal Phalangeal Joint Deformity Progression-R01. Registered 25 November 2015, https://clinicaltrials.gov/ct2/show/NCT02616263.

Botulinum toxin effects on gasatrocnemius strength and plantar pressure in diabetics with peripheral neuropathy and forefoot ulceration.

BACKGROUND: High forefoot plantar pressure is associated with plantar ulcers in people with diabetes and peripheral neuropathy. The purpose of this pilot study was to determine the safety and efficacy of botulinum toxin A injected into the gastrocnemius-soleus muscles to reduce muscle strength and plantar pressure. METHODS: This double blind, randomized clinical trial studied 17 people with diabetes mellitus, peripheral neuropathy and a forefoot plantar ulcer. Subjects were randomized into one of three groups receiving gastrocnemius-soleus muscle injections on the involved side with; 1) Saline (n = 5, weight =99± 21 kg), 2) 200-units of Botox® (n = 7, weight = 101± 5 kg), or 3) 300-units of Botox® (n = 5, weight = 129± 22 kg). Botox® dose was converted to units/kg, the majority received between 1.9 and 2.4 units/kg (n = 11) and one 3.2 units/kg. Plantarflexor peak torque and forefoot peak plantar pressure were quantified prior and 2 weeks post-injection. RESULTS: There were no complications from the injections. Plantarflexor peak torque on the involved side increased in the placebo and 300 groups (3± 4 Nm and 6± 10 Nm, respectively) and decreased -8± 11 Nm in the 200 group. There was no relationship between units/kg of Botox® for each subject and change in plantarflexor peak torque. Forefoot peak plantar pressure did not change in the placebo and 300 groups (0± 11 and 0± 5 N/cm(2), respectively) and decreased -4± 16 N/cm2 (4%) for the 200 group. CONCLUSION: There were no adverse events associated with the Botox® injections. This study was unable to determine the dose to consistently reduce plantarflexor strength and forefoot plantar pressure. Additional research is needed to investigate diabetes mellitus specific physiological changes and their impact of BoNT-A effectiveness in order to guide appropriate dosing.