Review and Evaluation of European National Clinical Practice Guidelines for the Treatment and Management of Active Charcot Neuro-Osteoarthropathy in Diabetes Using the AGREE-II Tool Identifies an Absence of Evidence-Based Recommendations.

Charcot neuro-osteoarthropathy (CNO) is a rare but devastating complication of diabetes associated with high rates of morbidity; yet, many nonfoot specialists are unaware of it, resulting in missed and delayed diagnosis. Clinical practice guidelines (CPGs) have proven useful in improving quality of care and standardizing practice in diabetes and diabetic foot care. However, little is known about the consistency in recommendations for identification and management of active CNO.

Infrared Thermography Shows That a Temperature Difference of 2.2°C (4°F) or Greater Between Corresponding Sites of Neuropathic Feet Does Not Always Lead to a Diabetic Foot Ulcer.

Background: There is emerging interest in the application of foot temperature monitoring as means of diabetic foot ulcer (DFU) prevention. However, the variability in temperature readings of neuropathic feet remains unknown. The aim of this study was to analyze the long-term consistency of foot thermograms of diabetic feet at the risk of DFU.

Grading Fractures on Foot and Ankle X-rays and MRI Scans in the Active Charcot Foot in Diabetes: How Strong Is the Agreement Between Modalities?

Objective: To compare X-ray and MRI as diagnostic tests of active Charcot neuro-osteoarthropathy (CNO) in diabetes.

Research Design And Methods: X-rays and MRI scans of 48 participants were rated for severity of fracture (0 = no fracture, 1 = fracture, 2 = collapse/fragmentation), and for absence/presence of bone marrow edema (BME) on MRI and absence/presence of bone injury on X-ray. The agreement between modalities was assessed with tests for symmetry, marginal homogeneity, and κ-coefficients.

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.

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.

Onset of an Active Charcot Foot in a Person with Longstanding Type 1 Diabetes and Normal Vibration Perception Threshold-A Case Report.

Charcot neuro-osteoarthropathy (CNO), or Charcot foot, is a disabling complication of diabetes, which is poorly understood and frequently overlooked. We describe an atypical presentation of an active Charcot foot in a woman with a long-standing type 1 diabetes who did not exhibit loss of protective sensation (sensate to a 10-gram monofilament) or loss of vibration sensation. These standard measures of large nerve fibre function ruled out "classical" neuropathy.

People living with diabetes are unaware of their foot risk status or why they are referred to a multidisciplinary foot team.

Aim: People with active diabetic foot disease should be rapidly referred by health professionals along a pathway of care to a multidisciplinary foot team. The aim was to investigate patients' self-reported understanding of their foot risk status and reasons for their referral to a multidisciplinary foot team.

Method: This seven-month service evaluation included consecutive newly referred patients.

Effect of Recombinant Human Parathyroid Hormone (1-84) on Resolution of Active Charcot Neuro-osteoarthropathy in Diabetes: A Randomized, Double-Blind, Placebo-Controlled Study.

Objective: Fractures in Charcot neuro-osteoarthropathy (CN) often fail to heal despite prolonged immobilization with below-knee casting. The aim of the study was to assess the efficacy of recombinant human parathyroid hormone (PTH) in reducing time to resolution of CN and healing of fractures.

Research Design And Methods: People with diabetes and acute (active) Charcot foot were randomized (double-blind) to either full-length PTH (1-84) or placebo therapy, both in addition to below-knee casting and calcium and vitamin D3 supplementation.

Stage 0 Charcot Neuroarthropathy in the Diabetic Foot: An Emerging Narrow Window of Opportunity?

In a world where popular culture and concepts can become the norm without all the rigors of normal scrutiny, our attention is focused on identifying Charcot neuroarthropathy (CN) at a stage before radiological bone destruction occurs. The rationale is that early recognition can prevent a destructive chain of events and thus potentially reduce the burden to patients and health care providers. In this article, we describe the evolution of stage 0 CN, and the use of modern imaging in characterizing the abnormalities recognized by these modalities and how they aid our understanding and supplement our knowledge.

The Role of Bone Scintigraphy with SPECT/CT in the Characterization and Early Diagnosis of Stage 0 Charcot Neuroarthropathy.

We describe the use of Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) in the investigation and diagnosis of Charcot neuroarthropathy (CN) in patients with a hot swollen foot but normal radiographs and clinical suspicion of CN, usually termed Stage 0. This was a retrospective cohort review of 46 diabetes patients who underwent 3 phase bone scintigraphy with "High Resolution" SPECT/CT. The imaging demonstrated that Stage 0 Charcot foot has a distinct bone pathology, which can be classified into three groups: (1) fractures on Computed Tomography (CT) with accompanying focal uptake of tracer on SPECT, (2) bony abnormalities apart from fracture on CT with focal uptake of tracer on SPECT, and (3) normal CT but focal bony uptake of tracer on SPECT.

Between visit variability of thermal imaging of feet in people attending podiatric clinics with diabetic neuropathy at high risk of developing foot ulcers.

Objective: People with diabetic neuropathy who have previously ulcerated are at high risk of re-ulceration. They should regularly attend podiatry clinics for surveillance and routine protective podiatric treatment. It has been suggested that inflammation prior to skin breakdown shows up as a hotspot on a thermal image even in the absence of clinical signs.

Thermal symmetry of healthy feet: a precursor to a thermal study of diabetic feet prior to skin breakdown.

Early identification of areas of inflammation may aid prevention of diabetic foot ulcers. A new bespoke thermal camera system has been developed to thermally image feet at risk. Hotspots (areas at least 2.

Conservative and Pharmacologic Treatments for the Diabetic Charcot Foot.

Charcot neuroarthropathy is a disabling complication of diabetic neuropathy. Prolonged immobilization in a total contact cast (TCC) is among the main treatments. Education of health care professionals in the application of TCC together with well-conducted clinical trials are required to overcome its frequent underuse.

Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy.

We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α).

Novel use of a Dektak 150 surface profiler unmasks differences in resorption pit profiles between control and Charcot patient osteoclasts.

We hypothesized that newly formed osteoclasts from patients with acute Charcot osteoarthropathy can resorb surfaces of bone more extensively compared with controls. Peripheral blood monocytes, isolated from eight Charcot patients and nine controls, were cultured in vitro on 24-well plates and bovine bone discs in duplicate with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κβ ligand (RANKL). Osteoclast formation was assessed by tartrate-resistant acid phosphatase staining (TRAcP) at day 17.

A prospective study of calcaneal bone mineral density in acute Charcot osteoarthropathy.

Objective: To measure prospectively bone mineral density (BMD) of the Charcot and non-Charcot foot in 36 diabetic patients presenting with acute Charcot osteoarthropathy.

Research Design And Methods: Calcaneal BMD was measured with quantitative ultrasound at presentation, at 3 months of casting, and at the time of the clinical resolution.

Results: BMD of the Charcot foot was significantly reduced compared with BMD of the non-Charcot foot at presentation (P = 0.

Emerging drugs for diabetic foot ulcers.

Diabetic foot ulceration results from factors extrinsic to the foot such as repeated trauma, ischaemia and infection, as well as intrinsic factors that lead to impairment of wound healing. Intrinsic factors are less well understood, but include deficiency of growth factors, changes in extracellular matrix components with excess proteases, reduced fibroblast activity, cellular abnormalities, deficiencies of angiogenesis, nitric oxide abnormalities and hyperglycaemia. The scientific rationale of therapy is to correct both the external factors that cause diabetic foot ulcers and the internal factors that lead to impairment of wound healing.

Dimerization of Rhizobium meliloti NifH protein in Saccharomyces cerevisiae cells requires simultaneous expression of NifM protein.

Compared to free living diazotrophs, the nitrogenase system of symbiotic microorganisms, like Rhizobium (Synorhizobium) meliloti, was poorly studied. The aim of our research was to investigate whether (by analogy with Klebsiella pneumoniae) the NifM product is required and sufficient to obtain active R. meliloti Fe-protein.