UNASSIGNED: The revolution of orthopedic implant manufacturing is being driven by 3D printing of titanium implants for large bony defects such as those caused by diabetic Charcot arthropathy. Unlike traditional subtractive manufacturing of orthopedic implants, 3D printing fuses titanium powder layer-by-layer, creating a unique surface roughness that could potentially enhance osseointegration. However, the metabolic impairments caused by diabetes, including negative alterations of bone metabolism, can lead to nonunion and decreased osseointegration with traditionally manufactured orthopedic implants. This study aimed to characterize the response of both healthy and diabetic primary human osteoblasts cultured on a medical-grade 3D-printed titanium surface under high and low glucose conditions.
UNASSIGNED: Bone samples were obtained from six patients, three with Type 2 Diabetes Mellitus and three without. Primary osteoblasts were isolated and cultured on 3D-printed titanium discs in high (4.5 g/L D-glucose) and low glucose (1 g/L D-Glucose) media. Cellular morphology, matrix deposition, and mineralization were assessed using scanning electron microscopy and alizarin red staining. Alkaline phosphatase activity and L-lactate concentration was measured in vitro to assess functional osteoblastic activity and cellular metabolism. Osteogenic gene expression of BGLAP, COL1A1, and BMP7 was analyzed using reverse-transcription quantitative polymerase chain reaction.
UNASSIGNED: Diabetic osteoblasts were nonresponsive to variations in glucose levels compared to their healthy counterparts. Alkaline phosphatase activity, L-lactate production, mineral deposition, and osteogenic gene expression remained unchanged in diabetic osteoblasts under both glucose conditions. In contrast, healthy osteoblasts exhibited enhanced functional responsiveness in a high glucose environment and showed a significant increase in osteogenic gene expression of BGLAP, COL1A1, and BMP7 (p<.05).
UNASSIGNED: Our findings suggest that diabetic osteoblasts exhibit impaired responsiveness to variations in glucose concentrations, emphasizing potential osteoblast dysfunction in diabetes. This could have implications for post-surgery glucose management strategies in patients with diabetes. Despite the potential benefits of 3D printing for orthopedic implants, particularly for diabetic Charcot collapse, our results call for further research to optimize these interventions for improved patient outcomes.

The prevalence of diabetes mellitus and its associated complications, particularly diabetic foot pathologies, poses significant healthcare challenges and economic burdens globally. This review synthesises current evidence on the surgical management of the diabetic foot, focusing on the interplay between neuropathy, ischemia, and infection that commonly culminates in ulcers, infections, and, in severe cases, amputations. The escalating incidence of diabetes mellitus underscores the urgency for effective management strategies, as diabetic foot complications are a leading cause of hospital admissions among diabetic patients, significantly impacting morbidity and mortality rates. This review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers, infections, and skeletal pathologies such as Charcot arthropathy, emphasising the critical role of early diagnosis, comprehensive management strategies, and interdisciplinary care in mitigating adverse outcomes. In addressing surgical interventions, this review evaluates conservative surgeries, amputations, and reconstructive procedures, highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot pathologies. The integration of advanced diagnostic tools, novel surgical techniques, and postoperative care, including offloading and infection control, are discussed in the context of optimising healing and preserving limb function.

BACKGROUND: Charcot arthropathy is a progressive disorder of the ankle and foot joints that can lead to foot deformity and instability. Surgical intervention is often necessary for deformity and ulcer management during the chronic phase. The device used for arthrodesis remains a challenge.
METHODS: This clinical trial study included diabetic patients aged 40 years or older with Charcot foot. Lateral approach with lateral malleolar osteotomy was used to access the ankle joints and remove the cartilage. A small incision was made on the plantar aspect of the foot to pass an appropriately sized intramedullary nail. Demographic information, medical history, surgical details and Clinical data were collected at 2-week and 1-year follow-ups using the Ankle-Hindfoot Scale (AOFAS) score and the EuroQol 5-Dimensional 5-Level (EQ-5D-5L) health utility score.
RESULTS: Twenty-six patients with a mean age of 63 ± 0.23 years were included in the study. The findings showed significant improvements in AOFAS questionnaire items related to pain score, length of the walk, walking surfaces, walking disorders, sagittal alignment, back leg alignment, sustainability, alignment and the total score (P value < 0.001). The EQ-5D-5L questionnaire also showed a significant improvement in the total score (P value = 0.002).
CONCLUSIONS: This study provides evidence supporting the effectiveness of tibiotalocalcaneal arthrodesis by hindfoot nailing in diabetic patients with Charcot foot joints and demonstrated comparable and superior outcomes in terms of patient satisfaction and complication rate when compared to previous studies.

Increasingly Charcot neuroarthropathy (CN) is being recognized in patients with Charcot-Marie-Tooth (CMT) disease. In this report, we describe a case of CN in a CMT patient, adding to the very scarce literature describing this association. We additionally report his unique evaluation with fluorodeoxyglucose (FDG) and sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) scanning, the study of which is limited in CN despite its promising role. A 54-year-old known case of CMT, presented with left foot pain, and swelling for 4 months. Weakness and sensory deficits as a result of CMT were evident in both lower and upper limbs. His x-ray was suggestive of CN. Both FDG and NaF PET/CT scanning demonstrated increased tracer uptake in the first tarsometatarsal joint (TMTJ), in keeping with CN. Recognition of the association of CMT with CN is of vital importance as early diagnosis relies on high clinical suspicion. Characterizing risk factors of CN in CMT patients is still under study. Moreover, there is lack of data evaluating the role of PET/CT in CN and specifically in the context of CMT.

UNASSIGNED: The objective of this case series is to investigate the efficacy and safety of intravenous infusion of Pamidronate, a second generation bisphosphonate, in the treatment of active Charcot arthropathy.
UNASSIGNED: All patients with active Charcot arthropathy treated at the medical centre from 1 January 2013 to 30 June 2020 were included in the study. Efficacy outcome was evaluated based on time to consolidate findings observed through radiographic examination, while safety outcome was evaluated based on the incidence of adverse event (AE) occurrence.
UNASSIGNED: A total of 81 patients (37 male, 44 female) diagnosed with active Charcot arthropathy were included. 64.2% of patients were at stage 1 of Charcot arthropathy whereas 35.8% were at stage 2. The mean time to consolidate for stage 1 and stage 2 was 6.50 ± 4.21 months and 3.63 ± 2.92 months respectively (p-value = 0.139). No significant association was observed between gender, ethnicity and disease stage with the consolidation time (p-value >0.05). The rate of AE incidence was 2.5%, observed in 2 patients who developed a fever during the treatment. No other serious AE was observed in the study.
UNASSIGNED: Intravenous Pamidronate infusion is a safe and effective treatment option for Charcot arthropathy.

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Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the human motor system, first described in the 19th Century. The etiology of ALS appears to be multifactorial, with a complex interaction of genetic, epigenetic, and environmental factors underlying the onset of disease. Importantly, there are no known naturally occurring animal models, and transgenic mouse models fail to faithfully reproduce ALS as it manifests in patients. Debate as to the site of onset of ALS remain, with three competing theories proposed, including (i) the dying-forward hypothesis, whereby motor neuron degeneration is mediated by hyperexcitable corticomotoneurons via an anterograde transsynaptic excitotoxic mechanism, (ii) dying-back hypothesis, proposing the ALS begins in the peripheral nervous system with a toxic factor(s) retrogradely transported into the central nervous system and mediating upper motor neuron dysfunction, and (iii) independent hypothesis, suggesting that upper and lower motor neuron degenerated independently. Transcranial magnetic stimulation studies, along with pathological and genetic findings have supported the dying forward hypothesis theory, although the science is yet to be settled. The review provides a historical overview of ALS, discusses phenotypes and likely pathogenic mechanisms.

Charcot neuroarthropathy is a progressive, destructive condition leading to deformity, dysfunction and, in some cases, amputation. Much evolution has occurred over the last couple of decades in the management of Charcot foot with a focus on developing limb salvage and reconstructive techniques. The aim has been to achieve a stable plantigrade foot that remains pain and ulcer-free whilst reducing amputation rates. Soft tissue and bony reconstructions have been explored, and various modalities of fixation, including internal, external, and combined techniques, have been described and their outcomes published. Currently, no strong evidence exists which supports a particular modality of treatment, nor have there been any randomised studies to this effect, but the results are nevertheless promising. Recent studies have reported on minimally invasive techniques, the use of super construct fixation, computer-navigated deformity correction, the efficacy of techniques such as subtalar arthrodesis or tendon balancing procedures and staged deformity corrections. There is a need for more controlled and comparative studies with consistent reporting of intended outcomes to create a stronger portfolio of evidence on the surgical management of Charcot foot.

Hereditary sensory and autonomic neuropathy type IV (HSAN) is a rare and debilitating disorder highlighted by congenital absence of pain and anhidrosis. Orthopedic sequelae include physeal fractures, Charcot joint development, excessive joint laxity, soft tissue infections and recurrent painless dislocations, all of which often present in a delayed fashion. While there is no accepted guideline on management of these patients, several case studies have highlighted the importance of early diagnosis and cautioned against surgical intervention in these patients due to their inability to perceive pain and comply with post-operative restriction. The purpose of this case report is to present the clinical course of a patient with HSAN IV and the unique orthopedic challenges it presented. While some of her orthopedic injuries healed appropriately following treatment, others have gone on to have devastating complications and progressive joint destruction. Level of Evidence: IV.

Jean-Martin Charcot described what he called amyotrophic lateral sclerosis in his 12th and 13th lessons published in 1873 by Bourneville. He distinguished the symptoms that were related to the lesion of the anterior horn of the spinal cord and those that were due to the degeneration (that he named \"sclerosis\") of its lateral column. He thought that \"inflammation\" progressed from the lateral column to the anterior horn (but the term inflammation is not to be taken in the current meaning): the lesion of the anterior horn was thus \"deuteropathic\". An album containing drawings made by Charcot is kept in La Salpêtrière Neuropathology Department. Four drawings are pasted on one of its pages, showing the degeneration of the pyramidal tract. They constitute the original of the engravings illustrating Charcot\'s 12th lesson. The illustration of the fascicular atrophy of the adductor pollicis presented in the album does not appear in the lessons, even though this alteration is widely discussed and linked to the lesion of the anterior horn, which was supposed to ensure the \"nutrition\" of the muscle. The technique used by Charcot and his interpretation of the microscopic pictures, as exposed in his lessons, are discussed.