An 8-month adapted motor activity program in a young CMT1A male patient.

Background: It is unclear whether prolonged periods of training can be well tolerated. In Charcot-Marie Tooth disease (CMT). We report the effects of an 8-month, adapted motor activity (AMA) program in a 16-years-old CMT1A male patient. The program included strength, mobility, and balance training (two sessions per week, 1 h per session). Measures: Walking ability and walking velocity (Six-Minute Walking Test-6MWT, Ten Meters Walking Test-10 mW T), balance (Y-Balance Test-YBT, Berg Balance Scale-BBS), functional mobility (Short Physical Performance Battery-Short physical performance battery), fatigue (Checklist Individual strength questionnaire - CIS20R), health and quality of life (Short Form Health Survey 36 questionnaire-SF-36) were evaluated in three moments: before (T0), after 5 (T1) and 8 (T2) months of adapted motor activity. Dorsal and plantar foot flexion strength (Maximal Voluntary Contraction-maximum voluntary contraction) and neuromuscular functions (Electromyography-sEMG, interpolated twitch technique-ITT) were measured at T1 and T2. Results: Relative to T0, an amelioration of walking ability (6MWT, +9,3%) and balance (with improvements on Y-balance composite normalized mean reach of the right and left limb of 15,3% and 8,5%, respectively) was appreciable. Relative to T1, an increase in foot strength in three out of four movements (right plantar flexion, +39,3%, left plantar flexion, +22,7%, left dorsal flexion, 11,5%) was observed. Concerning voluntary muscle activation, a greater recruitment in the left, unlike right, medial gastrocnemius was observed. Conclusion: Results suggest the safety of an 8-month AMA program in a young patient affected by CMT1A.

Effectiveness of Pamidronate Infusion in the Treatment of Charcot Arthropathy.

Introduction: 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. Materials and methods: 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. Results: 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. Conclusion: Intravenous Pamidronate infusion is a safe and effective treatment option for Charcot arthropathy.

Langerhans Cell Histiocytosis With Unusual Hexagonal Crystals in Addition to Usual Charcot-Leyden Crystals. Report of a Patient With Possible Process of Crystal Formation and Clinical Significance of a "Necrotic" Change.

Langerhans cell histiocytosis is a rare neoplastic disorder characterized by the proliferation of Langerhans cells and often accompanied by eosinophil infiltration. Charcot-Leyden crystals, composed of galectin 10, are occasionally observed in Langerhans cell histiocytosis; however, histological images are rarely reported. We herein present a patient with Langerhans cell histiocytosis with Charcot-Leyden crystals and hexagonal crystals by describing the histologic and immunohistochemical features of a lymph node. A unique distribution of Charcot-Leyden crystals and hexagonal crystals was observed in this patient, shedding light on their possible formation process of the latter. We discuss the biological significance of eosinophilic abscesses in Langerhans cell histiocytosis and propose that these crystals may be linked to extracellular trap-cell death (ETosis). This example challenges the conventional characterization of "necrosis" in Langerhans cell histiocytosis and underscores the importance of recognizing ETosis as a potential mechanism involved in the pathogenesis of Langerhans cell histiocytosis. Further studies are underway to validate significance of these findings in a larger cohort of Langerhans cell histiocytosis patients.

A study concept of expeditious clinical enrollment for genetic modifier studies in Charcot-Marie-Tooth neuropathy 1A.

BACKGROUND: Caused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets. In this study, we present a comprehensive analysis of clinical examination results from 1564 CMT1A patients sourced from a prospective natural history study conducted by the RDCRN-INC (Inherited Neuropathy Consortium). Our primary objective is to delineate extreme phenotype profiles (mild and severe) within this patient cohort, thereby enhancing our ability to detect genetic modifiers with large effects. METHODS: We have conducted large-scale statistical analyses of the RDCRN-INC database to characterize CMT1A severity across multiple metrics. RESULTS: We defined patients below the 10th (mild) and above the 90th (severe) percentiles of age-normalized disease severity based on the CMT Examination Score V2 and foot dorsiflexion strength (MRC scale). Based on extreme phenotype categories, we defined a statistically justified recruitment strategy, which we propose to use in future modifier studies. INTERPRETATION: Leveraging whole genome sequencing with base pair resolution, a future genetic modifier evaluation will include single nucleotide association, gene burden tests, and structural variant analysis. The present work not only provides insight into the severity and course of CMT1A, but also elucidates the statistical foundation and practical considerations for a cost-efficient and straightforward patient enrollment strategy that we intend to conduct on additional patients recruited globally.

Cochlear implantation in patients with Charcot-Marie-Tooth disease: two cases with a review of the literature.

PURPOSE: To report two cases of bilateral cochlear implantation (CI) in Charcot-Marie-Tooth disease (CMT) patients with novel mutations. Furthermore, we conducted a detailed literature review on the profile and outcomes of CI in this uncommon clinical circumstance. CASE PRESENTATION: Case 1 involved a 25-year-old woman who was referred for sudden hearing loss (HL) in her left ear and had a 7-year history of HL in her right ear. She was diagnosed with CMT type 1 with a thymidine phosphorylase gene mutation. CI was performed on her left side because her hearing gradually worsened to deafness in both ears. At 3 months post-operation, her speech discrimination score without lip-reading improved from 0 to 100%. She underwent a second CI on her right ear 6 months after her first CI. Two years from her first operation, the speech discrimination score was 100%. Case 2 received her first CI on her right ear at the age of nine for her bilateral HL. She was diagnosed with CMT type 2 with a Twinkle mitochondrial DNA helicase gene mutation. Preoperatively, the speech discrimination score in both ear-aided conditions was 70%. At the 7-year post-operation follow-up, the speech discrimination score was 76%. A second CI was performed due to decreasing hearing ability in her left ear. The speech discrimination score showed 100% at 7 months after the second CI. CONCLUSIONS: CI is an effective hearing rehabilitation option for CMT patients with severe-to-profound SNHL. Neuro-otologists should consider CI as a treatment option, even though hearing loss in CMT is associated with auditory neuropathy spectrum disease (ANSD).

Foot surgery for adults with Charcot-Marie-Tooth disease.

People with Charcot-Marie-Tooth (CMT) disease often undergo foot and ankle surgery, as foot deformities are common and cause a degree of functional limitations impairing quality of life. Surgical approaches are variable and there are no evidence-based guidelines. A multidisciplinary approach involving neurology, physical therapy and orthopaedic surgery is ideal to provide guidance on when to refer for surgical opinion and when to intervene. This review outlines the range of foot deformities associated with CMT, their clinical assessment, and their conservative and surgical and postoperative management.

Case report: Chronic inflammatory demyelinating polyneuropathy superimposed on Charcot-Marie-tooth type 1A disease after SARS-CoV-2 vaccination and COVID-19 infection.

Background: There is growing evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of immune mediated neuropathies like chronic inflammatory demyelinating polyneuropathy (CIDP), but the impact of SARS-CoV-2 vaccination and COVID-19 infection on genetic disorders such as Charcot-MarieTooth (CMT) remains unclear. Case presentation: A 42-year-old male with occulted CMT neuropathy type lA (CMT1A) who developed limb numbness and weakness after the second SARS-CoV-2-vaccination was confirmed by identifying characteristic repeats in the p11.2 region of chromosome 17. Due to the progressive deterioration of muscle strength over 8 weeks, limb atrophy, moderately elevated protein counts in the cerebrospinal fluid, and significant improvement with intravenous human immunoglobulin, which were characteristic of acquired inflammatory neuropathies, he was eventually diagnosed with CIDP superimposed on CMT1A. However, after a three-month plateau, the patient contracted COVID-19, which led to repeated and worsening symptoms of limb weakness and atrophy, thus was diagnosed with a recurrence of CIDP and treated with Intravenous immunoglobulin and methylprednisolone 500 mg/d for 5 consecutive days, followed by oral prednisone and mycophenolate mofetil tablets. On 2 month follow-up, he exhibited remarkable clinical improvement and could walk independently with rocking gait. After 1 year of follow-up, the patient's condition was stable without further change. Conclusion: Our case indicates that CMT1A can deteriorate after SARS-CoV-2 vaccination. Thus, SARS-CoV-2 vaccination should be considered a potential predisposing factor for CMT1A worsening. The possible superposition of CMTIA and CIDP in the context of SARS-CoV-2 infection or immunity suggests that any clinical exacerbation in patients with CMT1A should be carefully evaluated to rule out treatable superposition inflammation. In addition, electrophysiological and imaging examination of the proximal nerves, such as the axillary nerve, is helpful for the diagnosis of CIDP.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control: The pathobiology and therapeutic implications.

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus (DM) is a well-known precursor to complications such as diabetic retinopathy, neuropathy (including autonomic neuropathy), and nephropathy, a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin. Although, acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications, rarely other problems such as albuminuria, diabetic kidney disease, Charcot's neuroarthropathy, gastroparesis, and urinary bladder dysfunction are also encountered. The World Journal of Diabetes recently published a rare case of all these complications, occurring in a young type 1 diabetic female intensely managed during pregnancy, as a case report by Huret et al. It is essential to have a comprehensive understanding of the pathobiology, prevalence, predisposing factors, and management strategies for acute onset, or worsening of microvascular complications when rapid glycemic control is achieved, which serves to alleviate patient morbidity, enhance disease management compliance, and possibly to avoid medico-legal issues around this rare clinical problem. This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.

Diagnostic value of lower extremity ultrasonographic nerve enlargement for differentiating demyelinating Charcot-Marie-Tooth disease from chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: We previously reported that nerve enlargement assessment by nerve ultrasonography of the intermediate upper limb is applicable for distinguishing demyelinating Charcot-Marie-Tooth disease (CMT) from chronic inflammatory demyelinating polyneuropathy (CIDP). However, differences in the severity and distribution patterns of lower extremity nerve enlargement have not been established for either disease. Therefore, we examined the utility of lower extremity nerve ultrasonography for differentiating between CMT and CIDP. METHODS: Twelve patients with demyelinating CMT and 17 patients with CIDP were evaluated. The median, ulnar, tibial, and fibular nerves were evaluated in three regions: the distal upper extremity, intermediate upper extremity, and lower extremity. Of the 14 selected screening sites, the number of sites that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined. RESULTS: The screening ESNs in the intermediate region and lower extremities were greater in patients with demyelinating CMT than in patients with CIDP and greater than the ESN in the distal region (p = 0.010, p = 0.001, and p = 0.101, respectively). The ESNs in the intermediate region and lower extremities significantly differed among patients with typical CIDP, CIDP variants, and demyelinating CMT (p = 0.084 and p < 0.001). Among the 14 selected screening sites, the combined upper and lower extremity ESNs exhibited the highest AUC (0.92; p < 0.001). CONCLUSIONS: Combining the upper and lower extremities for ultrasonographic nerve measurement more accurately distinguishes CIDP from demyelinating CMT.

Forefoot Morphotypes in Cavovarus Feet: A Novel Assessment of Deformity.

BACKGROUND: The cavovarus foot is a complex 3-dimensional deformity. Although a multitude of techniques are described for its surgical management, few of these are evidence based or guided by classification systems. Surgical management involves realignment of the hindfoot and soft tissue balancing, followed by forefoot balancing. Our aim was to analyze the pattern of residual forefoot deformities once the hindfoot is corrected, to guide forefoot correction. METHODS: We included 20 cavovarus feet from 16 adult patients with Charcot-Marie-Tooth who underwent weightbearing CT (mean age 43.4 years, range: 22-78 years, 14 males). Patients included had flexible deformities, with no previous surgery. Using specialized software (Bonelogic 2.1, Disior) a 3-dimensional, virtual model was created. Using morphologic data captured from normal feet in patients without pathology as a guide, the talonavicular joint of the cavovarus foot was digitally reduced to a "normal" position to simulate the correction that would be achieved during surgical correction. Models of the corrected position were exported and geometrically analyzed using Blender 3.64 to identify anatomical trends. RESULTS: We identified 4 types of cavovarus forefoot morphotypes. Type 0 was defined as a balanced forefoot (2 cases, 10%). Type 1 was defined as a forefoot where the first metatarsal was relatively plantarflexed to the rest of the foot, with no significant residual adduction after talonavicular joint correction (12 cases, 60%). Type 2 was defined as a forefoot where the second and first metatarsals were progressively plantarflexed, with no significant adduction (4 cases, 20%). Type 3 was defined as a forefoot where the metatarsals were adducted after talonavicular derotation (2 cases, 10%). CONCLUSION: In this relatively small cohort, we identified 4 forefoot morphotypes in cavovarus feet that might help surgeons to recognize and anticipate the residual forefoot deformities after hindfoot correction. Different treatment strategies may be required for different morphotypes to achieve balanced correction. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PRPS1-associated retinopathy: a diagnostic odyssey.

PURPOSE: This study describes how the diagnosis of Usher syndrome was revised to PRPS1-associated retinopathy and Charcot-Marie-Tooth disease type 5. CASE REPORT: A 38-year-old female with bilaterally subnormal vision and non-congenital hearing loss was initially diagnosed with Usher syndrome, based on finding variants in three genes (MYO7A, USH2A, and PCDH15), was re-evaluated at the inherited retinal disorders clinic. She had asymmetric retinopathy and right macular pseudocoloboma. She was also found to have myopathic facies, poor grip strength and atrophy of the calf muscles. Whole exome sequencing including variants in PRPS1 showed a variant (NM_002764.4:c.287 G > A; p.Arg96Gln), which was not detected by targeted Sanger sequencing of the DNA from her mother and sister. CONCLUSION: The constellation of asymmetric retinopathy and non-congenital hearing impairment should prompt the clinician to search for other diagnoses that may not be covered by an Usher syndrome next generation sequencing panel. Interpretation of genetic testing results should be correlated with a detailed clinical phenotype.

Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest protein family genetically linked to CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate CMT type C (DI-CMTC) is caused by YARS1 mutations driving a toxic gain-of-function in the encoded tyrosyl-tRNA synthetase (TyrRS), which is mediated by exposure of consensus neomorphic surfaces through conformational changes of the mutant protein. In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not TyrRSWT, into muscles of wild-type mice. Augmenting BDNF in DI-CMTC muscles, through injection of recombinant protein or muscle-specific gene therapy, resulted in complete axonal transport correction. Therefore, this work identifies a non-cell autonomous pathomechanism common to ARS-related neuropathies, and highlights the potential of boosting BDNF levels in muscles as a therapeutic strategy.

Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest protein family genetically linked to CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate CMT type C (DI-CMTC) is caused by YARS1 mutations driving a toxic gain-of-function in the encoded tyrosyl-tRNA synthetase (TyrRS), which is mediated by exposure of consensus neomorphic surfaces through conformational changes of the mutant protein. In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not TyrRSWT, into muscles of wild-type mice. Augmenting BDNF in DI-CMTC muscles, through injection of recombinant protein or muscle-specific gene therapy, resulted in complete axonal transport correction. Therefore, this work identifies a non-cell autonomous pathomechanism common to ARS-related neuropathies, and highlights the potential of boosting BDNF levels in muscles as a therapeutic strategy.

Remediation of Perceptual Deficits in Progressive Auditory Neuropathy: A Case Study.

BACKGROUND: Auditory neuropathy (AN) is a hearing disorder that affects neural activity in the VIIIth cranial nerve and central auditory pathways. Progressive forms have been reported in a number of neurodegenerative diseases and may occur as a result of both the deafferentiation and desynchronisation of neuronal processes. The purpose of this study was to describe changes in auditory function over time in a patient with axonal neuropathy and to explore the effect of auditory intervention. METHODS: We tracked auditory function in a child with progressive AN associated with Charcot-Marie-Tooth (Type 2C) disease, evaluating hearing levels, auditory-evoked potentials, and perceptual abilities over a 3-year period. Furthermore, we explored the effect of auditory intervention on everyday listening and neuroplastic development. RESULTS: While sound detection thresholds remained constant throughout, both electrophysiologic and behavioural evidence suggested auditory neural degeneration over the course of the study. Auditory brainstem response amplitudes were reduced, and perception of auditory timing cues worsened over time. Functional hearing ability (speech perception in noise) also deteriorated through the first 1.5 years of study until the child was fitted with a "remote-microphone" listening device, which subsequently improved binaural processing and restored speech perception ability to normal levels. CONCLUSIONS: Despite the deterioration of auditory neural function consistent with peripheral axonopathy, sustained experience with the remote-microphone listening system appeared to produce neuroplastic changes, which improved the patient's everyday listening ability-even when not wearing the device.

Against vivisection: Charcot and Pitres' discovery of the human motor cortex and the birth of modern neurosurgery and of the surgical treatment of epilepsy.

This article addresses the discrepancy between Edouard Hitzig's and David Ferrier's findings on the cortical localization of movements in animals and Jean-Martin Charcot's findings in humans. The results of Hitzig's and Ferrier's vivisections were criticized by experimentalists in England and France as discordant, irreproducible, and inconclusive, and they were rejected by clinicians as irrelevant. Charcot addressed the gap between animal and human motor function by correlating motor deficits and focal epileptic seizures in patients to their autopsy findings. By this method he discovered the functional organization of the human motor cortex and produced the first accurate human motor brain map. Ferrier, William Osler, and Hughlings Jackson acknowledged Charcot's findings, and his findings guided the first neurosurgeons in localizing and resecting intracranial mass lesions presenting with focal epileptic seizures. Although his contributions in these fields have been neglected by modern historians, Charcot made significant contributions to the neurobiology of the human motor system, to epileptology, and to the birth of modern neurosurgery.

Mid- to Long-Term Results of Total Knee Arthroplasty for Charcot Arthropathy of the Knee.

Background: Total knee arthroplasty (TKA) for Charcot arthropathy of the knee is considered controversial because of its higher complication rate compared with that of TKA for osteoarthritis. In this study, we investigated the clinical outcomes, survival rates, and complications of primary TKA for Charcot arthropathy. Methods: We conducted a retrospective analysis of nine patients (12 knees) with Charcot arthropathy who underwent TKA. The mean age of the patients was 63.9 ± 9.4 years (range, 52-83 years). The most frequent causative disease was diabetes mellitus (three patients). Patients' clinical outcomes, including the 2011 Knee Society Score and the range of motion, were compared between preoperative and the most recent postoperative data. The 5- and 10-year survival rates for aseptic revision, revision due to infection, and complications were examined. The mean follow-up period was 7.3 ± 3.9 years (range, 3-14 years). Results: The 2011 Knee Society Score and the knee flexion angle significantly improved after TKA surgery (P < 0.05). The 5-year survival rates for aseptic revision, revision due to infection, and complications were 100%, 91.7%, and 83.3%, respectively; the 10-year survival rates for these parameters were the same. One patient underwent revision for insert replacement due to periprosthetic infection, and the other patient had varus/valgus instability due to soft tissue loosening. Conclusions: The mid- to long-term results of TKA for Charcot arthropathy were generally favorable. Our findings indicate that TKA may be a viable treatment option for Charcot arthropathy.

Eosinophil extracellular traps in eosinophilic chronic rhinosinusitis induce Charcot-Leyden crystal formation and eosinophil recruitment.

Eosinophil extracellular traps (EETs) are implicated in various eosinophil-associated diseases; however, their role in chronic rhinosinusitis (CRS) remains unclear. In the present study, 57 CRS patients were enrolled, and immunofluorescence was used to analyze EETs in eosinophilic (eCRS) and non-eosinophilic (Non-eCRS) tissues. MSD was used to examine IL-4, IL-5, and IL-13 concentrations in tissue homogenates. Charcot-Leyden crystals (CLCs) protein expression was detected in PMA, PMA+DNase I, and blank control eosinophils using ELISA. Eotaxin-3 mRNA and protein levels were measured in human nasal epithelial cells (HNECs) cultured with EETs, EETs+DNase I, DNase I, and unstimulated eosinophils using PCR and ELISA. EETs were significantly increased in eCRS tissues compared with Non-eCRS (P<0.001), and correlated with VAS and Lund-Mackay CT scores. IL-5 expression was related to EETs formation (r = 0.738, P<0.001). PMA-stimulated eosinophils exhibited higher CLCs protein levels (P<0.01). Co-culturing HNECs with EETs significantly increased eotaxin-3 mRNA and protein levels (P<0.0001, P<0.001) compared with other groups. The study suggests EETs formation is elevated in eCRS patients and is involved in CLCs formation and chemokine secretion, promoting eosinophilic inflammation.

Differential Diagnosis of Diabetic Foot Osteomyelitis and Charcot Neuropathic Osteoarthropathy with Deep Learning Methods.

Our study aims to evaluate the potential of a deep learning (DL) algorithm for differentiating the signal intensity of bone marrow between osteomyelitis (OM), Charcot neuropathic osteoarthropathy (CNO), and trauma (TR). The local ethics committee approved this retrospective study. From 148 patients, segmentation resulted in 679 labeled regions for T1-weighted images (comprising 151 CNO, 257 OM, and 271 TR) and 714 labeled regions for T2-weighted images (consisting of 160 CNO, 272 OM, and 282 TR). We employed both multi-class classification (MCC) and binary-class classification (BCC) approaches to compare the classification outcomes of CNO, TR, and OM. The ResNet-50 and the EfficientNet-b0 accuracy values were computed at 96.2% and 97.1%, respectively, for T1-weighted images. Additionally, accuracy values for ResNet-50 and the EfficientNet-b0 were determined at 95.6% and 96.8%, respectively, for T2-weighted images. Also, according to BCC for CNO, OM, and TR, the sensitivity of ResNet-50 is 91.1%, 92.4%, and 96.6% and the sensitivity of EfficientNet-b0 is 93.2%, 97.6%, and 98.1% for T1, respectively. For CNO, OM, and TR, the sensitivity of ResNet-50 is 94.9%, 83.6%, and 97.9% and the sensitivity of EfficientNet-b0 is 95.6%, 85.2%, and 98.6% for T2, respectively. The specificity values of ResNet-50 for CNO, OM, and TR in T1-weighted images are 98.1%, 97.9%, and 94.7% and 98.6%, 97.5%, and 96.7% in T2-weighted images respectively. Similarly, for EfficientNet-b0, the specificity values are 98.9%, 98.7%, and 98.4% and 99.1%, 98.5%, and 98.7% for T1-weighted and T2-weighted images respectively. In the diabetic foot, deep learning methods serve as a non-invasive tool to differentiate CNO, OM, and TR with high accuracy.