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Quantitative MRI and MRS have become important tools for the assessment and management of patients with neuromuscular disorders (NMDs). Despite significant progress, there is a need for new objective measures with improved specificity to the underlying pathophysiological alteration. This would enhance our ability to characterize disease evolution and improve therapeutic development. In this study, qMRI methods that are commonly used in clinical studies involving NMDs, like water T2 (T2 H2O ) and T1 and fat-fraction (FF) mapping, were employed to evaluate disease activity and progression in the skeletal muscle of golden retriever muscular dystrophy (GRMD) dogs. Additionally, extracellular volume (ECV) fraction and single-voxel bicomponent water T2 relaxometry were included as potential markers of specific histopathological changes within the tissue. Apart from FF, which was not significantly different between GRMD and control dogs and showed no trend with age, T2 H2O , T1, ECV, and the relative fraction of the long-T2 component, A 2 , were significantly elevated in GRMD dogs across all age ranges. Moreover, longitudinal assessment starting at 2 months of age revealed significant decreases in T2 H2O , T1, ECV, A 2 , and the T2 of the shorter-T2 component, T2 1 , in both control and GRMD dogs during their first year of life. Notably, insights from ECV and bicomponent water T2 indicate that (I) the elevated T2 H2O and T1 values observed in dystrophic muscle are primarily driven by an expansion of the extracellular space, likely driven by the edematous component of inflammatory responses to tissue injury and (II) the significant decrease of T2 H2O and T1 with age in control and GRMD dogs reflects primarily the progressive increase in fiber diameter and protein content during tissue development. Our study underscores the potential of multicomponent water T2 relaxometry and ECV to provide valuable insights into muscle pathology in NMDs., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

In necrotizing fasciitis, aggressive surgical debridement and broad-spectrum antibiotics are the cornerstone of treatment but cannot be proposed for the eyelid and periorbital area because of the risk of blindness, eyeball exposure and disfiguration. The aim of this review was to determine the most effective management of this severe infection while preserving eye function. A literature search of the PubMed, Cochrane Library, ScienceDirect and Embase databases was conducted for all articles published up to March 2022; 53 patients were included. Management was probabilistic, combining antibiotic therapy with skin (+/- orbicularis oculi muscle) debridement in 67.9% of cases, and probabilistic antibiotic therapy alone in 16.9% of cases. Radical surgery with exenteration was performed in 11.1% of patients; 20.9% of patients had complete loss of vision, and 9.4% died of the disease. Aggressive debridement was rarely necessary possibly because of the anatomical particularities of this region., Competing Interests: Declaration of Competing Interest Authors have no competing interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Duchenne muscular dystrophy (DMD) patients exhibit a late left ventricular systolic dysfunction preceded by an occult phase, during which myocardial fibrosis progresses and some early functional impairments can be detected. These latter include electrocardiographic (ECG) and heart rate variability (HRV) abnormalities. This longitudinal study aimed at describing the sequence of ECG and HRV abnormalities, using Holter ECG in the GRMD (Golden retriever muscular dystrophy) dog model, known to develop a DMD-like disease, including cardiomyopathy. Most of the known ECG abnormalities described in DMD patients were also found in GRMD dogs, including increased heart rate, prolonged QT and shortened PR intervals, ventricular arrhythmias, and several of them could be detected months before the decrease of fractional shortening. The HRV was impaired like in DMD patients, one of the earliest evidenced abnormalities being a decrease in the very low frequency (VLF) component of the power spectrum. This decrease was correlated with the further reduction of fractional shortening. Such decreased VLF probably reflects impaired autonomic function and abnormal vasomotor tone. This study provides new insights into the knowledge of the GRMD dog model and DMD cardiomyopathy and emphasizes the interest to monitor the VLF power in DMD patients, still unexplored in this disease, whilst it is highly predictive of deleterious clinical events in many other pathological conditions., (© 2024. The Author(s).)

Background and Objectives: Surgical correction of nonsyndromic craniosynostosis (NSC) aims to restore cranial shape. Reossification of bone defects is paramount for the best aesthetic prognosis. However, the literature on the quantitative evaluation of bone defects after NSC surgery is scarce. This study aimed to quantify and analyze the surface area of bone defects after NSC surgery and establish a threshold value for predicting persistent defects., Methods: We conducted a systematic review and a prospective study of 28 children undergoing surgical treatment for NSC. We analyzed 426 defects on the first computed tomography scan (1 year postoperative) and 132 defects on the second computed tomography scan (4.6 years postoperative). Statistical analysis was performed using Spearman's rank correlation coefficient, Mann-Whitney-Wilcoxon rank-sum test, and Youden's J statistic., Results: Our systematic review identified three studies reporting on bone defects' surface area and reossification rate. In our study, we found no statistically significant differences in the number or size of defects between sex or type of NSC. The threshold value for the surface area of bone defects above which there was a higher probability of persistent defects was 0.19 cm2 (Youden point), with an 89.47 % probability of persistence. Defects with a surface area below 0.19 cm2 had a considerably lower probability, only 15.07%, of persistence over time., Conclusion: Our study provides valuable quantitative data for managing bone defects after NSC surgery. Defects with a surface area above 0.19 cm2 should be monitored with radiological imaging because of the risk of persistence. Our findings highlight the importance of developing robust and reproducible methods for the quantitative analysis of bone defects after NSC surgery., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in DMD gene and loss of the protein dystrophin, which ultimately leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or cardiomyopathy. Among the developed therapeutic strategies for DMD, gene therapy approaches partially restore micro-dystrophin or quasi-dystrophin expression. However, despite extensive attempts to develop definitive therapies for DMD, the standard of care remains corticosteroid, which has only palliative benefits. Animal models have played a key role in studies of DMD pathogenesis and treatment development. The golden retriever muscular dystrophy (GRMD) dog displays a phenotype aligning with the progressive course of DMD. Therefore, canine studies may translate better to humans. Recent studies suggested that nicotinamide adenine dinucleotide (NAD + ) cellular content could be a critical determinant for striated muscle function. We showed here that NAD + content was decreased in the striated muscles of GRMD, leading to an alteration of one of NAD + co-substrate enzymes, PARP-1. Moreover, we showed that boosting NAD + content using nicotinamide (NAM), a natural NAD + precursor, modestly reduces aspects of striated muscle disease. Collectively, our results provide mechanistic insights into DMD., (© 2023. The Author(s).)

Background: Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder, culminating in a complete loss of ambulation, hypertrophic cardiomyopathy and a fatal cardiorespiratory failure. Necroptosis is the form of necrosis that is dependent upon the receptor-interacting protein kinase (RIPK) 3; it is involved in several inflammatory and neurodegenerative conditions. We previously identified RIPK3 as a key player in the acute myonecrosis affecting the hindlimb muscles of the mdx dystrophic mouse model. Whether necroptosis also mediates respiratory and heart disorders in DMD is currently unknown., Methods: Evidence of activation of the necroptotic axis was examined in dystrophic tissues from Golden retriever muscular dystrophy (GRMD) dogs and R-DMDdel52 rats. A functional assessment of the involvement of necroptosis in dystrophic animals was performed on mdx mice that were genetically depleted for RIPK3. Dystrophic mice aged from 12 to 18 months were analysed by histology and molecular biology to compare the phenotype of muscles from mdxRipk3 +/+ and mdxRipk3 -/- mice. Heart function was also examined by echocardiography in 40-week-old mice., Results: RIPK3 expression in sartorius and biceps femoris muscles from GRMD dogs positively correlated to myonecrosis levels (r = 0.81; P = 0.0076). RIPK3 was also found elevated in the diaphragm (P ≤ 0.05). In the slow-progressing heart phenotype of GRMD dogs, the phosphorylated form of RIPK1 at the Serine 161 site was dramatically increased in cardiomyocytes. A similar p-RIPK1 upregulation characterized the cardiomyocytes of the severe DMDdel52 rat model, associated with a marked overexpression of Ripk1 (P = 0.007) and Ripk3 (P = 0.008), indicating primed activation of the necroptotic pathway in the dystrophic heart. MdxRipk3 -/- mice displayed decreased compensatory hypertrophy of the heart (P = 0.014), and echocardiography showed a 19% increase in the relative wall thickness (P < 0.05) and 29% reduction in the left ventricle mass (P = 0.0144). Besides, mdxRipk3 -/- mice presented no evidence of a regenerative default or sarcopenia in skeletal muscles, moreover around 50% less affected by fibrosis (P < 0.05)., Conclusions: Our data highlight molecular and histological evidence that the necroptotic pathway is activated in degenerative tissues from dystrophic animal models, including the diaphragm and the heart. We also provide the genetic proof of concept that selective inhibition of necroptosis in dystrophic condition improves both histological features of muscles and cardiac function, suggesting that prevention of necroptosis is susceptible to providing multiorgan beneficial effects for DMD., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Frailty is a clinical presentation resulting from age-related cumulative declines in several physiological systems. The aim of this study was to adapt the concept of frailty to the domestic dog, as a model for frailty research, by characterizing a 5-criterion frailty phenotype using objective measurement, and to investigate its independent association with death. A prospective cohort including 80 Labrador and Golden Retriever dogs aged 9 years or older was conducted between March 2015 and July 2020. An adapted frailty phenotype was defined according to the presence of 5 criteria (weakness, slowness, poor endurance, low physical activity, and shrinking) evaluated at baseline from physical performance tests and items from questionnaire and physical examination. Survival analysis was used to investigate the association between frailty status and time to all-cause death over 5 years of follow-up. Frailty status was significantly associated with all-cause death, with median survival times of 10.5 months, 35.4 months, and 42.5 months, respectively for dogs with 3 or more criteria (frail dogs), dogs with 1 or 2 criteria (prefrail dogs), and nonfrail dogs. Independently of age, sex, breed, sterilization, and sex-sterilization interaction, frail dogs died significantly faster than nonfrail dogs at baseline (adjusted hazard ratio = 5.86; 95% confidence interval = 2.45-14.0; p < .01). This significant association persisted after controlling for other potential confounders. Frailty, assessed by a 5-criterion phenotype, was predictive of all-cause death, in geriatric Labrador and Golden Retriever dogs. The concept of frailty seems adaptable to the dog., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In centers for craniosynostosis surgery, the volume of activity does not necessarily reflect the quality of the treatment., Objective: Our aim was to analyze a retrospective series of patients over a period of 6 years in a low-volume craniosynostosis surgery center, and to study indicators that reflect the quality of treatment., Patients and Methods: The analysis included all patients who underwent a craniofacial surgery for all forms of craniosynostosis during the period 2012-2017 (annual follow-up for 4 years). Data on the type of synostosis, sex, age, weight, type of surgery, duration of surgery, blood transfusion, postinterventional care, and total length of hospital stay were collected. Medical and surgical complications were recorded using the Leeds classification., Results: Overall, 42 patients (33 male; 23 cases of scaphocephaly, 13 cases of trigonocephaly, 4 cases of coronal plagiocephaly, 1 case of lambdoid plagiocephaly, and 1 case of brachycephaly) underwent craniofacial surgery with a median age of 7.4 months [4.8; 10.4] and a mean weight of 8.40 ± 1.92 kg at surgery. The median hospital stay was 7 days [6;7] with 1 day in the postinterventional care unit for 83% of patients. The global complication rate was 12% (95% CI: 4%-26%) with three minor cutaneous and two major (cardiovascular and septic) complications., Conclusion: Complication rates reflect the quality of care in a center that treats craniosynostosis much more than do the number of procedures, mean hospital stay, and blood transfusion rates. It is essential to define new indicators capable of measuring the quality of life linked to surgical procedures and of using them to assess the competence of a center., Competing Interests: Conflict of Interest None., (Copyright © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Mutations in DNM2 cause autosomal dominant centronuclear myopathy (ADCNM), a rare disease characterized by skeletal muscle weakness and structural anomalies of the myofibres, including nuclear centralization and mitochondrial mispositioning. Following the clinical report of a Border Collie male with exercise intolerance and histopathological hallmarks of CNM on the muscle biopsy, we identified the c.1393C>T (R465W) mutation in DNM2, corresponding to the most common ADCNM mutation in humans. In order to establish a large animal model for longitudinal and preclinical studies on the muscle disorder, we collected sperm samples from the Border Collie male and generated a dog cohort for subsequent clinical, genetic and histological investigations. Four of the five offspring carried the DNM2 mutation and showed muscle atrophy and a mildly impaired gait. Morphological examinations of transverse muscle sections revealed CNM-typical fibres with centralized nuclei and remodelling of the mitochondrial network. Overall, the DNM2-CNM dog represents a faithful animal model for the human disorder, allows the investigation of ADCNM disease progression, and constitutes a valuable complementary tool to validate innovative therapies established in mice., Competing Interests: Competing interests J.L. is co-founder of Dynacure., (© 2022. Published by The Company of Biologists Ltd.)

Background: Duchenne muscular dystrophy is associated with progressive deterioration in left ventricular (LV) function. The golden retriever muscular dystrophy (GRMD) dog model recapitulates the pathology and clinical manifestations of Duchenne muscular dystrophy. Importantly, they develop progressive LV dysfunction starting at early age., Objectives: The authors tested the cardioprotective effect of chronic administration of the ARM036, a small molecule that stabilizes the closed conformation of the cardiac sarcoplasmic reticulum ryanodine receptor/calcium release channel (RyR2) in young GRMD-dogs., Methods: Two-month-old GRMD-dogs were treated with ARM036 or placebo for 4 months. Healthy-dogs of the same genetic background served as controls. Cardiac function was evaluated by conventional and 2-dimensional speckle-tracking echocardiography. Cardiac cellular and molecular analyses were performed at 6 months old., Results: Conventional echocardiography showed normal LV dimensions and ejection fraction in 6-month-old GRMD dogs. Interestingly, 2-dimensional speckle-tracking echocardiography revealed decreased global longitudinal strain and the presence of hypokinetic segments in placebo-treated GRMD dogs. Single-channel measurements revealed higher RyR2 open probability at low resting Ca 2+ in GRMD cardiomyocytes than in controls. ARM036 prevented those in vivo and in vitro dysfunctions in GRMD dogs. Myofilament Ca 2+ -sensitivity was increased in permeabilized GRMD cardiomyocytes at short sarcomere length. ARM036 had no effect on this parameter. Cross-bridge cycling kinetics were altered in GRMD myocytes and recovered with ARM036 treatment, which coincided with the level of myosin binding protein-C-S glutathionylation., Conclusions: GRMD-dogs exhibit early LV dysfunction associated with altered myofilament contractile properties. These abnormalities were prevented pharmacologically by stabilizing RyR2 with ARM036., Competing Interests: Funding Support and Author Disclosures This study was supported by the Association Française contre les Myopathies (AFM) (OC N°11590, AL N°15083, SB N° 14389, 15208, 15632, 16396, and 17124) and by Institut de Recherches Servier (Suresnes, France). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The advent of digital medical imaging, medical image analysis and computer vision has opened the surgeon horizons with the possibility to add virtual information to the real operative field. For oral and maxillofacial surgeons, overlaying anatomical structures to protect (such as teeth, sinus floors, inferior and superior alveolar nerves) or to remove (such as cysts, tumours, impacted teeth) presents a real clinical interest., Material and Methods: Through this work, we propose a proof-of-concept markerless augmented reality system for oral and maxillofacial surgery, where a virtual scene is generated preoperatively and mixed with reality to reveal the location of hidden anatomical structures intraoperatively. We devised a computer software to process still video frames of the operating field and to display them on the operating room screens., Results: Firstly, we give a description of the proposed system, where virtuality aligns with reality without artificial markers. The dental occlusion plan analysis and cusps detection allow us to initialise the alignment process. Secondly, we validate the feasibility with an experimental approach on a 3D printed jaw phantom and an ex-vivo pig jaw. Thirdly, we evaluate the potential clinical benefit on a patient., Conclusion: this proof-of-concept highlights the feasibility and the interest of augmented reality for hidden anatomical structures visualisation without artificial markers., Competing Interests: Declaration of Conflicting Interest The Authors declare that there is no conflict of interest, (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objectives: To identify the preferred surgical approach (intra- or extra-oral) to remove an ectopic third mandibular molar (ETMM) according on its location and presence of an associated cyst or cutaneous fistula, and to determine the indications for a graft or osteosynthesis., Materials and Methods: A surgical practice questionnaire was distributed to oral and maxillo-facial surgeons attending a National Congress of the French Society of Stomatology, Maxillo-facial and Oral Surgery. A systematic review of the literature and meta-analysis was carried on Pubmed, Cochrane, Embase and ScienceDirect databases using the MeSH terms: "Ectopic teeth", "Third molar", "Mandibular". One hundred and forty-three surgeons answered the questionnaire and the meta-analysis included 66 articles., Results: From the questionnaire, the preferred surgical approach was intra-oral except when the ETMM was in the condyle, when it was extra-oral (69.5%; p < 0.001). In the meta-analysis, an extra-oral approach was only indicated when a cutaneous fistula was present (90% vs. 35.9%; p = 0.002), irrespective of ETMM location. In the questionnaire and meta-analysis, the presence of a cyst did not change the approach (p < 0.05). The indications for a graft or osteosynthesis were a condylar location (p < 0.001), while a cutaneous fistula decreased the indication (p = 0.04) and a cyst (p = 0.009) was only associated with a graft., Conclusions: The preferential approach was intra-oral, except when the ETMM was condylar or a cutaneous fistula was present when an extra-oral approach was preferred. Osteosynthesis or a graft were more likely when the ETMM was in the condyle., Clinical Relevance: This study will help to orientate surgeons vis-à-vis ETMM treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To test the compatibility of intravenous (IV) lactated Ringer's injection (LR) with 94 injectable (IV) drugs during simulated Y-site administration. Methods: Ninety-four IV drugs were investigated for compatibility with LR (Baxter). Each sample was prepared in duplicate and performed at room temperature. Two observers performed visual evaluation independently immediately upon mixing and then 15 minutes, 1 hour, 2 hours, 3 hours, and 4 hours after admixture. Another observer performed a particle counting test on 1 of the 2 duplicates of each admixture that did not immediately show incompatibility and then after 4 hours by a light obscuration particle count test. Results: Of the 94 tested drugs, 86 were found to be compatible with LR. A total of 8 drugs were found to be physically incompatible. Of these incompatible drugs, 7 were directly identified visually and 1 was confirmed by the light obscuration particle count test. Conclusion: Lactated Ringer's injection was physically compatible for 4 hours with 86 tested drugs during simulated Y-site administration. Eight drugs, ciprofloxacin, cyclosporine, diazepam, ketamine, lorazepam, nitroglycerin, phenytoin, and propofol, were found to be incompatible and should not be administered with LR., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Ectopic maxillary third molars (EMTM) are extracted mainly by the Caldwell-Luc technique but also by nasal endoscopy. There is currently no consensus on the treatment of this eruption and its management is heterogeneous and multidisciplinary. Two literature searches were performed with no time restrictions via Pubmed. In the first, we used the keywords "ectopic AND third molar" and in the second the keywords "dentigerous cyst AND ectopic third molar". For both articles, epidemiological, symptomatic, radiological and surgical data were recorded. Overall, 33 eligible articles were identified involving 39 cases of EMTM. 79% of patients were symptomatic. 87% of the teeth were associated with a dental cyst. In only 13% of cases was the location of the tooth in the sinus specified in the three planes of the space. Surgery was performed in 77% of patients by the Caldwell-Luc technique, by nasal endoscopy in 10% and by the Le Fort I approach in 3%. The indications for avulsion of EMTM are symptomatic patients or asymptomatic patients with an associated cyst. The intra-sinusal location of the tooth is not a factor in the choice of technique used, which depends rather on the individual skills of the surgeon. Although for a trained operator the Le Fort I osteotomy is an easy procedure, its interest in the treatment of EMTM is limited owing to the rare but potentially severe complications involved., (Copyright © 2020. Published by Elsevier Masson SAS.)

Arthrogryposis multiplex congenita (AMC) is a rare entity gathering many diseases, isolated or included in more global syndromes. It affects symmetrically joints of lower limbs, back and maxillofacial area with temporomandibular joint (TMJ) impairment leading to deterioration of oral functions and mouth opening resulting in poor quality of life. Therapeutic strategy varies according to type and severity of impairment and could involve physical therapy and/or surgery. This article reported a case of AMC followed in our unit and highlighting various maxillo-facial impairments, especially restricted mouth opening and its consequences due to fibrotic TMJ and hypertrophic coronoid processes. We described our therapeutic approach based on surgery and postoperative physical therapy. A stable improvement of mouth opening was obtained, and patient's quality of life was increased. We performed a review of the literature and suggested a therapeutic management of mouth opening limitation in AMC., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Intraosseous hemangiomas are rare benign tumors that can develop in the skull. Orbitofrontal localization is uncommon. The complexity of orbitofrontal anatomy results in difficult reconstruction following trauma or tumoral resection., Case Presentation: A 50-year-old woman with a right orbitofrontal intraosseous hemangioma was referred to our department. The authors decided to perform tumoral bone resection and orbitofrontal reconstruction using virtual surgical planning in collaboration with Materialize engineers (Materialise, Leuven, Belgium). Three cutting guides and a patient-specific 3-dimensional (3D) titanium implant were designed and manufactured in 3 weeks. Surgery was performed with a double surgical team composed of maxillofacial surgeons and neurosurgeons. No perioperative or post-operative complications occurred. Post-operatively, the patient was completely asymptomatic and clinical examination showed symmetrical and satisfactory facial morphology., Conclusion: Virtual surgical planning, design of patient-specific guides and manufacturing of implants make surgery easier and increase surgical precision. This technique is recommended for wide use in cases of oncological or complex trauma craniomaxillofacial reconstruction., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by Mutaz B. Habal, MD.)

Background: Numerous biochemical datas support the noxious role of anti-inflammatory drugs on immune response. Those observations are often put forward for unfavorable evolution of odontogenic infection but has never been really proven in clinic. The aim of this study is to try to clarify this role based on the collection of the clinical course of odontogenic infections over a 10-year analysis period., Material and Methods: The investigators implemented a prospective observational study. The sample was composed of patients managed between January 2004 and December 2014 for severe odontogenic infection based on three criteria: hospital admission, intravenous antibiotic therapy, tooth extraction and collections drainage under general anesthesia. Clinical and pharmacological data were collected at admission, during hospitalization until discharged home. The population was first separated into two groups patients with or without anti-inflammatory drugs on admission, then on four groups (non-steroidal anti-inflammatory drugs, corticosteroids drugs, both and none on admission). Analysis were performed each time by univariate analysis, multivariate analysis and propensity score matching., Results: Six hundred and fifty-three patients were included in the study, 329 (50%) patients report orally anti-inflammatory treatment before presenting to hospital, 50 (7.6%) received corticosteroids, 242 (37%) received NSAIDs and 37 (5.6%) both. Evolution is worsening for patients under anti-inflammatory drugs in term of hospitalization in ICU (p=0.016), number of surgeries (p=0.003), risk of tracheotomy (p=0.036), duration of hospitalization (p=0.005) and spaces involved by the infection (p<0.001). When separating patients into 4 groups, dysphonia and odynophagia are more frequent for patients under corticosteroid and NSAID (35.14%, p<0.001), mediastinal erythema is more frequent for patients under corticosteroid (16%, p=0.004), fever is more frequent for patients under NSAID (35.5%, p=0.032), pain is higher for patients under corticosteroids (p=0.024). But, in order to reduce bias, linked to factors of gravity, a regression weighted by propensity scores was performed and any group of patients is different from the others., Conclusions: Patients under anti-inflammatory drugs have more severe dental infection on admission and their complex evolution seems to be linked to the severity of infection on admission.

Background : Dental cellulitis management is no longer a simple procedure, as more and more patients are needing long-time hospitalization, several surgeries and intensive care follow-up. This prospective study seeks to highlight criteria that can split patients with severe odontogenic infection into two groups: those with simple evolution and those for whom complex management is necessary. Methods : In this observational study, all patients considered with a severe odontogenic infection (which necessitated hospital admission, intravenous antibiotics and general anaesthesia) were enrolled between January 2004 and December 2014 from Clermont-Ferrand University Hospital (France). They were split into two groups: those who needed one surgical intervention with tooth extraction and collection drainage combined with probabilistic antibiotic to treat infection and those who need several surgeries, intensive care unit follow-up or tracheotomy to achieve healing. Results : 653 patients were included, of which 611 (94%) had one surgery, 42 (6%) had more than one surgery before healing. Penicillin allergy ( p < 0.001), psychiatric disorders ( p = 0.005), oropharyngeal oedema ( p = 0.008), floor oedema ( p = 0.004), fever ( p = 0.04) and trismus ( p = 0.018) on admission were the most relevant predictors of complex evolution. A conditional inference tree (CTREE) illustrated the association of prognostic factors and the need of multiple surgery. Conclusion s : Besides clinical symptoms of severity, complications of severe odontogenic infection are predicted by measurables and objectives criteria as penicillin allergy, mandibular molar, C-reactive protein level, psychiatric disorders and alcohol abuse. Their specific association potentialize the risks. IRB number: CE-CIC-GREN-12-08., Competing Interests: The authors declare that they have no competing interests.

Severe nasal septal deformities can be responsible for functional and aesthetic impairments. Correction of these deformities can be difficult and restoring perfect nasal shape and function is still challenging. Classical techniques can, sometimes, lead to disappointing results or relapse. In this article, the aim was to describe the different techniques of extracorporeal septorhinoplasty and fixation of the neoseptum. Three techniques are mainly used: "crisscross" suture, "U-shaped" suture and anterior septal reconstruction to fix the neoseptum after extracorporeal remodeling. All these techniques are technically demanding, especially concerning keystone area management; but, if well performed, could give satisfactory functional and aesthetic outcomes. We therefore think that extracorporeal septorhinoplasty should really improve our results concerning functional and aesthetic aspects in case of severe anterior or caudal septum deviation., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Canine models of Duchenne muscular dystrophy (DMD) are a valuable tool to evaluate potential therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been described in canines, but the Golden Retriever muscular dystrophy (GRMD) model remains the most used in preclinical studies. Here, we report a new spontaneous dystrophinopathy in a Labrador Retriever strain, named Labrador Retriever muscular dystrophy (LRMD)., Methods: A colony of LRMD dogs was established from spontaneous cases. Fourteen LRMD dogs were followed-up and compared to the GRMD standard using several functional tests. The disease causing mutation was studied by several molecular techniques and identified using RNA-sequencing., Results: The main clinical features of the GRMD disease were found in LRMD dogs; the functional tests provided data roughly overlapping with those measured in GRMD dogs, with similar inter-individual heterogeneity. The LRMD causal mutation was shown to be a 2.2-Mb inversion disrupting the DMD gene within intron 20 and involving the TMEM47 gene. In skeletal muscle, the Dp71 isoform was ectopically expressed, probably as a consequence of the mutation. We found no evidence of polymorphism in either of the two described modifier genes LTBP4 and Jagged1. No differences were found in Pitpna mRNA expression levels that would explain the inter-individual variability., Conclusions: This study provides a full comparative description of a new spontaneous canine model of dystrophinopathy, found to be phenotypically equivalent to the GRMD model. We report a novel large DNA mutation within the DMD gene and provide evidence that LRMD is a relevant model to pinpoint additional DMD modifier genes.

One of the main challenges in cell therapy for muscle diseases is to efficiently target the muscle. To address this issue and achieve better understanding of in vivo cell fate, we evaluated the relevance of a non-invasive cell tracking method in the Golden Retriever Muscular Dystrophy (GRMD) model, a well-recognised model of Duchenne Muscular Dystrophy (DMD). Mesoangioblasts were directly labelled with 111 In-oxine, and injected through one of the femoral arteries. The scintigraphy images obtained provided the first quantitative mapping of the immediate biodistribution of mesoangioblasts in a large animal model of DMD. The results revealed that cells were trapped by the first capillary filters: the injected limb and the lung. During the days following injection, radioactivity was redistributed to the liver. In vitro studies, performed with the same cells prepared for injecting the animal, revealed prominent cell death and 111 In release. In vivo, cell death resulted in 111 In release into the vasculature that was taken up by the liver, resulting in a non-specific and non-cell-bound radioactive signal. Indirect labelling methods would be an attractive alternative to track cells on the mid- and long-term.

Recently, several promising treatments have emerged for neuromuscular disorders, highlighting the need for robust biomarkers for monitoring therapeutic efficacy and maintenance of the therapeutic effect. Several studies have proposed circulating and tissue biomarkers, but none of them has been validated to monitor acute and long-term drug response. We previously described how the myostatin (MSTN) level is naturally downregulated in several neuromuscular diseases, including Duchenne muscular dystrophy (DMD). Here, we show that the dystrophin-deficient Golden Retriever muscular dystrophy (GRMD) dog model also presents an intrinsic loss of Mstn production in muscle. The abnormally low levels of Mstn observed in the GRMD dog puppies at 2 months were partially rescued at both mRNA and protein level after adeno-associated virus (AAV)-microdystrophin treatment in a dose-dependent manner. These results show that circulating Mstn is a robust and reliable quantitative biomarker, capable of measuring a therapeutic response to pharmaco-gene therapy in real time in the neuromuscular system, as well as a quantitative means for non-invasive follow-up of a therapeutic effect. Moreover, a 2-year follow-up also suggests that Mstn could be a longitudinal monitoring tool to follow maintenance or decrease of the therapeutic effect., (© 2020 The Authors.)

Duchenne Muscular Dystrophy (DMD) is a lethal muscle disorder, caused by mutations in the DMD gene and affects approximately 1:5000-6000 male births. In this report, we identified dysregulation of members of the Dlk1-Dio3 miRNA cluster in muscle biopsies of the GRMD dog model. Of these, we selected miR-379 for a detailed investigation because its expression is high in the muscle, and is known to be responsive to glucocorticoid, a class of anti-inflammatory drugs commonly used in DMD patients. Bioinformatics analysis predicts that miR-379 targets EIF4G2, a translational factor, which is involved in the control of mitochondrial metabolic maturation. We confirmed in myoblasts that EIF4G2 is a direct target of miR-379, and identified the DAPIT mitochondrial protein as a translational target of EIF4G2. Knocking down DAPIT in skeletal myotubes resulted in reduced ATP synthesis and myogenic differentiation. We also demonstrated that this pathway is GC-responsive since treating mice with dexamethasone resulted in reduced muscle expression of miR-379 and increased expression of EIF4G2 and DAPIT. Furthermore, miR-379 seric level, which is also elevated in the plasma of DMD patients in comparison with age-matched controls, is reduced by GC treatment. Thus, this newly identified pathway may link GC treatment to a mitochondrial response in DMD.

Untreated zygomaticomaxillary complex fractures may lead to aesthetical and functional sequelae needing secondary surgical correction. A 31-year-old male was addressed to our department for right enophthalmos and loss of cheek projection 3 months after facial trauma. Restauration of facial symmetry can be achieved by repositioning of the zygomaticomaxillary complex by osteotomies. To achieve good functional and aesthetical results, the reduction needs to be accurate. This is the main difficulty in delayed cases as there are less anatomical landmarks due to initial trauma and bone remodeling. Nowadays, in France, thanks to good care access, very few patients are not treated within the first two weeks after trauma; thus, surgeons have little experience on secondary reduction. It has been reported that navigation-guided surgery and use of stereolithographic models improve results. In small centers, access to both technologies and induced over-cost may limit their use. With the ease to access a 3D printer, small centers have to develop innovative, simple ways to offer comparative results. In the case presented, surgery planning and plate modeling were achieved using an office-based three-dimensional printed model. To reduce the cost, free open source software has been used. In this case, facial symmetry has been restored and post-operative computed tomography scan shows good stability. This simple, cost effective technique, is applicable in most centers equipped with a 3D printer and ensures a good and reproductive result even when this surgery is not routinely done.