Chemical painful post-traumatic trigeminal neuropathy induced by dental bleaching: A case report.

Background: Teeth whitening is a frequent request in clinical practice. The most widely used whitening agent on vital teeth is carbamide peroxide. This article reports a rare adverse effect following a whitening procedure. Case description: A 29-year-old patient was referred to the dental emergency department for severe pain that exhibited the characteristics of neuropathic pain. In the absence of any visible lesion or traumatic event, this pain was linked to the recent application of carbamide peroxide (10%) during a bleaching procedure. The diagnosis of painful post-traumatic trigeminal neuropathy (PTTN) of chemical origin was made. Treatment with the anticonvulsant gabapentin (900mg per day) gradually reduced the pain until its complete disappearance. After presenting the clinical characteristics of the case, the pathophysiological hypotheses are discussed. Practical implications: Carbamide peroxide application may elicit nerve damage through a cascade of cellular and biological reactions, resulting in neuropathic pain. The successful management of this clinical case may provide useful information for similar situations. Key words:Case report, carbamide peroxide, painful neuropathy, pain, gingiva.

[Oral cavity cancer: A distinct entity]. / Le cancer de la cavité orale : une entité spécifique ?

Oral Squamous cell carcinoma represent the 17th most frequent cancer in the world. The main risk factors are alcohol and tobacco consumption but dietary, familial, genetic, or oral diseases may be involved in oral carcinogenesis. Diagnosis is made on biopsy, but detection remains late, leading to a poor prognosis. New technologies could reduce these delays, notably Artificial Intelligence and the quantitative evaluation of salivary biological markers. Currently, management of oral cancer consists in surgery, which can be mutilating despite possible reconstructions. In the future, immunotherapies could become a therapeutic alternative and the immune microenvironment could constitute a source of prognostic markers.

Title: Le cancer de la cavité orale : une entité spécifique ? Abstract: Les carcinomes épidermoïdes de la cavité orale sont le 17e cancer le plus fréquent dans le monde. Les facteurs de risque principaux sont l'alcool et le tabac mais des facteurs alimentaires, familiaux, génétiques ou certaines maladies orales peuvent intervenir dans la genèse de ces cancers. Le diagnostic est tardif, entraînant un pronostic sombre. De nouvelles approches, comme l'utilisation de l'intelligence artificielle ou de marqueurs biologiques salivaires pourraient réduire ces délais. La prise en charge actuelle de ces cancers repose sur la chirurgie, la chimiothérapie et la radiothérapie, mais avec une iatrogénie importante. Les immunothérapies pourraient devenir une alternative à ces traitements et certaines caractéristiques du microenvironnement immunitaire pourraient constituer un/des marqueurs pronostiques.

Artificial intelligence for oral squamous cell carcinoma detection based on oral photographs: A comprehensive literature review.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) presents a significant global health challenge. The integration of artificial intelligence (AI) and computer vision holds promise for the early detection of OSCC through the analysis of digitized oral photographs. This literature review explores the landscape of AI-driven OSCC automatic detection, assessing both the performance and limitations of the current state of the art. MATERIALS AND METHODS: An electronic search using several data base was conducted, and a systematic review performed in accordance with PRISMA guidelines (CRD42023441416). RESULTS: Several studies have demonstrated remarkable results for this task, consistently achieving sensitivity rates exceeding 85% and accuracy rates surpassing 90%, often encompassing around 1000 images. The review scrutinizes these studies, shedding light on their methodologies, including the use of recent machine learning and pattern recognition approaches coupled with different supervision strategies. However, comparing the results from different papers is challenging due to variations in the datasets used. DISCUSSION: Considering these findings, this review underscores the urgent need for more robust and reliable datasets in the field of OSCC detection. Furthermore, it highlights the potential of advanced techniques such as multi-task learning, attention mechanisms, and ensemble learning as crucial tools in enhancing the accuracy and sensitivity of OSCC detection through oral photographs. CONCLUSION: These insights collectively emphasize the transformative impact of AI-driven approaches on early OSCC diagnosis, with the potential to significantly improve patient outcomes and healthcare practices.

Oral prosthetic rehabilitation in patients with Epidermolysis Bullosa Hereditaria: a systematic review.

Epidermolysis bullosa hereditaria (EBH) is a group of rare diseases characterized by a cutaneous-mucosal fragility with the formation of bullae, including the oral mucosa. Therapeutic choices, especially prosthetic rehabilitation, must anticipate the worsening of the limitation of oral opening while respecting the functional and aesthetic expectations of the patients. This review on the oral prosthetic rehabilitation of patients with epidermolysis bullosa hereditaria (EBH) to study the level of evidence and quality of the presented available articles and establish clinical recommendations for the prosthetic management of these patients. MATERIALS AND METHODS: An electronic search was done in July 2022 in five databases following PICOTS elements. The quality of the reports was established using the modified Pierson, Bradford Hills, and Ottawa Newcastle scale. RESULTS: Data extracted from 19 case reports for protocolized analysis corresponded to 64 patients and 80 dental prostheses with almost 9 out of 10 patients being completely edentulous. The distribution of EBH types was 84% dystrophic, 10.5% junctional, and 5.5% simplex. The difficulties encountered by the authors synthetized in this review characteristically reflected those most likely encountered in dental practice. Most rehabilitations were implant-supported prostheses (85%) followed by removable dentures (10%) and finally dental-supported rehabilitations (5%). Fixed full-arch implant-supported prostheses represented 76.4% of implant-supported prostheses and this last prosthetic solution described showed the highest scientific quality. CONCLUSIONS: In an individualized approach to treatment, we recommend that in cases of total edentulism, fixed full arch implant-supported prostheses are the most appropriate, as they allow the best computer-aided planning, design, manufacture, and fitting of the prosthesis in such a complex clinical context.

An Unusual Case of Recurrent Gingival Epstein-Barr Virus-Positive B-Cell Lymphoproliferation.

Epstein-Barr virus (EBV)-positive mucocutaneous ulceration commonly presents as a B-cell lymphoproliferative process with manifold aspects. There is scarce data on its oral manifestation in the scientific literature. We report the case of a 57-year-old male immunocompromised renal transplant patient who developed recurrent chronic and symptomatic mucosal ulceration facing the mandibular incisor teeth. Pathological examination with microscopic and immunohistochemistry studies revealed a B plasma cell infiltration as well as positive staining for EBV, leading to a diagnosis of EBV-positive mucocutaneous ulceration with B-cell lymphoproliferation after extensive workup. Treatment with rituximab was implemented and led to the healing of the lesion. This lesion develops in geriatric and immunodeficient patients and may require oncological therapies. While it is generally associated with an excellent prognosis, it may be indicative of underlying immunosuppression, and hence oral cavity specialists must be aware of this particular entity.

Implant retained prosthesis on a free fibula flap: A challenging procedure for prosthetic and soft tissue management.

A 39-year-old woman who had undergone fibular flap reconstruction and simultaneous implant placement after the surgical removal of a cemento-ossifying fibroma was experiencing mild discomfort 3 years later and requested an implant-supported prosthesis to restore her edentulous left maxillary quadrant. Initially, an interim removable partial denture was provided and later duplicated with clear resin. The interim prosthesis identified the excessive thickness of the grafted cutaneous soft tissue and the inadequate emergence angle of the nonfunctioning implants. By using the interim prosthesis as a surgical guide, vestibuloplasty was performed to thin the peri-implant soft tissue and the excessive skin graft from the initial maxillofacial surgery. Concurrently, the emergence angle of the implant was corrected with angled multi-unit abutments. A tissue compression stent was then made and attached to the abutments to guide the soft tissue healing process. When the peri-implant soft tissue had stabilized, a definitive implant-supported prosthesis was provided.

Cytomegalovirus-induced oral ulcers: A case report and literature review.

Cytomegalovirus (CMV) ulcerations are rare clinical entities, but their occurrence is favored in immunocompromised patients who present a favorable environment for opportunistic infections. We describe the case of a patient treated for a systemic lupus erythematosus suffering from deep oral ulcerations. The case illustrates the complexity of establishing a precise etiological diagnosis of CMV lesions, as the diagnostic hypothesis can be varied: related to an immunodeficiency disorder or drug-induced toxidermia.

Implementation of game-based training in oral rehabilitation of edentulous patients in an undergraduate dental course.

BACKGROUND: Coronavirus disease-19 dramatically changed the learning conditions of dental students, with restricted access to training sessions and clinical practice. The "Playdent" project proposed the integration of serious games (SGs) in the third-year curriculum, based on tailor-made scenarios questioning the first dental visit of edentulous patients, and examined whether training with the games would advance students' learning outcomes. MATERIALS AND METHODS: Test scores of 89 students, allocated either to a "test" group that accessed SGs during a 4-week test period in addition to conventional lectures or to a "control" group that benefited solely from conventional lectures, were measured before and immediately after the test period. The subsequent satisfaction of students was assessed in the "test" group. RESULTS: Scores obtained after the 4-week period significantly increased within the "test" group (11.1% ± 24.9%, p = 0.04, degree of freedom [df] = 30) while they did not change within the "control" group (p = 0.21, df = 57). Qualitative feedback expressed by students who played SGs during the 4-week period demonstrated that 71% of them rated the SGs as satisfactory and 91% of them judged the consistency of SGs content with lectures to be satisfactory. CONCLUSION: Game-based learning showed a positive impact on the learning outcomes of third-year students. Qualitative assessments provide insights into the pertinence of SGs offered in addition to traditional lectures of third-year complete denture courses. SGs may consolidate skills in oral rehabilitation acquired through traditional passive learning formats proposed in preclinical courses.

Effectiveness and patient satisfaction of dental emergencies in Pitié Salpêtrière Hospital, Paris, during the COVID 19 pandemic.

Background: A previous study reported the effectiveness and patient satisfaction in the dental emergency unit (DEU) of the Pitie Salpetrière Hospital in Paris before coronavirus disease 2019 (COVID-19). The same methodology was used during the COVID-19 pandemic to compare pain, anxiety, and patient satisfaction during the two periods. Methods: This prospective study was conducted in 2020 (NCT04354272) on adult patients. Data were collected on day zero (D0) on site and then by phone during the daytime on day one (D1), day three (D3), and day seven (D7). The primary objective was to assess the pain intensity at D1. Secondary objectives were to assess pain intensity at D3 and D7, anxiety intensity at D1, D3, and D7, and patient satisfaction. Patients were evaluated on a 0-10 numeric scale on D1, D3, and D7; mean scores were compared with non-parametric statistics (ANOVA, Dunn's). Results: A total of 445 patients were given the opportunity to participate in the study, and 370 patients consented. Seventy-one were lost during follow-up. Ultimately, 299 patients completed all the questionnaires and were included in the analysis. In the final sample (60% men, 40% women, aged 39 ± 14 years), 94% had health insurance. The mean pain scores were: D0, 6.1 ± 0.14; D1, 3.29 ± 0.16; D3, 2.08 ± 0.16; and D7, 1.07 ± 0.35. This indicates a significant decrease of 46%, 67%, and 82% at D1, D3, and D7, respectively, when compared to D0 (P < 0.0001). The mean anxiety scores were D0, 4.7 ± 0.19; D1, 2.6 ± 0.16; D3, 1.9 ± 0.61; and D7, 1.4 ± 0.15. This decrease was significant between D0 and D7 (ANOVA, P < 0.001). Perception of general health improved between D1 and D7. The overall satisfaction was 9.3 ± 0.06. Conclusion: DEU enabled a significant reduction in pain and anxiety with high overall satisfaction during COVID-19, which was very similar to levels observed pre-COVID-19 pandemic.

Defining biomarkers in oral cancer according to smoking and drinking status.

Introduction: Oral Squamous Cell Carcinomas (OSCC) are mostly related to tobacco consumption eventually associated to alcohol (Smoker/Drinker patients: SD), but 25-30% of the patients have no identified risk factors (Non-Smoker/Non-Drinker patients: NSND). We hypothesized that these patients have distinguishable immune profiles that could be useful for prognosis. Materials and Methods: Cells present in immune tumor microenvironment (TME) and blood from 87 OSCC HPV-negative patients were analyzed using a multiparameter flow cytometry assay, in a prospective case-control study. Cytokine levels in tumor supernatants and blood were determined by a cytometric bead array (CBA) assay. Results: Normal gingiva and blood from healthy donors (HD) were used as controls. A significant increase of granulocytes (p<0.05 for blood), of monocytes-macrophages (p<0.01 for blood) and of CD4+ T cells expressing CD45RO and CCR6 (p<0.001 for blood; p<0.0001 for TME) as well as higher levels of IL-6 (p<0.01 for sera, p<0.05 for tumor supernatant) were observed in SD patients as compared to NSND OSCC patients and HD. High percentages of CD4+ T cells expressing CD45RO and CCR6 cells in tumor tissue (p=0.05) and blood (p=0.05) of SD OSCC patients were also associated with a poorer prognosis while a high percentage of regulatory T cells (Treg) in tumor tissue was associated with a more favorable prognostic factor (p=0.05). Also, a higher percentage of blood CD8+ T lymphocytes among CD45+ cells in NSND patients was associated with a better disease-free survival (p=0.004). Conclusion: Granulocytes, monocytes-macrophages, and CD4+ T cells expressing CD45RO and CCR6 in blood and TME as well as serum IL-6 can therefore distinguish OSCC SD and NSND patients. Quantifying the proportion of CD4+ T cells expressing CD45RO and CCR6 and of Treg in SD patients and CD8+ T cells in NSND patients could help defining the prognostic of OSCC patients.

In-house 3D printing: Why, when, and how? Overview of the national French good practice guidelines for in-house 3D-printing in maxillo-facial surgery, stomatology, and oral surgery.

3D-printing is part of the daily practice of maxillo-facial surgeons, stomatologists and oral surgeons. To date, no French health center is producing in-house medical devices according to the new European standards. Based on all the evidence-based data available, a group of experts from the French Society of Stomatology, Maxillo-Facial Surgery and Oral Surgery (Société Française de Chirurgie Maxillofaciale, Stomatologie et Chirurgie Orale, SFSCMFCO), provide good practice guidelines for in-house 3D-printing in maxillo-facial surgery, stomatology, and oral surgery. Briefly, technical considerations related to printers and CAD software, which were the main challenges in the last ten years, are now nearly trivial questions. The central current issues when planning the implementation of an in-house 3D-printing platform are economic and regulatory. Successful in-house 3D platforms rely on close collaborations between health professionals and engineers, backed by regulatory and logistic specialists. Several large-scale academic projects across France will soon provide definitive answers to governance and economical questions related to the use of in-house 3D printing.

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation.

The tumor microenvironment is a complex ecosystem almost unique to each patient. Most of available therapies target tumor cells according to their molecular characteristics, angiogenesis or immune cells involved in tumor immune-surveillance. Unfortunately, only a limited number of patients benefit in the long-term of these treatments that are often associated with relapses, in spite of the remarkable progress obtained with the advent of immune checkpoint inhibitors (ICP). The presence of "hot" tumors is a determining parameter for selecting therapies targeting the patient immunity, even though some of them still do not respond to treatment. In human studies, an in-depth analysis of the organization and interactions of tumor-infiltrating immune cells has revealed the presence of an ectopic lymphoid organization termed tertiary lymphoid structures (TLS) in a large number of tumors. Their marked similarity to secondary lymphoid organs has suggested that TLS are an "anti-tumor school" and an "antibody factory" to fight malignant cells. They are effectively associated with long-term survival in most solid tumors, and their presence has been recently shown to predict response to ICP inhibitors. This review discusses the relationship between TLS and the molecular characteristics of tumors and the presence of oncogenic viruses, as well as their role when targeted therapies are used. Also, we present some aspects of TLS biology in non-tumor inflammatory diseases and discuss the putative common characteristics that they share with tumor-associated TLS. A detailed overview of the different pre-clinical models available to investigate TLS function and neogenesis is also presented. Finally, new approaches aimed at a better understanding of the role and function of TLS such as the use of spheroids and organoids and of artificial intelligence algorithms, are also discussed. In conclusion, increasing our knowledge on TLS will undoubtedly improve prognostic prediction and treatment selection in cancer patients with key consequences for the next generation immunotherapy.

French recommendations for the management of systemic sclerosis.

Systemic sclerosis (SSc) is a generalized disease of the connective tissue, arterioles, and microvessels, characterized by the appearance of fibrosis and vascular obliteration. There are two main phenotypical forms of SSc: a diffuse cutaneous form that extends towards the proximal region of the limbs and/or torso, and a limited cutaneous form where the cutaneous sclerosis only affects the extremities of the limbs (without passing beyond the elbows and knees). There also exists in less than 10% of cases forms that never involve the skin. This is called SSc sine scleroderma. The prognosis depends essentially on the occurrence of visceral damage and more particularly interstitial lung disease (which is sometimes severe), pulmonary arterial hypertension, or primary cardiac damage, which represent the three commonest causes of mortality in SSc. Another type of involvement with poor prognosis, scleroderma renal crisis, is rare (less than 5% of cases). Cutaneous extension is also an important parameter, with the diffuse cutaneous forms having less favorable prognosis.

[Oral cavity as a target and a marker of environmental exposures: diseases diagnosed during adulthood]. / La sphère orale, cible et marqueur de l'exposition environnementale - II. Maladies diagnostiquées chez l'adulte.

The oral cavity is one of the main route for environmental contaminations associated to many chronic diseases via alimentation, medications and respiration. Other factors may also impact the oral environment, some of them are endogenous, like microbiota, hormones and saliva, and others are exogenous, like dental materials and pathogens.

TITLE: La sphère orale, cible et marqueur de l'exposition environnementale - II. Maladies diagnostiquées chez l'adulte. ABSTRACT: La cavité buccale est l'une des voies majeures des contaminations environnementales connues pour être impliquées dans de nombreuses maladies chroniques via l'alimentation, les médications ou même la respiration. D'autres facteurs peuvent également influer sur l'environnement oral, certains endogènes, comme le microbiote, les variations hormonales, la salive, d'autres exogènes, comme les biomatériaux dentaires et les agents pathogènes. Cette synthèse fait le point sur l'état des connaissances, les questions et controverses sur les facteurs environnementaux courants au contact de la sphère orale impliqués dans les maladies de la cavité orale diagnostiquées chez l'adulte telles que les cancers des voies aéro-digestives supérieures, les ostéonécroses des mâchoires, et les parodontites, ces dernières pouvant d'ailleurs être directement liées à des pathologies systémiques comme les accidents vasculaires cérébraux, la maladie d'Alzheimer ou la maladie de Crohn notamment. La caractérisation des impacts environnementaux sur le microbiote oral, la salive, l'émail dentaire peut servir de marqueur pronostic précoce des maladies diagnostiquées ultérieurement, en lien avec ces expositions.

CCR2 Influences T Regulatory Cell Migration to Tumors and Serves as a Biomarker of Cyclophosphamide Sensitivity.

The CCL2 chemokine receptor CCR2 drives cancer by mediating the recruitment of monocytes and myeloid-derived suppressor cells to the tumor microenvironment. In this study, we extend the significance of CCR2 in this setting by identifying a new role for it in mediating recruitment of CD4+ T regulatory cells (Treg). Following tumor initiation, an expanded population of CCR2+ Tregs required CCR2 expression to traffic between draining lymph nodes (dLN) and the tumor. This Treg subset was enriched in the fraction of tumor antigen-specific cells in the dLN, where they displayed an activated immunosuppressive phenotype. Notably, in mouse models, low-dose cyclophosphamide treatment preferentially depleted CCR2+ Treg, enhancing priming of tumor-specific CD8+ T cells. In the MMTV-PyMT transgenic mouse model of breast cancer and in oral squamous cell carcinoma patients, tumor development was associated with decreased blood frequency and inversely increased tumor frequency of CCR2+ Tregs. Our results define a novel subset of CCR2+ Treg involved in tumoral immune escape, and they offer evidence that this Treg subset may be preferentially eradicated by low-dose cyclophosphamide treatment. Cancer Res; 76(22); 6483-94. ©2016 AACR.

Intra-cheek immunization as a novel vaccination route for therapeutic vaccines of head and neck squamous cell carcinomas using plasmo virus-like particles.

Despite current therapy, head and neck squamous cell carcinomas (HNSCCs) arising from various mucosal sites of the upper aero-digestive tract frequently relapse in a loco-regional manner and have a poor prognosis. Our objective was to validate an innovative mucosal route of vaccination using plasmo virus-like particles (pVLPs) in a pre-clinical orthotopic model of HNSCCs. For this purpose, we used pVLP-E7, that are plasmid DNA encoding retroviral virus-like particles carrying a truncated E7 oncoprotein from HPV-16 as antigen model, to vaccinate mice bearing pre-established TC-1 tumors implanted into the buccal mucosa. pVLP-E7 were combined with clinical grade TLR agonists (Imiquimod and CpG-ODN). In this pre-clinical orthotopic model, whose tumor microenvironment resembles to those of human HNSCCs, different mucosal vaccination routes were tested for their ability to elicit efficient immune and antitumoral responses. Results showed that mucosal intra-cheek (IC) vaccinations using pVLP-E7, comparatively to intradermic vaccinations (ID), gave rise to higher mobilization of mucosal (CD49a(+)) CD8(+) specific effector T cells in both tumor draining lymph nodes (TdLNs) and tumor microenvironment resulting in better antitumor effects and in a long-term protection against tumor rechallenge. In vivo CD8(+) depletion demonstrated that antitumoral effects were fully dependent upon the presence of CD8(+) T cells. Validation of IC mucosal vaccinations with pVLPs combined with adjuvants using a pre-clinical orthotopic model of HNSCC provides valuable pre-clinical data to rapidly envision the use of such therapeutic vaccines in patients with HNSCCs, inasmuch as vaccinal components and adjuvants can be easily obtained as clinical grade reagents.

Engineered mesenchymal stem cells as vectors in a suicide gene therapy against preclinical murine models for solid tumors.

Gene-directed enzyme pro-drug therapy (GDEPT) consists of expressing, in tumor cells, a suicide gene which converts a pro-drug into cytotoxic metabolites, in situ. In a previous work, we demonstrated that the combination of the suicide gene CYP2B6TM-RED (a fusion of a triple mutant of CYP2B6 with NADPH cytochrome P450 reductase) and cyclophosphamide (CPA) constituted a powerful treatment for solid tumors. In this work, we investigated the use of mesenchymal stem cells (MSCs) as cellular vehicles for the delivery of our suicide gene. MSCs were genetically engineered ex-vivo to stably express CYP2B6TM-RED. Ex vivo and in vivo investigations showed that MSCs expressing CYP2B6TM-RED were able 1) to bioactivate CPA and produce local cytotoxic metabolites in tumor sites and 2) to destroy neighboring tumor cells through a bystander effect. Intratumoral injections of CYP2B6TM-RED-MSCs and CPA completely eradicated tumors in 33% of mice without recurrence after 6months. Rechallenge experiments demonstrated an efficient immune response. These data suggest that MSCs expressing CYP2B6TM-RED with CPA could represent a promising treatment for solid tumors to test in future clinical trials.

A suicide gene therapy combining the improvement of cyclophosphamide tumor cytotoxicity and the development of an anti-tumor immune response.

Gene-directed enzyme prodrug therapy (GDEPT) consists in targeted delivery to tumor cells of a suicide gene responsible for in situ conversion of a prodrug into cytotoxic metabolites. One of the major limitations of this strategy in clinical application was the poor prodrug activation capacity of suicide gene. We built a highly efficient suicide gene capable of bioactivating the prodrug cyclophosphamide (CPA) by fusing a CYP2B6 triple mutant with NADPH cytochrome P450 reductase (CYP2B6TM-RED). Expression of this fusion gene via a recombinant lentivirus (LV) vector converted resistant human (A549) and murine (TC1) pulmonary cell lines into CPA-susceptible cell lines. We tested the efficiency of our GDEPT strategy in C57Bl/6 immunocompetent mice, using TC1 cells expressing the HPV-16 E6/E7 oncoproteins. In mice bearing tumors composed only of TC1-CYP2B6TM-RED cells, four CPA injections (140 mg/Kg once a week) completely eradicated the tumors for more than two months. Tumors having only 25% of TC1-CYP2B6TM-RED cells were also completely eradicated by five CPA injections, demonstrating a major in vivo bystander effect. Moreover, surviving mice were rechallenged with parental TC1 cells. The tumors regressed spontaneously 7 days after cell inoculation or grew more slowly than in control naive mice due to a strong immune response mediated by anti-E7CD8(+)T cells. These data suggest that combining the CYPB6TM-RED gene with CPA may hold promise as a highly effective treatment for solid tumors in humans.