World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a consensus study.

OBJECTIVE: A core outcome set (COS) is the minimum agreed-on data set required to be measured in interventional trials. To date, there is no COS for oral lichen planus (OLP). This study describes the final consensus project that brought together the results of the previous stages of the project to develop the COS for OLP. STUDY DESIGN: The consensus process followed the Core Outcome Measures in Effectiveness Trials guidelines and involved the agreement of relevant stakeholders, including patients with OLP. Delphi-style clicker sessions were conducted at the World Workshop on Oral Medicine VIII and the 2022 American Academy of Oral Medicine Annual Conference. Attendees were asked to rate the importance of 15 outcome domains previously identified from a systematic review of interventional studies of OLP and a qualitative study of OLP patients. In a subsequent step, a group of OLP patients rated the domains. A further round of interactive consensus led to the final COS. RESULTS: The consensus processes led to a COS of 11 outcome domains to be measured in future trials on OLP. CONCLUSION: The COS developed by consensus will help reduce the heterogeneity of outcomes measured in interventional trials. This will allow future pooling of outcomes and data for meta-analyses. This project showed the effectiveness of a methodology that could be used for future COS development.

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a systematic review of outcome domains.

OBJECTIVE: There is a lack of consensus regarding clinician- and patient-reported oral lichen planus (OLP) outcomes. The World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research (WONDER) Project aims to develop a core outcome set (COS) for OLP, which would inform the design of clinical trials and, importantly, facilitate meta-analysis, leading to the establishment of more robust evidence for the management of this condition and hence improved patient care. STUDY DESIGN: Ovid MEDLINE, Embase, CINAHL, CENTRAL, and Clinicaltrials.gov were searched for interventional studies (randomized controlled trials, controlled clinical trials, and case series including ≥5 participants) on OLP and oral lichenoid reactions published between January 2001 and March 2022 without language restriction. All reported primary and secondary outcomes were extracted. RESULTS: The searches yielded 9,135 records, and 291 studies were included after applying the inclusion criteria. A total of 422 outcomes were identified. These were then grouped based on semantic similarity, condensing the list to 69 outcomes. The most frequently measured outcomes were pain (51.9%), clinical grading of the lesions (29.6%), lesion size/extension/area (27.5%), and adverse events (17.5%). CONCLUSION: As a first step in developing a COS for OLP, we summarized the outcomes that have been used in interventional studies over the past 2 decades, which are numerous and heterogeneous.

Topical clobetasol treatment for oral lichen planus can cause adrenal insufficiency.

OBJECTIVE: Glucocorticoids suppress the hypothalamic-pituitary-adrenal axis, which may lead to glucocorticoid-induced adrenal insufficiency. The study aimed to investigate the prevalence of this state in patients with oral lichen planus treated with topical clobetasol propionate. METHODS: In this cross-sectional study, 30 patients with oral lichen planus receiving long-term (>6 weeks) clobetasol propionate gel 0.025% were invited to participate. Adrenal function was assessed by measuring morning plasma cortisol after a 48-h withdrawal of clobetasol treatment. In patients with plasma cortisol <280 nmol/L, a cosyntropin stimulation test was performed. RESULTS: Twenty-seven patients were included. Twenty-one (78%) patients presented with plasma cortisol ≥280 nmol/L (range 280-570 nmol/L), and six (22%) <280 nmol/L (range 13-260 nmol/L). Five of these six patients underwent cosyntropin stimulation that revealed severe adrenal insufficiency in two patients (cortisol peak 150 nmol/L and 210 nmol/L) and mild adrenal insufficiency in three patients (cortisol peak 350-388 nmol/L). CONCLUSION: In this study, approximately 20% of patients receiving intermittent topical glucocorticoid treatment for oral lichen planus had glucocorticoid-induced adrenal insufficiency. It is essential for clinicians to be aware of this risk and to inform patients about the potential need for glucocorticoid stress doses during intercurrent illness.

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: the patient perspective.

OBJECTIVE: This study aimed to explore the lived experience of patients with oral lichen planus (OLP) and investigate what treatment-related outcomes are the most important to them and should be included in a core outcome set (COS) for OLP. STUDY DESIGN: A qualitative study involving focus group work with 10 participants was conducted. Interviews with each focus group were held twice: session 1 explored the lived experience of patients with OLP, and session 2 allowed patients to review a summary of the outcome domains used in the OLP literature to date. The discussions were recorded, transcribed verbatim, and analyzed using framework analysis. RESULTS: In session 1, 4 themes and 8 sub-themes emerged from the data analysis. An additional outcome, 'knowledge of family and friends,' was suggested in session 2. CONCLUSIONS: We have gained valuable insight into the lived experience of patients with OLP via this qualitative study. To our knowledge, this study is the first to explore the patient perspective on what should be measured in clinical trials on OLP, highlighting an important additional suggested outcome. This additional outcome will be voted upon in a consensus process to determine a minimum COS for OLP.

Metataxonomic and metaproteomic profiling of the oral microbiome in oral lichen planus - a pilot study.

Background: A growing body of evidence demonstrates a different bacterial composition in the oral cavity of patients with oral lichen planus (OLP). Patients and methods: Buccal swab samples were collected from affected and non-affected sites of six patients with reticular OLP and the healthy oral mucosa of six control subjects. 16S rRNA gene MiSeq sequencing and mass spectrometry-based proteomics were utilised to identify the metataxonomic and metaproteomic profiles of the oral microbiome in both groups. Results: From the metataxonomic analysis, the most abundant species in the three subgroups were Streptococcus oralis and Pseudomonas aeruginosa, accounting for up to 70% of the total population. Principal Coordinates Analysis showed differential clustering of samples from the healthy and OLP groups. ANCOM-BC compositional analysis revealed multiple species (including P. aeruginosa and several species of Veillonella, Prevotella, Streptococcus and Neisseria) significantly over-represented in the control group and several (including Granulicatella elegans, Gemella haemolysans and G. parahaemolysans) in patients with OLP. The metaproteomic data were generally congruent and revealed that several Gemella haemolysans-belonging peptidases and other proteins with inflammatory and virulence potential were present in OLP lesions. Conclusion: Our data suggest that several bacterial species are associated with OLP. Future studies with larger cohorts should be conducted to determine their role in the aetiology of OLP and evaluate their potential as disease biomarkers.

Guanidino quinazolines and pyrimidines promote readthrough of premature termination codons in cells with native nonsense mutations.

Using small molecules to induce readthrough of premature termination codons is a promising therapeutic approach to treating genetic diseases and cancers caused by nonsense mutations, as evidenced by the widespread use of ataluren to treat nonsense mutation Duchene muscular dystrophy. Herein we describe a series of novel guanidino quinazoline and pyrimidine scaffolds that induce readthrough in both HDQ-P1 mammary carcinoma cells and mdx myotubes. Linkage of basic, tertiary amines with aliphatic, hydrophobic substituents to the terminal guanidine nitrogen of these scaffolds led to significant potency increases. Further potency gains were achieved by flanking the pyrimidine ring with hydrophobic substituents, inducing readthrough at concentrations as low as 120 nM and demonstrating the potential of these compounds to be used either in combination with ataluren or as stand-alone therapeutics.

Antioxidant and Inhibitory Capacity of Tomato Leaf Ethanolic Extract against Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans / Capacidad Antioxidante e Inhibitoria del Extracto Etanólico de la Hoja de Tomate contra Streptococcus mutans, Porphyromonas gingivalis y Candida albicans

Background: Tomato is a source of bioactive compounds, antimicrobials, and antioxidants. Tomato leaf preparations have been empirically used for anti-inflammatory, analgesic, antibiotic, and antiseptic purposes. However, research on the potential activity of tomato leaf extracts against oral microorganisms and in managing oropharyngeal infections is scarce. Objective: To investigate tomato leaf ethanolic extract's antioxidant and growth inhibitory capacity against common oral pathogenic microorganisms, namely, Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans.Methods: Ethanolic extracts were made from 'Chonto' tomato (Lycopersicon esculentum) leaves. The antimicrobial activity was measured with the microdilution technique using vancomycin and fluconazole as positive controls. The antioxidant capacity was measured with the ORAC assay using Trolox as a positive control. Results: We found a high percentage of growth inhibition (≥100%) against S. mutans and P. gingivalis at a concentration of 500 mg/L. However, the extract was ineffective in inhibiting the growth of C. albicans. Finally, we observed that the extract exerted a high antioxidant capacity (126%) compared to the positive control. Conclusions: This study provides new insights into the potential antimicrobial effect of tomato leaf extracts on common oral pathogenic bacteria, which may ultimately result in the development of new herbal products that might help prevent and treat oral infections, such as dental caries and periodontal disease. Our findings also support previous studies on the high antioxidant capacity of tomato leaf extracts

Antecedentes: El tomate es una fuente de compuestos bioactivos, antimicrobianos y antioxidantes. Las hojas de tomate se han utilizado empíricamente con fines antiinflamatorios, analgésicos, antibióticos y antisépticos. Sin embargo, los estudios sobre la actividad de los extractos de hojas de tomate contra los microorganismos orales y en el manejo de las infecciones orofaríngeas son escasos. Objetivo: Investigar la capacidad antioxidante del extracto etanólico de la hoja de tomate y su actividad inhibitoria de crecimiento contra microorganismos patógenos orales comunes, a saber, Streptococcus mutans, Porphyromonas gingivalis y Candida albicans.Métodos: Se realizaron extractos etanólicos a partir de hojas de tomate 'Chonto' (Lycopersicon esculentum). La actividad antimicrobiana se midió con la técnica de microdilución utilizando vancomicina y fluconazol como controles positivos. La capacidad antioxidante se midió con el ensayo ORAC utilizando Trolox como control positivo. Resultados: Encontramos un alto porcentaje de inhibición del crecimiento (≥100%) contra a S. mutans y P. gingivalis a una concentración de 500 mg/L. Sin embargo, el extracto fue ineficaz en la inhibición el crecimiento de C. albicans. Finalmente, observamos que el extracto tuvo una alta capacidad antioxidante (126%) en comparación con el control positivo. Conclusiones: Este estudio proporciona nuevos conocimientos sobre el posible efecto antimicrobiano de los extractos de hojas de tomate en bacterias patógenas orales comunes, lo cual puede resultar en el desarrollo de nuevos productos naturales que podrían ayudar a prevenir y tratar infecciones orales, como la caries dental y la enfermedad periodontal. Nuestros hallazgos también respaldan los estudios previos sobre la alta capacidad antioxidante de los extractos de hojas de tomate

Langerhans Cells, T Cells, and B Cells in Oral Lichen Planus and Oral Leukoplakia.

Although oral lichen planus (OLP) and oral leukoplakia (LPL) have different pathogenetic profiles, both may involve chronic inflammation. The aim of this observational study was to evaluate the inflammatory cell profiles of OLP and LPL. The inflammatory cell infiltrates in patients with OLP and LPL were analyzed for the presence of Langerhans cells (LCs; CD1a), T cells (CD3), and B cells (CD20), as well as for the proliferation marker Ki-67. Biopsied specimens from patients with OLP (N = 14) and LPL without dysplasia (N = 13) were immunohistochemically stained with antibodies directed against CD1a, CD3, CD20, and Ki-67, followed by quantitative analyses. A significant increase in the number of CD3+ cells and CD20+ cells was found in the submucosa of OLP, as compared to LPL (p < 0.01). Likewise, the number of CD3+ cells was significantly higher in the epithelium of OLP than of LPL (p < 0.05). No differences were found in the expression of Ki-67 and the number of CD1a+ cells between the two groups. Although an immune response is elicited in both conditions, there are differences at the cellular level between OLP and LPL. A more robust immune activation involving T cells and B cells is seen in OLP. The role of B cells in OLP needs to be further elucidated. Although the number of B cells in LPL is low, their role in the inflammatory response cannot be ruled out.

Chemical modifications of G418 (geneticin): Synthesis of novel readthrough aminoglycosides results in an improved in vitro safety window but no improvements in vivo.

G418 is currently the most potent and active aminoglycoside to promote readthrough of eukaryotic nonsense mutations. However, owing to its toxicity G418 cannot be used in vivo to study readthrough activity A robust and scalable method for selective derivatization of G418 was developed to study the biological activity and toxicity of a series of analogs. Despite our synthetic efforts, an improvement in readthrough potency was not achieved. We discovered several analogs that demonstrated reduced zebra fish hair cell toxicity (a surrogate for ototoxicity), but this reduction in cellular toxicity did not translate to reduced in vivo toxicity in rats.

Coexistence of thyroid disease and oral lichen planus in a Colombian population.

Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease of unknown etiology. OLP has recently been linked to thyroid disease, mainly hypothyroidism. The aim of this study was to determine the prevalence of thyroid disease in Colombian patients with OLP. A total of860 clinical records of patients attending the clinics of oral medicine and oral and maxillofacial surgery at IPS CES Sabaneta, Colombia, between 2010 and 2016 were reviewed. Fourteen patients (1.6%) had a diagnosis of OLP. The prevalence of hypothyroidism in patients with OLP was 35.7%, compared to 3.95% in the entire study population (OR 15.92, 95% CI: 5.63-50.09, P = 0.0001). Patients with concomitant hypothyroidism and OLP presented with less severe oral lesions compared to those without thyroid disease. This study supports the notion that patients with OLP should be screened for thyroid disease.

El liquen plano oral (LPO) es una enfermedad mucocutánea inflamatoria crónica de etiología desconocida. El LPO ha sido asociado recientemente con la enfermedad de la tiroides, especialmente con hipotiroidismo. El objetivo con este estudio fue determinar la prevalencia de la enfermedad de la tiroides en pacientes colombianos con LPO. Un total de 860 historias clínicas de pacientes que asistieron entre 2010 y 2016 a las clínicas de medicina oral y de cirugía oral y maxilofacial de la IPS CES Sabaneta, Colombia, fueron revisadas. Catorce pacientes (1.6%) habían sido diagnosticados con LPO. La prevalencia de hipotiroidismo en pacientes con LPO fue 35.7%, comparada con 3.95% en toda la población de estudio (RM 15.92, 95% IC: 5.63-50.09, P = 0.0001). Pacientes con hipotiroidismo y LPO concomitante presentaron lesiones orales menos severas comparado con aquellos sin enfermedad de la tiroides. Este estudio respalda la idea de que se debe investigar la presencia de enfermedad de la tiroides en pacientes con LPO.

Coexistence of thyroid disease and oral lichen planus in a Colombian population / Coexistencia de enfermedad de la tiroides y liquen plano oral en una población colombiana

Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease of unknown etiology. OLP has recently been linked to thyroid disease, mainly hypothyroidism. The aim of this study was to determine the prevalence of thyroid disease in Colombian patients with OLP. A total of860 clinical records of patients attending the clinics of oral medicine and oral and maxillofacial surgery at IPS CES Sabaneta, Colombia, between 2010 and 2016 were reviewed. Fourteen patients (1.6%) had a diagnosis of OLP. The prevalence of hypothyroidism in patients with OLP was 35.7%, compared to 3.95% in the entire study population (OR 15.92, 95% CI: 5.63-50.09, P = 0.0001). Patients with concomitant hypothyroidism and OLP presented with less severe oral lesions compared to those without thyroid disease. This study supports the notion that patients with OLP should be screened for thyroid disease.

El liquen plano oral (LPO) es una enfermedad mucocutánea inflamatoria crónica de etiología desconocida. El LPO ha sido asociado recientemente con la enfermedad de la tiroides, especialmente con hipotiroidismo. El objetivo con este estudio fue determinar la prevalencia de la enfermedad de la tiroides en pacientes colombianos con LPO. Un total de 860 historias clínicas de pacientes que asistieron entre 2010 y 2016 a las clínicas de medicina oral y de cirugía oral y maxilofacial de la IPS CES Sabaneta, Colombia, fueron revisadas. Catorce pacientes (1.6%) habían sido diagnosticados con LPO. La prevalencia de hipotiroidismo en pacientes con LPO fue 35.7%, comparada con 3.95% en toda la población de estudio (RM 15.92, 95% IC: 5.63-50.09, P = 0.0001). Pacientes con hipotiroidismo y LPO concomitante presentaron lesiones orales menos severas comparado con aquellos sin enfermedad de la tiroides. Este estudio respalda la idea de que se debe investigar la presencia de enfermedad de la tiroides en pacientes con LPO.

World Workshop on Oral Medicine VII: Targeting the oral microbiome Part 2: Current knowledge on malignant and potentially malignant oral disorders.

OBJECTIVE: The World Workshop on Oral Medicine VII chose the oral microbiome as a focus area. Part 1 presents the methodological state of the science for oral microbiome studies. Part 2 was guided by the question: What is currently known about the microbiome associated with oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa? MATERIALS AND METHODS: A scoping review methodology was followed to identify and analyse relevant studies on the composition and potential functions of the oral microbiota using high-throughput sequencing techniques. The authors performed searches in PubMed and EMBASE. After removal of duplicates, a total of 239 potentially studies were identified. RESULTS: Twenty-three studies on oral squamous cell carcinoma, two on oral leukoplakia and four on oral lichen planus were included with substantial differences in diagnostic criteria, sample type, region sequenced and sequencing method utilised. The majority of studies focused on bacterial identification and recorded statistically significant differences in the oral microbiota associated with health and disease. However, even when comparing studies of similar methodology, the microbial differences between health and disease varied considerably. No consensus on the composition of the microbiomes associated with these conditions on genus and species level could be obtained. Six studies on oral squamous cell carcinoma had included in silico predicted microbial functions (genes and/or pathways) and found some similarities between the studies. CONCLUSIONS: Attempts to reveal the microbiome associated with oral mucosal diseases are still in its infancy, and the studies demonstrate significant clinical and methodological heterogeneity across disease categories. The immense richness and diversity of the microbiota clearly illustrate that there is a need for additional methodologically comparable studies utilising deep sequencing approaches in significant cohorts of subjects together with functional analyses. Our hope is that following the recipe as outlined in our preceding companion paper, that is Part 1, will enhance achieving this in the future and elucidate the role of the oral microbiome in oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa.

World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists-Part 1. A methodological guide.

Advances in high-throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven-step "recipe" for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high-throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.

The minor gentamicin complex component, X2, is a potent premature stop codon readthrough molecule with therapeutic potential.

Nonsense mutations, resulting in a premature stop codon in the open reading frame of mRNAs are responsible for thousands of inherited diseases. Readthrough of premature stop codons by small molecule drugs has emerged as a promising therapeutic approach to treat disorders resulting from premature termination of translation. The aminoglycoside antibiotics are a class of molecule known to promote readthrough at premature termination codons. Gentamicin consists of a mixture of major and minor aminoglycoside components. Here, we investigated the readthrough activities of the individual components and show that each of the four major gentamicin complex components representing 92-99% of the complex each had similar potency and activity to that of the complex itself. In contrast, a minor component (gentamicin X2) was found to be the most potent and active readthrough component in the gentamicin complex. The known oto- and nephrotoxicity associated with aminoglycosides preclude long-term use as readthrough agents. Thus, we evaluated the components of the gentamicin complex as well as the so-called "designer" aminoglycoside, NB124, for in vitro and in vivo safety. In cells, we observed that gentamicin X2 had a safety/readthrough ratio (cytotoxicity/readthrough potency) superior to that of gentamicin, G418 or NB124. In rodents, we observed that gentamicin X2 showed a safety profile that was superior to G418 overall including reduced nephrotoxicity. These results support further investigation of gentamicin X2 as a therapeutic readthrough agent.

How general dentists could manage a patient with oral lichen planus

Background: The literature hardly contains information on how patients suffering from oral lichen planus could be managed by dentists. Material and Methods: Based on the limited available literature and particularly on the long-term clinical and histopathological experience of one of the authors, suggestions on how dentists could manage patients with oral lichen planus have been put forward. Results: In most cases, the dentist should be able to establish a correct diagnosis. Occasionally, the dentist may call upon a specialist, usually an oral medicine specialist or an oral and maxillofacial surgeon for confirmation of the diagnosis, possibly a biopsy procedure, and management of the patient in case of severe symptoms. Proper patient information is of utmost importance in the management. Conclusions: General dentists can be expected to manage the majority of patients with oral lichen planus. Some patients may need to be referred for diagnostic purposes to a specialist; this is also the case for the rare patient with severe symptoms, possibly requiring systemic treatment (AU)

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