How safe is off-label use of imiquimod in oral lesions?

DATA SOURCES: A comprehensive search was conducted on PubMed and Embase, adhering to the principles outlined in the PRISMA Extension for Scoping Reviews (PRISMA-ScR). The search strategy was subsequently registered on PROSPERO. STUDY SELECTION: Articles were chosen based on an analysis of titles and abstracts, with no restrictions on publication date, language, or participant age. In vitro studies, animal studies, and literature reviews were excluded from consideration. DATA EXTRACTION AND SYNTHESIS: Clinical trials in humans, case reports, or case series that reported the use of imiquimod for treating conditions in the oral or labial mucosa were included in this study. Results from duplicate articles were excluded from the analysis. RESULTS: Out of a total of 601 references initially identified, only 28 studies were included in the review. These studies were classified based on the use of imiquimod into three groups: potentially malignant disorders and oral cancer, lesions related to HPV, and autoimmune conditions. In all cases presented in the article, there is an occurrence of both local and systemic side effects. CONCLUSIONS: The study elucidated the off-label use of imiquimod in oral pathologies, whether potentially malignant, cancerous, autoimmune, or associated with HPV infection. However, it was observed that further research is warranted for the development of a specific formulation for the oral mucosa, ensuring the drug's sustained presence at its active site of action without interference from saliva and minimizing potential side effects.

Is preexisting inflamed jaw marrow a "hidden" co-morbidity affecting outcomes of COVID-19 infections? - Clinical comparative study.

Introduction: Exceedingly high levels of the chemokine CCL5/RANTES have been found in fatty degenerated osteonecrotic alveolar bone cavities (FDOJ) and aseptic ischemic osteolysis of the jaw (AIOJ) from toothless regions. Because CCL5/RANTES seems to have a prominent role in creating the COVID-19 "cytokine storm", some researchers have used the monoclonal antibody Leronlimab to block the CCR5 on inflammatory cells.Objective: Is preexisting FDOJ/AIOJ jaw marrow pathology a "hidden" co-morbidity affecting some COVID-19 infections? To what extent does the chronic CCL5/RANTES expression from preexisting FDOJ/AIOJ areas contribute to the progression of the acute cytokine storm in COVID-19 patients?Methods: Authors report on reducing the COVID-19 "cytokine storm" by treating infected patients through targeting the chemokine receptor 5 (CCR5) with Leronlimab and interrupting the activation of CCR5 by high CCL5/RANTES signaling, thus dysregulating the inflammatory phase of the viremia. Surgical removal of FDOJ/AIOJ lesions with high CCL5/RANTES from patients with inflammatory diseases may be classified as a co-morbid disease.Results: Both multiplex analysis of 249 FDOJ/AIOJ bone tissue samples as well as serum levels of CCL5/RANTES displayed exceedingly high levels in both specimens.Discussion: By the results the authors hypothesize that chronic CCL5/RANTES induction from FDOJ/AIOJ areas may sensitize CCR5 throughout the immune system, thus, enabling it to amplify its response when confronted with the virus. As conventional intraoral radiography does little to assess the quality of the alveolar bone, ultrasonography units are available to help dentists locate the FDOJ/AIOJ lesions in an office setting.Conclusion: The authors propose a new approach to containment of the COVID-19 cytokine storm by a prophylactic focus for future viral-related pandemics, which may be early surgical clean-up of CCL5/RANTES expression sources in the FDOJ/AIOJ areas, thus diminishing a possible pre-sensitization of CCR5. A more complete dental examination includes trans-alveolar ultrasono-graphy (TAU) for hidden FDOJ/AIOJ lesions.

Oral health related-quality of life before and during the COVID-19 pandemic in patients with non-alcoholic fatty liver disease

Background: Since the beginning of the COVID-19 pandemic, the number of medical appointments and the offer and use of oral health services have decreased sharply with the lockdown period. Restriction to regular dental care can increase the risk of oral diseases, capable of affecting general health and oral health-related quality of life, particularly among medically compromised patients. This study aimed to assess health-related quality of life (HRQoL) and oral health-related quality of life (OHRQoL) of patients with non-alcoholic liver disease (NAFLD) before and during the COVID-19 pandemic. Material and methods: Prospective cohort of 58 patients with NAFLD followed up from March 2020 (before the pandemic) to December 2021 (during the pandemic). RAND 36-Item Health Survey and Oral Health Impact Profile 14 (OHIP-14) questionnaires were used to assess HRQoL and OHRQoL, respectively, in the two points of time. Results: The scores of all scales HRQoL and of the question about health change in the last year decreased substantially with the advent of the pandemic. Large (>0.50) effect sizes were estimated for the scales Role functioning/physical, Pain, General health, and Energy/fatigue. Patients who had COVID-19 presented better HRQoL and OHIP-14 mean scores than those who did not have the disease. The OHIP-14 total score increased 3.6 points with the advent of the pandemic, representing a large effect size (0.62). Patients presented high probability (84.3%) of increasing OHIP14 score during the pandemic. Conclusions: The HRQoL and the OHRQoL scores of NAFLD patients decreased substantially with the advent of the pandemic. However, these decreases were not associated with the COVID-19 disease by itself, but probably to other factors related to the deep social changes brought by the social isolation measures to combat the pandemic. (AU)

Thirteen Synchronous Multifocal Calcifying Epithelial Odontogenic Tumors (CEOT): Case Report and Review of the Literature.

BACKGROUND: Calcifying epithelial odontogenic tumor (CEOT, Pindborg tumor) is a rare, benign, locally aggressive neoplasm of the jaws that accounts for approximately 1% of all odontogenic tumors. It was first defined by Pindborg in 1955 and has been reported approximately 350 times in the literature; 7 reported multiple (up to 4) synchronous lesions. MATERIALS AND METHODS: We report an individual with the largest number of CEOTs reported to date and provide a literature review of multifocal CEOT cases. RESULTS: A 30-year-old male presented to the Oral and Maxillofacial Surgery Department of the West Virginia University School of Dentistry (WVU SoD) to extract multiple impacted teeth previous to construction of a complete denture. A pantograph showed 15 impacted teeth, almost all associated with well-demarcated cyst-like radiolucencies, some with small, ill-defined radiopaque flecks. Microscopically, the lesions showed sheets and strands of polygonal epithelial cells with eosinophilic cytoplasm. Spread throughout the epithelium and connective tissue were small, spherical, amorphous, pale purplish calcifications. Each lesion was similar and consistent with a diagnosis of CEOT. CONCLUSION: We report a patient with 13 independent CEOTs scattered throughout all quadrants. This case represents the largest number of Pindborg tumors or any other type of odontogenic tumor yet reported in a single individual.

The pararadicular radiolucency with vital pulp: Clinicopathologic features of 21 cemental tears.

OBJECTIVE: The investigation was conducted to better characterize the clinical, radiographic, and histopathologic features of cemental tears from a review of 21 cases. STUDY DESIGN: This was a retrospective review of consecutive cases collected from patient records of the investigators. RESULTS: Twenty-one cases were identified during an 8-year period. Maxillary incisors were most often affected (47.6%). All lesions presented with pain. They occurred as radiolucencies along the root of a vital or endodontically treated tooth and were classified as D-shaped (38.1%), thin-vertical-line (23.8%), thick-vertical-line (14.3%), J-shaped (19.0%), or periapical radiolucencies (4.8%). All lesions showed focal destruction of the lamina dura, with 66.7% exhibiting extension into the medullary bone. Histopathologic diagnoses included intramedullary fibrous scar (28.6%) and chronic fibrosing osteomyelitis (71.4%), all associated with embedded cemental fragments. Five associated teeth were also examined: All showed tears beneath the remaining cementum. Four cases were successfully treated with curettage without tooth extraction; endodontic therapy was performed, probably mistakenly, in 8 cases. CONCLUSIONS: Cemental tears produced symptomatic, localized chronic inflammation characterized usually by a vertical radiolucency adjacent to a root. These lesions may not be as rare as previously thought and extraction may not be the best treatment.

Symmetrical palatal fibromatosis: Five new cases and a review of the literature.

OBJECTIVE: To present five cases of symmetrical palatal fibromatosis (SPF), a lesion reported very rarely in the English language literature, under more than a dozen different names, and to recommend the most appropriate name. METHODS: Five SPF cases are characterized with a literature review. RESULTS: Three females and two males, aged 20-39 years, presented with bilateral, symmetrical, asymptomatic, sessile, moderately firm, or soft (n = 2) masses of the lateral posterior hard palate; two were isolated to the tuberosities. All masses were normal in color, with smooth, non-ulcerated surfaces and occasional surface nodularity. Underlying bone was radiographically normal, and adjacent teeth were asymptomatic. All masses originated from supra-periosteal tissues over palatal bone, only secondarily extending to gingivae and/or crestal tuberosity. Cases were present between 4 months and 15 years, with no familial or environmental etiologies identified. Histopathologically, masses were comprised of dense, avascular fibrous tissue with scattered thick bands of collagen. Surface epithelium showed occasional long, thin, sometimes pointed rete processes, and subepithelial stroma contained scattered large, angular fibroblasts. Conservative surgical excision appeared curative in all cases. CONCLUSIONS: The present investigators propose SPF as the most accurate name for this rare entity.

'Cytology-on-a-chip' based sensors for monitoring of potentially malignant oral lesions.

UNLABELLED: Despite significant advances in surgical procedures and treatment, long-term prognosis for patients with oral cancer remains poor, with survival rates among the lowest of major cancers. Better methods are desperately needed to identify potential malignancies early when treatments are more effective. OBJECTIVE: To develop robust classification models from cytology-on-a-chip measurements that mirror diagnostic performance of gold standard approach involving tissue biopsy. MATERIALS AND METHODS: Measurements were recorded from 714 prospectively recruited patients with suspicious lesions across 6 diagnostic categories (each confirmed by tissue biopsy -histopathology) using a powerful new 'cytology-on-a-chip' approach capable of executing high content analysis at a single cell level. Over 200 cellular features related to biomarker expression, nuclear parameters and cellular morphology were recorded per cell. By cataloging an average of 2000 cells per patient, these efforts resulted in nearly 13 million indexed objects. RESULTS: Binary "low-risk"/"high-risk" models yielded AUC values of 0.88 and 0.84 for training and validation models, respectively, with an accompanying difference in sensitivity+specificity of 6.2%. In terms of accuracy, this model accurately predicted the correct diagnosis approximately 70% of the time, compared to the 69% initial agreement rate of the pool of expert pathologists. Key parameters identified in these models included cell circularity, Ki67 and EGFR expression, nuclear-cytoplasmic ratio, nuclear area, and cell area. CONCLUSIONS: This chip-based approach yields objective data that can be leveraged for diagnosis and management of patients with PMOL as well as uncovering new molecular-level insights behind cytological differences across the OED spectrum.

Interobserver agreement in dysplasia grading: toward an enhanced gold standard for clinical pathology trials.

OBJECTIVE: Interobserver agreement in the context of oral epithelial dysplasia (OED) grading has been notoriously unreliable and can impose barriers for developing new molecular markers and diagnostic technologies. This paper aimed to report the details of a 3-stage histopathology review and adjudication process with the goal of achieving a consensus histopathologic diagnosis of each biopsy. STUDY DESIGN: Two adjacent serial histologic sections of oral lesions from 846 patients were independently scored by 2 different pathologists from a pool of 4. In instances where the original 2 pathologists disagreed, a third, independent adjudicating pathologist conducted a review of both sections. If a majority agreement was not achieved, the third stage involved a face-to-face consensus review. RESULTS: Individual pathologist pair κ values ranged from 0.251 to 0.706 (fair-good) before the 3-stage review process. During the initial review phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the adjudication review by a third pathologist, an additional 22.8% of cases were given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the face-to-face review, the remaining 7.3% of cases had a consensus diagnosis. CONCLUSIONS: The use of the defined protocol resulted in a substantial increase (30%) in diagnostic agreement and has the potential to improve the level of agreement for establishing gold standards for studies based on histopathologic diagnosis.

Breastfeeding keratosis: this frictional keratosis of newborns may mimic thrush.

We report the first example, to our knowledge, of a frictional keratosis from exuberant sucking in a breastfeeding infant. A 2-month-old girl was referred for evaluation of a well-demarcated, nonsloughing white keratotic plaque of the lower lip mucosa, just inside the vermilion border. The plaque had a slightly irregular surface, had no surrounding erythema, and was the only such plaque in the mouth. It had been present for at least 3 weeks and had been unsuccessfully treated by her pediatrician via oral Mycostatin (nystatin). Her parents sought a second opinion when the infant was prescribed a full course of oral Diflucan (fluconazole). A cytopathology smear (Papanicolaou test) revealed abundant mature keratinocytes with no evidence of Candida. The mother admitted that the infant "worked hard" at sucking during breastfeeding and continued sucking long after feeding. The parents were unaware of any other habit or potential irritation of the lips. After 3 months of age the infant's sucking pattern became more "normal" and the keratosis disappeared; it did not recur during 3 years of follow-up. We propose the term "breastfeeding keratosis" for this entity.