Efficacy of topical agents in oral mucositis prevention: Systematic review and network meta-analysis.

BACKGROUND: Oral mucositis (OM) is considered one of the most common side effects of patients undergoing cancer therapy. OM prevention plays a crucial role in the effectiveness of cancer treatment and the patient's quality of life. Different preventive treatments have been proposed in clinical trials, however with inconclusive results. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: in cancer patients, do specific topical agents compared to standard treatments or placebo reduce the onset and severity of oral mucositis? The risk of bias was assessed, and a network meta-analysis was conducted. RESULTS: Of 2913 results, 30 randomized clinical trials were considered suitable for inclusion. A total of 2564 patients were analyzed, of which 1284 belonged to the test group and 1280 belonged to the control group. Natural products were the most used, followed mainly by antimicrobial agents, coating agents, and basic oral care measures. Topical sucralfate resulted in the most powerful intervention for the OM prevention (OR = 0.04, 95%C.I. = 0.01-0.25, p-value = 0.001). CONCLUSION: Due to its cytoprotective action, low cost, ease of administration, and safety, sucralfate could become a potential ally to prevent the onset of OM during cancer therapy.

Reduction of MRONJ risk after exodontia by virtue of ozone infiltration: A randomized clinical trial.

INTRODUCTION: Exodontia is commonly considered as a risk factor for the development of medication-related osteonecrosis of the jaw (MRONJ) in individuals exposed to bone modifying agents. This study was aimed at assessing the efficiency and safety of a gaseous oxygen-ozone mixture as an adjuvant to a standard exodontia to reduce the risk of MRONJ development. METHODS: A randomized, open-label, phase II, single-center clinical trial involving 117 patients at risk of MRONJ was conducted. The study protocol tested injections of an oxygen-ozone mixture in the post-extraction site. Participants were randomly assigned to two groups: oxygen-ozone therapy, and standard tooth extraction protocol. Post-extraction wound healing was assessed using the Inflammatory Proliferative Remodeling (IPR) Wound Healing Scale. RESULTS: The oxygen-ozone therapy group exhibited a significant improvement in wound healing post-extraction during the inflammatory and proliferative phases, as indicated by the IPR scale scores at 3-5 days (p = 0.006) and 14 days (p < 0.001) respectively. CONCLUSION: Oxygen-ozone therapy shows promise in improving post-extraction healing in patients at risk of MRONJ. Future studies with larger sample sizes and multicenter collaborations are recommended to confirm the validity of these findings and explore the long-term efficacy of ozone therapy.

Oral health status of 916 children in Tibetan settlement (Bylakuppe, India): A cross-sectional descriptive study.

BACKGROUND: Dietary and oral hygiene habits among integrated migrant cultural minorities can vary and could impact susceptibility to caries. AIM: This study aimed to assess and compare the oral health status of Tibetan schoolchildren living in the Tibetan settlement of Bylakuppe, India, stratified by type of residence. DESIGN: A descriptive cross-sectional study was conducted among Tibetan schoolchildren attending nine schools in the Bylakuppe region. RESULTS: The study population consisted of 916 children aged 5-17: 702 (76.6%) living in secular houses (LSH) and 214 (23.4%) living in monasteries (LM). The prevalence of dental caries was 70.9%, and the mean value of decayed, missing, filled teeth for mixed and primary dentition (DMFT*; dmft) of LSH children (1.56 ± 2.34/1.74 ± 2.66) was higher than of LM ones (1.14 ± 2.34/0.83 ± 2.80; p < .001). DMFT for LM children (1.46 ± 2.04) was slightly higher than for LSH children (1.38 ± 1.96; p > .05). Among the sample, 99.1% had a good simplified Oral Hygiene Index (OHI) and LM children showed higher rates of good values (99.5% vs. 98.2% in LSH children). Most children needed preventive/routine dental treatment, whereas 16.6% needed urgent dental treatment. In 4.5% of children, oral mucosal lesions were present. CONCLUSION: This study confirms the high need for dental treatment in the children of the Tibetan settlement investigated.

Italian position paper (SIPMO-SICMF) on medication-related osteonecrosis of the jaw (MRONJ).

OBJECTIVE: This paper aims to describe the 2023 update position paper on MRONJ developed by the Italian Societies of Oral Pathology and Medicine (SIPMO) and of Maxillofacial Surgery (SICMF). METHODS: This is the second update following the 2013 and 2020 Italian position papers by the Expert panel, which is a representation of the two scientific societies (SIPMO and SICMF). The paper is based on an extensive analysis of the available literature from January 2003 to February 2020, and the subsequent review of literature conducted between March 2020 and December 2022 to include all new relevant published papers to confirm or modify the previous set of recommendations. RESULTS: This position paper highlights the main issues of MRONJ on risk estimates, disease definition, diagnostic pathway, individual risk assessment, and the fundamental role of imaging in the diagnosis, classification, and management of MRONJ. CONCLUSION: The Expert Panel confirmed the MRONJ definition, the diagnostic work-up, the clinical-radiological staging system and the prophylactic drug holiday, as recognized by SIPMO-SICMF; while, it presented novel indications regarding the categories at risk of MRONJ, the prevention strategies, and the treatment strategies associated with the therapeutic drug holiday.

Polymorphous Adenocarcinoma: A Systematic Review of the Literature and Presentation of Two Cases in a Less-Considered Anatomical Site.

BACKGROUND: Polymorphous adenocarcinoma (PAC) is the second-most common malignant tumour of the minor salivary glands. Although PAC predominantly affects the palate, it can also involve the buccal mucosa. This systematic review aims to investigate the literature data about PAC. Furthermore, we report two cases of patients affected by PAC in an infrequently considered anatomical site. METHODS: According to PRISMA guidelines, a systematic review search was conducted on PubMed, Scopus, and Web of Science. Observational studies conducted on patients with a histological diagnosis of PAC were selected and analysed. Furthermore, two cases of patients with PAC affecting the buccal mucosa were reported. RESULTS: Twenty-nine studies were included, and 143 patients affected by PAC were analysed (62 males, 75 females, and 6 undefined, with a mean age of 57.4 ± 14.5 years). The palate was the most affected site (99/143, 69.2%), followed by the buccal mucosa (12/143, 8.4%). Moreover, we report two cases of patients with PAC affecting the buccal mucosa (one male and one female, with a mean age of 70.5 ± 2.5 years). CONCLUSIONS: The present study underscores the importance of considering the buccal mucosa as a possible location of minor salivary gland tumours; although it is a less-considered affliction, it is not uncommon.

Improving the cancer adult patient support network (iCAN): a pilot study on a communication model and modified focus group.

Background: Many consider that cancer has the greatest impact of any disease in the world, and it can drastically limit patients' quality of life. Combating such a life-threatening disease can pose many challenges to daily life, highlighted by demonstrating the need to discuss one's health status within a focus group and encourage treatment compliance. Aim: the purposes of this study were to share the authors' experience of a modified focus group in an Oral Medicine Unit, termed "Improving Cancer Adult Patients Support Network" (iCAN), and to evaluate how effective communication could improve patients' quality of life and empower them by virtue of enhanced knowledge and an awareness of cancer management. Methods: the paper adhered to the COREQ checklist regarding its reporting procedures. The iCAN format was precisely reproduced four times with four groups, consisting of 12 adult male and female patients with solid cancers. They discussed several main topics relating to cancer treatment, as chosen by a majority of the participants. Four specialists were involved in the discussion of the selected topics The iCAN format was faithfully reproduced during each meeting, with the participants in the roles of moderator and health specialists. Finally, a satisfaction questionnaire was administered. Results: the most reliable results demonstrated a marked change in lifestyle and eating habits in more than 50% of participants. More than 80% were unaware of the side effects of cancer treatments in general and the oral mucosa in particular. Each meeting reported a maximum degree of satisfaction experienced by the participants. Conclusion: iCAN focus group meetings appear to have facilitated a process of narrative interviewing, thereby improving the doctor-patient relationship underlying the humanization of the care process.

Reducing the anxiety of patients undergoing an oral biopsy by means of graphic novels: an open-label randomized clinical trial

Background: The use of graphic novels is a trending topic in health communication as a new form of visual storytelling which explores narratives of health care, cancer, healing, and disability. The objective of the present study was to evaluate - for the first time in the literature - the effect of graphic novels in reducing the anxiety of patients waiting for an incisional biopsy in an oral oncology setting. Material and Methods: This open-label randomized clinical trial comprised 50 patients with a clinical suspicion of oral potentially malignant disorders. Twenty-five patients were randomly allocated to the test group, and a colourful graphic novel was provided. Subsequently, the Beck Depression Inventory and the Depression Anxiety Stress Scales-21 were administered to all 50 recruited patients, after which a biopsy was performed on each patient. Results: No statistically significant difference was observed between the test and control groups for the variables regarding the demographic data (p>0.2). There was a significant difference after the introduction of the graphic novel, regardless of which questionnaire was used. The graphic novel demonstrated an improvement in the ability of the test group to tolerate anxiety while waiting for an oral biopsy in both psychological tests (p<0.05). Conclusions: In light of these initial positive results, the authors of this study would like to suggest the use of graphic novels in oral oncology, dentistry, and medicine with the aim of reducing patient anxiety. (AU)

Oral Secondary Syphilis in an HIV-Positive Transgender Patient: A Case Report and Review of the Literature.

BACKGROUND: Syphilis is a worldwide sexually transmitted infection caused by Treponema pallidum. In most cases, the oral manifestations of syphilis infection are associated with cutaneous involvement. However, the present case report is noteworthy since the oral lesions are the sole clinical sign in an HIV-positive transgender patient. CASE PRESENTATIONS: We reported an uncommon case of secondary syphilis in a 37-year-old seropositive transgender male, whose diagnostic suspect was based only on oral mucosal lesions. The patient was referred to the Oral Medicine Unit for the presence of multiple undiagnosed painful oral lesions. The intraoral examination revealed the presence of white and red plaques on the right and the left buccal mucosa and several painful lesions localized on the upper and lower labial mucosa. No cutaneous lesions were observed. Considering the sexual history of the patient and clinical findings, secondary syphilis infection was suspected. The serologic analysis was conducted, and the diagnosis of syphilis was confirmed. Moreover, to exclude the presence of oral epithelial dysplasia or malignant disease, an incisional biopsy was performed. DISCUSSION: Compared to the literature data, oral lesions as lone signs of secondary syphilis infection are uncommon, especially in HIV-positive patients. Syphilis and HIV coinfection create a concerning situation as they interact synergistically, leading to an increased risk of transmission and faster disease progression. CONCLUSIONS: This case report emphasizes the importance of considering syphilis as a diagnostic possibility, even when oral lesions are the only clinical manifestations, especially in HIV-positive patients. Comprehensive evaluation, including a detailed sexual history and careful oral examination, is essential for accurate diagnosis and appropriate management in such cases.

No Clear Clustering Dysbiosis from Salivary Microbiota Analysis by Long Sequencing Reads in Patients Affected by Oral Squamous Cell Carcinoma: A Single Center Study.

BACKGROUND: Advancements in DNA sequencing technology have facilitated the assessment of the connection between the oral microbiome and various diseases. The aim of the present study was to investigate the salivary microbiota composition employing for the first time in the literature the Oxford Nanopore Technology in patients affected by oral squamous cell carcinoma (OSCC). METHODS: Unstimulated saliva samples of 31 patients were collected (24 OSCC patients and 7 controls). DNA was extracted using the QIAamp DNA Blood Kit and metagenomic long sequencing reads were performed using the MinION device. RESULTS: In the OSCC group, 13 were males and 11 were females, with a mean age of 65.5 ± 13.9 years; in the control group, 5 were males and 2 were females, with a mean age of 51.4 ± 19.2 years. The border of the tongue was the most affected OSCC site. The microorganisms predominantly detected in OSCC patients were Prevotella, Chlamydia, Tissierellia, Calothrix, Leotiomycetes, Firmicutes and Zetaproteobacteria. CONCLUSIONS: This study confirmed the predominance of periodontopathic bacteria in the salivary microbiome in the OSCC group. If a direct correlation between oral dysbiosis and OSCC onset was proven, it could lead to new prevention strategies and early diagnostic tools.

Orogenital Human Papillomavirus Infection and Vaccines: A Survey of High- and Low-Risk Genotypes Not Included in Vaccines.

Knowledge of human papillomavirus transmission from the genital tract to the oral mucosa remains unsatisfactory, with poor and often inconsistent literature results. The increase in HPV-associated oral malignancies prompts further analysis of the simultaneous detection of the virus in the two anatomical areas and on the identification of genotypes to be included in future vaccines. Therefore, in this retrospective study, we evaluated orogenital HPV concurrence, hrHPV, lrHPV and type-concordance in 337 samples, as well as the prevalence of the most common genotypes not included in HPV vaccines. Concurrence was found in 12.5% (31/248) of cases, hr-concordance in 61.3% (19/31) and lr-concordance in 12.9% (4/31). Finally, type-concordance was found in 32.3% (10/31) of concurrent infections. Regarding the identification of non-vaccine genotypes, the significantly prevalent genotypes in the anogenital area were HPV66 (12.6%, p < 0.0001), HPV53 (11.1%, p < 0.0001), HPV51 (8.7%, p < 0.0001), HPV42 (8.2%, p < 0.0001) and HPV68 (5.6%, p = 0.0034) in women and HPV66 (14.6%, p = 0.0058), HPV42 (12.2%, p = 0.0428), HPV51 (12.2%, p = 0.0428), HPV53 (12.2%, p = 0.0428), HPV70 (12.2%, p = 0.0428) and HPV73 (12.2%, p = 0.0428) in men. Considering the results of our study, we recommend including the high-risk genotypes HPV51, HPV68, HPV53 and HPV66 in future HPV vaccine formulations.

Ranula: Modified Micro-Marsupialization: Case Report and Review of Literature.

Introduction: Ranula is a limited mucus retention on the floor of mouth. Due to the young age of patients, over the years, attempts were made to find minimally invasive and effective surgical techniques. To date, however, there is still no gold standard. The modified micro-marsupialization is an effective and minimally invasive technique, with minimal risk of relapse, although there are very few reports about it. Case Report: A 12-year-old male presented to our ENT Clinic with a rounded swelling with regular and defined margins, measuring 4x3 cm, soft and painless, non-compressible and bluish. Clinical diagnosis of ranula was made and a modified micro-marsupialization was performed: eight interrupted sutures using silk 3-0 were placed perpendicularly to the major axis of the lesion, from one side of the lesion to the other, without reaching the underlying tissue. No sutures were lost during follow-up, no complications occurred. Complete healing was reached after removing sutures on the 30th postoperative day. At 6 months control no relapse was observed. Conclusion: Modified micro-marsupialization is strongly indicated and recommended, especially in pediatric patient, due to its low invasiveness and its very low relapse rate. The poor case history found in the literature is probably an indication of the lack of knowledge of modified micro-marsupialization which, in our opinion, could be considered the gold standard.

Doctoral: A smartphone-based decision support tool for the early detection of oral potentially malignant disorders.

Oral potentially malignant disorders can be defined as mucosal lesions and conditions with an increased risk of malignant transformation. Oral potentially malignant disorders are a significant health burden, and they are often diagnosed late due to scant attention to routine dental practice and the low number of specialized oral medicine centres. This report summarizes the DoctOral experience, a research initiative, providing a free smartphone-based decision support tool for the general medical/dental practitioner; the tool is based on the clinical appearance of oral lesions. Captured, oral pictures can be immediately examined via interactive decision trees and constructed on the smartphone. Such decision trees are expressed in standard formats, and they are readily accessible for facilitating the completion of a hypothetical diagnostic path. Since October 2017 the DoctOral mobile app has been downloaded by 10K + users, achieving a score of 4.8 out of 5. DoctOral also supports an unfolding joint initiative, called DoctOralAI: this involves selecting reference images, with which to create an open-source model, and perform a Case-Based Reasoning method, both of which are combined with machine learning. The DoctOral mobile app has revolutionized oral pathology by providing dental students and professionals with an interactive platform for recognizing and diagnosing oral lesions.

Possible role for IL-40 and IL-40-producing cells in the lymphocytic infiltrated salivary glands of patients with primary Sjögren's syndrome.

OBJECTIVES: Aim of this study was to investigate the expression of interleukin (IL)-40, a new cytokine associated with B cells homoeostasis and immune response, in primary Sjögren syndrome (pSS) and in pSS-associated lymphomas. METHODS: 29 patients with pSS and 24 controls were enrolled. Minor salivary gland (MSG) biopsies from patients, controls and parotid gland biopsies from pSS-associated lymphoma were obtained. Quantitative gene expression analysis by TaqMan real-time PCR and immunohistochemistry for IL-40 were performed on MSG. MSG cellular sources of IL-40 were determined by flow-cytometry and immunofluorescence. Serum concentration of IL-40 was assessed by ELISA and cellular sources of IL-40 were determined by flow-cytometry. An in vitro assay with recombinant IL-40 (rIL-40) was performed to detect the effect on cytokine production from peripheral blood mononuclear cells (PBMCs). RESULTS: IL-40 was significantly increased in the lymphocytic infiltrated MSG of patients with pSS and correlated with focus score and with IL-4 and transforming growth factor-ß expression. In addition, IL-40 was increased in the serum of pSS and its levels correlated with the EULAR Sjögren's Syndrome Disease Activity Index score. B cells from patients were shown to be the major source of IL-40 at both tissue and peripheral level. PBMCs from patients, exposed to rIL-40 in vitro, released proinflammatory cytokines, specifically interferon-γ from B cells and T-CD8+ and tumour necrosis factor-α and IL-17 from both T-CD4+ and T-CD8+. IL-40 expression in parotid glands of pSS-associated lymphomas was also increased. Moreover, IL-40-driven NETosis was evidenced in neutrophils obtained from pSS. CONCLUSION: Our results suggest that IL-40 may play a role in pSS pathogenesis and pSS-associated lymphomas.

Oral lichen planus in children: An Italian case series.

Oral lichen planus usually occurs in adults; there are no clear data regarding the incidence and the clinical features of oral lichen planus in children. This paper reports clinical findings, treatments, and outcomes of 13 Italian patients with oral lichen planus in childhood diagnosed between 2001 and 2021. The most common finding was keratotic lesions with reticular or papular/plaque-like patterns, confined to the tongue in seven patients. Although oral lichen planus in childhood is rare and the malignant transformation index is unknown, specialists must be aware of its characteristics and oral mucosal lesions must be correctly diagnosed and managed.

MRONJ in breast cancer patients under bone modifying agents for cancer treatment-induced bone loss (CTIBL): a multi-hospital-based case series.

BACKGROUND: Cancer treatment-induced bone loss (CTIBL) is the most common adverse event experienced by patients affected by breast cancer (BC) patients, without bone metastases. Bone modifying agents (BMAs) therapy is prescribed for the prevention of CTIBL, but it exposes patients to the risk of MRONJ. METHODS: This multicentre hospital-based retrospective study included consecutive non-metastatic BC patients affected by MRONJ related to exposure to low-dose BMAs for CTIBL prevention. Patients' data were retrospectively collected from the clinical charts of seven recruiting Italian centres. RESULTS: MRONJ lesions were found in fifteen females (mean age 67.5 years), mainly in the mandible (73.3%). The mean duration of BMAs therapy at MRONJ presentation was 34.9 months. The more frequent BMAs was denosumab (53.3%). Ten patients (66.7%) showed the following local risk factors associated to MRONJ development: periodontal disease (PD) in three cases (20%) and the remaining six (40%) have undergone PD-related tooth extractions. One patient presented an implant presence-triggered MRONJ (6.7%). In five patients (33.3%) no local risk factors were observed. CONCLUSIONS: This is the first case series that investigated BC patients under BMAs for CTIBL prevention suffering from MRONJ. These patients seem to have similar probabilities of developing MRONJ as osteo-metabolic ones. Breast cancer patients under BMAs for CTIBL prevention need a regular prevention program for MRONJ, since they may develop bone metastases and be treated with higher doses of BMAs, potentially leading to a high-risk of MRONJ.

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO.

OBJECTIVES: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. METHODS: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. RESULTS: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). CONCLUSIONS: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. CLINICAL RELEVANCE: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

Chemopreventive and Anticancer Role of Resveratrol against Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most prevailing and aggressive head and neck cancers, featuring high morbidity and mortality. The available conventional treatments suffer from several adverse effects and are often inefficient in terms of their survival rates. Thus, seeking novel therapeutic agents and adjuvants is of the utmost importance for modern society. Natural polyphenolic compounds have recently emerged as promising chemopreventive and anticancer agents. Specifically, the natural compound resveratrol (RSV) has recently gained momentum for this purpose. RSV is useful for treating OSCC due to its antiproliferative, antimetastatic, and proapoptotic effects. Additionally, RSV acts against tumor cells while synergically cooperating with chemotherapeutics, overcoming drug resistance phenomena. Despite these wide-spectrum effects, there are few specific investigations regarding RSV's effects against OSCC animal models that consider different routes and vehicles for the administration of RSV. Interestingly, an injectable RSV-loaded liposome-based formulation was proven to be effective against both in vitro and in vivo OSCC models, demonstrating that the development of RSV-loaded drug delivery systems for systemic and/or loco-regional applications may be the turning point in oral cancer treatment, leading to benefits from both RSV's properties as well as from targeted delivery. Given these premises, this review offers a comprehensive overview of the in vitro and in vivo effects of RSV and its main derivative, polydatin (PD), against OSCC-related cell lines and animal models, aiming to guide the scientific community in regard to RSV and PD use in the treatment of oral precancerous and cancerous lesions.

Gender and Sex in Medical Practice: An Exploratory Study on Knowledge, Behavior, and Attitude among Sicilian Physicians.

Personalized medicine is a new paradigm in health care, and the concept of socio-cultural gender, as opposed to biological sex, emerged in several medical approaches. This exploratory study aimed to investigate the knowledge of sex and gender in clinical medicine among Sicilian physicians. Data collection was based on an online survey sent to the members of the Medical Councils of Sicily (Italy). The questionnaire included nine specific items about awareness and attitudes regarding gender medicine and its importance in clinical practice. 8023 Sicilian physicians received the solicitation e-mail and only 496 responded. Regarding the knowledge of gender medicine, 71.1% of participants stated that they know it, while 88.5% believe that gender medicine should be included in training programs. Similarly, a high percentage (77.6%) would like to keep up to date on this topic. Physicians sampled seem to understand the importance of gender medicine principles, although their experience of some gender issues (i.e., sex disparities in acute cardiovascular care and smoking cessation strategies) is low (55.44% and 21.57%, respectively). The results of this exploratory study should encourage facing the gender medicine gap in the current curricula of health professionals and should implement the transitional value of sex and gender principles in the clinical setting.