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.

Psychological profile and unexpected pain in oral lichen planus: A case-control multicenter SIPMO studya.

OBJECTIVES: To analyze psychological profiles, pain, and oral symptoms in patients with oral lichen planus (OLP). MATERIALS AND METHODS: 300 patients with keratotic OLP (K-OLP; reticular, papular, plaque-like subtypes), 300 patients with predominant non-keratotic OLP (nK-OLP; erythematosus atrophic, erosive, ulcerative, bullous subtypes), and 300 controls were recruited in 15 universities. The number of oral sites involved and oral symptoms were recorded. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The OLP patients, especially the nK-OLP, showed higher scores in the NRS, T-PRI, HAM-D, HAM-A and PSQI compared with the controls (p-value < .001** ). A positive correlation between the NRS, T-PRI, HAM-A, HAM-D, and PSQI was found with the number of oral symptoms and number of oral sites involved. Pain was reported in 67.3% of nK-OLP and 49.7% of K-OLP cases with poor correspondence between the site of lesions and the site of the symptoms. CONCLUSIONS: Mood disorders are frequently associated with OLP with an unexpected symptomatology correlated with the number of oral symptoms and with the extension of disease suggesting a peripheral neuropathy.

Gustatory dysfunction in COVID-19 patients: a rapid systematic review on 27,687 cases.

Objective: This is a rapid systematic review concerning taste alterations in 27,687 individuals infected with SARS-CoV-2, published in the worldwide literature.Material and methods: Of the 485 articles recovered, 67 eligible studies (27,687 confirmed COVID-19 cases) were included in this analysis. We analysed the prevalence of the taste alterations in patients considering the country of origin of the studies.Results: The results show strong important differences in the overall reported prevalence of taste alterations among the different countries (from 11% of Korea to 88.8% of Belgium).Conclusions: These data highlight that there is a different geographical distribution of taste alterations in COVID-19 patients. Gustatory dysfunction seems to be an understudied symptom of COVID-19 and this may explain the inconsistencies of diagnostic criteria for COVID-19 case definition. Furthermore, this diagnostic underestimation can lead to an increased risk of contagion for the whole population and for the working classes most at risk, including the dental one.

Leukoplakia and Immunology: New Chemoprevention Landscapes?

Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations frequently characterized by an architectural and cytological derangements upon histological analysis. Among them, oral leukoplakia is the most common type of these disorders. This work aims to analyze the possible use of drugs such as immunochemopreventive agents for OPMDs. Chemoprevention is the use of synthetic or natural compounds for the reversal, suppression, or prevention of a premalignant lesion conversion to malignant form. Experimental and in vivo data offer us the promise of molecular prevention through immunomodulation; however, currently, there is no evidence for the efficacy of these drugs in the chemoprevention action. Alternative ways to deliver drugs, combined use of molecules with complementary antitumor activities, diet influence, and better definition of individual risk factors must also be considered to reduce toxicity, improve compliance to the protocol treatment and offer a better individualized prevention. In addition, we must carefully reconsider the mode of action of many traditional cancer chemoprevention agents on the immune system, such as enhancing immunosurveillance and reversing the immune evasion. Several studies emphasize the concept of green chemoprevention as an alternative approach to accent healthy lifestyle changes in order to decrease the incidence of HNSCC.

Methods for Overcoming Chemoresistance in Head and Neck Squamous Cell Carcinoma: Keeping the Focus on Cancer Stem Cells, a Systematic Review.

According to the "cancer stem cell" (CSCs) theory, tumors are a diverse and expanding group of malignant cells that originate from a small number of CSCs. Despite treatment, these cells can still become active and proliferate, which can result in distant metastasis and local recurrences. A new paradigm in cancer treatment involves targeting both CSCs and the cancer cells in a tumor. This review aims to examine the literature on methods published to overcome chemoresistance due to the presence of CSCs in head and neck cancers. The review was registered with PROSPERO (ID# CRD42024512809). After Pub Med, Scopus, and WoS database searches, 31 relevant articles on oral squamous cell carcinoma (OSCC) were selected. Compounds that increased chemosensitivity by targeting CSCs in head and neck squamous cell carcinoma (HNSCC) were divided into (1) natural products, (2) adjuvant molecules to traditional chemotherapy, and (3) CSCs targeting patient-specific fresh biopsies for functional precision medicine.

Natural compounds may contribute in preventing SARS-CoV-2 infection: a narrative review.

Coronavirus pandemic infection is the most important health issue worldwide. Coronavirus disease 2019 is a contagious disease characterized by severe acute respiratory syndrome coronavirus 2. To date, excluding the possibility of vaccination, against SARS-CoV-2 infection it is possible to act only with supportive care and non-virus-specific treatments in order to improve the patient's symptoms. Pharmaceutical industry is investigating effects of medicinal plants, phytochemical extracts and aromatic herbs to find out natural substances which may act as antiviral drugs. Several studies have revealed how these substances may interfere with the viral life cycle, viral entry, replication, assembly or discharge, as well as virus-specific host targets or stimulating the host immune system, reducing oxidative stress and inflammatory response. A natural compound can be used as a prophylaxis by people professionally exposed to the risk of contagion and/or positive patients not in intensive care. The aim of this paper is to perform a narrative review of current literature in order to summarize the most studied natural compounds and their modes of action.

COVID-19 and periodontitis: reflecting on a possible association.

Recent studies have demonstrated a relationship between the severe clinical course of COVID-19 and other chronic diseases such as: cardiovascular disease, hypertension, diabetes mellitus, obesity and chronic renal disease. It may be possible to extend this association to a common and chronic oral disease in adults: periodontitis. Alternatively, the latter could be simply related to the systemic chronic diseases cited above, as already observed in the non-COVID-19 literature. In order to provide an overview and their opinion, the authors in this perspective article will report and discuss the most recent references of interest relating to COVID-19 and periodontitis pathophysiology. Within such a narrative review, the authors will hypothesize that the association between chronic periodontitis and COVID-19 could exist via two pathways: a direct link, through the ACEII and CD147 receptors used by the virus to infect the cells, which would occur in greater numbers in cases of periodontitis (thereby favoring a SARS-CoV-2 infection); and/or an indirect pathway involving the overexpression of inflammatory molecules, especially IL-6 and IL-17. An expression of the latter has been found to play a role in periodontitis, in addition to severe cases of COVID-19, although it is still unclear if it plays a direct role in the worsening of the clinical course.

Current Knowledge, Attitudes, and Practice among Health Care Providers in OSCC Awareness: Systematic Review and Meta-Analysis.

OSCC remain a global health problem. Lack of awareness leads to inadequate watchfulness regarding early signs/symptoms despite the ease of visual oral inspection. What clinicians know and feel, and how they behave on OSCC is crucial to understand the feasibility and effectiveness of screening programs. The aim of this systematic review was to assess knowledge, attitudes, and practice (KAP) regarding OSCC among health care providers (HCPs). Therefore, a systematic review was conducted with SPIDER and PICO as major tools. A meta-analysis was structured through common items in two comparison groups of medical and dental practitioners. Descriptive statistics and a Mantel-Haenszel test were used to validate data. Sixty-six studies were selected for systematic review, eight of which are useful for meta-analysis. A statistically significant difference was recorded between dentists and medical practitioners for questions regarding: Alcohol (p < 0.001); Elderly (p < 0.012); Sun exposure (p < 0.0001); Erythroplakia (p < 0.019); Red patch (p < 0.010); White patch (p < 0.020); Tobacco consultation (p < 0.0001); Intraoral examination (p < 0.0001) and Up-to-date knowledge (p < 0.002). Overall, the incidence of OSCC screening is low. Most HCPs feel the need to increase KAP. Data confirmed gaps in KAP, highlighting the need for a more efficient pre- and post-graduation training, necessary to increase competence worldwide.

Use of Diode Laser for Surgical Removal of Pyogenic Granuloma of the Lower Lip in a Pediatric Patient: A Case Report.

BACKGROUND A pyogenic granuloma is an inflammatory exophytic lesion that can occur in the oral cavity. Numerous factors are involved in the etiology of the lesion and can lead to the tissue proliferation underlying the lesion's characteristic appearance. The main treatment is surgical excision with careful curettage of the surrounding tissues. The use of a laser has been proposed because it enables performing deep and precise incisions with better hemostasis and less invasive procedures with less discomfort to patients. The aim of this study was to evaluate the possible advantages of using a diode laser in the surgical treatment of pyogenic granuloma, particularly in the management of a pediatric patient. CASE REPORT A swelling in the lower lip of an 11-year-old female patient was analyzed. After several evaluations, a 980-nm diode laser in continuous wave mode was chosen for excision of the lesion. The lesion was excised successfully with a diode laser as a conservative method that was nonstressful for the pediatric patient. CONCLUSIONS Among the techniques for surgical excision of a lesion, the use of a diode laser has the following advantages: less invasiveness, absence of intra- and postoperative discomfort and pain, effective hemostasis with better control of bleeding, absence of scarring, better postoperative management, and greater patient compliance.

Everolimus therapy and side­effects: A systematic review and meta­analysis.

Recent studies have focused on identifying novel targeted agents in order to reduce the undesired side­effects of conventional chemotherapeutic agents on normal cells. However, even targeted therapies may exert certain negative effects on healthy tissues. The present systematic review was performed in order to evaluate the type and the incidence of side­effects in patients treated with everolimus. The PubMed and Scopus databases were searched using the following free words and MESH terms: 'everolimus' AND 'side­effects' OR 'toxicities' OR 'adverse events'. A total of 912 potentially relevant studies that were screened based on the title and abstracts were identified. A total of 731 were excluded as they did not fulfil the inclusion criteria. Of the 181 remaining studies included, the adverse events reported were obtained. The primary adverse events reported were stomatitis, leukopenia, anorexia, anaemia and fatigue. The majority of the patients reported adverse events limited to grade 1 or 2. On the whole, the data presented herein confirm the findings of previous studies on the relative safety of everolimus, a targeted therapeutic agent, which differs from that of conventional chemotherapy, and highlight the potential adverse events associated with the therapeutic use of everolimus.

Clinico-Pathological Profile and Outcomes of 45 Cases of Plasma Cell Gingivitis.

Plasma cell gingivitis (PCG) is an infrequent inflammatory disease of the gingiva of unknown etiology, characterized by a dense polyclonal proliferation of plasma cells in the connective tissue. The aim of this study was to present a case series of patients affected by PCG, analyzing demographic, clinical, histopathological, and therapeutic data. A group of 36 females and 9 males with a mean age of 60.3 years was evaluated. Clinically, 25 cases were bullous, a clinical phenotype never reported to date, 4 erythematous, 4 keratotic, 4 verruciform, and 3 ulcerative. On histological examination, pure polyclonal plasma cell infiltrate was detected in 20 specimens, while in 25 specimens it was associated with a mixed infiltrate. The first-line therapy consisted of oral hygiene and topical corticosteroids in all patients. In 25 patients, doxycycline and sulfasalazine were added; in 10 of these patients, the disease persisted, and it was necessary to resort to systemic steroids. This study presented the clinico-pathological profile and outcomes of a case series of PCG. This could be an aid for clinicians to be aware of the heterogeneous clinical phenotype and of the possible pure bullous phenotype of PCG. Further studies are needed to improve the knowledge about this disorder.

Low-Grade Intraductal Carcinoma of the Parotid Gland: A Case Report and Literature Review.

Low-grade intraductal carcinoma is a rare neoplasia with an excellent prognosis, previously classified as low-grade cribriform cystadenocarcinoma and low-grade salivary duct carcinoma. The tumor mainly occurs in the parotid gland and presents a ductal phenotype and an intraductal/intracystic growth pattern. It resembles intraductal breast lesions such as atypical ductal hyperplasia, papillary and cribriform ductal carcinoma in situ. Despite its infrequency, discriminating low-grade intraductal carcinoma from other salivary gland tumors is crucial, especially because of its favorable prognosis. A 74-year-old woman with a history of neurofibromatosis underwent a superficial parotidectomy to remove a sharply demarcated multi-cystic mass, diagnosed as category 4 at FNAC. The histological examination revealed a demarcated but unencapsulated lesion composed of a bigger cyst surrounded by several smaller cysts, lined by a monolayer or bilayer epithelium alternated with a cribriform proliferation, characterized by "Roman-bridges", with occasional micro-papillae. A myoepithelial component, with a basal disposition, was present, confirmed by intense staining for protein p63 and SMA. Immunohistochemical stains showed intense, strong uniform positivity for pan-cytokeratin, protein S100, and SOX10. The Ki67 proliferation index was low (< 10%). A diagnosis of Low-grade Intraductal Carcinoma (LGIC) of the parotid was made. We performed a literature search in PUBMED for "Intraductal carcinoma", "Low-grade Intraductal Carcinoma", "Cribriform Cystadenocarcinoma", "Salivary Duct Carcinoma", and "Low-Grade Salivary Duct Carcinoma". We selected 17 papers published between 1983 and 2020; the most affected anatomical site was the parotid gland (77/90), followed by minor salivary glands (6/90), the intraparotid lymph nodes (3/90) and the submandibular gland (4/90). Their main histopathological features are reported in the paper. Here we present a case report and a review of scientific literature on this topic to provide some essential diagnostic tools to discriminate this rare entity.

Evaluation of Vitamin D (25OHD), Bone Alkaline Phosphatase (BALP), Serum Calcium, Serum Phosphorus, Ionized Calcium in Patients with Mandibular Third Molar Impaction. An Observational Study.

The aim of this study was to evaluate the levels of vitamin D (25OHD) and other bone biomarkers in patients with third molar impaction (TMI). Thirty males and 30 females with unilateral or bilateral impacted mandibular third molar, and 15 males and 15 females as a control group (CG) were recruited. Rx-OPT was used to evaluate dental position and Pederson index to measure the difficulty of the intervention. Bone biomarkers were measured through blood venous sample in TMI group and CG. Mann-Whitney test, Pearson's correlation coefficient, linear regression model were used to compare the different parameters in the two groups. 25OHD showed lower values in TMI group than in CG (p < 0.05) with values significantly lower in bilateral impaction (p < 0.05). Pearson's coefficient for 25OHD presented a negative correlation with the Pederson index (ρ = -0.75). Bone alkaline phosphatase (BALP) showed significantly lower dosage in TMI group than CG (p = 0.02), Pearson's coefficient for BALP presented a negative correlation with the Pederson index. Serum calcium, serum phosphorus, ionized calcium levels in TMI and CG groups were similar and Mann-Whitney test did not significantly differ between TMI and CG. TMI could be a sign of vitamin D deficiency and of low BALP levels that should be investigated.

Lung histopathological findings in COVID-19 disease - a systematic review.

Since December 2019, the global burden of the COVID-19 pandemic has increased rapidly and has impacted nearly every country in the world, affecting those who are elderly or with underlying comorbidities or immunocompromised states. Aim of this systematic review is to summarize lung histopathological characteristics of COVID-19, not only for diagnostic purpose but also to evaluate changes that can reflect pathophysiological pathways that can inform clinicians of useful treatment strategies. We identified following histopathological changes among our patients:: hyaline membranes; endothelial cells/ interstitial cells involvement; alveolar cells, type I pneumocytes/ type II pneumocytes involvement; interstitial and/ or alveolar edema; evidence of hemorrhage, of inflammatory cells, evidence of microthrombi; evidence of fibrin deposition and of viral infection in the tissue samples.The scenario with proliferative cell desquamation is typical of Acute Respiratory Distress Syndrome (ARDS) that can be classified as diffuse alveolar damage (DAD) and not DAD-ARDS. The proposed pathological mechanism concerns the role of both innate and adaptive components of the immune system. COVID-19 lethal cases present themselves as a heterogeneous disease, characterized by the different simultaneous presence of different histological findings, which reflect histological phases with corresponding different pathological pathways (epithelial, vascular and fibrotic changes), in the same patient.

Covid-19 Pandemic: What Changes for Dentists and Oral Medicine Experts? A Narrative Review and Novel Approaches to Infection Containment.

The authors performed a narrative review on Severe Acute Respiratory Syndrome- CoronaVirus-2 ( SARS-CoV-2) and all infectious agents with the primary endpoints to illustrate the most accepted models of safety protocols in dentistry and oral medicine, and to propose an easy view of the problem and a comparison (pre- vs post-COVID19) for the most common dental procedures. The outcome is forecast to help dentists to individuate for a given procedure the differences in terms of safety protocols to avoid infectious contagion (by SARS-CoV-2 and others dangerous agents). An investigation was performed on the online databases Pubmed and Scopus using a combination of free words and Medical Subject Headings (MESH) terms: "dentist" OR "oral health" AND "COVID-19" OR "SARS-CoV-2" OR "coronavirus-19". After a brief excursus on all infectious agents transmittable at the dental chair, the authors described all the personal protective equipment (PPE) actually on the market and their indications, and on the basis of the literature, they compared (before and after COVID-19 onset) the correct safety procedures for each dental practice studied, underlining the danger of underestimating, in general, dental cross-infections. The authors have highlighted the importance of knowing exactly the risk of infections in the dental practice, and to modulate correctly the use of PPE, in order to invest adequate financial resources and to avoid exposing both the dental team and patients to preventable risks.

The Management of Dental Practices in the Post-COVID 19 Era: An Economic and Operational Perspective.

BACKGROUND: In order to protect dental teams and their patients during the COVID-19 pandemic, dentists have had to adopt several measures (operating and post-operating procedures) which may increase the total treatment time and costs relating to individual protective measures. This paper will propose a thorough analysis of operating dentistry procedures, comparing the economic performance of the activity in a dental surgery before and after the adoption of these protective measures, which are required to contain the risk of SARS-COV-2 infections. METHODS: The economic analysis is articulated in three approaches. Firstly, it assesses a reduction in markup by maintaining current charges (A); alternatively, it suggests revised charges to adopt in order to maintain unvaried levels of markup (B). And the third Approach (C) examines available dental treatments, highlighting how to profitably combine treatment volumes to reduce markup loss or a restricted increase in dental charges. RESULTS: Maintaining dental charges could cause a loss in markup, even rising to 200% (A); attempting to maintain unvaried levels of markup will result in an increase in dental charges, even at 100% (B); and varying the volumes of the single dental treatments on offer (increasing those which current research indicates as the most profitable) could mitigate the economic impact of the measures to prevent the transmission of SARS-COV-2 (C). CONCLUSIONS: The authors of this paper provide managerial insights which can assist the dentist-entrepreneur to become aware of the boundaries of the economic consequences of governmental measures in containing the virus infection.

May VelScope Be Deemed an Opportunistic Oral Cancer Screening by General Dentists? A Pilot Study.

Early diagnosis of oral cancer through visual inspection followed by histopathological confirmation is a pivotal step for reducing rates of morbidity and mortality. There are several auxiliary devices used to improve oral examination. The purpose of this cross-sectional pilot study is to evaluate the sensitivity and specificity of the Visually Enhance Lesion Scope (VelScope) system when it is used by the general dentist after a yearly oral medicine training. Thirty-five patients with oral lesions were evaluated with clinical and VelScope examination by two general dentists, one of which trained with a specific course. A comparison of the histopathological results, clinical examination, and VelScope made by both dentists was performed through statistical analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting oral potentially malignant disorders (OPMDs) are 53.3%, 65%, 53.3%, 76.5% for unskilled dentist, 73.3%, 65%, 61.1%, 76.5% for skilled clinician. When both examiners use VelScope the values are 53.3%, 70%, 57.1%, 66.7% for unskilled general dentist (u-GD), 86.7%, 90%, 86.7%, 90% for skilled general dentist (s-GD). Improvement of a skilled general dentist for detecting malignancies is higher than inexperienced examiner when using VelScope. VelScope alone is unable to improve the general dentist's ability to detect malignancies, but it could be a useful adjunctive device for clinicians when a focused training program is performed.

Oral Dysplastic Complications after HSCT: Single Case Series of Multidisciplinary Evaluation of 80 Patients.

Oral squamous cell carcinoma (OSCC) is the most common secondary solid malignancy after hematopoietic stem-cell transplantation (HSCT). OSCC following HSCT is frequently preceded by chronic graft-versus-host disease (cGVHD). The aim of this study was to describe a cohort of post-HSCT patients and to evaluate the onset of oral epithelial dysplasia and/or OSCC over time. In this retrospective cohort study, we present a cohort of hematological patients that underwent HSCT. Demographic variables, clinical hematological data, data regarding acute graft-versus-host disease (aGVHD) and cGVHD, and oral clinical features were analyzed. We focused on clinicopathological features of a subgroup of 22 patients with oral cGVHD and OSCC after HSCT. Among 80 included patients, 46 patients (57.5%) developed aGVHD and 39 patients (48.7%) developed cGVHD. Oral mucosa was involved in 17 patients with aGVHD (36.9%) and in 22 patients (56.4%) with cGVHD. Out of a total of 22 oral biopsies, roughly 40% revealed mild to moderate dysplasia, and 32% were OSCC. In the absence of international agreement on the best timing of oral follow-up after HSCT, it is mandatory to establish a close multidisciplinary evaluation in order to prevent the onset of HSCT-related OSCC and to reduce post-transplant mortality due to secondary tumors.

From Bench to Bedside in Tongue Muscle Cancer Invasion and Back again: Gross Anatomy, Microanatomy, Surgical Treatments and Basic Research.

Tongue squamous cell carcinoma is the most common malignancy in the oral cavity. Despite advances in diagnosis and treatment, the prognosis of advanced states has not significantly improved. Depth of invasion, pattern of invasion such as tumor budding grade, lingual lymph node metastasis in early stages, collective cell migration and circulating tumor cells in peripheral blood are some examples of the mechanisms that are currently receiving increasing attention in the evaluation of the prognosis of tongue cancers. Anatomic-based surgery showed that it is possible to improve loco-regional control of tongue cancer. In patients with a "T-N tract involvement", there is significantly more distant recurrence (40%) in patients undergoing a compartmental tongue surgery. In general, the neoplastic infiltration of the lingual muscles is traced back to the finding of neoplastic tissue along the course of a muscle; however, the muscle fibers, due to their spatial conformation and the organization of the extracellular matrix, could influence the movement of tumor cells through the muscle, leaving its three-dimensional structure unchanged. We need to exclude the possibility that tongue muscle fibers represent a mechanism for the diffusion of cancer cells without muscle invasion.