Selected phytocannabinoids inhibit SN-38- and cytokine-evoked increases in epithelial permeability and improve intestinal barrier function in vitro.

Irinotecan use is linked to the development of gastrointestinal toxicity and inflammation, or gastrointestinal mucositis. Selected phytocannabinoids have been ascribed anti-inflammatory effects in models of gastrointestinal inflammation, associated with maintaining epithelial barrier function. We characterised the mucoprotective capacity of the phytocannabinoids: cannabidiol, cannabigerol, cannabichromene and cannabidivarin in a cell-based model of intestinal epithelial stress occurring in mucositis. Transepithelial electrical resistance (TEER) was measured to determine changes in epithelial permeability in the presence of SN-38 (5 µM) or the pro-inflammatory cytokines TNFα and IL-1ß (each at 100 ng/mL), alone or with concomitant treatment with each of the phytocannabinoids (1 µM). The DCFDA assay was used to determine the ROS-scavenging ability of each phytocannabinoid following treatment with the lipid peroxidant tbhp (200 µM). Each phytocannabinoid provided significant protection against cytokine-evoked increases in epithelial permeability. Cannabidiol, cannabidivarin and cannabigerol were also able to significantly inhibit SN-38-evoked increases in permeability. None of the tested phytocannabinoids inhibited tbhp-induced ROS generation. These results highlight a novel role for cannabidiol, cannabidivarin and cannabigerol as inhibitors of SN-38-evoked increases in epithelial permeability and support the rationale for the further development of novel phytocannabinoids as supportive therapeutics in the management of irinotecan-associated mucositis.

The Effect of Oral Care Intervention in Mucositis Management Among Pediatric Cancer Patients: An Updated Systematic Review.

Background: Chemotherapy-induced mucositis is inflammation that develops in the oral mucosal due to anticancer treatment. Mucositis has negative consequences that may lead to distress in pediatric patients, resulting in escalated expenses, diminished quality of life, hindrance in cancer therapy, and decreased survival rates. However, despite the numerous methods, oral care protocols are suggested for implementation in the pediatric population despite a lack of high-level evidence studies, particularly regarding which appropriate oral care agents should be administered. Purpose: This systematic review aimed to identify the effect of oral care intervention in mucositis management among pediatric cancer patients. Methods: Studies were published between 2014 and 2023 from five databases: PubMed, Embase, Medline, ScienceDirect, and Scopus. They were identified using a search strategy to identify relevant studies that identify oral care interventions for managing mucositis in children with cancer. This study used the Joanna Briggs Institute (JBI) critical appraisal tools to assess the quality of the studies and followed the recommended reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: Eight studies met the inclusion criteria, including seven RCTs and one quasi-experimental study. Oral care interventions involving tooth brushing, mouthwash, and lip care are performed entirely or partially. The frequency of oral care ranges from two to six times daily, and the duration of intervention is from 5 days to six weeks. Oral care interventions using honey, olive oil, Aloe Vera, Andiroba, and salivary enzyme toothpaste are beneficial to lower the severity of mucositis, reduce pain, minimize mucositis duration, and reduce the use of analgesics, but not significantly improve the child's quality of life. However, Caphosol mouthwash did not significantly reduce mucositis. Conclusion: Our study highlights that oral care intervention using effective agents integratively, including honey, olive oil, Aloe vera, Andiroba, and salivary enzyme toothpaste, is essential to manage chemotherapy-induced mucositis among children. Systematic Review Registration: PROSPERO registration number was CRD42023456278.

In vitro cytoprotective and in vivo anti-oral mucositis effects of melatonin and its derivatives.

According to our preliminary study, melatonin and its N-amide derivatives (N-(2-(1-4-bromobenzoyl-5-methoxy-1H-indol-3-yl)ethyl)acetamide (BBM) and 4-bromo-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)benzamide (EBM)) inhibited the marker of acute inflammation in tests in vitro and in vivo. The anti-inflammatory agent is intended for the prevention and treatment of chemotherapy-induced toxicity. In this study aimed to evaluate the effect of melatonin and its derivatives on mechanisms related to chemotherapy-induced oral mucositis by in vitro ROS and 5-FU-induced human keratinocyte cells as well as in vivo oral mucositis model. In in vitro H2O2-induced HaCaT cells, BBM had the highest level of protection (34.57%) at a concentration 50 µM, followed by EBM (26.41%), and melatonin (7.9%). BBM also protected cells against 5-FU-induced to 37.69-27.25% at 12.5-100 µM while EBM was 36.93-29.33% and melatonin was 22.5-11.39%. In in vivo 5-FU-induced oral mucositis in mice, melatonin, BBM, and EBM gel formulations protected tissue damage from 5-FU similar to the standard compound, benzydamine. Moreover, the weight of mice and food consumption recovered more quickly in the BBM group. These findings suggested that it was possible to develop BBM and EBM as new therapeutic agents for the treatment of oral mucositis.

Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework.

Advances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis in both the mouth and gastrointestinal tract is common following many anti-cancer agents, manifesting as ulcerative lesions and associated symptoms throughout the alimentary tract. The pathogenesis of mucositis was first defined in 2004 by Sonis, and almost 20 years on, the model continues to be updated reflecting ongoing research initiatives and more sophisticated analytical techniques. The most recent update, published by the Multinational Association for Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO), highlights the numerous co-occurring events that underpin mucositis development. Most notably, a role for the ecosystem of microorganisms that reside throughout the alimentary tract (the oral and gut microbiota) was explored, building on initial concepts proposed by Sonis. However, many questions remain regarding the true causal contribution of the microbiota and associated metabolome. This review aims to provide an overview of this rapidly evolving area, synthesizing current evidence on the microbiota's contribution to mucositis development and progression, highlighting (i) components of the 5-phase model where the microbiome may be involved, (ii) methodological challenges that have hindered advances in this area, and (iii) opportunities for intervention.

Comparing the risk of severe oral mucositis associated with methotrexate as graft-versus host-disease prophylaxis to other immunosuppressive prophylactic agents in hematopoietic cell transplantation: a systematic review and meta-analysis.

PURPOSE: This study examines the risk of severe oral mucositis (SOM) in graft-versus-host disease prophylaxis (GVHD) compared to other agents in hematopoietic cell transplantation patients. METHODS: A comprehensive search of four databases, including PubMed, Embassy, Web of Science, and Scopus, was conducted to identify studies reporting frequency and severity of oral mucositis in association with GVHD prophylactic regimens. RevMan 5.4 was used to perform the meta-analysis. Risk of bias assessment was carried out using the Rob-2 tool for randomized clinical trials (RCTs) and ROBINS-I tool for observational studies. RESULTS: Twenty-five papers, including 11 RCTs and 14 observational studies, met the inclusion criteria. The pooled results from eight RCTs showed a higher risk of SOM in patients receiving MTX or MTX-inclusive GVHD prophylaxis versus non-MTX alternatives (RR = 1.50, 95% CI [1.20, 1.87], I2 = 36%, P = 0.0003). Mycophenolate mofetil (MMF) and post-transplant cyclophosphamide (Pt-Cy) consistently showed lower risk of mucositis than MTX. Folinic acid (FA) rescue and mini-dosing of MTX were associated with reduced oral mucositis severity. CONCLUSION: Patients receiving MTX have a higher SOM risk compared to other approaches to prevent GVHD, which should be considered in patient care. When appropriate, MMF, FA, and a mini-dose of MTX may be an alternative that is associated with less SOM. This work also underlines the scarcity of RCTs on MTX interventions to provide the best evidence-based recommendations.

Development and clinical implementation of a digital workflow utilizing 3D-printed oral stents for patients with head and neck cancer receiving radiotherapy.

OBJECTIVES: We describe the development of 3D-printed stents using our digital workflow and their effects on patients enrolled in the lead-in phase of a multi-center, randomized Phase-II trial. MATERIALS AND METHODS: Digital dental models were created for patients using intraoral scanning. Digital processes were implemented to develop the mouth-opening, tongue-depressing, and tongue-lateralizing stents using stereolithography. Time spent and material 3D-printing costs were measured. Physicians assessed mucositis using the Oral Mucositis Assessment Scale (OMAS) and collected MD Anderson Symptom Inventory (MDASI) reports and adverse events (AEs) from patients at various time points (TPs). OMAS and MDASI results were evaluated using paired t-test analysis. RESULTS: 18 patients enrolled into the lead-in phase across 6 independent clinical sites in the USA. 15 patients received stents (average design and fabrication time, 8 h; average material 3D-printing cost, 11 USD). 10 eligible patients with complete OMAS and MDASI reports across all TPs were assessed. OMAS increased significantly from baseline to week 3 of treatment (mean difference = 0.34; 95 % CI, 0.09-0.60; p = 0.01). MDASI increased significantly from baseline to week 3 of treatment (mean difference = 1.02; 95 % CI, 0.40-1.70; p = 0.005), and week 3 of treatment to end of treatment (mean difference = 1.90; 95 % CI, 0.90-2.92; p = 0.002). AEs (grades 1-3) were reported by patients across TPs. Mucositis and radiation dermatitis were primarily attributed to chemoradiation. CONCLUSIONS: 3D-printed stents were successfully fabricated and well tolerated by patients. As patients enroll in the randomized phase of this trial, data herein will establish a baseline for comparative analysis.

Alginate oligosaccharide improves 5-fluorouracil-induced intestinal mucositis by enhancing intestinal barrier and modulating intestinal levels of butyrate and isovalerate.

Chemotherapy-induced mucositis (CIM) is the typical side effect of chemotherapy. This study investigates the potential of alginate oligosaccharide (AOS) in ameliorating CIM induced by 5-fluorouracil (5-FU) in a murine model and its underlying mechanisms. AOS effectively mitigated body weight loss and histopathological damage, modulated inflammatory cytokines and attenuated the oxidative stress. AOS restored intestinal barrier integrity through enhancing expression of tight junction proteins via MLCK signaling pathway. AOS alleviated intestinal mucosal damage by inhibiting TLR4/MyD88/NF-κB signaling pathway, downregulating the pro-apoptotic protein Bax and upregulating the anti-apoptotic protein Bcl-2. Moreover, AOS significantly enriched intestinal Akkermansiaceae and increased the production of short-chain fatty acids (SCFAs), most notably butyrate and isovalerate. Pre-treatment with butyrate and isovalerate also alleviated 5-FU-induced CIM. In conclusion, AOS effectively mitigated CIM through strenghthening intestinal barrier, attenuating inflammation, and modulating gut microbiota and intestianl levels of butyrate and isovalerate. These finding indicate that AOS could be potentially utilized as a supplemental strategy for prevention or mitigation of CIM.

Results of the study of factors predicting the risk of the development of grade III radiation-induced mucositis during radiation or chemoradiation therapy in patients with oral cavity and oropharynx cancer.

BACKGROUND: Today, a number of methods and ways of prevention and treatment of radiation- -induced mucositis of the oral cavity and oropharynx have been developed, but the represented approaches are still not effective enough. Therefore, to increase the effectiveness of the prevention and treatment of radiation-induced mucositis, it is necessary to approach this problem comprehensively and individually, and to evaluate the factors affecting the development of mucositis. MATERIALS AND METHODS: In this single-center prospective controlled non-randomized clinical trial, the results of clinical observation of the development of complications of radiation and chemoradiation therapy in 105 patients with a newly diagnosed squamous cell cancer of the oral cavity and oropharynx were analyzed. Factors affecting the risk of the development of grade III radiation-induced mucositis including the age, gender of the patients, their general condition before the treatment according to World Health Organisation scales, type of the treatment and its doses, additional use of immunotherapy with alpha/beta defensins, characteristic signs of the tumor process and all indices of the immune status of the patients before the treatment have been analyzed. RESULTS: The method of construction and analysis of one-factor logistic regression models, where 24 indices were analyzed as factorial features, showed that the reduction of the risk of the development of grade III radiation-induced mucositis is predicted by several factors: immunotherapy, gender, serum concentrations of IgG and IgA. A decrease (P < 0.001) in the risk of the development of grade III radiation-induced mucositis was revealed if immunotherapy with alpha/beta defensins (with a total dose of 40 mg) was included into the treatment scheme (relative odds (RO) 0.05; 95% reference interval (RI) 0.02-0.18), in comparison with patients of the groups where it was not present or this immune agent was used in a total dose of 60 mg (P = 0.001, RO 0.06; 95% RI 0.01-0.30). The next factorial sign was gender, namely the risk of the development of grade III radiation-induced mucositis was lower for men (P = 0.003; RO 0.15; 95% RI 0.04-0.53) compared to women. An increase (P = 0.024) in the risk of the development of grade III radiation-induced mucositis with an increase in the initial level of IgG serum concentration was revealed, (RO 1.08; 95% RI 1.01-1.16) for each 1 mg/mL, as well as an increase (P = 0.044) in the possibility of the appearance of grade III radiation-induced mucositis with an increase in the serum concentration of IgA (RO 1.23; 95% RI 1.01-1.50) for every 1 mg/mL also before the beginning of the treatment. Multifactorial analysis has also confirmed that the risk of the development of grade III radiation-induced mucositis increases (P = 0.008) with a high serum IgG concentration before the treatment or with an increase in this index during therapy (RO 1.13; 95% RI 1.03-1.09) for every 1 mg/mL (when standardized by other risk factors). It was determined that when standardizing according to other factors (gender, IgG level), the risk of the development of grade III radiation-induced mucositis in the use of the immune agent alpha/beta defensins in a total dose of 40 mg per course decreases (P < 0.001; RO 0.08; 95% RI 0.02-0.27) compared to patients with oral cavity and oropharynx cancer who were not treated with immunotherapy. The risk of the development of grade III radiation-induced mucositis also decreases (P = 0.001) in the use of immunotherapy in a higher dose, i.e. 60 mg per course (RO 0.03; 95% RI 0.004-0.24 compared to patients whose treatment did not include immunotherapy (when standardized by other factors). CONCLUSION: As a result of this controlled clinical study, some factors were determined in addition to the radiation as those affecting the risk of the development of grade III radiation-induced mucositis in patients with oral cavity and oropharynx cancer during special treatment. These factors comprise the inclusion of immunotherapy with alpha/beta defensins into the specific treatment; gender, and baseline levels of serum IgG and IgA concentrations suggest a pattern in which the higher the serum IgG and IgA concentrations are before the start of the treatment, the greater is the likelihood of severe radiation-induced mucositis degree during special therapy. The results of the study of humoral state of the immune system in patients with oral cavity and oropharynx cancer before the beginning of chemoradiation therapy can be used as prognostic risk factors for the development of severe gamma-irradiation-induced mucositis of the oropharyngeal area, as well as an indication for the use of immunotherapeutic agents (in particular, alpha/beta defensins) that are able to polarize the immune response towards type 1 T-helpers through their immunomodulatory action.

Oral Mucositis and Nutritional Status in Children Who Underwent Hematopoietic Cell Transplantation: A Comparison Between Nonmalignant and Malignant Primary Diseases.

BACKGROUND: There is a lack of studies analyzing the association between oral mucositis (OM) and nutritional imbalance in children during hematopoietic stem cell transplantation (HSCT). The aim of this study was to compare the risk factors for OM and nutritional imbalance during HSCT in pediatric patients with nonmalignant diseases (NMD) and malignant diseases (MD). METHODS: Data on age, sex, primary disease, transplantation type, conditioning regimen, GVHD prophylaxis, gastrointestinal toxicity, OM, percent body weight loss or gain, nutritional repositioning, and overall survival (OS) were retrospectively collected from the 132 medical records. The data were then compared between patients with NMD (n = 70) and MD (n = 62). RESULTS: OM had a similar severity between the groups. The primary risk factor for OM in the NMD group was the conditioning regimen with busulfan, while in the MD group it was GVHD prophylaxis with cyclosporin and methotrexate. OM did not have an impact on body weight loss or gain in any of the groups. In the NMD, body weight gain due to fluid overload was more pronounced and associated with a lower age range. OS was similar between the groups and was not affected by OM. CONCLUSIONS: OM pattern was similar in pediatric patients with or without MD, but the factors that determined these oral lesions were different. There were disparities in body weight changes between the two groups, and these changes were not associated to OM.

Recent advances in cancer therapy-associated oral mucositis.

Oral mucositis (OM) is a common and debilitating toxicity of cancer treatments - chemotherapy, radiotherapy, hematopoietic cell transplant, or combinations. OM is associated with severe oral pain and has negative impacts on patient function and quality of life. Additionally, OM has accompanying systemic complications that may have critical implications. These local and systemic consequences can alter cancer treatment, and add an economic burden. This review covers the clinical presentation and course of OM, differential diagnosis, clinical and economic impacts, pathogenesis, risk factors, assessment measures, biomarkers and prediction of OM, management, research advances in the development of new drugs and treatments, and big data.

Chemotherapy-induced oral mucositis: hierarchical analysis of recurrence factors.

PURPOSE: This study aimed to analyze, through a hierarchical model, the risk factors associated with the recurrence of chemo-induced oral mucositis (OM) in children and adolescents. METHODS: A retrospective cohort with 31 individuals of both sexes, aged 1-18 years, who were undergoing chemotherapy, and presented OM lesions was conducted. Data collection included analysis of medical records, interviews, and intraoral examination. Information regarding patients' socioeconomic and demographic profile, underlying disease, antineoplastic regimen, hematological condition, and oral health status were collected. To assess the association of independent variables with the outcome, the Chi-square, Fisher's Exact, and Mann-Whitney tests were used, in addition to a binary logistic regression model, with a maximum error of 5% and a 95% confidence interval. RESULTS: Significant associations were observed between the history of OM and the diagnosis of the child/adolescent, neutrophil count, previous cancer treatments and the chemotherapy scheme in use (p < 0.05). Binary logistic regression revealed a 13.69 higher risk of developing OM recurrence in individuals who received high-dose methotrexate (MTX) therapy. CONCLUSION: Socioeconomic and demographic factors did not influence OM recurrence. However, clinical variables, such as neutropenia, diagnosis of leukemia, and high-dose MTX protocols increase the chance of OM new cases.

Association of oral mucositis induced by anthracycline-cyclophosphamide and subsequent docetaxel treatment for perioperative breast cancer.

PURPOSE: Anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy is effective for perioperative breast cancer treatment. However, these treatments frequently induce oral mucositis (OM), with an incidence ranging from 20 to 50%. The association of OM development between different chemotherapeutic treatments remains unclear. Consequently, this study aimed to compare OM development during docetaxel-containing chemotherapy between patients with and without OM experience during previous anthracycline-cyclophosphamide treatments to assess the association between OM development and treatment regimens. METHODS: Seventy-two patients with breast cancer receiving anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy as a perioperative treatment were categorized into the control (no prior OM experience with anthracycline-cyclophosphamide) and OM-experience (OM development during previous treatment) groups and retrospectively evaluated. The primary endpoint was the incidence of all-grade OM in the first docetaxel-containing chemotherapy cycle. Additionally, the incidences of OM and dysgeusia during all treatment cycles and factors associated with the incidence of OM were evaluated. RESULTS: The incidence of all-grade OM in the first cycle was significantly higher in the OM-experience group (54.2%) than in the control group (10.4%; P < 0.0001). Furthermore, its incidence in all treatment cycles was higher in the OM-experience group (66.7%) than in the control group (12.5%, P < 0.0001). However, the incidence of dysgeusia did not differ between the groups. Multivariate logistic regression analysis revealed OM experience during previous anthracycline-cyclophosphamide treatment and concomitant pertuzumab use as independent risk factors for OM development in subsequent docetaxel-containing chemotherapy. CONCLUSION: Our study suggests that patients experiencing OM with anthracycline-cyclophosphamide during perioperative breast cancer treatment exhibit symptoms following subsequent docetaxel-containing chemotherapy.

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors-major drivers of mucositis development-could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

The effect of different parameters of low-level laser used in the treatment of oral mucositis, on the viability and apoptosis of oral squamous cell carcinoma cells: In vitro study.

Oral mucositis is a complication of chemo/radiotherapy. To assess the impact of various power levels of diode-laser on the survival and expression of apoptosis-related genes in oral cancer cells, it is crucial to consider the potential existence of malignant cells within the treatment region and the reliance of laser effectiveness on its specific characteristics. Cal-27 cells were cultivated and exposed to a 660 nm-diode-laser at power levels of 20, 40, and 80 mW, alongside non-irradiated control cells. Viability and expression of Bax and Bcl-2 mRNA were assessed with Methyl Thiazolyl Tetrazolium (MTT) and Real-time Polymerase Chain Reaction (RT-PCR), respectively. The results were analyzed using one-way ANOVA and Tukey post-hoc test (p < 0.05). A significant reduction in viability was found only in the 20 mW group compared to controls (p = 0.001). Cell survival was significantly lower in cells receiving 20 mW laser than those treated with 40 and 80 mW (p < 0.05). None of the laser groups showed significant changes in BcL-2, but Bax was significantly lower in cells receiving 40 and 80 mW (p < 0.05), compared to controls. Laser irradiation at 660 nm (2 J/cm2, 30 s) significantly reduced the viability of oral cancer cells when using 20 mW power. These specifications align with the recommendation that the lowest possible laser dose should be applied for treating cancer patients. The exact mechanism of cell death following laser therapy with these specifications requires further investigation.

Application of In Situ Mucoadhesive Hydrogel with Anti-Inflammatory and Pro-Repairing Dual Properties for the Treatment of Chemotherapy-Induced Oral Mucositis.

Chemotherapy-induced oral mucositis (CIOM) is a prevalent complication of chemotherapy and significantly affects the treatment process. However, effective treatment for CIOM is lacking due to the unique environment of the oral cavity and the single effect of current drug delivery systems. In this present study, we propose an innovative approach by combining a methacrylate-modified human recombinant collagen III (rhCol3MA) hydrogel system with hyaluronic acid-epigallocatechin gallate (HA-E) and dopamine-modified methacrylate-alginate (AlgDA-MA). HA-E is used as an antioxidant and anti-inflammatory agent and synergizes with AlgDA-MA to improve the wet adhesion of hydrogel. The results of rhCol3MA/HA-E/AlgDA-MA (Col/HA-E/Alg) hydrogel demonstrate suitable physicochemical properties, excellent wet adhesive capacity, and biocompatibility. Notably, the hydrogel could promote macrophage polarization from M1 to M2 and redress human oral keratinocyte (HOK) inflammation by inhibiting NF-κB activation. Wound healing evaluations in vivo demonstrate that the Col/HA-E/Alg hydrogel exhibits a pro-repair effect by mitigating inflammatory imbalances, fostering early angiogenesis, and facilitating collagen repair. In summary, the Col/HA-E/Alg hydrogel could serve as a promising multifunctional dressing for the treatment of CIOM.

Indian Society of Periodontology Good Clinical Practice Recommendations for Peri-implant Care.

Current implant therapy is a frequently employed treatment for individuals who have lost teeth, as it offers functional and biological advantages over old prostheses. Concurrently, active exploration of intervention strategies aims to prevent the progression of peri-implant diseases and manage the existing peri-implant tissue damage. Indian Society of Periodontology has recognized the need for systematic documents to update the everyday clinical practice of general dental practitioners and has provided evidence-based consensus documents, namely good clinical practice recommendations from time to time to raise the oral health-related awareness and standards of oral health-care delivery across the country. The current clinical practice recommendations focused on peri-implant care to bridge the gap between academic theory and clinical practice by compiling evidence-based suggestions for preventing and treating peri-implant diseases. Twenty-eight subject experts across the country prepared these recommendations after a thorough literature review and group discussions. The document has been prepared in three sections covering peri-implant health and maintenance, peri-implant mucositis, and peri-implantitis. It will be a quick and concise reference for oral implant practitioners in patient management. The guidelines provide distinct definitions, signs, and symptoms, treatment required; recall visit specifications for plausible clinical case situations, and home-care recommendations regarding maintaining peri-implant health. The document advocates combined efforts of oral implant practitioners and the population at large with evidence-based, integrated, and comprehensive peri-implant care. By providing accessible, applicable guidance, these guidelines would empower dental professionals to uphold the well-being of implant patients and ensure the long-term success of implant therapy.

Might photobiomodulation therapy interfere with the frequency of severe mucositis and oral candidiasis? A retrospective analysis in patients with head and neck carcinoma.

PURPOSE: Considering the tumor in the oral cavity or the oropharynx and nasopharynx region might be an aggravating factor for oral mucositis (OM) manifestation, the present study aimed to evaluate whether the location of the tumor and the use of photobiomodulation therapy (PBMT) might affect the frequency of oral candidiasis (OC) during radiotherapy (RT) and/or chemotherapy (CT) treatments. METHODS: The medial records of seventy-four patients with head and neck cancer treated in a public service from 2016 to 2019 were evaluated. All these patients were submitted to RT in an accumulated dose of 48 to 70 Gy of radiation. Data about OM and OC were collected and presented according to the application of a therapeutic protocol with laser photobiomodulation (PBMT) to control oral mucositis, or not (No-PBM), and the location of tumor (head and neck or oral cavity). In the PBMT group patients, a low-power laser device composed of InGaAlP diode (maximum output power of 86.7 mW, active tip area of 0.1256 cm2, and continuous wavelength of 660 nm), was applied to the lips (three points each), right and left jugal mucosa (three points each), the limit between hard and soft palate (three points), buccal floor/sublingual gland (one point), lateral edge of the tongue (three points on each side), and back of the tongue (six points), three times weekly, for 5 weeks. The dosimetry used in each application was 2 J for 3 s, thus totaling 56 J. The correlation between clinical characteristics such as age, tumor size (T), metastatic lymph node (N), number of RT and CT sessions, candidiasis, and OM were analyzed. RESULTS: Mucositis grades 1 and 2 were the most common among all patients, especially before the 12th radiotherapy session, regardless of the treatment with PBM (p > 0.05). Additionally, no difference in the grade of OM and OC was significantly observed when comparing the two laser therapy groups. OC was more frequent after the 12th radiotherapy session in all groups. Nonetheless, OM and OC had a different correlation regarding to tumor location (head and neck and oral cavity) being PBMT a positive therapy to delay OM. It was observed a positive and statistically significant correlation between tumors at oral cavity and OM, regardless PBMT (R = 0.84, p < 0.05 to PBMT and R = 0.13, p < 0.05 to No-PBM). Otherwise, OC was positively correlated to local metastasis in patients with oral tumors undergoing PBMT (R = 0.84, p < 0.05). CONCLUSION: Patients with oral cavity tumor presented more OM, especially high grades, then patients with tumors in other regions of the head and neck, which seems to be related to the irradiation parameters of radiotherapy and/or with the limitation of conduction of PBMT in tumor areas. OM and OC were not changed by PBMT, although it helped to reduce the incidence of severe cases of OM.

Jasminum grandiflorum oral gel as an add-on to standard of care in radiation induced grade 2 oral mucositis - an open label pilot clinical trial.

BACKGROUND: Radiation-induced oral mucositis is one of the most critical dose-limiting toxicities associated with radiation therapy for oral cancer which can result in treatment interruption and compromise the quality of the life of cancer patients. Jati (Jasminum grandiflorum) is used in Ayurveda to treat oral conditions like stomatitis and mouth ulcers. OBJECTIVE: To test the feasibility of Jati oral gel as an add on therapy in grade 2 radiation-induced oral mucositis. MATERIALS AND METHODS: A prospective, open-label, non-randomised pilot trial was conducted on 20 patients with grade 2 radiation-induced oral mucositis at a tertiary cancer hospital. The control group received sodium bicarbonate mouthwash 4-5 times daily as the standard of care, while the intervention arm also received Jati oral gel twice daily. We used the ImageJ software for objective assessment and the Visual Analogue Scale for subjective pain assessment. The study was continued for 15 days or until the mucositis progressed to grade 3 or resolved to grade 1. RESULT: There was a significant reduction in the mean pain score and mean area of mucositis in the intervention group compared to the control group. CONCLUSION: Jati oral gel is a suitable medicament as an add-on therapy in managing grade 2 radiation-induced oral mucositis.

Lycium barbarum Ameliorates Oral Mucositis via HIF and TNF Pathways: A Network Pharmacology Approach.

BACKGROUND: Oral mucositis is the most common and troublesome complication for cancer patients receiving radiotherapy or chemotherapy. Recent research has shown that Lycium barbarum, an important economic crop widely grown in China, has epithelial protective effects in several other organs. However, it is unknown whether or not Lycium barbarum can exert a beneficial effect on oral mucositis. Network pharmacology has been suggested to be applied in "multi-component-multi-target" functional food studies. The purpose of this study is to evaluate the effect of Lycium barbarum on oral mucositis through network pharmacology, molecular docking and experimental validation. AIM: To explore the biological effects and molecular mechanisms of Lycium barbarum in the treatment of oral mucositis through network pharmacology and molecular docking combined with experimental validation. METHODS: Based on network pharmacology methods, we collected the active components and related targets of Lycium barbarum from public databases, as well as the targets related to oral mucositis. We mapped protein- protein interaction (PPI) networks, performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, and constructed a 'components-disease-targets' network and 'components- pathways-targets' network using Cytoscape to further analyse the intrinsic molecular mechanisms of Lycium barbarum against oral mucositis. The affinity and stability predictions were performed using molecular docking strategies, and experiments were conducted to demonstrate the biological effects and possible mechanisms of Lycium barbarum against oral mucositis. RESULTS: A network was established between 49 components and 61 OM targets. The main active compounds were quercetin, beta-carotene, palmatine, and cyanin. The predicted core targets were IL-6, RELA, TP53, TNF, IL10, CTNNB1, AKT1, CDKN1A, HIF1A and MYC. The enrichment analysis predicted that the therapeutic effect was mainly through the regulation of inflammation, apoptosis, and hypoxia response with the involvement of TNF and HIF pathways. Molecular docking results showed that key components bind well to the core targets. In both chemically and radiation-induced OM models, Lycium barbarum significantly promoted healing and reduced inflammation. The experimental verification showed Lycium barbarum targeted the key genes (IL-6, RELA, TP53, TNF, IL10, CTNNB1, AKT1, CDKN1A, HIF1A, and MYC) through regulating the HIF and TNF signaling pathways, which were validated using the RT-qPCR, immunofluorescence staining and western blotting assays. CONCLUSION: In conclusion, the present study systematically demonstrated the possible therapeutic effects and mechanisms of Lycium barbarum on oral mucositis through network pharmacology analysis and experimental validation. The results showed that Lycium barbarum could promote healing and reduce the inflammatory response through TNF and HIF signaling pathways.

Pediococcus pentosaceus PP34 Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis via Inhibiting Oxidative Stress and Restoring the Gut Microbiota.

Chemotherapy-induced intestinal mucositis based on 5-fluorouracil (5-FU) slows down the progress of cancer treatment and causes significant suffering to patients. Pediococcus pentosaceus (P. pentosaceus), as a type of LAB, has a range of probiotic properties, including antioxidant, immune benefits, and cholesterol-lowering effects, which are attracting increasing attention. However, studies on the protective effect of P. pentosaceus against chemotherapeutic-induced intestinal mucositis caused by 5-FU remain unclear. Therefore, this study aimed to investigate the potential relieving effects of P. pentosaceus PP34 on 5-FU-induced intestinal mucositis and its mechanism. In the present study, a P. pentosaceus PP34 solution (2 × 109 CFU/mL) was administered daily by gavage followed by intraperitoneal injection of 5-FU to model intestinal mucositis. The body weight, serum biochemical indices, jejunal pathological organization, and expression levels of inflammatory cytokines in the jejunum were examined. The results indicated that the mice induced with 5-FU developed typical intestinal mucositis symptoms and histopathological changes with intense inflammatory and oxidative responses. Moreover, the gut microbiota was disturbed, while PP34 effectively decreased the oxidative reactions and the expression levels of inflammatory mediators and regulated the gut microbiota in 5-FU-exposed mice. Taken together, the study indicated that P. pentosaceus PP34 ameliorates 5-Fluorouracil-induced intestinal mucositis via inhibiting oxidative stress and restoring the gut microbiota.