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JAMA Network Open Oct 2023Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies...
IMPORTANCE
Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies examining associations between OM and clinical outcomes were performed in the era of 3-dimensional conformal RT planning with low rates of concurrent chemotherapy, and thus may not reflect current practice.
OBJECTIVE
To prospectively assess patient-reported OM and identify its associations with clinical outcomes and quality of life.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study performed at a single institution included 702 consecutive patients who underwent definitive or adjuvant intensity-modulated RT (IMRT) for primary HNC from February 9, 2015, to May 27, 2022. Data were analyzed from November 28, 2022, to August 18, 2023.
MAIN OUTCOMES AND MEASURES
Severity of OM was assessed based on highest reported mouth and throat soreness (MTS) score during radiotherapy according to the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer survey, which was administered weekly during IMRT. Linear mixed models were used to compare mean MTS scores grouped by disease site and chemotherapy regimen. Fisher exact tests and 1-way analysis of variance tests were performed to identify associations between severity of OM and clinical outcomes.
RESULTS
Among 576 eligible patients, the median age was 62.5 (IQR, 56.3-69.1) years, and 451 patients (78.3%) were men. In terms of race and ethnicity, 6 patients (1.0%) were American Indian or Alaska Native; 2 (0.3%), Asian; 31 (5.4%), Black; 8 (1.4%), Hispanic or Latino; 509 (88.4%), White; and 28 (4.9%), unknown. The most common treatment site was oropharynx (268 [46.5%]), and most patients received concurrent chemotherapy (464 [80.6%]). By the end of treatment, 360 patients (62.5%) developed severe OM and 568 (98.6%) developed some degree of OM. Linear mixed models found no significant differences in OM between HNC disease sites. Groups with greater highest severity of OM reported had higher rates of measured outcomes (listed respectively by MTS score 0, 1, 2, 3, and 4): feeding tube placement (0%, 3.6% [2 of 56], 6.6% [10 of 152], 14.7% [40 of 272], and 21.6% [19 of 88]; P = .001), hospitalization (12.5% [1 of 8], 10.7% [6 of 56], 15.1% [23 of 152], 23.9% [65 of 272], and 28.4% [25 of 88]; P = .02), opiate use (0%, 19.6% [11 of 56], 42.8%[65 of 152], 61.4% [167 of 272], and 64.8% [57 of 88]; P < .001) and experienced greater weight loss (median, -0.7 [IQR, -1.7 to -0.4] kg; median, 3.9 [IQR, 1.1 to 6.1] kg; median, 5.0 [IQR, 2.2 to 7.7] kg; median, 4.7 [IQR, 2.1 to 7.7] kg; and median, 7.7 [IQR, 2.8 to 10.6] kg; P < .001).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with HNC, 62.5% developed severe OM. Higher severity of OM was associated with feeding tube placement, hospitalization, opiate use, and weight loss. Improvements in OM prevention and management are needed.
Topics: Male; Humans; Middle Aged; Female; Radiotherapy, Intensity-Modulated; Cohort Studies; Quality of Life; Head and Neck Neoplasms; Stomatitis; Opiate Alkaloids; Weight Loss
PubMed: 37819659
DOI: 10.1001/jamanetworkopen.2023.37265 -
Nutrients Dec 2022In recent years, evidence has shown the potential therapeutic effects of different natural compounds for the prevention and treatment of radiotherapy-induced mucositis... (Review)
Review
In recent years, evidence has shown the potential therapeutic effects of different natural compounds for the prevention and treatment of radiotherapy-induced mucositis (RIOM). RIOM represents one of the most frequent side effects associated with anti-neoplastic treatments affecting patients' quality of life and treatment response due to radiation therapy discontinuation. The innate radio-protective ability of natural products obtained from plants is in part due to the numerous antioxidants possessed as a part of their normal secondary metabolic processes. However, oxygen presence is a key point for radiation efficacy on cancer cells. The aim of this review is to describe the most recent evidence on radiation-induced injury and the emerging protective role of natural compounds in preventing and treating this specific damage without compromising treatment efficacy.
Topics: Humans; Stomatitis; Quality of Life; Radiation Injuries; Mucositis; Antioxidants
PubMed: 36558533
DOI: 10.3390/nu14245374 -
Drug Design, Development and Therapy 2024Recurrent aphthous stomatitis (RAS) refers to a sore and frequently recurring inflammation of the oral tissues, distinguished by the presence of small ulcers that cause... (Review)
Review
Recurrent aphthous stomatitis (RAS) refers to a sore and frequently recurring inflammation of the oral tissues, distinguished by the presence of small ulcers that cause significant discomfort and cannot be attributed to any underlying disease. Different treatments have been used for RAS. This review aims to provide a comprehensive overview of the treatment options over the past decade for recurrent aphthous stomatitis (RAS), encompassing both natural and synthetic treatments. It will utilize clinical efficacy studies conducted in vivo and in vitro, along with a focus on the pharmaceutical approach through advancements in drug delivery development. We conducted a thorough literature search from 2013 to 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of recurrent aphthous stomatitis, and treatment. A total of 53 clinical trials with 3022 patients were included, with 35 using natural materials in their research and a total of 16 articles discussing RAS treatment using synthetic materials. All the clinical trials showed that natural and synthetic medicines seemed to benefit RAS patients by reducing pain score, ulcer size, and number of ulcers and shortening the healing duration.
Topics: Stomatitis, Aphthous; Humans; Biological Products; Synthetic Drugs
PubMed: 38681204
DOI: 10.2147/DDDT.S449370 -
Frontiers in Cellular and Infection... 2022Radiotherapy and/or chemotherapy-induced oral mucositis (RIOM/CIOM) is a common complication in cancer patients, leading to negative clinical manifestations, reduced... (Review)
Review
Radiotherapy and/or chemotherapy-induced oral mucositis (RIOM/CIOM) is a common complication in cancer patients, leading to negative clinical manifestations, reduced quality of life, and impacting compliance with anticancer treatment. The composition and metabolic function of the oral microbiome, as well as the innate immune response of the oral mucosa are severely altered during chemotherapy or radiotherapy, promoting the expression of inflammatory mediators by direct and indirect mechanisms. Commensal oral bacteria-mediated innate immune signaling Toll-like receptors (TLRs) ambiguously shapes radiotherapy- and/or chemotherapy-induced oral damage. To date, there has been no comprehensive overview of the role of TLRs in RIOM/CIOM. This review aims to provide a narrative of the involvement of TLRs, including TLR2, TLR4, TLR5, and TLR9, in RIOM/CIOM, mainly by mediating the interaction between the host and microorganisms. As such, we suggest that these TLR signaling pathways are a novel mechanism of RIOM/CIOM with considerable potential for use in therapeutic interventions. More studies are needed in the future to investigate the role of different TLRs in RIOM/CIOM to provide a reference for the precise control of RIOM/CIOM.
Topics: Antineoplastic Agents; Humans; Immunity, Innate; Quality of Life; Stomatitis; Toll-Like Receptors
PubMed: 35719331
DOI: 10.3389/fcimb.2022.831387 -
BMC Oral Health Dec 2023Recurrent aphthous stomatitis has a complex and inflammatory origin. Among the great variety of medications it is increasingly common to use herbal medicines due to the...
BACKGROUND
Recurrent aphthous stomatitis has a complex and inflammatory origin. Among the great variety of medications it is increasingly common to use herbal medicines due to the adverse side effects of chemical medications. Considering the anti-inflammatory properties of cinnamaldehyde and the lack of studies related to the effectiveness of its nano form; This study investigates the effect of cinnamaldehyde and nano cinnamaldehyde on the healing rate of recurrent aphthous stomatitis lesions.
METHODS
In a laboratory experiment, cinnamaldehyde was converted into niosomal nanoparticles. The niosome vesicles diameter and polydispersity index were measured at 25°C using a dynamic light scattering (DLS) Mastersizer 2000 (Malvern Panalytical technologies: UK) and Zetasizer Nano ZS system (Malvern Instruments Worcestershire: UK). After characterizing these particles, the (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) [XTT] assay was used to assess the toxicity of cinnamaldehyde and nano cinnamaldehyde on gingival fibroblast (HGF) and macrophage (THP-1) cells. By determining the release of TNF-α, IL-6, and TGF-β cytokines using ELISA kits, the level of tissue repair and anti-inflammatory capabilities of these two substances were evaluated.
RESULTS
The size and loading rate of the cinnamaldehyde nanoparticles were established after its creation. The optimized nanovesicle exhibited the following characteristics: particle size of 228.75 ± 2.38 nm, PDI of 0.244 ± 0.01, the zeta potential of -10.87 ± 1.09 mV and the drug encapsulation percentage of 66.72 ± 3.93%. PDIs range was between 0.242-0.274. The zeta potential values at 25°C were from -2.67 to -12.9 mV. The results of the XTT test demonstrated that nano cinnamaldehyde exhibited dose-dependent toxicity effects. Moreover, nano cinnamaldehyde released more TGF-β and had better reparative effects when taken at lower concentrations than cinnamaldehyde.
CONCLUSION
Nano cinnamaldehyde and cinnamaldehyde are effective in repairing tissue when used in non-toxic amounts. After confirmation in animal models, it is envisaged that these substances can be utilized to treat recurrent aphthous stomatitis.
Topics: Animals; Stomatitis, Aphthous; Macrophages; Anti-Inflammatory Agents; Fibroblasts; Transforming Growth Factor beta
PubMed: 38110929
DOI: 10.1186/s12903-023-03682-9 -
Dental and Medical Problems 2020Denture stomatitis (DS) is a multifactorial disease, but the proliferation of Candida albicans (C. albicans) is the main causative factor. Different modalities have been... (Review)
Review
Denture stomatitis (DS) is a multifactorial disease, but the proliferation of Candida albicans (C. albicans) is the main causative factor. Different modalities have been suggested for the prevention and treatment of DS. Among the different approaches that have been implemented to inhibit and control DS there are the topical application of antifungal agents, the surface modification of the denture base and the incorporation of antimicrobial agents into the denture base material. Antifungal agents can effectively control DS, but the recurrence of the disease is common. Accordingly, it has been suggested that coating the surface of the acrylic denture base may result in a decreased fungal adhesion. In recent years, nanotechnology has dominated the research, and several nanoparticles have demonstrated antifungal effects. Therefore, the aim of this article was to review the antifungal effects of the different methods that have been suggested for the prevention and/or control of DS as well as the antimicrobial activity of denture base acrylic resin additives, including nanoparticles. Studies reporting the incorporation of antifungal/antimicrobial agents into the polymethyl methacrylate (PMMA) denture base were included in this review. The PubMed, Web of Science, Google Scholar, and Scopus databases were searched for the articles published between January 2000 and December 2018 using the following key words: dental prosthesis, denture stomatitis, candidiasis, antifungal agents, biofilm formation, polymethyl methacrylate, and PMMA. The antimicrobial material incorporated into the resin may have a superior effect in preventing DS over simply coating the surface of the denture base. However, some antimicrobial fillers can have adverse effects on the physical and mechanical properties of the denture base resin.
Topics: Acrylic Resins; Antifungal Agents; Candida albicans; Denture Bases; Humans; Stomatitis, Denture
PubMed: 32307934
DOI: 10.17219/dmp/112861 -
Internal Medicine (Tokyo, Japan) Mar 2023
Topics: Humans; Stomatitis, Aphthous; Case-Control Studies; Recurrence
PubMed: 35989280
DOI: 10.2169/internalmedicine.9669-22 -
Journal of Dental Research Sep 2020Oral mucositis (OM), a common debilitating toxicity associated with chemo- and radiation therapies, is a significant unmet clinical need for head and neck cancer... (Review)
Review
Oral mucositis (OM), a common debilitating toxicity associated with chemo- and radiation therapies, is a significant unmet clinical need for head and neck cancer patients. The biological complexities of chemoradiotherapy-induced OM involve interactions among disrupted tissue structures, inflammatory infiltrations, and oral microbiome, whereby several master inflammatory pathways constitute the complicated regulatory networks. Oral mucosal damages triggered by chemoradiotherapy-induced cell apoptosis were further exacerbated by the amplified inflammatory cascades dominantly governed by the innate immune responses. The coexistence of microbiome and innate immune components in oral mucosal barriers indicates that a signaling hub coordinates the interaction between environmental cues and host cells during tissue and immune homeostasis. Dysbiotic shifts in oral microbiota caused by cytotoxic cancer therapies may also contribute to the progression and severity of chemoradiotherapy-induced OM. In this review, we have updated the mechanisms involving innate immunity-governed inflammatory cascades in the pathobiology of chemoradiotherapy-induced OM and the development of new interventional targets for the management of this severe morbidity in head and neck cancer patients.
Topics: Chemoradiotherapy; Dysbiosis; Head and Neck Neoplasms; Humans; Immunity, Innate; Mucositis; Stomatitis
PubMed: 32479139
DOI: 10.1177/0022034520925421 -
BMC Oral Health Oct 2021Nattokinase (NK) is a promising alternative in the prevention and treatment of cardiovascular diseases due to its potent fibrinolytic activity. In this study, we...
BACKGROUND
Nattokinase (NK) is a promising alternative in the prevention and treatment of cardiovascular diseases due to its potent fibrinolytic activity. In this study, we investigated the effect of crude nattokinase extract on the healing of acetic acid-induced oral mucositis in mice.
METHODS
Bacillus subtilis culture media (BSCM) was isolated into the supernatant, named nattokinase crude extract (NCE), and the pellet was named Bacillus subtilis mass (BSM). An oral mucositis model was established in mice by applying 50% glacial acetic acid to the buccal mucosa. According to the treatment conditions, the mice were divided into BSCM, NCE, BSM and phosphate buffered saline (PBS) groups. The weight of the mice, oral mucositis healing score and histopathological examination were used to evaluate the treatment.
RESULTS
Fibrinolytic activities of BSCM, NCE and BSM were approximately 8069, 10,800 and 80 U/ml, respectively. The weight gain of mice in the NCE group was significantly different from the PBS group after three days' treatment (p < 0.05). The oral mucositis score of NCE group was significantly higher than other groups (p < 0.05). The differences in histopathology scores between the NCE and other groups were statistically significant (p < 0.01).
CONCLUSIONS
NCE could possess remarkable potential to reduce pain and promote oral mucositis healing with minimal safety concerns. In this study, we first report that NCE from the supernatant of Bacillus subtilis can promote the healing of oral mucositis, which extends the application scope of NK.
Topics: Animals; Complex Mixtures; Fermentation; Mice; Stomatitis; Subtilisins
PubMed: 34717590
DOI: 10.1186/s12903-021-01914-4 -
Nutrients Mar 2020Zinc, a metal found in the Earth's crust, is indispensable for human health. In the human body, around 60% of zinc is present in muscles, 30% in bones, and the remaining... (Review)
Review
Zinc, a metal found in the Earth's crust, is indispensable for human health. In the human body, around 60% of zinc is present in muscles, 30% in bones, and the remaining 10% in skin, hair, pancreas, kidneys and plasma. An adequate zinc balance is essential for the maintenance of skeletal growth, development and function. It is also necessary for basic cellular functions including enzyme activation, cell signaling and energy metabolism. Inadequate zinc status is associated with a wide variety of systemic disorders including cardiovascular impairment, musculoskeletal dysfunctions and oromaxillary diseases. In this article, we briefly discuss the role of zinc deficiency in the genesis of various oromaxillary diseases, and explain why adequate zinc homeostasis is vital for the maintenance of oral and general health.
Topics: Bone and Bones; Female; Hair; Homeostasis; Humans; Kidney; Male; Mouth Neoplasms; Muscles; Oral Health; Pancreas; Periodontal Diseases; Skin; Stomatitis; Zinc
PubMed: 32235426
DOI: 10.3390/nu12040949