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Oral mucositis (OM) is a common and serious complication of cancer chemoradiotherapy. OM managements mainly focused on topical healthcare or analgesia, which offers limited wound healing. Herein, in situ gel-forming oil (LGF) have been developed as a physical shielding for OM treatment. LGF oil, composed of soybean phosphatidyl choline (40 %, w/w), glycerol dioleate (54 %, w/w), and alcohols (6 %, w/w), is a viscous oil-like liquid. The contact angle of LGF oil on porcine buccal mucosa were 30°, significantly smaller than that of water (60°), indicating its good wetting and spreading properties. Besides, the adhesion force and adhesion energy of LGF oil toward porcine buccal mucosa was as high as 3.9 ± 0.2 N and 60 ± 2 J/m 2 , respectively, indicating its good adhesive property. Moreover, the hydrophobic α-lipoic acid (LA) as a native antioxidative agent was highly solubilized in LGF oil, its solubility in which was above 100 mg/mL. Upon contacting with saliva, LA-loaded LGF oil (LA-LGF) could rapidly transform from oil into gel that adheres on oral mucosa. Moreover, LA was slowly released from the formed LA-LGF gel, which benefited alleviating oxidative stress caused by chemoradiotherapy. In vivo animal experiments showed that LA-LGF could effectively promote the repairing of oral mucosa wound of 5-fluorouracil induced OM rats. Besides, the mucosa edema was greatly improved and new granulation around wound was produced after LA-LGF treatment. Meanwhile, the production of proinflammatory cytokines such as IL-1β, TNF-α, 1L-6 was substantially inhibited by LA-LGF. Collectively, LGF oil as carrier of hydrophobic drug might be a promising strategy for oral mucositis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Oral mucositis affects about 20% of children undergoing high-dose methotrexate (HDMTX) for acute lymphoblastic leukemia (ALL), despite existing management strategies. Personalized HDMTX dosing, adjusted by pharmacokinetics and leukemia risk, has reduced mucositis incidence, but variations still occur with similar 24-h methotrexate levels., Methods: This retrospective study investigated risk factors for oral mucositis under individualized methotrexate protocols. Data from patients with ≥ Grade 2 oral mucositis (CTCAE v4.0) were analyzed from the St. Jude Children's Research Hospital total 16 trial. A 1:1 case-control matching method considered age, sex, risk classification, immunophenotype, and methotrexate course. McNemar's, Bowker's symmetry, and Wilcoxon signed-rank tests were used for statistical analyses. Risk factors for recurrent mucositis were identified in a case-only analysis., Results: The study found significant associations between methotrexate-induced mucositis and new-onset skin rashes (p = 0.0027), fever (p = 0.0016), neutropenic fever (p = 0.0008), lower absolute neutrophil count (p < 0.0001), acute kidney injury (AKI) (p = 0.0164), delayed methotrexate clearance (p = 0.0133), and higher 42-h methotrexate levels (p = 0.0179). In the standard/high-risk group, mercaptopurine dose was also linked to mucositis (p = 0.0495). Multivariable analysis showed that skin rashes (OR 6.5, p = 0.0016), fever (OR 2.8, p = 0.009), and neutropenia (OR 2.3, p = 0.0106) were independent risk factors for mucositis. Female sex (OR 7.12, p = 0.015) and AKI (OR 3.819, p = 0.037) were associated with recurrent mucositis., Conclusions: Fever, skin rashes, AKI, delayed methotrexate clearance, and higher 42-h methotrexate levels were key risk factors for HDMTX-induced oral mucositis. Skin rashes, fever, and neutropenia were independent predictors, while female sex and AKI were linked to recurrent mucositis., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Oral mucositis is a severe adverse event in patients undergoing chemotherapy and radiotherapy that may lead to the termination of cancer treatment. This study aimed to elucidate the relationship between salivary inflammatory mediators and oral mucositis in patients undergoing chemotherapy., Methods: This prospective cohort study included 167 patients who underwent chemotherapy at our institution between June 2020 and November 2023. We evaluated the association between chemotherapy-induced oral mucositis and salivary inflammatory mediators using multiple comparison tests and logistic regression analyses., Results: Of the 167 patients, 67 (40.1%) had oral mucositis. Dunn's multiple comparison test revealed that interleukin-6 was significantly higher in oral mucositis of grades 2 and ≥ 3 (P < 0.01) and tumor necrosis factor (TNF)-α was significantly higher in oral mucositis of grades 3-4 (P < 0.01). Logistic regression analysis showed that the risk of oral mucositis was significantly higher for tumor necrosis factor (TNF)-α > 4.4 pg/mL than for TNF-α ≤ 4.4 pg/mL (adjusted odds ratio, 2.4; 95% confidence interval, 1.1-5.3; P = 0.03)., Conclusion: Saliva is useful in evaluating inflammation in patients with chemotherapy-induced oral mucositis. Furthermore, TNF-α may be a predictive marker for the severity of oral mucositis in patients undergoing chemotherapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aimed to evaluate the severity of oral mucositis and the contributing factors among cancer patients undergoing chemotherapy., Methods: This study was planned cross-sectional. The study was conducted at a medical oncology clinic between January and July 2022. The sample consisted of 245 patients with cancer receiving chemotherapy. Data were collected using a personal, oral health and disease-related characteristics questionnaire and the World Health Organization Oral Mucositis Assessment Scale by researchers. Intraoral examination of the patients was carried out by researchers. The data were analyzed by independent-sample t-tests, Chi-square tests, paired-sample t-tests, and multivariate logistic regression (p < 0,05)., Results: The patients had mean age 62.31 ± 10.70. Patients of 32.7% were with lung cancer. 52%of the patients (n = 128) receiving chemotherapy developed oral mucositis. The independent variables the presence chronic disease(OR:1.85), chemotherapy protocol (OR:3.52) and the dependent variables ECOG performance score (OR:2.25) were variable that affected the development of oral mucositis (p < 0.05). Patients of 35.5% were oral mucositis score of 1. Patients those who had breast cancer, who received doxorubicin or cyclophosphamide chemotherapy protocols, and who had previously developed oral mucositis were found to have a higher rate of oral mucositis (p < 0.05). In addition, oral mucositis was more prevalent in patients with chronic diseases other than cancer (57%), those who used medication continuously (57.2%), those with oral and dental diseases (56.9%), those who had dental check-ups before cancer treatment (79.2%), and those who had information about oral mucositis(70.2%) (p < 0.05)., Conclusion: In conclusion, nearly half of the patients (52%, n = 128) receiving chemotherapy developed oral mucositis and of all patients of 35.5% had an oral mucositis score of 1 in the second round of chemotherapy. Patients those who had breast cancer, who received doxorubicin or cyclophosphamide chemotherapy protocols, and who had previously developed oral mucositis were found to have a higher rate of oral mucositis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to develop a semi-interpenetrating network (IPN) hydrogel system suitable for the oral environment, capable of controlled release of DNase-I and oridonin (ORI), to exert antimicrobial, anti-inflammatory, and reparative effects on chemoradiotherapy-induced oral mucositis (OM). This IPN was based on the combination of ε-polylysine (PLL) and hetastarch (HES), loaded with DNase-I and ORI (ORI/DNase-I/IPN) for OM treatment. In vitro studies were conducted to evaluate degradation, adhesion, release analysis, and bioactivity including cell proliferation and wound healing assays using epidermal keratinocyte and fibroblast cell lines. Furthermore, the therapeutic effects of ORI/DNase-I/IPN were investigated in vivo using Sprague-Dawley (SD) rats with chemoradiotherapy-induced OM. The results demonstrated that the IPN exhibited excellent adhesion to wet mucous membranes, and the two drugs co-encapsulated in the hydrogel were released in a controlled manner, exerting inhibitory effects on bacteria and degrading NETs in wound tissues. The in vivo wound repair effect, microbiological assays, H&E and Masson staining supported the non-toxicity of ORI/DNase-I/IPN, as well as its ability to accelerate the healing of oral ulcers and reduce inflammation. Overall, ORI/DNase-I/IPN demonstrated a therapeutic effect on OM in rats by significantly accelerating the healing process. These findings provide new insights into possible therapies for OM.

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., (© 2024. The Author(s), under exclusive licence to European Academy of Paediatric Dentistry.)

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.

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 H 2 O 2 -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., Competing Interests: The authors declare that they have no competing interests., (© 2024 Mahakunakorn et al.)

Background: Chemotherapy, a cornerstone treatment for childhood cancers, can negatively impact oral health. This study aimed to evaluate the prevalence and evolution of oral complications in these patients., Materials and Methods: A prospective observational study enrolled 44 children diagnosed with malignancy undergoing chemotherapy at a tertiary care institute in central India. Oral examinations were performed at baseline, with follow-ups at 3-6 and 9-12 months. Data collected included demographics, medical history, oral hygiene practices, and oral lesions. Blood counts and World Health Organization grading for mucositis were used. Descriptive statistics and appropriate statistical tests analyzed the data (P ≤ 0.05)., Results: Acute lymphoblastic leukemia (ALL) was the most prevalent malignancy. Children reported various oral complaints such as ulcers, bleeding gums, and difficulty eating. Mucositis prevalence significantly decreased over follow-up visits (baseline: 56.8% and second follow-up: 13.3%). Gingival inflammation was present, though mean scores decreased over time. Oral hygiene scores varied without significant changes. Caries experience scores increased from baseline to follow-up., Conclusion: This study identified a high prevalence of ALL and diverse oral complications in children undergoing chemotherapy. While mucositis severity lessened over time, other issues such as caries persisted. These findings highlight the critical need for preventive oral care strategies to safeguard this vulnerable population's oral health., (Copyright © 2024 Copyright: © 2024 Journal of Indian Society of Pedodontics and Preventive Dentistry.)

Background: Oral mucositis (OM) is a prevalent side effect of chemotherapy that negatively impacts patient quality of life (QoL). Educational guidelines may provide strategies to mitigate these effects., Objective: To evaluate the effectiveness of educational guidelines on the severity of OM and QoL in oncology patients undergoing chemotherapy., Methods: A quasi-experimental study was conducted. Patients (n = 108) were randomly assigned to an intervention group receiving educational guidelines or a control group receiving routine care. Outcomes were assessed at baseline and at one and three months post-intervention. Data were collected using a structured interview including assessments of personal characteristics, clinical data, chemotherapy side effects, OM severity, and QoL., Results: Baseline QoL scores were comparable between groups. Post-intervention, the intervention group experienced significant improvements in QoL (p ≤ 0.05), while the control group showed a decline. OM severity was significantly reduced in the intervention group compared to the control group at both time points (p ≤ 0.05)., Conclusion: Educational guidelines are an effective intervention for reducing OM severity and improving QoL in oncology patients receiving chemotherapy. Implementation of these guidelines can enhance patient well-being and support optimal treatment outcomes.

Background: Chemotherapy is a common treatment for cancer, but it is associated with adverse drug reactions like oral mucositis. This condition destroys basal cells in the oral mucosal layer, causing inflammation and ulceration. This can impact the patient's physical, emotional, and psychological well-being, affecting treatment outcomes and quality of life. This study aims to determine the prevalence, severity, and risk factors of chemotherapy-induced oral mucositis among adult cancer patients., Methods: The study was a cross-sectional study conducted among adult cancer patients receiving chemotherapy at the cancer unit of Mbarara Regional Referral Hospital in southwestern Uganda. Data was collected through patient interviews, oral examinations, and patient chart reviews., Results: Out of 268 patients, 115 (42.9%) experienced oral mucositis. Grade 2 oral mucositis was the most common (44.3%) followed by grade 1 (35.7%) and grade 3 (20.0%). Independent risk factors of chemotherapy-induced oral mucositis were female gender (Adjusted Odds Ratio (AOR) = 2.19, 95% confidence interval [CI]: 1.27-3.78; p-value = 0.005), poor oral hygiene (AOR = 3.70, 95% CI: 1.51-9.10; p-value = 0.04), and receiving chemotherapy containing an alkylating agent (AOR = 3.17, 95% CI: 1.63-6.19; p-value < 0.001)., Conclusion: The study found that two out of five chemotherapy patients developed oral mucositis, with nearly half being grade 2. The risk factors identified in our study were comparable to those reported in previous studies. Therefore, identification and assessment of cancer patients at high risk for chemotherapy-induced oral mucositis should be routinely done for proper and timely management., (© 2023 John Wiley & Sons Australia, Ltd.)

Atezolizumab is an immune checkpoint inhibitor specific for the programmed death-1 (PD-1) receptor. In this case report, we describe two cases of oral mucositis that developed following the initiation of a systemic chemotherapy regimen comprising atezolizumab and bevacizumab for recurrent hepatocellular carcinoma. After 2 or 3 cycles of treatment, each patient presented with mucosal ulcers in the mouth, oral pain, difficulty in speech and oral intake, and both were admitted to our hospital for management. Following rule out of other conditions such as pharyngeal ulcers, herpetic mucositis, denture or oral trauma, or necrotizing mucositis, both patients were diagnosed with oral mucositis as a severe immune-related adverse event. Oral candidiasis was observed in both cases and should be considered a risk factor for the development of oral mucositis. Chemotherapy was discontinued and treatment with prednisolone was started, along with supportive care. The oral mucositis improved, and prednisolone was gradually reduced; however, in one patient, discontinuation of chemotherapy led to a recurrence of hepatocellular carcinoma. The other patient was lost to follow-up. In patients with risk factors, attention must be paid to the development of oral mucositis during immune checkpoint inhibitor treatment., (© 2024. Japanese Society of Gastroenterology.)

Background: Progestogen hypersensitivity (PH) is a rare phenomenon reported in women with an immunologic response to rising progesterone levels in the luteal phase. This disease's rarity and clinical spectrum make it challenging to diagnose., Case: In this case report, we will discuss a 14-year-old female with monthly oral mucositis and palmar lesions consistent with erythema multiforme. Over 2 years, she underwent an extensive multidisciplinary workup and was trialed on many different medical therapies., Summary and Conclusion: The prevalence of PH has grown in the literature over the past decade. Due to progesterone's role in many biochemical pathways, the pathophysiology is complex. Although many modalities are efficacious for treating PH's cyclical eruptions, we propose treatment with a Janus kinase inhibitor when hormonal management alone is insufficient., Competing Interests: Conflicts of Interest We have no financial disclosure or conflicts of interest. Written consent was obtained from our patient and the patient's guardian before writing this case., (Copyright © 2024. Published by Elsevier Inc.)

Background: Concerns regarding contact allergies and intolerance reactions to dental materials are widespread among patients. Development of novel dental materials and less frequent amalgam use may alter sensitization profiles in patients with possible contact allergy., Objectives: To analyse current sensitization patterns to dental materials in patients with suspected contact allergy., Methods: This retrospective, multicentre analysis from the Information Network of Departments of Dermatology (IVDK) selected participants from 169 834 people tested in 2005-2019 and registered with (i) an affected area of 'mouth' (and 'lips'/'perioral'), (ii) with the dental material in question belonging to one of three groups (dental filling materials, oral implants or dentures or equivalents) and (iii) with patch-testing done in parallel with the German baseline series, (dental) metal series and dental technician series., Results: A total of 2730 of 169 834 tested patients met the inclusion criteria. The patients were predominantly women (81.2%) aged ≥ 40 years (92.8%). The sensitization rates with confirmed allergic contact stomatitis in women (n = 444) were highest for metals (nickel 28.6%, palladium 21.4%, amalgam 10.9%), (meth)acrylates [2-hydroxyethyl methacrylate (HEMA) 4.8%] and the substances propolis (6.8%) and 'balsam of Peru' (11.4%). The most relevant acrylates were HEMA, 2-hydroxypropyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate and pentaerythritol triacrylate. Few men were diagnosed with allergic contact stomatitis (n = 68); sensitization rates in men were highest for propolis (14.9%) and amalgam (13.6%)., Conclusions: Allergic contact stomatitis to dental materials is rare. Patch testing should not only focus on metals such as nickel, palladium, amalgam and gold, but also (meth)acrylates and the natural substances propolis and 'balsam of Peru'., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The aim of this study was to investigate the DNA methylation profile in genes encoding catalase (CAT) and superoxide dismutase (SOD3) enzymes, which are involved in oxidative stress mechanisms, and in genes encoding pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor-alpha (TNF-α) in the oral mucosa of oncopediatric patients treated with methotrexate (MTX®). This was a cross-sectional observational study and the population comprised healthy dental patients (n = 21) and those with hematological malignancies (n = 64) aged between 5 and 19 years. Oral conditions were evaluated using the Oral Assessment Guide and participants were divided into 4 groups: 1- healthy individuals; 2- oncopediatric patients without mucositis; 3- oncopediatric patients with mucositis; 4- oncopediatric patients who had recovered from mucositis. Methylation of DNA from oral mucosal cells was evaluated using the Methylation-Specific PCR technique (MSP). For CAT, the partially methylated profile was the most frequent and for SOD3 and IL6, the hypermethylated profile was the most frequent, with no differences between groups. For TNF-α, the hypomethylated profile was more frequent in the group of patients who had recovered from mucositis. It was concluded that the methylation profiles of CAT, SOD3, and IL6 are common profiles for oral cells of children and adolescents and have no association with oral mucositis or exposure to chemotherapy with MTX®. Hypomethylation of TNF-α is associated with oral mucosal recovery in oncopediatric patients who developed oral mucositis during chemotherapy.

Background: Oral mucositis is one of the side effects developed post-hematopoietic stem cell transplant. This retrospective study aimed to assess the efficacy of a mouthwash mixture (lidocaine, sodium alginate, sucralfate, pheniramine) versus hyaluronic acid and a solution of sodium bicarbonate in terms of healing time and weight gain in the treatment of oral mucositis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation with hemato-oncological malignancies., Methods: A total of 171 patients that received chemotherapy for the hematopoietic stem cell transplant were divided into three groups; group 1, treated with a mixed mouthwash of lidocaine, sodium alginate, sucralfate, and pheniramine; group 2, treated with hyaluronic acid; and group 3, treated with an aqueous solution of 5% sodium bicarbonate. Weight and mucositis scale scores derived from medical records of patients., Results: There was a statistically significant difference in the mucositis scale scores between the groups on the transplant day and days 5, 10, 15 and 20 after the transplantation. At these measurement points, Group 2 (receiving hyaluronic acid) had a lower score, and Group 3 (who received sodium bicarbonate) had a higher score, especially on days 5 and 10 after the transplantation., Conclusion: The results suggest that hyaluronic acid is a more effective treatment option than the other oral care solutions that are frequently used for prophylaxis and treatment of oral mucositis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Oral mucositis is an inflammatory condition of oral cavity which is a common and serious side effect of cancer treatment. Severe oral mucositis compromises basic functions like eating and swallowing causing malnutrition also affecting overall patient's oral health related quality of life. The aim of the study was to find the frequency of oral mucositis in patients with breast cancer during their chemotherapy, the factors associated with oral mucositis & the overall patient's oral health related quality of life., Methods: A cross-sectional study was conducted and a total of 160 women diagnosed with breast cancer, receiving chemotherapy and who had undergone at least one cycle of chemotherapy were recruited from two hospital settings. In-person interviews were done, patients were asked questions about their sociodemographic history, personal habits, oral history and oral findings, breast cancer stage, chemotherapy history and Oral Health Related Quality of Life. Their oral examination was done at the end of the interview to assess presence or absence of oral mucositis, using World Health Organization oral mucositis tool. Oral Health Related Quality of Life was assessed using Oral Health Impact Profile-14 questionnaire., Results: Our results showed that out of 160 patients 88 (55%) of the breast cancer cases developed oral mucositis during chemotherapy. The mean Oral Health Impact Profile -14 scores in patients with oral mucositis was high 18.36±0.96 showing poor Oral Health Related Quality of Life. Occasional frequency of brushing was significantly associated with oral mucositis (Prevalence ratio:2.26, 95%&#95;CI 1.06-4.84) compared to those patients who brushed once and twice daily. Low level of education showed negative association with oral mucositis (Prevalence ratio:0.52, 95%&#95;CI 0.31-0.88)., Conclusion: Our study showed significant positive association of occasional brushing with OM and protective association of low level of education with the development of OM. Emphasis should be given to oral hygiene instructions and dental education to cancer patients in oncology clinics with the prescription of mouth washes, gels and toothpaste to patients to decrease OM during chemotherapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Allana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase., Methods: COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety., Results: During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, P = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only., Conclusions: SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase., Clinical Trial Registration: NCT03905512., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Treatment modalities for cancer including surgery, radiotherapy and chemotherapy, have some complications even in the oral cavity. The literature describes oral lesions that may arise as a result of chemotherapy. However, information regarding oral symptoms in advanced cancer patients is poor., Objective: To identify the oral manifestations like oral mucositis, dry mouth and loss of taste in patients undergoing chemotherapy treatment., Methods: We evaluated 60 patients affected by malignancy undergoing chemotherapy treatment. The clinical and pathological data such as age, gender, diagnosis of malignancy and types of treatments with anticancer chemotherapeutic drug treatment, were obtained. Patients were routinely evaluated for the presence of oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale for adverse effects and graded. Other findings like dry mouth and loss of taste were recorded., Results: Of the 60 patients, 40 (66.6%) were male, and 20 (33.3%) females with a mean age of 53.7 years. Most patients about 63% and 83% were diagnosed with dry mouth and loss of taste, respectively and 71% of patients had mucositis. Chemotherapy drugs like Cyclophosphamide, carboplatin, nanoxel, paclitaxel, oxaliplatin, docetaxel and doxorubicin, were directly associated with oral mucositis., Conclusion: Patients treated with chemotherapy for cancer most often suffer from a multitude of intense and debilitating oral dysfunctions. Oral lesions found in patients undergoing chemotherapy were mucositis, dry mouth and loss of taste. These adverse effects and an appropriate symptomatic therapy need to be discussed with the patients. Chemotherapy has a significant but transient effect on the oral symptoms., (Copyright © 2024 Copyright: © 2024 Indian Journal of Dental Research.)

Renal cell carcinoma is the predominant histological type of kidney cancer with historically poor patient outcomes. Lenvatinib in combination with pembrolizumab is an approved first-line regimen for people with advanced renal cell carcinoma that showed clinically meaningful improvements in efficacy over sunitinib in the CLEAR trial; however, reduced patient exposure to treatment (often stemming from adverse reactions) is a potential therapeutic barrier that must be addressed. Here, we present management strategies for adverse reactions associated with this treatment combination: fatigue, diarrhea, musculoskeletal pain, hypertension, stomatitis, decreased appetite, rash, nausea, and proteinuria. Dosing modification of lenvatinib and pembrolizumab should be made according to the prescribing information for each medication. Clinicians should consider that some adverse reactions, such as diarrhea, may be attributable to lenvatinib, or may be a symptom of immune-related adverse reactions to pembrolizumab (such as colitis). Adverse reactions can generally be managed by: (1) advising the patient on precautionary measures (eg, for stomatitis, practice dental hygiene, avoid irritating foods, and maintain adequate hydration), (2) monitoring for changes in symptoms from baseline (eg, changes in bowel movements, blood pressure or level of fatigue), (3) interrupting/dose reducing lenvatinib or interrupting pembrolizumab, if warranted, and advising the patient to manage their current symptoms via self-care (managing diarrhea with antidiarrheal agents and hydration), and (4) implementing medical interventions (eg, thyroid replacement or antihypertensive therapy) when needed. Through successful management of adverse reactions, oncology clinicians can improve the well-being of their patients and likely enhance adherence rates to treatment with lenvatinib and pembrolizumab., Competing Interests: Disclosures Viktor Grünwald reports receiving stock and other ownership interests from AstraZeneca, Bristol Myers Squibb, MSD, and Seagen; honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, EUSA Pharma, Ipsen, Janssen-Cilag, Lilly, Merck Serono, MSD Oncology, Novartis, Pfizer, PharmaMar, and Roche; has a consulting or advisory role for Bristol Myers Squibb, Ipsen, Janssen-Cilag, Lilly, MSD Oncology, Novartis, and Pfizer; has received research funding (inst) from Novartis; and has received travel/accommodations/expenses from AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, and Pfizer. James Larkin reports receiving honoraria from Eisai, Novartis, Incyte, Merck, touchIME, touchEXPERTS, Pfizer, Royal College of Physicians, Cambridge Healthcare Research, Royal College of General Practitioners, Ujoncology, Agence Unik, and BMS; a consulting or advisory role from iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm, and Incyte; institutional research funding from BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Aveo, Immunocore, Pharmacylics; and travel, accommodations and expenses from Roche/Genentech, GlaxoSmithKline, and Pierre Fabre. Javier Puente reports receiving honoraria from Pfizer, Bristol Myers Squibb, Ipsen, AstraZeneca, Roche, MSD Oncology, Janssen-Cilag, Astellas Pharma, EUSA Pharma, Eisai, Pierre Fabre, Sanofi, and Bayer; a consulting or advisory role from Pfizer, Astellas Pharma, Janssen-Cilag, Merck Sharp & Dohme, Bayer, Roche, Bristol Myers Squibb, Clovis Oncology, Ipsen, Eisai, and Sanofi; research funding from Astellas Pharma and Pfizer; and travel accommodations and expenses from Pfizer, Roche, Janssen-Cilag, Bristol Myers Squibb, and MSD Oncology. Jens Bedke reports receiving institutional honoraria from BMS and MSD; personal honoraria from AstraZeneca, Astellas, BMS, Eisai, EUSA Pharma, Ipsen, MSD, Merck Serono, Novartis, Pfizer, and Roche; and institutional research funding from AstraZeneca, Astellas, BMS, Eisai, Ipsen, MSD, Novartis, Nektar, Pfizer, Roche, and Seattle Genetics. Camillo Porta reports receiving a consulting, advisory, and/or speaker role from Angelini Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Ipsen, Merck, and MSD Oncology; is a protocol steering committee member for BMS, Eisai, and MSD., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM)., Methods: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes., Results: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response.", Conclusions: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Human β-defensin 1 (hBD-1) is a antimicrobial peptide that is constantly secreted by oral tissues. Hangeshashinto (HST), a traditional Japanese medicine, has been reported to be effective against stomatitis. This study aimed to clarify the profile of HST by comparing the system of production of interleukin-1α (IL-1α) and hBD-1 in human oral mucosal epithelial cells with dexamethasone (DEX), a steroid used for the treatment of stomatitis., Methods: Human oral keratinocytes (HOK) were treated with HST, DEX, or HST components (baicalein, baicalin, berberine, and glycyrrhizin) for 24 h, and subsequently cultured for 24 h with or without Pam3CSK4 or lipopolysaccharide (LPS). The cell supernatants, total RNA, and intracellular proteins were collected, and changes in IL-1α and hBD-1 protein production and gene expression were evaluated using ELISA and RT-PCR. The phosphorylation of NF-kB and the cell proliferative ability of HOK were evaluated by western blotting and XTT assay, respectively., Results: DEX (0.01-10 μM) significantly suppressed IL-1α and hBD-1 production induced by either Pam3CSK4 or LPS, and also decreased cell growth. In contrast, HST inhibited Pam3CSK4- and LPS-induced IL-1α production at a concentration range of 12.5-100 μg/mL without affecting the cell proliferative capacity and hBD-1 production of HOK. Baicalein and baicalin, which are flavonoid ingredients of HST, showed anti-IL-1α production., Conclusion: HST may be useful as a therapeutic agent for stomatitis and other inflammatory diseases of the oral cavity., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Background: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment., Material and Methods: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05)., Results: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM., Conclusions: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution.

Objective: The impact of anxiety and depression on chemotherapy-induced oral mucositis has not been extensively explored in the literature. The aim of the present study was to evaluate anxiety/depressive symptoms, health-related quality of life, and oral health-related quality of life and their association with oral mucositis among individuals receiving chemotherapy., Methods: This is a prospective longitudinal study carried out at a Brazilian referral service. The Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Oral Health Impact Profile questionnaire (OHIP-14) were applied at D0 (before chemotherapy) and D15 of chemotherapy. Clinicodemographic data and oral mucositis severity scores were evaluated., Results: A total of 37 individuals (median age: 49 years) were included in the study. Nearly 38% of patients developed chemotherapy-induced oral mucositis and had higher anxiety/depression scores at baseline. Oral mucositis had a negative impact on oral health-related quality of life regarding functional limitation, physical pain, physical disability, and handicap., Conclusion: Anxiety/depressive symptoms are associated with oral mucositis that affects overall health and oral health-related quality of life., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Indigo naturalis, a herbal medicine effective against ulcerative colitis, exhibits anti-inflammatory effects and induces interleukin-22-mediated antimicrobial peptide production. Anti-inflammatory activity and the prevention of secondary infection are essential for the management of chemotherapy-induced oral mucositis (CIOM); therefore, we developed an indigo naturalis ointment to be administered topically for CIOM and evaluated its feasibility., Methods: We performed a single-centre, open-label, prospective feasibility study from March 2017 to December 2018. The key eligibility criteria for the subjects were as follows: (1) receiving chemotherapy for a malignant tumour; (2) grade 1 or 2 CIOM and (3) receiving continuous oral care. The treatment protocol comprised topical indigo naturalis ointment application three times a day for 7 days. The primary endpoint assessed was feasibility. The secondary endpoints assessed were the changes in oral findings, oral cavity pain and safety., Results: Nineteen patients with CIOM were enrolled. The average feasibility (the proportion of prescribed applications that were carried out) observed in this study was 94.7%±8.9% (95% CI 90.5% to 99.0%), which was higher than the expected feasibility. The revised oral assessment guide scores of the mucous membrane domain and total scores were significantly improved. All patients reported a reduction in oral cavity pain, with a median pain resolution duration of 6 days. No serious adverse events were observed., Conclusions: The indigo naturalis ointment was feasible, and showed the potential for efficacy and safety. Larger randomised controlled trials are needed to further assess the efficacy and safety of indigo naturalis compared with a placebo., Trial Registration Number: UMIN000024271., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Anticancer drug-induced stomatitis can affect a patient's quality of life and the continuation of drug treatment. Although there have been reports of the occurrence of stomatitis associated with anticancer agents in clinical trials, few Japanese participants have been enrolled in clinical trials and have not been sufficiently investigated. In addition, there has been little attention on research on anticancer drugs associated with stomatitis by patient stratification with different carcinogenic sites. Therefore, the aim of this study was to determine the disproportionality associated with stomatitis for various types of anticancer drugs in different types of cancer patients using the Japanese Adverse Drug Event Report (JADER) database., Methods: The aim of this study was to identify the disproportionality of stomatitis by analyzing the type of anticancer drug and cancer patients using the Japanese Pharmacovigilance Database. Data obtained from spontaneous reports of adverse events with more than 10 stomatitis outbreaks reported in the JADER database between April 2004 and March 2023 were analyzed. The safety signal for an adverse event was defined as the lower limit of the 95% confidence interval of the reported odds ratio of &gt;1., Results: There were 6,178 reports of drugs associated with stomatitis. Among these, 41 drugs were suggested to be associated with stomatitis, and 41 drugs were detected as signals. These drugs were classified based on their efficacy: antipyrimidines (six drugs), folate metabolism antagonists (three drugs), alkylating agents (four drugs), platinum (three drugs), topoisomerase inhibitors (three drugs), microtubule inhibitors (three drugs), mammalian target of rapamycin (mTOR) inhibitors (two drugs), kinase inhibitors (seven drugs), anti-growth factor antibodies (five drugs) immune checkpoint inhibitors (one drug), and others (four drugs)., Conclusion: The drugs that may be associated with stomatitis were cell cycle-dependent drugs, epidermal growth factor receptor-tyrosine kinase inhibitors, and mTOR inhibitors. Moreover, this study suggested that anti-growth factor antibodies and immune checkpoint inhibitors may be associated with stomatitis development., (© 2024 S. Karger AG, Basel.)

Objectives: To prove our hypothesis that acyclovir prophylaxis in autologous hematopoietic stem cell transplantation (AHSCT) recipients with hematologic malignancies (HM) reduces the incidence of chemotherapy-induced oral mucositis (CIOM) by inhibiting the intraoral HSV reactivation during the neutropenic period, we conducted a randomized phase II study of acyclovir for the prevention of CIOM in adult HSV sero-positive AHSCT recipients., Methods: Patients were randomized to either the study group (acyclovir 400 mg PO bid until neutrophil engraftment) or the control group (no prophylaxis) and received AHSCT. Oral examination and sampling for HSV were performed at three timepoints of AHSCT., Results: In 54 patients who were randomized (for intention-to-analysis), the incidence of CIOM was 16.0% (4/25 patients) and 58.6% (17/29 patients) in the study group and the control group, respectively (P = 0.001). In 49 patients who completed the study (for per-protocol analysis), the incidence of CIOM was 13.0% (3/23 patients) and 61.5% (16/26 patients) in the study group and the control group, respectively (P = 0.001). In addition, HSV-1 PCR positivity in the study group was significantly lower than that the control group (4.3% vs. 46.2%, P = 0.001). A strong association between the HSV-1 reactivation status and CIOM was reconfirmed., Conclusions: Prophylactic use of oral acyclovir effectively reduced the incidence of CIOM in patients with HM who were undergoing AHSCT., Trial Registrations: This trial was registered at the Clinical Research Information Service in the Republic of Korea under the number KCT0003885 (registration date 03/05/2019)., (© 2023. The Author(s).)

Objective: The present study aimed to develop and validate an animal model of chemotherapy-induced oral mucositis due to cisplatin administration., Materials and Methods: Oral mucositis was induced in Wistar rats by cisplatin. Twenty healthy male Wistar rats were divided into four groups: a control group, and cisplatin 3 mg/kgBW (D1), cisplatin 5 mg/kgBW (D2), and cisplatin 6 mg/kgBW groups (D3). The D1, D2, and D3 groups received the cisplatin intraperitoneally on days 1, 3, and 5, whereas the control group did not receive anything. On day 7 and day 14 the entire experiment was terminated in all groups and the changes in body weight, oral mucositis grades, and histopathological scores were evaluated., Results: Cisplatin administration created a strong oral mucositis effect on groups D2 and D3. All the cisplatin doses decreased the rats' body weight by day 14. The worst oral mucositis grades and histopathological scores resulted from the administration of cisplatin at a dose of 5 mg/kgBW., Conclusions: In conclusion the cisplatin 5 mg/kgBW administered on days 1, 3, and 5 by intraperitoneal administration was the optimum dose to induce oral mucositis., (Copyright © 2023 Kadarullah et al. This article is available under a Creative Commons License (Attribution 4.0 International).)

Background : Dipeptidyl peptidase (DPP)-4 inhibitors are commonly used agents to treat type 2 diabetes mellitus (T2DM). Although generally well tolerated, stomatitis has been previously reported as an adverse event with sitagliptin and linagliptin. Stomatitis with alogliptin has not been reported in post-marketing data to date. Objective : To report a case of suspected drug-induced stomatitis in a patient who received alogliptin for T2DM which resolved upon discontinuation of the offending agent. Summary : A 60-year-old male with T2DM began treatment with a DPP-4 inhibitor, alogliptin. After 4 doses of alogliptin, the patient reported inflammation and irritation along the lateral borders of his tongue, along with open fissures and oral ulcerations on the dorsal surface of the mucosa. He was subsequently diagnosed with stomatitis. Patient discontinued alogliptin and reported improvement in symptoms within 48 hours. Lesions re-epithelialized within 4 weeks after cessation of alogliptin. The Naranjo Algorithm was used to assess causality. The total score was 7, which when interpreted, implicates alogliptin as a "probable" cause of the reaction. Conclusion : A causality assessment determined alogliptin was a "probable" cause of stomatitis experienced by this patient. This adverse effect has not been reported with alogliptin to the authors' knowledge., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Neither author has any conflict of interest to report. This material is the result of work supported with resources at the Veterans Health Care System of the Ozarks. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.

Objective: To evaluate the efficacy of NAHAO® oral mucosal antibacterial care solution (NAHAO® spray) on attenuating oral mucositis (OM) symptoms and related mechanisms investigation., Material and Methods: Experimental OM models were established by acetic acid and 5-fluorouracil combined with mechanical trauma. We investigated spontaneous pain of conscious OM rats after using NAHAO®. The expression of NF-κB in affected trigeminal ganglion was measured by western blot. In clinical study, 60 patients who developed post-treatment OM of grade 2 or above or persistent mucosal pain with a score equal to or greater than 4 points were selected. All patients were required to receive NAHAO® spray 8 times a day and were examined for OM degrees and oral mucosal pain scores before and after application., Results: Experimental data from experimental model suggested that clinical efficacy of NAHAO® spray was involved in inflammation inhibition via NF-κB pathway. The results of clinical study showed that NAHAO® spray improved the symptoms of OM, there is statistically significant difference in oral mucosal pain scores after treated with NAHAO, and the dietary restrictions were also improved., Conclusion: NAHAO® spray alleviates pain and improves the diet situation in OM patients, which is partly mediated through the inhibition of NF-κB pathway., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Anlotinib plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) achieves good efficacy, but there is still room for improvement. This clinical study examined the effectiveness of anlotinib plus etoposide for maintenance therapy in ES-SCLC., Methods: The current single-arm, prospective phase II study was performed at Jiangsu Cancer Hospital (March 2019 to March 2022). After successful primary etoposide-based therapy, anlotinib was administered at 12 mg/day on days 1 to 14 of 21-day cycles until disease progression or consent withdrawal. All patients also received etoposide at 50 mg/day on days 1 to 14 of 21-day cycles for a maximum of six cycles. Progression-free survival (PFS) constituted the primary study endpoint. Secondary endpoints were overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and safety. In addition, adverse events (AEs) were assessed., Results: Twenty-eight patients were treated. Median PFS and OS were 8.02 (95%CI 5.36-10.67) and 11.04 (95%CI 10.37-11.68) months, respectively. Totally 9 and 18 participants showed a partial response and stable disease, respectively; ORR and DCR were 32.14% and 96.43%, respectively. The commonest all-grade AEs were fatigue (n = 11, 39.28%), hypertension (n = 11, 39.28%), loss of appetite (n = 9, 32.14%), oral mucositis (n = 7, 25.00%) and proteinuria (n = 6, 21.40%). Grade 3-4 AEs included fatigue (n = 4, 14.28%), hypertension (n = 2, 7.14%), hand and foot syndrome (n = 2, 7.14%), oral mucositis (n = 1, 3.57%), hemoptysis (n = 1, 3.57%), proteinuria (n = 1, 3.57%), gingival bleeding (n = 1, 3.57%), and serum creatinine elevation (n = 1, 3.57%)., Conclusion: Maintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC., Registration Number: ChiCTR1800019421., (© 2023. The Author(s).)

Purpose: Oral mucositis (OM) is a side effect associated with cancer treatment. Hangeshashinto (HST), a Kampo medicine, was originally prescribed to treat diarrhea, gastritis, and stomatitis. Several reports have described the effects of HST for OM induced by chemotherapy in patients with gastric or colorectal cancer. In this study, the effects of HST for prevention of OM were investigated in patients undergoing hematopoietic stem cell transplantation (HSCT)., Methods: Thirty patients scheduled to receive allogeneic grafts were enrolled from July 2020 to December 2021. They were randomly assigned to two groups and instructed to wash their mouth using HST dissolved in saline solution or using only saline solution three times a day. The observation period was from the initiation date of the conditioning regimen to the date of engraftment, and the end point was the incidence of OM., Results: Eighteen patients developed OM, the most severe of which was Grade (G)3. There was no significant difference in the incidence of OM between the HST group and the control group. However, a negative correlation tended to be observed between the duration using HST use and the duration of OM (G2-3: P = 0.027, G3: P = 0.047)., Conclusions: The present study demonstrated that HST use did not clearly inhibit onset of OM but showed a tendency to inhibit OM exacerbation. However, further studies are necessary to fully understand the effects of HST on OM in patients undergoing HSCT., Trial Registration: This study was registered in the Japan Registry of Clinical Trials on 7 May 2020 (jRCTs071200012)., (© 2023. The Author(s).)

Purpose: Medical therapies, such as the use of anti-inflammatory agents, are commonly used for the treatment of oral mucositis (OM). However, these treatments have limited efficacy in treating severe cases of OM. In this study, we aimed to develop a carbopol gel incorporating troxipide (TRO) nanoparticles and methylcellulose (TRO-NP gel) and demonstrate its efficacy in accelerating wound healing in a hamster model of OM (OM model) induced by acetic acid injection., Methods: TRO nanoparticles were prepared using bead milling. The crystalline form was determined by powder X-ray diffraction, and the particle size was measured using a NanoSight LM10 instrument. The drug release was determined using a Franz diffusion cell, and the hamsters injected with acetic acid were selected to evaluate the therapeutic effect of OM., Results: After preparing TRO nanoparticles, we observed a mixture of crystals and amorphous TRO, and the particle size of TRO in the TRO-NP gel ranged from 50 to 280 nm. The TRO-NP gel exhibited a more uniform TRO distribution and viscosity compared to the Carbopol gel containing TRO microparticles (TRO-MP gel). However, the solubility of TRO was comparable in both TRO-MP and TRO-NP gels. The TRO-NP gel released a higher amount of TRO than that from the TRO-MP gel, with detectable release of TRO nanoparticles. TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were higher than those treated with TRO-MP gel. The increased TRO levels in the cheek pouches of hamsters treated with TRO-NP gel were attenuated by treatment with 40 μM dynasore, an inhibitor of clathrin-dependent endocytosis (CME). Moreover, the therapeutic effect of the TRO-NP gel was superior to that of the TRO-MP gel in the hamster model of OM., Conclusion: We have designed a TRO-NP gel, and this gel showed excellent TRO delivery into the cheek pouch tissue through the CME pathway. Moreover, the TRO-NP gel treatment enhanced wound healing after acetic acid injection., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Kadowaki et al.)

Photobiomodulation therapy (PBMT) is widely used in oncology settings, but lack of assessment standardization is the main barrier to optimization of clinical protocols. This study analyzed three PBMT protocols for preventing oral and oropharyngeal mucositis (OM) in patients undergoing chemotherapy (CT) and/or hematopoietic stem cell transplantation (HSCT). This is a preliminary randomized blind clinical trial. Group 1 received intraoral prophylactic PBMT, Group 2 received intraoral and oropharyngeal PBMT, and Group 3 received intraoral, oropharyngeal, and extraoral PBMT. The applications were from the first day of CT to day + 10. Clinicodemographic data, CT regimens, types of HSCT, hematological exams, occurrence/severity of OM, odynophagia, and OM-related opportunistic infections were assessed. Sixty participants (age range: 18-74 years) were included; 70% of them underwent CT and 30% HSCT. About 43.3% of patients had OM, while odynophagia was reported by 23.3%. Both Groups 1 and 2 revealed better results. Multivariate analysis showed that HSCT directly influenced the occurrence of OM. Individuals who had undergone allogeneic HSCT were 1.93 times more likely to develop OM (p < 0.001). Group 3 exhibited a higher frequency of OM, albeit of lower grades. This group consisted of half the population who had undergone HSCT, had the highest percentage of melphalan use, and had the lowest mean leukocyte count. The three proposed protocols were effective in preventing and reducing OM, with good tolerance and no reported adverse effects. PBMT is a safe and effective approach to OM prophylaxis in adults undergoing CT/HSCT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objectives: Considering the prevalence of oral mucositis, we aimed to use the analgesic effects of doxepin with chitosan's antimicrobial and bio-adhesive nature to fabricate a nano-formulation for treating chemotherapy-induced oral mucositis., Materials and Methods: Nanogel was fabricated via ionic gelation and characterized. Sixty patients were randomly divided and received four different treatments for 14 days: diphenhydramine + aluminum-magnesium mouthwash (control), doxepin mouthwash (DOX MW), chitosan nanogel (CN), and doxepin/chitosan nanogel (CN + DOX). Lesions were assessed with four indices, National Cancer Institute (NCI), World Health Organization (WHO), World Conference on Clinical and Research in Nursing (WCCNR) and visual analog scale (VAS) before and 3, 7, and 14 days after interventions. Kruskal-Wallis test was used for pairwise comparison., Results: CN had semisolid consistency, uniform spherical shape, an average size of 47.93 ± 21.69 nm, and a zeta potential of + 1.02 ± 0.16 mV. CN + DOX reduced WHO, WCCNR, and VAS scores significantly more than the control three days after the intervention. Seven days after the intervention, CN + DOX reduced NCI and WCCNR considerably more than the control; it reduced WCCNR significantly more than CN. Fourteen days after the intervention, CN + DOX decreased NCI markedly more than the control., Conclusion: Chitosan-based doxepin nano-formulation might be a promising alternative for routine treatments of oral mucositis., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Anxiety and depression are frequent conditions among individuals undergoing antineoplastic therapy, but their relationship with oral mucositis is unclear. This systematic review evaluated the potential association of anxiety and depression with frequency and severity of chemo/radiotherapy-induced oral mucositis., Materials and Methods: Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature searches in three other databases. The risk of bias was assessed using the Joanna Briggs Institute tool., Results: Eight observational studies conducted on 954 individuals (male-to-female ratio: 1.1:1; age range: six-82 years). Three (37.5%) studies included patients with solid tumors, two (25%) studies included hematopoietic/lymphoid tissue tumors, and two (25%) studies comprised mixed types of malignant neoplasms. Eight different instruments were used to assess oral mucositis, while seven different instruments were used to evaluate anxiety and depression. Associations of anxiety and/or depression with oral mucositis severity were reported in six (75.0%) studies. Oral mucositis-related symptoms, especially pain, were linked with depression in three (37.5%) studies., Conclusion: A relatively low number of cases and data heterogeneity hamper definitive conclusion about the potential association between anxiety/depression and oral mucositis. Further studies that could guide more personalized treatments are warranted to investigate this plausible bidirectional interaction., (© 2022 Wiley Periodicals LLC.)

Current study aimed to research the effect of Hippophae rhamnoides (HRE) on potantial oral oxidative and inflammatory damage of 5-FU in rats. The rats were assigned to three groups; healthy (HG), 5-FU 100mg/kg (FUG) and HRE 50mg/kg +5-FU 100mg/kg (HRFU). The 5-FU was injected in the FUG group intraperitoneally. The HRFU was injected 5-FU at 100mg/kg IP one hour after the 50mg/kg HRE was given orally. Olive oil was used as a solvent for the HG. HRE was given to the rats three times a day for ten days. 5-FU was given one dose on the 1st, 3rd and 5th days. On the 10th day, the tissues removed from the animals were euthanized with high-dose anaesthesia and were macroscopically examined. The levels of the oxidant, antioxidant and proinflammatory cytokines were investigated.It was seen that HRE alleviated the symptoms of severe mucositis by antagonizing the effects of 5-FU on oxidant, antioxidant and proinflammatory cytokines such as malondialdehyde, total glutathione, superoxide dismutase, catalase, nuclear factor kappa-B and interleukin-6 in inner cheek and tongue tissue. These results recommend that HRE may be benefical in the cure of 5-FU-associated oral mucositis.

Background: Oral mucositis (OM) considerably affects the experience of patients with cancer during treatment. This study investigated the effects of cryotherapy on cancer therapy-induced OM., Objective: This study aimed to systematically appraise evidence on whether cryotherapy can reduce the incidence and severity of OM., Methods: We conducted an umbrella review to examine the effect of cryotherapy on cancer-related OM. The primary outcome was the incidence and severity of OM. We performed a subgroup analysis including solid cancers and hematological malignancies., Results: Five meta-analyses were included. Cryotherapy could more effectively reduce the incidence of severe OM (risk ratio [RR], 0.37; 95% prediction interval [PI], 0.22-0.64). In the subgroup analyses of solid cancers or hematological malignancies, cryotherapy significantly reduced the incidence of grades 2 to 4 OM in patients with solid cancers (RR, 0.51; 95% PI, 0.34-0.78 and RR, 0.52; 95% PI, 0.36-0.74). However, no significant difference was observed in the incidence of OM in patients with hematological malignancies regarding any grade or grade 3 or 4 OM. Moreover, cryotherapy did not significantly reduce the OM duration (mean difference, -0.13; 95% PI, -20.89 to 20.63; mean difference, -2.99, 95% PI, -8.10 to 2.12)., Conclusion: Cryotherapy can reduce the incidence of severe OM induced by chemotherapy or radiotherapy., Implication for Practice: We recommend the inclusion of this safe, simple, and convenient intervention in chemotherapy or radiotherapy plans. Additional clinical trials are warranted to extend the limited evidence on the effectiveness of cryotherapy in reducing the severity and duration of OM., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The objective of this study was to investigate the pharmacokinetic characteristics of pegylated liposomal doxorubicin (PLD) in Chinese female patients with advanced breast cancer by constructing population pharmacokinetic (popPK) models of liposome-encapsulated and free doxorubicin. Additionally, the relationship between pharmacokinetic parameters and drug-related adverse events (AEs) was explored through toxicity correlation analysis., Methods: A total of 20 patients with advanced breast cancer were selected from a PLD bioequivalence study. All patients received a single intravenous dose of 50 mg/m 2 PLD. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A popPK model was simultaneously built to characterize the pharmacokinetic profiles of liposome-encapsulated and free doxorubicin by non-linear mixed effects model (NONMEM). PLD-related toxicities were graded according to the common terminology criteria for adverse events (CTCAE) v5.0. The Spearman correlation analysis was conducted to explore the relationship between pharmacokinetic parameters and drug-related AEs of both liposome-encapsulated doxorubicin and free doxorubicin., Results: The concentration-time profiles of both liposome-encapsulated doxorubicin and free doxorubicin were well described by a one-compartment model. The most common AEs to PLD were nausea, vomiting, neutropenia, leukopenia, and stomatitis, most of which were grade I-II. The toxicity correlation analysis results indicated that stomatitis was related to the C max of liposome-encapsulated doxorubicin (P < 0.05). No other AEs were found to be correlated with the pharmacokinetic parameters of either free or liposome-encapsulated doxorubicin., Conclusion: A one-compartment model adequately described the popPK characteristics of both liposome-encapsulated and free doxorubicin in Chinese female patients with advanced breast cancer. Most AEs to PLD were mild. Additionally, the occurrence of mucositis may be positively correlated with the C max of liposome-encapsulated doxorubicin., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer., Basic Procedures: Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2., Main Findings: Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed., Principal Conclusions: The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens., Methods: Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis., Results: Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (β = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use., Conclusion: Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis., (© 2023. The Author(s).)

Reactive oxygen species (ROS) are highly reactive molecules generated in living organisms and an excessive production of ROS culminates in oxidative stress and cellular damage. Notably, oxidative stress plays a critical role in the pathogenesis of a number of oral mucosal diseases, including oral mucositis, which remains one of cancer treatments' most common side effects. We have shown previously that oral keratinocytes are remarkably sensitive to oxidative stress, and this may hinder the development and reproducibility of epithelial cell-based models of oral disease. Here, we examined the oxidative stress signatures that parallel oral toxicity by reproducing the initial events taking place during cancer treatment-induced oral mucositis. We used three oral epithelial cell lines (an immortalized normal human oral keratinocyte cell line, OKF6, and malignant oral keratinocytes, H357 and H400), as well as a mouse model of mucositis. The cells were subjected to increasing oxidative stress by incubation with hydrogen peroxide (H 2 O 2 ) at concentrations of 100 μM up to 1200 μM, for up to 24 h, and ROS production and real-time kinetics of oxidative stress were investigated using fluorescent dye-based probes. Cell viability was assessed using a trypan blue exclusion assay, a fluorescence-based live-dead assay, and a fluorometric cytotoxicity assay (FCA), while morphological changes were analyzed by means of a phase-contrast inverted microscope. Static and dynamic real-time detection of the redox changes in keratinocytes showed a time-dependent increase of ROS production during oxidative stress-induced epithelial injury. The survival rates of oral epithelial cells were significantly affected after exposure to oxidative stress in a dose- and cell line-dependent manner. Values of TC50 of 800 μM, 800 μM, and 400 μM were reported for H400 cells (54.21 ± 9.04, p < 0.01), H357 cells (53.48 ± 4.01, p < 0.01), and OKF6 cells (48.64 ± 3.09, p < 0.01), respectively. Oxidative stress markers (MPO and MDA) were also significantly increased in oral tissues in our dual mouse model of chemotherapy-induced mucositis. In summary, we characterized and validated an oxidative stress model in human oral keratinocytes and identified optimal experimental conditions for the study of oxidative stress-induced oral epithelial toxicity.

Context: To date, the efficacy of nutritional interventions on oral mucositis (OM) in patients with cancer, and the quality of this evidence have not been explored., Objective: The goal of this umbrella review was to provide a comprehensive evaluation of nutritional interventions for patients with cancer with OM, as well as to assess the quality of this evidence., Data Sources: Meta-analyses were searched for using PubMed, Scopus, and ISI Web of Science databases until December 2021, with no time restrictions., Data Extraction: Meta-analyses of randomized control trials that evaluated the effects of nutritional interventions on the incidence of OM in patients with cancer had inclusion criteria for this umbrella review. Data extraction, quality assessment of meta-analyses, and primary studies were done independently by 2 authors. The Grading of Recommendations Assessment, Development, and Evaluation technique was used to grade the certainty of evidence., Data Analysis: A total of 26 meta-analyses were included in this umbrella review. The results showed that honey, glutamine, and propolis can reduce the incidence of severe OM, based on moderate evidence quality. In addition, zinc supplementation significantly reduced the incidence of OM, regardless of symptom severity; however, low certainty of the evidence was observed. The effects of vitamin E, curcumin, and probiotics on OM were not statistically significant., Conclusion: This umbrella review shows that honey, glutamine, and propolis can significantly reduce the incidence of severe OM. These findings need to be confirmed with well-designed, longitudinal randomized controlled trials., Systematic Review Registration: PROSPERO registration no. CRD42022301010., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to report a case series of patients with metastatic colorectal cancer (mCRC) undergoing panitumumab-containing regimens affected by oral lesions and to review the current literature., Study Design: Electronic medical records of mCRC patients referred to treat mouth sores during the treatment with the anti-epithelial growth factor receptor (EGFR)-panitumumab-were retrospectively reviewed. Patients' characterization, clinical profile of oral lesions, and management outcomes were documented. Additionally, modifications or discontinuation of the antineoplastic treatment as well as the occurrence of other adverse events (AEs) were analyzed., Results: A total of 7 patients were included. The oral lesions appeared in a median time of 10 days (range 7-11 days) after the drug administration. The median reported pain score was 5 (range 1-9), causing feeding discomfort. Oral lesions with a marked aphthous-like appearance, among others, occurred in all cases and involved nonkeratinized mucosa more likely. At least 1 patient had dose reduction of the treatment and 1 patient needed discontinuation due to panitumumab-associated stomatitis. Dermatologic AEs were the most prevalent. Clinical improvement was obtained with topical corticosteroid therapy and/or photobiomodulation., Conclusions: In summary, panitumumab-containing regimens were associated with a particular pattern of oral lesions consistent with stomatitis. This event may eventually affect the tolerability of the treatment in patients with mCRC., Competing Interests: Declarations of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Waldeyer lymphatic ring surrounds the nasopharynx and oropharynx, and no study to date has correlated its microbiome with the severity of oral mucositis (OM) in patients with nasopharyngeal carcinoma (NPC) receiving chemoradiotherapy., Methods: We performed 16S rRNA sequencing to characterize bacterial microbiome in tumor-affected nasopharynx and the surrounding normal oropharynx. We plotted the abundance and diversity of bacterial taxa and their phylogenetic distance and networks to visualize and compare the differences in pretreatment overall bacterial communities between the nasopharynx and oropharynx in patients with NPC with varying degrees of chemoradiotherapy-induced OM and quality of life., Results: We found microbial signatures in nasopharynx around NPC were not only dissimilar to those in the surrounding oropharynx but were almost unique to each patient. The genetic distance metrics further showed that different tumor microbiota distributions in the nasopharynx among patients with NPC were well-correlated with OM severity and quality of life during chemoradiotherapy., Conclusions: At Waldeyer ring, the tumor-associated microbiome risk profiles of the respiratory region of nasopharynx, but not commensal microbiota of the alimentary region of oropharynx, could be noninvasive biomarkers for OM susceptibility and might include drug targets for the prevention of chemoradiation-induced OM in patients with Waldeyer ring-derived NPC., (© 2023 Wiley Periodicals LLC.)

Purpose: Oral mucositis (OM) is a common complication of cancer treatment that has an impact on a patient's quality of life and the outcome of cancer therapy. This trial evaluated the effect of thyme honey oral gel for the prevention of chemotherapy-induced OM., Methods: One hundred ten breast cancer patients who received their first cycle of chemotherapy with adriamycin (60 mg/m 2 ) and cyclophosphamide (600 mg/m 2 ) were randomly recruited into two groups: group A were patients who followed general oral hygiene recommendations and rinsing saline 3 times a day, and group B were patients with similar protocol but supplied with our formulated oral gel to be applied 2 to 4 times a day. Patients were assessed by the World Health Organization (WHO) oral mucositis grading scales and self-assessment daily questionnaire., Results: The use of thyme honey was associated with diminishing incidence of OM grade ≥ 2 (95% CI, 0.12 to 0.90; P = 0.030), duration of OM (- 3.36 days; 95% CI, - 5.50 to - 1.22; P = 0.037) and delayed occurrence of OM grade ≥ 2 (95% CI, 0.10 to 0.80; P = 0.017)., Conclusion: Thyme honey can be considered as a prophylactic agent for OM and decrease the severity of its symptoms., Trial Registrations: This protocol was registered at the Iranian Registry of Clinical Trials: registration number IRCT201506063106N25, on June 12, 2015; approved by the institutional review board at the Deputy of Research, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran; and approved by the Ethics Committee of Medical Researches of Pharmaceutical Sciences Branch of Islamic Azad University, Tehran, Iran-reference number 5936, on August 17, 2014., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oral and intestinal mucositis (OIM) are debilitating inflammatory diseases initiated by oxidative stress, resulting in epithelial cell death and are frequently observed in cancer patients undergoing chemo-radiotherapy. There are currently few preventative strategies for this debilitating condition. Therefore, the development of a safe and effective mucositis mitigating strategy is an unmet medical need. Hyaluronic acid (HA) preparations have been tentatively used in oral mucositis. However, the protective effects of HA in chemotherapy-induced mucositis and their underlying mechanisms remain to be fully elucidated. This study aimed to assess these mechanisms using multiple formulations of enriched HA (Mucosamin ® ), cross-linked (xl-), and non-crosslinked high molecular weight HA (H-MW-HA) in an oxidative stress-induced model of human oral mucosal injury in vitro and an in vivo murine model of 5-flurouracil (5-FU)-induced oral/intestinal mucositis. All tested HA formulations protected against oxidative stress-induced damage in vitro without inducing cytotoxicity, with H-MW-HA also significantly reducing ROS production. Daily supplementation with H-MW-HA in vivo drastically reduced the severity of 5-FU-induced OIM, prevented apoptotic damage and reduced COX-2 enzyme activity in both the oral and intestinal epithelium. In 5-FU-injected mice, HA supplementation also significantly reduced serum levels of IL-6 and the chemokine CXCL1/KC, while the serum antioxidant activity of superoxide dismutase was elevated. Our data suggest that H-MW-HA attenuates 5-FU-induced OIM, at least partly, by impeding apoptosis, inhibiting of oxidative stress and suppressing inflammatory cytokines. This study supports the development of H-MW-HA preparations for preventing OIM in patients receiving chemotherapy., (© 2023. The Author(s).)

Objective: The objective of this systematic review was to determine whether oral and dental hygiene protocols (DHPs) reduce the incidence and severity of oral mucositis (OM) during antineoplastic treatment., Materials and Methods: This PROSPERO-registered systematic review (CRD42021295322) was based on searches of publicly accessible databases, including PubMed, Scopus, Web of Science, LILACS, EBSCOhost, LIVIVO, Embase, and gray literature (Google Scholar, ProQuest, and Energy) until December 2021. Twenty-five articles from these searches and 14 articles retrieved from the references therein were evaluated in this systematic review and meta-analysis. The risk of bias (RoB) was assessed using RoB-2 and ROBINS-I for randomized (RCT) and non-randomized (n-RCT) clinical trials, respectively. A meta-analysis was performed on RCTs and n-RCTs in two subgroups to evaluate oral mouth rinses or DHP. GRADE-pro was used to assess the degree of certainty of the evidence., Results: Of the 3367 articles retrieved, 25 RCTs and 14 n-RCTs involving 2109 and 754 patients, respectively, were included in the analyses. RoB was low for RCTs and moderate-to-very severe for n-RCTs. High heterogeneity and publication RoB were identified. In RCTs, mouth rinses (p = 0.830) and DHP (p = 0.100) did not reduce the incidence of OM. However, mouth rinses strongly reduced the severity of OM (p < 0.001; Cohen's d =  - 1.87, 95% confidence interval [CI] =  - 2.49 to - 1.24). In non-RCTs, mouth rinses (p < 0.001) and DHP (p < 0.001) reduced the relative risk of OM 0.38 (95% CI = 0.24 to 0.59) and 0.64 (95% CI = 0.53 to 0.70) times, respectively. In addition, DHP strongly reduced OM severity (Cohen's d =  - 0.81, 95% CI =  - 1.03 to - 0.59). GRADE-pro showed high certainty of OM severity and incidence in RCTs and non-RCTs, respectively, and low (OM incidence in RCTs) to very low (OM severity in non-RCTs) certainty in other outcomes., Conclusion: DHPs strongly reduce the severity and moderately reduce the incidence of OM. However, further studies with low heterogeneity are needed to validate these findings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Management of head and neck cancers requires a multidisciplinary approach where surgery followed by radio and chemotherapy is the mainstay of treatment. The above-mentioned treatment can cause mucositis, a severely debilitating side effect. This can have a significant impact on quality of life. A recent advancing mode of drug delivery is the bioadhesive system. This interacts with mucosa by adhering to it and thereby improving the efficacy of the therapeutic agent delivered., Aim and Objective: The purpose of this systematic review is to evaluate the effectiveness of bioadhesives in reducing oral mucositis and relieving pain associated with mucositis in head and neck cancer patients receiving radio-chemotherapy., Materials and Method: Studies assessing the effectiveness of bioadhesives for the treatment of radiation-induced oral mucositis were retrieved from specialized databases (PubMed/MEDLINE, Scopus, ProQuest, Google Scholar, LILACS, OpenGrey) as well as institutional repositories. Data on incidence, pain reduction, resolution, and improvement of oral mucositis using bioadhesive were compiled. A Cochrane tool was used for randomized controlled trials and a JBI tool for non-randomized controlled trials and observational studies to assess the quality of included studies. Based on the eligible study data, a meta-analysis was conducted with STATA version 16, 2019 software, and 95% confidence intervals and p values greater than 0.05., Results: A total of 15 studies were included which assessed the effectiveness of bioadhesives in managing mucositis and its associated pain. Studies included in the review described either reduction, resolution, or incidence of oral mucositis respectively. A total of three meta-analyses were conducted to assess the incidence of oral mucositis and the pain associated with it, as well as the reduction in incidence. Bioadhesives showed statistically significant differences in the incidence of severe mucositis (p = 0.04). A meta-analysis comparing bioadhesives efficacy in reducing mucositis and pain associated with it found no statistically significant differences (p = 0.36)., Conclusion: Bioadhesives are emerging as a novel drug delivery method for treating radio-chemotherapy-induced oral mucositis because of their rapid absorption and easy application. Regardless of its benefits, clinical trials comparing it with conventional treatment methods are necessary to assess its efficacy in treating oral mucositis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)