Impact of Educational Guidelines on Oral Mucositis Severity and Quality of Life in Oncology Patients Receiving Chemotherapy: A Quasi-Experimental Study.

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.

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

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

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

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

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

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

TNF-α promoter hypomethylation is frequent in oncopediatric patients who recovered from mucositis.

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.

The Efficacy of Three Different Oral Hygiene Regimens in Preventing Chemotherapy-Induced Oral Mucositis in Pediatric Patients Receiving Hematopoietic Stem Cell Transplantation.

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.

Oral mucositis & oral health related quality of life in women undergoing chemotherapy for breast cancer in Karachi, Pakistan: A multicenter hospital based cross-sectional study.

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%_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%_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.

Two cases of severe oral mucositis caused by atezolizumab plus bevacizumab combination therapy for hepatocellular carcinoma.

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.

Single nucleotide polymorphisms conferring susceptibility to leukemia and oral mucositis: a multi-center pilot study of patients prior to conditioning therapy for hematopoietic cell transplant.

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.

Comparison between hangeshashinto and dexamethasone for IL-1α and ß-defensin 1 production by human oral keratinocytes.

OBJECTIVE: Human ß-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.

Management of Adverse Reactions Related to Lenvatinib Plus Pembrolizumab Treatment Among Patients With Renal Cell Carcinoma.

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.

Risk factors for oral mucositis in patients with solid tumors under treatment with cetuximab: a retrospective cross-sectional study.

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.

The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout.

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.

Contact allergies to dental materials in patients.

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'.

Progesterone Hypersensitivity: The Utility of a Janus Kinase Inhibitor for Recurrent Erythema Multiforme.

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.

Prevalence and risk factors of chemotherapy-induced oral mucositis among adult cancer patients at the cancer unit of Mbarara Regional Referral Hospital.

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.

Influence of anxiety/depression on chemotherapy-induced oral mucositis and related quality of life: A prospective cohort study.

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.

A randomized phase II study of acyclovir for the prevention of chemotherapy-induced oral mucositis in patients undergoing autologous hematopoietic stem cell transplantation.

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).

Hangeshashinto for prevention of oral mucositis in patients undergoing hematopoietic stem cell transplantation: a randomized phase II study.

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).

Therapeutic Effects of Hydrogel Formulations Incorporating Troxipide Nanoparticles on Oral Mucositis in Hamsters.

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.