Mucositis oral como efecto adverso al uso del metotrexato en el tratamiento de la artritis reumatoide: una revisión sistematizada de casos / Oral mucositis as an adverse effect of the use of methotrexate in the treatment of rheumatoid arthritis: a systematized review of cases

Introducción: el metotrexato se usa ampliamente para el tratamiento de una variedad de enfermedades neoplásicas y autoinmunes. Sin embargo, como todo fármaco, su eficacia viene marcada por cierto grado de toxicidad debido a la farmacocinética del medicamento. El metotrexato se creó como un fármaco anticancerígeno; sin embargo, se ha convertido en el tratamiento de elección contra la artritis reumatoide. Principalmente, el metotrexato causa inflamación de las mucosas epiteliales. La mayoría de los efectos secundarios del metotrexato se pueden detectar de forma temprana y son reversibles. La mucositis del tracto alimentario es el principal efecto secundario de la quimioterapia contra el cáncer. Se le conoce colectivamente como lesión de la mucosa inducida por quimioterapia, afecta todo el canal alimentario desde la boca hasta el ano, ocasionando la mucositis oral y la mucositis intestinal. Material y métodos: se buscaron casos clínicos en los que se reporte mucositis causada por metotrexato en tratamiento de artritis reumatoide. Se empleó un diagrama de flujo, PRISMA modificado para la búsqueda de artículos. Finalmente, se cotejó que los casos clínicos cumplieran con los fundamentos de la CARE guide, para manejar una correcta estructura y bajo riesgo a sesgo. Conclusiones: una correcta anamnesis y exploración clínica oral es lo más importante de la medicina oral. Es relevante indagar sobre las enfermedades que presentan los pacientes, así como la historia de medicamentos que se administren, especialmente en pacientes mayores, con mayores padecimientos de enfermedades sistémicas (AU)

Introduction: methotrexate is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, like all drugs its efficacy is marked by a certain degree of toxicity due to the pharmacokinetics of the drug. Methotrexate was developed as an anticancer drug, however, it has become the treatment of choice for rheumatoid arthritis. Methotrexate primarily causes inflammation of the epithelial mucous membranes. Most of the side effects of methotrexate can be detected early and are reversible. Mucositis of the alimentary tract is the main side effect of cancer chemotherapy. It is collectively known as chemotherapy-induced mucosal injury, affecting the entire alimentary canal from the mouth to the anus, where oral mucositis and intestinal mucositis are both common. Material and methods: we searched for clinical cases reporting mucositis caused by methotrexate in the treatment of rheumatoid arthritis, using a modified PRISMA flowchart to search for articles. Finally, the clinical cases were checked for compliance with the fundamentals of the CARE guide, in order to manage a correct approach to oral medicine. It is important to inquire about the diseases the patients present, as well as the history of medications administered, especially in older patients, with more systemic disease conditions, structure, and low risk of bias. Conclusion: a correct anamnesis and oral clinical examination is the most important aspect of oral medicine. It is important to inquire about the diseases that the patients present, as well as the history of medications that are administered, especially in older patients with major systemic diseases (AU)

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

Abstract 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.

Patient-, implant- and prosthetic-related factors on peri-implant mucositis and bone loss

Abstract Peri-implant diseases, including peri-implant mucositis (PIM) and peri-implantitis, are a chronic inflammatory disorder triggered by bacterial biofilm in susceptible hosts. Potential risk factors for peri-implant diseases include smoking, dental plaque accumulation, poor oral hygiene, genetics, and absence of peri-implant keratinized mucosa. This cohort study aimed to evaluate the influence of patient-, implant-, and prosthetic-related factors on PIM and peri-implant bone loss (PBL) around dental implants after 1 year of loading. A total of 54 subjects (22 males and 32 females) were included in the study. Peri-implant clinical parameters were assessed and standardized periapical radiographs of each dental implant were obtained 15 days after the definitive prosthesis installation (baseline) and at 3, 6, and 12 months of follow-up. A total of 173 implants were evaluated. PIM affected 44.8% of the implants and no significant association was found between the investigated parameters and PIM incidence, except for type of implant connection. A significantly higher incidence of PIM (80.0%) was observed for implants with internal hexagon connection type after 1 year of follow-up (p = 0.015). Moreover, a mean PBL of 0.35 ± 1.89 mm was observed and no dental implant was affected by peri-implantitis after 1 year of function. No specific influence of patient, implant, or prosthetic factors on PBL was observed. No association was found between the occurrence of PIM/PBL and the patient-, implant-, and prosthetic-related factors investigated in this cohort study, except for the type of dental-implant connection.

Plant extracts used in Brazil for treatment of oral ulcers and mucositis: systematic review / Extratos vegetais utilizados no Brasil para tratamento de úlceras orais e mucosite: revisão sistemática

Objective: To identify and analyze plant extracts used in Brazil for the treatment of oral ulcers and oral mucositis. Material and Methods: A systematic review was registered in PROSPERO (CRD 42018102184) and performed following the PRISMA protocol. The databases searched were PubMed, Web of Science, Scopus, Lilacs, Scielo, the Brazilian Dentistry Library. Manual searches were also performed. Results: Initially, 440 studies were found, of which 392 were excluded after reading the titles and abstracts. A total of 29 articles were read in full and 11 studies were excluded, resulting in 18 articles included in the systematic review. Nine plant species were identified in five clinical trials and 13 in vivo studies, with Chamomila recutita being the most used (33.3% of the studies). Chamomila recutita showed more promising results for analgesic, anti-inflammatory, and healing properties. Calotropis procera latex significantly decreased (p<0.05) inflammatory mediators, such as TNF-α and IL-1ß in oral mucositis induced in rats. Eupatorium laevigatum showed anti-inflammatory activity and analgesic action on oral ulcers. Carapa guianensis Aubl. reduced the severity and painful symptoms of oral mucositis and exhibited better results compared to the use of low power laser. Curcuma longa L accelerated re-epithelialization and resolution of inflammatory processes. Spondias mombin reduced oxidative stress and inflammation caused by oral mucositis and helped on healing it. Extracts of Aloe barbadensis Miller or Aloe vera showed anti-inflammatory action but did not help in the healing process of oral ulcers. Copaifera reticulata Ducke oil did not induce improvement in the healing process, nor did it show an anti-inflammatory effect. Malva sylvestrisdid not show an anti-inflammatory action on oral lesions in humans or rats. The assessment of methodological heterogeneity showed the impossibility of performing a meta-analysis. Risk of bias varied from low to high. Conclusion: The plant species most used and with the best results for the treatment of oral ulcerations and oral mucositis was Chamomilla recutita. Spondias mombin L., Curcuma longa L., Carapa guianensis Aubl and Calotropis procera showed good results in the treatment of oral mucositis, while Eupatorium laevigatum was efficient in the treatment of ulcers of traumatic origin. Malva sylvestris, Copaifera reticulata Ducke, and Aloe barbadensis Miller did not exhibit significant results (AU)

Objetivo: Identificar e analisar extratos vegetais utilizados no Brasil para o tratamento de úlceras orais e mucosite oral. Material e Métodos: Uma revisão sistemática foi registrada no PROSPERO (CRD 42018102184) e realizada seguindo o protocolo PRISMA. As bases de dados pesquisadas foram PubMed, Web of Science, Scopus, Lilacs, Scielo, Biblioteca Brasileira de Odontologia. Buscas manuais também foram realizadas. Resultados: Inicialmente, foram encontrados 440 estudos, dos quais 392 foram excluídos após a leitura dos títulos e resumos. Um total de 29 artigos oram lidos na íntegra e 11 estudos foram excluídos, resultando em 18 artigos incluídos na revisão sistemática. Nove espécies vegetais foram identificadas em cinco ensaios clínicos e 13 estudos in vivo, sendo a Chamomila recutita a mais utilizada (33,3% dos estudos). A Chamomila recutita apresentou resultados mais promissores quanto às propriedades analgésicas, anti-inflamatórias e cicatrizantes. O látex de Calotropis procera diminuiu significativamente (p<0,05) os mediadores inflamatórios, como TNF-α e IL-1ß, na mucosite oral induzida em ratos. Eupatorium laevigatumapresentou atividade anti-inflamatória e ação analgésica em úlceras orais. Carapa guianensis Aubl. reduziu a gravidade e os sintomas dolorosos da mucosite oral e apresentou melhores resultados em comparação com o uso do laser de baixa potência. Curcuma longa L. acelerou a reepitelização e resolução de processos inflamatórios. Spondias mombinreduziu o estresse oxidativo e a inflamação causadas pela mucosite oral e ajudou na sua cicatrização. Extratos de Aloe barbadensis Miller ou Aloe vera apresentaram ação anti-inflamatória, mas não auxiliaram no processo de cicatrização de úlceras orais. O óleo de Copaifera reticulata Ducke não induziu melhora no processo cicatricial, nem apresentou efeito anti-inflamatório. Malva sylvestris não apresentou ação anti-inflamatória em lesões orais em humanos ou ratos. A avaliação da heterogeneidade metodológica mostrou a impossibilidade de realizar uma meta-análise. O risco de viés variou de baixo a alto. Conclusão: A espécie vegetal mais utilizada e com melhores resultados para o tratamento de ulcerações orais e mucosite oral foi a Chamomilla recutita. Spondias mombin L., Curcuma longa L., Carapa guianensis Aubl e Calotropis procera apresentaram bons resultados no tratamento da mucosite oral, enquanto Eupatorium laevigatum foi eficiente no tratamento de úlceras de origem traumática. Malva sylvestris, Copaifera reticulata Duckee Aloe barbadensis Miller não apresentaram resultados significativos(AU)

O efeito das abordagens herbais na mucosite oral em pacientes adultos com câncer - uma revisão sistemática de estudos de enfermagem / The effect of herbal approaches on oral mucositis in adult cancer patients - a systematic review of nursing studies / El efecto de los enfoques herbales sobre la mucositis oral en pacientes adultos con cáncer - una revisión sistemática de estudios de enfermería

Objetivo: examinar os efeitos das abordagens herbais na mucosite oral em pacientes adultos com câncer. Método: revisão sistemática seguindo as diretrizes da Cochrane, com uma busca por estudos experimentais e randomizados entre 2013 e 2023. Foram incluídos estudos em inglês sobre intervenções herbais em pacientes com mais de 18 anos. Resultados: foram avaliados oito estudos que usaram intervenções herbais para tratar a mucosite oral. As ervas testadas incluíram aloe vera, raiz de althaea, cúrcuma, camomila, vinagre de uva, água de rosas, suco de frutas/vegetais e extrato de amoreira. As intervenções variaram em frequência e duração, mas mostraram resultados positivos, reduzindo a intensidade da mucosite oral, dor e outros sintomas. Algumas intervenções foram tão eficazes quanto tratamentos convencionais como a clorexidina. Conclusão: a pesquisa sugere que abordagens herbais podem ser benéficas no manejo da mucosite oral em pacientes com câncer, mas mais estudos são necessários para confirmar esses resultados

Objective: to examine the effects of herbal approaches on oral mucositis in adult cancer patients. Method: systematic review following Cochrane guidelines, with a search for experimental and randomized studies from 2013 to 2023. English studies on herbal interventions in patients over 18 years were included. Results: eight studies that used herbal interventions to treat oral mucositis were evaluated. The herbs tested included aloe vera, althaea root, turmeric, chamomile, grape vinegar, rose water, fruit/vegetable juice, and mulberry extract. The interventions varied in frequency and duration but showed positive results, reducing oral mucositis inten-sity, pain, and other symptoms. Some interventions were as effective as conventional treatments like chlorhexidine. Conclusion: the research suggests that herbal approaches can be beneficial in managing oral mucositis in cancer patients, but more studies are needed to confirm these results

Objetivo: examinar los efectos de los enfoques herbales en la mucositis oral en pacientes adultos con cáncer. Método: revisión sistemática siguiendo las directrices de Cochrane, con una búsqueda de estudios experimentales y aleatorizados entre 2013 y 2023. Se incluyeron estudios en inglés sobre intervenciones herbales en pacientes mayores de 18 años. Resultados: se evaluaron ocho estudios que utilizaron intervenciones herbales para tratar la mucositis oral. Las hierbas probadas incluyeron aloe vera, raíz de althaea, cúrcuma, manzanilla, vinagre de uva, agua de rosas, jugo de frutas/verduras y extracto de moras. Las intervenciones variaron en frecuencia y duración, pero mostraron resultados positivos, reduciendo la intensidad de la mucositis oral, el dolor y otros síntomas. Algunas intervenciones fueron tan eficaces como tratamientos convencionales como la clorhexidina. Conclusión: la investigación sugiere que los enfoques herbales pueden ser beneficiosos para el manejo de la mucositis oral en pacientes con cáncer, pero se nece-sitan más estudios para confirmar estos resultados

Uso da laserterapia de baixa intensidade na prevenção e tratamento da mucosite oral induzida por tratamentos antineoplásicos / Use of low-intensity lasertherapy in the prevention and treatment of oral mucositis induced by antineoplastic treatments

Sabe-se que para o combate de células cancerígenas, é imprescindível a submissão de pacientes oncológicos a tratamentos antineoplásicos, sessões de quimioterapia e radioterapia são as terapêuticas mais utilizadas em pacientes neoplásicos, sendo capazes de originar inúmeras reações adversas, como a mucosite oral, que é considerada um dos principais efeitos adversos do tratamento com quimioterapia e radioterapia. A laserterapia vem sendo considerada um grande aliado na prevenção e tratamento da mucosite, visto que de forma preventiva retarda o aparecimento desta condição, e de forma terapêutica proporciona alívio da dor, além de reduzir a gravidade da mucosite oral. Dessa forma, a presente revisão de literatura teve por objetivo denotar os benefícios da laserterapia de baixa intensidade na prevenção e tratamento da mucosite oral induzida por tratamentos antineoplásicos. Para a confecção deste trabalho, foram pesquisados artigos científicos publicados entre 2012 e 2022, nas bases de dados PubMed, Portal BVS, Scielo e google acadêmico, nos idiomas inglês e português. Como resultado foram encontrados 59 trabalhos, onde após leitura dos títulos e resumos, e do tipo de estudo, foram excluídos 32 artigos. Sendo 27 selecionados para leitura integral do texto, onde dentre eles somente 19 se encaixaram nos critérios de inclusão e foram utilizados neste trabalho. Portanto, conclui-se que a literatura mostra que embora haja bastante discussão, a maior parte dos estudos mostram evidências que a laserterapia de baixa intensidade possui muitos benefícios na prevenção e no tratamento da mucosite oral devido sua capacidade moduladora nos eventos metabólicos por meio de processos fotofísicos e bioquímicos(AU)

It is known that in order to fight cancer cells, it is essential to submit cancer patients to antineoplastic treatments, chemotherapy and radiotherapy sessions are the most used therapies in cancer patients, being capable of causing numerous adverse reactions, such as oral mucositis, which is considered one of the main adverse effects of chemotherapy and radiotherapy treatment. Laser therapy has been considered a great ally in the prevention and treatment of mucositis, since in a preventive way it delays the onset of this condition, and in a therapeutic way it provides pain relief, in addition to reducing the severity of oral mucositis. Thus, the present literature review aims to denote the benefits of low-level laser therapy in the prevention and treatment of oral mucositis induced by antineoplastic treatments. For the preparation of this work, scientific articles published between 2012 and 2022 were searched in PubMed, Portal BVS, Scielo and academic google databases, in English and Portuguese. As a result, 59 studies were found, where after reading the titles and abstracts, and the type of study, 32 articles were excluded. 27 were selected for full text reading, among which only 19 met the inclusion criteria and were used in this work. Therefore, it is concluded that the literature shows that, although there is a lot of discussion, most studies show evidence that low-level laser therapy has many benefits in the prevention and treatment of oral mucositis due to its modulating capacity in metabolic events through processes photophysical and biochemical(AU)

Dental consensus on HSCT - Part II: dental Care during HSCT

ABSTRACT During the state of immune vulnerability in hematopoietic stem cell transplantation (HSCT), the patient has an increased risk of developing a vast number of complications, including severe problems in the oral cavity. These situations require professional oral care to act in the diagnosis and treatment of these conditions, as well as to develop prevention protocols to minimize patient's complications. Oral mucositis, opportunistic infections, bleeding, specific microbiota, taste, and salivary alterations are complications that can occur during HSCT and interfere with various aspects, such as pain control, oral intake, nutrition, bacteremia and sepsis, days of hospitalization and morbidity. Several guidelines have been published to address the role of professional oral care during the HSCT, we describe a consensus regarding these recommendations.

Ação da própolis no manejo de lesões não infecciosas em cavidade oral: uma revisão integrativa / The effects of Propolis in the management of non-infectious lesions in the oral cavity: an integrative review

ntrodução: a própolis é um produto natural que apresenta inúmeras propriedades terapêuticas, dentre elas a ação cicatrizante e anti-inflamatória. Diversos estudos têm sugerido o seu emprego no manejo da mucosite oral (MO) e de lesões ulceradas em mucosa bucal. A MO é uma inflamação da mucosa oral, resultante do tratamento quimio e/ou radioterápico. Já as lesões ulceradas caracterizam-se como um distúrbio ulcerativo inflamatório doloroso. Objetivo: discutir a ação da própolis sobre a prevenção e cicatrização de lesões de origem não infecciosa que acometem a cavidade oral. Metodologia: trata-se de uma revisão integrativa da literatura em que foram utilizadas as bases de dados LILACS, PubMed, SciELO e Cochrane, por meio do cruzamento dos descritores em português: "própolis", "úlceras orais" e "mucosite oral"; e em inglês: "propolis", "oral ulcer" e "mucositis". Os seguintes critérios de inclusão foram estabelecidos: ensaios clínicos e revisões sistemáticas, na íntegra, escritos em inglês ou português, entre 2005 e 2018, que utilizaram a própolis de forma tópica ou sistêmica. Resultados: foram incluídos um total de 10 estudos, onde 2 abordaram o uso da própolis em úlceras orais e 8 tiveram como foco a aplicação deste agente no manejo da MO. Quanto ao desfecho, a aplicação da própolis na mucosite se mostrou eficaz em 7 dos 8 estudos. Já se tratando de úlceras orais, a administração deste agente foi efetiva nos 2 estudos. Conclusão: os estudos analisados demostraram que a própolis apresenta propriedades capazes de favorecer a prevenção e cicatrização de lesões de MO e úlceras orais.

Introduction: propolis is a natural product that has numerous therapeutic properties, including healing and anti-inflammatory action. Several studies have suggested its use in the management of oral mucositis (OM) and ulcerated lesions in the oral mucosa. OM is an inflammation of the oral mucosa resulting from chemotherapy and/or radiotherapy. Whereas ulcerated lesions are characterized as a painful inflammatory ulcerative disorder. Objective: to discuss the action of propolis on the prevention and healing of non-infectious lesions that affect the oral cavity. Methodology: this is an integrative literature review in which LILACS, PubMed, SciELO and Cochrane databases were used, by crossing descriptors in Portuguese: "própolis", "úlceras orais" and "mucosite oral"; and in English: "propolis", "oral ulcer" and "mucositis". The following inclusion criteria were established: clinical trials and systematic reviews, in full, written in English or Portuguese, between 2005 and 2018, which used propolis topically or systemically. Results: a total of 10 studies were included, where 2 addressed the use of propolis in oral ulcers and 8 focused on the application of this agent in the management of OM. As for the outcome, the application of propolis in mucositis proved to be effective in 7 of the 8 studies. As for oral ulcers, the administration of this agent was effective in both studies. Conclusion: the analysed studies demonstrated that propolis has properties capable of help the prevention and healing of OM lesions and oral ulcers.

Prevalencia del pseudoquiste antral y mucositis apical en los senos maxilares como entidades frecuentes encontradas en radiografías panorámicas en pacientes de un centro radiológico de Huacho, Lima-Perú, 2019 / Prevalence of antral pseudocyst and apical mucositis in the maxillary sinus as common entities found in panoramic x-rays among patients at a radiological center in Huacho, Lima, Peru, 2019

RESUMEN Antecedentes: Los senos maxilares están directamente relacionados con el proceso dentoalveolar, por lo que el conocimiento de las patologías que pueden afectar y comprometer cualquiera de ambas estructuras facilitará un correcto diagnóstico y tratamiento. Objetivo: Determinar la prevalencia de pseudoquiste antral y mucositis como entidades frecuentes encontradas en radiografías panorámicas en pacientes de un centro radiológico de Huacho, Lima-Perú, en 2019. Material y métodos: Estudio transversal, observacional, descriptivo y retrospectivo. De un total de 1646 radiografías panorámicas virtuales recolectadas en el centro radiológico de Huacho, se asignó como población muestral 1224 radiografías, luego de tener en cuenta los criterios de inclusión y exclusión. Las variables fueron pseudoquiste antral, engrosamiento de la mucosa, periodontitis apical, mucositis, edad, sexo y mes de toma radiográfica. Se realizó análisis descriptivo y bivariado. Resultados: La prevalencia de pseudoquiste antral de origen respiratorio fue de 5,71 %; de mucositis, 13,07 %; y de ambas entidades correlacionadas, 0,90 %. Se encontró asociación significativa entre la presencia de pseudoquiste antral de origen respiratorio y el sexo masculino (p = 0,007). Conclusiones: La presencia de lesiones apicales que condicionan tanto el engrosamiento de la mucosa antral como la presencia de pseudoquiste antral odontogénico, correlacionadas, resultó poco prevalente (y no rara).

ABSTRACT Maxillary sinuses are directly related to the dentoalveolar process, so knowledge of the pathologies that may affect and compromise either of the two structures can facilitate a correct diagnosis and treatment. Objective: To determine antral pseudocyst and apical mucositis prevalence as frequent entities found in panoramic x-rays among patients at a radiological center in Huacho, Lima, Peru, 2019. Material and Methods: Cross-sectional, observational, descriptive and retrospective study. From a total of 1,646 virtual panoramic x-rays collected at a radiological center in Huacho, 1,224 x-rays were used as sample population after taking into account the inclusion and exclusion criteria. The variables were antral pseudocyst, thickening of the mucosa, apical periodontitis, apical mucositis, age, gender, and month in which x-ray was taken. Descriptive and bivariate analysis was performed. Results: Antral pseudocyst of respiratory origin prevalence was 5.71%, mucositis prevalence was 13.07%, and prevalence of both correlated entities was 0.90%. A significant association was found between the presence of antral pseudocyst of respiratory origin and male gender (p=0,007). Conclusion: The occurrence of apical lesions leading to both thickening of the antral mucosa and the presence of odontogenic antral pseudocysts, while not rare, was found to be of low prevalence.

Update on the treatment of chemotherapy and radiotherapy-induced buccal mucositis: a systematic review / Actualización en el tratamiento de la mucositis oral inducida por quimioterapia y radioterapia: una revisión sistemática

ABSTRACT Oral mucositis (OM) is a frequent complication in cáncer patients who are undergoing chemotherapy or radiotherapy. It manifests as an inflammation of the oral mucosa, sometimes provoking severe consequences such as eating limitations, difficulty in speaking, and possibly superinfection. Aim: The aim of this review was to update the evidence published during the last five years on the treatment of oral mucositis induced by radiotherapy and/or chemotherapy in patients with cancer. Materials and Method: A search was conducted in Pubmed, Scielo and Scopus, using the search terms mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, with Mesh terms and free terms, from 2017 to January 2023. The systematic review was conducted in accordance with the PRISMA guidelines. Results: A total 287 articles were retrieved, of which 86 were selected by title and abstract, and 18 were included after full-text analysis. The most frequently assessed variables were OM severity, pain intensity and healing time. Treatment types were diverse, and included drugs, mouthwashes, medicines based on plant extracts, cryotherapy and low-intensity laser therapies. Conclusión: Dentoxol mouthwashes, Plantago major extract, thyme honey extract, zinc oxide paste, vitamin B complex combined with GeneTime, and the consumption of L-glutamine are effective in diminishing the severity of OM. Pain intensity was lower with doxepin mouthwashes and diphenhydramine-lidocaine-antacid mouthwashes.

RESUMEN La mucositis oral (MO) es una complicación frecuente en pacientes oncológicos sometidos a quimioterapia o radioterapia. Se manifiesta como una inflamación de la mucosa oral, provocando en ocasiones graves consecuencias como limitaciones en la alimentación, dificultad para hablar y posiblemente sobreinfección. Objetivo: El objetivo de esta revisión fue actualizar la evidencia publicada durante los últimos cinco años sobre el tratamiento de la mucositis oral inducida por radioterapia y/o quimioterapia, en pacientes con cáncer. Materiales y Método: Se realizó una búsqueda en Pubmed, Scielo y Scopus, con las palabras de búsqueda mucositis, stomatitis, therapy, treatment, oral cancer, oral squamous cell carcinoma, head and neck cancer and head and neck carcinoma, utilizando términos Mesh y libres, de 2017 a enero de 2023. La revisión sistemática se realizó de acuerdo con los lineamientos de declaración del PRISMA. Resultados: Se obtuvieron un total de 287 artículos, de los cuales 86 fueron seleccionados por título y resumen y finalmente 18 fueron incluidos por texto completo. Las variables evaluadas con mayor frecuencia fueron la severidad de la MO, la intensidad del dolor y el tiempo de cicatrización. Los tipos de tratamientos fueron diversos, desde medicamentos, colutorios bucales, medicamentos a base de extractos de plantas, crioterapia y terapias con láser de baja intensidad. Conclusiones: Los enjuagues bucales de Dentoxol, extracto de Plantago major, extracto de miel de tomillo, pasta de óxido de zinc, mezcla de compuestos de vitamina B combinados con GeneTime y el consumo de L-glutamina son efectivos para disminuir la severidad de la MO. La intensidad del dolor fue menor con los colutorios de doxepina y también con los colutorios de difenhidramina-lidocaína-antiácido. Palabras clave: mucositis bucal;cáncer;quimioterapia;radioterapia;tratamiento

Influência da via hippo no reparo da mucosite oral quimicamente induzida em modelo murino submetida a tratamento com laser, geleia real ou própolis / Influence of the hippo pathway on the repair of chemically induced oral mucositis in a murine model subjected to treatment with laser, royal jelly or propolis

A via hippo é uma via de transdução de sinal altamente conservada que está implicada no desenvolvimento, homeostase e regeneração celular/tecidual. A YAP tem papel fundamental na via hippo uma vez que junto com a TAZ ativam fatores de transcrição que levam ao crescimento, diferenciação e migração celular. O mecanismo de fosforilação da YAP/TAZ pela LATS1/LATS2 cria um sítio de ligação para manter a YAP no citoplasma (fosforilada) impedindo suas funções a nível nuclear. Diante das importantes funções desta via no reparo e crescimento tecidual, esta pesquisa avaliou se a via hippo exerceu influência na resposta ao tratamento da MO através da expressão das proteínas YAP e LATS2 em mucosite oral (MO) quimicamente induzida pelo 5- fluoracil (5-FU), em modelo murino, tratada com própolis (P), geleia real (GR) ou laser (L) comparadas ao grupo controle (C), sem tratamento. Foram utilizadas amostras de ratos machos wistar divididos nos seguintes grupos: C, P, GR e L (intraoral 6 J/cm2 ) separados em três tempos experimentais: dias 08, 10 e 14. O perfil de imunomarcação foi feito por escores padronizados entre 0 a 3 levando em consideração a marcação nuclear e/ou citoplasmática. Na análise de imunomarcação da YAP, no dia 08, o grupo controle obteve os escore 0 e 1 na maioria das amostras, já nos dias 10 e 14 a maior parte das amostras obteve os escore 2 e 3. Nos grupos experimentais (L, GR e P), o escore 2 prevaleceu em todos os tempos experimentais. Para LATS2 houve prevalência do escore 2 tanto no grupo controle quanto nos grupos teste em todos os tempos experimentais. Em relação a análise estatística da imunoexpressão da proteína YAP, verificou-se diferença estatítica significativa (p= 0,020), apenas no dia 08 entre o grupo controle comparado aos grupos experimentais (L, GR e P). Já para LATS2 nenhuma diferença estatística foi encontrada. Na avaliação estatística dos diferentes tempos experimentais dentro um mesmo grupo, só foi encontrada diferença estatística significativa no grupo laser e apenas para LATS2 (p=0,025). Adicionalmente foi realizada a correlação de spearman, entre YAP e LATS2 para todos os grupos, porém não houve associação estatística significativa. A maior imunoexpressão de YAP e LATS2 (escores 2 e 3) observada nos grupos experimentais, indica que a via hippo é ativada e parece influenciar o processo de reparo nas mucosites orais quimioinduzidas e tratadas pelos diferentes métodos (AU).

The hippo pathway is a highly conserved signal transduction pathway that is implicated in cell/tissue development, homeostasis and regeneration. YAP plays a key role in the hippo pathway since, together with TAZ, they activate transcription factors that lead to cell growth, differentiation and migration. The YAP/TAZ phosphorylation mechanism by LATS1/LATS2 creates a binding site to keep YAP in the cytoplasm (phosphorylated) preventing its functions at the nuclear level. Given the important functions of this pathway in tissue repair and growth, this research evaluated whether the hippo pathway exerted influence on the response to OM treatment through the expression of YAP and LATS2 proteins in oral mucositis (OM) chemically induced by 5-fluororacil (5- FU), in a murine model, treated with propolis (P), royal jelly (GR) or laser (L) compared to the control group (C), without treatment. Samples of male Wistar rats divided into the following groups were used: C, P, GR and L (intraoral 6 J/cm2) separated into three experimental times: days 08, 10 and 14. The immunostaining profile was performed by standardized scores between 0 to 3 taking into account nuclear and/or cytoplasmic labeling. In the YAP immunostaining analysis, on day 08, the control group obtained scores 0 and 1 in most samples, while on days 10 and 14 most samples obtained scores 2 and 3. In the experimental groups (L, GR and P), score 2 prevailed at all experimental times. For LATS2 there was a prevalence of score 2 both in the control group and in the test groups at all experimental times, showing a very heterogeneous expression. Regarding the statistical analysis of YAP protein immunoexpression, there was a statistically significant difference (p= 0.020), only on day 08 between the control group compared to the experimental groups (L, GR and P). As for LATS2, no statistical difference was found. In the statistical evaluation of the different experimental times within the same group, a statistically significant difference was only found in the laser group and only for LATS2 (p=0.025). Additionally, the Spearman correlation was performed between YAP and LATS2 for all groups, but there was no statistically significant association. The greater immunoexpression of YAP and LATS2 (scores 2 and 3) observed in the experimental groups indicates that the hippo pathway is activated and seems to influence the repair process in chemoinduced oral mucositis treated by different methods (AU).

Mucosite oral em pacientes com câncer de cabeça e pescoço: limitações das escalas de graduação, avaliação da terapia fotodinâmica antimicrobiana no tratamento e associação com microbioma oral / Oral mucositis in patients with head and neck cancer: limitations of grading scales, evaluation of antimicrobial photodynamic therapy in treatment and association with oral microbiome

O câncer de cabeça e pescoço (CCP) é uma das principais causas de morbidade e mortalidade em todo mundo. Cirurgia, radioterapia (RT) e quimioterapia (QT) são os principais tratamentos empregados. Contudo, pacientes submetidos a RT e QT podem apresentar complicações como mucosite oral (MO). A terapêutica mais recomendada para MO é a fotobiomodulação (FTBM). Há diversas escalas para graduação da MO, entretanto elas apresentam limitações quando aplicadas em pacientes com CCP. Por esse motivo, foi desenvolvido uma revisão da literatura para descrever as escalas mais utilizadas e apontar as limitações. Microrganismos podem agravar a cicatrização da MO. Diante disso, a terapia fotodinâmica antimicrobiana (aPDT), poderia complementar a ação da FTBM. Assim, foi realizado estudo comparativo entre o uso da FTBM isolada e FTBM + aPDT no tratamento da MO. Mudanças no microbioma oral induzidas pela RT e seu papel no agravamento das complicações, como MO, vem sendo descrito. Em razão disso, amostras da cavidade oral dos pacientes com CCP foram coletadas com swab antes da RT (T0), entre 12 e 16 Grays (Gy) (T1), entre 30 e 36 Gy (T2) e acima de 60 Gy (T3) para caracterização molecular por meio da amplificação e sequenciamento das regiões v1-v2 do gene 16S rRNA. As escalas da World Health Organization - WHO, Radiation Therapy Oncology Group - RTOG e National Cancer Institute ­ NCI foram as mais utilizadas e todas apresentaram limitações associadas principalmente com a dificuldade de diferenciar entre os sinais e sintomas da MO e os do tumor, como por exemplo a disfagia. O estudo comparativo (FTBM isolada X FTBM + aPDT) foi composto por 14 pacientes, com câncer de boca e orofaringe submetidos a RT e QT concomitantes, com 6 pacientes no grupo FTBM isolada e 8 no grupo FTBM + aPDT. A média de redução no tamanho da MO no grupo intervenção foi de 0,70 cm2 (±0,35) e 0,30 cm2 (±1,10) no grupo controle. A média de duração foi de 18,37 dias (±12,12) para o grupo intervenção e 23 dias (±14,78) para o grupo controle. O grupo intervenção teve redução média de 3,40 pontos na escala de dor (±2,44), enquanto o grupo controle teve 0,17 (±2,28). O estudo prospectivo que avaliou o microbioma oral (filo e gênero) ao longo da RT foi composto por 49 pacientes com CCP. Intrigantemente não foi observado diferença no microbioma oral dos pacientes que apresentaram MO (n=31) daqueles que não apresentaram (n=18). Interessantemente foi observado ao final da RT (T3) diminuição de Porphyromonas (p=<0.0001), Prevotella (p=0.010), Fusobacterium (p=<0.0001), gêneros associados ao câncer. Não há uma escala ideal para a avaliação da mucosite oral em pacientes com CCP. A mensuração das lesões de MO associada aos dados de dor e duração da MO pode ser uma forma mais eficaz de avaliação. A combinação de FTBM + aPDT parece ser uma abordagem promissora para descontaminar lesões de MO. Não foi observado diferença no microbioma oral de pacientes com e sem MO. Mudanças na composição do microbioma oral foram observadas durante a RT.

Head and neck cancer (HNC) is one of the main causes of morbidity and mortality worldwide. Surgery, radiotherapy (RT) and chemotherapy (CT) are the main treatments used. However, patients undergoing RT and CT may present complications such as oral mucositis (OM). The most recommended therapy for OM is photobiomodulation (PBM-T). There are several scales for grading OM, however they have limitations when applied to patients with HNC. For this reason, a literature review was developed to describe the most used scales and point out the limitations. Microorganisms can aggravate OM healing. Therefore, antimicrobial photodynamic therapy (aPDT) could complement the action of PBM-T. Thus, a comparative study was carried out between the use of PBM-T alone and PBM-T + aPDT in the treatment of OM. RT-induced changes in the oral microbiome and its role in worsening complications such as OM have been described. For this reason, samples from the oral cavity of patients with HNC were collected with a swab before RT (T0), between 12 and 16 Grays (Gy) (T1), between 30 and 36 Gy (T2) and above 60 Gy (T3) for molecular characterization through amplification and sequencing of regions v1-v2 of the 16S rRNA gene. The World Health Organization - WHO, Radiation Therapy Oncology Group - RTOG and National Cancer Institute - NCI scales were the most used and all had limitations mainly associated with the difficulty of differentiating between the signs and symptoms of OM and those of the tumor, such as example dysphagia. The comparative study (isolated PBM-T X PBM-T + aPDT) consisted of 14 patients with oral and oropharyngeal cancer who underwent concomitant RT and CT, with 6 patients in the isolated PBM-T group and 8 in the PBM-T + aPDT group. The mean reduction in OM size in the intervention group was 0.70 cm2 (±0.35) and 0.30 cm2 (±1.10) in the control group. The mean duration was 18.37 days (±12.12) for the intervention group and 23 days (±14.78) for the control group. The intervention group had an average reduction of 3.40 points on the pain scale (±2.44), while the control group had 0.17 (±2.28). The prospective study that evaluated the oral microbiome (phylum and genus) during RT consisted of 49 patients with HNC. Intriguingly, no difference was observed in the oral microbiome of patients who had OM (n=31) and those who did not (n=18). Interestingly, a decrease in Porphyromonas (p=<0.0001), Prevotella (p=0.010), Fusobacterium (p=<0.0001) was observed at the end of RT (T3), genera associated with cancer. There is no ideal scale for assessing oral mucositis in patients with HNC. Measurement of OM lesions associated with data on pain and duration of OM may be a more effective form of evaluation. The combination of PBM- T + aPDT appears to be a promising approach to decontaminate OM lesions. No difference was observed in the oral microbiome of patients with and without OM. Changes in oral microbiome composition were observed during RT.

Aplicação do plasma de baixa temperatura sob pressão atmosférica como adjuvante ao tratamento da mucosite oral / Application of low temperature atmospheric pressure plasma as an adjuvant in treatment oral mucositis

A mucosite oral é um quadro clínico que acomete frequentemente pacientes sob terapia antineoplásica na região de cabeça e pescoço e caracteriza-se por ulcerações na mucosa que geram intensa dor local, odinofagia, aumento do risco de infecções, do uso de antibióticos e do tempo de hospitalização. A correlação entre mucosite oral, infecção fúngica e o potencial de disseminação fúngica sistêmica foi recentemente descrita. Apesar do impacto desse quadro clínico sobre a qualidade e tempo de vida dos pacientes oncológicos, não há consenso sobre a profilaxia e o protocolo terapêutico. O plasma de baixa temperatura sobre pressão atmosférica (LTAPP) apresenta efeito antimicrobiano, anti-inflamatório e reparador tecidual, o que sugere que possa ser promissor no tratamento da mucosite oral. Os objetivos gerais deste projeto foram divididos em dois subprojetos: 1) Definir os melhores parâmetros in vitro com efeito antifúngico e não tóxico e avaliar o LTAPP no tratamento de lesão de mucosite oral em modelo murino de mucosite por quimioterapia e 2) avaliar se o tratamento com LTAPP pode prevenir a disseminação fúngica sistêmica em ratos a partir de infecção experimental de lesões de mucosite oral por Candida albicans. Para tal, foram incluídos no estudo 100 ratos (Rattus norvegicus) com 90 a 100 dias de idade. No subprojeto 1, a lesão de mucosite oral foi induzida por administração de 5 fluorouracila (5-FU), enquanto no subprojeto 2, utilizou-se 5-FU associada à cisplatina ambas associadas à aplicação tópica de ácido acético 50%. Para o subprojeto 1, os animais foram randomicamente divididos em 2 grupos experimentais (n=30): a) Grupo mucosite; b) Grupo mucosite tratado com LTAPP, avaliados após 1, 5 e 12 dias do tratamento. Durante o período experimental, as lesões foram fotografadas e a gravidade da mucosite classificada por meio da atribuição de escores. Após a eutanásia e o processamento, os cortes histológicos corados por hematoxilina-eosina (HE) foram analisados microscopicamente. Para o subprojeto 2, o estudo de disseminação sistêmica fúngica nos grupos de mucosite infectada com C. albicans tratado ou não com LTAPP foi conduzido pelo isolamento fúngico a partir de amostras de sangue total e macerado dos órgãos. Para tanto foram estudados 2 grupos de ratos (n=20): c) Grupo mucosite infectado com C. albicans e d) Grupo mucosite infectado com C. albicans tratada com LTAPP, avaliados após 24 e 72 h do tratamento. Para ambos os projetos, o melhor parâmetro in vitro foi selecionado, isto é aquele com maior atividade antifúngica e baixa toxicidade. Dessa forma, as lesões foram expostas ao LTAPP de hélio por 5 min na distância de 1,5 cm na potência de 1 W. Os resultados in vitro mostraram que o LTAPP teve efeito antifúngico e baixa toxicidade para células de mamíferos. Os resultados in vivo mostraram que 5-FU afetou a saúde geral dos animais, evidenciada pela perda de peso corporal. Em ambos os grupos, houve reparo tecidual após 12 dias do tratamento, com resolução quase completa da lesão, o que foi corroborado pelos achados microscópicos. O grupo LTAPP exibiu uma tendência maior de redução da lesão, após 12 dias de tratamento. Além disso, o LTAPP apresentou efeito inibitório sobre C. albicans após 5 minutos, de exposição, com redução da recuperação fúngica da língua após 24 h (p<0.05). A disseminação fúngica sistêmica foi reduzida significativamente após 24 e 72 h do tratamento. Com base nos resultados obtidos, conclui-se que o LTAPP é uma ferramenta promissora para futura aplicação clínica em pacientes com mucosite oral. (AU)

Oral mucositis is a clinical condition that frequently affects patients undergoing antineoplastic therapy in the head and neck region and is characterized by mucosal ulcerations that generate intense local pain, odynophagia, increased risks of infections, use of antibiotics and the length of hospital stay. The correlation among oral mucositis, fungal infection and the potential for systemic fungal dissemination has recently been described. Despite the impact of this clinical condition on the quality and life expectancy of cancer patients, there is no consensus on prophylaxis and the therapeutic protocols. Low temperature atmospheric pressure plasma (LTAPP) has antimicrobial, anti-inflammatory and tissue repairing effects, which suggests that it can be promising in the treatment of oral mucositis. The general objectives of this project were divided into two subprojects: 1) Define the best antifungal and non-toxic in vitro parameters and to evaluate the application of LTAPP in the treatment of oral mucositis in murine model for chemotherapy, and 2) to evaluate whether treatment with LTAPP can prevent systemic fungal dissemination in rats from experimental infection of oral mucositis lesions by Candida albicans. A total of 100 rats (Rattus norvegicus) aged 90 to 100 days were included in the study. In subproject 1, oral mucositis lesion was induced by administration of only 5- fluorouracil (5-FU), while in subproject 2, administration and systemic administration of 5-FU associated with cisplatin, both associated with topical application of 50% acetic acid. For subproject 1, the animals were randomly divided into 2 experimental groups (n=30):a) Mucositis group and b) Mucositis group treated with LTAPP evaluated after 1, 5 and 12 days of treatment. During the experimental period, the lesions were photographed, and the severity of mucositis was classified into scores. After euthanasia and processing, the histological cuts stained by hematoxylin-eosin (HE) were analyzed. For subproject 2, the study of fungal systemic dissemination in groups of mucositis infected with C. albicans treated or not with LTAPP was conducted by fungal isolation from whole blood and macerated organs. Therefore, 2 groups of rats (n=20) were studied: c) Mucositis group infected with C. albicans and d) Mucositis group infected with C. albicans treated with LTAPP, evaluated after 24 and 72 h of treatment. For both subprojects, the best in vitro parameter was selected, that is, the one with the greatest antifungal effect and low toxicity. Thus, the lesions were exposed to helium LTAPP for 5 min at a distance of 1.5 cm at power of 1 W. In vitro results showed that LTAPP has an antifungal effect and low toxicity. In vivo results showed that 5-FU affected the general health of animals evidenced by body weight loss. In both groups, there was tissue repair after 12 days of treatment, with almost complete resolution of the lesion, which was corroborated by the microscopic findings. LTAPP group showed a greater trend of reduction of lesion, after 12 days of the treatment. Furthermore, LTAPP showed inhibitory effect on C. albicans after 5 min of exposition, with reduction in fungal recovery from the tongue after 24 h (p<0.05). Reduction in fungal dissemination was observed after 24 and 72 h of LTAPP treatment (p<0.05). Based on the obtained results, it was concluded that LTAPP is a promising tool for future clinical application in patients with oral mucositis.(AU)

Impacto na deglutição e manejo da mucosite hipofaríngea em pacientes submetidos à quimiorradioterapia na região de cabeça e pescoço: uma revisão integrativa da literatura / Management of hypopharyngeal mucositis in patients undergoing chemoradiotherapy in the head and neck region and its impact on swallowing: an integrative literature review

RESUMO Objetivo Investigar o impacto da mucosite hipofaríngea quimiorradioinduzida na deglutição e o seu manejo, a partir de uma revisão integrativa de literatura. Estratégia de pesquisa A busca e a seleção dos artigos foram realizadas nas seguintes bases de dados: PubMed, Embase, Scopus, ScienceDirect e LILACS. Critérios de seleção Os termos de busca utilizados foram ''Pharyngeal Mucositis", ''Radiotherapy" e ''Esophagitis", com auxílio do operador booleano (AND). A equação de busca utilizada foi: ''Pharyngeal Mucositis" AND "Radiotherapy" AND "Esophagitis". A seguinte questão central orientou o estudo: "Qual a forma de avaliação e manejo da mucosite hipofaríngea induzida pela radiação na região de cabeça e pescoço e seu impacto na deglutição?". Resultados Foram identificados 75 estudos, sendo que 6 foram excluídos devido à duplicidade e 60 foram excluídos por não se encaixarem nos critérios de inclusão; os artigos restantes foram lidos na íntegra e 4 foram selecionados para fazerem parte desta revisão integrativa da literatura. Conclusão Apesar da escassa literatura e das poucas informações sobre os métodos de avaliação da mucosite hipofaríngea, os artigos apontam que, independentemente da dose de radiação, a radioterapia na região cervical causa mucosite hipofaríngea. A mucosite hipofaríngea provoca grande impacto na deglutição, resultando na necessidade de uso de via alternativa de alimentação. Além da ausência de informações quanto à avaliação e graduação da mucosite hipofaríngea, os estudos não discutem o tratamento direto ou a prevenção desse tipo de doença.

ABSTRACT Purpose To investigate the impact of chemoradiation-induced hypopharyngeal mucositis on swallowing and its management, based on an integrative literature review. Research strategy Two researchers were responsible for the search and selection of articles, within the following databases: PubMed, Embase, Scopus, Science Direct, and Lilacs. Selection criteria The search terms used were "Pharyngeal Mucositis", "Radiotherapy" and "Esophagitis", with the aid of the Boolean operator (AND). The search equation used was "Pharyngeal Mucositis" AND Radiotherapy AND Esophagitis. The following central question guided the study: "What is the assessment and management of radiation-induced hypopharyngeal mucositis in the head and neck region and its impact on swallowing?" Results 75 studies were identified, of which 6 were excluded due to duplicity and 60 were excluded for not meeting the inclusion criteria; the remaining articles were read in full and 4 were selected to be part of the integrative literature review. Conclusion Despite the scarce literature and little information on methods for evaluating hypopharyngeal mucositis, the articles point out that, regardless of the radiation dose, radiotherapy in the cervical region causes hypopharyngeal mucositis. Hypopharyngeal mucositis causes a great impact on swallowing, resulting in the need to use an alternative feeding route. In addition to the lack of information regarding the assessment and grading of hypopharyngeal mucositis, the studies do not discussitsdirect treatment or prevention.

Oral Mucositis in Children with Leukemia Undergoing Chemotherapy: A Case Series

ABSTRACT Objective: To report nine cases of pediatric patients with Acute Lymphoid Leukemia (ALL) or Acute Myeloid Leukemia who developed severe oral mucositis (SOM) at the first week of chemotherapy. Material and Methods: The cases were selected from a sample of 105 children followed for 10 consecutive weeks. Hematological and personal data were obtained from the patient's medical records. The oral cavity was examined weekly using the modified Oral Assessment Guide. Results: More of the patients were male (55.6%), had black/brown skin (55.6%), with ALL (66.7%), and the mean age was 5.55. Two patients had values below normal for leukocytes, platelets, and creatinine over the follow-up. However, all patients showed changes in the normality of hematological data in most weeks. The most used chemotherapeutic agents were aracytin, etoposide, and methotrexate, known for their high stomatotoxic potential. Patients had 2 to 6 (mean of 4) episodes of SOM and 4 to 7 (mean of 5.5) episodes of OM. One patient at week 7, one patient at week 5, and one patient at weeks 2 and 10 did not have OM. Saliva (84 times) and lips (44 times) were the most affected items. Conclusion: The patients showed oscillations in the severity of oral mucositis and hematological parameters over the follow-up. All patients were exposed to stomatotoxic drugs during the initial phase of cancer treatment.

Lacticaseibacillus casei decrease long-chain fatty acids and most substances in an experimental model of intestinal mucositis

Purpose: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. Methods: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. Results: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. Conclusions: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.

Can NLR be a biomarker for mucositis and gvhd in patients undergoing allogeneic HSCT?

Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment for many diseases; however, it can induce complications such as Oral Mucositis (OM) and Graft-versus- Host Disease (GVHD). The neutrophil-lymphocyte ratio (NLR) is a peripheral biomarker of systemic inflammation and an independent prognostic factor for several inflammatory diseases. Aim: This study aimed to evaluate the association of NLR with OM and GVHD in patients undergoing allogeneic HSCT. Methods: Patients who underwent allogeneic HSCT at the Bone Marrow Transplant Service of the Hospital de Clínicas Complex of the Federal University of Paraná were included in the study. Socio-demographic data and blood counts were collected from patients' medical records. The NLR was calculated and associated with OM and GVHD. Results: 45 patients were included in the study. Although NLR was higher in patients with OM and oral GVHD, no statistical difference was observed, and no relationship between OM and GVHD with NLR could be stated. Conclusion: Although both OM and GVHD are associated with an inflammatory response as well as the immune system, it was not associated with NLR. Further investigation considering other variables related to HSCT might find possible associations, as it could favor patient management and prevention

Oral mucositis and microbial status in acute lymphoblastic leukemia subjects undergoing high-dose chemotherapy

Aim: To assess oral microbial status in patients with acute lymphoblastic leukemia (ALL) undergoing high-dose chemotherapy and to unravel possible associations between nosocomial pathogens and the establishment of chemotherapy-induced oral mucositis (CIOM). Methods: Oral mucosa, saliva, and peripheral blood samples were collected from 46 ALL subjects one day prior to chemotherapy (D0) and 2 weeks after treatment initiation (D14). Clinical intraoral inspection was performed by a single practitioner, with mucositis classification performed according to the WHO oral toxicity scale. Blood components were quantified by automatic flow cytometry, while oral Staphylococcus aureus and Pseudomonas aeruginosa were detected by Polymerase Chain Reaction with species-specific primers. Associations among bacteria and clinical findings were determined by Fisher's Exact test, longitudinal bacterial changes by paired Macnemar, and correlations among blood parameters and mucositis status or bacteria via Mann-Whitney. Results: S. aureus displayed higher detection rates at D14 (p < 0.05) and was positively associated with mucositis, adoption of a non-solid diet (all p < 0.001), nausea and fever (all p < 0.05). Conversely, P. aeruginosa did not correlate to CIOM clinical parameters. At the systemic standpoint, lower hemoglobin levels associated with CIOM and fever events (all p < 0.01). Conclusion: The study evidences S. aureus as a potential pathogen in ALL-CIOM, reaffirming microbial control as an important preventive measure during high-dose immunosuppressive therapy. The weight of non-white-blood-cell parameters should be validated as novel CIOM biomarkers in prospective research

Desafios terapêuticos da mucosite oral em oncopediatria / Therapeutic challenges of oral mucositis in pediatric oncology

O Neuroblastoma (NB) é uma neoplasia do sistema nervoso simpático, e o segundo tumor sólido maligno extracraniano mais comum da infância. Na terapia antineoplásica, complicações orais podem ser observadas, dentre elas a mucosite oral (MO). Trata-se de uma inflamação aguda da mucosa, proveniente da toxicidade dos quimioterápicos. Este relato de caso enfatiza o manejo da MO, bem como sua influência na condição sistêmica e qualidade de vida. Paciente do sexo feminino, nove anos, apresentou recidiva de NB metastático, após tratamento de primeira linha. Admitida na unidade hospitalar para tratamento oncológico na enfermaria de pediatria oncológica, queixando-se de dor intensa em cavidade bucal e orofaringe, associada a pancitopenia severa febril. Ao exame físico apresentava disfagia e déficit ponderal grave, que debilitava a deglutição da própria saliva. O exame intraoral revelou lesões de MO grau 3, segundo a Organização Mundial de Saúde (OMS), em lábios, gengiva anterior e orofaringe. O tratamento consistiu em remoção de debris local, higiene da cavidade bucal com clorexidina 0,12% e utilizando haste flexível de algodão estéril tipo "Swab", visando controle microbiano local, diariamente. Além disso, foi aplicado no leito eritematoso e hemorrágico fotobiomodulação (660 nm, 50 mW, 2 J/cm2, 90 segundos) pontualmente nas áreas do leito da lesão e em varredura na região de orofaringe (sessões intercaladas). Foi prescrito acetato de racealfatocoferol (vitamina E) para ação antioxidante e hidratação dos lábios. Concomitante a mucosite, a paciente apresentou pancitopenia febril severa, sendo necessário uso de cefepima 150 mg/kg/dia, com coleta prévia de hemoculturas, fator estimulador de colônias de granulócitos, Fluconazol, hidratação e suporte nutricional. As hemoculturas foram negativas. As consequências da mucosite contribuíram para desnutrição e piora da qualidade de vida. Conclui-se que a intervenção odontológica em interdisciplinaridade, possibilitou o restabelecimento físico e emocional, possibilitando melhor uma qualidade de vida da paciente (AU).

Neuroblastoma (NB) is a neoplasia of the sympathetic nervous system and the second most common extracranial malignant solid tumor in childhood. In antineoplastic therapy, oral complications can be observed in antineoplastic therapy, among them oral mucositis (OM). It is an acute mucosa inflammation resulting from the toxicity of chemotherapy drugs. This case report emphasizes the management of OM and its influence on the systemic condition and quality of life. A female patient, nine years old, presented a recurrence of metastatic NB after first-line treatment. She was admitted to the hospital unit for oncological therapy in the pediatric oncology ward, complaining of severe pain in the oral cavity and oropharynx associated with severe febrile pancytopenia. On physical examination, she presented dysphagia and severe weight deficit, which weakened the swallowing of her saliva. According to the World Health Organization (WHO), the intraoral exam revealed third-grade OM lesions on the lips, anterior gum, and oropharynx. Treatment consisted of removing local debris, cleaning the oral cavity with 0.12% chlorhexidine, and using a flexible, sterile cotton swab, aiming for daily local microbial control. In addition, photobiomodulation (660 nm, 50 mW, 2 J/cm2, 90 seconds) was applied to the erythematous and hemorrhagic bed, punctually in the areas of the lesion and sweeps in the oropharynx region (interspersed sessions). Racealphatocopherol acetate (vitamin E) was prescribed for antioxidant action and lip hydration. Concomitant with mucositis, the patient had severe febrile pancytopenia, requiring cefepime 150 mg/kg/day, with previous collection of blood cultures, granulocyte colony-stimulating factor, fluconazole, hydration, and nutritional support. Blood cultures were negative. The consequences of mucositis contributed to malnutrition and worsened quality of life. It is concluded that the interdisciplinary dental intervention enabled physical and emotional restoration, enabling a better quality of life for the patient (AU).

Study of application of 3D printed oral stents in radiotherapy for head and neck malignancies / 中华放射肿瘤学杂志

Objective:To analyze the dosimetric differences between 3D printed oral stents and corked oral stents in the target area and perioral organ at risk (OAR) in radiotherapy for head and neck cancer, and the effectiveness in reducing acute adverse reactions associated with radiotherapy.Methods:A total of 58 patients with head and neck cancer admitted to Department of Oncology of Affiliated Hospital of North Sichuan Medical College were selected and divided into experimental group (Group A, n=28, wearing 3D printed oral stents during radiotherapy) and control group (Group B, n=30, wearing corked oral stents during radiotherapy) in this retrospective cohort study. The incidence of radiotherapy - induced oral mucositis (RTOM), xerostomia and oropharyngeal mucosal pain was compared between two groups. Meanwhile, informed consent was obtained from 21 patients in Group A. Using the self control method, each patient wore a 3D printed oral stent (Group C) and a corked oral stent (Group D) to make two radiotherapy plans. The differences in the conformity index (CI), homogeneity index (HI) and exposure dose of OAR (D max, D mean) in the target area were analyzed between two groups. SPSS 25.0 statistical software was used for statistical analysis. Measurement data were expressed as Mean±SD. Comparison between two groups was conducted by paired t-test or repeated measurement analysis. Count data were expressed as ratio. Comparison between two groups was performed by Chi - square test or Fisher's exact test. P<0.05 was considered as statistically significant difference. Results:The severity of RTOM ( P<0.05), oropharyngeal mucosal pain ( P=0.004) and xerostomia score ( P<0.001) in Group A were significantly lower than those in Group B. There was no significant difference in the HI and CI of the target area between Group C and Group D (both P>0.05). The D max ( P=0.014, 0.009) and D mean ( P<0.001, P=0.033) of the upper lip and the affected buccal mucosa in Group C were significantly lower than those in Group D. Conclusion:3D printed oral stents obtain favorable HI and CI in radiotherapy for head and neck cancer, significantly reduce the irradiated dose to perioral OAR, and effectively lower the incidence and mitigate the severity of acute RTOM, xerostomia and oropharyngeal mucosal pain associated with radiotherapy.