Validación de un instrumento para medir la calidad de vida en niños con mucositis orofaríngea en tratamiento por cáncer / Validation of an instrument to measure the quality of life in children with oropharyngeal mucositis undergoing cancer treatment

Resumen Introducción: La mucositis orofaríngea (MO) es una de las principales complicaciones del tratamiento oncológico que reduce significativamente la calidad de vida (CV) del paciente. El objetivo fue traducir, adaptar de manera cultural y validar una nueva versión en español del instrumento Oropharyngeal Mucositis-Specific Quality-of-Life (OMQoL) en pacientes pediátricos. Métodos: Estudio transversal de validación, multicéntrico, realizado para la traducción y adaptación del OMQoL del inglés al español en pacientes de entre 8 y 16 años con MO. Se midió la confiabilidad mediante el Alfa de Cronbach; la validez del contenido y el constructo, con un análisis factorial exploratorio; y la validez convergente, con las correlaciones de las escalas para MO de la Organización Mundial de la Salud (OMS), la Oropharingeal Mucositis Assessment Scale (OMAS) y con el Pediatric Quality of Life-3 (PedsQL-3) módulo cáncer en español. Resultados: Participaron en el estudio 193 niños con una media de edad de 10.91 ± 2.38 años, de los cuales 101 (52.3%) fueron de sexo femenino. En esta muestra, 80 niños (41.5%) presentaron leucemia aguda linfoblástica y 111 (57.5%) presentaron MO grado 2 y 3. El análisis factorial resultó con cuatro dimensiones con cargas > 0.40. De los 31 ítems del OMQoL, seis fueron eliminados. El Alfa de Cronbach del OMQoL español fue de 0.954. Las correlaciones de Spearman (r) con las escalas de la OMS y OMAS fueron significativas (r = −0.720 y r = −0.689; p<0.01, respectivamente); con el PedsQL-3 módulo cáncer existió una moderada correlación (r = 0.426; p < 0.01). Conclusiones: La nueva versión del OMQoL en español demostró propiedades psicométricas adecuadas, y resulta un instrumento confiable y válido para medir la CV en niños con MO.

Abstract Background: Oropharyngeal mucositis (OM) is one of the primary complications arising during oncological treatment, which significantly reduces the patient's quality of life (QoL). The aim of this study was to translate, culturally adapt, and validate the use of a new Spanish version of the Oropharyngeal Mucositis-Specific Quality-of-Life instrument (OMQoL) for pediatric patients. Methods: A multicentric, cross-sectional validation study was conducted to translate and adapt OMQoL from English to Spanish for its use by children with OM aged 8-16 years. Reliability was measured using Cronbach's alpha; content and construct validity, in conjunction with exploratory factor analysis. The convergent validity, with the correlations of the scales for OM defined by the WHO, OMAS (Oropharingeal Mucositis Assessment Scale) and the PedsQL-3 cancer module in Spanish. Results: One hundred and ninety-three children with mean age of 10.91 ± 2.38 years participated in the study, out of which 101 (52.3%) were females. In this sample, 80 children (41.5%) suffered from acute lymphoblastic leukemia and 111 (57.5%) had grade 2 and 3 OM. The factorial analysis resulted in four dimensions with loads >0.40. Among the 31 items of the OMQoL, six were eliminated. Cronbach alpha of OMQoL-Spanish was 0.954. Spearman´s correlations (r) with the OMS and OMAS scales were significant (with r = −0.720 and r = −0.689; p < 0.01, respectively). Moderate correlation was observed with the PedsQL-3 cancer module (r = 0.426; p < 0.01). Conclusions: OMQoL-Spanish demonstrated adequate psychometric properties, resulting in a reliable and valid instrument for measuring QoL in children with MO.

Efeitos da sinvastatina na mucosite gastrointestinal induzida por 5-fluorouracil em ratos / Effects of simvastatin on 5-fluorouracil-induced gastrointestinal mucositis in rats

RESUMO Objetivo: examinar os efeitos da sinvastatina na mucosite gástrica e intestinal após o tratamento com 5-fluorouracil (5-FU), determinados pela expressão de citocinas e histologia em ratos. Métodos: ratos pesando 270±15g foram divididos em dois grupos. O grupo 5-FU+salina foi tratado com 5-FU (50mg/kg) mais solução salina a 0,9% por gavagem uma vez ao dia por cinco dias. O grupo 5-FU+sinvastatina foi tratado com 5-FU (50mg/kg), mais sinvastatina (10mg/kg), da mesma forma. Foi feita a eutanásia dos animais no sexto dia. O estômago e o intestino foram fotografados e removidos para exame. Dosagens séricas de TNF-a, IL-1ß, IL-6 e histopatologia (coloração HE) do estômago e intestino foram realizadas. Resultados: o peso corporal diminuiu em ratos no grupo 5-FU+salina. A sinvastatina não inibiu a perda de peso induzida pelo 5-FU. Danos significativos da mucosa no estômago e no jejuno foram observados em ratos que receberam apenas 5-FU. As dosagens séricas de citocinas foram significativamente menores no grupo 5-FU+sinvastatina do que no grupo 5-FU (p<0,05). A sinvastatina causou efeitos protetores significativos contra as lesões da mucosa gástrica e jejunal induzidas por 5-FU. Conclusão: a sinvastatina atenua a mucosite gástrica e intestinal relacionada à terapêutica com 5-FU. Nossos dados encorajam futuros estudos pré-clínicos e clínicos sobre a utilidade das estatinas na prevenção da mucosite gastrointestinal.

ABSTRACT Objective: simvastatin has pleiotropic anti-inflammatory and immunomodulatory effects potentially usefull to prevent chemotherapy-induced gastrointestinal mucositis. Studies on this are scarce. This study aimed to examine the effects of simvastatin on gastric and intestinal mucositis after 5-fluorouracil (5-FU) treatment in rats. Methods: rats weighing 270±18g were divided into two groups. The 5-FU+saline group (5-FU/SAL) rats were treated with 5-FU (50mg/kg) plus 0.9% saline orally (gavage) once daily for five days. The 5-FU+simvastatin (5-FU/SIMV) group was treated with 5-FU (50mg/kg), plus simvastatin (10mg/kg), in the same way. The rats were euthanased on the sixth day, then their stomach and intestine were photographed and removed for exams. Dosages of serum TNF-a, IL-1ß, IL-6 and histopathology were done for stomach and intestine. Results: body-weight was significantly lower in rats treated with 5-FU+saline than the weight loss of the 5-FU/SIMV group rats. TNF-a expression was lower in 5-FU/SIMV group (172.6±18pg/ml) than in 5-FU/SAL (347.5±63pg/ml). Serum IL-1b was lower in 5-FU/SAL group (134.5±23pg/ml) than in 5-FU/SIMV (48.3±9pg/ml). Serum IL-6 was 61.8±15pg/ml in 5-FU/SIMV and 129.4±17pg/ml in 5-FU/SAL groups. These differences were significant (p<0.05). Mucosal damage in stomach and jejunum were observed in rats receiving 5-FU alone. In the stomach and jejunum, simvastatin caused significant protective effects against 5-FU-induced mucosal injury. Conclusion: simvastatin attenuated gastric and intestinal mucositis related to 5-FU therapeutics in animal model. These data encourage forthcoming clinical studies addressing the usefulness of statins in the prevention and treatment of gastrointestinal mucositis.

Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

Piodermatite-pioestomatite vegetante: relato de caso e revisão de literatura / Pyodermatitis-pyostomatitis vegetans: case report and review of medical literarture

A piodermatite-pioestomatite vegetante é uma rara dermatose inflamatória de etiologia desconhecida, com típico comprometimento mucocutâneo. Relatamos caso de paciente feminina com lesões pustulosas e vesiculosas em axilas, evoluindo com placas vegetantes e pústulas com agrupamento anular. Houve progressão com comprometimento vulvar, inguinal e mucosas oral, nasal e ocular. Proposto o diagnóstico, optou-se por iniciar prednisona 40mg ao dia, com remissão das lesões após um mês de uso da medicação. A associação com doença inflamatória intestinal ocorre em 70 por cento dos casos. A imunofluorescência é um fator que ajuda a caracterizar a doença, sendo tipicamente negativa. A rápida resposta à terapêutica com corticosteroides sistêmicos é esperada.

Pyodermatitis-pyostomatitis vegetans is a rare inflammatory dermatosis of unknown etiology, with a typical mucocutaneous involvement. We report the case of a woman with pustular and vesicular lesions in the axillae, evolving with vegetating plaques and pustules with annular grouping. The disease progressed with vulvar and inguinal involvement as well as involvement of the oral, nasal and ocular mucous membranes. She started the treatment with prednisone (40 mg/day), with remission of the lesions after one month of use of such medication. Association with inflammatory bowel disease occurs in 70 percent of the cases. Immunofluorescence, which is typically negative, helps to characterize the disease. A rapid response to systemic steroids is expected.

Papel de los staphylococcus spp. en la mucositis oral: revisión de la literatura / Rule of staphylococcus spp in oral mucusitis: review of the literature

It is estimated that more than 500 bacterial species inhabit the human oral environment. Among them, more than 400 species are known, and also a huge diversity of microorganisms that have been discovered because of the innovations in molecular biology techniques. Talking about staphylococcus spp., its presence in oral environment of health individuals and local or systemic wounded ones is at least controversial, what guides to the necessity of accurate studies in order to clarify this bacteria profile in this microenvironment ecology, as well as in oral and systemic disease etiology. This study aimed to gather the current knowledge concerning the staphylococcal presence in oral environment and its implications in oral mucositis development, in this case called "oral staphylococcal mucositis", a clinical condition that affects more commonly ancient patients, systemic weakened or immunologically wounded

Se estima que más de 500 especies bacterianas habitan el medio ambiente oral de seres humanos. Entre ellas, son conocidas más de 400 especies, además de una gran diversidad de microorganismos que han sido descubiertos gracias a innovaciones en las técnicas de biología molecular. Con relación a los staphylococcus spp., su presencia en el medio ambiente oral de individuos saludables, local o sistémicamente comprometidos es bastante controversia, lo que remite a la necesidad de estudios cuidadosos con intención de aclarar el papel de esas bacterias en la ecología de ese microambiente, así como en la etiología de enfermedades orales y sistémicas. Ese estudio propuso reunir los conocimientos actuales sobre la presencia de staphylococcus en el medio ambiente oral y sus implicaciones en el desarrollo de mucositis oral, denominada en ese caso de "mucositis estafilocócica oral", una condición clínica que afecta más comúnmente pacientes mayores, sistémicamente debilitados o inmunológicamente comprometidos