Dysphagia-related mucositis in children undergoing chemotherapy: The COMEDY pattern

Objectives Children undergoing chemotherapy can experience dysphagia due to non-erosive reflux disease (NERD). Oral mucositis (OM) associated with NERD-dysphagia in children with cancer has recently been defined with the acronym COMEDY (Clenching, Oral Mucositis, closed Eyes, DYsphagia). This study aims to identify the prevalence of the COMEDY pattern among chemotherapy-induced OM. Subjects and methods Forty-two medical records of children undergoing chemotherapy for haemato-oncologic diseases and presenting OM were reviewed. The following data were collected: age, type of haemato-oncologic disease, presence of dysphagia, type of oral mucosal lesions (i.e. traditional oral mucositis or COMEDY pattern), site of oral lesions, ear-nose-throat (ENT) assessment for the indirect signs of NERD and paediatric neuro-psychiatric (PNP) assessment. Results Among 42 children with chemotherapy-related OM, 6 patients (14.2%) showed the COMEDY pattern. Besides the characteristic clinical aspect of the oral mucosa, initially classified as grade II OM, these children suffered from NERD-related dysphagia and PNP issues. Conclusion A COMEDY pattern can occur in a number of cases of chemotherapy-induced OM; recognizing this pattern may improve the effectiveness of treatment

Updating our understanding of health-related quality of life issues in children with cancer: a systematic review of patient-reported outcome measures and qualitative studies

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The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries.

The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2- positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2- dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies

In vitro phototoxic properties of triamcinolone 16,17-acetonide and its main photoproducts

The phototoxicity of triamcinolone 16,17-aectonide has been estimated through a panel of in vitro tests. The main target involved in phototoxicity induced by triamcinolone appeared to be the cell membrane. Oxygen-independent photohemolysis was observed. A photochemical study in water and buffered solutions supported the conclusion that this is related to the action of radicals formed upon UV irradiation (in particular UV-B) by Norrish Type-I fragmentation of the C-20 ketone group. Peroxy radicals were formed in the presence of oxygen and were the active species in that case. Three photoproducts, isolated from the photodegradation of the drug, were submitted to the same toxicity tests. Two of them were proved to possess toxic or phototoxic properties on erythrocytes, primarily induced by UV-B light, and may participate in the photosensitizing activity of triamcinolone 16,17-acetonide. Our in vitro results suggest that the drug can elicit weak photosensitizing properties in vivo

Photochemistry and Phototoxicity of Fluocinolone 16,17-Acetonide

Fluocinolone 16,17-acetonide is a corticosteroid used topically to treat various inflammatory skin diseases. Its photoreactivity was studied under UV-A and UV-B light in aqueous buffer in the presence of oxygen. This drug is photolabile under UV-B light and, to a lesser extent, under UV-A light, which is absorbed far less. In phosphate buffer, approximately 80% of fluocinolone acetonide decomposes after 5 J/cm2 of UV-B irradiation, whereas under 30 J/cm2 of UV-A light approximately only 20% decomposes. Both the drug and its photoproducts have been evaluated through a battery of in vitro studies and found to cause photohemolysis and induce photodamage to proteins (erythrocyte ghosts, bovine serum albumin) and linoleic acid. In addition, one of the photoproducts (the 17-hydroperoxy derivative) is highly toxic in the dark. Therefore, both loss of therapeutic activity and light-induced adverse effects may be expected when patients expose themselves to sunlight after drug administration. A major mechanism for phototoxicity involves radicals forming from drug breakdown, at least under UV-B, although reactive oxygen species may play a role, particularly under UV-A

Updating our understanding of health-related quality of life issues in children with cancer: a systematic review of patient-reported outcome measures and qualitative studies

Background: health-related quality of life (HRQOL) is a key concept in pediatric oncology. This systematic review aims to update the conceptual HRQOL model by Anthony et al. (Qual Life Res 23(3):771–789, 2014), covering physical, emotional, social and general HRQOL aspects, and to present a comprehensive overview of age- and disease-specific HRQOL issues in children with cancer. Methods: Medline, PsychINFO, the Cochrane Database for Systematic Reviews (CDSR), and the COSMIN database were searched (up to 31.12.2020) for publications using patient-reported outcome measures (PROMs) and qualitative studies in children with cancer (8–14-year) or their parents. Items and quotations were extracted and mapped onto the conceptual model for HRQOL in children with cancer mentioned above. Results: of 2038 identified studies, 221 were included for data extraction. We identified 96 PROMS with 2641 items and extracted 798 quotations from 45 qualitative studies. Most items and quotations (94.8%) could be mapped onto the conceptual model. However, some adaptations were made and the model was complemented by (sub)domains for ‘treatment burden’, ‘treatment involvement’, and ‘financial issues’. Physical and psychological aspects were more frequently covered than social issues. Discussion: this review provides a comprehensive overview of HRQOL issues for children with cancer. Our findings mostly support the HRQOL model by Anthony et al. (Qual Life Res 23(3):771–789, 2014), but some adaptations are suggested. This review may be considered a starting point for a refinement of our understanding of HRQOL in children with cancer. Further qualitative research will help to evaluate the comprehensiveness of the HRQOL model and the relevance of the issues it encompasses.</p

Effects of probiotic administration on immune responses of children and adolescents with type 1 diabetes to a quadrivalent inactivated influenza vaccine

This study was planned to evaluate whether a 3-month treatment with Lactobacillus rhamnosus GG (LGG) can modify immune system functions in children and adolescents with type 1 diabetes (T1D), leading to an increased immune response to an injectable quadrivalent inactivated influenza vaccine (QIV). A total of 87 pediatric patients with T1D were screened, although 34 patients in the Probiotic group and 30 in the Control group accepted to be vaccinated with QIV and completed the study. Vaccine immunogenicity and safety and the inflammatory cytokine response were studied. Results showed that QIV was immunogenic and safe in T1D pediatric patients and pre-administration of LGG for three months did not substantially modify the QIV humoral immunity. The combination of QIV and LGG reduced inflammatory responses (i.e., IFN-γ, IL17A, IL-17F, IL-6, and TNF-α) from activated PBMCs of pediatric patients with T1D, without dampening the production of seroprotective antibodies. In conclusion, QIV is associated with an adequate immunogenicity in children and adolescents with T1D in presence of a good safety profile. Although a systematic administration of LGG did not result in an improvement of humoral responses to an influenza vaccine, the probiotic did induce important anti-inflammatory effects