Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities

Background Epidermal growth factor receptor inhibitors (EGFRI) produce various dermatologic side effects in the majority of patients, and guidelines are crucial for the prevention and treatment of these untoward events. The purpose of this panel was to develop evidence-based recommendations for EGFRI-associated dermatologic toxicities. Methods A multinational, interdisciplinary panel of experts in supportive care in cancer reviewed pertinent studies using established criteria in order to develop first-generation recommendations for EGFRI-associated dermatologic toxicities. Results Prophylactic and reactive recommendations for papulopustular (acneiform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis/fissures, and paronychia are presented, as well as general dermatologic recommendations when possible. Conclusion Prevention and management of EGFRI-related dermatologic toxicities is critical to maintain patients’ health-related quality of life and dose intensity of antineoplastic regimens. More rigorous investigation of these toxicities is warranted to improve preventive and treatment strategies

Evaluation of the Cervical Vertebrae Maturation Index in Lateral Cephalograms Taken in Different Head Positions

The aim of this study was to evaluate if upward or downward head inclination might interfere with determination of the growth stage, using cervical vertebrae maturation index (CVMI), in order to verify the accuracy of such diagnosis when radiographs are taken with errors. Forty-nine patients, 26 females and 23 males, aged 9 to 15 years, were submitted to 3 lateral cephalograms: normal (NHP), with 15° upward head inclination (NHP-Up), and with 15° downward head inclination (NHP-Down). Three examiners evaluated the CVMI on the 147 cephalograms. The agreement among examiners was higher in the evaluation of cephalograms taken in NHP. The weighted Kappa test revealed moderate to substantial agreement between NHP and NHP-Up and between NHP and NHP-Down. There was greater agreement between NHP-Up and NHP-Down. It may be concluded that the evaluation of the CVMI on cephalograms in NHP is different as compared with radiographs taken with inclinations. Both NHP-Up and NHP-Down exhibited greater disagreement in the interpretation among examiners, since the evaluation method was not designed for cephalograms with positioning errors.O objetivo deste estudo foi avaliar se a inclinação da cabeça para cima ou para baixo interfere na determinação do estágio de crescimento por meio do Índice de maturação das vértebras cervicais (IMVC), verificando a acurácia deste método de diagnóstico, quando as radiografias são tomadas com erros. Quarenta e nove pacientes, 26 do gênero feminino e 23 do masculino, entre 9 e 15 anos de idade, foram submetidos a 3 telerradiografias em norma lateral: posição natural de cabeça (PNC), cabeça inclinada 15° para cima (PNC-alta), e 15° para baixo (PNC-baixa). Três examinadores avaliaram o IMVC nas 147 telerradiografias. A concordância entre os examinadores foi alta na avaliação das telerradiografias obtidas em PNC. O teste Kappa revelou concordância moderada a substancial entre PNC e PNC-alta e entre PNC e PNC-baixa. Houve concordância significante entre PNC-alta e PNC-baixa. Pode-se concluir que a avaliação do IMVC em telerradiografias obtidas em PNC difere em comparação com as radiografias tomadas com inclinações. Tanto PNC-alta quanto PNC-baixa demonstraram maior discordância na interpretação entre os examinadores, uma vez que o método de avaliação não foi preconizado para telerradiografias com erros de posicionamento.Departamento de Odontologia, Universidade Cidade de São Paulo (UNICID), São Paulo, SP, BrasilDepartamento de Odontologia, Universidade Metodista de São Paulo (UMESP), São Bernardo do Campo, SP, BrasilDepartamento de Materiais Odontológicos e Prótese, Instituto de Ciência e Tecnologia (ICT), Universidade Estadual Paulista (UNESP), São José dos Campos, SP, BrasilDepartamento de Odontologia, Universidade Federal de Sergipe (UFS), Lagarto, SE, BrasilDepartamento de Ciência da Saúde, Universidade do Sagrado Coração (USC), Bauru, SP, BrasilUniversidade Estadual Paulista, Departamento de Materiais Odontológicos e Prótese, Instituto de Ciência e Tecnologia de São José dos Campo

Localization of SUCLA2 and SUCLG2 subunits of succinyl CoA ligase within the cerebral cortex suggests the absence of matrix substrate-level phosphorylation in glial cells of the human brain.

We have recently shown that the ATP-forming SUCLA2 subunit of succinyl-CoA ligase, an enzyme of the citric acid cycle, is exclusively expressed in neurons of the human cerebral cortex; GFAP- and S100-positive astroglial cells did not exhibit immunohistoreactivity or in situ hybridization reactivity for either SUCLA2 or the GTP-forming SUCLG2. However, Western blotting of post mortem samples revealed a minor SUCLG2 immunoreactivity. In the present work we sought to identify the cell type(s) harboring SUCLG2 in paraformaldehyde-fixed, free-floating surgical human cortical tissue samples. Specificity of SUCLG2 antiserum was supported by co-localization with mitotracker orange staining of paraformaldehyde-fixed human fibroblast cultures, delineating the mitochondrial network. In human cortical tissue samples, microglia and oligodendroglia were identified by antibodies directed against Iba1 and myelin basic protein, respectively. Double immunofluorescence for SUCLG2 and Iba1 or myelin basic protein exhibited no co-staining; instead, SUCLG2 appeared to outline the cerebral microvasculature. In accordance to our previous work there was no co-localization of SUCLA2 immunoreactivity with either Iba1 or myelin basic protein. We conclude that SUCLG2 exist only in cells forming the vasculature or its contents in the human brain. The absence of SUCLA2 and SUCLG2 in human glia is in compliance with the presence of alternative pathways occurring in these cells, namely the GABA shunt and ketone body metabolism which do not require succinyl CoA ligase activity, and glutamate dehydrogenase 1, an enzyme exhibiting exquisite sensitivity to inhibition by GTP