Decreased CD1a + and CD83 + cells in tonsillar squamous cell carcinoma regardless of HPV status

Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. Objective: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. Methodology: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). Results: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). Conclusion: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Mis casos clínicos de especialidades odontológicas

Libro que muestra la atención de casos clínicos particulares referente a las diferentes especialidades odontológicasLibro que muestra la atención de casos clínicos particulares referente a las diferentes especialidades odontológicasUniversidad Autónoma de Campeche Universidad Autónoma del Estado de Hidalgo Universidad Autónoma del Estado de Méxic

Avaliação imunoistoquímica das células dendríticas em lesões orais benignas e malignas asscoiadas com HPV

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Odontologia, Florianópolis, 2018.As células dendríticas (CDs) são células apresentadoras de antígenos que participam ativamente da resposta imune, especialmente após infeccões virais tais como as causadas pelo vírus do Papiloma Humano (HPV). O objetivo deste estudo foi quantificar e comparar o número de CD maturas e imaturas em lesões orais benignas e malignas associadas ao HPV. Vinte e um casos de papiloma oral (PO), 33 casos de carcinoma de células escamosas tonsilar (CCET) e 12 amostras de tecido normal de mucosa oral coletadas de autopsias (grupo controle), foram obtidos dos laboratórios de Patologia Bucal da Universidade Federal de Santa Catarina (LPB-UFSC) e Anatomia Patológica da Faculdade de Ciências Médicas da Universidade de Campinas (FCM-UNICAMP). Reações imunoistoquímicas contra CD1a e CD83 foram realizadas para identificar CDs imaturas e maturas, respectivamente. A presença do HPV em PO e CCET foi avaliada através da imunoexpressão do anticorpo p16. A quantidade de CDs foi analisada com o software Image J 1.51k e as diferenças entre os grupos foram comparadas estatisticamente por testes paramétricos e não-paramétricos utilizando o software SPSS versão 18.0. Os valores foram expressos como média e desvio padrão (DP) e um nível de significância de 5% (P 0,05). Assim, a positividade de p16 em PO e CCET não contribui para a depleção das CDs.Abstract : Dendritic cells (DCs) are cells that participate in the immune response, especially after viral infections such as papillomaviruses (HPV). The aim of this study was to quantify and compare the number of mature and immature dendritic cells in HPV associated benign and malignant oral lesions. Twenty-one cases of oral papilloma (OP), 33 cases of tonsillar squamous cell carcinoma (TSCC), and 12 cases of normal oral mucosa samples collected from autopsies (control group), were obtained from the Oral Pathology Laboratory of the Federal University of Santa Catarina (UFSC) and Pathological Anatomy Service of Medical Science Faculty of Campinas University (FCM-UNICAMP). Immunohistochemical reactions against CD1a and CD83 were performed to identify mature and immature DCs, respectively. The presence of HPV in OP and TSCC was assessed by expression of p16 antibody. The number of DCs was analyzed using the Image J 1.51k software and the differences between the groups were compared statistically by parametric and non-parametric tests using SPSS software version 18.0. Values were expressed as mean and standard deviation (SD) and a significance level of 5% (P 0.05). Thus, the positivity of p16 in OP and TSCC does not contribute to the depletion of CDs