Short-term effects of underwater treadmill therapy on ground reaction forces of canine orthopaedic patients

Dissertação de Mestrado Integrado em Medicina VeterináriaThis dissertation aimed to use kinetic gait analysis to study the effects of an underwater treadmill therapy (UWT) session on ground reaction forces of dogs with lameness caused by an orthopaedic condition, located in one or both contralateral limbs of a pair. Fourteen clientowned dogs presenting appendicular orthopaedic conditions were recruited. All dogs had previously undergone UWT. The nine selected candidates were divided into two groups: Group A comprised dogs diagnosed with an orthopaedic condition in the forelimbs, and Group B individuals diagnosed with orthopaedic conditions in the hindlimbs. Pressure plate gait analysis was performed to determine ground reaction forces baseline data of all individuals. Afterwards, the dogs completed an UWT session, and gait analysis was repeated to determine postsession values. Peak and impulse of vertical forces (PFz and IFz), stance phase duration (SPD), paw pressure contact area (PCA), and step length were measured. A correlation between step length and withers height was assessed using the collective data of all participants. Contralateral limb pair symmetry was calculated using a symmetry index (SI) for the parameters PFz, IFz, SPD and PCA (SIPFz, SIIFz, SISPD and SIPCA, respectively). Nonlame dogs were excluded, using a SI cut-off value of <3% for PFz and IFz between contralateral limbs. All participants presented baseline hindlimb lameness, regardless of their diagnosis. Before and after measurements were evaluated using a paired student t-test. No statistically significant alterations were observed in any of the parameters. However, baseline and post-session values showed a strong positive correlation in Group A step length and forelimb SIPFz and SIIFz, as well as in Group B step length, mean velocity, hindlimb SIPFz and forelimb SIPCA. In Group B, post-UWT measurements showed an overall decrease in hindlimb SIPFz. In both groups, mean SIPCA increased in the forelimbs and decreased in the hindlimbs. Mean step length increased in 6 dogs and remained equal in 2 dogs. Step length and withers height exponential correlation presented a R value of 0.78. After UWT, 1 out of the 9 participants was considered nonlame. Further research is required to determine the shortterm effects of UWT in temporospatial and pressure gait parameters of dogs with orthopaedic lameness.RESUMO - EFEITOS A CURTO-PRAZO DE HIDROTERAPIA EM PASSADEIRA AQUÁTICA NAS FORÇAS DE REAÇÃO AO SOLO DE CANÍDEOS COM PATOLOGIA ORTOPÉDICA - Esta dissertação teve como objetivo estudar o efeito de uma sessão de terapia em passadeira aquática (UWT) nas forças de reação ao solo de cães com claudicação de origem ortopédica, localizada em um ou ambos membros do mesmo par, através de análise de movimento. Foram pré-avaliados 14 cães que apresentavam condições ortopédicas apendiculares, e já submetidos a UWT anteriormente. Os 9 candidatos selecionados foram separados em dois grupos: o Grupo A incluiu cães com claudicação dos membros torácicos e o Grupo B indivíduos com claudicação dos membros pélvicos. Realizou-se análise de movimento com placa de pressão para determinar os valores base das forças de reação ao solo. Depois de terem completado uma sessão de UWT, os animais foram novamente submetidos a análise de movimento para determinar os valores pós-sessão. Mediu-se o pico e impulso das forças verticais (PFz e IFz), duração da fase de estação (SPD), área de contacto do membro (PCA), e comprimento da passada. A correlação entre o comprimento da passada e a altura do garrote foi avaliada usando os dados de todos os participantes. A simetria dos membros contralaterais foi calculada através de um índice de simetria (SI) para os parâmetros PFz, IFz, SPD e PCA (SIPFz, SIIFz, SISPD and SIPCA). Cães com um valor de SIPFz e SIIFz inferior a 3% foram considerados não claudicantes e excluídos. Todos os participantes apresentaram valores de claudicação nos membros pélvicos, independentemente do diagnóstico. Os valores pré e pós-UWT foram avaliados com o teste t de student para amostras emparelhadas. Não se observaram alterações significativas em nenhum dos parâmetros. No entanto, no Grupo A os valores pré e pós-UWT do comprimentos da passada, e do SIPFz e SIIFz nos membros torácicos demonstraram uma forte correlação positiva, o que também se verificou nos valores do comprimento da passada, velocidade média, SIPFz dos membros pélvicos e SIPCA dos membros torácicos no Grupo B. No Grupo B, observou-se uma diminuição geral no SIPFz dos membros pélvicos. Em ambos grupos, o valor médio de SIPCA aumentou nos membros torácicos e diminuiu nos pélvicos. O valor médio do comprimento da passada aumentou em 6 cães, e manteve-se inalterado em 2. A correlação exponencial entre o comprimento da passada e a altura do garrote apresentou um valor de R = 0.78. Após UWT, 1 dos 9 participantes passou a ser considerado não claudicante. Investigação adicional é necessária para determinar os efeitos a curto prazo da UWT nos parâmetros temporo-espaciais e pressão ao solo em cães com claudicação de origem ortopédica.N/

DEFICIÊNCIA DE PROLIDASE – UMA CAUSA RARA DE ÚLCERAS DE PERNA EM IDADE PEDIáTRICA

Prolidase deficiency is a rare, autosomal recessive disease resulting from a mutation of the prolidase gene (PEPD) located on chromosome 19. The deficiency of this enzyme impairs proline recycling and consequently the synthesis of collagen. This defect may be asymptomatic or associated with different clinical manifestations, being the most frequently reported chronic skin ulcers, recurrent infections, hepatosplenomegaly, mental retardation and a cha- racteristic facies, which commonly emerge during pediatric age. The authors describe a case of a 14-year-old boy with the diagnosis of prolidase deficiency, who was sent to the department of Pediatric Dermatology due to the appearance of an ulcer in the external maleolar region of the left foot. Surgical debridement was performed and he started treatment with 5% glycine and 5% proline ointment. Complete healing one month later was observed.KEYWORDS – Dipeptidases, Deficiency; Leg Ulcer.A deficiência de prolidase (DP) é uma condição rara, autossómica recessiva, que resulta de uma muta- ção no gene da prolidase (PEPD), localizado no cromossoma 19. A deficiência desta enzima diminui a reciclagem de prolina e, consequentemente, a síntese de colagénio. Este defeito pode ser assintomático ou estar associado a mani- festações clínicas, tais como úlceras crónicas dos membros inferiores, infecções recorrentes, hepato-esplenomegalia, oligofrenia e fácies evocativa, as quais surgem habitualmente em idade pediátrica. Os autores descrevem o caso de uma criança de 14 anos de idade, com o diagnóstico de deficiência de prolidase, enviado à consulta de Dermatolo- gia Pediátrica pelo aparecimento de úlcera na região maleolar lateral do pé esquerdo. Foi realizado desbridamento cirúrgico e encetada a aplicação diária de manipulado de glicina e prolina (ambas a 5%) em vaselina purificada, tendo-se observado a cicatrização da lesão ao fim de 1 mês.PALAVRAS-CHAVE – Deficiência de Prolidase; Úlcera de Perna

Genetic Alterations in Poorly Differentiated and Undifferentiated Thyroid Carcinomas

Thyroid gland presents a wide spectrum of tumours derived from follicular cells that range from well differentiated, papillary and follicular carcinoma (PTC and FTC, respectively), usually carrying a good prognosis, to the clinically aggressive, poorly differentiated (PDTC) and undifferentiated thyroid carcinoma (UTC)

Best Practice Recommendations for the Implementation of a Digital Pathology Workflow in the Anatomic Pathology Laboratory by the European Society of Digital and Integrative Pathology (ESDIP)

The interest in implementing digital pathology (DP) workflows to obtain whole slide image (WSI) files for diagnostic purposes has increased in the last few years. The increasing performance of technical components and the Food and Drug Administration (FDA) approval of systems for primary diagnosis led to increased interest in applying DP workflows. However, despite this revolutionary transition, real world data suggest that a fully digital approach to the histological workflow has been implemented in only a minority of pathology laboratories. The objective of this study is to facilitate the implementation of DP workflows in pathology laboratories, helping those involved in this process of transformation to identify: (a) the scope and the boundaries of the DP transformation; (b) how to introduce automation to reduce errors; (c) how to introduce appropriate quality control to guarantee the safety of the process and (d) the hardware and software needed to implement DP systems inside the pathology laboratory. The European Society of Digital and Integrative Pathology (ESDIP) provided consensus-based recommendations developed through discussion among members of the Scientific Committee. The recommendations are thus based on the expertise of the panel members and on the agreement obtained after virtual meetings. Prior to publication, the recommendations were reviewed by members of the ESDIP Board. The recommendations comprehensively cover every step of the implementation of the digital workflow in the anatomic pathology department, emphasizing the importance of interoperability, automation and tracking of the entire process before the introduction of a scanning facility. Compared to the available national and international guidelines, the present document represents a practical, handy reference for the correct implementation of the digital workflow in Europe.publishedVersio

TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.We acknowledge GENZYME for funding our work through a research project. This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology

TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas

Funding: This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/ 2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology.Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives:Weaimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P< .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P=.001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P=.001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01-53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36-415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.publishersversionpublishe

Follicular thyroid carcinoma with an unusual glomeruloid pattern of growth.

We describe an uncommon thyroid tumor in a 56-year-old woman. The widely infiltrating, angioinvasive neoplasm, 5 cm in diameter, exhibited a peculiar architectural growth pattern characterized by follicles with round to oval epithelial tufts growing within, often supported by a fibrovascular core mimicking the renal glomerulus. Colloid-empty follicles, tubular or elongated, were lined by pseudostratified tall, columnar cells with clear cytoplasm. Nuclei were round to oval, with evenly distributed, slightly coarse chromatin. Tumor cells were positive for thyroid transcription factor-1, thyroperoxidase, thyroglobulin, cytokeratin 18, Hector Battifora mesothelial cell, and vimentin. Scattered cells positive for S100, Wilms tumor 1 (WT1), and cytokeratins AE1/AE3 were found, with no reaction detected for cytokeratins 34betaE12, 5/6, 7, 19, or 20. There were PAX8-PPARgamma rearrangement and N-RAS mutation. No mutations were found for APC or BRAF genes, nor were RET/PTC rearrangements detected. Because of the distinctive histologic features, we propose naming this tumor follicular thyroid carcinoma with an unusual glomeruloid pattern of growth

HEROHE Challenge: Predicting HER2 Status in Breast Cancer from Hematoxylin–Eosin Whole-Slide Imaging

Breast cancer is the most common malignancy in women worldwide, and is responsible for more than half a million deaths each year. The appropriate therapy depends on the evaluation of the expression of various biomarkers, such as the human epidermal growth factor receptor 2 (HER2) transmembrane protein, through specialized techniques, such as immunohistochemistry or in situ hybridization. In this work, we present the HER2 on hematoxylin and eosin (HEROHE) challenge, a parallel event of the 16th European Congress on Digital Pathology, which aimed to predict the HER2 status in breast cancer based only on hematoxylin–eosin-stained tissue samples, thus avoiding specialized techniques. The challenge consisted of a large, annotated, whole-slide images dataset (509), specifically collected for the challenge. Models for predicting HER2 status were presented by 21 teams worldwide. The best-performing models are presented by detailing the network architectures and key parameters. Methods are compared and approaches, core methodologies, and software choices contrasted. Different evaluation metrics are discussed, as well as the performance of the presented models for each of these metrics. Potential differences in ranking that would result from different choices of evaluation metrics highlight the need for careful consideration at the time of their selection, as the results show that some metrics may misrepresent the true potential of a model to solve the problem for which it was developed. The HEROHE dataset remains publicly available to promote advances in the field of computational pathology