Mecanismos fisiopatológicos en la rumiación

La fisiopatología del síndrome de rumiación es mal conocida. Por ello, el objetivo del estudio es determinar las características clínicas, fisiológicas y psicopatológicas de los pacientes con rumiación respecto a un grupo de dispepsia funcional. Se estudiaron ambos grupos de forma prospectiva durante dos años, realizándose manometría gastrointestinal y esofágica, vaciamiento gástrico, barostato gástrico y valoración psipatológica. Concluimos que el síndrome de rumiación se presenta en pacientes con características funcionales de dispepsia funcional, sin evidenciarse diferencias en la patología psiquiátrica pero con una mejor percepción de la enfermedad respecto al grupo de dispépticos.La fisiopatologia de la síndrome de rumiació és mal coneguda. Per això, l'objectiu de l'estudi és determinar les característiques clíniques, fisiològiques i psicopatològiques dels pacients amb rumiació respecte a un grup de dispèpsia funcional. Es van estudiar ambdós grups de forma prospectiva durant dos anys, realitzant-se manometria gastrointestinal i esofàgica, buidament gàstric, baròstat gàstric i valoració psicopatològica. Concloem que la síndrome de rumiació es presenta en pacients amb característiques funcionals de dispèpsia funcional, sense evidenciar-se diferències en la patologia psiquiàtrica, però amb una millor percepció de la malaltia respecte al grup de dispèptics

Analysis of hepatic stiffness after viral eradication in a population with chronic hepatitis C treated with DAAs

Introduction and objectives: Despite chronic hepatitis C (CHC) is still a global burden as the high morbidity and mortality, the recently approved direct-acting antivirals (DAAs) permit a very high rate of sustained virologic response (SVR) in these patients. The clinical improvement due to viral eradication is being documented, however it is not clear why a subset of patients does not benefit in terms of fibrosis regression or hepatocellular carcinoma (HCC) development. Aim of the study was to assess the hepatic stiffness regression at SVR24 and detect factors impacting stiffness course. Patients and methods: Hepatic stiffness assessed by acoustic radiation force impulse (ARFI) and anthropometric- and biochemical parameters were retrospectively collected by 166 CHC patients treated with DAAs, form baseline and SVR24. Results: Viral eradication significantly improved overall hepatic stiffness and other related hepatitis hallmarks such as ALT, AST, γGT, platelets count, AST to Platelets ratio Index (APRI), total- and LDL cholesterol. The multiple regression analysis showed that patients with baseline glucose > 110mg/dl presented a stiffness regression significantly lower when compared to low glucose patients (<110mg/dl), moreover baseline HbA1c strongly correlated with DeltaStiffness. 7 patients (4.2%) developed HCC and importantly, presented hyperglycaemia and no stiffness regression nor platelets count recover. Conclusions: Although viral eradication with DAAs entails overall benefits, glycaemic decompensation negatively affects fibrosis regression and probably facilitates HCC development

Risk stratification and natural history of intraductal papillary mucinous neoplasms of the pancreas

Uno de los principales objetivos del manejo del cáncer de páncreas es definir e identificar lesiones precursoras, como los neoplasias quísticas de páncreas (NQP), que permitan un diagnóstico temprano, En los últimos años, ha habido un aumento dramático en sus tasas de detección, particularmente en los tumores papilares mucinosos intraductales (TPMI), un subtipo de las NQP. Pese a ésto, su verdadera prevalencia sigue siendo incierta. Esta tesis doctoral abarca aspectos importantes de las NQP, y más específicamente de los TPMIs, como la prevalencia de las NQP halladas de forma incidental, los factores de riesgo para la progresión hacia malignidad de los TPMI y la validez de las pruebas diagnósticas rutinarias como la citología, el antígeno carcinoembrionario (CEA) y la amilasa en líquido aspirado del quiste. Como resultados, este trabajo demuestra la asociación entre la tendencia creciente de quistes pancreáticos hallados de forma incidental en los últimos años y el desarrollo de resonancias magnéticas abdominales (RMN) más sofisticadas. Aunque no podemos afirmar que esta tendencia en alza es únicamente debida a estas mejoras en las RMNs, podemos concluir que este factor juega un papel importante, cosa que no había sido descrito en ningún estudio con anterioridad. Por otro lado, se creó y analizó un registro multicéntrico de TPMIs, actualizado de forma prospectiva, para determinar los factores de riesgo de progresión a malignidad, así como la validez de las pruebas diagnósticas actualmente disponibles. El análisis logístico multivariable mostró una asociación estadísticamente significativa entre malignidad en TPMIs y hábito tabáquico, índice de masa corporal y presencia de síntomas. El análisis univariable mostró una asociación intensa entre el tamaño del quiste, los nódulos murales y la afectación del ducto pancreático principal y la presencia de malignidad. Por último, la citología del líquido quístico aspirado mostró resultados muy modestos. De acuerdo con la literatura actual, el CEA del líquido contenido en el quiste resultó ser una herramienta útil para diferenciar quistes mucinosos de no mucinosos (AUC 0.87) con un valor de referencia óptimo de 129 ng/ml. La amilasa, por otro lado, mostró una eficacia insuficiente, sin poder diferenciar entre estas dos lesiones y tampoco discriminar malignidad. En conclusión, ha habido una tendencia creciente de las lesiones quísticas de páncreas detectadas de forma incidental en la última década, en parte debido a los cambios en las características técnicas de las RMNs. Los factores de riesgo de malignidad en los TPMIs incluyen variables demográficas como el índice de masa corporal y el hábito tabáquico; variables morfológicas como la afectación del conducto pancreático principal y la presencia de nódulos murales; y síntomas específicos del páncreas como esteatorrea o ictericia. La citología del fluido quístico tiene una sensibilidad insuficiente, las concentraciones de CEA en este mismo fluido tienen una efectividad modesta para diferencias entre TPMIs y lesiones no mucinosas, y una efectividad claramente insuficiente para discriminar entre lesiones benignas y malignas. Los niveles de amilasa en el líquido contenido en el quiste no aportan ningún valor en el diagnóstico de los TPMIs o en la diferenciación de estas lesiones de los cistoadenomas mucinosos.One of the main aims in the management of pancreatic cancer is to define and identify precursor lesions that allow an early diagnosis, such as pancreatic cystic neoplasms (PCNs). In recent years, there has been a dramatic increase in their detection rates, particularly in intraductal papillary mucinous neoplasms (IPMNs), a subtype of PCNs. Despite this, their true prevalence remains uncertain. This doctoral thesis addresses several important aspects regarding PCNs, and more specifically IPMNs, such as the real prevalence of incidentally found PCNs, the risk factors for malignant progression in IPMNs and the accuracy of routinely performed tests such as cystic fluid cytology, carcinoembriogenic antigen (CEA) and amylase. As results, this work demonstrates the association between the higher trend of incidentally found pancreatic cysts observed in the recent years and the development of more sophisticated magnetic resonance imaging (MRI) studies. Although we cannot state that this higher trend is solely due to the improvements in the MRI technical features, we can conclude that this factor plays an important role on it, which to our knowledge had not yet been addressed by any study. Secondly, a prospectively updated multicenter longitudinal IPMN registry was generated and analyzed to determine the risk factors for malignant progression, as well as the accuracy of the currently available diagnostic tests. The multivariate logistic analysis showed a statistically significant association between malignancy in IPMNs and a positive smoking history, body mass index and the presence of symptoms. Univariate analysis showed a strong association between cyst size, mural nodules and main duct involvement and the presence of malignancy. Finally, cytology of cyst fluid showed very modest results. Accordingly to current literature, cyst-fluid CEA proved to be a valuable tool for differentiating mucinous from non-mucinous cysts (AUC 0.87) with an optimal cut-off value of 129 ng/ml. Amylase, on the other hand, showed an insufficient accuracy and was unable to differentiate among these lesions, as well as to discriminate malignancy. In conclusion, there has been an increased trend of incidentally detected pancreatic cystic lesions in the last decade, partly due to the changes in the magnetic resonance imaging capabilities. The risk factors for malignancy in IPMNs include demographic variables, such as body mass index and positive smoking history; morphological features, such as main duct involvement and presence of mural nodules; and specific pancreatic symptoms, such as steatorrhea or jaundice. Cytology of cyst fluid lacks of sensitivity, CEA concentrations in cyst fluid have modest accuracy for differentiating between IPMNs and non-mucinous lesions, and lack of sufficient accuracy to discriminate between malignant and benign lesions. Cyst fluid amylase levels yield no diagnostic contribution to diagnosing IPMNs or differentiating these lesions from mucinous cystadenomas

Estudo retrospectivo do tratamento da ruptura de ligamento cruzado cranial no cão por técnica cirúrgica extra-articular

Extra-articular techniques have been widely used on cranial cruciate ligament rupture repair; among these techniques fabelo-tibial suture is one of the most popular. The purpose of the present study was to evaluate the clinical results following at least 4 months of post-operative of cranial cruciate ligament deficiency in 19 dogs (20 joints) using the fabelo-tibial technique. After interviewing the owners a clinical exam was performed by the veterinary and it included gait evaluation, withdraw test and objective measurements of the thigh circumference, stifle angle and stifle diameter of the affected and the contra lateral limbs. The owners evaluated 90% of the dogs as having an excellent to good recovery, without or with sporadic lameness. The gait and withdraw tests of the clinical evaluation showed satisfactory results. Nevertheless, the objectives measurements don´t showed the same results.As técnicas extra-capsulares têm sido amplamente utilizadas para a reparação da ruptura do ligamento cruzado cranial no cão (RLCC); e, a sutura fabelo tibial tem se tornado uma das mais populares. A presente pesquisa teve por finalidade avaliar a evolução clínica de pelo menos 4 meses de pós-operatório de 19 cães (20 articulações) portadores de RLCC e submetidos a técnica acima descrita. Realizou-se entrevista com o proprietário e exame clínico consistindo de avaliação do escore de claudicação, teste de gaveta e mensuração do diâmetro da coxa, volume e ângulo da articulação do joelho. De acordo com os proprietários 90% dos animais apresentaram recuperação boa ou ótima após o tratamento cirúrgico, variando de ausência de claudicação com claudicação esporádica. A avaliação clínica denotou resultado favorável no que tange ao teste de gaveta e escore de claudicação. As mensurações objetivas, contudo, não corroboraram na mesma proporção com os resultados clínicos

Estudo epidemiológico retrospectivo de cães portadores de ruptura do ligamento cruzado cranial: 323 casos (1999 a 2005)

The aim of this research was to characterize in the canine population the risk factors for cranial cruciate ligament rupture, which are breed, age, sex and body weight. The data base consisted of collected information from medical records of 323 dogs bearing cranial cruciate ligament rupture attended during a period of 7 years (1999 to 2005) in the Small Animal Surgical Service of the Veterinary Hospital of the Veterinary Medicine Faculty at São Paulo University. The results showed that the most prevalent breed were Leonberger (100%), Cane Corso (66,7%), Dogue de Bordeau (50%), Starffordshire Terrier (40%) e o Chow Chow (36%). Also, Rottweiller (11,16%) and Labrador Retriever (8,1%) occupied the 10º e 13º positions, respectively. The ages 2, 4, 3, 7 and 6 (mean = 5,58) years old had the highest prevalence of cranial cruciate ligament rupture. Female (59,14%) were more represented than males (40,86%) and sexually intact animals (76,15%) were more represented than neutered dogs (17,76%). The group f dogs weighing between 6 and 15 kg and between 36 and 45 kg showed the highest incidence. In this research was observed that the database of the risk factors for the dogs bearing cranial cruciate ligament rupture examined were similar to the that seen in the foreign literature. There is a tendency for rupture of ligament in an earlier age, large breeds and giant dogs. The Rottweiler was a common breed among our study and that of the foreign literature. Also, female were more represented than male dogs.O objetivo do presente trabalho foi caracterizar a população de cães portadores de ruptura do ligamento cruzado cranial (RLCC) para fatores considerados de risco como raça, idade, sexo e peso corporal. A base de dados consistiu de informações resgatadas de prontuários de 323 cães com diagnóstico de ruptura de ligamento cruzado cranial atendidos no Serviço de Cirurgia de Pequenos Animais do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo em um período de 7 anos (1999 a 2005). Os resultados mostraram que as raças de maior prevalência foram o Leonberger (100%), Cane Corso (66,7%), Dogue de Bordeau (50%), Starffordshire Terrier (40%) e o Chow Chow (36%), estando ainda o Rottweiler (11,6%) e o Labrador Retriever (8,1%) em 10º e 13º lugares, respectivamente. As idades de maior freqüência foram 2, 4, 3, 7 e 6 anos (média = 5,58 anos). Fêmeas (59,14%) foram mais acometidas do que machos (40,86%) e animais inteiros (76,15%) foram mais representativos do que animais castrados (17,76%). Quanto ao peso, entre 6 e 15 kg (32,82%) seguido por animais entre 36 e 45 kg (17,03%). Pode-se observar que os dados em nosso meio tendem a se assemelhar com a literatura estrangeira: ocorrência da RLCC em animais mais jovens de raças de grande porte e gigantes, o Rottweiler como uma raça em comum a fêmea é mais representativa do que o macho

ANÁLISE DO PROCESSO PRODUTIVO DE FILMES POLIMÉRICOS UTILIZANDO A METODOLOGIA DE PRODUÇÃO MAIS LIMPA

The current technological advance guides the actions that have contributed to the study and implementation of a structured environmental management within companies. Thereby, this article discusses the application of Cleaner Production Methodology in a company engaged in the business of flexible films in the region of Sorocaba, São Paulo, Brazil. The study aims to identify opportunities of improvements that might reduce the environmental impact. There were visits in the enterprise during the execution of the project in order to get quantitative and qualitative data, which supported the mapping and understanding of the productive process. The application of Cleaner Production has allowed the identification of improvements in the process, better use of raw material, reduction of water use and minimization of waste generation. In this case, it has been used an adapted transformation model to map the system. Opportunities for future improvements have been identified and classified into the strategic levels of the Cleaner Production; some of them are related to the progress in the use of raw materials, reduction of water leaks through the process in the pipes, change of raw material from nonrenewable to renewable source, performance of preventive maintenance, minimization of waste generation, use of regranulated material generated in the process, etc. Therefore, for futures studies, it may be accomplished the analysis of economic and technical feasibility of each proposal identified in this reportO avanço tecnológico norteia ações que contribuem para o estudo e implantação de um sistema de gestão ambiental estruturado dentro das empresas. Dentro deste contexto, este trabalho aborda o estudo da aplicação da metodologia da Produção Mais Limpa (PML) em uma empresa de embalagens de filmes poliméricos flexíveis de BOPP (Polipropileno Biorientado) na região de Sorocaba, que almejou identificar oportunidades de melhorias que podem impactar na redução de impactos ambientais. As visitas técnicas realizadas na empresa auxiliaram no mapeamento e entendimento do processo produtivo. O uso da metodologia de PML permitiu a identificação de possíveis melhorias no processo visando minimização de geração de resíduos, matéria-prima, água e energia. No caso foi utilizado um modelo de transformação para realizar o mapeamento do processo produtivo. As oportunidades de futuras melhorias foram identificadas e enquadradas nos níveis estratégicos da PML, algumas delas estão relacionadas às melhorias na utilização de matérias-primas, redução de vazamento de água para o processo nas tubulações, alteração de matéria-prima de fonte não renovável para renovável, realização de manutenção preventiva, minimização da geração de resíduos, utilização do material regranulado gerado no processo etc. Para futuros trabalhos devem ser realizadas as viabilidades econômica e técnica de cada proposta identificada no presente trabalho

High prevalence of false positive SARS-CoV2 serology in a cohort of patients with liver autoimmune diseases

Aim Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases. Methods From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with (reverse transcription-polymerase chain reaction) RT-PCR of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up. Results The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. The presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as well. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP). Conclusions Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category

The multikinase inhibitor EC‐70124 synergistically increased the antitumor activity of doxorubicin in sarcomas

Cytotoxic drugs like doxorubicin remain as the most utilized agents in sarcoma treatment. However, advanced sarcomas are often resistant, thus stressing the need for new therapies aimed to overcome this resistance. Multikinase inhibitors provide an efficient way to target several pro-tumorigenic pathways using a single agent and may constitute a valuable strategy in the treatment of sarcomas, which frequently show an aberrant activation of pro-tumoral kinases. Therefore, we studied the antitumor activity of EC-70124, an indolocarbazole analog that have demonstrated a robust ability to inhibit a wide range of pro-survival kinases. Evaluation of the phospho-kinase profile in cell-of-origin sarcoma models and/or sarcoma primary cell lines evidenced that PI3K/AKT/mTOR, JAK/STAT or SRC were among the most highly activated pathways. In striking contrast with the structurally related drug midostaurin, EC-70124 efficiently prevented the phosphorylation of these targets and robustly inhibited proliferation through a mechanism associated to the induction of DNA damage, cell cycle arrest and apoptosis. In addition, EC-70124 was able to partially reduce tumor growth in vivo. Importantly, this compound inhibited the expression and activity of ABC efflux pumps involved in drug resistance. In line with this ability, we found that the combined treatment of EC-70124 with doxorubicin resulted in a synergistic cytotoxic effect in vitro and an increased antitumor activity of this cytotoxic drug in vivo. Altogether, these results uncover the capability of the novel multikinase inhibitor EC-70124 to counteract drug resistance in sarcoma and highlight its therapeutic potential when combined with current treatmentsPeer ReviewedPostprint (author's final draft

Cartography of neoplasms in dogs from different regions of the city of São Paulo, SP, Brazil: a survey (2002-2003) of data from the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil

Avanços na medicina veterinária resultaram em benefícios significativos na vida de animais de estimação nos últimos 20 anos, e o aumento da expectativa de vida para animais levou a uma maior prevalência de neoplasias em cães. A Epidemiologia do Câncer e as ferramentas de análise espacial, embora bem desenvolvidas na pesquisa oncológica humana, estão começando a serem exploradas na Oncologia Veterinária. A cidade de São Paulo, capital do estado de São Paulo, Brasil, é dividida em cinco regiões: Norte, Sul, Leste, Oeste e centro. O Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo (HOVET-SVMAS-USP) está localizado na região Oeste de São Paulo, Brasil, e admite casos de pequenos e grandes animais. Tumores mamários caninos são tão numerosos que não são tratados na rotina do HOVET. O objetivo deste trabalho foi realizar um estudo cartográfico para descrever a distribuição espacial dos casos prevalentes de neoplasias em cães a partir do HOVET. Dos 3.620 casos atendidos em 2002 e 2003, 380 (10,5%) casos eram de cães acometidos por tumores benignos e malignos. Não foi encontrada diferença estatística entre a distribuição dos 380 endereços entre as cinco regiões da cidade. Os resultados mostraram que o HOVET atende pacientes caninos de todas as regiões de São Paulo e que há uma distribuição espacial homogênea das neoplasias. Os autores incentivam estudos mais amplos, envolvendo vários hospitais veterinários, clínicas e laboratórios, a fim de obter dados mais precisos sobre a distribuição das neoplasias caninas em São Paulo, SP, Brasil.Improvements in veterinary medicine have resulted in a significant benefit in the life of pets in the last 20 years, and increased pet life expectancy led to an increased prevalence of canine neoplasia. Cancer epidemiology and spatial analysis tools, although well developed for human oncology research, is just beginning to be explored in veterinary oncology. São Paulo city, capital of the state of São Paulo, Brazil, is divided into five regions: North, South, East, West and downtown. The Veterinary Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo (HOVET-SVMAS-USP), is located in the West region of São Paulo, Brazil, and admits cases of small and large animals. Canine mammary tumors are so numerous that they are not routinely treated at the HOVET. The aim of this work was to perform a cartographic study to describe the spatial distribution of prevalent cases of neoplasms in dogs from the HOVET. Of the 3,620 cases seen in 2002 and 2003, 380 cases (10.5%) were of dogs affected with benign and malignant neoplasms. No statistical difference was found for the 380 addresses distributed among the five regions of the city. These results showed that the HOVET receives canine patients from all regions of São Paulo and there is a homogeneous spatial distribution of neoplasms. Authors encourage additional broader studies, involving several veterinary hospitals, clinics or laboratories in order to obtain more accurate data on distribution of canine neoplasms in São Paulo, SP, Brazil