Errors in Surgical Pathology Laboratory

Pathology must aim at a correct and complete diagnosis for the patient, which is timely, useful, and understandable to the physician assistant. However, in daily practice, there are multiple possibilities of errors in the pathology laboratory, with several impacts on patient care and prognosis. In this chapter, we discuss the different concepts of error and diagnostic concordances in pathology, at which point in the diagnostic process the errors are more frequent, and propose solutions to minimize the chance of their occurrence

Implantação da Puericultura na UBS Nossa Senhora do Perpétuo Socorro em Manacapuru/AM

A puericultura no Brasil representa complemento e seguimento fundamental para as estratégias de redução de mortalidade materno-infantis, iniciadas nos cuidados pré-natais e nas maternidades. Com a realização da Análise Situacional da Unidade Básica de Saúde da Família Nossa Senhora do Perpétuo Socorro, no bairro Biribiri (Manacapuru-AM), observou-se que uma das áreas de Atenção à Saúde com necessidade de organização de Ação Programática foi a Puericultura. O objetivo da Intervenção foi ampliar para 35% a cobertura da atenção à saúde para as crianças entre zero e 72 meses pertencentes à área de abrangência da referida Unidade Básica. Considerou-se tal meta como exequível dentro do pouco tempo para a execução da Ação, bem como dentro das dificuldades de processo de trabalho e estruturais da UBSF encontradas. A intervenção foi executada em 10 semanas, sendo incluídas 108 crianças da área de abrangência da Unidade Básica, entre 0 a 72 meses de idade. Foi utilizado como protocolo para atendimento da população-alvo o Caderno de Atenção Básica nº 33, "Saúde da criança: crescimento e desenvolvimento", do Ministério da Saúde, de 2012. Foi realizado um levantamento de dados, a partir dos registros de famílias de cada agente comunitário de saúde, a fim de estimarmos a população alvo do programa: crianças pertencentes à área de abrangência da UBSF, de 0 a 72 meses de idade, totalizando 286 crianças. Para o alcance dos objetivos e metas, foram executadas as seguintes ações: cadastramento de toda a população elegível, seguida de convite e agendamento de consultas clínicas com médico, enfermeiro e odontólogo para as crianças, avaliação de crescimento/desenvolvimento, peso, estado vacinal, necessidade de suplementação de ferro e avaliação odontológica, busca ativa de crianças faltosas, registro completo e legível de todos os atendidos, treinamento da equipe e atividades de sala de espera. Ao final das 10 semanas de execução (meses 1 a 3), foram incluídas 108 crianças, sendo 16 (14,8%) atendidas também pelo odontólogo da UBSF. Foi alcançada, após a intervenção, uma cobertura da área adscrita de 36,4% (n=108). Observou-se que um grande número de crianças não foi submetido à triagem neonatal e teste da orelhinha, bem como não tinha acompanhamento odontológico regular. É necessário investir maiores esforços para aumentar a cobertura dos mesmos e assim poder oferecer uma Atenção à Saúde da Criança de melhor qualidade no município de Manacapuru

Macrophage Gal/GalNAc lectin 2 (MGL2)+ peritoneal antigen presenting cells during Fasciola hepatica infection are essential for regulatory T cell induction

Fasciola hepatica, one of the agents that causes fasciolosis, modulates the host immune system to allow parasite survival in the host. F. hepatica expresses carbohydrate-containing glycoconjugates that are decoded by C-type lectin receptors, such as Dectin-1, mannose receptor, DC-SIGN and MGL, that are mainly present on myeloid antigen presenting cells (APCs) and can mediate immunoregulatory properties on T cells. In particular, Macrophage Gal/GalNAc lectin 2 (MGL2) expands modified Th2 immune responses, while suppressing Th1 polarization, upon recognition of GalNAc-glycosylated parasite components. In this study, by using MGL2-DTR transgenic mice that encode human diphtheria toxin receptor in MGL2+ cells, we demonstrate the role of peritoneal APCs during F. hepatica infection in favoring parasite survival. This process might be mediated by the induction of splenic Tregs in vivo, since the depletion of MGL2+ cells conferred mice with partial resistance to the infection and abrogated the increase of CD4+/CD25+ FoxP3+ Tregs induced by the parasite. Therefore, MGL2+ cells are critical determinants of F. hepatica infection and could constitute immune checkpoints to control parasite infection.Agencia Nacional de Investigación e InnovaciónPrograma de Desarrollo de las Ciencias Básica

Heme-Oxygenase-1 Attenuates Oxidative Functions of Antigen Presenting Cells and Promotes Regulatory T Cell Differentiation during Fasciola hepatica Infection

Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis.Agencia Nacional de Investigación e InnovaciónPrograma de Desarrollo de las Ciencias Básica

Gastric-resistant isoniazid pellets reduced degradation of rifampicin in acidic medium

Isoniazid and rifampicin are considered the first-line medication for preventing and treating tuberculosis. Rifampicin is degraded in the stomach acidic environment, especially when combined with isoniazid, factor contributing to treatment failure. In this study, gastric-resistant isoniazid pellets were obtained to physical contact of this drug with rifampicin and to bypass the stomach´s acidic environment. The pellets were fabricated using the extrusion-spheronization technique. The coating process was conducted in a fluid spray coater using Acrycoat L 100(r) solution as the coating agent. The pellets obtained were submitted to a dissolution test in HCl 0.1 N and phosphate buffer media. The results indicated that optimum gastric-resistance was only attained with the highest amount of coating material, with isoniazid almost fully released in phosphate buffer. The amount of rifampicin released from its mixture with non-coated isoniazid pellets in HCl 0.1 N was less than that released from its mixture with the enteric-coated pellets. Acrycoat L 100(r) was shown to be an effective enteric/gastric-resistant coating since the stability of rifampicin appeared to be enhanced when physical contact of this drug with isoniazid was prevented at low pH.Isoniazida e rifampicina são fármacos de primeira escolha para a prevenção e tratamento da tuberculose. A rifampicina degrada-se em condições ácidas do estômago, principalmente na presença da isoniazida, o que contribui para a falha do tratamento. O presente trabalho teve como objetivo a obtenção de péletes de isoniazida gastrorresistentes, visando a evitar contato da rifampicina com isoniazida e consequente degradação no meio ácido estomacal. Os péletes foram produzidos pela técnica de extrusão-esferonização. O processo de revestimento foi conduzido em leito fluidizado com solução orgânica de Acrycoat L 100(r). Os péletes obtidos foram submetidos ao teste de dissolução em HCl 0,1 N e tampão fosfato. Os resultados indicam que a gastrorresistência foi obtida somente com a maior quantidade de revestimento, sendo a isoniazida liberada completamente no meio tampão fosfato. A quantidade de rifampicina dissolvida em meio ácido, quando associada a péletes de isoniazida não revestidos, foi menor do que a observada na presença de péletes de liberação entérica. O polímero Acrycoat L 100(r) mostrou-se eficiente para o recobrimento com a função de gastrorresistência, indicando que a instabilidade da rifampicina pode ser reduzida nas associações com a isoniazida através do revestimento entérico da isoniazida

Liver function markers and haematological dynamics during acute and chronic phases of experimental Fasciola

Fasciola hepatica, a worldwide-distributed liver fluke, is one of the causative agents of fasciolosis, a zoonotic disease that affects livestock and humans. In livestock, fasciolosis causes huge economic losses worldwide, reducing animal fertility, milk production, weight gain and condemnation of livers. In spite of the availability of drugs, such as triclabendazole (TCZ), for the treatment of fasciolosis, they do not necessarily prevent liver damage or parasite reinfection and can eventually increase parasite resistance. The aim of this research was to relate the hepatic function, haematological parameters, leukocyte counts in circulation and parasite egg shedding during F. hepatica acute and chronic phases of infection in cattle as well as to determine how these parameters change with TCZ-treatment of chronically infected cattle. Our results show that increased levels of serum aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) were detected in early stages of the experimental infection. Moreover, high circulating eosinophil count and plateletcrit levels were correlated with fluke number in livers from infected cattle. On the other hand, although TCZ-treatment in the chronic phase of infection reduced parasite burden and damage in the liver, it was not able to completely avoid them. In conclusion, our work sheds light into the physiopathological mechanisms induced during fluke infection in cattle, revealing the complexity of the host response to the infection, together with the effects of TCZ-treatment in chronically infected animals.Agencia Nacional de Investigación e InnovaciónInstituto Nacional de Investigación Agropecuari

The tumor-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer

Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay -- Contacto: [email protected] is a leading cause of death worldwide, accounting for nearly 10 million deaths. Among breast cancers (BC) subtypes, triple-negative (TN) BC is characterized by metastatic progression and poor patient prognosis. Although TNBC is initially sensitive to chemotherapy, many TNBC patients rapidly develop resistance, at which point metastatic disease is highly lethal. Cancer cells present phenotypic changes or molecular signatures that distinguish them from healthy cells. The Tn antigen (GalNAc-O-Thr/Ser), which constitutes a powerful tool as tumor marker, was recently reported to contribute to tumor growth. However, its role in BC-derived metastasis has not yet been addressed. In this work, we generated a pre-clinical orthotopic Tn+ model of metastatic TNBC, which mimics the patient surgical treatment and is useful to study the role of Tn in metastasis and immunoregulation. We obtained two different cell clones, which differed in their Tn antigen expression: a high Tn-expressing and a non-expressing clone. Interestingly, the Tn-positive cell line generated significantly larger tumors and higher degree of lung metastases associated with a lower survival rate than the Tn-negative and parental cell line. Furthermore, we also found that both tumors and draining-lymph nodes from Tn+-tumor-bearing mice presented a higher frequency of CD4+ FoxP3+ T cells, while their splenocytes expressed higher levels of IL-10. In conclusion, this work suggests that the Tn antigen participates in breast tumor growth and spreading, favoring metastases to the lungs that are associated with an immunoregulatory state, suggesting that Tn-based immunotherapy could be a strategy of choice to treat these tumors

Evaluation of early nephrostomy in patients with post-renal acute renal failure with advanced Cervical Cancer

Introduction: Cervical cancer is the fourth most common type of cancer among women, except for cases of non-melanoma skin. However, the state of Amazonas has the highest incidence rate of new cases per year. Objectives: To determine the prognostic impact of early nephrostomy in patients with advanced cervical cancer who present post-renal acute renal failure. Methods: This prospective cohort study was carried out with patients with locally advanced cervical cancer, who evolved with post-renal acute renal failure. Results: 25 patients were included in the study, 52% (13/25) died, 32% (8/25) lost outpatient follow-up and 16% (4/25) returned for follow-up. Of the total, 16% (04/25) underwent renal ultrasonographic reassessment, with 75% (3/4) having unilateral nephrostomy and 25% (1/4) having bilateral. It was not possible to assess the impact of cortical thickness on renal function, due to the lack of indicators used to assess the improvement in renal function. Conclusion: In this study, the relationship between low socioeconomic levels and late diagnosis of cervical cancer was observed. Knowledge of this population's clinical, and socioeconomic profile, and outcomes is essential to guide more robust studies and improve the clinical management of these patients. In addition, promote discussions on the importance of access to information, health services, and preventive measures essential to survival

STUCK IN A MOMENT: TONIC IMMOBILITY PREDICTS POOR QUALITY OF LIFE IN TREATED PTSD PATIENTS

Background: Posttraumatic stress disorder (PTSD) is a prevalent and disabling multisystem disorder, with significant physical and psychiatric morbidity and poor quality of life (QOL). Although peritraumatic reactions - tonic immobility and dissociation - are established predictors of PTSD severity and development, there is a dearth of investigation assessing the impact of peritraumatic reactions on QOL of PTSD patients. Quality of life has become increasingly important in health care and research as a reliable outcome measure. It comprises psychological, physical, social and environmental domains, providing important information about the impact of diseases on patient\u27s life. This study aims to investigate the impact of peritraumatic tonic immobility and peritraumatic dissociation on QOL of PTSD civilian outpatients. Subjects and methods: It is a cross-sectional study of 50 victims of urban violence with current PTSD, recruited in a specialized outpatient clinic. Instruments used were: Structured Clinical Interview IV, Peritraumatic Dissociative Experiences Questionnaire, Tonic Immobility Scale and WHOQOL-BREF (psychological, physical, social and environmental domains). Linear regression models were fitted to evaluate the impact of peritraumatic reactions - tonic immobility and dissociation - on WHOQOL-BREF scores. We controlled for sex as potential confounding. Results: The severity of peritraumatic tonic immobility negatively impacted on psychological and environment domains of quality of life. For each additional point on the Tonic Immobility Scale, there was a decreased of 0.8 points on the scores of these domains of WHOQOL-BREF. Neither the peritraumatic reactions showed effects on physical nor social domains. Possible limitations of this study include cross-sectional design, relatively small sample size of tertiary center outpatients and recall bias. Conclusions: Peritraumatic tonic immobility is related to poor quality of life, adding new insights about the relationship between this immobility reaction and PTSD