Hospital Universitário Getúlio Vargas

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.

This article describes the positive and transforming experience of the 'health education' practice, highlighting the results produced on both educators and the people who participated in the education process. The work took place in 2003 in the city of Manacapuru-Amazonas, and it consisted of educational activities designed for teenagers from a public school of the city The educative activities were based on a methodology for nursing assistance to collective health, using its phases. The results showed, in fact, that health education is essential to the reflection and change of behavior in people's lives. Therefore, health education must be systematically planned and adopted as an important role of the nursing professional.

BACKGROUND AND OBJECTIVES: Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH. METHODS: Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment. RESULTS: Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76). CONCLUSION: Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.

The presence of enthesitis is associated with higher disease activity, more disability and incapacity to work and a poorer quality of life in spondyloarthritis (SpA). There is currently no consensus on which clinical score should be used to assess enthesitis in SpA. The objective of the present work was to compare the correlation of three enthesitis indices (MASES, SPARCC and LEI) with measures of disease activity and function in a heterogeneous population of patients with axial and peripheral SpA. A cross-sectional study was conducted in three Brazilian public university hospitals; patients fulfilling ASAS classification criteria for peripheral or axial SpA were recruited and measures of disease activity and function were collected and correlated to three enthesitis indices: MASES, SPARCC and LEI using Spearman’s Correlation index. ROC curves were used to determine if the the enthesitis indices were useful to discriminate patients with active disease from those with inactive disease. Two hundred four patients were included, 71.1% ( N = 145) fulfilled ASAS criteria for axial SpA and 28.9% ( N = 59) for peripheral SpA. In axial SpA, MASES performed better than LEI ( p = 0.018) and equal to SPARCC ( p = 0.212) regarding correlation with disease activity (BASDAI) and function (BASFI). In peripheral SpA, only MASES had a weak but statistical significant correlation with DAS28-ESR (r s 0.310 p = 0.05) and MASES had better correlation with functional measures (HAQ) than SPARCC ( p = 0.034). In this sample composed of SpA patients with high coexistence of axial and peripheral features, MASES showed statistical significant correlation with measures of disease activity and function in both axial and peripheral SpA.

UNLABELLED: There are limited data regarding prevalence of Chlamydia trachomatis infection among northern Brazilian pregnant women. OBJECTIVE: The purpose of this study was to estimate the prevalence of chlamydial infection among pregnant women in their third trimester and to determine the repercussion of this infection on their offspring. METHODS: In the first phase of this study 100 pregnant women receiving prenatal care in a local public university hospital were examined to assess the prevalence of genital C. trachomatis infection by polymerase chain reaction technique. In the second phase, 88 pregnant women were prospectively evaluated for premature rupture of membranes, puerperal consequences associated with chlamydial infection, and neonates were checked for low-birth weight. RESULTS: The prevalence rate of chlamydial infection was 11%, and 72.7% of the positive participants were predominantly less than 30 years of age (p=0.1319). A total of 36.4% of the participants had premature rupture of membranes (p=0.9998). Neither low-birth weight infants nor preterm delivery were observed. A cohort of 16 newborn babies were followed-up up to 60 days of life to ascertain outcome: 50% had respiratory symptoms. Neonates born to infected mothers had a higher risk to develop respiratory symptoms in the first 60 days of life. CONCLUSION: The scarcity of data about the effects of chlamydial infection on pregnancy and neonatal outcomes justified this study. Diagnosing and treating chlamydial infection during the third trimester of pregnancy may prevent neonate infection. Therefore, preventive screening should be seen as a priority for early detection of asymptomatic C. trachomatis infection as part of local public health strategies.

Introdução: Os preceptores são profissionais do serviço/assistência que, aliado a um conhecimento pedagógico, acompanham o desenvolvimento profissional de futuros profissionais de saúde. Objetivo: Analisar a percepção sobre a atividade de preceptoria quanto aos desafios e perspectivas no Programa de Residência Multiprofissional em Saúde (PRMS). Métodos: Trata-se de um estudo quanti-qualitativo baseado na construção e validação de uma escala Atitudinal do tipo Likert. Resultados: Os resultados obtidos foram organizados em quatro dimensões: (D1) Preceptoria como fator contributivo para o processo de formação em saúde; (D2) Formação do preceptor e as competências para o exercício da preceptoria; (D3) A articulação da teoria/prática na atividade de preceptoria no programa de residência multiprofissional em saúde e (D4) Características do preceptor ideal. Conclusão: Constatou-se que o preceptor ao ampliar seu repertório técnico/profissional e pedagógico, estará favorecendo também a articulação da teoria com a prática.

SARS-CoV-2 affects mainly the lungs, however, other manifestations, including neurological manifestations, have also been described during the disease. Some of the neurological findings have involved intracerebral or subarachnoid hemorrhage, strokes, and other thrombotic/hemorrhagic conditions. Nevertheless, the gross pathology of hemorrhagic lesions in the central nervous system has not been previously described in Brazilian autopsy cases. This study aimed to describe gross and microscopic central nervous system (CNS) pathology findings from the autopsies and correlate them with the clinical and laboratory characteristics of forty-five patients with COVID-19 from Manaus, Amazonas, Brazil. Forty-four patients were autopsied of which thirty-eight of these (86.36%) were positive by RT-PCR for COVID-19, and six (13.3%) were positive by the serological rapid test. Clinical and radiological findings were compatible with the infection. The patients were classified in two groups: presence (those who had hemorrhagic and/or thrombotic manifestations in the CNS) and absence (those who did not present hemorrhagic and/or thrombotic manifestations in the CNS). For risk assessment, relative risk and respective confidence intervals were estimated. Macroscopic or microscopic hemorrhages were found in twenty-three cases (52,27%). The postmortem gross examination of the brain revealed a broad spectrum of hemorrhages, from spots to large and confluent areas and, under microscopy, we observed mainly perivascular discharge. The association analyses showed that the use of corticosteroid, anticoagulant and antibiotic had no statistical significance with a risk of nervous system hemorrhagic manifestations. However, it is possible to infer a statistical tendency that indicates that individuals with diabetes had a higher risk for the same outcome (RR = 1.320, 95% CI = 0.7375 to 2.416, p = 0.3743), which was not observed in relation to other comorbidities. It is unknown whether the new variants of the virus can cause different clinical manifestations, such as those observed or indeed others. As a result, more studies are necessary to define clinical and radiologic monitoring protocols and strategic interventions for patients at risk of adverse and fatal events, such as the extensive hemorrhaging described here. It is imperative that clinicians must be aware of comorbidities and the drugs used to treat patients with COVID-19 to prevent CNS hemorrhagic and thrombotic events.

ABSTRACT Pathology must aim at a correct and complete diagnosis for the patient, 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 review, 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.

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Liver test abnormalities are frequently observed in patients with coronavirus disease 2019 (COVID-19) and are associated with worse prognosis. However, information is limited about pathological changes in the liver in this infection, so the mechanism of liver injury is unclear. Here we describe liver histopathology and clinical correlates of 27 patients who died of COVID-19 in Manaus, Brazil. There was a high prevalence of liver injury (elevated alanine aminotransferase and aspartate aminotransferase in 44% and 48% of patients, respectively) in these patients. Histological analysis showed sinusoidal congestion and ischemic necrosis in more than 85% of the cases, but these appeared to be secondary to systemic rather than intrahepatic thrombotic events, as only 14% and 22% of samples were positive for CD61 (marker of platelet activation) and C4d (activated complement factor), respectively. Furthermore, the extent of these vascular findings did not correlate with the extent of transaminase elevations. Steatosis was present in 63% of patients, and portal inflammation was present in 52%. In most cases, hepatocytes expressed angiotensin-converting enzyme 2 (ACE2), which is responsible for binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), even though this ectoenzyme was minimally expressed on hepatocytes in normal controls. However, SARS-CoV-2 staining was not observed. Most hepatocytes also expressed inositol 1,4,5-triphosphate receptor 3 (ITPR3), a calcium channel that becomes expressed in acute liver injury. Conclusion: The hepatocellular injury that commonly occurs in patients with severe COVID-19 is not due to the vascular events that contribute to pulmonary or cardiac damage. However, new expression of ACE2 and ITPR3 with concomitant inflammation and steatosis suggests that liver injury may result from inflammation, metabolic abnormalities, and perhaps direct viral injury.

Migraine adds to the burden of patients suffering from multiple sclerosis (MS). The ID-migraine is a useful tool for screening migraine, and the Migraine Disability Assessment questionnaire can evaluate disease burden. The aim of the present study was to assess the presence and burden of migraine in patients with MS. METHODS Patients diagnosed with MS attending specialized MS units were invited to answer an online survey if they also experienced headache. RESULTS The study included 746 complete responses from patients with MS and headache. There were 625 women and 121 men, and 69% of all the patients were aged between 20 and 40 years. Migraine was identified in 404 patients (54.1%) and a moderate-to-high burden of disease was observed in 68.3% of the patients. CONCLUSION Migraine is a frequent and disabling type of primary headache reported by patients with MS.

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin associated with oxidative stress. The present study aimed to investigate the presence of oxidative stress in patients with newly diagnosed SLE. SLE patients (n = 36) and control subjects (n = 28) were enrolled in this study. Blood samples were used for malondialdehyde (MDA), sulfhydryl groups (SH) and uric acid determination. MDA levels (µmol/L) were higher in patients (3.9 ± 2.6) than in control subjects (1.6 ± 2.6). SH were significantly lower in SLE patients. The findings suggest that MDA can be a good marker of oxidative stress in SLE.

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

INTRODUCTION: Electron microscopy (EM) is a rapid and effective tool that can be used to create images of a whole spectrum of virus-host interactions and, as such, has long been used in the discovery and description of viral mechanisms. METHODS: Electron microscopy was used to evaluate the pulmonary pathologies of postmortem lung sections from three patients who died from infection with SARS-associated coronavirus 2 (SARS-CoV-2), a new member of the Coronaviridae family. RESULTS: Diffuse alveolar damage (DAD) was predominant in all three patients. The early exudative stage was characterized principally by edema and extravasation of red blood cells into the alveolar space with injury to the alveolar epithelial cells; this was followed by detachment, apoptosis, and necrosis of type I and II pneumocytes. The capillaries exhibited congestion, exposure of the basement membrane from denuded endothelial cells, platelet adhesion, fibrin thrombi, and rupture of the capillary walls. The proliferative stage was characterized by pronounced proliferation of type II alveolar pneumocytes and multinucleated giant cells. The cytopathic effect of SARS-CoV-2 was observed both in degenerated type II pneumocytes and freely circulating in the alveoli, with components from virions, macrophages, lymphocytes, and cellular debris. CONCLUSIONS: Viral particles consistent with the characteristics of SARS-CoV-2 were observed mainly in degenerated pneumocytes, in the endothelium, or freely circulating in the alveoli. In the final stage of illness, the alveolar spaces were replaced by fibrosis.

Case of a Retroperitoenal Mucinous Cystadenoma in Korea: A Case Report. The Korean Journal of Internal Medicine 2004;19:282-284. 6. Matsubara M, Shiozawa T, Tachibana R, Hondo T, Osasda K, Kawaguchi K, et al. Primary retroperitoneal mucinous cystadenoma of borderline malignancy: a case report and review of the literature. International Journal of Gynecological Pathology 2005;24:218–23. 7. Pennell TC, Gusdon Jr JP. Retroperitoneal mucinous cystadenoma. American Journal of Obstetrics and Gynecology 1989;160:1229–31. 8. Lai KKT, Chan YYR, Chin ACW, Ng WF, Huang YHH, Mak YLM, et al. Primary retroperitoneal mucinous cystadenoma in a 52-year-old man. Journal of Hong Kong College Of Radiologists 2004;7:223–5. 9. Tapper EB, Shrewsberry AB, Oprea G, Majmudar B. A unique benign mucinous cystadenoma of the retroperitoneum: a case report and review of the literature. Archives of Gynecology and Obstetrics 2010;281:167–9.

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

Silicosis is the most frequent pneumoconiosis, resulting from the inhalation of mineral dust containing silica or silicates. It is mainly characterized by irreversible lung fi brosis, being associated with the development of other diseases, such as pulmonary tuberculosis, lung cancer and autoimmune conditions. The connective tissue disease following exposure to silica occurs usually 15 years after the initial exposure. Erasmus syndrome consists of the association of systemic sclerosis following exposure to silica with or without silicosis. We report the cases of two patients diagnosed with silicosis, who developed systemic sclerosis. A silicose é a pneumoconiose mais frequente, decorrente da inalação de sílica ou de poeiras minerais contendo silicatos, caracterizada principalmente pela fi brose pulmonar de caráter irreversível. Está associada com o desenvolvimento de outras doenças, incluindo tuberculose pulmonar, câncer pulmonar e doenças autoimunes. A doença do tecido conjuntivo posterior à exposição à sílica ocorre geralmente após 15 anos do início da exposição. A síndrome de Erasmus refere-se ao desenvolvimento de esclerose sistêmica em indivíduos previamente expostos à sílica e que apresentavam ou não silicose. Os autores relatam dois casos de pacientes com diagnóstico de silicose que desenvolveram esclerose sistêmica.

American cutaneous leishmaniasis (ACL) is a zoonosis caused by Leishmania genusflagellates. ACL develop in man when he enters zoonotic areas in deforestation andextractivism sites. In Brazil, ACL has an endemic character and it is distributed in allstates of the country. In Amazonas, according to the State Department of Health data(2005), the municipalities of Manaus and Rio Preto da Eva are the first and secondcities, respectively, in number of cases. In Rio Preto da Eva, about 80% cases of ACLderive from rural settlements along the AM-010 road. In Rio Preto da Eva’s hospital,113 cases of ACL were diagnosed from 141 examined patients from all ages and bothsexes. The patients consisted predominantly of males (68.1%), with ages varyingbetween 20 and 39 years old (40.4%), and farmers (49.1%). All patients presentedcutaneous lesions, mainly in lower extremities (36.2%). New studies to map riskareas, as well as the identification of the causing and transmitting agents of ACL, mayhelp to recommend more effective proposals for the control of this disease.

INTRODUCTION: Post-traumatic diaphragmatic hernias are not commonly diagnosed immediately after the initial trauma. There is a greater prevalence of left hernias due to the fragility or injury in diaphragm muscle and the lack of solid and fixed structures on the left side. PRESENTATION OF CASE: A male patient, 30 years old, he was admitted to the emergency department presenting diffuse abdominal pain, vomiting, dyspnea, pain in the left hemithorax with worsening during forced inspiration. After performing X-ray and computed tomography (CT), the presence of organs in the abdominal cavity outside the usual position was evidenced and with discrete deviation. Immediate surgery was performed with posterolateral thoracic access through the sixth left intercostal space combined with left subcostal access. Initially, it was found jejunum, ileum and left colonic flexure and accessory spleen filling the hernial sac. DISCUSSION: This report is the first case to report two accessory spleens in manual reduction of herniation between thoracic and abdominal cavities after trauma and percutaneous perforation. The splenectomy performed in both organs occurred due to their advanced ischemia that was due to reduced vascularity. CONCLUSION: The presence of the reported accessory spleen inside the thoracic cavity is only a possible variation within the possibilities in cases of diaphragmatic hernias, which does not modify the surgical procedure in a relevant way.