Cetacean Intracytoplasmic Eosinophilic Globules: A Cytomorphological, Histological, Histochemical, Immunohistochemical, and Proteomic Characterization.

The nature, etiopathogenesis, and clinicopathologic relevance of the prevalent intracytoplasmic eosinophilic globules (IEGs) within hepatocytes of cetaceans are unknown. This study aims to evaluate the presence and characterize the IEGs in the hepatocytes of cetaceans using histochemical and immunohistochemical electron microscopy, Western blot, lectin histochemistry, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry techniques. A total of 95/115 (83%) animals (16 species) exhibited histologically evident intracytoplasmic round to oval, single to multiple, hyaline eosinophilic globules within the hepatocytes. These globules were largely PAS-positive, diastase resistant, and were immunopositive for fibrinogen (FB, 97%), albumin (Alb, 85%), and α1-antitrypsine (A1AT, 53%). The IEG positivity for FB and A1AT were correlated with live-stranding, hepatic congestion and a good nutritional status. The cetaceans lacking IEGs were consistently dead stranded and had poor body conditions. The IEGs in 36 bycaught cetaceans were, all except one, FB-positive and A1AT-negative. The IEGs exhibited morphologic and compositional variations at the ultrastructural level, suggesting various stages of development and/or etiopathogenesis(es). The glycocalyx analysis suggested an FB- and A1AT-glycosylation pattern variability between cetaceans and other animals. The proteomic analyses confirmed an association between the IEGs and acute phase proteins, suggesting a relationship between acute stress (i.e., bycatch), disease, and cellular protective mechanisms, allowing pathologists to correlate this morphological change using the acute hepatocytic cell response under certain stress conditions.

Fetal Deaths in SARS-CoV-2-Infected Pregnant Women: A Portuguese Case Series.

Introduction: Stillbirth has been documented as an outcome of SARS-CoV-2 infection in pregnancy. Placental hypoperfusion and inflammation secondary to maternal immune response seem to play a role in the cascade of events that contribute to fetal death. The aim of our study is to report a perinatal outcome of SARS-CoV-2 infection in pregnancy adding information to the pool of data on COVID-19 pregnancy outcomes. Case Presentation. This is the first stillbirth case series occurring in pregnant women infected with SARS-CoV-2 in a Portuguese cohort. Between April 2020 and March 2021, we had 2680 births in our centre, of which 130 (4.95%) involved mothers infected with SARS-CoV-2. Of total births, there were 14 stillbirths (0.52%), accounting for the highest stillbirth rate we have had in the last 5 years. Among these 14 stillbirths, 5 (35.71%) occurred in SARS-CoV-2-infected mothers. We report the clinical features and placental histopathologic findings of 4 stillbirth cases that occurred in our hospital. Discussion. The stillbirth rate among SARS-CoV-2-infected pregnant women (5/130; 3.84%) was significantly increased compared to noninfected patients (9/2550; 0.35%). Most women (3/4) were asymptomatic for COVID-19, a surprising outcome, given the current literature. All cases had histologic exams showing placental signs of vascular malperfusion, although we acknowledge that 3/5 had obstetric conditions related to placental vascular impairment such as preeclampsia and HELLP syndrome. Conclusion: Stillbirth can be a perinatal consequence of SARS-CoV-2 infection in pregnancy, even in asymptomatic patients. We urge more studies to explore the association between SARS-CoV-2 infection and the risk of stillbirth.

Dietary patterns and associated factors of children under two years of age born prematurely.

OBJECTIVE: To identify the dietary patterns and associated factors of children aged between 6 and 23 months, born prematurely and assisted at a University Hospital in Curitiba, state of Paraná, Brazil. METHODS: The parents or guardians of the 135 children were asked about their children's eating habits and the family's socioeconomic and demographic conditions. Information regarding birth and health history were obtained from medical records. Data on food consumption were subjected to exploratory factor analysis and the principal component analysis method was used to estimate the factor loads. Multiple linear regression was performed to verify possible associations. RESULTS: Two dietary patterns were observed: "unhealthy" and "healthy." The "unhealthy" pattern was significantly associated with maternal age, the child's corrected age, and gestational age at birth. The "healthy pattern" was associated with the child's corrected age. Maternal age and child's corrected age remained significant after multiple regression analyses. For the "unhealthy" pattern, a positive effect was observed, suggesting that the consumption of this pattern is higher as the child's age increases and less intense for children with mothers aged 30 years or older. For the "healthy" dietary pattern, the same two variables showed statistical significance. The authors observed a direct proportion between the age and consumption of food groups in both patterns. CONCLUSIONS: These results indicate the importance of nutritional education for younger mothers regarding their children's eating practices, especially as the child grows.

Consumption of food groups and associated factors among children aged 6 to 23 months.

OBJECTIVE: To assess the consumption of food groups among children aged 6 to 23 months in day care centers and at home and its associated factors. METHODS: This is a population-based cross-sectional study conducted with children from nursery schools in Guaratuba, Paraná. Parents answered a socioeconomic and demographic questionnaire. Food consumption was assessed by directly weighing the meals offered at the day care center. At home, parents filled an estimated food record. The reported foods were classified into seven food groups. Minimum dietary diversity was calculated by the proportion of children who consumed foods from four or more groups. Data were analyzed by simple and multiple logistic regression, presented as odds ratios. RESULTS: A total of 213 children participated in this study. The average number of food groups consumed was 4.2±1.0 at home and 4.2±1.2 in day care centers. At the day care center, all children consumed grains, roots, and tubers, while at home, this rate was 99.1%. The egg group was the least consumed both at day care (6.6%) and at home (2.8%). At home, more than 60% of children consumed sweets and sugar-sweetened beverages. Children aged 12 to 23 months were more likely to consume milk and dairy products, as well as flesh foods. Higher income was associated with the consumption of legumes, and older maternal age with the consumption of fruits and vegetables. CONCLUSIONS: At home, children had a predominantly dairy-based diet and a high intake of ultra-processed foods. In day care centers, the consumption of healthy foods was higher, indicating the need for families to participate in the formation of healthy eating habits.

Dietary patterns and associated factors of children under two years of age born prematurely / Padrões alimentares e fatores associados de crianças menores de dois anos nascidas prematuramente

ABSTRACT Objective: To identify the dietary patterns and associated factors of children aged between 6 and 23 months, born prematurely and assisted at a University Hospital in Curitiba, state of Paraná, Brazil. Methods: The parents or guardians of the 135 children were asked about their children's eating habits and the family's socioeconomic and demographic conditions. Information regarding birth and health history were obtained from medical records. Data on food consumption were subjected to exploratory factor analysis and the principal component analysis method was used to estimate the factor loads. Multiple linear regression was performed to verify possible associations. Results: Two dietary patterns were observed: "unhealthy" and "healthy." The "unhealthy" pattern was significantly associated with maternal age, the child's corrected age, and gestational age at birth. The "healthy pattern" was associated with the child's corrected age. Maternal age and child's corrected age remained significant after multiple regression analyses. For the "unhealthy" pattern, a positive effect was observed, suggesting that the consumption of this pattern is higher as the child's age increases and less intense for children with mothers aged 30 years or older. For the "healthy" dietary pattern, the same two variables showed statistical significance. The authors observed a direct proportion between the age and consumption of food groups in both patterns. Conclusions: These results indicate the importance of nutritional education for younger mothers regarding their children's eating practices, especially as the child grows.

RESUMO Objetivo: Identificar os padrões alimentares e fatores associados de crianças entre seis e 23 meses de idade, nascidas prematuramente e assistidas em um Hospital Universitário de Curitiba, Paraná. Métodos: Os pais ou responsáveis pelas 135 crianças foram questionados quanto aos hábitos alimentares dos filhos e as condições socioeconômicas e demográficas da família. Informações relativas ao nascimento e ao histórico de saúde foram obtidas dos prontuários. Os dados de consumo alimentar foram submetidos a análise fatorial exploratória e o método dos componentes principais foi utilizado para estimar as cargas fatoriais. Regressão linear múltipla foi realizada para verificar possíveis associações. Resultados: Foram observados dois padrões alimentares distintos. Aquele denominado de "não saudável" apresentou associação significativa com a idade materna, a idade corrigida da criança e a idade gestacional ao nascer. Por sua vez, o padrão denominado de "saudável" esteve associado à idade corrigida da criança. As variáveis idade materna e idade corrigida da criança permaneceram significativas após as análises de regressão múltipla. Para o padrão "não saudável", observou-se um efeito positivo, o que sugere que seu consumo é maior conforme a idade da criança aumenta e menos intenso para crianças com mães de 30 anos de idade ou mais. Para o padrão "saudável", as mesmas duas variáveis mostraram significância estatística. Observamos uma proporção direta entre idade e consumo dos grupos alimentares em ambos os padrões. Conclusões: Esses resultados apontam para a importância da educação nutricional de mães mais jovens quanto às práticas alimentares de seus filhos, especialmente à medida que a criança cresce.

Characteristics of Reliever Inhaler Users and Asthma Control: A Cross-Sectional Multicenter Study in Portuguese Community Pharmacies.

PURPOSE: SABA overuse might indicate poorly managed or uncontrolled asthma and be responsible for poor health outcomes. The aim of this study integrated in new fourth multi-design SABINA+ pillar was to characterize the population using short-acting ß2-agonists for asthma and examine the patterns of its use among community pharmacy customers in Portugal, as well as identify characteristics associated with disease control and explore potential differences between GINA treatment steps. PATIENTS AND METHODS: This cross-sectional multicenter study was conducted in Portuguese community pharmacies between 29 May 2018 and 15 August 2018. Participants were adults (age ≥18 years) self-reporting asthma diagnosis recruited in the context of a short-acting ß2-agonist dispense. A two-part questionnaire (pharmacist interview and self-administered) was used to collect information about sociodemographic characteristics, comorbidities, reliever inhaler use, healthcare resource consumption and self-reported disease control (assessed by the Control of Allergic Rhinitis and Asthma Test - CARAT®). Descriptive statistics was done to characterize the study sample. After categorizing patients according to GINA steps, based on their therapeutic regimen, we performed an exploratory subgroup analysis to evaluate if there were any differences between such groups in terms of the variables collected. A logistic regression was used to identify the potential determinants of overall disease control. RESULTS: Around 50.8% of patients were male, and the average age was 52 years old. Half of the patients never smoked, and 51.9% were employed. More than half of the patients report inhaler overreliance - purchasing more than 1 pack in 3 months (65.0%) or using the inhaler on more than 8 days over the previous 4 weeks (50.2%). Of the total number of patients in the study, 79.1% had poorly controlled asthma symptoms, and 78.7% had overall poorly controlled respiratory symptoms. We found statistically significant differences between GINA treatment steps in all sociodemographic characteristics (sex, mean age, education level, employment status); maximum number of SABA uses in 24h, CARAT score (total an asthma sub-score); history of exacerbations requiring ED visits or treatment with OCS for at least 3 days in the previous 12 months. Logistic regression revealed that patients reporting SABA use in more than 8 days in the previous 4 weeks and patients with at least 1 exacerbation requiring treatment with OCS for at least 3 days in the previous 12 months have greater odds of poor disease control [adjusted OR (95% CI): 2.6 (1.3-5.2) and 3.0 (1.3-6.6)]. CONCLUSION: Based on the results of this study, it can be inferred that the asthma population using SABA is largely uncontrolled and uses reliever inhalers excessively.

Association between physical activity practice and food consumption in school teenagers / Associação entre prática de atividade física e consumo alimentar em adolescentes escolares

ABSTRACT Adolescence is a period of transition, marked by habits that can influence the health of individuals in the long run. This study aimed to analyze the association between physical activity and food consumption in adolescents. This is a cross-sectional study with a probabilistic sample of 1.570 school adolescents from Montes Claros, MG, Brazil. The level of physical activity and consumption of fruits, vegetables, sweets, and soda/soft drinks was analyzed. Logistic regression was performed (significance level 5%). Among adolescents, 80.8% were classified as not active and practiced physical activity for at least 60 minutes in less than five days a week. In relation to food, 85.2% and 34.3% of adolescents reported consuming legumes and fruits less than three times a week, respectively. Consumption five times a week or more of treats was 64.1% and soft drinks 90.3%. Those who consumed fruit three times a week or less were 40% more likely to be less active. Those who consumed soda more than five times a week were twice as likely to be little active. Low levels of physical activity were associated with consumption of fruit less than or equal to three times a week and soft drinks greater than five times a week. There is a need to encourage the promotion of healthy lifestyle habits regarding the practice of physical activity and food consumption among adolescents, in school and family contexts.

RESUMO A adolescência é um período de transição, marcado por hábitos que podem influenciar a saúde dos indivíduos a longo prazo. Este estudo objetivou analisar a associação entre a prática de atividade física e o consumo alimentar em adolescentes. Trata-se de estudo transversal com amostra probabilística de 1.570 adolescentes escolares de Montes Claros, MG. Analisou-se nível de atividade física e consumo de frutas, leguminosas, guloseimas e refrigerante. Foi realizada regressão logística (nível de significância 5%). Entre os adolescentes 80,8% foram classificados como pouco ativos e praticavam atividade física por pelo menos 60 minutos em menos do que cinco dias por semana. Em relação à alimentação, 85,2% e 34,3% dos adolescentes relataram consumo de leguminosas e frutas com frequência menor que três vezes por semana, respectivamente. O consumo cinco vezes por semana ou mais de guloseimas foi de 64,1% e refrigerantes de 90,3%. Os que consumiam frutas três vezes por semana ou menos apresentaram chance 40% maior de serem pouco ativos. Os que consumiam refrigerante com frequência superior a cinco vezes por semana apresentaram chance duas vezes mais alta de serem pouco ativos. Baixos níveis de atividade física foram associados ao consumo de frutas menor ou igual a três vezes por semana e de refrigerantes superior a cinco vezes por semana. Há necessidade de incentivo à promoção de hábitos de vida saudáveis quanto à prática de atividade física e ao consumo alimentar entre os adolescentes nos contextos escolar e familiar.

Retrospective Study of Fishery Interactions in Stranded Cetaceans, Canary Islands.

Estimating cetacean interactions with fishery activities is challenging. Bycatch and chronic entanglements are responsible for thousands of cetacean deaths per year globally. This study represents the first systematic approach to the postmortem investigation of fishery interactions in stranded cetaceans in the Canary Islands. We retrospectively studied 586 cases necropsied between January 2000 and December 2018. Of the cases with a known cause of death, 7.4% (32/453) were due to fishery interactions, and the Atlantic spotted dolphin (Stenella frontalis) was the most affected species [46.9% (15/32)]. Three types of fishery interactions were recognized by gross findings: bycatch [65.6% (21/32)], chronic entanglements [18.8% (6/32)], and fishermen aggression [15.6% (5/32)]. Among the bycaught cases, we differentiated the dolphins that died because of ingestion of longline hooks [23.8% (5/21)] from those that died because of fishing net entrapments [76.2% (16/21)], including dolphins that presumably died at depth due to peracute underwater entrapment (PUE) [37.5% (6/16)], dolphins that were hauled out alive and suffered additional trauma during handling [43.8% (7/16)], and those that were released alive but became stranded and died because of fishery interactions [18.7% (3/16)]. Gross and histologic findings of animals in each group were presented and compared. The histological approach confirmed gross lesions and excluded other possible causes of death. Cetaceans in good-fair body condition and shallow diving species were significantly more affected by fishery interactions, in agreement with the literature. Low rates of fishery interactions have been described, compared with other regions. However, within the last few years, sightings of entangled live whales, especially the minke whale (Balaenoptera acutorostrata) and Bryde's whale (B. edeni), have increased. This study contributes to further improvement of the evaluation of different types of fishery interactions and may facilitate the enforcement of future conservation policies to preserve cetacean populations in the Canary Islands.

The Pathology of Cetacean Morbillivirus Infection and Comorbidities in Guiana Dolphins During an Unusual Mortality Event (Brazil, 2017-2018).

Cetacean morbillivirus (CeMV; Paramyxoviridae) is the most significant pathogen of cetaceans worldwide. The novel "multi-host" Guiana dolphin (Sotalia guianensis; GD)-CeMV strain is reported in South American waters and infects Guiana dolphins and southern right whales (Eubalaena australis). This study aimed to describe the pathologic findings, GD-CeMV viral antigen distribution and detection by RT-PCR (reverse transcriptase polymerase chain reaction), and infectious comorbidities in 29 Guiana dolphins that succumbed during an unusual mass-mortality event in Rio de Janeiro state, Brazil, between November 2017 and March 2018. The main gross findings were lack of ingesta, pulmonary edema, ascites, icterus, hepatic lipidosis, multicentric lymphadenomegaly, as well as pneumonia, polyserositis, and multiorgan vasculitis caused by Halocercus brasiliensis. Microscopically, the primary lesions were bronchointerstitial pneumonia and multicentric lymphoid depletion. The severity and extent of the lesions paralleled the distribution and intensity of morbilliviral antigen. For the first time in cetaceans, morbilliviral antigen was detected in salivary gland, optic nerve, heart, diaphragm, parietal and visceral epithelium of glomeruli, vulva, and thyroid gland. Viral antigen within circulating leukocytes suggested this as a mechanism of dissemination within the host. Comorbidities included disseminated toxoplasmosis, mycosis, ciliated protozoosis, and bacterial disease including brucellosis. These results provide strong evidence for GD-CeMV as the main cause of this unusual mass-mortality event.

Cetuximab versus bevacizumab in metastatic colorectal cancer: a comparative effectiveness study.

PURPOSE: Uncertainty exists regarding comparative effectiveness of cetuximab versus bevacizumab in metastatic colorectal cancer (mCRC). We conducted a retrospective head-to-head multi-cohort study comparing clinical outcomes from both antibodies METHODS: Cohorts were defined by treatment line and subgroups by (K)RAS status and tumour sidedness. Among other outcomes, we estimated and compared response rates, progression-free (PFS) and overall survival (OS). RESULTS: Between January 2010 and April 2018, 311 patients were included. Except for (K)RAS mutation status, baseline characteristics were balanced across treatment groups. In the full analysis of first and second-line cohorts, PFS (first-line: HR = 0.85; 95% CI 0.64 to 1.13; P = 0.26; second-line: HR = 1.16; 95% CI 0.74 to 1.83; P = 0.51) and OS (first-line: HR = 0.83; 95% CI 0.61 to 1.15; P = 0.26; second-line: HR = 0.88; 95% CI 0.56 to 1.38; P = 0.58) were similar between bevacizumab and cetuximab arms. In subgroup analyses of first-line therapy, we found a survival difference favouring bevacizumab in right-sided tumours (PFS: HR = 0.52; 95% CI 0.29 to 0.93; P = 0.025; OS: HR = 0.60; 95% CI 0.32 to 1.12; P = 0.11), but not in left-sided (HR = 1.04; 95% CI 0.75 to 1.46; P = 0.81; OS: HR = 0.94; 95% CI 0.65 to 1.36; P = 0.74), or (K)RAS wild-type tumours (PFS: HR = 0.91; 95% CI 0.60 to 1.40; P = 0.67; OS: HR = 0.79; 95% CI 0.50 to 1.25; P = 0.31). Response rates were similar across treatment groups, except for the subgroup of patients bearing right-sided primaries, where bevacizumab performed substantially better. CONCLUSION: This study provides evidence suggesting bevacizumab and cetuximab lead to similar effectiveness outcomes in mCRC, except for right-sided tumours, where cetuximab seemed to show considerably poorer outcomes. Further research is needed to confirm these results.

Detection of live M. bovis BCG in tissues and IFN-γ responses in European badgers (Meles meles) vaccinated by oropharyngeal instillation or directly in the ileum.

BACKGROUND: Oral vaccination with Mycobacterium bovis Bacille of Calmette and Guerin (BCG) has provided protection against M. bovis to badgers both experimentally and in the field. There is also evidence suggesting that the persistence of live BCG within the host is important for maintaining protection against TB. Here we investigated the capacity of badger inductive mucosal sites to absorb and maintain live BCG. The targeted mucosae were the oropharyngeal cavity (tonsils and sublingual area) and the small intestine (ileum). RESULTS: We showed that significant quantities of live BCG persisted within badger in tissues of vaccinated badgers for at least 8 weeks following oral vaccination with only very mild pathological features and induced the circulation of IFNγ-producing mononuclear cells. The uptake of live BCG by tonsils and drainage to retro-pharyngeal lymph nodes was repeatable in the animal group vaccinated by oropharyngeal instillation whereas those vaccinated directly in the ileum displayed a lower frequency of BCG detection in the enteric wall or draining mesenteric lymph nodes. No faecal excretion of live BCG was observed, including when BCG was delivered directly in the ileum. CONCLUSIONS: The apparent local loss of BCG viability suggests an unfavorable gastro-enteric environment for BCG in badgers, which should be taken in consideration when developing an oral vaccine for use in this species.

Incidência de tuberculose extrapulmonar / Incidence of extrapulmonary tuberculosis

Objetivo: Analisar casos de tuberculose extrapulmonar no um Estado brasileiro e comparar com valores de países industrializados. Métodos: Estudo epidemiológico descritivo, de delineamento retrospectivo e transversal na coleta de dados, com abordagem quantitativa. Os dados foram obtidos por meio de consulta às bases de dados do sistema TABNET, disponibilizados pelo Departamento de Informática do Sistema Único de Saúde (DATASUS), com acesso em março de 2017. A população do estudo foi constituída pelos casos de tuberculose extrapulmonar do Estado de Minas Gerais registrados no período entre 2011 e 2016. Resultados: Foram contados 3.663 casos de tuberculose extrapulmonar no período considerado para estudo, com estabilização do número de casos no primeiro triênio ­ 715 (2011), 706 (2012) e 715 (2013). Apesar da tendência observada na primeira metade do período estudado, houve diminuição do número de casos nos 3 meses seguintes ­ 716 (2014), 663 (2015) e 148 (2016). Com a redução no número de casos na metade mais recente do período estudado, o Estado de Minas Gerais acompanhou a tendência de países desenvolvidos em relação à redução no número de casos de tuberculose. No entanto, apesar da diminuição dos casos para o acometimento extrapulmonar, esse número ainda foi elevado. Conclusão: Ainda é elevada a incidência de casos de tuberculose extrapulmonar, mesmo com a implementação da vacina BCG. Faz-se necessária a realização de pesquisas, a fim de melhor esclarecer a questão, além de comparar também os casos de manifestação pulmonar no Estado. (AU)

Objective: To analyze cases of extrapulmonary tuberculosis in a Brazilian state, and to compare it with values from industrialized countries. Methods: This is a descriptive epidemiological study, with a retrospective and cross-sectional design in data collection, with a quantitative approach. Data were obtained by consulting the databases of the TABNET system, made available by the Department of Informatics of the Unified Health System (DATASUS), with access in March 2017. The study population consisted of cases of extrapulmonary tuberculosis in the state of Minas Gerais, recorded in the period between 2011 and 2016. Results: A total of 2,979 cases of extrapulmonary tuberculosis were counted in the study period, with stabilization in the number of cases in the first triennium - 715 (2011), 706 (2012), and 715 (2013). Despite the trend observed in the first half of the study period, there was a decrease in the number of cases in the following three months - 716 (2014), 663 (2015) and 148 (2016). With the reduction in the number of cases for the most recent half of the studied period, the state of Minas Gerais followed the tendency of developed countries in relation to the reduction in the number of cases of tuberculosis. However, despite the decrease in cases of extrapulmonary involvement, this number was still high. Conclusion: There is still a high incidence of cases of extrapulmonary tuberculosis, even with the implementation of the BCG vaccine. IMore research is required to better clarify this issue, and to compare cases of pulmonary manifestation in the state. (AU)

Prevalência de lesões em órgãos-alvo em diabéticos tipo 2 / Prevalence of lesions in target organs in type 2 diabetes patients

Objetivo: Analisar a prevalência de lesões em órgãos-alvo. Métodos: Foi realizado estudo transversal e retrospectivo utilizando dados do Sistema de Cadastramento e Acompanhamento de Hipertensos e Diabéticos considerando diabéticos tipo 2 do Estado de Minas Gerais, entre os anos de 2003 e 2012. Foram analisadas quatro lesões características da má evolução do diabetes mellitus tipo 2: infarto agudo do miocárdio, acidente vascular cerebral, pé diabético e doença renal crônica. Resultados: Foram encontrados 36.270 diabéticos tipo 2. O infarto agudo do miocárdio acometeu 2,9% dos pacientes, gerando 1.087 casos. A idade mais atingida foi acima de 40 anos. O acidente vascular cerebral acometeu 2,4% dos diabéticos, provocando 892 ocorrências. A idade de maior prevalência se situou entre 50 e 64 anos, sendo responsável por 41,4% dos casos. O sexo feminino apresentou superioridade, sendo responsável por 56% dos casos. O pé diabético foi registrado em 1.160 pacientes, somando 3,1% do total de diabéticos. A doença renal crônica foi a lesão secundária ao diabetes mellitus tipo 2 mais prevalente no estado, gerando 2.094 registros, o que representa 5,7% do total de diabéticos. O sexo feminino foi consideravelmente mais acometido (65,1% dos casos), sendo a faixa etária entre 45 e 64 anos a mais prevalente. Conclusão: Este estudo sobre a prevalência e os fatores de risco para o desenvolvimento de lesões secundárias em diabéticos tipo 2 de Minas Gerais permitiu identificar que se trata de complicações muito prevalentes no Estado, e que os aspectos clínicos analisados constituem importantes fatores de risco para a má evolução da doença. (AU)

Objective: To analyze the prevalence of target organ damage. Methods: A cross-sectional and retrospective study was performed using data from the Hypertensive and Diabetic Patients Registry and Monitoring System considering type 2 diabetes patients from the state of Minas Gerais, from 2003 to 2012. Four characteristic lesions due to poor evolution of type 2 diabetes mellitus were analyzed: acute myocardial infarction; Stroke; Diabetic foot; Chronic kidney disease. Results: A total of 36,270 type 2 diabetic patients was found. Acute myocardial infarction affected 2.9% of the patients, generating 1,087 cases. The most affected age was over 40 years. Stroke affected 2.4% of diabetics, causing 892 occurrences. The highest prevalence age was between 50 and 64 years, accounting for 41.4% of the cases. The female gender was prevalent, being responsible for 56% of the cases. The diabetic foot was recorded in 1,160 patients, accounting for 3.1% of the total number of diabetics. Chronic kidney disease was the most prevalent lesion secondary to diabetes mellitus in the state, generating 2,094 records, representing 5.7% of the total number of diabetics. The female gender was considerably more affected (65.1% of the cases), with the age group between 45 and 64 years being more prevalent. Conclusion: This study of the prevalence and risk factors for the development of secondary lesions in type 2 diabetics from Minas Gerais allowed us to identify that these are very prevalent complications in the state, and that the clinical aspects analyzed are important risk factors for poor outcome of the disease. (AU)

Prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma - A review.

The prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma patients was reviewed, based on reports cited in two major scientific databases. Data were collected on the following types of antibodies: antinuclear, anti-double-stranded DNA, anticentromere, anti-CENP-A, anti-CENP-B, anti-bicaudal D2, anti-nucleolar, anti-Scl-70 (anti-topoisomerase I), anti-topoisomerase II α, anti-RNP, anti-U1RNP, anti-U3RNP, anti-RNA polymerase III, anti-Th/To, anti-histone, antiphospholipid, anti-PmScl, anti-Sm, anti SSA (anti-Ro),anti SSB (La), anti-Ro52 (TRIM 21), anti-Ku, anti-B23, anti-RuvBL1, anti-RuvBL2, anti-fibrin bound tissue plasminogen activator, anti-endothelial cell, anti-phosphatidylserine-prothrombin complex, anti-endothelin-1 type A receptor, anti-angiotensin II type 1 receptor, anti­carbonic anhydrase II, anti-fibroblast, anti-cyclic citrullinated peptide, anti-4-sulfated N-Acetyl-lactosamine, class I and II anti-human leukocyte antigen. Auto-antibodies were shown by different authors to be associated to this condition, with different prevalence values for each type of auto-antibody. Antinuclear antibodies, anti-centromere antibodies, antiphospholipid antibodies, anti-U3 RNP antibodies and anti-Th/To antibodies would appear to show a particularly important prevalence in scleroderma patients with pulmonary hypertension, appearing in about 8/10 (antinuclear), 1/ 2 (anti-centromere, anti-phospholipid), and 1/4 (anti-U3RNP, anti-Th/To) of patients. The available evidence points in the direction of a strong association between auto-immune mechanisms and pulmonary hypertension in the setting of scleroderma.

Factor XIII-guided treatment algorithm reduces blood transfusion in burn surgery / Algoritmo de tratamento guiado pelo fator XIII reduz a transfusão sanguínea na cirurgia de queimados

Abstract Background and objectives: Major burn surgery causes large hemorrhage and coagulation dysfunction. Treatment algorithms guided by ROTEM® and factor VIIa reduce the need for blood products, but there is no evidence regarding factor XIII. Factor XIII deficiency changes clot stability and decreases wound healing. This study evaluates the efficacy and safety of factor XIII correction and its repercussion on transfusion requirements in burn surgery. Methods: Randomized retrospective study with 40 patients undergoing surgery at the Burn Unit, allocated into Group A those with factor XIII assessment (n = 20), and Group B, those without assessment (n = 20). Erythrocyte transfusion was guided by a hemoglobin trigger of 10 g.dL-1 and the other blood products by routine coagulation and ROTEM® tests. Analysis of blood product consumption included units of erythrocytes, fresh frozen plasma, platelets, and fibrinogen. The coagulation biomarker analysis compared the pre- and post-operative values. Results and conclusions: Group A (with factor XIII study) and Group B had identical total body surface area burned. All patients in Group A had a preoperative factor XIII deficiency, whose correction significantly reduced units of erythrocyte concentrate transfusion (1.95 vs. 4.05, p = 0.001). Pre- and post-operative coagulation biomarkers were similar between groups, revealing that routine coagulation tests did not identify factor XIII deficiency. There were no recorded thromboembolic events. Correction of factor XIII deficiency in burn surgery proved to be safe and effective for reducing perioperative transfusion of erythrocyte units.

Resumo Justificativa e objetivos: A cirurgia no grande queimado causa hemorragia de grande porte e disfunção da coagulação. Os algoritmos de tratamento guiados por ROTEM® e fator VIIa reduzem as necessidades de hemoderivados, mas falta evidência em relação ao fator XIII. A deficiência do fator XIII altera a estabilidade do coágulo e diminui a cicatrização. Este estudo avalia a eficácia e a segurança da correção do fator XIII e sua repercussão nas necessidades transfusionais na cirurgia do queimado. Métodos: Estudo retrospectivo randomizado de 40 doentes submetidos à cirurgia na Unidade de Queimados alocados em grupo A com estudo do fator XIII (n = 20) e grupo B sem estudo (n = 20). A transfusão eritrocitária foi guiada por gatilho de hemoglobina de 10 g.dL-1 e os outros hemoderivados por testes de coagulação de rotina e ROTEM®. A análise do consumo de hemoderivados incluiu unidades de eritrócitos, plasma fresco congelado, plaquetas e fibrinogênio. A análise dos biomarcadores da coagulação comparou os valores pré e pós-operatórios. Resultados e conclusões: O grupo A (com estudo de fator XIII) e o grupo B apresentaram área de superfície corporal total queimada idêntica. Todos os doentes do grupo A revelaram déficit pré-operatório de fator XIII, cuja correção reduziu significativamente a transfusão de unidades de concentrado eritrocitário (1,95 vs. 4,05, p = 0,001). Os biomarcadores de coagulação pré e pós-operatórios foram semelhantes entre os grupos, revelaram que os testes de coagulação de rotina não identificam o déficit de fator XIII. Sem eventos tromboembólicos registrados. A correção do fator XIII na cirurgia do queimado revelou-se segura e eficaz na redução da transfusão perioperatória de unidades de eritrócitos.

High resolution mass spectrometry-based methodologies for identification of Etravirine bioactivation to reactive metabolites: In vitro and in vivo approaches.

Drug bioactivation to reactive metabolites capable of covalent adduct formation with bionucleophiles is a major cause of drug-induced adverse reactions. Therefore, elucidation of reactive metabolites is essential to unravel the toxicity mechanisms induced by drugs and thereby identify patient subgroups at higher risk. Etravirine (ETR) was the first second-generation Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) to be approved, as a therapeutic option for HIV-infected patients who developed resistance to the first-generation NNRTIs. Additionally, ETR came into market aiming to overcome some adverse effects associated with the previously used efavirenz (neurotoxicity) and nevirapine (hepatotoxicity) therapies. Nonetheless, post-marketing reports of severe ETR-induced skin rash and hypersensitivity reactions have prompted the U.S. FDA to issue a safety alert on ETR. Taking into consideration that ETR usage may increase in the near future, due to the possible use of the drug for coinfection with malaria and HIV, the development of reliable prognostic tools for early risk/benefit estimations is urgent. In the current study, high resolution mass spectrometry-based methodologies were integrated with MS3 experiments for the identification of reactive ETR metabolites/adducts: 1) in vitro incubation of the drug with human and rat liver S9 fractions in the presence of Phase I and II co-factors, including glutathione, as a trapping bionucleophile; and 2) in vivo, using urine samples from HIV-infected patients on ETR therapy. We obtained evidence for multiple bioactivation pathways leading to the formation of covalent adducts with glutathione and N-acetyl-L-cysteine. These results suggest that similar reactions may occur with cysteine residues of proteins, supporting a role for ETR bioactivation in the onset of the toxic effects elicited by the drug. Additionally, ETR metabolites stemming from amine oxidation, with potential toxicological significance, were identified in vitro and in vivo. Also noteworthy is the fact that new metabolic conjugation pathways of glucuronide metabolites were demonstrated for the first time, raising questions about their potential toxicological implications. In conclusion, these results represent not only a contribution towards the elucidation of new metabolic pathways of drugs in general but also an important step towards the elucidation of potentially toxic ETR pathways, whose understanding may be crucial for reliable risk/benefit estimations of ETR-based regimens.

Postpartum septic pelvic thrombophlebitis after caesarean delivery: a case report.

Septic pelvic thrombophlebitis is a rare puerperal complication. It is an important differential diagnosis of postpartum fever and abdominal pain and although the condition is well known its diagnosis can be challenging. We report a case of a 41-year-old woman with fever and right abdominal pain three days after an uncomplicated caesarean delivery. Clinical, laboratory and imaging exams were unremarkable and the patient was treated for endometritis. In the absence of improvement despite an antibiotic adjustment, a clinical diagnosis of septic pelvic thrombophlebitis was made, and the patient presented a good response to anticoagulation in conjunction with broad-spectrum antibiotic therapy.

[Factor XIII-guided treatment algorithm reduces blood transfusion in burn surgery]. / Algoritmo de tratamento guiado pelo fator XIII reduz a transfusão sanguínea na cirurgia de queimados.

BACKGROUND AND OBJECTIVES: Major burn surgery causes large hemorrhage and coagulation dysfunction. Treatment algorithms guided by ROTEM® and factor VIIa reduce the need for blood products, but there is no evidence regarding factor XIII. Factor XIII deficiency changes clot stability and decreases wound healing. This study evaluates the efficacy and safety of factor XIII correction and its repercussion on transfusion requirements in burn surgery. METHODS: Randomized retrospective study with 40 patients undergoing surgery at the Burn Unit, allocated into Group A those with factor XIII assessment (n = 20), and Group B, those without assessment (n = 20). Erythrocyte transfusion was guided by a hemoglobin trigger of 10g.dL-1 and the other blood products by routine coagulation and ROTEM® tests. Analysis of blood product consumption included units of erythrocytes, fresh frozen plasma, platelets, and fibrinogen. The coagulation biomarker analysis compared the pre- and post-operative values. RESULTS AND CONCLUSIONS: Group A (with factor XIII study) and Group B had identical total body surface area burned. All patients in Group A had a preoperative factor XIII deficiency, whose correction significantly reduced units of erythrocyte concentrate transfusion (1.95 vs. 4.05, p = 0.001). Pre- and post-operative coagulation biomarkers were similar between groups, revealing that routine coagulation tests did not identify factor XIII deficiency. There were no recorded thromboembolic events. Correction of factor XIII deficiency in burn surgery proved to be safe and effective for reducing perioperative transfusion of erythrocyte units.