Treatment Strategies And Outcomes Of Thoracic Aortic Blunt Injuries In Adults: A Systematic Review.

INTRODUCTION: Blunt thoracic aortic injuries (BTAI) once had mortality rates up to 32%, but the advent of thoracic endovascular aortic repair (TEVAR) has significantly improved outcomes. However, concerns persist regarding long-term devicerelated complications, device integrity in aging aortas, and the criteria for selecting patients for endovascular repair. We aimed to assess BTAI treatment strategies based on injury grade and their associated outcomes. METHODS: A systematic search of MedLine and Scopus databases was conducted to identify original articles published after 2013, which provided information on injury characteristics, outcomes, secondary effects, and reinterventions following BTAI. We classified aortic injuries following the SVS Clinical Practice Guidelines. RESULTS: We included 28 studies involving 1888 BTAI patients, including 5 prospective studies. Most patients were under 45 years old (86.4%), and grade III injuries were the most common (901 patients), followed by grades I and II (307 and 291 patients, respectively). TEVAR was performed in 1458 patients, mainly with grade III and IV injuries (1040 patients). Approximately half of the grade I injuries (153 of 307) were treated with TEVAR. Thirty-day mortality rate was 11.2%, primarily due to associated injuries. Aortic-related deaths were reported in 21 studies, with an overall rate of 2.2%, but none occurred beyond the first 30 days. Partial or complete coverage of the left subclavian artery was performed in 522 patients, with 27.9% requiring immediate or delayed revascularization. Aortic reintervention rates were relatively low (3.9%). CONCLUSION: TEVAR effectively treats BTAI grades III and IV, with potential benefit for some grade II injuries with more aggressive early intervention. Despite SVS guidelines suggesting conservative management for grade I injuries, there is a substantial rate of intervention with positive outcomes and low mortality. Long-term follow-up data, extending up to almost 20 years, reveal the durability of grafts, aortic remodeling, and minimal reintervention and complications.

Chelation of Mitochondrial Iron as an Antiparasitic Strategy.

Iron, as an essential micronutrient, plays a crucial role in host-pathogen interactions. In order to limit the growth of the pathogen, a common strategy of innate immunity includes withdrawing available iron to interfere with the cellular processes of the microorganism. Against that, unicellular parasites have developed powerful strategies to scavenge iron, despite the effort of the host. Iron-sequestering compounds, such as the approved and potent chelator deferoxamine (DFO), are considered a viable option for therapeutic intervention. Since iron is heavily utilized in the mitochondrion, targeting iron chelators in this organelle could constitute an effective therapeutic strategy. This work presents mitochondrially targeted DFO, mitoDFO, as a candidate against a range of unicellular parasites with promising in vitro efficiency. Intracellular Leishmania infection can be cleared by this compound, and experimentation with Trypanosoma brucei 427 elucidates its possible mode of action. The compound not only affects iron homeostasis but also alters the physiochemical properties of the inner mitochondrial membrane, resulting in a loss of function. Furthermore, investigating the virulence factors of pathogenic yeasts confirms that mitoDFO is a viable candidate for therapeutic intervention against a wide spectrum of microbe-associated diseases.

Latin America consensus statement inflammatory bowel disease: importance of timely access to diagnosis and treatment.

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively interferes with the quality of life of the patients, on a physical, emotional, and social level. Its symptoms can vary including diarrhea, bleeding, abdominal pain, fever, and weight loss, depending on the type and location and severity of the disease. Despite evolving treatment, they do not always achieve control of the symptoms, so between 23% and 45% of people with idiopathic chronic ulcerative colitis, and up to 75% of those with Crohn's disease, eventually, will need surgery. Objective: The increase in its incidence in Latin America has promoted a renewed interest on the part of the medical and scientific community in standardizing and unifying criteria for the proper diagnosis and management of the disease, which is part of the current discussions of various events; however, this interest has not yet been reflected in policies and initiatives by governments to address the disease. We decided to develop a consensus meeting in order to elucidate the actual situation of IBD care in our region. Design: The methodology employed to build the consensus document derived from a review of literature, evidence, and policies on IBD, followed by a process of validation and feedback with a group of 10 experts in the field. Methods: Nine experts from different countries in Latin America were reunited in web meetings on 2 days and voted on topics derived from the consensus document. A full agreement with 100% approval was needed, so topics were discussed to reach the consensus otherwise were removed. Results: There is still a lack of information about IBD in Latin America, therefore IBD continues to be an 'invisible' disease and is little recognized by decision-makers. Conclusion: This document describes the current situation of IBDs in the Latin American region, highlighting the main barriers and challenges in timely access to diagnosis and treatment, in order to demonstrate the need to promote the development and implementation of policies, in order to improve the quality of care of patients with IBD.

Paraneoplastic Aquagenic Pruritus: A Case of Pancreatic Cancer.

Paraneoplastic pruritus has been reported mostly in association with haematological malignancies, and rarely with solid tumours. Aquagenic pruritus is itching without any skin lesion that develops a few minutes after contact with water of any temperature and it is associated with polycythaemia vera or other lymphoproliferative diseases. Here we report a case of a previously healthy 78-year-old Portuguese woman, who had been treated unsuccessfully for aquagenic pruritus for the previous eight months, and presented to the emergency department complaining of pain and swelling in her left leg. Deep vein thrombosis was diagnosed and oral anticoagulation was initiated. Blood tests revealed a normal blood count and normal liver enzymes, except for alkaline phosphatase and lactate dehydrogenase levels, which were slightly elevated. Hypercobalaminaemia and folic acid deficiency were also noted. JAK2 V617F/12 exon mutation was not present. Thoracic, abdominal and pelvic computed tomography revealed a locally advanced pancreatic tumour. Ultrasound-guided fine-needle aspiration cytology of the lesion revealed a moderately differentiated adenocarcinoma of pancreatic ductal origin. Tumour marker assays showed elevation of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). Aquagenic pruritus should be thoroughly investigated to exclude a neoplastic disease, especially if treatment is refractory or if another paraneoplastic syndrome is present. Although aquagenic pruritus is more commonly associated with haematological malignancies than solid tumours, a rare case of aquagenic pruritus is described here as a paraneoplastic syndrome of pancreatic cancer. To the best of our knowledge, this is the first case of pancreatic cancer that presented with aquagenic pruritus and dual paraneoplastic syndromes.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

Total Pelvic Exenteration surgery - Considerations for healthcare professionals.

BACKGROUND: Associated with considerable risk of morbidity, Total Pelvic Exenteration (TPE) is a life-altering procedure involving a significant prolonged recovery. As a result, and with the view of achieving the best outcomes and lessen short and long-term morbidities, a well-thought-out and coordinated multidisciplinary team approach, is crucial to the provision of safe and high-quality care. METHOD: Using a nominal group technique and qualitative methodology, this article explores the current practices in the care of oncology patients who undergo TPE surgery, in a tertiary cancer centre, by highlighting considerations of a collaboratively multi-disciplinary team. RESULTS: This article provides guidance on the multi-disciplinary team approach, relating to TPE surgery, with discussion of clinical concerns, and with the goal of high patient satisfaction, provision of effective care and the lessening of short and long-term morbidities. CONCLUSION: Oncology patients that undergo TPE surgery benefit from the contribution of a diversified multidisciplinary team as skilled and competent care that meets patient's health and social care needs is provided in a holistic, comprehensive, and timely care manner. Improving patient's care, pathway and postoperative outcomes, with the use of clinical expertise and support from professionals in the multidisciplinary team, can maximise care.

Repurposing of MitoTam: Novel Anti-Cancer Drug Candidate Exhibits Potent Activity against Major Protozoan and Fungal Pathogens.

Many of the currently available anti-parasitic and anti-fungal frontline drugs have severe limitations, including adverse side effects, complex administration, and increasing occurrence of resistance. The discovery and development of new therapeutic agents is a costly and lengthy process. Therefore, repurposing drugs with already established clinical application offers an attractive, fast-track approach for novel treatment options. In this study, we show that the anti-cancer drug candidate MitoTam, a mitochondria-targeted analog of tamoxifen, efficiently eliminates a wide range of evolutionarily distinct pathogens in vitro, including pathogenic fungi, Plasmodium falciparum, and several species of trypanosomatid parasites, causative agents of debilitating neglected tropical diseases. MitoTam treatment was also effective in vivo and significantly reduced parasitemia of two medically important parasites, Leishmania mexicana and Trypanosoma brucei, in their respective animal infection models. Functional analysis in the bloodstream form of T. brucei showed that MitoTam rapidly altered mitochondrial functions, particularly affecting cellular respiration, lowering ATP levels, and dissipating mitochondrial membrane potential. Our data suggest that the mode of action of MitoTam involves disruption of the inner mitochondrial membrane, leading to rapid organelle depolarization and cell death. Altogether, MitoTam is an excellent candidate drug against several important pathogens, for which there are no efficient therapies and for which drug development is not a priority.

Renal Autotransplantation for The Treatment of Renal Artery Aneurysm.

OBJECTIVE: Renal artery aneurysms are a rare condition; however, the rate of diagnosis has been increasing, because of the increasing use of complementary diagnostic methods. The best treatment strategy for RAAs remains controversial. Data on ex-vivo surgery associated with kidney autotransplantation are scarce. As a result, the goal of this study was to describe this technique and to report our results. METHODS: A retrospective monocentric study was undertaken using the clinical records and images of 35 patients diagnosed with renal artery aneurysm from 01/01/2010 to 31/12/2018. Indications for ex vivo surgery and autotransplantation were complex aneurysms with diameter >20 mm or rapid growth or symptomatic aneurysms or women wishing to become pregnant. Complex aneurysms were defined by anatomical criteria (bifurcation of the renal artery and its primary branches or hilar aneurysms) and/or physiological criteria (when time of warm ischemia in in-situ reconstruction is expected to last more than 45 minutes). The technique of ex-vivo surgery and autotransplantation consists of performing a nephrectomy, renal cooling, treatment of aneurysm in banking and implantation of the kidney in the homolateral iliac fossa. RESULTS: A total of 35 patients with 56 renal artery aneurysms (26 women, mean age 52.4 years-minimum and maximum 16 and 74 years) were included. Of these, 27 were treated by surgery and 8 were followed clinically. Among those treated surgically, 24 performed ex vivo surgery associated with autotransplantation. Regarding ex vivo surgery, nephrectomy was performed by laparoscopic surgery in 24 of the 27 surgeries, the mean surgical time was 5.3 hours, the median warm ischemia time was 4 minutes and the length of hospital stay was 12.2 days. Mortality was 0% and the kidney patency rate was 93% with a follow up of 47.2 months. Of the 17 patients with hypertension, 6 cured it, 4 improved and 7 maintained hypertension. CONCLUSION: Kidney autotransplantation appears to be efficient for most complex RAA with the possibility to minimize surgical aggression by performing laparoscopic nephrectomy.

Segundo Consenso Brasileiro de Manejo da Doença de Crohn em adultos: um consenso da Organização Brasileira de Doença de Crohn e Colite (GEDIIB) / Second brazilian consensus on the management of crohn's disease in adults: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. Objective: To guide the safest and effective medical treatments of adults with CD. Methods: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. Results and conclusion: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

RESUMO Contexto: A doença inflamatória intestinal (DII) é uma doença imunomediada que inclui a doença de Crohn (DC) e a retocolite ulcerativa. A DC é caracterizada por um envolvimento intestinal transmural da boca ao ânus com sintomas recorrentes e remitentes que podem levar a danos intestinais progressivos e incapacidade ao longo do tempo. Objetivo: Orientar os tratamentos médicos mais seguros e eficazes de adultos com DC. Métodos: Este consenso foi desenvolvido por autores que representam gastroenterologistas e cirurgiões brasileiros especialistas em doenças colorretais (GEDIIB, Organização Brasileira de Doença de Crohn e Colite). Uma revisão sistemática das evidências mais recentes foi realizada para apoiar as recomendações/declarações. Todas as recomendações e declarações incluídas foram endossadas em um painel Delphi modificado pelas partes interessadas e especialistas em DII com uma concordância de pelo menos 80% ou mais. Resultados e conclusão: As recomendações médicas (intervenções farmacológicas e não farmacológicas) foram mapeadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, e acompanhamento/monitoramento do paciente após o tratamento inicial. O consenso é direcionado a clínicos gerais, gastroenterologistas e cirurgiões interessados em tratar e gerenciar adultos com DC e apoia a tomada de decisões de companhias de seguro de saúde, agências reguladoras e líderes ou administradores de instituições de saúde.

Segundo Consenso Brasileiro no manejo da retocolite ulcerativa em adultos: um consenso da Organização Brasileira para Doença de Crohn e Colite (GEDIIB) / Second brazilian consensus on the management of ulcerative colitis in adults: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. Objective: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. Methods: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. Results and conclusion: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

RESUMO Contexto: As doenças inflamatórias intestinais são doenças imunomediadas que incluem a doença de Crohn (DC) e a retocolite ulcerativa (RCU). A RCU é uma doença progressiva que acomete a mucosa colorretal causando sintomas debilitantes levando a alta morbidade e incapacidade laboral. Como consequência da inflamação crônica do cólon, a RCU também está associada a um risco aumentado de câncer colorretal. Objetivo: Este consenso visa fornecer orientações sobre o manejo médico mais eficaz de pacientes adultos com RCU. Métodos: As recomendações do consenso foram desenvolvidas por gastroenterologistas e cirurgiões colorretais referências no Brasil (membros da Organização Brasileira para Doença de Crohn e Colite [GEDIIB]). Uma revisão sistemática, incluindo as evidências mais recentes, foi conduzida para apoiar as recomendações. Todas as recomendações foram endossadas pelas partes interessadas/especialistas em doença inflamatória intestinal usando um Painel Delphi modificado. O nível de concordância para alcançar consenso foi de 80% ou mais. Resultados e conclus ão: As recomendações médicas (farmacológicas e não farmacológicas) foram mapeadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, e acompanhamento/monitoramento do paciente após o tratamento inicial. O consenso foi direcionado a clínicos gerais, gastroenterologistas e cirurgiões que tratam pacientes com RCU e apoia os processos de tomada de decisão por companhias de seguro de saúde, agências reguladoras, líderes institucionais de saúde e administradores.

Biosimilar knowledge and viewpoints among Brazilian inflammatory bowel disease patients.

BACKGROUND: In this analysis we aimed to describe Brazilian inflammatory bowel disease (IBD) patients' knowledge and perceptions regarding biosimilars and compare with viewpoints from non-Brazilian patients. METHODS: An online survey consisting of 19 questions was made available by the European Federation of Crohn's and Ulcerative Colitis Associations between July 2018 and December 2018. Only respondents who had heard of biosimilars were asked to respond to all of the questions. RESULTS: A total of 102 Brazilian IBD patients responded to the survey. The majority (78.4%) of patients had been exposed to anti-tumor-necrosis-factor drugs and 63.4% of them had heard of biosimilars. Brazilian respondents worried significantly more about biosimilars being less effective than the originator (62.5% versus 47.9%, p value 0.03) and molecular differences between biosimilars and originators (53.1% versus 31.8, p value 0.001) as compared with non-Brazilian IBD patients. The majority of Brazilian (75%) and non-Brazilian (64.1%) respondents thought that the lower cost of biosimilars should not come before their safety and efficacy (p value 0.09). In addition, 79.1% of Brazilian respondents believed that the arrival of biosimilars will have an impact on the management of IBD. CONCLUSIONS: Brazilian patients reported higher rates of misconceptions regarding biosimilars than non-Brazilian IBD patients. Although patients still worry about different aspects regarding biosimilars, they also tend to be confident that biosimilars will have an impact on the management of their disease. With the recent approval of many biosimilars in Brazil and the imminent widespread use of these drugs, our data raise awareness for the need of providing patient education to prevent negative expectations toward switching to biosimilars.

Plasmodium Reproduction, Cell Size, and Transcription: How to Cope With Increasing DNA Content?

Plasmodium, the unicellular parasite that causes malaria, evolved a highly unusual mode of reproduction. During its complex life cycle, invasive or transmissive stages alternate with proliferating stages, where a single parasite can produce tens of thousands of progeny. In the clinically relevant blood stage of infection, the parasite replicates its genome up to thirty times and forms a multinucleated cell before daughter cells are assembled. Thus, within a single cell cycle, Plasmodium develops from a haploid to a polypoid cell, harboring multiple copies of its genome. Polyploidy creates several biological challenges, such as imbalances in genome output, and cells can respond to this by changing their size and/or alter the production of RNA species and protein to achieve expression homeostasis. However, the effects and possible adaptations of Plasmodium to the massively increasing DNA content are unknown. Here, we revisit and embed current Plasmodium literature in the context of polyploidy and propose potential mechanisms of the parasite to cope with the increasing gene dosage.

Avaliação prognóstica de lesão renal aguda em pacientes cirróticos / Impact of acute kidney injury staging on prognosis of patients with cirrhosis

ABSTRACT BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cirrhosis. OBJECTIVE: To evaluate the impact of AKI staging on 30-day mortality of patients with cirrhosis. METHODS: We performed a retrospective cohort study of hospitalized patients with cirrhosis. Acute kidney injury (AKI) was diagnosed according to the International Club of Ascites recommendations and staged according to the European Association for the Study of the Liver guidelines. Comparisons between groups were made by one-way analysis of variance and Tukey test. Chi-square was calculated for dichotomous variables. Comparisons of renal impairment status among patients were performed using Kaplan-Meier statistics and differences between groups were analyzed using the log-rank test. A P-value <0.05 was considered to be statistically significant. RESULTS: Two hundred and thirty-two patients were included in the study. The diagnosis of AKI was performed in 98 (42.2%) of them. The overall 30-day mortality was 19.8% (46/232). Mortality increased as the degree of AKI progressed. Among patients who did not have AKI, mortality was 5.2% (7/134). When compared to patients without AKI, patients diagnosed with AKI stage 1a had mortality of 12.1% (4/33, P=0.152); patients with AKI stage 1b had mortality of 45% (18/40, P<0.001); and patients with AKI stages 2 or 3 had mortality of 68% (17/25, P<0.001). Moreover, it is noteworthy that full response to treatment was associated to a decreased mortality when compared to patients who did not show complete recovery of renal function (14.3% vs 57.9%, P<0.001). CONCLUSION: AKI stages 1b or greater, but not AKI stage 1a, are associated to higher 30-day mortality of patients with cirrhosis.

RESUMO CONTEXTO: A lesão renal aguda (LRA) é uma complicação comum e grave na cirrose. OBJETIVO: Avaliar o impacto dos estágios da LRA na mortalidade em 30 dias de pacientes com cirrose. MÉTODOS: Realizou-se um estudo de coorte retrospectivo com pacientes com cirrose hospitalizados. LRA foi diagnosticada de acordo com as recomendações do International Club of Ascites e o estadiamento foi feito de acordo com as recomendações da European Association for the Study of the Liver. Comparações entre os grupos foram feitas por análise de variância unidirecional e teste de Tukey. O teste do qui-quadrado foi calculado para variáveis categóricas. Comparações quanto à lesão renal entre os pacientes foram realizadas com estatísticas de Kaplan-Meier, e diferenças entre os grupos foram analisadas pelo teste de log-rank. Um P-valor <0,05 foi considerado estatisticamente significativo. RESULTADOS: Duzentos e trinta e dois pacientes foram incluídos no estudo. O diagnóstico de LRA foi realizado em 98 (42,2%) deles. A mortalidade geral em 30 dias foi de 19,8% (46/232). A mortalidade aumentou de acordo com a progressão dos estágios de LRA. Entre pacientes sem LRA, a mortalidade foi de 5,2% (7/134). Quando comparados aos pacientes sem LRA, pacientes diagnosticados com LRA estágio 1a tiveram mortalidade de 12,1% (4/33, P=0,152); pacientes com LRA estágio 1b tiveram mortalidade de 45% (18/40, P<0,001); e pacientes com LRA estágios 2 ou 3 tiveram mortalidade de 68% (17/25, P<0,001). Além disso, é importante ressaltar que a resposta completa ao tratamento associou-se à menor mortalidade quando comparada à ausência de recuperação completa da função renal (14,3% vs 57,9%, P<0,001). CONCLUSÃO: LRA estágios 1b ou superior, mas não estágio 1a, estão associadas à maior mortalidade em 30 dias de pacientes com cirrose.

[Congenital or Early Acquired Deafness: An Overview of the Portuguese Situation, from Diagnosis to Follow-Up]. / Surdez Congénita ou Precocemente Adquirida: Do Rastreio ao Seguimento, um Retrato de Portugal.

INTRODUCTION: Congenital deafness or early acquired deafness affects 1 to 3 out of 1000 newborns without risk factors and 20 to 40 out of 1000 newborns with risk factors. The universal newborn hearing screening enables its early identification. Children with congenital deafness/early acquired deafness have a higher prevalence of other conditions, especially ophthalmologic and neurodevelopmental ones, and at least 30% to 40% have at least one associated comorbidity. MATERIAL AND METHODS: We carried out a cross-sectional, multicenter study in which 83% (n = 30) of the hospitals/maternity hospitals of the National Health Service participated. RESULTS: All surveyed hospitals/maternity hospitals routinely performed universal newborn hearing screening to all newborns before discharge; 63% referred children with risk factors for hearing loss to Otorhinolaryngology. All children with congenital deafness/early acquired deafness are referred to: Pediatrics in 23% hospitals/maternity hospitals. In 23 hospitals/maternity hospitals, all children with congenital deafness/early acquired deafness are referred to: Speech Therapy in 44% hospitals/ maternity hospitals; Ophthalmology in 17% hospitals/maternity hospitals; National System of Early Intervention in Childhood in 30% hospitals/maternity hospitals; 22% of hospitals/maternity hospitals refer all children with congenital deafness/early acquired deafness, with no identified cause, to Clinical Genetics clinics. The number of diagnoses of deafness in the years 2014 and 2015 was 2.5 and 1.5 per 1000 newborns, respectively, in 15 hospitals/maternity hospitals. DISCUSSION: Awareness of universal newborn hearing screening seems to be widely spread in the National Health Service. The number of children with SC / SPA, as well as the percentage of different types of deafness diagnosed, were identical to those found in other studies and shows its importance. The assessment / follow-up of these children by specialties other than the otolaryngology was heterogeneous in different health entities and revealed that not all children with risk factors for deafness follow up advised by existing standards. CONCLUSION: Results show that Portugal made an important path in the screening and follow-up of children with SC / SPA. It is important, with the ultimate aim of continually improving the care of these children, to reflect on the involvement of specialties other than otolaryngology, such as the National Early Childhood Intervention System in the follow-up of these children.

Introdução: A surdez congénita ou precocemente adquirida afeta 1 a 3 por cada 1000 recém-nascidos sem fatores de risco e 20 a 40/1000 com fatores de risco. O rastreio auditivo neonatal universal permite a sua identificação precoce. As crianças com surdez congénita/precocemente adquirida têm uma maior prevalência de outras patologias, especialmente oftalmológicas e do neurodesenvolvimento, tendo pelo menos 30% a 40% uma comorbilidade associada.Material e Métodos: Realizámos um estudo transversal, multicêntrico onde participaram 83% (n = 30) dos hospitais/maternidades do Serviço Nacional de Saúde.Resultados: Todos os hospitais/maternidades inquiridos realizam, por rotina, o rastreio auditivo neonatal universal a todos os recém-nascidos antes da alta; 63% encaminham para Otorrinolaringologia crianças com fatores de risco de surdez. Todas as crianças com surdez congénita/precocemente adquirida são encaminhadas para Pediatria em 23% hospitais/maternidades. Em 23 hospitais/maternidades todas as crianças com surdez congénita/precocemente adquirida são encaminhadas para: Terapia da Fala em 44% hospitais/maternidades; Oftalmologia em 17% hospitais/maternidades; Sistema Nacional de Intervenção Precoce na Infância (SNIPI) em 30% hospitais/maternidades; referenciação para Genética de todas as crianças com surdez congénita/ precocemente adquirida, sem causa identificada, em 22% hospitais/maternidades. O número de diagnósticos de surdez nos anos de 2014 e 2015 foi de 2,5 e 1,5 por cada1000 recém-nascidos, respetivamente, em 15 dos  hospitais/maternidades.Discussão: O rastreio auditivo neonatal universal parece estar amplamente difundido no Serviço Nacional de Saúde. O número de crianças com SC/SPA tal como a percentagem dos diferentes tipos de surdez diagnosticados, foram idênticos aos encontrados noutros estudos e mostra a indiscutível importância do rastreio. A avaliação/acompanhamento destas crianças por outras especialidades, além da Otorrinolaringologia, mostrou-se heterogéneo nas diferentes entidades de saúde e revelou que nem todas as crianças com fatores de risco de surdez realizam o seguimento aconselhado pelas normas existentes.Conclusão: Os resultados mostram que Portugal realizou um percurso importante no âmbito do rastreio e seguimento das crianças com SC/SPA. Importa, com o fim último da melhoria continua da prestação de cuidados a estas crianças, refletir sobre o envolvimento de outras especialidades, além da Otorrinolaringologia, tal como do Sistema Nacional de Intervenção Precoce na Infância no seguimento destas crianças.

Diffusion-weighted imaging and apparent diffusion coefficient values for evaluating terminal ileitis in patients with Crohn's disease.

OBJECTIVE: To determine the accuracy of diffusion-weighted imaging (DWI) in identifying terminal ileitis in patients with Crohn's disease. MATERIALS AND METHODS: This was a retrospective study of 38 consecutive patients with Crohn's disease who underwent magnetic resonance enterography with DWI in a 3.0 T scanner. The patients were divided into two groups, on the basis of colonoscopy and biopsy findings: active inflammation; and inactive disease. Apparent diffusion coefficient (ADC) values were determined, as were the magnetic resonance index of activity (MaRIA) and the Clermont score. RESULTS: Of the 38 patients evaluated, 18 (47%) had active inflammation. The patients with active inflammation showed greater restricted diffusion, more pronounced mucosal edema, greater wall thickening, a higher MaRIA, and a higher Clermont score than did those with inactive disease. The level of interobserver agreement (intraclass correlation coefficient) was excellent for the MaRIA and the Clermont score, whereas it was substantial for the ADC values. For identifying colonoscopy-proven inflammation, the best ADC cut-off point was 2.1 × 10-3 mm2/s, which had a sensitivity of 88.8% and a specificity of 95.0%, whereas DWI presented an overall accuracy of 89.4%, with a sensitivity of 88.9% and a specificity of 90.0%. CONCLUSION: Visual analysis of the DWI sequence has good accuracy in detecting terminal ileitis in patients with Crohn's disease. In addition, low ADC values have good sensitivity for detecting colonoscopy-proven inflammation.

Prevalência de anticorpos e fatores de risco associados à infecção por Toxoplasma gondii em galinhas domésticas da zona rural de Santa Maria, Rio Grande do Sul / Prevalence of antibodies and risk factors associated with infection by Toxoplasma gondii in free range chickens of rural area of Santa Maria, Rio Grande do Sul, Brazil

RESUMO: Toxoplasma gondii é um protozoário apicomplexa que infecta animais de sangue quente, podendo ser considerado um dos principais parasitas capazes de infectar os seres humanos. Galinhas domésticas podem ser facilmente infectadas por protozoários, uma vez que estas podem ingerir oocistos encontrados no solo, sendo consideradas boas indicadoras de contaminação ambiental por T. gondii. O objetivo deste estudo foi determinar a presença de anticorpos anti-T. gondii em galinhas domésticas criadas extensivamente e avaliar os fatores de risco associados ao protozoário, na zona rural de Santa Maria, RS, Brasil. No período de março de 2013 a fevereiro 2014 foram coletadas 597 amostras de sangue de galinhas domésticas em 74 propriedades, oriundas de nove estratos que representam cada distrito da zona rural. Para avaliar os fatores de risco, nessas propriedades foi aplicado um questionário epidemiológico aos moradores. As amostras de soro foram testadas por imunofluorescência indireta, e 49,2% (294/597) foram positivas para anticorpos anti-T. gondii, com títulos variando de 16 a 4096. Das 74 propriedades analisadas, em 63 (85,1%) houve relatos que os gatos têm acesso ao deposito de alimentos, com associação significativa quando associado à presença de galinhas positivas (p=0,04) e o OR de 4,07. A variável "abate de animais" (aves e bovinos), em 51 (68,9%) das propriedades foi relatado o abate de bovinos e aves na propriedade, com valor de p significativo (p=0,05). A maioria das propriedades 59 (79,7%) foi relatada a presença de gatos domésticos, o que poderia estar associada com a alta soroprevalência encontrada em galinhas e a taxa de contaminação ambiental. A elevada prevalência de anticorpos encontrada neste estudo, além da alta frequência de propriedades com casos positivos, sugere uma grande contaminação ambiental nos distritos pesquisados, sendo assim um risco potencial para a saúde humana e animal.

ABSTRACT: Toxoplasma gondii is an apicomplex protozoan that infects warm-blooded animals and can be considered a major parasite capable of infecting humans. Domestic chickens can be easily infected by protozoa, since they can ingest oocysts found in the soil and are considered good indicators of environmental contamination by T. gondii. The aim of this study was to determine the presence of anti-T. gondii antibodies in free range chickens and to evaluate the risks factors associated with the protozoan in rural area of Santa Maria, RS, Brazil. From March 2013 to February 2014, 597 blood samples from domestic chickens were collected from 74 farms, from nine layers representing each district in the rural area. To evaluate the risk factors, in these farms an epidemiological questionnaire was applied to the residents. Serum samples were tested by indirect immunofluorescence and 49.2% (294/597) were positive for anti-T.gondii antibodies, with titres varying from 16 to 4096. Of the 74 analyzed farms, 63 (85.1%) reported that cats had access to food deposits, with a significant association when positive chickens were present (p = 0.04) and the OR of 4.07. The variable "slaughter of animals" (poultry and cattle) in 51 (68.9%) of the farms was reported the slaughter of cattle and birds in the farm, with significant p value (p = 0.05). Most farms 59 (79.7%) reported the presence of domestic cats, which could be associated with the high seroprevalence found in chickens and the rate of environmental contamination. The high prevalence of antibodies found in this study, in addition to the high frequency of farms with positive cases, suggests a great environmental contamination in the studied districts, thus being a potential risk to human and animal health.

Alkaloids from Narcissus poeticus cv. Pink Parasol of various structural types and their biological activity.

Fifteen Amaryllidaceae alkaloids (1-15) of various structural types were isolated by standard chromatographic methods from fresh bulbs of Narcissus poeticus cv. Pink Parasol. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic analyses, and by comparison with literature data. Narcipavline (5) and narcikachnine (6) are reported here for the first time. In their structure are combined two basic structural types of Amaryllidaceae alkaloids (galanthamine- and galanthindole-structural types), which represent a new structural type of these compounds. Alkaloids isolated in sufficient amounts were evaluated for their human erythrocytic acetylcholinesterase, and human serum butyrylcholinesterase (HuBuChE) inhibition activity using Ellman's method. Z-Gly-Pro-p-nitroanilide was used as substrate in the prolyl oligopeptidase (POP) assay. Untested alkaloids were also screened for their cytotoxic activity against a small panel of human cancer cells, which spanned cell lines from different tissue types. In parallel, MRC-5 human fibroblasts were employed to determine overall toxicity against noncancerous cells. Some compounds were evaluated for their antiprotozoal activity. The newly isolated alkaloid narcipavline (5) showed interesting HuBuChE inhibition activity (IC50 = 24.4 ± 1.2 µM), and norlycoramine (11) demonstrated promising POP inhibition (IC50 = 0.21 ± 0.01 mM).

Recidiva oncológica: olhares dos profissionais hospitalares sobre as dificuldades do paciente pediátrico / Cancer recurrence: perspectives of hospital staff on the difficulties of pediatric patients / Recaída oncológica: observación de los profesionales de hospitales sobre las dificultades del paciente pediátrico

Em pediatria oncológica, a taxa de sobrevivência tem sofrido um aumento acentuado, sendo considerável a probabilidade de cura. Não obstante, o processo de confronto com a doença pode sofrer alguns contratempos, nomeadamente uma recidiva. Esta última é responsável por elevado sofrimento, o qual poderá ser ainda maior que o confronto com o diagnóstico. Procurando conhecer as percepções dos profissionais de oncologia, relativamente às principais dificuldades experienciadas pelas crianças e adolescentes cuja doença recidivou, as autoras desenvolveram um estudo investigando o olhar desses profissionais. Entrevistaram-se 17 profissionais, de dois hospitais portugueses, exercendo funções hospitalares na área da saúde, serviço social, psicologia e educação. Suas reflexões apontaram como principais dificuldades a aceitação de ter que passar novamente por um processo física e psicologicamente penoso sendo que, entre os adolescentes ­ mais conscientes da gravidade da doença e suas implicações ­ acrescem as dificuldades em ter esperança na cura. Para os mais pequenos, os profissionais apontaram como mais comum a dificuldade em compreender os motivos de nova submissão a tratamentos dolorosos e do afastamento dos seus contextos de vida. Dando a conhecer uma etapa particularmente desafiante da doença oncológica, o presente estudo traz um olhar multifocal de um grupo de profissionais que acompanham de perto essas crianças/adolescentes (e respectivas famílias). A sua longa e diversa experiência ­ em termos de tipologias de câncer, evolução do quadro clínico, idade ou temperamento dos pacientes (e dos próprios pais) ­ fazem desses profissionais informantes-chave no mapeamento das dificuldades associadas ao processo de recidiva oncológica em pediatria, bem como no desenho e implementação de respostas mais ajustadas à fenomenologia destes processos. (AU)

In pediatric oncology, the survival rate has risen considerably, and nowadays the probability of cure is very high. However, the process of fighting the disease can suffer some setbacks, namely a relapse. This event is responsible for high suffering, which may be even greater than dealing with the diagnosis of cancer. Aiming to understand the perceptions of oncology professionals regarding the main difficulties experienced by children/adolescents whose cancer relapsed, the authors developed a study in which the professionals' perspective was explored. A group of 17 professionals (from the areas of health, social work, psychology and education), working in two Portuguese hospitals, was interviewed. Their reflections indicated that the main difficulties during relapse were the acceptance of having to undergo such a - physically and psychologically - painful process all over again, and among adolescents, who are more aware of the severity of the disease and its implications, also difficulties in keeping up hope. Among the youngest, professional pointed out as more common the difficulty in understanding why they have to be resubmitted to such painful treatments and be parted from their life contexts. Emphasizing recurrence as a particularly challenging stage of the oncologic disease, this study brings a multifocal view of a group of professionals who closely follow these children/adolescents (and their families) all the way trough. Their long and diverse experience - in terms of type of cancer, evolution of the disease, age and/or temperament of the patients (and the parents' themselves) - make these professionals key informants in the mapping of the difficulties related to the pediatric oncological relapse, as well as in the design and implementation of more adjusted responses to the phenomenology of these processes. (AU)

En pediatría oncológica, el índice de sobrevivencia ha experimentado un aumento acentuado, siendo considerable la probabilidad de cura. Sin embargo, el proceso de enfrentar la enfermedad puede sufrir algunos contratiempos, en particular una recaída; ésta es responsable por mucho sufrimiento, el cual puede ser incluso mayor que enfrentar el propio diagnóstico. Tratando de conocer las percepciones de los profesionales de oncología y las principales dificultades experimentadas por los niños/adolescentes que tuvieron recaída, los autores desarrollaron un estudio con participación de 17 profesionales de la salud, trabajo social, psicología y educación de dos hospitales portugueses. Las reflexiones recogidas a través de entrevistas indicaron que las principales dificultades de los niños es aceptar y entender porqué razón tienen que pasar nuevamente por un proceso físico y psicológico tan doloroso y estar lejos de sus contextos naturales. Entre los adolescentes - más conscientes de la gravedad e implicaciones de la enfermedad ­ son mayores las dificultades para creer y tener esperanza en la cura. Describindo la recaída como una etapa particularmente difícil de la enfermedad oncológica, este estudio proporciona una mirada multifocal de un grupo de profesionales que siguen de cerca estos niños/adolescentes (y respectivas familias). Su larga y variada experiencia - en términos de tipos de cáncer, evolución de cuadro clínico, edad y temperamento de los pacientes (y de los propios padres) ­ hace que estos profesionales pasen a ser informantes clave para identificar las dificultades asociadas con la recaída del cáncer pediátrico, así como en el diseño e implementación de respuestas más ajustadas a la fenomenología de estos procesos. (AU)

Tratamento antissecretor da doença do refluxo gastroesofágico pediátrica - uma revisão sistemática / Antisecretory treatment for pediatric gastroesophageal reflux disease - a systematic review

ABSTRACT BACKGROUND: Proton pump inhibitors and histamine H2 receptor antagonists are two of the most commonly prescribed drug classes for pediatric gastroesophageal reflux disease, but their efficacy is controversial. Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux, even that causal relation is not proven. OBJECTIVE: To evaluate the use of proton pump inhibitors and histamine H2 receptor antagonists in pediatric gastroesophageal reflux disease through a systematic review. METHODS: A systematic review was performed, using MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. The search was limited to studies published in English, Portuguese or Spanish. There was no limitation regarding date of publication. Studies were considered eligible if they were randomized-controlled trials, evaluating proton pump inhibitors and/or histamine H2 receptor antagonists for the treatment of pediatric gastroesophageal reflux disease. Studies published only as abstracts, studies evaluating only non-clinical outcomes and studies exclusively comparing different doses of the same drug were excluded. Data extraction was performed by independent investigators. The study protocol was registered at PROSPERO platform (CRD42016040156). RESULTS: After analyzing 735 retrieved references, 23 studies (1598 randomized patients) were included in the systematic review. Eight studies demonstrated that both proton pump inhibitors and histamine H2 receptor antagonists were effective against typical manifestations of gastroesophageal reflux disease, and that there was no evidence of benefit in combining the latter to the former or in routinely prescribing long-term maintenance treatments. Three studies evaluated the effect of treatments on children with asthma, and neither proton pump inhibitors nor histamine H2 receptor antagonists proved to be significantly better than placebo. One study compared different combinations of omeprazole, bethanechol and placebo for the treatment of children with cough, and there is no clear definition on the best strategy. Another study demonstrated that omeprazole performed better than ranitidine for the treatment of extraesophageal reflux manifestations. Ten studies failed to demonstrate significant benefits of proton pump inhibitors or histamine H2 receptor antagonists for the treatment of unspecific manifestations attributed to gastroesophageal reflux in infants. CONCLUSION: Proton pump inhibitors or histamine H2 receptor antagonists may be used to treat children with gastroesophageal reflux disease, but not to treat asthma or unspecific symptoms.

RESUMO CONTEXTO: Inibidores de bomba de prótons e antagonistas dos receptores H2 da histamina são duas das mais comumente prescritas classes de medicações para a doença do refluxo gastroesofágico pediátrica, mas sua eficácia é controversa. Muitos pacientes são tratados com essas drogas por manifestações atípicas atribuídas ao refluxo gastroesofágico, mesmo que uma relação causal não esteja comprovada. OBJETIVO: Avaliar os inibidores da bomba de prótons e os antagonistas dos receptores H2 da histamina na doença do refluxo gastroesofágico pediátrica através de uma revisão sistemática. MÉTODOS: Realizou-se uma revisão sistemática, utilizando as bases de dados MEDLINE, EMBASE e Cochrane Central Register of Controlled Trials. A pesquisa foi limitada a estudos publicados em inglês, português e espanhol. Não houve limitação quanto à data de publicação. Os estudos foram considerados elegíveis se fossem ensaios controlados randomizados que avaliassem inibidores da bomba de prótons e/ou antagonistas dos receptores H2 da histamina para o tratamento da doença do refluxo gastroesofágico pediátrica. Estudos publicados apenas como resumos, estudos que não avaliassem desfechos clinicamente relevantes e estudos que comparassem exclusivamente diferentes doses do mesmo fármaco foram excluídos. A extração de dados foi realizada por pesquisadores independentes. O protocolo do estudo foi registrado na plataforma PROSPERO (CRD42016040156). RESULTADOS: Após a análise das 735 referências identificadas, 23 estudos (1598 pacientes randomizados) foram incluídos na revisão sistemática. Oito estudos demonstraram que tanto os inibidores da bomba de prótons como os antagonistas dos receptores H2 da histamina eram eficazes contra as manifestações típicas da doença de refluxo gastroesofágico e que não havia evidências de benefício na combinação dessas classes de drogas ou na prescrição rotineira de tratamentos de manutenção de longo prazo. Três estudos avaliaram o efeito dos tratamentos em crianças com asma e, nem os inibidores da bomba de prótons, nem os antagonistas dos receptores H2 da histamina se mostraram significativamente melhores do que o placebo. Um estudo comparou diferentes combinações de omeprazol, betanecol e placebo para o tratamento de crianças com tosse, e não há uma definição clara sobre a melhor estratégia terapêutica. Outro estudo demonstrou que o omeprazol apresentou melhor desempenho do que a ranitidina para o tratamento de manifestações extraesofágicas da doença do refluxo gastroesofágico. Dez estudos não tiveram sucesso em demonstrar benefícios significativos dos inibidores da bomba de prótons ou dos antagonistas dos receptores H2 da histamina para o tratamento de manifestações inespecíficas atribuídas ao refluxo gastroesofágico em crianças menores de 1 ano de idade. CONCLUSÃO: Inibidores da bomba de prótons ou antagonistas dos receptores H2 da histamina podem ser utilizados para tratar crianças com doença de refluxo gastroesofágico, mas não para tratar asma ou sintomas inespecíficos.