Febre mediterrânica familiar : caso clínico e revisão bibliográfica

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2017Introdução: As Síndromes Periódicas Febris são um conjunto heterogéneo de patologias, cujo denominador comum é a auto-inflamação. A Febre Mediterrânica Familiar (FMF) é a síndrome periódica hereditária mais comum e caracteriza-se por episódios recorrentes de febre e polisserosite. É uma doença autossómica recessiva provocada por mutações no gene MEFV, que codifica a pirina. Atinge sobretudo grupos étnicos da Bacia do Mediterrâneo, nomeadamente Turcos, Judeus, Arménios e Árabes. O diagnóstico é essencialmente clínico, mas em determinadas situações, pode ser auxiliado pelo teste genético. A complicação mais grave é a amiloidose. A terapêutica com colchicina pode, não só prevenir a amiloidose, como diminuir a frequência e a gravidade das crises. Caso clínico: A autora descreve o caso de um rapaz português de 8 anos de idade, previamente saudável, que inicia episódios de febre recorrente, dor abdominal e torácica em intervalos irregulares. Laboratorialmente, destacava-se um aumento dos parâmetros inflamatórios, nomeadamente da Proteína C Reativa, Velocidade de Sedimentação e Fibrinogénio durante as crises. No período intercrítico, manteve-se assintomático, realizando a sua atividade normal. A investigação diagnóstica excluiu causas neoplásicas, infeciosas ou imunológicas, estabelecendo o diagnóstico presuntivo de FMF. Os testes genéticos para a mutação MEFV foram negativos. Assim, iniciou-se prova terapêutica com colchicina. Após seis meses, não houve recorrência dos sintomas. Procede-se à discussão do caso com recurso a uma revisão bibliográfica. Conclusão: As Síndromes Periódicas Febris, particularmente a FMF, são causa de febre recorrente e manifestações sistémicas. Apesar de globalmente rara, a FMF atinge elevada prevalência nos países da bacia do Mediterrâneo. Em Portugal, é provavelmente subdiagnosticada. Neste sentido, é fundamental alertar os clínicos para a sua existência e para os principais dados da anamnese que podem ser sugestivos, aumentando assim o grau de suspeição.Introduction: Periodic Fever Syndromes are a heterogeneous group of Mendelian disorders classified as auto-inflammatory. Familial Mediterranean Fever (FMF) is the most common autoinflammatory syndrome and is characterized by recurrent attacks of fever associated with polyserositis. FMF results from autosomal recessive mutations in the MEFV gene, encoding pyrin. This disorder occurs mainly among individuals of Mediterranean descent, namely Turkish, Jewish, Armenian and Arabic communities. The diagnosis is based on clinical findings, but genetic tests can also be used to confirm the diagnosis. Amyloidosis is the most important complication. Colchicine is the mainstay of FMF treatment and prevents amyloidosis and the frequency and severity of the episodes. Case Report: The author describes the case of a previously healthy 8-year-old Portuguese boy, who was brought to the hospital for recurrent fever, abdominal and thoracic pain. The laboratory tests showed increased acute phase markers, such as the erythrocyte sedimentation rate (ESR), C-reactive protein and fibrinogen during the attacks. Between the episodes, he was asymptomatic. Neoplastic, infectious and immunologic causes were excluded. We admitted the FMF diagnosis, although the genetic tests were negative. Colchicine was started as a therapeutic trial. The patient remained free of attacks for 6 months. A bibliographic review regarding the discussion of the clinical case was made. Conclusions: Periodic Fever Syndromes, particularly FMF, are cause of recurrent fever and systemic manifestations and can mimic many diseases. Despite being a rare condition worldwide, FMF reaches high prevalence in the Mediterranean area. In Portugal, it is probably underdiagnosed. It is therefore crucial to improve knowledge of these disorders in order to increase the degree of suspicion and diagnosis

Does It Matter?

Funding Information: This research was partially co-financed by Hospital da Luz Lisboa under the initiative “Luz Investigação” in the context of the Group GENIUS (Reference LH.INV.F2019015).We investigated the impactof microsatellite instability (MSI) and Epstein–Barr virus (EBV) status in gastric cancer (GC), regarding response to perioperative chemotherapy (POPChT), overall survival (OS), and progression-free survival (PFS). We included 137 cases of operated GC, 51 of which were submitted to POPChT. MSI status was determined by multiplex PCR and EBV status by EBV-encoded RNA in situ hybridization. Thirty-seven (27%) cases presented as MSI-high, and seven (5.1%) were EBV+. Concerning tumor regression after POPChT, no differences were observed between the molecular subtypes, but females were more likely to respond (p = 0.062). No significant differences were found in OS or PFS between different subtypes. In multivariate analysis, age (HR 1.02, IC 95% 1.002–1.056, p = 0.033) and positive lymph nodes (HR 1.82, IC 95% 1.034–3.211, p = 0.038) were the only prognostic factors for OS. However, females with MSI-high tumors treated with POPChT demonstrated a significantly increased OS compared to females with MSS tumors (p = 0.031). In conclusion, we found a high proportion of MSI-high cases. MSI and EBV status did not influence OS or PFS either in patients submitted to POPChT or surgery alone. However, superior survival of females with MSI-high tumors suggests that sex disparities and molecular classification may influence treatment options in GC.publishersversionpublishe

EBV and MSI status in gastric cancer: does it matter?

We investigated the impactof microsatellite instability (MSI) and Epstein–Barr virus (EBV) status in gastric cancer (GC), regarding response to perioperative chemotherapy (POPChT), overall survival (OS), and progression-free survival (PFS). We included 137 cases of operated GC, 51 of which were submitted to POPChT. MSI status was determined by multiplex PCR and EBV status by EBV-encoded RNA in situ hybridization. Thirty-seven (27%) cases presented as MSI-high, and seven (5.1%) were EBV+. Concerning tumor regression after POPChT, no differences were observed between the molecular subtypes, but females were more likely to respond (p = 0.062). No significant differences were found in OS or PFS between different subtypes. In multivariate analysis, age (HR 1.02, IC 95% 1.002–1.056, p = 0.033) and positive lymph nodes (HR 1.82, IC 95% 1.034–3.211, p = 0.038) were the only prognostic factors for OS. However, females with MSI-high tumors treated with POPChT demonstrated a significantly increased OS compared to females with MSS tumors (p = 0.031). In conclusion, we found a high proportion of MSI-high cases. MSI and EBV status did not influence OS or PFS either in patients submitted to POPChT or surgery alone. However, superior survival of females with MSI-high tumors suggests that sex disparities and molecular classification may influence treatment options in GC.info:eu-repo/semantics/publishedVersio

Análise comparativa de tabela de composição nutricional de biscoito salgado cream cracker com resultados laboratoriais / Comparative analysis of table of nutritional composition of biscoito salgado cream cracker with laboratory results

O estudo da composição centesimal serve de ferramenta para a análise de alimentos, tornando-se essencial para o consumo equilibrado de nutrientes, seguindo a Ingestão Diária Recomendada. A determinação dos componentes existentes nos alimentos possibilita a rotulagem nutricional fiel ao conteúdo disponibilizado ao consumidor, sem a qual ele não poderia exercer seu direito de escolha do produto. Este trabalho objetivou realizar um estudo comparativo da composição nutricional apresentada pela embalagem comercial de biscoito salgado cream cracker, com os achados a partir da análise centesimal do produto. A análise centesimal seguiu a metodologia estabelecida pelo Instituto Adolfo Lutz. Os resultados a partir dos dados experimentais diferem dos informados pela embalagem, sendo confirmados pela análise estatística. Portanto, através da análise centesimal realizada foi possível detectar que as informações contidas na embalagem do produto não condizem com as evidenciadas em laboratório

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Groove Pancreatitis: Clinical Cases and Review of the Literature

Introduction: Groove pancreatitis (GP) is a type of chronic segmental pancreatitis that affects the pancreatoduodenal groove area, and it is often misdiagnosed. Outflow obstruction of the minor papilla associated with alcohol consumption seems to be the main pathophysiological mechanism, and it affects mainly middle-aged males. Symptoms include nausea and postprandial vomiting from gastric outlet obstruction, weight loss, and abdominal pain. Despite modern advances, such as radiological and endoscopic methods, distinction between GP and pancreatic cancer remains a challenge, and histological examination is sometimes necessary. When a diagnosis can be obtained without a surgical specimen, management can be conservative in the absence of acute or chronic complications. Case Presentation: The authors present 2 clinical cases which portray the diagnostic workup and management decisions of this entity. Discussion/Conclusion: GP is a clinical entity, offering diagnostic and therapeutic challenges. Imaging exams are crucial in the diagnosis and follow-up, but surgery may be necessary in a significant number of cases due to the incapacity to rule out malignancy

Role of endoscopic biopsies and morphologic features in predicting microsatellite instability status in gastric cancer

Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.Evaluation of mismatch repair (MMR) protein and microsatellite instability (MSI) status plays a pivotal role in the management of gastric cancer (GC) patients. In this study, we aimed to evaluate the accuracy of gastric endoscopic biopsies (EBs) in predicting MMR/MSI status and to uncover histopathologic features associated with MSI. A multicentric series of 140 GCs was collected retrospectively, in which EB and matched surgical specimens (SSs) were available. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMR status and by multiplex polymerase chain reaction (mPCR) for MSI status. IHC allowed accurate evaluation of MMR status in EB (sensitivity: 97.3%; specificity: 98.0%) and high concordance rates between EB and SS (Cohen κ=94.5%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in evaluating MSI status (91.3% vs. 97.3%), while maintaining maximal specificity (100.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as a confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified specific histopathologic features that are significantly associated with MMR/MSI status in GC, despite the morphologic heterogeneity of GC cases harboring this molecular phenotype. In SS, these features included the presence of mucinous and/or solid components ( P =0.034 and <0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation ( P <0.001). In EB, both solid areas and extracellular mucin lakes were also discriminating features for the identification of MSI-high cases ( P =0.002 and 0.045).info:eu-repo/semantics/publishedVersio