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BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.
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COVID-19 , Doenças do Sistema Nervoso , Humanos , Doenças do Sistema Nervoso/epidemiologia , Portugal/epidemiologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Aberrant crypt foci (ACF) are important biomarkers of sporadic CRC risk. Their correlation with the risk of intraepithelial neoplasia (IN) in UC remains unclear. AIMS: To assess whether ACF are a risk factor for IN in long-standing UC and to investigate any correlation between the clinico-epidemiological characteristics and prevalence/number of ACF in these patients. METHODS: Seventy-six patients with long-standing UC were prospectively screened by colonoscopy with chromoendoscopy-guided endomicroscopy. ACF were sought in the lower rectum. RESULTS: Eight INs were detected in seven (9.2%) patients. The ACF prevalence and mean number were 60.5% and 2.4 ± 2.8, respectively. The number of ACF was independently associated with the risk of having IN (odds ratio = 1.338; 95% confidence interval 1.030-1.738). ACF number revealed a good calibration (area under the receiver operating characteristic curve = 0.829) and discriminative ability (p = 0.205, Hosmer-Lemeshow test) for the prediction of synchronous IN. Patients with ≥3 ACF have a significantly higher prevalence of IN than patients with <3 ACF (22.6% vs. 0%, p = 0.001). Using this cut-off value, the performance of ACF in predicting the presence of IN was as follows: sensitivity = 100%, specificity = 65.2%, positive predictive value = 22.6%, and negative predictive value = 100%. Age >40 years, family history of CRC, and increased body mass index (BMI) were associated with a significantly higher number of ACF. CONCLUSION: Long-standing UC patients with ≥3 ACF have a significantly higher likelihood of having IN. Age >40 years, family history of CRC, and increased BMI have significant positive associations with the number of ACF.
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Focos de Criptas Aberrantes/patologia , Carcinoma in Situ/patologia , Colite Ulcerativa/patologia , Neoplasias Colorretais/patologia , Focos de Criptas Aberrantes/complicações , Focos de Criptas Aberrantes/epidemiologia , Focos de Criptas Aberrantes/genética , Adulto , Fatores Etários , Idoso , Área Sob a Curva , Índice de Massa Corporal , Carcinoma in Situ/complicações , Carcinoma in Situ/epidemiologia , Colite Ulcerativa/complicações , Colonoscopia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Estudos Transversais , Feminino , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Curva ROC , Reto , Fatores de RiscoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Current clinical/pathological criteria contribute to risk stratification, but are far from the desired on individualized medicine. Recently, HCC classifications have been published based on immunohistochemical and morphological features. METHODS: A retrospective review of patients submitted to surgical treatment-partial hepatectomy (PH) or liver transplantation (LT), with pathological diagnosis of HCC, in a 9-year period (2007-2015) was performed. RESULTS: Applying the classification of Srivastava et al. (#1), based on the expression of CD31, p53, AFP and CD44, tumour size and presence of vascular invasion, HCC were categorized as low- and high-risk HCC. With the classification of Tsujikawa et al. (#2), HCC were classified into biliary/stem cell marker positive, Wnt signalling positive and the "all negative" HCC, according to the expression of CK19, SALL4, ß-catenin glutamine synthetase, EpCAM and p53. There were sixty-six patients (53 males; 13 females), with median age of 64.5 ± 9.46 years (range 38-86), with solitary HCC, comprehending 37 PH (56.1%) and 29 LT (43.9%). The mean overall survival (OS) was 75.4 ± 6.9 months. Biliary/stem cell type of HCC was a predictive factor of worse OS on the overall population (24.4 versus 78.3 months, p = 0.032) and in PH cohort (11.5 versus 64.01 months, p = 0.016), on uni- and multivariate analyses. CONCLUSION: These results support the relevance of a risk stratification classification of HCC. Classification #2 seems adequate to our reality demonstrating OS impact, allowing its application in future biopsies, prompting individualized medicine.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Seleção de Pacientes , Estudos Retrospectivos , Células-TroncoRESUMO
Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases.
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Isquemia Encefálica/complicações , Fatores de Troca do Nucleotídeo Guanina/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , Acidente Vascular Cerebral/etiologia , Proteínas rho de Ligação ao GTP/genética , Adulto , Idade de Início , Idoso , Feminino , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/genéticaRESUMO
INTRODUCTION: Mesenchymal tumors of the liver are rare, and in this group, myxoid leiomyomas are even rarer. So far, only 2 cases have been reported in the literature. CASE PRESENTATION: We aim to report the case of a 16-year-old female with a large lesion on the right hepatic lobe, grossly composed of gelatinous and heterogeneous tissue. DISCUSSION: Histological evaluation revealed a benign mesenchymal neoplasm with expansive growth, paucicellular, with monotonous and dispersed spindle and ovoid cells, positive for α-smooth actin and h-caldesmon, without atypia or mitoses, consistent with the diagnosis of primary myxoid leiomyoma.
INTRODUÇÃO: Tumores mesenquimatosos do fígado são raros, e deste grupo os leiomiomas mixoides são ainda mais incomuns. Até ao momento foram apenas descritos dois casos na literatura. CASO CLÍNICO: Pretendemos efetuar a descrição de uma caso de uma menina de 16 anos com uma volumosa lesão no lobo hepático direito, que macroscopicamente era composta por um tecido gelatinoso e heterogéneo. CONCLUSÃO: Estudo histológico revelou uma lesão mesenquimatosa benigna de crescimento expansive, pouco celular, com células fusiformes e ovaladas, monótonas, com expressão de actina do músculo liso e h-caldesmon, sem atipia nem mitoses, consistente com o diagnóstico de leiomioma mixoide.
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BACKGROUND: The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk. METHODS: We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk. RESULTS: Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect. CONCLUSION: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.
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Isquemia Encefálica/genética , DNA Mitocondrial/genética , Predisposição Genética para Doença , Haplótipos/genética , Acidente Vascular Cerebral/genética , Adulto , Isquemia Encefálica/complicações , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Portugal , Fatores de Risco , Acidente Vascular Cerebral/etiologiaAssuntos
Neoplasias do Apêndice , Apêndice , Tumor de Células Granulares , Humanos , Neoplasias do Apêndice/diagnóstico por imagem , Neoplasias do Apêndice/cirurgia , Neoplasias do Apêndice/patologia , Apêndice/diagnóstico por imagem , Apêndice/cirurgia , Apêndice/patologia , Apendicectomia , Tumor de Células Granulares/diagnóstico por imagem , Tumor de Células Granulares/cirurgia , Tumor de Células Granulares/patologiaRESUMO
BACKGROUND AND AIMS: Histological healing has emerged as a promising therapeutic goal in ulcerative colitis. This is especially important in the context of biological therapies. The objectives of the present study were to investigate the ability of infliximab to induce histological remission in ulcerative colitis [UC] patients and to explore the utility of faecal calprotectin and lactoferrin in predicting histological activity. METHODS: Multi-centre, single-cohort, open-label, 52-week trial including moderately to severely biological-naïve UC patients receiving intravenous infliximab [5mg/kg]. The primary outcome was the proportion of patients with histological remission [Geboes index ≤ 3.0] after 8 weeks of treatment, scored by two independent pathologists. RESULTS: Twenty patients were included. The rate of histological remission increased from 5% at baseline to 15% and 35% at Week 8 and Week 52, respectively. At Week 8, 40% of patients were in clinical remission [Mayo ≤ 2] and 45% achieved mucosal healing [Mayo endoscopy subscore 0-1]. At Week 52, 25% of patients had clinical, endoscopic and histological remission. Faecal calprotectin and lactoferrin showed the highest correlation with histological activity at Week 8 (area under the curve [AUC] 94%, p = 0.017; and 96%, p = 0.013, respectively) and both markers revealed an excellent positive predictive value for this outcome at this time point [100%, p = 0.017; and 94%, p = 0.013, respectively]. CONCLUSIONS: Infliximab was able to induce histological remission. There was a good agreement between histology and faecal biomarkers. Faecal calprotectin and lactoferrin were good predictors of histological remission. Our data support inclusion of histology as a treatment target complementary to endoscopy in clinical trials when evaluating therapeutic response in UC.
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Colite Ulcerativa/tratamento farmacológico , Colo/patologia , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Adulto , Biomarcadores/análise , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Fezes/química , Feminino , Humanos , Lactoferrina/análise , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
OBJECTIVE: Description of the demographic, clinical and neuropathological features of 11 cases of Creutzfeldt-Jakob disease (CJD). METHOD: Review of the clinical and neuropathological features of patients with CJD diagnosed in hospitals in the North of Portugal between 1993 and 2002. RESULTS: Eleven patients were identified, 4 females: mean age of onset of symptoms--64 years, mean duration of disease--8 months. All presented with a syndrome of progressive dementia with myoclonus, with four patients presenting with cerebellar signs. Neuropathological examination of brain at autopsy showed spongiosis and reactive gliosis associated with neuronal loss. In eight cases immunocytochemistry for prion protein (PrP) was carried out and was positive. CONCLUSION: The group of patients described represents the heterogeneity of the clinical phenotypes possible in CJD. Neuropathological examination is still indispensable to make the definitive diagnosis of the disease.
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Encéfalo/patologia , Síndrome de Creutzfeldt-Jakob/patologia , Idade de Início , Idoso , Atrofia , Síndrome de Creutzfeldt-Jakob/genética , Diagnóstico Diferencial , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Portugal , Príons/análise , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND/AIM: Differences in stroke incidence and mortality between regions could stem from differences in the incidence of particular stroke types and long-term prognosis. The aim of this study was to investigate whether different risk profiles and stroke types underlie the difference in stroke incidence and patient long-term survival in rural and urban populations. METHODS: All suspected first-ever-in-a-lifetime strokes occurring between October 1998 and September 2000 in 37,290 residents of rural municipalities and in 86,023 individuals living in the city of Porto were entered into a population-based registry. Standard definitions of stroke types and overlapping comprehensive sources of information were used for patient identification. Patients were examined by neurologists at 3 months, 1 year and 7 years after the index event. RESULTS: From a total of 688 patients included (226 in rural and 462 in urban areas), 76.2% had an ischaemic stroke (IS; 75.3 vs. 77.9%), 16.1% a primary intracerebral haemorrhage (PICH; 16.3 vs. 14.6%) and 3.3% a subarachnoid haemorrhage (SAH; 2.7 vs. 3.7%); in 4.4% (4.9 vs. 4.1%), the stroke type could not be determined. The annual incidence rate per 1,000 was 2.13 (95% CI, 1.95-2.31), 0.45 (95% CI, 0.37-0.53), 0.09 (95% CI, 0.06-0.14) and 0.12 (95% CI, 0.08-0.17), respectively. The age-specific rural/urban incidence rate ratios for IS in the youngest group (<55 years) was 0.27 (95% CI, 0.11-0.69), increasing to 1.47 (95% CI, 1.07-2.01) for those aged 65-74 years and to 1.87 (95% CI, 1.39-2.52) for those between 75 and 84 years. Rural compared to urban patients with an IS were predominantly men, had a prevalence ratio (PR) of 1.28 (95% CI, 1.05-1.56), were 65 years or older (PR = 1.18; 95% CI, 1.08-1.30) and had in general a lower prevalence of risk factors. There was no evidence of rural/urban differences in 28-day case fatality for the stroke types, although IS tended to be less fatal among urban patients (10.3 vs. 13.1%), whereas PICH (33.3 vs. 24.2%) and SAH (35.3 vs. 16.7%) were less fatal among rural patients. Independently of rural/urban residence, predictors of poor survival after the acute phase (28 days) were age >65 years (HR = 3.57; 95% CI, 2.6-4.9), diabetes (HR = 1.5; 95% CI, 1.2-1.9), ischaemic heart disease (HR = 1.8; 95% CI, 1.3-2.6), atrial fibrillation (HR = 1.5; 95% CI, 1.1-2.0) and smoking habits (HR = 1.6; 95% CI, 1.1-2.3). CONCLUSIONS: The age pattern of IS incidence marks the difference between rural and urban populations; the youngest urban and the oldest rural residents were at a higher risk. Although patients from rural areas were older, the relatively lower prevalence of simultaneously occurring risk and prognostic factors among them as well as the similar management of rural and urban patients may justify why rurality is not associated with long-term survival.
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We hereby propose a novel approach to the identification of ischemic stroke (IS) susceptibility genes that involves converging data from several unbiased genetic and genomic tools. We tested the association between IS and genes differentially expressed between cases and controls, then determined which data mapped to previously reported linkage peaks and were nominally associated with stroke in published genome-wide association studies. We first performed gene expression profiling in peripheral blood mononuclear cells of 20 IS cases and 20 controls. Sixteen differentially expressed genes mapped to reported whole-genome linkage peaks, including the TTC7B gene, which has been associated with major cardiovascular disease. At the TTC7B locus, 46 tagging polymorphisms were tested for association in 565 Portuguese IS cases and 520 controls. Markers nominally associated in at least one test and defining associated haplotypes were then examined in 570 IS Spanish cases and 390 controls. Several polymorphisms and haplotypes in the intron 5-intron 6 region of TTC7B were also associated with IS risk in the Spanish and combined data sets. Multiple independent lines of evidence therefore support the role of TTC7B in stroke susceptibility, but further work is warranted to identify the exact risk variant and its pathogenic potential.
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Isquemia Encefálica/genética , Ligação Genética , Proteínas do Tecido Nervoso/genética , Polimorfismo Genético , Acidente Vascular Cerebral/genética , Idoso , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/metabolismo , Estudos de Casos e Controles , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Portugal , Fatores de Risco , Espanha , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/metabolismoRESUMO
ABSTRACT Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm that usually originates from abdominal soft tissues. A female patient aged 50 years presented with a 1.2 cm gallbladder polyp. The microscopic study showed spindle cell proliferation in an edematous background rich in lymphocytes and plasma cells. Immunohistochemistry showed positivity for vimentin, smooth muscle actin, and anaplastic lymphoma kinase (ALK), and negativity for other markers. Fluorescent in situ hybridization (FISH) revealed ALK gene rearrangement. The diagnosis was IMT of the gallbladder, a unique case considering that it was identified at the early stage of development of these neoplasms.
RESUMO Tumor miofibroblástico inflamatório (IMT) é uma neoplasia mesenquimatosa rara, geralmente com origem nos tecidos moles abdominais. Uma paciente do sexo feminino com 50 anos apresentou-se com pólipo da vesícula biliar com 1,2 cm. No estudo microscópico, observou-se proliferação de células fusiformes em fundo edematoso, rico em plasmócitos e linfócitos. Imuno-histoquicamente, notou-se positividade para vimentina, actina músculo liso e cinase do linfoma anaplásico (ALK), com negatividade de outros marcadores. Observou-se rearranjo do gene ALK por hibridização fluorescente in situ (FISH). O diagnóstico foi IMT da vesícula biliar, um caso único, considerando que foi identificado no estadio inicial de desenvolvimento dessas neoplasias.
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INTRODUÇÃO E OBJETIVO: Descrição das características demográficas, clinicas e neuropatológicas de 11 doentes com doença de Creutzfeldt-Jakob (DCJ). MÉTODO: Revisão clínica e neuropatológica de doentes com DCJ diagnosticados entre 1993 e 2002 em hospitais do Norte de Portugal. RESULTADOS: Foram identificados 11 doentes (4 do sexo feminino; idade média de início dos sintomas, 64 anos; média de duração da doença, 8 meses). Todos apresentaram síndrome demencial progressiva associada a mioclonias, sendo a síndrome cerebelar a forma de apresentação inicial em quatro deles. O estudo neuropatológico revelou sempre espongiose e gliose reativa associada a perda neuronal. O estudo imunocitoquímico para proteína priônica (PrP) foi positivo nos oito casos em que foi executado. CONCLUSÃO: O grupo de doentes descritos constitui uma série clinica representativa da heterogeneidade de fenótipos possíveis da DCJ esporádica. O estudo neuropatológico é ainda indispensável para o diagnóstico definitivo da doença