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OBJECTIVE: To develop and validate in-hospital mortality risk score comprising radiological aberrances in chest computed tomography (CT) performed on admission. PATIENTS AND METHODS: Single-center, longitudinal cohort study in adult patients admitted with Coronavirus Disease 2019 (COVID-19) to our ward. Patients were followed-up during hospitalization until discharge or death. Eligibility criteria for the study comprised positive real-time reverse transcription-polymerase chain reaction test (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and ground-glass opacities in chest CT. In-hospital death was the outcome of interest. Radiological, laboratory, and clinical data were analyzed. Radiological determinants of mortality were used as variables in multivariate logistic regression analysis, and results were used to build a radiological risk score. RESULTS: 371 patients were enrolled in development and validation cohorts (181 and 190 respectively), with a total of 47 non-survivors. Univariate analysis data determined 12 predictive factors (nine risk and three protective). In multivariate analysis, we developed COVID-RRS (COVID-19 Radiological Risk Score) - a radiological score predicting in-hospital COVID-19 mortality risk comprising estimated lung involvement percentage, pleural effusion, and domination of consolidation-type changes in chest CT. Our score was superior in the prediction of COVID-19 mortality to the percentage of lung involvement alone, Chest Computed Tomography Severity Score (CTSS), and Total Severity Score (TSS) in both groups with AUC of 0.910 and 0.902, respectively (p <0.001). CONCLUSIONS: Additional imaging features independently contribute to COVID-19 mortality risk. Our model comprising lung involvement estimation, pleural effusion, and domination of consolidations performed significantly better than scores based on the extent of the changes alone. COVID-RRS is a simple, reliable, and ready-to-use tool for clinical practice.
Assuntos
COVID-19 , Derrame Pleural , Adulto , Humanos , COVID-19/diagnóstico por imagem , Mortalidade Hospitalar , SARS-CoV-2 , Estudos Longitudinais , Estudos Retrospectivos , Pulmão/diagnóstico por imagemRESUMO
Chronic hepatitis C (CHC) infection is known to induce important changes in host cholesterol metabolism. MicroRNAs (miRNAs) regulate the expression of many genes and, in consequence, control various processes, including human metabolism and response to viral infection. Recently, the alteration of the immune-associated miR-146a, which is abundantly present in peripheral blood mononuclear cells (PBMCs), was found in some viral infections. The study aimed to analyse the influence of hepatitis C virus (HCV) infection on miR-146a expression in PBMCs in vivo and in vitro, as well as to assess the possible impact of miR-146a alteration on the intracellular cholesterol level in PBMCs. Blood samples collected from 42 healthy donors and 72 CHC patients were the source of materials. HCV RNA, intracellular cholesterol level and miR-146a expression were determined in PBMCs, as well as HCV genotype and interferon (IFN)α concentration in sera. The influence of miR-146a inhibition on cholesterol expression in PBMCs was analysed in vitro after transient cell transfections with mirVana™ anti-miR-146a Inhibitor. Our data demonstrated an alteration of miR-146a and intracellular cholesterol expression in PBMCs and of IFNα concentration in sera of genotype 1, HCV-infected patients compared to the healthy donors. Also, in cultured PBMCs, miR-146a expression and intracellular cholesterol level were significantly decreased in CHC patients compared to the healthy donors. In vitro blockage of miR-146a expression in PBMCs of CHC patients greatly impaired intracellular cholesterol expression. In these conditions, miR-146a expression was positively correlated with the intracellular cholesterol level. These results suggest that genotype 1 HCV infection may alter miR-146a expression in PBMCs and, consequently, contribute to the observed dysregulation of cholesterol synthesis.
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Colesterol/análise , Expressão Gênica , Hepatite C Crônica/patologia , Leucócitos Mononucleares/química , MicroRNAs/análise , Adulto , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Humanos , Interferon-alfa/sangue , Masculino , MicroRNAs/genética , Adulto JovemRESUMO
The modulation of the gamma-aminobutyric acid type A (GABA A) receptors activity was observed in several chronic hepatitis failures, including hepatitis C. The expression of GABA A receptor subunits α1 and ß3 was detected in peripheral blood mononuclear cells (PBMCs) originated from healthy donors. The aim of the study was to evaluate if GABA A α1 and ß3 expression can also be observed in PBMCs from chronic hepatitis C (CHC) patients and to evaluate a possible association between their expression and the course of hepatitis C virus (HCV) infection. GABA A α1- and ß3-specific mRNAs presence and a protein expression in PBMCs from healthy donors and CHC patients were screened by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. In patients, HCV RNA was determined in sera and PBMCs. It was shown that GABA A α1 and ß3 expression was significantly different in PBMCs from CHC patients and healthy donors. In comparison to healthy donors, CHC patients were found to present an increase in the expression of GABA A α1 subunit and a decrease in the expression of ß3 subunit in their PBMCs. The modulation of α1 and ß3 GABA A receptors subunits expression in PBMCs may be associated with ongoing or past HCV infection.
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Expressão Gênica , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Receptores de GABA-A/biossíntese , Adolescente , Adulto , Western Blotting , Feminino , Perfilação da Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Subunidades Proteicas/biossíntese , Subunidades Proteicas/genética , RNA Viral/sangue , Receptores de GABA-A/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
Chronic hepatitis caused by Hepatitis C virus (HCV) is the main source of liver cirrhosis, hepatocellular carcinoma, and extra-hepatic diseases. After treatment-induced resolution of hepatitis C, the persistence of HCV RNA in serum and peripheral blood mononuclear cells (PBMCs) is often observed. An expression of the precursor of microRNA-155 (miR-155) called BIC can be the factor responsible for a course of HCV infection. Therefore, we assessed the relationship between BIC expression and HCV RNA status in sera and PBMCs samples of 64 hepatitis C patients treated with interferon alpha(IFN-alpha)+ribavirin. High expression of BIC in PBMCs was determined in 100% of patients that harbored HCV RNA in serum and PBMCs. Further, we found that 83% of PBMCs samples were BIC-positive in a group of patients that eliminated HCV RNA only from serum. The lowest expression of BIC was found in patients that eliminated HCV RNA from both serum and PBMCs.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Leucócitos Mononucleares/metabolismo , MicroRNAs/sangue , Precursores de RNA/sangue , RNA Viral/sangue , Adolescente , Criança , Quimioterapia Combinada , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Leucócitos Mononucleares/virologia , MicroRNAs/genética , Precursores de RNA/genética , RNA Viral/genética , Proteínas Recombinantes , Ribavirina/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Data on the role of Chlamydia pneumoniae in patients with ischemic stroke are inconsistent. We investigated the presence of anti-C. pneumoniae antibodies in young adults with ischemic stroke. METHODS: 94 patients (<55 years) with ischemic stroke and 103 controls were enrolled. Indices of anti-C. pneumoniae IgA and IgG were assessed with an ELISA. We determined OR and 95% CI for the IgA and IgG seropositivity in stroke cases. RESULTS: Mean IgA and IgG indices were higher in stroke patients vs controls (IgA: 1.40 vs 0.56; P < 0.001; IgG: 0.85 vs. 0.78; P < 0.003). The IgA seropositivity was associated with stroke risk (11.92; 5.94-23.92; P < 0.001) as well as IgG seropositivity was (2.31; 1.15-4.61; P < 0.016). Seropositivity assessed with combined IgA and IgG indices was associated with increased stroke risk (OR 9.35; 95% CI 4.78-18.29; P < 0.0001). After controlling for age and sex, the IgA seropositivity yielded a significantly adjusted OR for stroke (8.95; 4.44-18.07; P < 0.002), while IgG seropositivity did not (0.85; 0.53-1.63). CONCLUSIONS: We find an increased risk of stroke in young patients seropositive to C. pneumoniae in the IgA antibody class. Further studies to explore this finding are warranted.
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Isquemia Encefálica/sangue , Chlamydophila pneumoniae/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Acidente Vascular Cerebral/sangue , Adulto , Fatores Etários , Isquemia Encefálica/complicações , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
UNLABELLED: The correlations between the severity of hepatic lesions, age, gender, HBV co-infection and negativisation of HCV-RNA from serum and peripheral blood mononuclear cells (PBMC) after treatment of chronic hepatitis C (CHC) were analysed. 41 children (11 F/ 30 M), aged 5-16 years (mean 10 +/- 2.8), were treated with IFN-alpha and ribavirin for 12 months. Sustained negativisation of HCV-RNA from serum was achieved in 25 patients (61%), in 3 (7%) it reappeared after treatment, and in 13 (32%) it was ineffective. Clearance of HCV did not correlate with age (p = 0.65), sex (p = 0.13), past HBV infection (n = 22 anti-HBc +) (p = 0.24), maximum pre-treatment ALT activity (p = 0.06), grade of inflammation (p = 0.33) or stage of fibrosis (p = 0.9) in liver biopsy. It was achieved in 6/16 children previously resistant to IFN-a monotherapy and in 19/25 naive (p = 0.017). HCV-RNA was detected in PBMC in 9/24 (37%) seronegative children and in 1/21 (5%) in comparative group of seronegative adults; p = 0.004. Persistence of HCV-RNA in PBMC after combined treatment occurred in 5/10 (50%) patients resistant to previous IFN-alpha monotherapy, 6/35 (20%) of them cleared HCV from PBMC (p = 0.04). CONCLUSIONS: Age and gender, infection route, history of HBV infection or severity of histopathologic liver lesions had no influence on the efficacy of treatment with IFN-alpha and ribavirin. Clearance of HCV from serum and from PBMC occurs less frequently in patients previously resistant to IFN-alpha. Children with CHC require longitudinal observation after successful antiviral treatment as in 37% of those considered to be free from the virus by ordinary measures, HCV-RNA was found in PBMC.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , RNA Viral/sangue , RNA Viral/efeitos dos fármacos , Ribavirina/uso terapêutico , Adolescente , Criança , Pré-Escolar , Farmacorresistência Viral Múltipla/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Masculino , Polônia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Reliable data on stroke incidence and prevalence are essential for calculating the burden of stroke and the planning of prevention and treatment of stroke patients. In the current study we have reviewed the published data from EU countries, Iceland, Norway, and Switzerland, and provide WHO estimates for stroke incidence and prevalence in these countries. Studies on stroke epidemiology published in peer-reviewed journals during the past 10 years were identified using Medline/PubMed searches, and reviewed using the structure of WHO's stroke component of the WHO InfoBase. WHO estimates for stroke incidence and prevalence for each country were calculated from routine mortality statistics. Rates from studies that met the 'ideal' criteria were compared with WHO's estimates. Forty-four incidence studies and 12 prevalence studies were identified. There were several methodological differences that hampered comparisons of data. WHO stroke estimates were in good agreement with results from 'ideal' stroke population studies. According to the WHO estimates the number of stroke events in these selected countries is likely to increase from 1.1 million per year in 2000 to more than 1.5 million per year in 2025 solely because of the demographic changes. Until better and more stroke studies are available, the WHO stroke estimates may provide the best data for understanding the stroke burden in countries where no stroke data currently exists. A standardized protocol for stroke surveillance is recommended.
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Vigilância da População/métodos , Acidente Vascular Cerebral/epidemiologia , Distribuição por Idade , Fatores Etários , Estudos Epidemiológicos , Europa (Continente)/epidemiologia , Saúde Global , Humanos , Incidência , MEDLINE , Prevalência , Índice de Gravidade de DoençaRESUMO
Migraine is one of the most common neurological disorders and one of the most frequent primary headaches. It imposes a significant burden on the affected individuals, society and health care system. As the etiology and pathophysiology of migraine are not well understood, treatment is largely symptomatic. Patent foramen ovale is a remnant of a fetal circulation and is highly prevalent in the general population. Its presence was linked to several disorders including migraine. The aim of this review was to search in the available data the answer to the question whether the link between migraine and patent foramen ovale is coincidental or whether they represent a pathophysiological entity.
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Transtornos Cerebrovasculares/etiologia , Embolia Paradoxal/etiologia , Comunicação Interatrial/complicações , Transtornos de Enxaqueca/etiologia , Cateterismo Cardíaco , Comunicação Interatrial/terapia , Humanos , Transtornos de Enxaqueca/terapiaRESUMO
Although the major target organ for hepatitis B virus (HBV) is the liver, the possibility of infection of peripheral blood mononuclear cells (PBMCs) with HBV has also been reported. This study was performed to analyze the course of HBV infection of PBMCs and to investigate the influence of interleukin-6 (IL-6) on the efficiency of infection of PBMCs with HBV in vitro. PBMCs isolated from a healthy donor were infected by exposing to a HBsAg-, HBeAg-positive serum in the presence or absence of exogenous IL-6. The efficiency of infection was estimated by HBV DNA determination in the cells and medium in the course of infection. The results of this study show that the presence of IL-6 during the PBMCs infection with HBV increased the efficiency of this infection.
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Vírus da Hepatite B/crescimento & desenvolvimento , Interleucina-6/farmacologia , Leucócitos Mononucleares/virologia , Células Cultivadas , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Fatores de Tempo , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Although diabetes mellitus (DM) is a risk factor for stroke, it is unclear whether stroke features are different in diabetic vs nondiabetic individuals. OBJECTIVE: To assess the role of DM in stroke patients. METHODS: Risk factors, etiology, lesion topography, clinical features, and outcome were assessed in 611 diabetic individuals (history of DM or fasting plasma glucose level of > or =7.0 mmol/L) among 4,064 consecutive patients of the Lausanne Stroke Registry. RESULTS: Patients with DM were 5.3 years older than non-DM patients. After multivariate analysis, DM was associated with lower relative prevalence of intracerebral hemorrhage (ICH; odds ratio [95% CI]: 0.63 (0.45 to 0.9); p = 0.022), higher relative prevalence of subcortical infarction (SCI; 1.34 [1.11 to 1.62]; p = 0.009), and higher relative frequency of small-vessel (SVD; 1.78 [1.31 to 3.82]; p = 0.012) and large-artery (LAD; 2.02 [1.31 to 2.02]; p = 0.002) disease. In the cohort of diabetic stroke patients, there was no interaction of DM with either hypertension or age for the outcomes of ICH, SCI, SVD, and LAD. Moderate to severe deficit on admission (31.1 vs 31.6%; p = 0.4) and poor functional outcome at 1 month (14.1 vs 15.3%; p = 0.24) did not differ in patients with DM compared with non-DM patients. In multivariate analysis, neither DM (0.86 [0.63 to 1.11]; p = 0.15) nor hypertension (1.09 [0.91 to 1.39]; p = 0.32) was associated with poor functional outcome. CONCLUSIONS: Diabetic stroke patients are associated with specific patterns of stroke type, etiology, and topography but not with poor functional outcome. There was no interaction between DM and hypertension or age.
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Diabetes Mellitus/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Fatores Etários , Idoso , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiologia , Infarto Cerebral/diagnóstico , Infarto Cerebral/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde , Prevalência , Prognóstico , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Given the recent correlation between nutrition and risk for eye disease, there is keen interest in a possible correlation between nutrient intake and eye-tissue nutrient levels. In this work, the objective was (1) to determine, for the first time, the relation between dietary intake of vitamin C and eye tissue levels of the vitamin in free-living humans, (2) to determine the relation between levels of the vitamin in plasma, lens and aqueous, and (3) to compare this information to data gathered for a carefully reared group of guinea pigs that were fed different levels of vitamin C. METHODS: Two hundred sixty-five cataract patients (mean age = 72 years) from a clinical practice were recruited for this study. One hundred thirty-two patients provided the dietary intake data via a food frequency questionnaire, which we used for this work. Plasma, aqueous humor, and lens samples were obtained at the time of lentectomy and preserved for vitamin C analysis. Comparable samples were obtained from male Hartley white guinea pigs that were fed known amounts of vitamin C. Linear and log10-linear statistical models were also used to characterize the relation between vitamin C intake and human ocular tissue levels of the vitamin and to examine potential confounding and the effect of modification by age and sex. RESULTS: In humans, plasma and aqueous vitamin C concentrations were related to intake in a log-linear fashion, with slopes of 0.03 mM plasma vitamin C/log10-mg daily vitamin C intake and 0.41 mM aqueous vitamin C/log10-mg daily vitamin C intake. The best fit of vitamin C levels in lens and diet predicts a linear relationship with a sex-adjusted slope of 0.00094 mM lens vitamin C/mg daily vitamin C intake, although a log-linear relation can also be modeled. In guinea pigs, diet was related to eye tissue and plasma levels of the vitamin by a log10 linear relationship in all cases. Vitamin C in human lens was linearly related to plasma and aqueous vitamin C with slopes of 8.8 and 0.23, respectively. Vitamin C in aqueous was related to plasma in a log10-linear fashion with a slope of 1.6 mM aqueous vitamin C/log10 mM plasma vitamin C. In guinea pigs, vitamin C in plasma was related to aqueous and lens vitamin C by log10-linear relationships, whereas lens and aqueous vitamin C were clearly linearly related. CONCLUSIONS: Plasma and aqueous appear to be saturated in humans with intakes of < 250 mg vitamin C/day. However, a saturating relationship between lens vitamin C and dietary intake in humans was not indicated in this study, although such a relationship is seen in guinea pigs. Intertissue relations between vitamin C levels in humans and guinea pigs are similar for some but not all relations.