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1.
Eur J Neurol ; 26(2): 230-237, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30153363

RESUMO

BACKGROUND AND PURPOSE: The aim of this study was to describe the clinical and epidemiological characteristics of acute ischaemic stroke (AIS) in patients with atrial fibrillation (AF) previously treated with oral anticoagulants (OACs) according to the type of OAC prescribed. Also, to analyze the outcomes of the patients and the therapeutic approach adopted by the neurologist in the acute phase and for secondary prevention. METHODS: We performed a multicenter, observational study based on prospective registries. We included patients with AF treated with OACs admitted for AIS over a 1-year period. Detailed clinical data and functional outcome at 3 months (modified Rankin Scale score) were collected. Patients were divided into two groups according to their pre-AIS anticoagulant therapy: vitamin K antagonists (AIS-VKA) and direct-acting OACs (AIS-DOAC). RESULTS: We recruited 1240 patients (80.4% AIS-VKA and 19.6% AIS-DOAC). In the AIS-DOAC group, transient ischaemic attack was more frequent (18.1% vs. 10.8%; P = 0.001), symptomatic hemorrhagic transformation was less frequent (1.6% vs. 4.6%; P = 0.035) and hospital stay was shorter (median 6 vs. 7 days; P = 0.03). Intravenous thrombolysis was more commonly used in AIS-VKA (9.2% vs. 1.6%; P < 0.001). There were no differences between the groups with respect to mechanical thrombectomy, mortality and modified Rankin Scale score at 3 months. At 3 months, 54% of patients required a DOAC as antithrombotic treatment for secondary prevention. CONCLUSIONS: Patients with AF treated with DOACs who experienced AIS more frequently had transient symptoms (transient ischaemic attack), less symptomatic hemorrhagic transformation and a shorter mean stay than those treated with VKAs. Most patients who had been previously anticoagulated with AIS received long-term treatment with DOACs.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Infarto Cerebral/tratamento farmacológico , Ataque Isquêmico Transitório/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Infarto Cerebral/complicações , Feminino , Hospitalização , Humanos , Ataque Isquêmico Transitório/complicações , Masculino , Estudos Prospectivos , Sistema de Registros , Prevenção Secundária , Acidente Vascular Cerebral/complicações
2.
Neurologia ; 31(6): 395-400, 2016.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25529172

RESUMO

INTRODUCTION: Cardioembolic stroke is associated with poorer outcomes. Prevention is based on oral anticoagulant (OAC) therapy. Haemorrhage is the main complication of OACs, which are sometimes ineffective. PATIENTS AND METHODS: We retrospectively reviewed 1014 consecutive patients who suffered an ischaemic stroke between 2011 and 2013, analysing those who were receiving OAC treatment at stroke onset (107 patients in total) with special attention to aetiology, outcomes, and INR value in the acute phase. RESULTS: The mean age (SD) was 71.9 (10) years. Patients had been treated with OACs for 5.9 (5.5) years; 98.1% of them were being treated for heart disease. INR was <2 in 77 patients (72%), and 30 patients (28%) had an INR≥2. Nine patients (8.4%) had INR values within the therapeutic range. According to TOAST classification criteria, 88.8% of strokes were cardioembolic and 1.9% were atherothrombotic. Anticoagulation therapy was discontinued in 48 patients (44.9%) due to haemorrhagic transformation (24 patients), extensive infarction (23), or endarterectomy (1). Therapy was resumed in 24 patients (50%) after a mean lapse of 36 days. This was not possible in the remaining patients because of death or severe sequelae. New OACs (NOACs) were prescribed to 9 patients (18.7% of all potential candidates). At 3 months, patients with INR>1.7 in the acute phase exhibited better outcomes than patients with INR≤1.7 (mRS 0-2 in 62% vs 30.8%; death in 10% vs 38.4%; P=.0004). CONCLUSIONS: Some patients taking OACs suffer ischaemic strokes that are usually cardioembolic, especially if INR is below the therapeutic range. OACs can be resumed without complications, and NOACs are still underused. Despite cases in which treatment is ineffective, outcomes are better when INR is above 1.7 at stroke onset.


Assuntos
Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Adolescente , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Isquemia Encefálica/complicações , Estudos de Coortes , Feminino , Humanos , Coeficiente Internacional Normatizado , Hemorragias Intracranianas/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
3.
Sci Rep ; 14(1): 10775, 2024 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-38730261

RESUMO

Accurate short-term predictions of COVID-19 cases with empirical models allow Health Officials to prepare for hospital contingencies in a two-three week window given the delay between case reporting and the admission of patients in a hospital. We investigate the ability of Gompertz-type empiric models to provide accurate prediction up to two and three weeks to give a large window of preparation in case of a surge in virus transmission. We investigate the stability of the prediction and its accuracy using bi-weekly predictions during the last trimester of 2020 and 2021. Using data from 2020, we show that understanding and correcting for the daily reporting structure of cases in the different countries is key to accomplish accurate predictions. Furthermore, we found that filtering out predictions that are highly unstable to changes in the parameters of the model, which are roughly 20%, reduces strongly the number of predictions that are way-off. The method is then tested for robustness with data from 2021. We found that, for this data, only 1-2% of the one-week predictions were off by more than 50%. This increased to 3% for two-week predictions, and only for three-week predictions it reached 10%.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/virologia , Humanos , SARS-CoV-2/isolamento & purificação , Fatores de Tempo , Modelos Estatísticos
5.
Cerebrovasc Dis ; 33(2): 182-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22237056

RESUMO

BACKGROUND: Several clinical scales have been developed for predicting stroke recurrence. These clinical scores could be extremely useful to guide triage decisions. Our goal was to compare the very early predictive accuracy of the most relevant clinical scores [age, blood pressure, clinical features and duration of symptoms (ABCD) score, ABCD and diabetes (ABCD2) score, ABCD and brain infarction on imaging score, ABCD2 and brain infarction on imaging score, ABCD and prior TIA within 1 week of the index event (ABCD3) score, California Risk Score, Essen Stroke Risk Score and Stroke Prognosis Instrument II] in consecutive transient ischemic attack (TIA) patients. METHODS: Between April 2008 and December 2009, we included 1,255 consecutive TIA patients from 30 Spanish stroke centers (PROMAPA study). A neurologist treated all patients within the first 48 h after symptom onset. The duration and typology of clinical symptoms, vascular risk factors and etiological work-ups were prospectively recorded in a case report form in order to calculate established prognostic scores. We determined the early short-term risk of stroke (at 7 and 90 days). To evaluate the performance of each model, we calculated the area under the receiver operating characteristic curve. Cox proportional hazards multivariate analyses determining independent predictors of stroke recurrence using the different components of all clinical scores were calculated. RESULTS: We calculated clinical scales for 1,137 patients (90.6%). Seven-day and 90-day stroke risks were 2.6 and 3.8%, respectively. Large-artery atherosclerosis (LAA) was observed in 190 patients (16.7%). We could confirm the predictive value of the ABCD3 score for stroke recurrence at the 7-day follow-up [0.66, 95% confidence interval (CI) 0.54-0.77] and 90-day follow-up (0.61, 95% CI 0.52-0.70), which improved when we added vascular imaging information and derived ABCD3V scores by assigning 2 points for at least 50% symptomatic stenosis on carotid or intracranial imaging (0.69, 95% CI 0.57-0.81, and 0.63, 95% CI 0.51-0.69, respectively). When we evaluated each component of all clinical scores using Cox regression analyses, we observed that prior TIA and LAA were independent predictors of stroke recurrence at the 7-day follow-up [hazard ratio (HR) 3.97, 95% CI 1.91-8.26, p < 0.001, and HR 3.11, 95% CI 1.47-6.58, p = 0.003, respectively] and 90-day follow-up (HR 2.35, 95% CI 1.28-4.31, p = 0.006, and HR 2.20, 95% CI 1.15-4.21, p = 0.018, respectively). CONCLUSION: All published scores that do not take into account vascular imaging or prior TIA when identifying stroke risk after TIA failed to predict risk when applied by neurologists. Clinical scores were not able to replace extensive emergent diagnostic evaluations such as vascular imaging, and they should take into account unstable patients with recent prior transient episodes.


Assuntos
Indicadores Básicos de Saúde , Ataque Isquêmico Transitório/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Sistema de Registros , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Fatores de Tempo
7.
Neurologia ; 27(6): 330-5, 2012.
Artigo em Espanhol | MEDLINE | ID: mdl-22341984

RESUMO

INTRODUCTION: Cerebellar infarction (CI) is uncommon, but may result in severe complications. The aim of our study was to determine the characteristics of patients with CI, as well as their outcomes as regards the territories affected. PATIENTS AND METHODS: Data were collected from 124 patients admitted to our department during a five-year period, with a radiological diagnosis of CI, and with or without involvement of other brain territories. RESULTS: The mean age in our series was 65.2 years, with most being male (68.5%). The posterior inferior cerebellar artery (PICA) was the most commonly affected territory at 49.2%, followed by superior cerebellar artery (SCA) at 17.7%, and anterior inferior cerebellar artery (AICA) at 10.5%. There was simultaneous supratentorial involvement in 13.7%, and two or three cerebellar arteries involved in 8.9%. The main aetiology in PICA was atherothrombosis (P=.02). On the other hand, cardio-embolism was the main origin in cases with more than one affected territory (P=.04). No particular aetiology could be found in SCA and AICA. There was haemorrhagic transformation in 29 patients (23.4%), particularly in the PICA and when other territories were involved. There was hydrocephalus in 15 patients (12.1%, 12 of them PICA; P=.02) in 2.9 ± 1.5 days from stroke onset. At discharge, the degree of disability was worse if more than one arterial territory was involved (Rankin ≥ 3, 64% versus 31-36%; P=.05). Four (3.2%) patients died. CONCLUSIONS: CI is very heterogeneous. Nevertheless, it is noteworthy that PICA infarction is the most frequent type and its aetiology is usually atherothrombotic. Moreover, it is the territory most frequently associated with severe complications, which take place during the first week of the stroke.


Assuntos
Doenças Cerebelares/terapia , Infarto Cerebral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cerebelares/complicações , Doenças Cerebelares/patologia , Artérias Cerebrais/patologia , Infarto Cerebral/complicações , Infarto Cerebral/patologia , Avaliação da Deficiência , Feminino , Humanos , Hidrocefalia/complicações , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/patologia , Trombose Intracraniana/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
8.
Neurologia (Engl Ed) ; 37(2): 136-150, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34906541

RESUMO

INTRODUCTION: Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. METHODS: A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. CONCLUSIONS: PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels < 20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients.


Assuntos
Anticolesterolemiantes , Isquemia Encefálica , Acidente Vascular Cerebral , Anticolesterolemiantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Humanos , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Prevenção Secundária , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Subtilisinas
9.
J Econ Entomol ; 104(4): 1406-14, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21882710

RESUMO

The majority of plant viruses are dependent on arthropod vectors for spread between plants. Wheat streak mosaic virus (family Potyviridae, genus Tritimovirus, WSMV) is transmitted by the wheat curl mite, Aceria tosichella Keifer, and this virus and vector cause extensive yield losses in most major wheat (Triticum aestivum L.)-growing regions of the world. Many cultivars in use are susceptible to this vector-virus complex, and yield losses of 10-99% have been documented. wheat curl mite resistance genes have been identified in goat grass, Aegilops tauschii (Coss) Schmal., and transferred to hexaploid wheat, but very few varieties contain effectively wheat curl mite resistance, due to virulent wheat curl mite populations. However, wheat curl mite resistance remains an effective strategy to reduce losses due to WSMV. The goal of our project was to identify the most effective, reproducible, and rapid method for assessing wheat curl mite resistance. We also wanted to determine whether mite resistance is affected by WSMV infection, because the pathogen and pest commonly occur together. Single and group wheat curl mite infestations produced similar amounts of leaf rolling and folding on wheat curl mite-susceptible wheat varieties that were independent of initial wheat curl mite infestation. This finding will allow accurate, efficient, large-scale screening of wheat germplasm for wheat curl mite resistance by infesting plants with sections of wheat leaf tissue containing mixed stages of wheat curl mite. The wheat curl mite-resistant breeding line 'OK05312' displayed antibiosis (reduced wheat curl mite population development). The effect of WSMV infection on wheat curl mite reproduction was genotype-dependent. Mite populations increased on infected wheat curl mite- and WSMV-susceptible plants compared with uninfected plants, but WSMV infection had no significant effect on wheat curl mite populations on resistant plants. OK05312 is a strong source of wheat curl mite resistance for wheat breeding programs.


Assuntos
Interações Hospedeiro-Parasita , Insetos Vetores/imunologia , Ácaros/imunologia , Potyviridae/fisiologia , Triticum/imunologia , Animais , Antibiose , Comportamento Alimentar , Insetos Vetores/virologia , Ácaros/virologia , Doenças das Plantas/virologia , Triticum/parasitologia , Triticum/virologia
10.
Acta Ortop Mex ; 35(2): 211-214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34731926

RESUMO

Epithelioma cuniculatum is characterized as a slow growing lesion on the sole of the foot. A diagnosis is usually delayed by a low clinical suspicion and misdirection due to its similarity to an infection. This tumor rarely metastasize but a local invasion of adjacent soft tissues is common, requiring ample surgical resection or even amputation in advanced cases. We report a case a 76-year-old patient with a 5-year-old lesion on the sole of the foot, which was originally treated as a wart without improvement while the lesion slowly evolved. The patient was referred to our center with a diagnosis of chronic osteomyelitis. An excisional biopsy revealed an invasive keratinizing squamous carcinoma. In this advanced phase of the disease the only possible treatment was a Syme amputation.


El epitelioma cuniculatum se caracteriza por una lesión de crecimiento lento en la planta del pie cuyo diagnóstico suele retrasarse por la baja sospecha clínica y por su similitud con una infección. Este tumor raramente metastatiza, pero es común que produzca una invasión local a los tejidos blandos adyacentes, requiriendo una amplia resección quirúrgica o incluso una amputación en casos avanzados. Presentamos un caso de un paciente de 76 años con una lesión de 5 años de edad en la planta del pie, que originalmente fue tratada como una verruga plantar común sin mejoría, mientras que la lesión evolucionó lentamente. El paciente fue remitido a nuestro centro con un diagnóstico de osteomielitis crónica. Una biopsia excisional reveló un carcinoma escamoso queratinizante invasivo. En esta fase avanzada de la enfermedad el único tratamiento posible fue una amputación de Syme.


Assuntos
Neoplasias Ósseas , Carcinoma Verrucoso , Doenças do Pé , Idoso , Amputação Cirúrgica , Pré-Escolar , , Doenças do Pé/diagnóstico , Doenças do Pé/cirurgia , Humanos
11.
Seizure ; 89: 5-9, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33933947

RESUMO

INTRODUCTION: New treatments for acute ischaemic stroke, such as mechanical thrombectomy, can achieve reperfusion of large ischaemic tissue. Some studies have suggested that reperfusion therapies can increase the risk of suffering acute symptomatic seizure (ASS) and poststroke epilepsy (PSE). The aim of the study was to determine the incidence of ASS and PSE in patients undergoing thrombectomy, and related factors. PATIENTS AND METHODS: This was a retrospective single-centre study including patients with ischaemic stroke and NIHSS> 8 treated with thrombectomy with a follow-up ≥5 years. We evaluated several epidemiological, radiological, clinical and electroencephalographic variables. RESULTS: Of the 344 included patients, 21 (6.1%) presented ASS, 53 (15.40%) died in the acute phase, and 13 (4.46%) died during the first year. The degree of reperfusion (p 0.029), advanced age (p 0.035), and haemorrhagic transformation (p 0.038) increased the risk of suffering ASS, with degree of reperfusion being an independent factor, OR 2.02 (1.21-4.64). The incidence of PSE was 4.12% in the first year, 3.72% in the second, and 1.61% in the fifth. The accumulated incidence at 5 years was 8.93%. Related risk factor for suffering PSE was ASS (p < 0.001), yielding an OR value of 2.00 (1.28-3.145). CONCLUSIONS: Thrombectomy doesn´t increase the risk of ASS. A higher percentage of reperfusion, advanced age, and haemorrhagic transformation are associated with an increased risk of ASS. ASS is a risk factor for suffering PSE. In terms of mortality, having suffered ASS and/or PSE does not increase acute or long-term mortality.


Assuntos
Isquemia Encefálica , Epilepsia , Acidente Vascular Cerebral , Isquemia Encefálica/epidemiologia , Epilepsia/epidemiologia , Epilepsia/etiologia , Seguimentos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Convulsões/epidemiologia , Convulsões/etiologia , Acidente Vascular Cerebral/epidemiologia , Trombectomia , Resultado do Tratamento
13.
J Econ Entomol ; 103(3): 938-48, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20568641

RESUMO

The Russian wheat aphid, Diruaphis noxia (Kurdjumov) (Hemiptera: Aphididae), is globally one of the most devastating pests of bread wheat, Tritium aestivum L.; durum wheat, Triticum turgidum L.; and barley, Hordeum vulgare L. Host plant resistance is the foundation for cereal insect pest management programs, and several sources of D. noxia resistance have been incorporated in cultivars to manage D. noxia damage. The emergence of D. noxia North American biotype 2 (RWA2) in Colorado has made all known Dn genes vulnerable except the Dn7 gene from rye, Secale cereale, and has warranted exploration for sources of resistance to both RWA1 and RWA2. The category of resistance in resistant donor plants may exert selection pressure over the aphid population to form a new virulent population. In the current study, we report tolerance and antibiosis resistance to RWA1 and RWA2 in the barley genotype 'Stoneham'. The rate and degree of expression of resistance in Stoneham against RWA1 and RWA2, although not similar, are greater than the partial resistance in 'Sidney'. Antixenosis resistance to RWA1 or RWA2 was not observed in Sidney or Stoneham. The tolerance identified in Stoneham is encouraging because it may delay D. noxia biotype selection and fits well in a dryland barley cropping system.


Assuntos
Afídeos/fisiologia , Hordeum , Animais , Variação Genética
14.
AJNR Am J Neuroradiol ; 41(8): 1365-1369, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32527842

RESUMO

The rapid spread of the coronavirus disease 2019 (COVID-19) pandemic has shaken hospitals worldwide. Some authors suggest that neurologic involvement could further complicate the disease. This descriptive study is a cross-sectional review of 103 patients diagnosed with COVID-19 who underwent neuroimaging (of a total of 2249 patients with COVID-19 in our center). Analyzed variables were neurologic symptoms and acute imaging findings. The most frequent symptoms that motivated neuroimaging examinations were mild nonfocal neurologic symptoms, code stroke (refers to patients presenting with signs and symptoms of stroke whose hyperacute assessment and care is prioritized), focal neurologic symptoms, postsedation encephalopathy, and seizures. No cases of encephalitis or direct central nervous system involvement were detected. Thirteen patients presented with acute ischemic events, and 7, with hemorrhagic events; however, most reported multiple vascular risk factors. Despite the large cohort of patients with COVID-19, we found a large number of symptomatic patients with negative neuroimaging findings, and no conclusions can be drawn concerning concrete associations between neuroimaging and COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Neuroimagem , Pneumonia Viral/complicações , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Estudos Transversais , Encefalite , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , SARS-CoV-2
15.
Neurologia (Engl Ed) ; 2020 Dec 21.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33358061

RESUMO

INTRODUCTION: Patients with history of stroke or transient ischaemic attack present considerable risk of future vascular events. Reducing levels of low-density lipoprotein (LDL) cholesterol decreases the incidence of new vascular events, although in a substantial number of patients, the currently available lipid-lowering therapies fail to achieve the therapeutic goals recommended in clinical guidelines. The aim of this consensus statement is to provide updated information on the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab in the secondary prevention of vascular events in patients with history of ischaemic stroke. METHODS: A literature review was performed to identify the main evidence on the use of PCSK9 inhibitors in these patients and the recommended therapeutic targets of LDL cholesterol. The results were discussed in 2 consensus meetings that constituted the basis for the drafting of the document. CONCLUSIONS: PCSK9 inhibitors are effective in reducing vascular risk in secondary prevention; evolocumab specifically has achieved this reduction in patients with history of ischaemic stroke. Moreover, both alirocumab and evolocumab present good safety profiles, even in patients achieving LDL cholesterol levels <20 mg/dL, and no signs of cognitive impairment have been observed in patients treated with evolocumab who achieved very low levels of LDL cholesterol. In the light of this evidence, we provide practical recommendations about the use of PCSK9 inhibitors in secondary prevention of vascular events in patients with history of ischaemic stroke and follow-up of these patients.

16.
Eur Respir J ; 33(5): 956-73, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19407047

RESUMO

Tuberculosis control relies on the identification and preventive treatment of individuals who are latently infected with Mycobacterium tuberculosis. However, direct identification of latent tuberculosis infection is not possible. The diagnostic tests used to identify individuals latently infected with M. tuberculosis, the in vivo tuberculin skin test and the ex vivo interferon-gamma release assays (IGRAs), are designed to identify an adaptive immune response against, but not necessarily a latent infection with, M. tuberculosis. The proportion of individuals who truly remain infected with M. tuberculosis after tuberculin skin test or IGRA conversion is unknown. It is also uncertain how long adaptive immune responses towards mycobacterial antigens persist in the absence of live mycobacteria. Clinical management and public healthcare policies for preventive chemotherapy against tuberculosis could be improved, if we were to gain a better understanding on M. tuberculosis latency and reactivation. This statement by the TBNET summarises knowledge and limitations of the currently available tests used in adults and children for the diagnosis of latent tuberculosis infection. In summary, the main issue regarding testing is to restrict it to those who are known to be at higher risk of developing tuberculosis and who are willing to accept preventive chemotherapy.


Assuntos
Testes Imunológicos/métodos , Mycobacterium tuberculosis/imunologia , Seleção de Pacientes , Tuberculose/diagnóstico , Tuberculose/imunologia , Antígenos de Bactérias , Antituberculosos/farmacologia , Busca de Comunicante , Medicina Baseada em Evidências , Humanos , Programas de Rastreamento/métodos , Técnicas de Diagnóstico Molecular , Valor Preditivo dos Testes , Teste Tuberculínico , Tuberculose/tratamento farmacológico , Tuberculose/transmissão
17.
Scand J Immunol ; 69(6): 500-7, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19439010

RESUMO

The identification of a herd of goats with tuberculosis let us test a new treatment regimen against latent tuberculosis infection (LTBI). Using large animal experimental models allows a better approach to understanding human tuberculosis according to immunopathological parameters. Based on an initial study showing a correlation between the ESAT-6-specific interferon (IFN)-gamma secretion and the severity of pulmonary lesions, this parameter was used in combination with an X-ray examination to screen the animals to be included in the efficacy and safety studies. All the animals proved to be infected with Mycobacterium caprae. The efficacy study was run in animals distributed in three experimental groups according to treatment: untreated (CT), treated with isoniazid (INH), and treated with INH + RUTI (a vaccine based on M. tuberculosis cell fragments) inoculated twice. RUTI temporarily increased the IFN-gamma production after stimulating the peripheral blood with ESAT-6, purified protein derivative and RUTI in vitro. The INH chemotherapy reduced both pulmonary and extra pulmonary affectation, but not disease in pulmonary lymph nodes. The addition of RUTI may have decreased extrapulmonary disease further but had no benefit to lung or lung lymph-nodes itself. Safety studies showed that inoculation of RUTI caused a temporary increase of rectal temperature (1-2 degrees C) and local swelling, both adverse effects being well tolerated. Neither systemic toxicity nor mortality was induced by the vaccination. The control of goats' infection by the therapeutic regimen consisting in INH chemotherapy + RUTI as well as its safety, represented a further step towards testing its effects in human LTBI in a future.


Assuntos
Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Mycobacterium/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose/terapia , Tuberculose/veterinária , Animais , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/uso terapêutico , Feminino , Cabras , Interferon gama/biossíntese , Tuberculose/patologia
18.
Infection ; 37(2): 80-6, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19308318

RESUMO

BACKGROUND: It has been traditionally postulated that individuals, once infected by Mycobacterium tuberculosis, will retain throughout their entire lifetime latent bacilli which will remain dormant in old lesions. This bacillus would then be the source of a later reactivation of active tuberculosis (TB), with the aid of resuscitation factors. Unfortunately, the presence of these bacilli can only be predicted by indirect immunological methods, such as the tuberculin skin test (TST) or T cell interferon-gamma release assays. Other evidence shows that a 9-month isoniazid treatment of TST+ individuals converting to TB reduces the incidence of TB by approximately 90%. QUESTIONS: Taking into account this widely accepted framework, I suggest that there are at least three relevant questions to answer: (1) How can dormant bacilli remain in the lungs for an entire lifetime, taking into account constant cellular turnover and the healing of damaged tissues? (2) What provides the resuscitation factor to dormant bacilli, assuming that these latent bacilli are indeed present inside old lesions? (3) Why can a 9-month treatment with isoniazid eliminate dormant bacilli? As isoniazid is active only against growing bacilli, and thus is only able to destroy them after reactivation of latent bacilli, this treatment should have to be provided for life if the traditionally accepted postulate is correct. HYPOTHESIS: For a better understanding of latent TB infection. I propose a hypothesis that describes a dynamic scenario of constant endogenous reinfection with M. tuberculosis which explains the efficacy of the current standard of treatment. If this hypothesis is true, new strategies for the management of TB may arise.


Assuntos
Pulmão/microbiologia , Mycobacterium tuberculosis/fisiologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Recidiva
19.
Scand J Immunol ; 67(6): 610-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18397200

RESUMO

RUTI is a vaccine consisting of Mycobacterium tuberculosis bacilli grown in stress conditions that is fragmented, detoxified and liposomed. RUTI was designed to shorten the treatment of latent tuberculosis infection (LTBI) with isoniazid from 9 months to just 1 month, by additional treatment with two inoculations of RUTI 4 weeks apart. During the validation process for monitoring the immunogenicity of administration of RUTI in a Phase I clinical trial, the question arose whether to introduce the tuberculin skin test (TST) in the screening of non-LTBI volunteers. This study was designed to evaluate the effect of TST on subsequent different T-cell interferon-gamma release assay (TIGRA) responses, using a spectrum of M. tuberculosis-related antigens (ESAT-6, CFP-10, 16 kDa, 19 kDa, MPT64, Ag 85B, 38 kDa, hsp65, PPD and BCG). The results showed an increase in post-TST response even in non-LTBI subjects for most antigens tested, as measured both by whole blood assay (WBA) and ELISPOT. Increased ELISPOT response decreased toward pre-TST levels within 1 month whereas the WBA response did not. Taking into account that there is no definitive correlation between TST and TIGRA tests to diagnose LTBI and the feasibility that TST might alter the immune monitoring included in clinical trials, these data suggest that TST determination should be carefully planned to avoid any interference with TIGRA.


Assuntos
Interferon gama/biossíntese , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Teste Tuberculínico , Tuberculose/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Mycobacterium bovis/imunologia , Sensibilidade e Especificidade , Linfócitos T/metabolismo , Tuberculina/imunologia , Tuberculose/diagnóstico
20.
Rev Clin Esp (Barc) ; 218(7): 327-335, 2018 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29983190

RESUMO

OBJECTIVE: To identify factors associated with poor anticoagulation control with vitaminK antagonists (VKA) among outpatients with nonvalvular atrial fibrillation (NVAF) attended in Neurology and Internal Medicine in Spain. METHODS: Cross-sectional and multicenter study, from the ALADIN database, of outpatients with NVAF treated with VKA and attended in Internal Medicine and Neurology in Spain. Rates of anticoagulation control were determined with the direct and Rosendaal methods, considering data from the 6months before the inclusion. RESULTS: Out of 1,337 patients included in the ALADIN study, 750 were taking VKA, and complete information about INR values in the last 6months was available in 383 patients. Mean scores of Charlson Index, CHADS2, CHA2DS2-VASc and HAS-BLED were 1.94±1.54; 3.10±1.26; 4.63±1.54, and 2.20±0.90, respectively. 46.2% and 47.0% of patients had an adequate anticoagulation control according to the direct and Rosendaal methods, respectively. Inadequate anticoagulation control according to the direct method was associated with diabetes (OR: 2.511; 95%CI: 1.144-5.659), prior labile INR (OR: 35.371; 95%CI: 15.058-83.083) and the determination of >6INR controls in the last 6months (OR: 4.747; 95%CI: 2.094-10.759), and according to the Rosendaal method, with prior labile INR (P<.001) and HAS-BLED score (OR: 3.991; 95%CI: 2.520-6.319). CONCLUSIONS: Despite the high thromboembolic risk, only a little more than a half of patients were well controlled. Factors associated with poor anticoagulation control were diabetes, labile INR, >6INR controls and HAS-BLED.

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