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1.
J Endocrinol Invest ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499935

RESUMO

PURPOSE: The main study goal is to assess the relationship between adherence to the mediterranean diet (MD) and the presence of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). METHODS: Observational pilot study of 174 patients diagnosed with T2DM. Sociodemographic and anthropometric variables, physical activity, smoking habits, blood biochemical parameters and comorbidities were recorded. The presence of alterations in sensitivity to pressure, pain, thermal and vibration was explored. Good MD adherence was a score ≥ 9 the 14-point MD adherence questionnaire (MEDAS-14). RESULTS: The study population consisted of 174 patients (61.5% men and 38.5% women), with a mean age of 69.56 ± 8.86 years; 19% of these patients adhered to the MD. The score obtained in the MEDAS-14 was higher in patients who did not present alterations in sensitivity to pressure (p = 0.047) or vibration (p = 0.021). The patients without diabetic peripheral neuropathy were more likely to comply with the MD and had a higher score on the MEDAS-14 (p = 0.047). However, multivariate analysis showed that only altered sensitivity to pressure was associated with adherence to the MD (altered sensitivity OR = 2.9; 95%CI 1.02-8.22; p = 0.045). CONCLUSIONS: Although the patients with DPN had lower scores on the MEDAS questionnaire and therefore poorer adherence to the mediterranean diet, the only parameter significantly associated with the MD was that of sensitivity to pressure (monofilament test).

2.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. Impr.) ; 50(1): [e102090], ene.- feb. 2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-229436

RESUMO

Objetivos Analizar el riesgo de COVID-19 con relación a la morbilidad previa, así como el riesgo de nuevos eventos cardiovasculares (ECV) en pacientes COVID-19 y la supervivencia a un año. Metodología Estudio casos-control y estudio de cohortes prospectivo. Se incluyeron 275 pacientes aleatorizados >18 años diagnosticados de COVID-19 y se aparearon con 825 COVID-19 negativos por edad y sexo (proporción 1:3). Las variables principales fueron diagnóstico de COVID-19 y eventos post-COVID-19. Se estudiaron variables sociodemográficas, comorbilidad y ECV previo. Se realizaron sendos modelos predictivos de factores asociados al desarrollo de COVID-19 y de ECV post-COVID-19, así como un análisis de supervivencia a un año. Resultados Los varones con ECV previo duplican el riesgo de padecer COVID-19 (odds ratio [OR] 2,11; intervalo de confianza [IC] 95% 1,32–3,36). En las mujeres el riesgo aumenta con la edad (OR 1,01; IC 95% 1,00–1,02), la diabetes mellitus (DM) (OR 1,90; IC 95% 1,14–3,17) y el deterioro cognitivo (OR 4,88; IC 95% 2,50–9,53). La inmunosupresión actúa como factor protector en ambos sexos. La edad (OR 1,02; IC 95% 1,00–1,04), hipertensión arterial (HTA) (OR 2,21; IC 95% 1,17–4,17), la infección COVID-19 (OR 4,81; IC 95% 2,89–7,98) y el ECV previo (OR 4,46; IC 95% 2,56–7,75) predicen el desarrollo de un nuevo ECV post-COVID-19. Los pacientes COVID-19 positivos tienen menor supervivencia (mediana de siete vs. 184 días). Conclusiones El ECV previo en varones y la DM junto al deterioro cognitivo en mujeres aumentan el riesgo de presentar COVID-19. La edad, HTA, ECV previo y la infección COVID-19 predicen la aparición de un ECV (AU)


Aim To analyze the risk of COVID-19 in relation to previous morbidity; to analyze the risk of new cardiovascular events (CVE) in COVID-19 patients and one-year survival. Methodology Case–control study and prospective cohort study. Two hundred and seventy-five randomized patients >18 years old with COVID-19 were included and matched with 825 without COVID-19 by age and sex (ratio 1:3). The main variables were diagnosis of COVID-19 and post-COVID-19 events. Sociodemographic variables, comorbidity, and previous CVD were studied. Two predictive models of factors associated with the development of COVID-19 and post-COVID-19 CVE were performed, as well as a one-year survival analysis. Results Men with a previous CVE double the risk of suffering from COVID-19 (OR 2.11; 95% CI: 1.32–3.36). In women, the risk increases with age (OR 1.01; 95% CI: 1.00–1.02), diabetes (DM) (OR 1.90; 95% CI: 1.14–3.17) and cognitive impairment (OR 4.88; 95% CI: 2.50–9.53). Immunosuppression acts as a protective factor in both sexes. Age (OR 1.02; 95% CI: 1.00–1.04), arterial hypertension (OR 2.21; 95% CI: 1.17–4.17), COVID-19 infection (OR 4.81; 95% CI: 2.89–7.98) and previous CVE (OR 4.46; 95% CI: 2.56–7.75) predict the development of a new post-COVID-19 CVE. Positive COVID-19 has lower survival (median 7 days vs. 184 days). Conclusions Previous CVE in men and DM along with cognitive impairment in women increase the risk of presenting COVID-19. Age, arterial hypertension, previous CVE, and COVID-19 infection predict the appearance of new CVE (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , /epidemiologia , Estudos de Casos e Controles , Estudos Prospectivos , Estudos de Coortes , Análise de Sobrevida , Fatores Socioeconômicos , Incidência , Comorbidade , Espanha/epidemiologia
3.
Semergen ; 50(1): 102090, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-37864925

RESUMO

AIM: To analyze the risk of COVID-19 in relation to previous morbidity; to analyze the risk of new cardiovascular events (CVE) in COVID-19 patients and one-year survival. METHODOLOGY: Case-control study and prospective cohort study. Two hundred and seventy-five randomized patients >18 years old with COVID-19 were included and matched with 825 without COVID-19 by age and sex (ratio 1:3). The main variables were diagnosis of COVID-19 and post-COVID-19 events. Sociodemographic variables, comorbidity, and previous CVD were studied. Two predictive models of factors associated with the development of COVID-19 and post-COVID-19 CVE were performed, as well as a one-year survival analysis. RESULTS: Men with a previous CVE double the risk of suffering from COVID-19 (OR 2.11; 95% CI: 1.32-3.36). In women, the risk increases with age (OR 1.01; 95% CI: 1.00-1.02), diabetes (DM) (OR 1.90; 95% CI: 1.14-3.17) and cognitive impairment (OR 4.88; 95% CI: 2.50-9.53). Immunosuppression acts as a protective factor in both sexes. Age (OR 1.02; 95% CI: 1.00-1.04), arterial hypertension (OR 2.21; 95% CI: 1.17-4.17), COVID-19 infection (OR 4.81; 95% CI: 2.89-7.98) and previous CVE (OR 4.46; 95% CI: 2.56-7.75) predict the development of a new post-COVID-19 CVE. Positive COVID-19 has lower survival (median 7 days vs. 184 days). CONCLUSIONS: Previous CVE in men and DM along with cognitive impairment in women increase the risk of presenting COVID-19. Age, arterial hypertension, previous CVE, and COVID-19 infection predict the appearance of new CVE.


Assuntos
COVID-19 , Doenças Cardiovasculares , Hipertensão , Feminino , Humanos , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico , Estudos de Casos e Controles , COVID-19/complicações , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Estudos Prospectivos , Fatores de Risco , Adulto
4.
J Med Chem ; 65(24): 16801-16817, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36475697

RESUMO

Inhibition of leucine-rich repeat kinase 2 (LRRK2) kinase activity represents a genetically supported, chemically tractable, and potentially disease-modifying mechanism to treat Parkinson's disease. Herein, we describe the optimization of a novel series of potent, selective, central nervous system (CNS)-penetrant 1-heteroaryl-1H-indazole type I (ATP competitive) LRRK2 inhibitors. Type I ATP-competitive kinase physicochemical properties were integrated with CNS drug-like properties through a combination of structure-based drug design and parallel medicinal chemistry enabled by sp3-sp2 cross-coupling technologies. This resulted in the discovery of a unique sp3-rich spirocarbonitrile motif that imparted extraordinary potency, pharmacokinetics, and favorable CNS drug-like properties. The lead compound, 25, demonstrated exceptional on-target potency in human peripheral blood mononuclear cells, excellent off-target kinase selectivity, and good brain exposure in rat, culminating in a low projected human dose and a pre-clinical safety profile that warranted advancement toward pre-clinical candidate enabling studies.


Assuntos
Doença de Parkinson , Ratos , Humanos , Animais , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença de Parkinson/tratamento farmacológico , Indazóis/farmacologia , Indazóis/uso terapêutico , Leucócitos Mononucleares/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/química , Encéfalo/metabolismo , Trifosfato de Adenosina
5.
J Med Chem ; 65(1): 838-856, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-34967623

RESUMO

The leucine-rich repeat kinase 2 (LRRK2) protein has been genetically and functionally linked to Parkinson's disease (PD), a disabling and progressive neurodegenerative disorder whose current therapies are limited in scope and efficacy. In this report, we describe a rigorous hit-to-lead optimization campaign supported by structural enablement, which culminated in the discovery of brain-penetrant, candidate-quality molecules as represented by compounds 22 and 24. These compounds exhibit remarkable selectivity against the kinome and offer good oral bioavailability and low projected human doses. Furthermore, they showcase the implementation of stereochemical design elements that serve to enable a potency- and selectivity-enhancing increase in polarity and hydrogen bond donor (HBD) count while maintaining a central nervous system-friendly profile typified by low levels of transporter-mediated efflux and encouraging brain penetration in preclinical models.


Assuntos
Antiparkinsonianos/síntese química , Antiparkinsonianos/farmacologia , Encéfalo/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/antagonistas & inibidores , Quinazolinas/síntese química , Quinazolinas/farmacologia , Antiparkinsonianos/farmacocinética , Disponibilidade Biológica , Desenho de Fármacos , Humanos , Modelos Moleculares , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacocinética , Relação Estrutura-Atividade
6.
Bioorg Med Chem Lett ; 44: 128082, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33991626

RESUMO

A focused SAR study was conducted on a series of N1-substituted pyrazolopyrimidinone PDE2 inhibitors to reveal compounds with excellent potency and selectivity. The series was derived from previously identified internal leads and designed to enhance steric interactions with key amino acids in the PDE2 binding pocket. Compound 26 was identified as a lead compound with excellent PDE2 selectivity and good physicochemical properties.


Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/antagonistas & inibidores , Descoberta de Drogas , Inibidores de Fosfodiesterase/farmacologia , Pirazóis/farmacologia , Pirimidinonas/farmacologia , Cristalografia por Raios X , Nucleotídeo Cíclico Fosfodiesterase do Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Fosfodiesterase/síntese química , Inibidores de Fosfodiesterase/química , Pirazóis/síntese química , Pirazóis/química , Pirimidinonas/síntese química , Pirimidinonas/química , Relação Estrutura-Atividade
7.
Clin Transl Oncol ; 21(1): 31-45, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30617924

RESUMO

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.


Assuntos
Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/terapia , Guias de Prática Clínica como Assunto/normas , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico , Sociedades Médicas
8.
Clin. transl. oncol. (Print) ; 21(1): 31-45, ene. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-183342

RESUMO

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference


No disponible


Assuntos
Humanos , Feminino , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/patologia , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias da Mama/terapia , Qualidade de Vida/psicologia , Padrões de Prática Médica
9.
Clin. transl. oncol. (Print) ; 20(9): 1136-1144, sept. 2018. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-173698

RESUMO

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib


No disponible


Assuntos
Humanos , Animais , Inibidor p16 de Quinase Dependente de Ciclina/farmacocinética , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Inibidores da Aromatase/uso terapêutico , Ensaios Clínicos como Assunto , Biomarcadores Tumorais/análise , Piperazinas/uso terapêutico
10.
Clin Transl Oncol ; 20(9): 1136-1144, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29564714

RESUMO

Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinases Ciclina-Dependentes/antagonistas & inibidores , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Animais , Ciclo Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Humanos , Piperazinas/farmacologia , Piridinas/farmacologia
11.
Radiología (Madr., Ed. impr.) ; 60(1): 64-72, ene.-feb. 2018. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-170438

RESUMO

Objetivo. Comprobar si es posible determinar el grado de resección de macroadenomas hipofisarios en la resonancia magnética (RM) hipofisaria posquirúrgica inmediata. Material y métodos. Se revisaron las RM hipofisarias de pacientes intervenidos desde enero de 2010 hasta octubre de 2014. Se incluyeron aquellos que tenían RM diagnóstica, RM posquirúrgica inmediata y al menos un control posterior. Se comprobó si los hallazgos entre la RM posquirúrgica inmediata y las RM posteriores eran concordantes. Se excluyeron los casos sin controles evolutivos y las reintervenciones por recidivas. El grado de resección tumoral lo dividimos en grupos: resección total, resección parcial y dudoso. Los estudios se realizaron en una máquina de 1.5 Tesla siguiendo el mismo protocolo de secuencias: una parte morfológica, otra dinámica con contraste intravenoso y otra con contraste tardío. Resultados. De 73 casos incluidos, la RM posquirúrgica inmediata se interpretó como resección total en 38 casos y resto tumoral en 28 casos, habiendo dudas en 7 casos. En los controles evolutivos se determinó resección total en 41 casos y resto tumoral en 32. Se obtuvo una sensibilidad para detección de restos tumorales de 0,71, una especificidad de 0,82, un valor predictivo positivo de 0,89 y un valor predictivo negativo de 0,85 en la RM posquirúrgica inmediata respecto a los controles evolutivos. Conclusión. La RM posquirúrgica inmediata de macroadenomas hipofisarios es útil para valorar el grado de resección tumoral y es un buen predictor del grado de resección real definitivo al comparar con las RM posteriores, permitiendo plantear el tratamiento adecuado de forma precoz (AU)


Objective. To evaluate if it is possible to determine the extent of pituitary macroadenomas resection in the immediate postoperative pituitary magnetic resonance imaging (MRI). Material and methods. MRI of patient with pituitary macroadenomas from January 2010 until October 2014 were reviewed. Those patients who had diagnostic MRI, immediate post-surgical MRI and at least one MRI control were included. We evaluate if the findings between the immediate postsurgical MRI and the subsequent MRI were concordant. Cases which didn’t have evolutionary controls and those who were reoperation for recurrence were excluded. The degree of tumor resection was divided into groups: total resection, partial resection and doubtful. All MRI studies were performed on a1.5T machine following the same protocol sequences for all cases. One morphological part, a dynamic contrast iv and late contrast part. Results. Of the 73 cases included, immediate postoperative pituitary MRI was interpreted as total resection in 38 cases and tumoral rest in 28 cases, uncertainty among rest or inflammatory changes in 7 cases. Follow- up MRI identified 41 cases total resection and tumoral rest in 32. Sensitivity and specificity of 0.78 and 0.82 and positive and negative predictive value (PPV and NPV) 0.89 and 0.89 respectively were calculated. Conclusion. Immediate post-surgery pituitary MRI is useful for assessing the degree of tumor resection and is a good predictor of the final degree of real resection compared with the following MRI studies. It allows us to decide the most appropriate treatment at an early stage (AU)


Assuntos
Humanos , Prolactinoma/cirurgia , Neoplasias Hipofisárias/cirurgia , Imageamento por Ressonância Magnética/métodos , Margens de Excisão , Neoplasia Residual/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Cuidados Pós-Operatórios/métodos
12.
Radiologia (Engl Ed) ; 60(1): 64-72, 2018.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29179978

RESUMO

OBJECTIVE: To evaluate if it is possible to determine the extent of pituitary macroadenomas resection in the immediate postoperative pituitary magnetic resonance imaging (MRI). MATERIAL AND METHODS: MRI of patient with pituitary macroadenomas from January 2010 until October 2014 were reviewed. Those patients who had diagnostic MRI, immediate post-surgical MRI and at least one MRI control were included. We evaluate if the findings between the immediate postsurgical MRI and the subsequent MRI were concordant. Cases which didn't have evolutionary controls and those who were reoperation for recurrence were excluded. The degree of tumor resection was divided into groups: total resection, partial resection and doubtful. All MRI studies were performed on a1.5T machine following the same protocol sequences for all cases. One morphological part, a dynamic contrast iv and late contrast part. RESULTS: Of the 73 cases included, immediate postoperative pituitary MRI was interpreted as total resection in 38 cases and tumoral rest in 28 cases, uncertainty among rest or inflammatory changes in 7 cases. Follow- up MRI identified 41 cases total resection and tumoral rest in 32. Sensitivity and specificity of 0.78 and 0.82 and positive and negative predictive value (PPV and NPV) 0.89 and 0.89 respectively were calculated. CONCLUSION: Immediate post-surgery pituitary MRI is useful for assessing the degree of tumor resection and is a good predictor of the final degree of real resection compared with the following MRI studies. It allows us to decide the most appropriate treatment at an early stage.


Assuntos
Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Cuidados Pós-Operatórios , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/métodos , Fatores de Tempo , Adulto Jovem
13.
ACS Med Chem Lett ; 8(12): 1292-1297, 2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29259750

RESUMO

Using the HIV-1 protease binding mode of MK-8718 and PL-100 as inspiration, a novel aspartate binding bicyclic piperazine sulfonamide core was designed and synthesized. The resulting HIV-1 protease inhibitor containing this core showed an 60-fold increase in enzyme binding affinity and a 10-fold increase in antiviral activity relative to MK-8718.

14.
Clin Microbiol Infect ; 23(10): 775.e1-775.e6, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28192235

RESUMO

OBJECTIVES: This study aimed to characterize the chronically infected general hepatitis C virus (HCV) population in Barcelona using a highly sensitive subtyping method that can identify the 67 recognized HCV subtypes and diagnose mixed infection by various genotypes/subtypes in a single individual. The resulting information has implications for selecting optimal direct-acting antiviral (DAA) treatment for each patient and establishing public healthcare policies in our setting. METHODS: Consecutive HCV patients (treatment-naïve or interferon-based failures) attending Vall d'Hebron Hospital outpatient clinics from February 2015 to May 2016 (N=1473) were included in the study. Patient samples were characterized using HCV subtyping by next-generation ultra-deep pyrosequencing. RESULTS: The following genotypes (G) were found: G1 (1126/1473 (76.4%)), G4 (145/1473 (9.8%)), G3 (135/1473 (9.2%)), G2 (51/1473 (3.5%)), and G5 (1/1473 (0.1%)). Twenty-two subtypes were seen: 1b (790/1473 (53.6%)), 1a (332/1473 (22.5%)), 3a (133/1473 (9.0%)), 4d (105/1473 (7.1%)), 4a (29/1473 (2.0%)), and 2c (25/1473 (1.7%)), with 16 low-prevalence subtypes accounting for the remaining 3.0% (44/1473). There was a worrisome 1.0% (15/1473) of mixed infections. G2 (51/1473 (3.5%)) showed a high level of heterogeneity. Analyses by age groups showed a predominance of G1b over G1a (428/506 (84.6%) vs. 24/506 (4.7%)) in patients born before 1950 (N=506/1473), and similar percentages of these subtypes in those born between 1951 and 1975 (N=834/1473) (315/834, 37.8% vs. 266/834, 31.9%) and after 1976 (N=133/1473) (47/133, 35.3% vs. 42/133, 31.6%). CONCLUSIONS: Subtype distribution showed a higher level of heterogeneity than was expected, particularly for G2. Prevalence of mixed infections was around 1%. HCV subtype distribution related to patient age group suggested that patients born from 1936 to 1975 in our setting should undergo screening for the infection. Next-generation sequencing enabled better classification of candidates for DAA-based treatment.


Assuntos
Variação Genética , Genótipo , Técnicas de Genotipagem/métodos , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/virologia , Adolescente , Adulto , Idoso , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , Hepacivirus/isolamento & purificação , Hepatite C Crônica/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Prevalência , Espanha/epidemiologia , Adulto Jovem
15.
Clin Transl Oncol ; 19(2): 149-161, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27314861

RESUMO

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease.


Assuntos
Antineoplásicos/normas , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
16.
Ecancermedicalscience ; 10: 647, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27433280

RESUMO

BACKGROUND: The appropriate selection criteria for breast-conserving surgery (BCS) or mastectomy after neoadjuvant chemotherapy (NAC) are poorly defined. The aim of this study is to analyse the incidence and prognostic factors for locoregional recurrence (LRR) in patients with breast cancer (BC) treated with NAC to develop a prognostic score to help with clinical decision-making. MATERIALS AND METHODS: Using our retrospective maintained BC database, we identified 730 patients treated with NAC (327 patients treated with BCS and 403 patients treated with mastectomy) between 1998 and 2014. To identify variables associated with an increased LRR rate, we performed firstly Kaplan-Meier curves, with comparisons among groups using log-rank test, and then, significant variables were included in a multivariate analysis using Cox proportional hazards. The prognostic index was developed by assigning score 0 (favourable) or score 1 (unfavourable) for each significant variable of multivariate analysis and was created separately for patients with BCS and mastectomy. RESULTS: At a median follow-up of 72 months, the 6-year cumulative incidence of LRR was 7.2% ( ± 3%) for BCS and 7.9% ( ± 3%) for mastectomy. By univariate analysis, variables associated with an increased LRR were for BCS: HER2 positive, grade III, ductal carcinoma in situ (DCIS), No-pCR (ypTis, ypN0), and age < 40 years; and for mastectomy, HER2-positive, DCIS, No-pCR, and LVI. By multivariate analysis, variables associated with an increased LRR were for BCS: HER2 positive (HR: 11.1, p = 0.001), DCIS (HR: 3.1, p = 0.005), and age < 40 years (HR: 2.8, p = 0.02); and for mastectomy: HER2 positive (HR: 9.5, p = 0.03), DCIS (HR: 2.7, p = 0.01), No-pCR (HR: 11.4, p = 0.01), and age < 40 years (HR: 2.8, p = 0.006). The score stratified patients into three subsets with statistically different levels of risk for LRR. For BCS, the six-year LRR rates were 3%, 13%, and 33% for the low (score 0, n = 120), intermediate (score 1, n = 95) and high (score 2-3, n = 27) risk groups, respectively (p = 0.001). For mastectomy, the six-year LRR rates were 0%, 8%, and 27% for the low (score 0, n = 20), intermediate (score 1-2, n 191), and high (score 3-4, n = 30) risk groups, respectively (p = 0.001). Of note, 21 patients that had a LRR event were HER2 positive, all of them had received trastuzumab. CONCLUSIONS: Patients with a score of 0, which made up to 19% of the study population, had very low risk of LRR. The score enabled the identification of a small group (7%) of patients with very high risk of LRR, and who may benefit from alternative treatment.

17.
Emergencias ; 28(1): 21-25, 2016 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-29094822

RESUMO

OBJECTIVES: To determine the validity of 2 triage systems: the 3M Triage Assistance System (3M-TAS) and the combined Spanish Triage System and Andorran Triage Model (SET-MAT) for predicting hospitalization and use of emergency resources; and to estimate the level of agreement between them. MATERIAL AND METHODS: Prospective observational study of consecutive cohorts classified with the studied triage systems in the emergency department (ED) of a secondary-level hospital between March 24 and April 30, 2014. Patients were classified blindly and simultaneously between 9 AM and 10 PM by a clinical nurse using the SET-MAT program and a researcher nurse using the 3M-TAS software. We collected patients' demographic details and assigned triage level, laboratory and imaging tests ordered, specialist consultations requested in the ED, length of stay until discharge from the department, and destination on discharge. Outcome variables were hospitalization and use of at least 1 resource in the ED. RESULTS: A total of 3379 emergencies were included. The conventionally weighted κ statistic for agreement between the 2 triage systems was 0.26, but the triage-weighted κ was 0.17. The 3M-TAS software was better able to predict hospitalization than the SET-MAT (P<.001); however, the 2 systems, predictions of resource usage were similar (P=.111). CONCLUSION: Agreement between the 3M-TAS and SET-MAT triage systems was poor, although they predicted similar use of resources in the ED. The 3M-TAS was better able to predict hospital admission than the SET-MAT.


OBJETIVO: Determinar el grado de concordancia y validez, a la hora de predecir la hospitalización y el consumo de recursos en urgencias, del Sistema de Ayuda al Triaje 3M TAS y su comparación con el Sistema Español de Triaje - Model Andorrà de Triatge (SET-MAT). METODO: Estudio observacional de cohortes prospectivo que incluyó de forma consecutiva los episodios filiados de 9 a 22 horas en un servicio de urgencias de un hospital secundario entre el 24 de marzo y el 30 de abril de 2014. Los pacientes se clasificaron de forma enmascarada y simultánea por una enfermera asistencial mediante el programa de ayuda al triaje SET-MAT y por una enfermera de investigación mediante el 3M TAS. Se recogieron variables demográficas, de gravedad, las pruebas de laboratorio, radiológicas e interconsulta a especialistas realizadas en urgencias, el tiempo de estancia y el destino final. Las variables de resultado fueron la hospitalización y el consumo de al menos un recurso en urgencias. RESULTADOS: Se incluyeron 3.379 episodios. El índice de concordancia mediante el kappa ponderado cuadrático entre los sistemas de triaje fue de 0,26 y el kappa triaje de 0,17. El sistema 3M TAS presentó una mayor capacidad predictiva de hospitalización en comparación con el SET-MAT (p < 0,001), no siendo así en lo que respecta al consumo de recursos en urgencias (p = 0,111). CONCLUSIONES: La concordancia entre los sistemas de triaje 3M TAS y SET-MAT fue baja, sin diferencias para predecir el consumo de recursos en urgencias, aunque el 3M TAS predijo mejor ingreso hospitalario que el SET-MAT.

20.
Cerebrovasc Dis ; 35(6): 554-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23838705

RESUMO

BACKGROUND: Early recanalization and increase in collateral blood supply are powerful predictors of favourable outcome in acute ischaemic stroke. The factors contributing to the heterogeneous response to intravenous thrombolysis therapy in individual patients, however, are not fully understood. The on-going single-centre 'MR perfusion imaging during thrombolysis' study uses repetitive arterial spin labelling (ASL) measurements to characterize the haemodynamic processes in acute stroke during therapy. The first milestone was to develop an appropriate infrastructure for thrombolysis in the magnetic resonance imaging (MRI) scanner without time delay and ensuring optimal patient safety and care. METHODS: Between February and December 2011, 16 patients with acute neurological symptoms suggestive of hemispheric stroke within 4.5 h after symptom onset were included. In addition to clinical data, we documented the time from onset to arrival at the hospital, start and duration of MRI examination, start of thrombolytic therapy, and complications. The decision to thrombolyse was made after a routine stroke MRI protocol. During the 60-min systemic thrombolysis, repetitive ASL perfusion imaging was acquired, providing non-invasive information on cerebral perfusion. Continuous ECG monitoring, pulse oximetry, blood pressure measurements every 5 min, and short neurological assessments every 15 min were performed in every patient. RESULTS: The median initial NIHSS score of the patients presenting with a mean of 84 min after onset was 4 (range 2-18). MRI examination was initiated within a mean of 45 min after arrival at the hospital. Five patients identified as stroke mimics were not treated with recombinant tissue plasminogen activator (rt-PA), and in 1 case with basilar artery occlusion bridging therapy was performed outside the scanner. In the remaining 10 patients, rt-PA therapy was started in the scanner directly after decision making on the basis of clinical information and baseline MRI. The mean door-to-needle time was 60 min (range 44-115) including approximately 10 min needed for acquiring informed consent. While 4 patients required antihypertensive treatment, no relevant complications were encountered. CONCLUSIONS: Fast and safe medical care in patients during systemic thrombolysis in the MRI scanner is feasible. Despite the process of obtaining informed consent, with a dedicated and experienced stroke team the door-to-needle time can be kept in a range recommended by current guidelines. Continuous real-time information about the dynamics of cerebral perfusion from ASL perfusion in acute stroke patients undergoing thrombolysis may provide additional information for the understanding of the events following acute arterial obstruction and its course.


Assuntos
Isquemia Encefálica/patologia , Imageamento por Ressonância Magnética , Imagem de Perfusão , Acidente Vascular Cerebral/patologia , Terapia Trombolítica , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Humanos , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Radiografia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/métodos , Resultado do Tratamento
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