Pacientes con fibrilación auricular no valvular tratados con antivitamina K o anticoagulantes directos: perfil de paciente y efectos a largo plazo / Patients with non-valvular atrial fibrillation on vitamin k antagonists or direct-acting oral anticoagulants: patients profile and long-term follow up outcomes

Resumen Introducción: La llegada de los anticoagulantes directos (ACD) ha supuesto un cambio en el tratamiento de la fibrilación auricular no valvular (FANV) en los últimos años. Los objetivos de este estudio son determinar el grado de control de la anticoagulación con antivitamina K (AVK) y su posible implicación en efectos cardiovasculares adversos mayores (ECAM) y evaluar las diferencias entre el grupo en tratamiento con AVK respecto del grupo con ACD. Pacientes y métodos: Estudio de cohorte prospectivo que incluyó a pacientes consecutivos diagnosticados con FANV valorados en el Servicio de Cardiología con un seguimiento de 18 meses. Se analizaron diferencias demográficas, clínicas y analíticas entre grupos, incluido el grado de control de la anticoagulación del grupo AVK y su posible relación con ECAM. Resultados: Se incluyó a 273 pacientes: 46.5% tratados con AVK, 42.5% con ACD y 11% sin tratamiento anticoagulante. El control de la anticoagulación con AVK fue del 62.1%, sin diferencias en ECAM en función de control. El grupo ACD presentó menos ECAM que el grupo de AVK (13.4 vs. 4.3%; HR, 0.90; 0.83-0.98; p = 0.01), con una menor mortalidad cardiovascular (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) y total (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p menor que 0,01), aunque sin diferencias significativas en eventos hemorrágicos (0.9 vs. 4.7%; p = 0.07) ni isquémicos (2.6 vs. 0.8%; p = 0.27). Discusión: Los pacientes con AVK poseen un perfil clínico diferente en comparación con los que reciben ACD. El control de anticoagulación del grupo de AVK fue inadecuado en casi la mitad de los casos. El grupo de AVK presentó más ECAM que el grupo de ACD.

Abstract Introduction: The arrival of direct-acting oral anticoagulants (DOACs) has led to a change in the management of non-valvular atrial fibrillation (NVAF) in recent years. The objectives of this study are to determine the level of therapeutic control of anticoagulation with vitamin K antagonists (VKA) and its possible involvement in major adverse cardiovascular events (MACE) and to evaluate differences between the group on VKA with respect to the group on DOACs. Patients and methods: Prospective cohort study that included consecutive patients diagnosed with NVAF in Cardiology Consultations with a clinical follow-up of 18 months. Demographic, clinical and analytical differences between groups were analyzed, including the level of therapeutic control of anticoagulation on the VKA group and its association with MACE. Results: Overall, 273 patients were included: 46.5% on VKA, 42.5% on DOACs, 11% without antithrombotic treatment. Patients on VKA spent 62.1% of their time within therapeutic range (TTR by the Rosendaal formule). There were no differences in MACE depending on anticoagulation control. The DOACs group presented lesser MACE rate than the VKA group (13.4 vs. 4.3%; 0.90; HR 0.90; 0.83-0.98 p = 0.01) with lower cardiovascular mortality (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) and total mortality (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p less 0.01) although without significant differences in hemorrhagic (0.9 vs. 4.7 %; p = 0.07), or ischemic events (2.6 vs. 0.8%, p = 0.27). Conclusions: Patients on VKA have a different clinical profile than those who receive DOACs. Patients on VKA have an inadequate control of the anticoagulation in quite the half of the cases. The VKA group presented more MACE than the DOACs group.

Yeast HXK2 gene reverts glucose regulation mutation of penicillin biosynthesis in P. chrysogenum

The mutant Penicillium chrysogenum strain dogR5, derived from strain AS-P-78, does not respond to glucose regulation of penicillin biosynthesis and β-galactosidase, and is partially deficient in D-glucose phosphorilating activity. We have transformed strain dogR5 with the (hexokinase) hxk2 gene from Saccharomyces cerevisiae. Transformants recovered glucose control of penicillin biosynthesis in different degrees, and acquired a hexokinase (fructose phosphorylating) activity absent in strains AS- P-78 and dogR5. Interestingly, they also recovered glucose regulation of β-galactosidase. On the other hand, glucokinase activity was affected in different ways in the transformants; one of which showed a lower activity than the parental dogR5, but normal glucose regulation of penicillin biosynthesis. Our results show that Penicillium chrysogenum AS-P-78 and dogR5 strains lack hexokinase, and suggest that an enzyme with glucokinase activity is involved in glucose regulation of penicillin biosynthesis and β-galactosidase, thus signaling glucose in both primary and secondary metabolism; however, catalytic and signaling activities seem to be independent.

Enfermedad pulmonar obstructiva: diferencias entre hombres y mujeres / Chronic obstructive pulmonary disease: differences between men and women

La enfermedad pulmonar obstructiva crónica (EPOC) ha aumentado su prevalencia en el sexo femenino. Los casos de mujeres se describen como más sintomáticas. A pesar de que la EPOC se ha vinculado a elevado riesgo cardiovascular, hay pocos estudios sobre diferencias por sexo. El objetivo de nuestro estudio fue determinar la influencia del sexo sobre calidad de vida y síntomas, tratamiento, factores de riesgo y enfermedad cardiovascular (ECV) en una población de pacientes con EPOC. En este estudio prospectivo observacional de corte transversal, se incluyeron pacientes con EPOC ingresados consecutivamente entre el 1 de septiembre de 2008 al 1 de marzo de 2010. Se registraron edad, sexo, habito tabáquico, factores de riesgo y enfermedad cardiovascular, tratamiento y gravedad de la EPOC. Se midió índice tobillo-brazo (ITB) y se realizó Euroqol-5D. Se incluyeron 246 pacientes (195 hombres). Los hombres fueron más ex fumadores (68.7% vs. 15.7%, p < 0.001), tuvieron un VEF1 menor (48.7% ± 15.7 vs. 58.2% ± 10.9 de teórico, p < 0.001) y mayor frecuencia de cardiopatía isquémica (16.4% vs. 5.9%, p = 0.04). Las mujeres presentaron más prevalencia de EPOC sin exposición al tabaco (64.7% vs. 7.2%, p < 0.001), más síntomas de ansiedad y depresión (p = 0.004) e ITB alterado en menor frecuencia (20% vs. 41.6%, p = 0.01). Concluimos que hubo diferencias en la EPOC en relación al sexo, con compromiso pulmonar y cardiovascular más grave en hombres y más síntomas de ansiedad y depresión en mujeres.

Chronic obstructive pulmonary disease (COPD) has increased its prevalence in females. Women have been described as more symptomatic. There are few studies considering gender differences in COPD. The aim of our study was to determine the influence of gender on quality of life, symptoms, treatment, risk factors and cardiovascular disease in a population of patients with COPD. In this prospective observational cross-sectional study, the included COPD patients were consecutively admitted between September 1, 2008 to March 1, 2010. We registered age, sex, smoking history, risk factors and cardiovascular disease, treatment and severity of COPD. We measured ankle-brachial index (ABI) and performed EuroQol-5D. Two hundred forty six patients were included (195 men). There were more former smokers among men (68.7% vs. 15.7%, p < 0.001), men had a lower FEV1 (48.7% ± 15.7 vs. 58.2% ± 10.9 of theoretical, p < 0.001) and higher frequency of ischemic heart disease (16.4% vs. 5.9%, p = 0.04). Women showed a higher prevalence of COPD without exposure to smoke cigarette (64.7% vs. 7.2%, p < 0.001), more symptoms of anxiety and depression (p = 0.004) and less frequently altered ABI (20% vs. 41. 6%, p = 0.01).There were differences in COPD with respect to sex with more severe pulmonary and cardiovascular disease in men and more symptoms of anxiety and depression in women.

Physiological, morphological, and mannanase production studies on Aspergillus niger uam-gs1 mutants

Mutant strains from Aspergillus niger UAM-GS1 were produced by UV radiation to increase their hemicellulolytic and cellulolytic activity production. The mutant strains showing more enzymatic activity were those labelled GS1-S059 and GS1-S067. These strains also showed the largest relationship between diameter of hydrolysis zone and colony diameter. The mutant GS1-S067 showed a colony radial extension rate and a biomass growth rate g biomass/(cm² h), 1.17 times higher than that achieved by strain UAM-GS1. The high invasive capacity makes this mutant strain a promising alternative for its use in solid substrate fermentation (SSF). The morphological properties of the two mutant strains were evaluated by using scanning electron microscopy. The diameter of the sporangium of the mutant strains GS1-S059 and GS1-S067 was significantly larger (P < 0.05) than that found for the parental strain. The hypha length and diameter of the mutant strains significantly changed (P < 0.05) compared to the parental strain. A Pearson correlation analysis on hypha length, sporangium diameter, and cellulase and xylanase activities indicated that there was a strong relationship among these variables in relation to mannanase activity. Mutant strains GS1-S059 and GS1-S067 significantly increased their level of mannanase, xylanase and cellulase production, compared to the parental strain, improving their potential industrial applications.