Estrategias diuréticas en insuficiencia cardiaca aguda con disfunción renal: terapia convencional frente a guiada por el antígeno carbohidrato 125. Diseño de ensayo clínico / Diuretic strategies in acute heart failure and renal dysfunction: conventional vs carbohydrate antigen 125-guided strategy. Clinical trial design

Introducción y objetivos: El tratamiento óptimo de pacientes con insuficiencia cardiaca aguda (ICA) y síndrome cardiorrenal tipo 1 (SCR-1) no está bien definido. La hipoperfusión arterial y la congestión venosa tienen un papel fundamental en la fisiopatología del SCR-1. El antígeno carbohidrato 125 (CA125) ha emergido como marcador indirecto de sobrecarga de volumen en la ICA. El objetivo de este estudio es evaluar la utilidad del CA125 para el ajuste del tratamiento diurético de pacientes con SCR-1. Métodos: Ensayo clínico multicéntrico, abierto y paralelo, que incluye a pacientes con ICA y creatinina ≥ 1,4 mg/dl al ingreso, aleatorizados a: a) estrategia convencional: titulación basada en la evaluación clínica y bioquímica habitual, o b) estrategia basada en CA125: dosis altas de diuréticos si CA125 > 35 U/ml y bajas en caso contrario. El objetivo principal es el cambio en la función renal a las 24 y las 72 h tras el comienzo del tratamiento. Como objetivos secundarios: a) cambios clínicos y bioquímicos a las 24 y las 72 h, y b) cambios en la función renal y eventos clínicos mayores a 30 días. Resultados: Los resultados de este estudio aportarán datos relevantes sobre la utilidad del CA125 para guiar el tratamiento diurético en el SCR-1. Además, permitirá ampliar el conocimiento de la fisiopatología de esta compleja entidad clínica. Conclusiones: La hipótesis del presente estudio es que las concentraciones de CA125 aumentadas pueden identificar a una población de pacientes con SCR-1 para quienes una estrategia diurética más intensa puede ser beneficiosa. Por el contrario, las concentraciones bajas de esta glucoproteína seleccionarían a los pacientes para los que serían perjudiciales las dosis altas de diuréticos (AU)

Introduction and objectives: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Methods: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4 mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72 hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72 hours, and b) renal function changes and major clinical events at 30 days. Results: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. Conclusions: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses (AU)

Different distribution of the common HFE variants between western and eastern Spanish populations evidences an independent haplotype gene flow / Diferencias en la distribución de las variantes comunes del gen HFE entre poblaciones del oeste y este de España evidencian un flujo independiente de sus distintos haplotipos

Introduction. Hereditary hemochromatosis is a disease responsible for excess blood iron. The hemochromatosis gene has two predominant variants, H63D and C282Y single nucleotide polymorphisms. Our study aims to analyze the diagnostic utility of genotyping the 63 and 282 loci, and examine the geographic distribution of these mutations in Spain. Methods and materials. Genotyping was performed on 94 healthy control individuals and 324 patients suspected of hereditary hemochromatosis, and also biochemical test to 313 individuals in the patients group. Results. The comparison of allelic frequencies between East and West of Spain, as well as other countries located at a similar longitude, evidenced a west-east distribution gradient of the C282Y allele. In addition, heterogeneous distribution of the H63D mutation in Spain was observed. Patients who carried the 282YY genotype showed significantly higher biochemical parameters (ferritin>300μg/L, Fe>180μg/L, IST>60%, UIBC>355μg/L and CTFH>370μg/dL), which confirmed the correlation between the mutated homozygous genotype and the associated hemochromatosis phenotype. Conclusion. Our results strengthen the importance of executing genetic tests to increase the efficiency of hereditary hemochromatosis diagnosis, which reveal an interesting variability among geographical regions (AU)

Introducción. La hemocromatosis hereditaria es una enfermedad responsable del exceso de hierro en sangre. El gen de la hemocromatosis tiene dos variantes predominantes, los polimorfismos de un solo nucleótido H63D y C282Y. Nuestro estudio trata de analizar la utilidad diagnóstica del genotipado de los loci 282 y 63, y examinar la distribución geográfica de estas mutaciones en España. Material y métodos. Se realizó genotipado en 94 controles sanos y 324 pacientes con sospecha de hemocromatosis hereditaria y además, test bioquímico a 313 individuos del grupo de pacientes. Resultados. La comparación de frecuencias alélicas entre poblaciones del este y el oeste de España, así como de otros países localizados en longitudes similares, evidenció una distribución en gradiente del alelo C282Y. Además se observó una distribución heterogénea de la mutación H63D en España. Los pacientes portadores del genotipo 282YY mostraron parámetros bioquímicos significativamente más elevados (ferritina >300μg/L, Fe > 180μg/L, IST > 60%, UIBC > 355μg/L y CTFH>370μg/dL), confirmando la correlación entre el genotipo homozigoto mutado y el fenotipo característico de hemocromatosis. Conclusión. Nuestros resultados refuerzan la importancia de realizar pruebas genéticas para confirmar el diagnóstico de la hemocromatosis hereditaria, teniendo en cuenta la variabilidad de los datos entre ámbitos geográficos (AU)

Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

INTRODUCTION AND OBJECTIVES: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. METHODS: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. RESULTS: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. CONCLUSIONS: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses.

Estudio prospectivo de los valores de hormonas y péptidos relacionados con el metabolismo glucolipídico en pacientes obesos mórbidos sometidos a una gastrectomía vertical / Prospective study of gluco-lipidic hormone and peptide levels in morbidly obese patients after sleeve gastrectomy

INTRODUCCIÓN: Diferentes hormonas y péptidos implicados en el apetito y el metabolismo lipídico e hidrocarbonado se han estudiado en relación con la obesidad mórbida y su variación tras cirugía bariátrica. El objetivo de nuestro trabajo es evaluar las variaciones de diferentes moléculas relacionadas con el metabolismo glucolipídico durante el primer año tras una gastrectomía vertical en pacientes obesos mórbidos. MATERIAL Y MÉTODO: Estudio prospectivo en pacientes operados mediante gastrectomía vertical entre noviembre de 2009 y enero de 2011. Se determinaron y analizaron las variaciones en diferentes parámetros clínicos, antropométricos y analíticos relacionados con el metabolismo glucolipídico en todos los pacientes en el preoperatorio, al primer y quinto días, al mes, a los 6 meses y al año postoperatorio, realizando el estudio estadístico con ayuda del programa SPSS 20.0. RESULTADOS: De los 20 pacientes estudiados, el 60% eran mujeres con una mediana de edad de 45 años. La mediana del índice de masa corporal (IMC) preoperatorio fue de 48,5 kg/m2 y el 70% padecían síndrome de apnea obstructiva del sueño (SAOS), el 65% hipertensión arterial (HTA), el 45% dislipidemia y el 40% diabetes mellitus. Al año de la cirugía, el porcentaje de exceso de IMC perdido fue del 72% y la tasa de curación o mejoría de la dislipidemia fue del 100%, de diabetes el 87,5%, de HTA el 84,6% y de SAOS el 57,1%. En ese período los niveles de glucemia en ayunas disminuyeron de forma significativa (p < 0,001), mostrando los niveles de IGF-1 y colesterol HDL un aumento significativo. Los niveles de adiponectina aumentaron y los de leptina (p = 0,003), insulina (p = 0,004) y triglicéridos (p = 0,016) disminuyeron de forma significativa al año de la intervención. Los valores de ACTH (que disminuyeron durante los 6 primeros meses), hemoglobina glucosilada, colesterol total y LDL no experimentaron cambios significativos al año de la intervención. CONCLUSIÓN: La gastrectomía vertical es una técnica que presenta buenos resultados ponderales y de curación de comorbilidades, produciendo modificaciones significativas durante el primer año postoperatorio en los niveles sanguíneos de diferentes parámetros relacionados con el metabolismo glucolipídico como la glucosa, IGF-1, insulina, leptina, triglicéridos y colesterol HDL

INTRODUCTION: Different hormones and peptides involved in lipid and carbohydrate metabolism have been studied in relation to morbid obesity and its variation after bariatric surgery. The aim of this study is toevaluate variations in different molecules related to glico-lipidic metabolism during the first year after sleeve gastrectomy in morbidly obese patients. MATERIAL AND METHODS: Prospective study in patients undergoing sleeve gastrectomy between November 2009 and January 2011. We analyzed changes in different clinical, anthropometric and analytic parameters related with glico-lipidic metabolism in all patients in the preoperative period, first postoperative day, fifth day, one month, 6 months and one year after surgery. Statistical analysis was performed using SPSS 20.0. RESULTS: We included 20 patients, 60% were women with a median of age of 45 years. Median of body mass index (IMC) was 48,5 kg/m2 and 70% had obstructive sleep apnea syndrome (SAOS), 65% arterial hypertension (HTA), 45% dyslipidemia and 40% diabetes mellitus. One year after surgery, the percentage of excess of BMI loss was 72% and the rate of cure or improvement of dyslipidemia was 100%, diabetes 87,5%, HTA 84,6% and SAOS 57,1%. At this time, glycemia levels decreased significantly (P < .001), and levels of IGF-1 and HDL-cholesterol increased significantly. Levels of adiponectine increased and leptine (P = .003), insulin (P = .004) and triglycerides (P = .016) decreased significantly one year after the surgery. ACTH levels (that decreased during first 6 months after surgery), glycosilated hemoglobin, total cholesterol and LDL-cholesterol had no changes one year after surgery. CONCLUSIONS: Sleeve gastrectomy is a surgical technique with good results of weight loss and cure of comorbidities. This procedure induces significant modifications in blood levels of glico-lipidic metabolism related peptides and hormones, such as glucose, IGF-1, insulin, leptin, triglycerides and HDL-cholesterol

A prospective study on inflammatory parameters in obese patients after sleeve gastrectomy.

Different hormones and peptides involved in inflammation have been studied in and related to obesity. The aim of our work is to assess the variations of different molecules related to inflammation in obese patients during the first year following sleeve gastrectomy. This was a prospective study on patients who underwent sleeve gastrectomy. The variations in different clinical, anthropometric, and analytical parameters related to inflammation were determined and analysed in all patients at the preoperative visit and at the first and fifth days, first and sixth months, and 1 year following surgery. We enrolled 20 patients to the study. The median body mass index (BMI) before intervention was 48.5 kg/m2. With respect to comorbidities, 70% of the patients had obstructive sleep apnoea syndrome (OSA), 65% high blood pressure, 45% dyslipidaemia, and 40% diabetes mellitus (DM). The median percentage of BMI lost (%BMIL) 1 year after the intervention was 71%. The dyslipidaemia healing or improvement rate was 100%, whereas it was 87.5% for diabetes, 84.6% for hypertension, and 57.1% for OSA. During the 1-year postintervention period, the average levels of adiponectin increased, although not significantly, whereas those of leptin significantly decreased. In addition, the blood levels of MCP-1, IL-6, CRP, ferritin, and PAI-1 significantly decreased in that period. Sleeve gastrectomy is a surgical technique that is associated with improvements in body weight and comorbid conditions from the first postoperative months, which lead to significant variations in the levels of different inflammation-related parameters and a decrease in the levels of leptin, IL-6, CRP, MCP-1, ferritin, and serpin (PAI-1).

[Prospective study of gluco-lipidic hormone and peptide levels in morbidly obese patients after sleeve gastrectomy]. / Estudio prospectivo de los valores de hormonas y péptidos relacionados con el metabolismo glucolipídico en pacientes obesos mórbidos sometidos a una gastrectomía vertical.

INTRODUCTION: Different hormones and peptides involved in lipid and carbohydrate metabolism have been studied in relation to morbid obesity and its variation after bariatric surgery. The aim of this study is toevaluate variations in different molecules related to glico-lipidic metabolism during the first year after sleeve gastrectomy in morbidly obese patients. MATERIAL AND METHODS: Prospective study in patients undergoing sleeve gastrectomy between November 2009 and January 2011. We analyzed changes in different clinical, anthropometric and analytic parameters related with glico-lipidic metabolism in all patients in the preoperative period, first postoperative day, fifth day, one month, 6 months and one year after surgery. Statistical analysis was performed using SPSS 20.0. RESULTS: We included 20 patients, 60% were women with a median of age of 45 years. Median of body mass index (IMC) was 48,5 kg/m(2) and 70% had obstructive sleep apnea syndrome (SAOS), 65% arterial hypertension (HTA), 45% dyslipidemia and 40% diabetes mellitus. One year after surgery, the percentage of excess of BMI loss was 72% and the rate of cure or improvement of dyslipidemia was 100%, diabetes 87,5%, HTA 84,6% and SAOS 57,1%. At this time, glycemia levels decreased significantly (P<.001), and levels of IGF-1 and HDL-cholesterol increased significantly. Levels of adiponectine increased and leptine (P=.003), insulin (P=.004) and triglycerides (P=.016) decreased significantly one year after the surgery. ACTH levels (that decreased during first 6 months after surgery), glycosilated hemoglobin, total cholesterol and LDL-cholesterol had no changes one year after surgery. CONCLUSIONS: Sleeve gastrectomy is a surgical technique with good results of weight loss and cure of comorbidities. This procedure induces significant modifications in blood levels of glico-lipidic metabolism related peptides and hormones, such as glucose, IGF-1, insulin, leptin, triglycerides and HDL-cholesterol.

Trends in the prevalence and distribution of HTLV-1 and HTLV-2 infections in Spain.

BACKGROUND: Although most HTLV infections in Spain have been found in native intravenous drug users carrying HTLV-2, the large immigration flows from Latin America and Sub-Saharan Africa in recent years may have changed the prevalence and distribution of HTLV-1 and HTLV-2 infections, and hypothetically open the opportunity for introducing HTLV-3 or HTLV-4 in Spain. To assess the current seroprevalence of HTLV infection in Spain a national multicenter, cross-sectional, study was conducted in June 2009. RESULTS: A total of 6,460 consecutive outpatients attending 16 hospitals were examined. Overall, 12% were immigrants, and their main origin was Latin America (4.9%), Africa (3.6%) and other European countries (2.8%). Nine individuals were seroreactive for HTLV antibodies (overall prevalence, 0.14%). Evidence of HTLV-1 infection was confirmed by Western blot in 4 subjects (prevalence 0.06%) while HTLV-2 infection was found in 5 (prevalence 0.08%). Infection with HTLV types 1, 2, 3 and 4 was discarded by Western blot and specific PCR assays in another two specimens initially reactive in the enzyme immunoassay. All but one HTLV-1 cases were Latin-Americans while all persons with HTLV-2 infection were native Spaniards. CONCLUSIONS: The overall prevalence of HTLV infections in Spain remains low, with no evidence of HTLV-3 or HTLV-4 infections so far.

HTLV infection among foreign pregnant women living in Spain.

BACKGROUND: The overall seroprevalence of HTLV infection among pregnant women in Spain is below 0.02% and accordingly universal antenatal screening is not recommended. However, as the number of immigrants has significantly increased during the last decade, this population might warrant specific considerations. OBJECTIVE: To evaluate the seroprevalence of HTLV infection among immigrant pregnant women living in Spain. METHODS: From January 2009 to December 2010 a cross-sectional study was carried out in all foreign pregnant women attended at 14 Spanish clinics. All were tested for HTLV antibodies using a commercial enzyme-immunoassay, being reactive samples confirmed by Western blot or PCR. RESULTS: A total of 3337 foreign pregnant women were examined. Their origin was as follows: Latin America 1579 (47%), North Africa 507 (16%), East Europe 606 (18%), Sub-Saharan Africa 316 (9%), North America and West Europe 116 (3.5%) and Asia and Australia 163 (5%). A total of 7 samples were confirmed as HTLV positive, of which 6 were HTLV-1 and 1 HTLV-2. HTLV-1 infection was found in 5 women coming from Latin America and 1 from Morocco. The only woman with HTLV-2 came from Ghana. The overall HTLV seroprevalence was 0.2%, being 0.3% among Latin Americans and 0.2% among Africans. It was absent among women coming from other regions. CONCLUSIONS: The seroprevalence of HTLV infection among foreign pregnant women in Spain is 0.2%, being all cases found in immigrants from Latin America and Africa. Given the benefit of preventing vertical transmission, antenatal screening should be recommended in pregnant women coming from these regions.