Clinical application of amino-terminal pro-brain natriuretic peptide concentration in amniotic fluid for the prediction of preterm birth in symptomatic women.

BACKGROUND: Preterm birth accounts for 60% to 80% of neonatal mortality. Approximately one-third of preterm births are caused by the spontaneous onset of preterm labor. Nevertheless, 70% to 90% of women diagnosed with preterm labor will not deliver within 7 days. Thus, many women will be unnecessarily treated by preterm labor with risk medications. Better tools are needed to categorize women in preterm labor into high or low risk of preterm delivery. OBJECTIVE: This study aimed to evaluate the amino-terminal pro-brain natriuretic peptide concentration in the amniotic fluid as a prognostic test to predict the risk of delivery within 48 hours or 7 days and before 34 0/7 or 37 0/7 weeks of gestation in women in preterm labor. STUDY DESIGN: A total of 102 pregnant women presenting signs and symptoms of spontaneous preterm birth (22 0/7 to 34 0/7 weeks of gestation) were included. Amniotic fluid was obtained by amniocentesis, and amino-terminal pro-brain natriuretic peptide concentration was measured. Below normal concentration was defined as <0.5 multiples of the median of the standard curve according to gestational age. The risk of preterm delivery was estimated according to normal or lower-than-normal amino-terminal pro-brain natriuretic peptide concentrations. The predictive capacity of the test (below normal amino-terminal pro-brain natriuretic peptide concentration) was evaluated to identify spontaneous preterm birth at 48 hours or 7 days from amniocentesis and less than 34 0/7 or 37 0/7 weeks at delivery. RESULTS: For the outcome delivery within 48 hours, lower-than-normal amino-terminal pro-brain natriuretic peptide concentration had 94.6% sensitivity, 73.8% specificity, 96.0% negative predictive value, 3.61 positive likelihood ratio, and 0.07 negative likelihood ratio. For the outcome delivery within 7 days, the test had 93.9% sensitivity, 88.7% specificity, 94.0% negative predictive value, 8.31 positive likelihood ratio, and 0.07 negative likelihood ratio. For the outcomes of spontaneous preterm birth before 34 0/7 and 37 0/7 weeks of gestation, below normal amino-terminal pro-brain natriuretic peptide concentrations had 80.0% sensitivity, 83.0% specificity, 78.0% negative predictive value, 4.70 positive likelihood ratio, and 0.24 negative likelihood ratio and 64.1% sensitivity, 91.7% specificity, 44.0% negative predictive value, 7.70 positive likelihood ratio, and 0.39 negative likelihood ratio, respectively. CONCLUSION: Among patients in spontaneous preterm labor, the detection of lower-than-normal amino-terminal pro-brain natriuretic peptide concentrations (<0.5 multiples of the median) in amniotic fluid has an excellent predictive capacity to identify those patients at low risk of preterm delivery within 48 hours or 7 days.

B-type natriuretic peptide and N-terminal Pro-B-type natriuretic peptide in severe aortic stenosis: a comprehensive literature review.

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro BNP) are cardiac biomarkers that are released in response to increased ventricular and atrial wall stress. Aortic stenosis (AS) leads to hemodynamic changes and left ventricular hypertrophy and may be associated with natriuretic peptide levels. Several studies have shown that increased natriuretic peptide levels are correlated with AS severity and can predict the need for intervention. It can be useful in risk stratification, monitoring follow-up, and predicting cardiovascular outcomes of patients with severe AS. This paper aims to summarize the evidence of the role of BNP and NT-pro BNP in AS, before and after intervention.

Multimodality imaging methods and systemic biomarkers in classical low-flow low-gradient aortic stenosis: Key findings for risk stratification.

Objectives: The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS). Background: Elevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS. Methods: Prospective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 (n = 17) when BNP and hsTnI levels were below median [BNP < 1.98 fold upper reference limit (URL) and hsTnI < 1.8 fold URL]; Group 2 (n = 14) when BNP or hsTnI were higher than median; and Group 3 (n = 18) when both hsTnI and BNP were higher than median. Results: 49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance (P = 0.03) and lower left ventricular ejection fraction (P = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31-47] vs. 32 [29-41] vs. 26 [19-33]%; p < 0.01) and right ventricular EF (62 [53-69] vs. 51 [35-63] vs. 30 [24-46]%; p < 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8-30.7] vs. 28.2 [26.9-34.5] vs. 31.8 [28.9-35.5]%; p = 0.03) and indexed ECV (iECV) (28.7 [21.2-39.1] vs. 28.8 [25.4-39.9] vs. 44.2 [36.4-51.2] ml/m2, respectively; p < 0.01) from Group 1 to Group 3. Conclusions: Higher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis.

Utilidad del NT-proBNP en la evaluación pronóstica de pacientes con estenosis aórtica grave asintomáticos, con fracción de eyección ventricular izquierda preservada / Prognostic Value of NT-proBNP in Asymptomatic Patients with Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction

RESUMEN Introducción : La indicación de reemplazo valvular aórtico (RVA) en pacientes con estenosis aórtica (EA) grave asintomáticos con función conservada es motivo de creciente debate. Objetivos : Evaluar si la elevación de la fracción aminoterminal del pro-péptido natriurético tipo B (NT-proBNP) predice la aparición de síntomas y la indicación de reemplazo valvular en pacientes inicialmente asintomáticos, con EA grave y fracción de eyección ventricular izquierda (FEVI) conservada. Material y métodos : Se incluyeron en forma prospectiva pacientes con EA grave, FEVI conservada (≥55%) que fueron considerados asintomáticos, sin indicación inicial de RVA. A todos se les realizó laboratorio con medición de NT-proBNP en forma basal y ecocardiograma con Doppler tisular consignando la onda S de la pared lateral (S lat) y la relación E/e´. Se consideró como punto final el requerimiento de reemplazo valvular durante el seguimiento. Resultados : Se incluyeron 133 pacientes con una edad de 69 ± 8 años, 49% mujeres. Luego de un seguimiento de 570 (rango intercuartilo 380-680) días, el 23,3% (n = 31) de los pacientes presentaron requerimiento de reemplazo valvular. En el aná lisis multivariado, el NT-proBNP y la relación E/e´ fueron predictores independientes de requerimiento de cirugía (HR 1,02, IC95% 1,001-1,03, p <0,001; y HR 1,42, IC95% 1,21-2,45, p<0,001, respectivamente). El NT-proBNP presentó un Área Bajo la Curva (ABC) mayor que la relación E/e´ (0,88 versus 0,64, p = 0,02). Se estableció como mejor punto de corte de NT-proBNP un valor >350 pg./mL (HR ajustado 1,55, IC95% 1,38-2,01, p <0,001). Conclusiones : El NT-proBNP y la relación E/e´ fueron predictores independientes de requerimiento de cirugía. El NT-proBNP presentó una muy buena capacidad de discriminación, mayor que la relación E/e´.

ABSTRACT Background : The aortic valve replacement (AVR) indication in asymptomatic patients with severe aortic stenosis (AS) and preserved function is being increasingly discussed. Objective : The aim of this study was to evaluate whether the elevation of the N-terminal fraction of the pro-B-type natriuretic peptide (NT-proBNP) predicts the occurrence of symptoms and the AVR indication in patients with severe AS and preserved left ventricular ejection fraction (LVEF), initially asymptomatic. Methods : Asymptomatic patients with severe AS, preserved EF (≥55%) and no initial AVR indication were prospectively included. All patients underwent laboratory tests measuring NT-proBNP at baseline and an echocardiogram with tissue Doppler recording the lateral wall S wave (lat. S) and the E/e´ ratio. The endpoint was the aortic valve replacement indication at follow-up. Results : We included 133 patients aged 69 ± 8 years, 49% of which were women. After a follow-up of 570 (interquartile range 380-680) days, 23.3% (n=31) of them required aortic valve replacement. In the multivariate analysis, NT-proBNP value and the E/e´ ratio were 2 independent predictors of surgery (HR 1.02, 95% CI 1.001-1.03) p<0.001 and HR 1.42, 95% CI 1.21- 2.45, p< 0.001, respectively). NT-proBNP presented an area under the curve (AUC) greater than the E/e' ratio (0.88 versus 0.64, p=0.02). The best NT-proBNP cut-off point was determined >350 pg/mL (adjusted HR 1.55, 95% CI 1.38-2.01, p<0.001) Conclusion : NT-proBNP value and the E/e´ ratio were independent predictors of the AVR requirement. NT-proBNP had a very good discrimination capacity, greater than the E/e´ ratio.

Síndrome inflamatorio multisistémico en pediatría: importancia de la evaluación inicial de los parámetros de laboratorio / Multisystem Inflammatory Syndrome in children: the importance of evaluation of early laboratory parameters

RESUMEN Introducción : El síndrome inflamatorio multisistémico en pediatría (SIM-C) es una infrecuente entidad asociada a COVID-19 con un amplio espectro de presentación: desde un cuadro similar a la enfermedad de Kawasaki a una afectación multisistémica con shock. Se han descripto asociaciones entre valores de laboratorio y mala evolución, pero no existen puntos de corte que predigan la misma. Objetivo : El objetivo de este estudio fue describir y analizar las características de los pacientes con SIM-C y las relaciones de estas con los hallazgos de laboratorio. Material y métodos : Se realizó un estudio analítico y retrospectivo de niños internados con diagnóstico de SIM-C entre mayo 2020 y junio 2021 en el HNRG. Se estudiaron 32 pacientes, 17 femeninas (53,13%) y 15 masculinos (46,87%), edad promedio de 7,67 años (rango 0,5-14,91). Diez de los pacientes (31,25%) presentaron shock. Se obtuvieron datos clínicos, ecocardiográficos y valores de troponina I ultrasensible, NT-proBNP, plaquetas y linfocitos al momento del diagnóstico; y se analizaron comparativamente entre quienes presentaron shock durante la evolución (Grupo 1) y quienes no (Grupo 2). Resultados : La diferencia en un valor inicial de NT-proBNP elevado fue estadísticamente significativa entre ambos grupos (p=0,008), en tanto que la troponina y el recuento de linfocitos y plaquetas, no. De los 13 pacientes que requirieron inotrópicos, el 58% presentó linfopenia inicialmente (p=0,006 vs aquellos que no los necesitaron). Conclusiones : Si bien la mortalidad debido al SIM-C es baja, la afectación cardiovascular y el compromiso hemodinámico en los paci entes que presentaron este síndrome puede ser frecuente. Poder contar con una herramienta de laboratorio ampliamente difundida para la categorización de pacientes podría ayudar a mitigar riesgos y obtener una derivación temprana a centros especializados.

ABSTRACT Background : Multisystem inflammatory syndrome in children (MIS-C) is an uncommon condition associated with COVID-19 with a wide spectrum of presentations, ranging from Kawasaki-like disease to multisystem involvement with shock. The as sociation between the laboratory characteristics and unfavorable outcome has been described, but the cut-off points associated with higher risk have not yet been defined. Objective : The aim of this study was to describe and analyze the characteristics of patients with MIS-C and their associations with the laboratory findings. Methods : We conducted an analytical and retrospective study of pediatric patients hospitalized between May 2020 and June 2021 with diagnosis of MIS-C in Hospital General de Niños Dr. Ricardo Gutiérrez (HNRG). The cohort was made up of 23 patients, 17 female (53.13%) and 15 male (46.87%); mean age was 7.67 years (range 0.5-14.91). Ten patients (31.25%) presented shock. Clinical and echocardiographic data and values of high-sensitive troponin I, N-terminal pro-B-type natriuretic peptide (NT-proBNP), platelets and lymphocytes at the time of diagnosis were obtained and compared between those with shock during evolution (group 1) and those without shock (group 2). Results : There was a significant difference in baseline elevated NT-proBNP values between both groups (p = 0.008), but not in troponin levels and lymphocyte and platelet counts. Of the 13 patients who required inotropic agents, 58% had baseline lymphopenia (p = 0.006 vs those who did not require inotropic drugs). Conclusions : Although mortality due to MIS-C is low, cardiac involvement and hemodynamic impairment may be common. The availability of a commonly used laboratory tool for patient categorization could help to mitigate risks and obtain early referral to specialized centers.

N-terminal del péptido natriurético tipo B y la amplitud de distribución eritrocitaria como factor pronóstico de severidad en pacientes con insuficiencia cardiaca aguda descompensada

Introducción: El estudio de predictores de desenlaces negativos en pacientes con insuficiencia cardiaca ha incluido la combinación de péptidos natriuréticos y el ancho de distribución eritrocitaria (RDW). Objetivo: Evaluar el uso combinado de la porción N-terminal del propéptido natriurético tipo B (NT-proBNP) y el RDW como pronóstico de fallecimiento por cualquier causa, hospitalización prolongada y reingreso al año del alta en pacientes con insuficiencia cardiaca aguda (ICA) descompensada. Métodos: Realizamos un estudio observacional retrospectivo. Construimos un índice combinado = NT-proBNP x RDW/100. Elaboramos curvas ROC, se estimó la sensibilidad y especificidad en base a los puntos de corte y se estimó el riesgo relativo para desarrollar los desenlaces. Comparamos las áreas bajo las curvas del índice combinado versus el NT-proBNP y RDW, por separado. Resultados: Analizamos los datos de 471 pacientes. El índice combinado tuvo su mejor corte en 927,79 para pronosticar fallecimiento durante el primer año de ingreso. Aquellos con valores ≥ 927,79 tuvieron un riesgo relativo de 32,7 (IC95%: 4,8 - 222,3). Para hospitalización ≥7 días el punto de corte fue 752,67, aquellos con este valor o superiores tuvieron un riesgo relativo de 22,4 (IC95%: 9,7 - 51,8). Para pronosticar reingreso al año del alta el corte fue 858,47 y el riesgo relativo fue 4,7 (IC95%: 3,3 - 6,8). Conclusiones: El índice combinado generó riesgos relativos que muestran una fuerte fuerza de asociación para fallecimiento por cualquier causa, hospitalización ≥ 7 días y reingresos al año del alta. Sin embargo, la superioridad para discriminar no fue concluyente respecto a los componentes individuales.

Introduction: The study of predictors of negative outcomes in patients with heart failure has included the combination of natriuretic peptides and red cell distribution width (RDW). Objective: To evaluate the combined use of the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and RDW as a prognostic factor for death from any cause, prolonged hospitalization, and readmission one year after discharge in patients with decompensated acute heart failure (AHF). Methods: We conducted a retrospective observational study. We constructed a combined index = NT-ProBNP x RDW/100. ROC curves were constructed, sensitivity and specificity were estimated based on the cut-off points, and the relative risk was estimated to develop the outcomes studied. We compared the area under curve of combined index versus NT-proBNP and RDW, separately. Results: We analyzed data from 471 patients. The combined index had its best cut of 927.79 to predict death during the first year of admission. Those with values ≥ 927,79 had a relative risk of 32.7 (95% CI: 4.8 - 222.3). To predict hospitalization ≥ 7 days, the cut-off point was 752.67; those with this value or higher had a relative risk of 22.4 (95% CI: 9.7 - 51.8). To predict readmission one year after discharge, the cutoff was 858.47 and the relative risk was 4.7 (95% CI: 3.3 - 6.8). Conclusions: The combined index used generate relative risks that show a strong strength of association for death from any cause, hospitalization ≥7 days, and readmissions one year after discharge. However, the superiority to discriminate was inconclusive with respect to the individual components.

Xanthomonas natriuretic peptide is recognized by the Arabidopsis natriuretic peptide receptor 1 and through this interaction triggers similar plant responses to its plant counterpart.

Plant natriuretic peptides (PNPs) are hormone peptides that participate in the regulation of ions and water homeostasis in plants. Xanthomonas citri subsp. citri (Xcc) the causal agent of citrus canker disease also possesses a PNP-like peptide (XacPNP). This peptide, similarly to AtPNP-A, the most studied PNP from Arabidopsis thaliana, causes stomatal aperture and enhances photosynthetic efficiency in plant leaves. Thus, the function that has been attributed to XacPNP is to contribute to maintain photosynthetic efficiency and water homeostasis in plant tissue during the infection process, to create favorable conditions for biotrophic pathogens survival. A PNP receptor (AtPNP-R1) for AtPNP-A has been identified and the AtPNP-A activity in regulation of water homeostasis has been observed to depend on the presence of AtPNP-R1. Here, we demonstrated that both AtPNP-A and XacPNP require the presence of AtPNP-R1 to induce plant stomatal aperture. Also, less necrotic tissue was found in infections with pathogens expressing XacPNP and this was dependent on the presence of AtPNP-R1, suggesting that XacPNP interacts with this receptor to exert its function. Finally, we confirmed that AtPNP-A and XacPNP interact with AtPNP-R1 in planta, which support the idea that XacPNP triggers similar plant responses to its plant counterpart.

Clinical value of combined plasma brain natriuretic peptide and serum cystatin C measurement on the prediction of heart failure in patients after acute myocardial infarction

This research investigated the predictive value of combined detection of brain natriuretic peptide (BNP) and cystatin C (Cys C) in heart failure after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Sixty-five AMI patients complicated by heart failure (HF) after PCI and 79 non-heart failure (non-HF) patients were involved in this research. The levels of Cys C and BNP were measured. Risk factors for heart failure in AMI patients after PCI were analyzed by multivariate logistic regression analysis. Efficacy of BNP and Cys C on predicting heart failure were analyzed by receiver operating characteristic (ROC) curve. Cys C and BNP levels were significantly higher in the HF group than in the non-HF group. BNP and Cys C levels were the independent influencing factors causing heart failure within one year after PCI. The area under the predicted curve (AUC) of Cys C, BNP, and combined Cys C and BNP were 0.763, 0.829, and 0.893, respectively. The combined detection of Cys C and BNP was highly valuable in predicting heart failure in AMI patients after PCI, which can be regarded as the serum markers for diagnosis and treatment of heart failure.

Enuresis and upper airway obstruction: BNP and ADH hormones behavior before and after airway surgery

ABSTRACT Introduction: Upper airway obstruction (UAO) is a common condition in all pediatric population, with a 27% prevalence. Primary monosymptomatic nocturnal enuresis (PMNE) is a condition related to UAO in 8% to 47% of these children. The specific pathophysiological mechanism of this bond is not well understood. Some authors suggest a connection between brain natrituretic peptide (BNP) and anti-diuretic hormone (ADH) during sleep. The aim of this study was to evaluate hormone profile (ADH and BNP) and improvement in dry nights in a sample of children before and after surgical treatment of the UAO. Methods: This is a longitudinal prospective interventionist study in children, 5 to 14 years of age, with UAO and PMNE recruited in a specialty outpatient clinic. Children presenting UAO and PMNE were evaluated with a 30-day dry night diary and blood samples were collected to evaluate ADH and BNP before and after upper airway surgery. Data were analyzed prior to surgery and 90-120 days after surgery. Results: Twenty-one children with a mean age of 9.7 years were included. Mean BNP before surgery was 116.5 ± 126.5 pg/mL and 156.2 ± 112.3 pg/mL after surgery (p<0.01). Mean ADH was 5.8 ± 3.2 pg/mL and 14.6 ± 35.4 before and after surgery, respectively (p=0.26). The percentage of dry nights went from 32.3 ± 24.7 before surgery to 75.4 ± 33.4 after surgery (p<0.01). Conclusion: Surgery for airway obstruction contributed to an increase in BNP without increasing ADH. A total of 85.8% of the children presented partial or complete improvement of their enuresis.

Predictive value of serum initial brain natriuretic peptide and troponin on functional prognosis in noncardiogenic patients with anterior and posterior circulation cerebral infarction / Valor preditivo dos níveis séricos iniciais do peptídeo natriurético cerebral e da troponina no prognóstico funcional em pacientes não cardiogênicos com acidente vascular cerebral isquêmico de circulação anterior e posterior

Abstract Background Brain natriuretic peptide (BNP) and troponin have a close relationship with cardiogenic cerebral embolism (CCE), but their relationship with noncardiogenic patients with anterior circulation ischemia (ACI) and posterior circulation ischemia (PCI) is not clear. Objective To explore the predictive value of serum initial BNP and troponin on the functional prognosis of patients with noncardiogenic ACI and PCI. Methods Consecutive patients with first-episode cerebral infarction within 12 hours of symptom onset were enrolled in the present 1-year prospective cohort study. Serum levels of BNP and troponin were collected within 12 hours of onset. Infarction location was classified as ACI and PCI by magnetic resonance imaging (MRI). According to the modified Rankin Scale (mRS) score at 90 days after onset, ACI and PCI cases were respectively divided into a good prognosis group (mRS score between 0 and 2) and a poor prognosis group (mRS score between 3 and 6). The general state of health and results of laboratory examinations and other auxiliary examinations of all patients were recorded. Single-factor analysis and multivariate logistic regression analysis were used to assess the relationship between serum levels of BNP, troponin, and functional outcome. Results The multivariate logistic regression found that higher levels of initial BNP (odds ratio [OR] = 1.024; 95% confidence interval [CI]: 1.006-1.041; p = 0.007) and C-reactive protein (CRP) (OR = 1.184; 95%CI: 1.024-1.369; p = 0.022) were independent predictors of poor functional prognosis of noncardiogenic PCI at 90 days after onset after adjusting for age, gender, ethnicity, history of hypertension and of diabetes. Conclusions The levels of initial BNP and CRP were related to poor functional outcomes in noncardiogenic PCI patients at 3 months, independent of troponin.

Resumo Antecedentes O peptídeo natriurético cerebral (BNP, na sigla em inglês) e a troponina estão intimamente relacionados com a embolia cerebral cardiogênica (CCE, na sigla em inglês), mas a relação com pacientes não cardioembólicos com isquemia de circulação anterior (ICA) e isquemia de circulação posterior (ICP) não é clara. Objetivo Investigar o valor preditivo dos níveis séricos iniciais do BNP e da troponina no prognóstico de pacientes com AVC isquêmico não cardiogênico. Métodos Os níveis séricos de BNP e de troponina foram recolhidos de pacientes com primeiro episódio de acidente vascular cerebral (AVC) isquêmico dentro de 12 horas após o início dos sintomas, com localização classificada como ICA e ICP de acordo com exame de ressonância magnética (RM). De acordo com a pontuação modificada da escala de Rankin (mRS), aos 90 dias após o início dos sintomas, ICA e ICP foram divididas respectivamente em um grupo de bom prognóstico (mRS entre 0 e2) e em um grupo de mau prognóstico (mRS entre 3 e 6). Foram registrados exames laboratoriais e outros exames complementares de todos os pacientes. Foram utilizadas análise fatorial única e análise de regressão logística multivariada para investigar a relação entre os níveis séricos de BNP e de troponina e o resultado funcional. Resultados A regressão logística multivariada evidenciou que os níveis mais altos de BNP inicial (odds ratio [OR] = 1,024, intervalo de confiança [IC] de 95%: 1,006-1,041; p = 0,007) e proteína C reativa (CRP, na sigla em inglês) (OR = 1,184; 95%CI: 1,024-1,369; p = 0,022) foram preditores independentes de mau prognóstico funcional da ICP não cardiogênica aos 90 dias após o início dos sintomas. Conclusões Os níveis iniciais de BNP e CRP se associaram a maus resultados funcionais em pacientes com ICP não cardiogênica aos três meses, independentemente da troponina.

Enuresis and upper airway obstruction: BNP and ADH hormones behavior before and after airway surgery.

INTRODUCTION: Upper airway obstruction (UAO) is a common condition in all pediatric population, with a 27% prevalence. Primary monosymptomatic nocturnal enuresis (PMNE) is a condition related to UAO in 8% to 47% of these children. The specific pathophysiological mechanism of this bond is not well understood. Some authors suggest a connection between brain natrituretic peptide (BNP) and anti-diuretic hormone (ADH) during sleep. The aim of this study was to evaluate hormone profile (ADH and BNP) and improvement in dry nights in a sample of children before and after surgical treatment of the UAO. METHODS: This is a longitudinal prospective interventionist study in children, 5 to 14 years of age, with UAO and PMNE recruited in a specialty outpatient clinic. Children presenting UAO and PMNE were evaluated with a 30-day dry night diary and blood samples were collected to evaluate ADH and BNP before and after upper airway surgery. Data were analyzed prior to surgery and 90-120 days after surgery. RESULTS: Twenty-one children with a mean age of 9.7 years were included. Mean BNP before surgery was 116.5 ± 126.5 pg/mL and 156.2 ± 112.3 pg/mL after surgery (p<0.01). Mean ADH was 5.8 ± 3.2 pg/mL and 14.6 ± 35.4 before and after surgery, respectively (p=0.26). The percentage of dry nights went from 32.3 ± 24.7 before surgery to 75.4 ± 33.4 after surgery (p˂0.01). CONCLUSION: Surgery for airway obstruction contributed to an increase in BNP without increasing ADH. A total of 85.8% of the children presented partial or complete improvement of their enuresis.

O Papel dos Níveis Séricos de ANP na Perda de Peso, Risco Cardiometabólico e Composição Corporal de Adolescentes com Obesidade Submetidos a Terapia Interdisciplinar / The Role of ANP Level Response in Interdisciplinary Weight Loss Therapy on Cardiometabolic Risk and Body Composition in Adolescents with Obesity

Resumo Fundamento A ação do peptídeo natriurético atrial (ANP) na natriurese, diurese e vasodilatação, resistência à insulina, fígado, rim e tecido adiposo pode contribuir para o desenvolvimento metabólico e cardiovascular saudável. Embora o nível circulante de ANP seja reduzido em pacientes com obesidade, sua resposta à perda de peso ainda é pouco explorada em populações pediátricas. Objetivo Avaliar os efeitos das variações do ANP em resposta à intervenção interdisciplinar para perda de peso na Síndrome Metabólica (SMet) e nos riscos cardiometabólicos em adolescentes com obesidade. Métodos 73 adolescentes com obesidade participaram de uma terapia interdisciplinar para perda de peso de 20 semanas, incluindo uma abordagem clínica, nutricional, psicológica e de exercícios físicos. A composição corporal, análises bioquímicas e pressão sanguínea foram avaliadas. A SMet foi classificada de acordo com a Federação Internacional de Diabetes (IDF) (2007). Após o tratamento, os voluntários foram divididos de acordo com os níveis de plasma do ANP aumento (n=31) ou ANP redução (n=19). Resultados Ambos os grupos apresentaram redução significativa de peso corporal, índice de massa corporal (IMC) e circunferências de cintura, pescoço e quadril (CC, CP e CQ, respectivamente), e aumento da massa livre de gordura (MLG). É interessante observar que houve uma redução significativa na gordura corporal, na razão de TG/HDL-c e na prevalência de SMet (de 23% para 6%) somente no grupo com ANP aumento. Conclusão Este estudo sugere que o aumento nos níveis séricos de ANP após a terapia para perda de peso pode estar associado a melhorias nos riscos cardiometabólicos e na prevalência reduzida de SMet em adolescentes com obesidade.

Abstract Background The action of atrial natriuretic peptide (ANP) on natriuresis, diuresis and vasodilatation, insulin resistance, liver, kidney, and adipose tissue may contribute to the healthy metabolic and cardiovascular development. Even though the circulating level of ANP is reduced in patients with obesity, its response to weight loss remains poorly explored in pediatric populations. Objective To evaluate the effects of ANP variations in response to interdisciplinary weight loss intervention on metabolic syndrome (MetS) and cardiometabolic risks in adolescents with obesity. Methods 73 adolescents with obesity attended a 20-week clinical interdisciplinary weight loss therapy including clinical, nutritional, psychological and exercise training approach. Body composition, biochemical analyses and blood pressure were evaluated. MetS was classified according to the International Diabetes Federation (IDF) (2007). After the treatment, volunteers were divided according to Increasing (n=31) or Decreasing (n=19) ANP plasma levels. Results Both groups present significant reduction of body weight, Body Mass Index (BMI), waist, neck and hip circumferences (WC, NC and HC, respectively) and increasing fat-free mass (FFM). Interestingly, a significant reduction in body fat, TG/HDL-c ratio and MetS prevalence (from 23% to 6%) was observed in the Increased ANP group only. Conclusion This study suggests that an increase in ANP serum levels after weight loss therapy could be associated with improvements in cardiometabolic risks and the reduced prevalence of MetS in adolescents with obesity.

[Prognostic value of the absolute decrease of the N-terminal portion of B-type natriuretic propeptide in decompensated heart failure: secondary analysis of the CLUSTER-HF study]. / Valor pronóstico del descenso absoluto de la porción N-terminal del propéptido natriurético tipo B en insuficiencia cardiaca descompensada: análisis secundario del estudio CLUSTER-HF.

Objective: The purpose of this study is to determine the prognostic value of the absolute decrease in the N-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) to prevent fewer clinical events, in the population of CLUSTER-HF (efficacy of ultrasound lung to guide therapy and prevent readmissions in heart failure). Materials and methods: This study was conducted in a subgroup of ninety-four patients with available NT-proBNP information at hospital discharge and prior to randomization in the CLUSTER-HF study. The primary objective of the study was to determine the prognostic value of absolute NT-proBNP decline below which fewer events of all-cause death, emergency room visits, and rehospitalization for heart failure at 180 days. Results: The absolute decrease in NT-proBNP below 3,350 pg/mL has a moderate discriminative capacity with AUC= 0.602, with a prognostic value in the combined event at 180 days (log-rank test, p=0.01). Also, according to the multivariable analysis, it is an independent marker of clinical events at 180 days OR 0.319 (0.102-0.995, p=0.04) above other clinical variables. Conclusions: An absolute decrease to 3,350 pg/mL of NT-proBNP or less at discharge from the hospitalization due to heart failure, was associated with fewer clinical events at 180 days.

Ceiling effect of Postconditioning and Atrial Natriuretic Peptide in Cardioprotection against Ischemia Reperfusion Injury in Ovariectomized rat hearts

Abstract Ischemic postconditioning (IPTC) brings cardioprotection endogenously, Atrial natriuretic peptide (ANP) produces the same effect. It happens due to down expression of endothelial nitric oxide synthase (eNOS). Thus, experimental protocol associating IPTC has been formulated to find the role of ANP in the cardioprotection of heart in OVX rats. For this experiment, heart was isolated from OVX rat and held tightly on Langendorff's apparatus in a manner that ischemia of 30 min and reperfusion of 120 min were also given. Simultaneously, IPTC with four cycles of 5 min ischemia and 5 min reperfusion of each was applied. Parameters like size of myocardial infarct, levels of lactate dehydrogenase (LDH) and release of creatine kinase- MB (CK-MB) in coronary effluent were noted after each stage of experiment for ensuring the extent of myocardial injury. Some significant changes were also seen in the histopathology of cardiovascular tissues. The cardio-protection has been made by four cycles of IPTC. It was confirmed by decline in the size of myocardial infarct. It diminishes the release of LDH and CK-MB in heart of OVX rat. Thus, IPTC induces cardio-protection in the isolated heart from OVX rat. Perfusion of ANP associating with IPTC favors the cardioprotection which is further confirmed by rise in the NO release and heart rate. The level of myocardial damage changes using IPTC, IPTC+OVX, IPTC+OVX+ANP, IPTC+ OVX+ANP+L-NAME and other groups were observed significantly and were found to be less than those in I/R control group. Thus, it is recommended that ANP involving IPTC restores attenuated cardio-protection in OVX rat heart. Therefore, Post-conditioning is useful in various clinical aspects.

Assessment of clinical and laboratorial parameters and the usefulness of the Brain Natiuretic Peptide as a predictor for successful extubation in the ICU

Introduction: Identification of predictors for successful extubation in an Intensive Care Unity and use of Brain Natriuretic Peptides (BNP) in predicting mechanical ventilation weaning and extubation outcome. Aims: Evaluation of the effect of variables such as patient ́s age, severity score, use of sedation, use of vasoactive drugs, hydric balance, blood gas data, days under mechanical ventilation, the occurrence of adverse events and plasma BNP levels on the success of extubation.Method: A prospective cohort study of adult patients admitted to a 12- bed-general ICU, from April 1st 2016 to August 10th 2017, under mechanical ventilation for > 24 h, accompanied until discharge or death. Clinical variables were analyzed and BNP was assessed before initiation of Spontaneous Breathing Trial (SBT) and then again before extubation. Statistical Analysis: a descriptive and comparative data analysis, univariate and logistic regression analysis for verification of variables independently related to successful extubation (p < 0.05).Results: Study of 105 patients, mean age of 53.9 ± 19.8 years, 81% of success in extubation; the overall mortal-ity rate of 11.4%; variables associated to successful extubation: age, APACHE II, SAPS II, days of hospitalization before ICU admittance, days under mechanical ventilation, days of stay in ICU and occurrence of nosocomial infec-tion (p < 0.05); BNP levels were lower in patients with successful extubation although not statistically significant; multivariate analysis showed that patient's age and days of hospitalization before ICU admittance were each in-dependently linked to extubation failure; APACHE II score and days of hospitalization before ICU admittance were each independently associated to risk of death.Conclusion: Despite being older and with higher severity scores, patients had a higher success rate in extubation than found in similar studies. However, the mortality rate in cases of failed extubation was higher. Data obtained was in agreement to studies that suggested that patient ́s age, severity score, days of hospitalization before ICU admittance, days of stay in ICU, days under MV and infection occurrence were all variables associated as much extubation failure as to risk of death. A direct association between BNP levels and successful extubation and the usefulness of assessing BNP in the conduction of WMV was not confirmed. (AU)

Introdução: Identificação de fatores preditivos do sucesso da extubação em Unidade de Terapia Intensiva e uso do Peptídeo Natriurético Cerebral (BNP) como preditor do sucesso do desmame da ventilação mecânica e extubação.Objetivo: Avaliação do efeito de variáveis como idade, escores de gravidade, uso de sedação, uso de drogas va-soativas, balanço hídrico, gasometria, dias sob ventilação mecânica, ocorrência de eventos adversos e níveis plas-máticos de BNP no sucesso da extubação .Método: Estudo de coorte prospectivo de pacientes adultos internados em UTI geral com 12 leitos, de 1º de abril de 2016 a 10 de agosto de 2017, sob ventilação mecânica (VM) por > 24 horas, acompanhados até a alta ou óbito. Variáveis clínicas foram analisadas e o BNP dosado antes do início do Teste de Respiração Espontânea (TRE) e, novamente, antes da extubação. Análise estatística: análise descritiva e comparativa dos dados, análise univariada e regressão logística para verificação de variáveis independentemente relacionadas ao sucesso da extubação (p <0,05).Resultados: Avaliados 105 pacientes, idade média 53,9 ± 19,8 anos, sucesso na extubação de 81%; taxa de mortalidade geral de 11,4%; variáveis associadas ao sucesso da extubação: idade, APACHE II, SAPS II, dias de internação antes da admissão na UTI, dias em ventilação mecânica, dias de permanência na UTI e ocorrência de infecção hospitalar (p <0,05); os níveis de BNP foram mais baixos em pacientes com sucesso da extubação, embora não estatisticamente significativos; a análise multivariada mostrou que as variáveis, idade e dias de internação, antes da admissão na UTI, estavam, independentemente, ligadas ao fracasso da extubação; as variáveis APACHE II e dias de internação antes da admissão na UTI estavam, independentemente, associados ao risco de morte.Conclusão: Apesar de mais velhos e com escores de gravidade mais elevados, nossos pacientes apresentaram maior taxa de sucesso na extubação quando comparados a estudos semelhantes. No entanto, a taxa de mortalidade em casos de falha da extubação foi maior. Os dados obtidos estão de acordo com estudos que sugerem que variá-veis como idade, escores de gravidade, dias de internação antes da admissão na UTI, dias de permanência na UTI, dias em VM e ocorrência de infecção estão associadas tanto ao fracasso de extubação quanto ao risco de morte. Não foi possível confirmar a associação direta entre os níveis plasmáticos de BNP e o sucesso da extubação, assim como sua utilidade na condução do desmame da ventilação mecânica. (AU)

NPCdc, a synthetic natriuretic peptide, is a substrate to neprilysin and enhances blood pressure-lowering induced by enalapril in 5/6 nephrectomized rats.

NPCdc is a natriuretic peptide synthesized from the amino acid sequence of the Crotalus durissus cascavella snake venom peptide, NP2Casca. NPCdc presents hypotensive and antioxidants effects. This study aimed to investigate in vivo whether angiotensin I-converting enzyme (ACE) inhibition would influence the impact of NPCdc in arterial pressure of rats submitted to 5/6 nephrectomy (Nx). Adult male Wistar rats following a 5/6 Nx were treated with enalapril (NxE group, 10 mg/kg/day, n = 9) or vehicle (Nx group, n = 8) for two weeks. On the 15th day after Nx, rats were anaesthetized and submitted to mean arterial pressure (MAP) determination before and after receiving two intravenous injections of saline (vehicle, n = 9) or NPCdc (0.3 µg/kg dissolved in saline, n = 18) separated by a 20-min interval. The kidneys were submitted to oxidative stress analysis. The basal MAP of the NxE group was nearly 20% lower (P < 0.05) than non-treated rats. NPCdc administration decreased the MAP in both groups; however, in the NxE group, the effects were observed only in the second injection. The peptide also decreased the NADPH oxidase activity in the renal cortex. Additionally, the hydrolysis of NPCdc by recombinant neprilysin (NEP) was monitored by mass spectrometry. NPCdc was cleaved by NEP at different peptides with an inhibition constant (Ki) of 1.5 µM, determined by a competitive assay using the NEP fluorescence resonance energy transfer (FRET) peptide substrate Abz-(d)Arg-Gly-Leu-EDDnp. Docking experiments confirmed the high affinity of NPCdc toward NEP. These findings provide new insights into the antihypertensive and antioxidant mechanism of action of NPCdc. Altogether, the results presented here suggest that NPCdc must be further studied as a potential therapy for cardiorenal syndromes.

Design of a multifaceted strategy based on automated text messaging in patients with recent heart failure admission.

AIMS: To evaluate a telemonitoring strategy based on automated text messaging and telephone support after heart failure (HF) hospitalization. METHODS AND RESULTS: The MESSAGE-HF study is a prospective multicentre, randomized, nationwide trial enrolling patients from 30 clinics in all regions of Brazil. HF patients with reduced left ventricular ejection fraction (<40%) and access to mobile phones are eligible after an acute decompensated HF hospitalization. Patients meeting eligibility criteria undergo an initial feasibility text messaging assessment and are randomized to usual care or telemonitoring intervention. All patients receive a HF booklet with basic information and recommendations about self-care. Patients in the intervention group receive four daily short text messages (educational and feedback) during the first 30 days of the protocol to optimize self-care; the feedback text messages from patients could trigger diuretic adjustments or a telephone call from the healthcare team. After 30 days, the frequency of text messages can be adjusted. Patients are followed up after 30, 90, and 180 days, with final status ascertained at 365 days by telephone. Our primary endpoint is the change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels after 180 days. Secondary endpoints include changes in NT-proBNP after 30 days; health-related quality of life, HF self-care, and knowledge scales after 30 and 180 days; and a composite outcome of HF hospitalization and cardiovascular death, adjudicated by a blinded and independent committee. CONCLUSIONS: The MESSAGE-HF trial is evaluating an educational and self-care promotion strategy involving a simple, intensive, and tailored telemonitoring system. If proven effective, it could be applied to a broader population worldwide.

Hormone resistance and short stature: A journey through the pathways of hormone signaling.

Hormone resistances have been described in association with growth disorders, the majority involving the growth hormone (GH)/insulin-like growth factor 1(IGF-1) axis or hormones with specific paracrine-autocrine actions in the growth plate. Defects in hormone receptors or in proteins involved in intracellular signal transduction (post-receptor defects) are the main mechanisms of hormone resistance leading to short stature. The characteristic phenotypes of each of these hormonal resistances are very distinct and bring with them important insights into the role of each hormone and its signaling pathway. In this review, we discuss the molecular and clinical aspects of the main hormone resistances associated with short stature in humans.

Protective Renal Effects of Atrial Natriuretic Peptide: Where Are We Now?

Atrial natriuretic peptide belongs to the family of natriuretic peptides, a system with natriuretic, diuretic, and vasodilator effects that opposes to renin-angiotensin system. In addition to its classic actions, atrial natriuretic peptide exerts a nephroprotective effect given its antioxidant and anti-inflammatory properties, turning it as a beneficial agent against acute and chronic kidney diseases. This minireview describes the most relevant aspects of atrial natriuretic peptide in the kidney, including its renal synthesis, physiological actions through specific receptors, the importance of its metabolism, and its potential use in different pathological scenarios.

Cardiac Natriuretic Peptide Profiles in Chronic Hypertension by Single or Sequentially Combined Renovascular and DOCA-Salt Treatments.

The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.