Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40 and beyond

More than 40 years after the 1978 Bethesda Conference on the Declining Mortality from Coronary Heart Disease provided the scientific community with a blueprint for systematic analysis to understand declining rates of coronary heart disease, there are indications the decline has ended or even reversed despite advances in our knowledge about the condition and treatment. Recent data show a more complex situation, with mortality rates for overall cardiovascular disease, including coronary heart disease and stroke, decelerating, whereas those for heart failure are increasing. To mark the 40th anniversary of the Bethesda Conference, the National Heart, Lung, and Blood Institute and the American Heart Association cosponsored the "Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40" symposium. The objective was to examine the immediate and long-term outcomes of the 1978 conference and understand the current environment. Symposium themes included trends and future projections in cardiovascular disease (in the United States and internationally), the evolving obesity and diabetes epidemics, and harnessing emerging and innovative opportunities to preserve and promote cardiovascular health and prevent cardiovascular disease. In addition, participant-led discussion explored the challenges and barriers in promoting cardiovascular health across the lifespan and established a potential framework for observational research and interventions that would begin in early childhood (or ideally in utero). This report summarizes the relevant research, policy, and practice opportunities discussed at the symposium

Deep phenotyping classical galactosemia: clinical outcomes and biochemical markers

Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 6 14) and was <85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome < 85) and normal intellectual outcome (intellectual outcome 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently no long-term complications, demonstrated significantly lower galactose-1-phospate levels than classical patients (P < 0.0005). Qualitative analysis of the MRI’s demonstrated brain abnormalities in 18 of the 21 patients, more severely in patients with a lower intellectual outcome and/or with movement disorders. This study demonstrates a large variability in clinical outcome, which varies from a below average intelligence, movement disorders and in females primary ovarian insufficiency to a normal clinical outcome. In our cohort of classical galactosemia patients, galactose-1-phosphate levels and N-glycan variations were not associated with clinical outcomes, but galactose-1-phosphate levels did differentiate between classical and variant patients detected by newborn screening. The correlation between brain abn

Deep phenotyping classical galactosemia: clinical outcomes and biochemical markers

Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 +/- 14) and was = 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently no long-term complications, demonstrated significantly lower galactose-1-phospate levels than classical patients (P< 0.0005). Qualitative analysis of the MRI's demonstrated brain abnormalities in 18 of the 21 patients, more severely in patients with a lower intellectual outcome and/or with movement disorders. This study demonstrates a large variability in clinical outcome, which varies from a below average intelligence, movement disorders and in females primary ovarian insufficiency to a normal clinical outcome. In our cohort of classical galactosemia patients, galactose-1-phosphate levels and N-glycan variations were not associated with clinical outcomes, but galactose-1-phosphate levels did differentiate between classical and variant patients detected by newborn screening. The correlation between brain abnormalities and clinical outcome should be further investigated by quantitative analysis of the MR images. The variability in clinical outcome necessitates individual and standardized evaluation of all classical galactosemia patients

Efeitos cardiorrespiratórios da buprenorfina em cães anestesiados pelo desfluorano Cardiorespiratory effects of buprenorphine in dogs anesthetized with desflurane

Objetivou-se, com este estudo, avaliar os efeitos da buprenorfina sobre variáveis cardiovasculares e respiratórias em cães durante anestesia com desfluorano. Para tanto, foram utilizados 20 cães adultos, distribuídos em dois grupos (GB e GC). A anestesia foi induzida com propofol (8mg kg-1 IV) e em seguida os animais foram intubados com sonda de Magill, a qual foi conectada ao aparelho de anestesia para administração de desfluorano (1,5 CAM). Após 30 minutos, foi aplicado no GB buprenorfina (0,02mg kg-1) e no GC solução de NaCl à 0,9% (0,05ml kg-1). Avaliaram-se: freqüências cardíaca e respiratória (FC e <FONT FACE=Symbol>&brvbar;</FONT>); pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM); débito cardíaco (DC); pressão venosa central (PVC); e as variáveis hemogasométricas pH, PaCO2, PaO2, HCO3, SatO2 e DB. As colheitas dos dados foram feitas aos 30 minutos após o início da administração do desfluorano (MO), 15 minutos após a administração do opióide ou placebo (M15), e a cada 15 minutos após Ml5 (M30, M45, M60 e M75). A avaliação estatística dos dados foi efetuada por meio de Análise de Perfil (P<0,05). Houve discreta redução da FC no GB, enquanto as outras variáveis cardiovasculares não tiveram redução significativa. A <FONT FACE=Symbol>&brvbar;</FONT> e o pH tiveram reduções no GB, enquanto a PaCO2 esteve aumentada. Concluiu-se que a inclusão da buprenorfina durante anestesia inalatória pelo desfluorano determina discretas alterações cardiovasculares, bem-como potencializa a hipoventilação promovida pelo desfluorano, com a manifestação de hipercapnia, o que não contra-indica o seu uso em pacientes estáveis.<br>The aim of this study was to evaluate the effects of buprenorphine on cardiovascular and respiratory variables in dogs anesthetized with desflurane. Twenty adult healthy male and female mongrel dogs were randomly distributed in two groups of ten animals each (GB and GC). The anesthetic induction was done using propofol (8mg kg-1, IV), and immediately, the dogs were intubated and submited to desflurane anesthesia administrated at 1.5 MAC. After 30 minutes of induction, animals from GB received buprenorphine (0.02mg kg-1) and GC saline solution at 0.9% (0.05ml kg-1), both applied intramuscularly. Heart Rate (HR); Systolic, Diastolic and Mean Arterial Blood Pressure (SAP, DAP and MAP); Cardiac Output (CO); Venous Central Pressure (VCP); Respiratory Rate (RR); Corporal Temperature (CT) and hemogasometrics variables. The measurement were realized 30 minutes after beginning the inhalatory anesthesia (MO); 15 minutes after opioid or saline administration (M15). Serial measurements were carried out in 15-minute intervals after M15 (M30, M45, M60 and M75). The numerical data were submited to ANOVA (P<0.05). The HR, RR and pH decreased after opioid administration, while for PaCO2 increased. The results allow us to conclude that buprenorphine determine discreet reduction in the cardiovascular parameters and promotes potentially hypoventilation in dogs anesthetized with desflurane