Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites.

ObjectiveInhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery.Study designA subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites.ResultiNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome.ConclusioniNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments

Potential role for clinical calibration to increase engagement with and application of home telemonitoring: a report from the HeartCycle programme

Aims: There is a need for alternative strategies that might avoid recurrent admissions in patients with heart failure. Home Telemonitoring (HTM) to monitor patient’s symptoms from a distance may be useful. This study attempts to assess changes in HTM vital signs in response to daily life activities (variations in medication, salt intake, exercise and stress) and to stablish which variations affect weight, blood pressure (BP) and heart rate (HR). Methods and results: We assessed 76 patients with heart failure (mean age 76 ± 10.8 years, 75% male, mainly in NYHA class II/III and from ischaemic etiology cause). Patients were given a calendar of interventions scheduling activities approximately twice-a-week before measuring their vital signs. Eating salty food or a large meal were the activities that had a significant impact on weight gain (+0.3 kg; p<0.001 and p=0.006, respectively). Exercise and skipping a dose of medication other than diuretics increased heart rate (+3 bpm, p=0.001 and almost +2 bpm, p=0.016, respectively). Conclusions: Our HTM system was able to detect small changes in vital signs related to these activities. Further studies should assess if providing such a schedule of activities might be useful for patient education and could improve long-term adherence to recommended lifestyle changes

Blood pressure and lipid goal attainment in the hypertensive population in the primary care setting in Spain

[Abstract] Although blood pressure (BP) control is crucial in hypertensive patients, clinical practice guidelines agree that the goal of treatment should be aimed at not only decreasing BP but reducing global cardiovascular risk. The aim of this cross-sectional study was to evaluate BP, low-density lipoprotein cholesterol (LDL-C), and composite control rates in a hypertensive population in a primary care setting in Spain. Good BP control was defined as <140/90 mm Hg (<130/80 mm Hg for diabetics).LDL-C control rate was established according to the third report of the National Cholestrol Education Program Adult Treatment Panel criteria. A total of 12,954 patients (49.9% women, aged 62.1±10.7 years) were included. BP was controlled in 24.8% of patients, LDL-C in 26% of patients and, when combined, in only 8.6%. The rates of control were significantly worse in high-risk subgroups, such as high-coronary-risk, diabetic, or metabolic syndrome patients. The BP and LDL-C control rates in the hypertensive population attended to daily in primary care settings in Spain are low

Differential Features of Culprit Intracranial Atherosclerotic Lesions: A Whole-Brain Vessel Wall Imaging Study in Patients With Acute Ischemic Stroke.

BackgroundIntracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole-brain vessel wall imaging, we sought to study the differences in plaque features among various types of plaques in patients with a recent unilateral anterior circulation ischemic stroke.Methods and resultsSixty-one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole-brain vessel wall imaging (before and after contrast) within 1&nbsp;month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque-wall contrast ratio, high signal on T1-weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole-brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1-weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9-44.1; P=0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8-164.9; P=0.013), and type 2 (≥50% cross-sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3-82.2; P=0.030) were independently associated with culprit lesions.ConclusionsHigh signal on T1-weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification

The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections.

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_ 3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day

Eating Pattern Response to a Low-Fat Diet Intervention and Cardiovascular Outcomes in Normotensive Women: The Women's Health Initiative.

BackgroundWomen without cardiovascular disease (CVD) or hypertension at baseline assigned to intervention in the Women's Health Initiative Dietary Modification (DM) trial experienced 30% lower risk of coronary heart disease (CHD), whereas results in women with hypertension or prior CVD could have been confounded by postrandomization use of statins.ObjectivesIntervention participants reported various self-selected changes to achieve the 20% total fat goals. Reviewed are intervention compared with comparison group HRs for CHD, stroke, and total CVD in relation to specific dietary changes in normotensive participants.MethodsDietary change was assessed by comparing baseline with year 1 FFQ data in women (n&nbsp;=&nbsp;10,371) without hypertension or CVD at baseline with intake of total fat above the median to minimize biases due to use of the FFQ in trial eligibility screening.ResultsIntervention participants self-reported compensating reduced energy intake from total fat by increasing carbohydrate and protein. Specifically they increased plant protein, with those in the upper quartile (increased total protein by ≥3.3% of energy) having a CHD HR of 0.39 (95% CI: 0.22, 0.71), compared with 0.92 (95% CI: 0.57, 1.48) for those in the lower quartile of change (decreased total protein ≥0.6% of energy), with P-trend of 0.04. CHD HR did not vary significantly with change in percentage energy from carbohydrate, and stroke HR did not vary significantly with any macronutrient changes. Scores reflecting adherence to recommended dietary patterns including the Dietary Approaches to Stop Hypertension Trial and the Healthy Eating Index showed favorable changes in the intervention group.ConclusionsIntervention group total fat reduction replaced with increased carbohydrate and some protein, especially plant-based protein, was related to lower CHD risk in normotensive women without CVD who reported high baseline total fat intake. This trial was registered at clinicaltrials.gov as NCT00000611. Link to the WHI trial protocol: https://www.whi.org/about/SitePages/Dietary%20Trial.aspx

Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene.

BackgroundPreserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.MethodsData from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.ResultsThe prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value &lt;0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter's syndrome (47XXY) was observed (p-value &lt; 0.001). Subgroups identified through k-means clustering include a putative "COPD-subtype", "Restrictive-subtype", and a highly symptomatic "Metabolic-subtype".ConclusionsPRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.Trial registrationClinicaltrials.gov Identifier: NCT000608764