Improved diagnostic tools, timely closure of the shunt and a better understanding of the complexity of Eisenmenger syndrome (ES) have led to improved care and treatment in tertiary centres. These may ...have decreased the incidence of ES and improved survival of patients with ES, although evidence is still lacking. The aim of this study was to investigate temporal changes in incidence, prevalence and mortality in patients with ES for 35 years in the Nordic region.
This was a retrospective population-based study including 714 patients with ES. Survival analysis was performed based on all-cause mortality and accounting for immortal time bias.
The incidence of ES decreased from 2.5/million inhabitants/year in 1977 to 0.2/million inhabitants/year in 2012. Correspondingly, prevalence decreased from 24.6 to 11.9/million inhabitants. The median survival was 38.4 years, with 20-year, 40-year and 60-year survival of 72.5%, 48.4%, and 21.3%, respectively. Complex lesions and Down syndrome were independently associated with worse survival (HR 2.2, p<0.001 and HR 1.8, p<0.001, respectively). Age at death increased from 27.7 years in the period from 1977 to 1992, to 46.3 years from July 2006 to 2012 (p<0.001).
The incidence and prevalence of ES in the Nordic region have decreased markedly during the last decades. Furthermore, the median age at death increased throughout the study period, indicating prolonged life expectancy in the ES population. However, increasing age represents decreased incidence, rather than improved survival. Nonetheless, longevity with ES is still shorter than in the background population.
The aim of this study was to analyze the prevalence of frailty and physical health limitations among long-term survivors of high-risk neuroblastoma (HR NBL) and to investigate whether frail health is ...associated with variables of cardiovascular function, markers of inflammation and telomere length. A national study cohort of 19 (median age 22, range 16-30 years) long-term (>10 years) HR NBL survivors was studied and the findings were compared with 20 age- and sex-matched controls. Frailty was defined as ⩾3 of the following conditions: low muscle mass, low energy expenditure, slow running and weakness. The prevalence of frailty was significantly higher among the HR NBL survivors 9/19 (47%) than among the controls (0%). Thirteen (68%) of the survivors reported significant physical health limitations in vigorous activities, as opposed to none of the controls. The HR NBL survivors had significantly shorter telomere length and higher serum levels of high sensitivity C-reactive protein than did the controls. Frail health and poor physical functioning are prevalent among HR NBL survivors and suggest premature aging. Survivors with gonadal damage, very low fat mass percentage, low glycosylated hemoglobin A1c and increased common carotid artery intima-media thickness may be more prone to early aging after high dose therapy.
Eisenmenger syndrome (ES) is associated with considerable morbidity and mortality. Therapeutic strategies have changed during the 2000s in conjunction with an emphasis on specialist follow-up. The ...aim of this study was to determine the cause-specific mortality in ES and evaluate any relevant changes between 1977 and 2015.
This is a retrospective, descriptive multicentre study. A total of 1546 patients (mean age 38.7 ± 15.4 years; 36% male) from 13 countries were included. Cause-specific mortality was examined before and after July 2006, 'early' and 'late', respectively. Over a median follow-up of 6.1 years (interquartile range 2.1-21.5 years) 558 deaths were recorded; cause-specific mortality was identified in 411 (74%) cases. Leading causes of death were heart failure (34%), infection (26%), sudden cardiac death (10%), thromboembolism (8%), haemorrhage (7%), and peri-procedural (7%). Heart failure deaths increased in the 'late' relative to the 'early' era (P = 0.032), whereas death from thromboembolic events and death in relation to cardiac and non-cardiac procedures decreased (P = 0.014, P = 0.014, P = 0.004, respectively). There was an increase in longevity in the 'late' vs. 'early' era (median survival 52.3 vs. 35.2 years, P < 0.001).
The study shows that despite changes in therapy, care, and follow-up of ES in tertiary care centres, all-cause mortality including cardiac remains high. Patients from the 'late' era, however, die later and from chronic rather than acute cardiac causes, primarily heart failure, whereas peri-procedural and deaths due to haemoptysis have become less common. Lifelong vigilance in tertiary centres and further research for ES are clearly needed.
Aim
This study determined the use of standardised procedures for infant noninvasive blood pressure (NIBP) measurements in the Nordic countries and aimed to identify factors included in the ...standardisation and interpretation of NIBP measurements in infants.
Methods
A cross‐sectional electronic questionnaire survey was sent to 84 physicians in all 23 university hospitals in Sweden, Norway, Denmark, Finland and Iceland and was completed from February to March 2017. The survey contained respondent characteristics, the presence and description of standardised procedures for NIBP measurements, daily practice of NIBP measurements and methodological considerations and interpretation of NIBP measurements in a healthy six‐month‐old child.
Results
We received responses from 55 of 84 physicians working in all 23 Nordic university hospitals, in paediatric cardiology (n = 22), general paediatrics (n = 16), paediatric nephrology (n = 14) and other fields (n = 3). Less than a quarter (23%) said their hospital issued specific NIBP procedures relating to infants and they referred to 19 different sources of information. The factors that were most commonly assessed for interpretation were age (100%), arousal state (78%) and cuff size (76%).
Conclusion
Most of the university hospital units treating children lacked age‐specific written procedures for measuring and interpreting infant NIBP, and there is a strong need for common Nordic guidelines.
Background
Patients with high‐risk neuroblastoma (HR NBL) treated with myeloablative regimens are reported to be at risk for cardiovascular morbidity, and this risk may be increased by impaired renal ...function.
Procedure
Long‐term renal function was assessed in a national cohort of 18 (age 22.4 ± 4.9 years) HR NBL survivors by plasma creatinine (P‐Cr), urea, and cystatin C (P‐Cys C) concentrations, urine albumin/creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). Ambulatory blood pressure was monitored, and common carotid intima‐media thickness (CIMT) and left ventricular mass index (LVMI) were evaluated.
Results
No significant difference in P‐Cr, P‐Cys C, or eGFR was found between the NBL survivors and the age‐ and sex‐matched 20 controls. P‐Cys C–based eGFR (eGFRcysc) was significantly lower than the P‐Cr–based eGFRcr (97 ± 17 mL/min/1.73 m2 vs 111 ± 19 mL/min/1.73 m2, P < 0.001) among the NBL survivors. The eGFRcysc was below normal in 28%, and ACR was above normal in 22% of the NBL survivors. Abnormal blood pressure was found in 56% of the survivors, and an additional 17% were normotensive at daytime but had significant nocturnal hypertension. Both ACR and P‐Cys C were associated with nighttime diastolic hypertension.
Conclusions
Long‐term survivors of childhood HR NBL showed signs of only mild renal dysfunction associated with diastolic hypertension. Elevated ACR and P‐Cys C were the most sensitive indicators of glomerular renal dysfunction and hypertension in this patient cohort.
Both osteoporosis and cardiovascular disease (CVD) are diseases that comprise a growing medical and economic burden in ageing populations. They share many risk factors, including ageing, low physical ...activity, and possibly overweight. We aimed to study associations between individual risk factors for CVD and bone mineral density (BMD) and turnover markers (BTMs) in apparently healthy cohort.
A cross-sectional assessment of 155 healthy 32-year-old adults (74 males) was performed for skeletal status, CVD risk factors and lifestyle factors.
We analysed serum osteocalcin, procollagen I aminoterminal propeptide (P1NP), collagen I carboxy-terminal telopeptide (ICTP) and urine collagen I aminoterminal telopeptide (U-NTX), as well as serum insulin, plasma glucose, triglyceride and HDL-cholesterol levels. BMD, fat and lean mass were assessed using DXA scanning. Associations were tested with partial correlations in crude and adjusted models. Bone status was compared between men with or without metabolic syndrome (defined according to the NCEP-ATPIII criteria) with multivariate analysis.
Osteocalcin and P1NP correlated inversely with insulin (R = -0.243, P = 0.003 and R = -0.187, P = 0.021) and glucose (R = -0.213, P = 0.009 and R = -0.190, P = 0.019), but after controlling for fat mass and lifestyle factors, the associations attenuated with insulin (R = -0.162, P = 0.053 and R = -0.093, P = 0.266) and with glucose (R = -0.099, P = 0.240 and R = -0.133, P = 0.110), respectively. Whole body BMD associated inversely only with triglycerides in fully adjusted model. In men with metabolic syndrome, whole body BMD, osteocalcin and P1NP were lower compared to healthy men, but these findings disappeared in fully adjusted model.
In young adults, inverse associations between BTM/BMD and risk factors of CVD appeared in crude models, but after adjusting for fat mass, no association continued to be present. In addition to fat mass, lifestyle factors, especially physical activity, modified the associations between CVD and bone characteristics. Prospective studies are needed to specify the role of mediators and lifestyle factors in the prevention of CVD and osteoporosis.
Therapy with inhaled nitric oxide is usually given with high concentrations of oxygen. As nitric oxide (NO) is a free radical and hyperoxia increases oxygen radical production, we examined the effect ...of short exposure to NO or oxygen (O2) or both, on free radical‐mediated changes in macromolecules, i.e. lipids and proteins, in vivo. Wistar rats were exposed to >95% O2 or 40 ppm NO, or both, for 6 h. Rats in 21% O2 served as controls. Lipid peroxidation was quantified as expired pentane, oxidative protein modification as carbonyl concentration, and pulmonary neutrophil accumulation as myeloperoxidase activity in the lungs. Hyperoxia for 6 h caused higher expired pentane (4.83 ± 1.39 pmol/min/100 g) and protein carbonylation (15.91 ± 2.49 nmol/mg) compared to controls (2.26 ± 1.00 pmol/min/100 g, and 7.40 ± 1.12 nmol/mg, respectively; both p < 0.05). After exposure to NO in air, protein carbonylation (14.50 ± 5.44 nmol/mg) and myeloperoxidase activity (4.85 ± 1.52 mU/mg) were higher than in controls (myeloperoxidase 2.49 ± 0.56 mU/mg; both p < 0.05). NO with hyperoxia decreased pentane (2.56 ± 1.51 pmol/min/ 100 g) and protein carbonylation (11.38 ± 3.58 nmol/mg) compared to hyperoxia (both p < 0.05).
Conclusion: In vivo, 6 h exposure to hyperoxia or to 40 ppm NO induces free radical‐mediated lung injury. The combination of hyperoxia and 40 ppm NO significantly attenuates free radical‐mediated effects in the lungs compared to hyperoxia or 40 ppm NO in air.
Objective To test the vasodilatory response of the pulmonary vascular bed in children with pulmonary hypertension. Design Prospective dose response study in which the effects of inhaled nitric oxide ...(NO) are compared with those of oxygen and intravenous prostacyclin. Patients and interventions The vasodilator test was performed in 20 patients in whom mean pulmonary artery pressure (PAPm) was ⩾ 40 mm Hg and/or pulmonary vascular resistance index was ⩾ 4 Um2. Haemodynamic effects of inhaled NO (20, 40, and 80 ppm) at a fractional inspired oxygen (FiO2) value of 0.3, pure oxygen, oxygen at FiO2 0.9–1.0 combined with NO as above or with intravenous prostacyclin at 10 and 20 ng/kg/min were measured. Result NO decreased PAPm with a dose response from 20 to 40 ppm (mean change at 40 ppm −5.50, 95% confidence interval (CI) −7.98 to −3.02 mm Hg). Maximal decrease in the ratio of pulmonary to systemic vascular resistance was achieved with a combination of NO 80 ppm and oxygen (−0.18, 95% CI −0.26 to −0.10). Increase in the pulmonary flow index was greatest with pure oxygen in those with an intracardiac shunt (8.52, 95% CI −0.15 to 17.20 l/min/m2). Neither NO nor oxygen altered systemic arterial pressure but intravenous prostacyclin lowered systemic arterial pressure and resistance. Conclusions NO selectively reduces pulmonary vascular resistance and pressure maximally at 40 ppm. Oxygen reduces pulmonary vascular resistance and NO potentiates this reduction without affecting the systemic circulation. Prostacyclin vasodilates the pulmonary and the systemic circulations.
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