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Background: Lymphedema is a highly feared complication of breast cancer treatment, but the underlying complex mechanisms are still unknown. Thus, we investigated the lymphatic morphology and contractility in the lymphatic vessels of arms of high-risk breast cancer patients treated for node-positive early breast cancer. Methods: In this prospective cohort study 32 women treated for unilateral node-positive breast cancer were enrolled and studied 36 ± 23 days after loco-regional radiotherapy. Near-infrared fluorescence imaging was used to assess morphology and function of the superficial lymphatic vessels. Strain-gauge plethysmography was performed to evaluate the capillary filtration of fluid. Both arms were investigated, with the non-treated arm acting as control. The patients were questioned about the presence of lymphedema yearly and finally 574 ± 118 days after ended radiotherapy. Results: Morphologically, 25% of the treated arms expressed lymphatic vessel abnormalities compared to the control arms (p = 0.0048). No difference in functional parameters (maximal pumping pressure, p = 0.20; contraction frequency, p = 0.63; contraction velocity, p = 0.55) was found between the treated and control arms. Patients who later developed lymphedema had a difference in velocity compared to those who did not develop lymphedema (p = 0.02). The capillary filtration rate was similar between the two arms (p = 0.18). Conclusions: Peripheral lymphatic vessels were morphologically changed in the ipsilateral arm in 25% of the patients and patients who later developed lymphedema showed an early increase in velocity. Other functional parameters and capillary filtration were unchanged in this early phase. These discrete changes might be early indicators of later development of lymphedema.

Background: Patients with congenital heart defects have a well-established risk of neuropsychiatric comorbidities. Inattention and hyperactivity are three to four times more frequent in children with complex congenital heart defects. We have previously shown a higher burden of overall attention deficit/hyperactivity disorder (ADHD) symptoms in adults with simple congenital heart defects as well. However, it is unknown whether the higher burden of ADHD symptoms is mainly driven by hyperactivity, inattention, or both. Methods: The participants [simple congenital heart defect = 80 (26.6 years old), controls = 36 (25.3 years old)] and a close relative for each (n = 107) responded to the long version of the Conners' Adults ADHD Rating Scales questionnaire. Our primary and secondary outcomes are mean T-scores in the ADHD scores and symptom sub-scores. Results: Patients with simple congenital heart defects reported a higher mean T-score at all three DSM-IV ADHD scores (ADHD—combined: 52.8 vs. 44.9, p = 0.007, ADHD—inattention: 55.5 vs. 46.4, p = 0.002, and ADHD—hyperactivity: 49.4 vs. 44.0, p = 0.03) and in all four ADHD symptom sub-scores (inattention/memory problems: 50.3 vs. 44.2, p = 0.001, hyperactivity/restlessness: 49.7 vs. 45.9, p = 0.03, impulsivity/emotional lability: 50.0 vs. 41.3, p = 0.001, and self-esteem problems: 53.8 vs. 46.3, p = 0.003). The results were maintained after the removal of outliers (incongruent responses), albeit the hyperactivity/restlessness ADHD symptom sub-score lost significance. Self- and informant ratings differed significantly on the ADHD—inattention score for the congenital heart defect group, where informants rated the ADHD—inattention scores better than the congenital heart defect patients rated themselves. Conclusions: Patients with a simple congenital heart defect have a higher symptom burden across all ADHD scores and all symptom sub-scores. The higher burden of ADHD is driven by both inattention and hyperactivity symptoms, t

Background: Many children born with congenital heart defects are faced with cognitive deficits and psychological challenges later in life. The mechanisms behind are suggested to be multifactorial and are explained as an interplay between innate and modifiable risk factors. The aim was to assess whether there is a relationship between mean arterial pressure during surgery of a septal defect in infancy or early childhood and intelligence quotient scores in adulthood. Methods: In a retrospective study, patients were included if they underwent surgical closure of a ventricular septal defect or an atrial septal defect in childhood between 1988 and 2002. Every patient completed an intelligence assessment upon inclusion, 14-27 years after surgery, using the Wechsler Adult Intelligence Scale Version IV. Results: A total of 58 patients met the eligibility criteria and were included in the analyses. No statistically significant correlation was found between blood pressure during cardiopulmonary bypass and intelligence quotient scores in adulthood (r = 0.138; 95% CI-0.133-0.389). Although amongst patients with mean arterial pressure < 40 mmHg during cardiopulmonary bypass, intelligence quotient scores were significantly lower (91.4; 95% CI 86.9-95.9) compared to those with mean arterial pressure > 40 mmHg (99.8; 95% CI 94.7-104.9). Conclusions: Mean arterial pressure during surgery of ventricular septal defects or atrial septal defects in childhood does not correlate linearly with intelligence quotient scores in adulthood. Although there may exist a specific cut-off value at which low blood pressure becomes harmful. Larger studies are warranted in order to confirm this, as it holds the potential of partly relieving CHD patients of their cognitive deficits.

BACKGROUND: Congenital ventricular septal defects (VSDs) are considered to have benign long-term outcome when treated correctly in childhood. However, abnormal parameters are described in younger adults, including impaired heart rate variability (HRV). It is not known whether such abnormalities will deteriorate with age. Therefore, HRV and cardiac events, such as premature ventricular contraction, were evaluated in patients aged >40 years with congenital VSDs and compared with healthy peers. METHODS AND RESULTS: A total of 30 surgically closed VSDs (51±8 years, repair at median age 6.3 years with total range 1.4– 54 years) with 30 healthy controls (52±9 years) and 30 small, unrepaired VSDs (55±12 years) with 30 controls (55±10 years) were all equipped with a Holter monitor for 24 hours. Compared with healthy peers, surgically closed patients had lower SD of the normal-to-normal (NN) interbeat interval (129±37 versus 168±38 ms; P<0.01), SD of the average NN intervals for each 5-minute segment of a 24-hour HRV recording (116±35 versus 149±35 ms; P<0.01) and 24-hour triangular index (31±9 versus 44±11; P<0.01). SD of the NN intervals, SD of the average NN intervals for each 5-minute segment of a 24-hour HRV recording, and triangular index were comparable between unrepaired VSDs and healthy peers. SD of the NN intervals was <100 ms in 22% of surgically closed and 10% of unrepaired VSDs, whereas controls were within normal ranges. A high number of premature ventricular contractions (>200 events) was registered in 57% of surgical patients compared with 3% of controls (P<0.01), and 53% of unrepaired VSDs compared with 10% in controls (P<0.01). CONCLUSIONS: Adults aged >40 with congenital VSDs demonstrate impaired HRV, mainly among surgically closed VSDs. More than half demonstrated a high number of premature ventricular contractions. These novel findings could indicate long-term cardiovascular disturbances. This necessitates continuous follow

OBJECTIVES: To estimate the association between major types of congenital heart defects (CHD) and spontaneous preterm birth, and to assess the potential underlying mechanisms.STUDY DESIGN: This nationwide, registry-based study included a cohort of all singleton pregnancies in Denmark from 1997 to 2013. The association between CHD and spontaneous PTB was estimated by multiple Cox regression, adjusted for potential confounders. The following potential mechanisms were examined: Maternal genetics (sibling analyses), polyhydramnios, preterm prelabor rupture of membranes (PPROM), preeclampsia, and indicators of fetal and placental growth.RESULTS: The study included 1,040,474 births. Compared with the general population CHD was associated with an increased risk of spontaneous PTB, adjusted hazard ratio 2.1 (95% CI, 1.9-2.4). Several subtypes were associated with increased risks, including pulmonary stenosis combined with a septal defect, 5.2 (95% CI, 3.7-7.5), pulmonary stenosis or atresia, 3.1 (95% CI, 2.4-4.1), tetralogy of Fallot 2.5 (95% CI, 1.6-3.8), coarctation or interrupted aortic arch 2.2 (95% CI, 1.5-3.2), hypoplastic left heart syndrome, 2.0 (95% CI, 1.0-4.1). Overall, PPROM mediated more than half of the association. Maternal genetics, polyhydramnios, or indicators of fetal or placental growth did not explain the reported associations.CONCLUSIONS: CHD, especially right ventricular outflow tract obstruction, , were associated with an increased risk of spontaneous PTB. The risk was carried by the CHD and not by maternal genetics. Moreover, PPROM was identified as a potential underlying mechanism.

Introduction Cardiac rehabilitation improves physical capacity, health-related quality of life, and reduces morbidity and mortality among cardiac patients. Telemonitored exercise-based cardiac rehabilitation may innovate existing programmes and increase participation rates. Objective The purpose of this study was to investigate if telemonitored exercise-based cardiac rehabilitation improves physical capacity, muscle endurance, muscle power, muscle strength and health-related quality of life in cardiac patients. Methods A follow-up study on moderate risk patients with ischaemic heart and heart valve disease referred to a 12-week telemonitored exercise-based cardiac rehabilitation intervention at Aarhus University Hospital (Denmark). Participants were encouraged to exercise 60 min three times weekly with moderate/high intensity for 20 min per session. Intensity and duration of training sessions were visualised on a smartphone and uploaded to a website. Participants received individual feedback from physiotherapists on their training efforts by telephone/email. Outcome measures were changes in physical capacity (peak oxygen uptake), muscle endurance, power, and strength, and health-related quality of life between baseline end of telemonitored exercise-based cardiac rehabilitation intervention, and at six and 12 months after end of telemonitored exercise-based cardiac rehabilitation. Results Thirty-four participants completed telemonitored exercise-based cardiac rehabilitation. We identified a significant increase in peak oxygen uptake of 10%, in muscle endurance of 17%, in muscle power of 7%, and in muscle strength of 10% after the telemonitored exercise-based cardiac rehabilitation programme. Health-related quality of life was significantly improved by 19% in the physical and 17% in the mental component scores. We found no significant improvement in peak oxygen uptake between baseline and 12 months follow-up, but a significant improvement in muscle endurance (0.3 w

Background Ventricular septal defects (VSD), when treated correctly in childhood, are considered to have great prognoses, and the majority of patients are discharged from follow-up when entering their teens. Young adults were previously found to have poorer functional capacity than healthy peers, but the question remains whether functional capacity degenerates further with age. Methods and Results A group of 30 patients with surgically closed VSDs (51±8 years) with 30 matched, healthy control participants (52±9 years) and a group of 30 patients with small unrepaired VSDs (55±12 years) and 30 matched control participants (55±10 years) underwent cardiopulmonary exercise testing using an incremental workload protocol and noninvasive gas measurement. Peak oxygen uptake was lower in participants with closed VSDs than matched controls (24±7 versus 34±9 mL/min per kg, P<0.01) and with unrepaired VSDs than matched controls (26±5 versus 32±8 mL/min per kg, P<0.01). Patients demonstrated lower oxygen uptake from exercise levels at 20% of maximal workload compared with respective control groups (P<0.01). Peak ventilation was lower in patients with surgically closed VSDs than control participants (1.0±0.3 versus 1.4±0.4 L/min per kg, P<0.01) but similar in patients with unrepaired VSDs and control participants (P=0.14). Exercise capacity was 29% lower in older patients with surgically closed VSDs than healthy peers, whereas younger patients with surgically closed VSDs previously demonstrated 18% lower capacity compared with peers. Older patients with unrepaired VSDs reached 21% lower exercise capacity, whereas younger patients with unrepaired VSDs previously demonstrated 17% lower oxygen uptake than healthy peers. Conclusions Patients with VSDs demonstrate poorer exercise capacity than healthy peers. The difference between patients and control participants increased with advancing age-and increased most in patients with operated VSDs-compared with previous findin

BACKGROUND: The evaluation of the patent ductus arteriosus (PDA) in the very premature neonate is a challenge. Echocardiography provides an interpretation of the hemodynamic condition. It is however, only a snapshot. Biomarkers may represent a physiological response to the hemodynamic alterations brought on by the PDA and may add to the identification of the clinical significant PDA.AIM: To investigate the association between mid regional proadrenomodulin (MR-proADM), N-terminal pro b-type natriuretic peptide (NT-proBNP), mid regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro endothelin-1 (CT-proET1) and copeptin and echocardiographic measures of PDA.STUDY DESIGN: Cohort study with echocardiography performed on day 3 and 6. Blood samples from day 3.SUBJECT: 139 consecutive neonates born at a gestational age <32 weeks.OUTCOME MEASURES: The main outcomes were presence of a PDA day 3 and 6, PDA diameter, left atrium to aorta ratio (LA:Ao-ratio), and descending aorta diastolic flow (DADF).RESULTS: Adjusted plasma levels of all investigated biomarkers, except CT-proET1, were found to be associated with both PDA diameter and LA:Ao-ratio, and also the presence of a large PDA. CT-proET1 and copeptin was found to be associated with abnormal DADF. Using pre-specified cut-off values NT-proBNP and MR-proANP day 3 seemed to be of value in identifying a large PDA day 3 and 6 in very preterm neonates.CONCLUSION: Among the investigated biomarkers NT-proBNP and MR-proANP performed best in relation to echocardiographic markers of PDA severity in very preterm neonates.

Background In this nationwide study, we used the unique Danish registries to estimate the risk of suicide and deliberate self-harm in patients with congenital heart disease (CHD). Methods and Results We identified all Danish citizens receiving a diagnosis of CHD between 1977 and 2007. As a reference cohort, we randomly selected 10 citizens for each patient, matched by sex and birth year. Using the Fine and Gray competing risk regression, we estimated the cumulative incidences of suicide and self-harm, and Cox proportional regression analysis was used to compare the risk of suicide and deliberate self-harm in patients with CHD with the reference cohort. We identified 14 433 patients with CHD. Mean follow-up was 21.3 years, with a maximum follow-up of 42 years. Since the time of diagnosis, 2659 patients had died, with a median age of death of 23 years. A total of 15 patients had died by suicide, compared with 232 suicides in the reference cohort. Patients with CHD had a low and similar risk of dying by suicide when compared with the reference cohort (cause-specific hazard ratio, 0.81; 95% CI, 0.48-1.37; and subhazard ratio, 0.68; 95% CI, 0.41-1.16). We identified 336 events of self-harm among patients with CHD, and 3484 events in the reference group. The overall risk of deliberate self-harm was not increased in patients with CHD when compared with the reference group (subhazard ratio, 0.95; 95% CI, 0.85-1.06). Conclusions This is the first study to estimate the risk of suicide and deliberate self-harm in patients with CHD. We found that patients with CHD do not have an increased risk of suicide or deliberate self-harm when compared with a large reference cohort.