Ralf Minkenberg

Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries

Aims: To evaluate behavioural outcome and quality of life in children aged 8–14 years after neonatal arterial switch operation for transposition of the great arteries. Methods: Sixty children operated as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were evaluated at age 7.9–14.3 years by the Child Behaviour Checklist (CBCL) and the Inventory for the Assessment of the Quality of Life in Children and Adolescents (IQCL). Results: Parent reported behavioural outcome on all CBCL problem and competence scores was worse, whereas quality of life on self reported IQCL scores was not reduced compared to the normal population. On multivariate analysis, severe preoperative hypoxia was related to parent reported social problems; peri- and postoperative cardiocirculatory insufficiency was associated with internalising, externalising, attention, and total behavioural problems. Reduced expressive language was associated with total behavioural problems, and poor academic achievement was related to parent reported deficits in school performance. Impaired neurological status and reduced endurance capacity both predicted self reported stress by illness. Conclusions: The neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with parent reported long term behavioural impairment, but not with self reported general reduction in quality of life. This discrepancy may be a result of different perception of illness. In our experience, increased risk of long term psychosocial maladjustment after neonatal corrective cardiac surgery is related to the presence of neurological impairment and reduced endurance capacity.

Long-Term Behavior and Quality of Life After Corrective Cardiac Surgery in Infancy for Tetralogy of Fallot or Ventricular Septal Defect

The objective of this study was to evaluate behavior and quality of life in children after corrective cardiac surgery in infancy. Twenty cyanotic (tetralogy of Fallot) and 20 acyanotic children (ventricular septal defect), operated at a mean age of 0.7 years with deep hypothermic circulatory arrest (DHCA) and low-flow cardiopulmonary bypass (CPB), were assessed at a mean age of 7.4 years by the Child Behavior Checklist (CBCL) and the German KINDL. Test results were related to perioperative and neurodevelopmental outcome. Compared to healthy children and not significantly different between the groups, internalizing and externalizing problems were elevated, school performance and total competence were reduced, and self- and parent-reported quality of life was not reduced. Parent-reported problems and reduced physical status were correlated with longer durations of DHCA and CPB. Internalizing and externalizing problems, reduced school competence, and reduced self-esteem were associated with reduced endurance capacity. Externalizing problems were related to reduced gross motor function. Poor school competence was related to reduced intelligence and academic achievement. Children with preoperative hypoxemia in infancy due to cyanotic cardiac defects are not at significantly higher risk for behavioral problems and reduced quality of life than those with acyanotic heart defects. The risk of long-term psychosocial maladjustment after corrective surgery in infancy is increased compared to that for normal children and related to the presence of neurodevelopmental dysfunction.

Survival in second primary malignancies of patients with head and neck cancer.

Second primary tumours occur frequently in patients with a history of head and neck malignancies. Delays in making an early and correct diagnosis can seriously affect the therapy management and survival. This was a retrospective study of 120 patients with a history of head and neck cancer, presenting with a second primary tumour. Current follow-up strategies and the use of routine sonographic imaging of the head and neck regions were evaluated, and the impact that tumour chronology, the tumour site and the various treatment modalities have on the survival were assessed. Forty-two per cent of patients developed a metachronous second malignancy more than five years after diagnosis of the index tumour. The accuracy of colour-duplex sonography in detection of second primaries in the head and neck was 82.3 per cent. First and second primary tumours located in the larynx were observed to have the highest five-year survival rate. Patients who developed metachronous tumours had a five-year survival rate of 68.9 per cent for the index tumours, and a 26 per cent five-year survival rate with the occurrence of a second neoplasm. With synchronous tumours a mean survival time of 18 months and a five-year survival rate of 11.9 per cent was found (p < 0.0001). Where clinically appropriate an aggressive treatment strategy was employed and yielded the most favourable results with a five-year survival rate of 66.8 per cent and 35.9 per cent for index tumours and second primary malignancies, respectively. Since more than 40 per cent of the metachronous second primaries in patients with a history of head and neck malignancy occur beyond the five-year follow-up period, an extended protocol with individually adjusted close monitoring of high-risk patients seems appropriate. Colour-duplex sonography is a valuable screening investigation for the early detection of second primary tumours. The treatment of a second primary is often less successful than for the same malignancy occurring primarily. The prognosis of synchronous tumours is significantly lower when compared to malignancies of a metachronous nature, despite some encouraging individual results. Only the early implementation of aggressive treatment methods for second primaries is successful in terms of survival.

Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation

Abstract Background . Neurodevelopmental outcome after neonatal arterial switch operation for complete transposition of the great arteries is an important topic needing prospective assessment. Methods . A group of 33 unselected children (3.0 to 4.6 years) operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass and a control group of 32 age-matched healthy children (3.0 to 4.8 years) underwent evaluation of socioeconomic and clinical neurological status and a standardized test comprising all areas of child development. Results of patients were related to those of the control group, to population norms, and to preoperative, perioperative, and postoperative cerebral risk factors. Results . Clinical neurological status was normal in 26 patients (78.8%) and reduced in 7 (21.2%). Complete developmental score and the subscores for motor function, visual perception, learning and memory, cognitive function, language, and socioemotional functions were not different compared to population norms. Compared to the patients, the children of the control group scored higher on tests of complete development, cognition, and language, but also on socioeconomic status. Complete developmental score and the scores for motor, cognitive, and language functions were weakly inversely related to the duration of circulatory arrest, but not to the duration of bypass. Cerebral risk factors such as serum levels of the neuron-specific enolase, perinatal acidosis, perinatal asphyxia, peri- and postoperative cardiocirculatory insufficiency, or clinical seizures were not correlated to the test results. Conclusions . Neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with neurological impairment, but not with reduced development as assessed by formal testing of motor, cognitive, language, and behavioral functions. Perioperative serum level of the neuron-specific enolase is not a valid marker for later developmental impairment.

Long-Term Results of Cardiac and General Health Status in Children After Neonatal Arterial Switch Operation

BACKGROUND The purpose of this study was to assess cardiac and general health status 8 to 14 years after neonatal arterial switch operation for transposition of the great arteries. METHODS Sixty unselected children with intact ventricular septum (78.3%) or ventricular septal defect (21.7%) without or with aortic isthmic stenosis (5.1%) were examined 10.5 +/- 1.6 (mean +/- SD) years after neonatal switch and 5.3 +/- 1.6 years after mid-term evaluation. Complete clinical examination, standard and 24-hour Holter electrocardiogram, M-mode, 2D-, Doppler, and color Doppler echocardiography were performed. Results were compared with normal values and to mid-term follow-up results. RESULTS Rates of reoperation after arterial switch operation and operation to correct concomitant coarctation were 3.3% and 5.1%, respectively. No patient needed medication, and 93.3% had no limitation of physical activity. All children had normal height and weight; 31.6% had abnormal thoracic configuration after median sternotomy. Most patients (91.7%) were in sinus rhythm. Incidence of complete right bundle branch block (10.0%) was unchanged, as was prevalence of ectopic activity (occasional atrial ectopy 20.0%, ventricular ectopy: occasional 21.7%; frequent 1.7%). Left ventricular dimensions and shortening fraction did not change over time. Diameters of neo-aortic valve annulus and neo-aortic root did not increase, and z-scores decreased between mid-term and present evaluation. Incidence of neo-aortic insufficiency was 13.3% and remained unchanged in comparison with the pre-examination value. Neo-aortic stenosis was not seen. Compared with mid-term follow-up, incidence (41.6%) and degree of supravalvular pulmonary stenosis increased. CONCLUSIONS Good cardiac results persist 10 years after neonatal arterial switch operation for transposition of the great arteries. Encouraging findings include preservation of left ventricular function, low incidence of rhythm disturbances, lack of further neo-aortic root dilatation, and unchanged incidence of neo-aortic insufficiency compared with mid-term follow-up. Increased incidence and degree of supravalvular pulmonary stenosis are of concern.

The use of moderate hypothermia during cardiac surgery is associated with repression of tumour necrosis factor-α via inhibition of activating protein-1: an experimental study

IntroductionThe use of moderate hypothermia during experimental cardiac surgery is associated with decreased expression of tumour necrosis factor (TNF)-α in myocardium and with myocardial protection. In order to identify the cellular mechanisms that lead to that repression, we investigated the effect of hypothermia during cardiac surgery on both main signalling pathways involved in systemic inflammation, namely the nuclear factor-κB (NF-κB) and activating protein-1 pathways.MethodTwelve female pigs were randomly subjected to standardized cardiopulmonary bypass with moderate hypothermia or normothermia (temperature 28°C and 37°C, respectively; six pigs in each group). Myocardial probes were sampled from the right ventricle before, during and 6 hours after bypass. We detected mRNA encoding TNF-α by competitive RT-PCR and measured protein levels of TNF-α, inducible nitric oxide synthase and cyclo-oxygenase-2 by Western blotting. Finally, we assessed the activation of NF-κB and activating protein-1, as well as phosphorylation of p38 mitogen-activated protein kinase by electrophoretic mobility shift assay with super shift and/or Western blot.ResultsDuring and after cardiac surgery, animals subjected to hypothermia exhibited lower expression of TNF-α and cyclo-oxygenase-2 but not of inducible nitric oxide synthase. This was associated with lower activation of p38 mitogen-activated protein kinase and of its downstream effector activating protein-1 in hypothermic animals. In contrast, NF-κB activity was no different between groups.ConclusionThese findings indicate that the repression of TNF-α associated with moderate hypothermia during cardiac surgery is associated with inhibition of the mitogen-activated protein kinase p38/activating protein-1 pathway and not with inhibition of NF-κB. The use of moderate hypothermia during cardiac surgery may mitigate the perioperative systemic inflammatory response and its complications.