Stent graft surface movement after infrarenal abdominal aortic aneurysm repair: comparison of patients with and without a type 2 endoleak.

OBJECTIVES: The aim was to compare multidirectional stent graft movement in patients with and without a type 2 endoleak. METHODS: This was a retrospective case control study of patients being followed up after elective endovascular aneurysm repair of abdominal aortic aneurysms. The post-procedural and final follow up multislice computed tomography (MSCT) of 69 patients with and 74 without a type 2 endoleak were analyzed. Three dimensional (3D) surface models of the stent graft, delimited by landmarks using custom built software, were derived from these MSCT data. The stent graft was segmented in different zones, and the proportion of the total stent graft surface moving >9 mm between the post-procedural and the final follow up MSCT was calculated, given in percentages, and compared between groups. Changes of infrarenal neck, renal artery to stent graft distance, and freedom from stent graft related endoleaks were evaluated. RESULTS: Overall surface movement was higher in the no endoleak (18.8%, IQR 0.1-45.1%) than in the type 2 endoleak group (5.3%, IQR 0-29.7%; p = .06). Furthermore, significantly higher surface movement in the no endoleak group was found in the proximal anchoring zone (p = .04) and the distal left limb (p = .01), which was the modular limb in 81.1% (p < .01). Neck diameter increase (1.0 mm, IQR 0-3.0 mm; p < .01) and renal artery to stent graft distance difference (0 mm, IQR 0-3.3 mm; p < .01) were significantly higher in the no endoleak group. Five patients in the no endoleak and one patient in the type 2 endoleak group suffered from a stent graft related endoleak (p = .27). CONCLUSIONS: The presence of a type 2 endoleak is associated with decreased surface movement of the proximal anchoring zone and the distal modular limb of bifurcated stent grafts.

Amniocentesis for the detection of congenital toxoplasmosis: results from the nationwide Austrian prenatal screening program.

Prenatal diagnosis of congenital toxoplasmosis (CT) influences therapeutical management in pregnant women and their offspring. In Austria, a nationwide serological healthcare program to identify potential maternal toxoplasma infections during pregnancy exists. We assessed the clinical use of amniocentesis for toxoplasma-specific polymerase chain reaction (PCR) on amniotic fluid to detect CT. Data on serology, amniocentesis, PCR, complications, treatment, and paediatric clinical outcome were collected retrospectively among the birth cohort 1992-2008. There were 1386 women with amniocentesis, but only in 707 cases (51%) was acute maternal infection confirmed serologically. A high proportion (49%) of amniocenteses with negative PCR results in women with chronic infection or seronegativity were performed without clinical justification for the women or their foetuses. The positive and negative predictive values of PCR were 94.4% and 99.3%, respectively. Thirty-nine foetuses with CT, including four deaths, were reported. The five PCR-negative but infected infants were identified by the serological and clinical follow-up program. Thirty percent of amniocenteses were performed in the third trimester, and gestational age or treatment did not influence PCR sensitivity. Amniocentesis is indicated in women with acute maternal infection, and facilitated targeted therapies in pregnant women and their offspring. In women with late toxoplasma infection, negative amniotic fluid PCR made treatment of infants unnecessary. Serological and clinical follow-up of infants is important to confirm the infection status of the infant. Recommendations, based on our 17-year experience, to improve the current diagnostic strategies and to reduce unnecessary amniocentesis, are given.

Diagnostic workup of primary sclerosing cholangitis: the benefit of adding gadoxetic acid-enhanced T1-weighted magnetic resonance cholangiography to conventional T2-weighted magnetic resonance cholangiography.

AIM: To evaluate the value of gadoxetic acid-enhanced T1-weighted (T1W) magnetic resonance cholangiography (MRC) versus conventional T2-weighted (T2W) MRC compared to endoscopic retrograde cholangiopancreatography (ERCP) in patients with primary sclerosing cholangitis (PSC). MATERIALS AND METHODS: Based on T1W MRC, PSC patients were classified into a regular (RG) and a delayed (DG) excreting group, with an absence of gadoxetic acid in the common bile duct at 20 min. Beading, pruning, and gradation of central bile duct stenosis, evaluated by T1W and T2W MRC, were compared to ERCP. Liver parenchymal enhancement was measured in both study groups and compared to a reference group (n = 20) without a history of liver disease. Two readers performed all measurements. RESULTS: Based on beading and pruning of the peripheral bile ducts, sensitivities, specificities, and accuracies for reader 1 were 0.17/0.43, 0/0.17, and 0.15/0.31 for T1W MRC, and 0.83/0.86, 1/0.83, and 0.85/0.85 for T2W MRC (p = 0.004). For reader 2 sensitivities, specificities, and accuracies were 0.25/0.57, 0/0.33, and 0.23/0.46 for T1W MRC, and 0.92/1, 1/0.83, and 0.92/0.92 for T2W MRC (p = 0.012). Compared to ERCP, central bile duct stenoses were significantly overestimated (p < 0.001) by T2W MRC. A significantly lower parenchymal enhancement was found in the DG (n = 7) compared to the RG (n = 13), and compared to the reference group (p < 0.001). CONCLUSION: The combined performance of T2W and T1W MRC may provide a comprehensive imaging workup of PSC, including morphological and functional information resulting in optimal management.

Preterm neonates display altered plasmacytoid dendritic cell function and morphology.

Bacterial and viral infections cause high rates of morbidity and mortality in premature newborns. In the setting of viral infection, pDCs play a key role as strong producers of IFN-α upon TLR9 activation. We analyzed pDC frequency, phenotype, morphology, and function in CB of preterm and term newborns in comparison with adults. Whereas all age groups show similar pDC numbers, BDCA-2, CD123, and TLR9 levels, the expression of BDCA-4 and capacity to produce IFN-α upon TLR9 challenge were decreased significantly in preterm neonates. Furthermore, we show by means of electron microscopy that pDCs from preterm newborns exhibit a distinct, "immature" morphology. Taken together, these findings suggest decreased functionality of pDCs in the premature newborn. The reduced capacity to produce IFN-α is likely to render such infants more susceptible to viral infections.

Aortomonoiliac endografting after failed endovascular aneurysm repair: indications and long-term results.

OBJECTIVES: To present long-term results of endoleak/endograft migration treatment by aortomonoiliac (AMI) endografting after failed endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms. DESIGN: Post hoc analysis of a prospectively gathered database at a tertiary care university hospital. MATERIALS AND METHODS: From March 1995 to November 2010, 23 patients were identified who underwent modification into AMI configuration after failed elective EVAR. Major causes for modification were type I (with/without endograft migration) or type III endoleaks with aneurysm expansion. An average increase in aneurysm size of 1.6 cm (range: -1.5 to 10.5 cm) since initial aneurysm treatment was observed. Interventional outcomes and long-term results were recorded for analysis. RESULTS: Technical success rate of AMI endografting was 95.65% (n = 22). All except two endoleaks could be successfully sealed with this manoeuvre (94.44%). Median time to modification was 5.3 years (interquartile range Q1-Q3: 1.3-9.3 years). No intra-operative conversion to open surgery was necessary and mortality was 0%. Median follow-up was 44 months (interquartile range Q1-Q3: 17-69 months). CONCLUSIONS: Treatment of graft-related endoleaks/endograft migration by AMI endografting after failed EVAR represents a safe and feasible procedure. This approach broadens the minimal invasive opportunities of aneurysm treatment, and open surgical conversion may be avoided except in selected patients.

Elective abdominal aortic aneurysm repair: does the aneurysm diameter influence long-term survival?

OBJECTIVES: The aim of this study was to investigate whether initial abdominal aortic aneurysm (AAA) diameter influences long-term survival after elective repair. DESIGN: Retrospective analysis of database. MATERIAL AND METHODS: Between March 1995 and December 2006, a consecutive series of 895 patients underwent elective treatment of an AAA either by open surgical or endovascular repair. An AAA diameter of 5.5cm was chosen as threshold to distinguish between small and large aneurysms, according to the definition given by the UK small aneurysm trial. Patient characteristics and distribution of basic risk factors were assessed. Survival estimates (Kaplan-Meier) and Cox proportional hazards regression results are reported. RESULTS: Patients with small aneurysms were more likely to survive the first 6 years after AAA repair, even after adjustment for treatment modality and baseline risk factors. After adjustment for age and sex aneurysms with smaller diameter were related to a lower risk of death (p<0.0016). CONCLUSIONS: Patients with small aneurysms (< or =5.5cm) have an improved long-term survival than patients with larger aneurysms.

Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis.

BACKGROUND: We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres. METHODS: Prospective cohort study of 3 year old children, with and without congenital toxoplasmosis, who were identified by prenatal or neonatal screening for toxoplasmosis in 11 centres in 7 countries. Parents were mailed a questionnaire that comprised all or part of existing validated tools. We determined the effect of characteristics of the centre and child on response, age at questionnaire completion, and response to child drawing tasks. RESULTS: The questionnaire took 21 minutes to complete on average. 67% (714/1058) of parents responded. Few parents (60/1058) refused to participate. The strongest determinants of response were the score for organisational attributes of the study centre (such as direct involvement in follow up and access to an address register), and infection with congenital toxoplasmosis. Age at completion was associated with study centre, presence of neurological abnormalities in early infancy, and duration of prenatal treatment. Completion rates for individual questions exceeded 92% except for child completed drawings of a man (70%), which were completed more by girls, older children, and in certain centres. CONCLUSION: Differences in response across European centres were predominantly related to the organisation of follow up and access to correct addresses. The questionnaire was acceptable in all six countries and offers a low cost tool for assessing development, behaviour, and parental concerns and anxiety, in multinational studies.

Prediction of congenital toxoplasmosis by polymerase chain reaction analysis of amniotic fluid.

OBJECTIVE: To determine the accuracy of polymerase chain reaction (PCR) analysis of amniotic fluid for fetal toxoplasmosis according to clinical predictors of outcome and study centre. DESIGN: Prospective cohort study. SETTING: Nine European centres. POPULATION: Women with suspected toxoplasma infection identified by prenatal screening. METHODS: Logistic regression was used to examine the effects of gestational age at maternal seroconversion, treatment and timing of amniocentesis, on PCR accuracy, and to calculate the post-test probability of congenital toxoplasmosis. MAIN OUTCOME MEASURES: Infants had congenital toxoplasmosis if specific IgG persisted beyond 11.5 months. Uninfected infants had undetectable IgG in the absence of anti-toxoplasma treatment. RESULTS: Of 593 PCR results, 64 were positive (57 confirmed infected), and 529 were negative (23 confirmed infected). The likelihood ratio for a positive PCR result decreased significantly with trimester at seroconversion, but did not change significantly for a negative result. Weak associations were detected between sensitivity and, inversely, with specificity, and gestational age at maternal seroconversion. There was no significant association between sensitivity and centre, type or duration of treatment, or timing of amniocentesis. Specificity differed significantly between centres (P < 0.001). The change in pre- to post-test probability of infection was maximal for a positive PCR after first trimester seroconversion, affecting 1% of women tested, and a negative PCR after third trimester seroconversion, affecting half the women tested. CONCLUSIONS: Prediction of the risk of congenital toxoplasmosis should combine estimates of test accuracy and maternal-fetal transmission, which take account of the gestational age at which the mother seroconverted. Local laboratory standards will affect the generalisability of these results.

The impact of endovascular stent grafting on reducing mortality rates after surgical treatment of abdominal aortic aneurysms.

OBJECTIVES: to investigate whether appropriate selection in patients with infrarenal abdominal aortic aneurysms (AAA) for transfemoral endovascular aneurysm management (TEAM) or open graft replacement (OGR) may decrease in-hospital mortality rates (MR). DESIGN: analysis of a clinical series over three periods in an university vascular center. Conclusions of the second period were drawn and prospectively applied in a third period and compared. METHODS: during the period 1989-1994 only OGR was available (n=170). In the interval 1995-2000 either OGR or TEAM were carried out (n=454). During the period 01/2001-07/2002 the conclusions concerning selection of treatment modality were drawn and prospectively applied in 132 consecutive patients. MR were recorded and possible significant differences were checked. RESULTS: during the first period MR was 6.5%. Overall MR decreased to 3.7% in the second interval. Overall MR of the last period was improved to 1.5% (p<0.05). No patient died after OGR (0% vs 6.5%, p<0.04). As all patients with significant individual risk profiles were treated by TEAM, MR slightly increased (2.9%), but the difference remained insignificant (2.4% in period 2). CONCLUSIONS: risk adjusted selection of treatment modality influences the results after OGR significantly, thereby reducing overall MR of elective AAA treatment.

Prenatal diagnosis of a de novo inversion of chromosome (2)(p21q11).

Prenatal diagnosis of "apparently balanced" chromosomal rearrangements, if not inherited from a parent, are problematic for genetic counsellors and families. Although the parents need to be informed about the increased risk of multiple congenital anomalies, the anomalies that the fetus is at risk can not be discussed unless a similar breakpoint and accompanying phenotype have been reported in the literature. In the reported case prenatal ultrasound examination revealed a massive hydrocephalus internus and IUGR. The karyotype of the fetus was inv(2)(p21q11) de novo. Postmortem examination revealed short palpebral fissures, hypertelorism, atypical nasiolabial configuration, microgenia, extended position of the fingers, atypical proximal inserted first toe, hydrocephalus internus, hypoplasia of the cerebellum and bulbi olfactorii, bilateral hypoplastic lungs, atrial septal defect II, small right ventricle, dysplasia of the pulmonary valve, hypoplastic pulmonary artery, right proximal ureterostenosis, hypoplastic gall bladder. This is the first description of a de novo inversion (2)(p21q11) in a fetus with multiple malformations.

Prenatal diagnosis of a supernumerary aberrant chromosome 9.

For counselling of parents, as well as to basically understand how chromosome aneuploidies affect embryonic or fetal development, it is of great importance to analyse and collect genotypes of fetuses with clinical anomalies. This report describes the first prenatal diagnosis of a supernumerary chromosome 9 with deletion of the chromosome region 9q34. Ultrasound examination in the 13th week of gestation detected increased nuchal translucency of 6.9 mm, fetal ascites and a pronounced facial anomaly. Hysteroscopic examination before curettage made it possible to describe this facial anomaly as a double-sided, median defect of the superior lip with protrusion of parts of intersegments. This report provides evidence that the absence of trisomy 9 in 9q34 does not prevent abnormal facial development.

Evaluation of a netilmicin-loading dose in very low birthweight infants.

BACKGROUND: The bactericidal efficacy of aminoglycosides is directly related to maximum serum concentrations, particularly the initial one. Therefore, several groups have recommended an aminoglycoside loading dose. Our goal was to develop a simplified dosage regimen for preterm infants which would result in therapeutic maximum serum concentrations early in the course of therapy. METHODS: Open, noncomparative study during November 2000 to April 2001. The modified netilmicin-dosing protocol included a loading dose of 5 mg/kg in the first week of life, followed by a maintenance regimen of 3.5 mg/kg every 24 h. After the first week of life the corresponding doses were 6 (loading) and 5 mg/kg (maintenance). A peak level was measured 30 min after the second dose, and a trough level immediately before the third dose. RESULTS: Thirty-five very low birthweight infants (mean birthweight 876 +/- 170, range 536-1,385 g; mean gestational age 26 +/- 1.8, range 23-30 weeks) who had 46 episodes of netilmicin treatment were included in the analysis. Mean netilmicin peak and trough values were 15.9 +/- 3.7 (range 8.9-28.9) and 3.4 +/- 1.3 (range 1.0-7.8) micromol/l, respectively. Ninety-one percent of all peak levels were within the targeted range of > or =10 micromol/l. Eleven trough values (24%) were > or =4 micromol/l: in 7 instances netilmicin was administered within the first week of life, 5 of these patients had concomitant indomethacin treatment. Only 1 of the 35 neonates had a rise in serum creatinine of > or =0.5 mg/dl during netilmicin therapy. Hearing evaluations were performed in 25 of the 29 surviving infants at discharge home, all of which gave normal results. CONCLUSIONS: The new netilmicin-dosing protocol yielded therapeutic maximum serum concentrations in 91% of cases after the second dose. However, a significant number of very low birthweight infants had elevated trough levels, particularly when netilmicin was administered in the first week of life with concomitant indomethacin treatment. We speculate that a longer interval between the loading dose and the first maintenance dose would result in fewer elevated trough levels with a similarly high number of therapeutic peak levels.

Cell cycle and cell size regulation in Down syndrome cells.

Although the neuropathological features typical for Down Syndrome obviously result from deregulation of both, cell cycle control and differentiation processes, so far research focused on the latter. Considering the known similarities between the neuropathology of Down Syndrome and Alzheimer's disease and the knowledge, that in Alzheimer's disease neuronal degeneration is associated with the activation of mitogenic signals and cell cycle activation, it is tempting to investigate the consequences of an additional chromosome 21 on mammalian cell cycle regulation. We analysed the distribution of cells in different cell cycle phases on the flowcytometer and the cell size of human amniotic fluid cells with normal karyotypes and with trisomy 21. We could not detect any significant differences suggesting that the presence of an additional copy of the about 225 genes on human chromosome 21 does not trigger cell cycle effects in amniotic fluid cells. These data provide new insights into the cell biology of trisomy 21 cells.

Stem cell marker expression in human trisomy 21 amniotic fluid cells and trophoblasts.

Down Syndrome is the most frequent genetic cause of mental retardation. Deregulation of specific differentiation processes is a major cause for the neuropathological cell features typical for this syndrome. The molecular mechanisms leading to Down Syndrome are likely to be operative from the very earliest time of embryonic/fetal development. We therefore analysed human amniotic fluid cell samples and cytotrophoblastic cells from placental biopsies, both with normal karyotypes and with trisomy 21, for the mRNA expression of stem cell marker genes. Here we describe for the first time that these human primary cell sources contain cells that express telomerase reverse transcriptase, leukemia inhibitory factor receptor, and bone morphogenetic protein receptor II. A specific difference between aneuploid and normal cells could not be detected. These data provide evidence that human amniotic fluid and cytotrophoblastic cell cultures might provide a new source for research on primary cell systems expressing these stem cell markers. In addition, it is suggested that early deregulation of the expression of these genes in the here analysed cell sources does not contribute to the molecular development of Down Syndrome.

Knowledge-based interpretation of toxoplasmosis serology test results including fuzzy temporal concepts--the ToxoNet system.

Transplacental transmission of Toxoplasma gondii from an infected, pregnant woman to the unborn that occurs with a probability of about 60 percent [1] results in fetal damage to a degree depending on the gestational age. The computer system ToxoNet processes the results of serological antibody tests having been performed during pregnancy by means of a knowledge base containing medical knowledge on the interpretation of Toxoplasmosis serology tests. By applying this knowledge ToxoNet generates interpretive reports consisting of a diagnostic interpretation and recommendations for therapy and further testing. For that purpose it matches the results of all serological investigations of maternal blood with the content of the knowledge base returning complete textual interpretations for all given findings. The interpretation algorithm derives the stage of maternal infection from these that is used to infer the degree of fetal threat. To consider varying immune responses of particular patients, certain time intervals have to be kept between two subsequent tests in order to guarantee a correct interpretation of the test results. These time intervals are modelled as fuzzy sets, since they allow the formal description of the temporal uncertainties. ToxoNet comprises the knowledge base, an interpretation system, and a program for the creation and modification of the knowledge base. It is available from the World Wide Web by starting a standard browser like the Internet Explorer or the Netscape Navigator. Thus ToxoNet supports the physician in Toxoplasmosis diagnostics and in addition allows to adopt the way of making decisions to the characteristics of the particular laboratory by modifying the underlying knowledge base.

Ecological comparison of the risks of mother-to-child transmission and clinical manifestations of congenital toxoplasmosis according to prenatal treatment protocol.

We compared the relative risks of mother-to-child transmission of Toxoplasma gondii and clinical manifestations due to congenital toxoplasmosis associated with intensive prenatal treatment in Lyon and Austria, short term treatment in 51% of Dutch women, and no treatment in Danish women. For each cohort, relative risks were standardized for gestation at seroconversion. In total, 856 mother-child pairs were studied: 549 in Lyon, 133 in Austria, 123 in Denmark and 51 in The Netherlands. The relative risk for mother-to-child transmission compared to Lyon was 1.24 (95% CI: 0.88, 1.59) in Austria; 0.59 (0.41, 0.81) in Denmark; and 0.65 (0.37, 1.01) in The Netherlands. Relative risks for clinical manifestations compared with Lyon (adjusted for follow-up to age 3 years) were: Austria 0.19 (0.04, 0.51); Denmark 0.60 (0.13, 1.08); and The Netherlands 1.46 (0.51, 2.72). There was no clear evidence that the risk of transmission or of clinical manifestations was lowest in centres with the most intensive prenatal treatment.

Sleep-wake cycles in preterm infants below 30 weeks of gestational age. Preliminary results of a prospective amplitude-integrated EEG study.

In the newborn, presence of sleep-wake cycles indicates integrity and maturity of the central nervous system. By spectral EEG analysis and polygraphic recordings subtle variations of EEG background activity and behavioural patterns corresponding to early sleep-wake cycles have been found in preterm infants as young as 27 weeks of gestation. The emergence of sleep-wake cycles at early gestational ages may have a positive predictive value for long-term neurological outcome. Sleep-wake cycles and their significance for later outcome have not been studied in very preterm infants so far. Accordingly, we prospectively investigated maturational changes of EEG activity and sleep-wake cycles in preterm infants below 30 weeks of gestational age using the Cerebral Function Monitor, an amplitude-integrated EEG. We present preliminary data on the emergence of sleep-wake cycles in preterm infants from this ongoing study. Of 100 infants enrolled during a 1-year period, 38 infants without neurological complications were included in the reference group. In this group (mean gestational age 27 weeks), we observed cyclical variations of EEG background activity resembling early sleep-wake cycles at a mean gestational age of 28 weeks and a median postnatal age of 6 days. It is hypothesised that these cyclical variations of EEG background activity may represent switches between thalamo-cortical and neo-cortical pattern generators and indicate integrity of central nervous system function. Amplitude-integrated EEG may thus serve as a useful noninvasive test for brain function in preterm infants.

[Preoperative risk factors as deciding criteria in surgical treatment strategy of infrarenal aortic aneurysm]. / Präoperative Risikofaktoren als Entscheidungskriterien in der chirurgischen Behandlungsstrategie des infrarenalen Aortenaneurysmas.

Significant risk factors of operative therapy in patients with infrarenal aortic aneurysms (AAA) were determined. Best treatment strategy (open surgical repair, transluminal endovascular aneurysm management (TEAM) or conservative treatment) was selected on the base of evaluated risk factors, tendency of rupture and life expectancy. Of the typical risk factors impaired renal and/or lung function showed a significant influence on hospital mortality. In patients without these significant risk factors open surgical repair leads to good clinical results. Acceptable postoperative mortality rates after elective exclusion of an AAA with average size in patients presenting significant comorbidities can only be achieved using TEAM. If TEAM can not be performed, open surgery is only justified in the case of very large AAA diameter.