Changes in neonatal morbidity, neonatal care practices, and length of hospital stay of surviving infants born very preterm in the Netherlands in the 1980s and in the 2000s: a comparison analysis with identical characteristics definitions.

BACKGROUND: This study evaluates changes in the neonatal morbidity, the neonatal care practices, and the length of hospital stay of surviving very preterm (VP) infants born in the Netherlands in the 1980s and in the 2000s; a period over which historical improvements were introduced into neonatal care. We, herein, also study whether these changes in neonatal morbidity, neonatal care practices and length of hospital stay are associated with sociodemographic, prenatal, and infant characteristics. METHODS: Two community-based cohorts from 1983 (POPS) and 2002-03 (LOLLIPOP) have provided the perinatal data for our study. The analysis enrolled 1,228 participants born VP (before the 32nd week of gestation) and surviving to 2 years of age without any severe congenital malformation. A rigorous harmonisation protocol ensured a precise comparison of the cohorts by using identical definitions of the perinatal characteristics. RESULTS: In 2003, mothers were older when giving birth, had higher multiple birth rates, and significantly more parents had received higher education. In 2003, less VP infants had severe intraventricular haemorrhage and sepsis and relatively more received continuous positive airway pressure, mechanical ventilation and caffeine therapy than in 1983. Antenatal corticosteroids and surfactant therapy were provided only in 2003. The length of the stay in the neonatal intensive care unit and in hospital had decreased in 2003 by 22 and 11 days, respectively. Differences persisted after adjustment for sociodemographic, prenatal, and infant characteristics. CONCLUSIONS: Neonatal morbidities of the surviving VP infants in this study have not increased, and exhibit improvements for various characteristics in two cohorts born 20 years apart with comparable gestational age and birth weight. Our data suggest that the improvements found are associated with more advanced therapeutic approaches and new national protocols in place, and less so with sociodemographic changes. This analysis provides a basis for further comparative analyses of the health and the development of VP children, particularly with regard to long-term outcomes.

Small-scaled association between ambient temperature and campylobacteriosis incidence in Germany.

Campylobacteriosis is the leading bacterial cause of human diarrheal illness worldwide. Campylobacteriosis incidence exhibits seasonality and has been attributed to ambient temperature. However, the role of ambient temperature on campylobacteriosis remains poorly understood. To examine the impact of ambient temperature on local campylobacteriosis in Germany, weekly incidences on NUTS-3 level were analysed using a novel small-scaled approach, regression and time lags. Campylobacteriosis incidence correlated positively with temperatures between - 5 and 28 °C. The sigmoid regression model estimated an incidence increase of 0.52 per 5 °C temperature rise in the observation period. The weekly average of daily minimum temperature was most significant at a time lag of two weeks and showed the steepest incidence increase of 0.13 per 1 °C temperature increase in a temperature corridor of 5.1 to 12.2 °C. The impact of average minimum temperatures on campylobacteriosis incidence is crucial, likely to be indirect and especially relevant in the recent part of the infection chain. Vectors or human behaviour are presumably more directly linked with temperature than the pathogen's microbiology and should be examined. These variables outweigh the direct temperature-pathogen relationship when the whole chain of infection is considered. In the context of climate change, campylobacteriosis is likely to increase in Germany due to an increased temperature effect.

A pilot study of magnetic resonance fingerprinting in Parkinson's disease.

Parkinson's disease (PD) affects more than six million people, but reliable MRI biomarkers with which to diagnose patients have not been established. Magnetic resonance fingerprinting (MRF) is a recent quantitative technique that can provide relaxometric maps from a single sequence. The purpose of this study is to assess the potential of MRF to identify PD in patients and their disease severity, as well as to evaluate comfort during MRF. Twenty-five PD patients and 25 matching controls underwent 3 T MRI, including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 maps were generated by voxel-wise matching the measured MRF signal to a precomputed dictionary. All participants also received standard inversion recovery T1 and multi-echo T2 mapping. An ROI-based analysis of relaxation times was performed. Differences between patients and controls as well as techniques were determined by logistic regression, Spearman correlation and t-test. Patients were asked to estimate the subjective comfort of the MRF sequence. Both MRF-based T1 and T2 mapping discriminated patients from controls: T1 relaxation times differed most in cortical grey matter (PD 1337 ± 38 vs. control 1386 ± 37 ms; mean ± SD; P = .0001) and, in combination with normal-appearing white matter, enabled correct discrimination in 85.7% of cases (sensitivity 83.3%; specificity 88.0%; receiver-operating characteristic [ROC]) area under the curve [AUC] 0.87), while for T2 mapping the left putamen was the strongest classifier (40.54 ± 6.28 vs. 34.17 ± 4.96 ms; P = .0001), enabling differentiation of groups in 84.0% of all cases (sensitivity 80.0%; specificity 88.0%; ROC AUC 0.87). Relaxation time differences were not associated with disease severity. Standard mapping techniques generated significantly different relaxation time values and identified other structures as different between groups other than MRF. Twenty-three out of 25 PD patients preferred the MRF examination instead of a standard MRI. MRF-based mapping can identify PD patients with good comfort but needs further assessment regarding disease severity identification and its potential for comparability with standard mapping technique results.

Pyramidal tract and alternate motor fibers complementarily mediate motor compensation in patients after hemispherotomy.

Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.

Follow-up study to investigate symmetry and stability of cranioplasty in craniosynostosis - Introduction of new pathology-specific parameters and a comparison to the norm population.

PURPOSE: Cranioplasty and modulation of frontoorbital advancement (FOA) in children with craniosynostosis aims to achieve an attractive aesthetic and functional rehabilitation of the forehead area, comparable to that in unaffected children. Based on a three-dimensional surface scan, a cephalometric data evaluation with new parameters for the quantification of physiological and pathological cranial morphologies, and objective evaluation of postoperative follow-up in comparison to an age-equivalent standard population, were performed. MATERIALS AND METHODS: In a prospective study, 80 children were operated on with non-syndromic craniosynostosis (trigonocephalus, n = 30; plagiocephalus, n = 10; scaphocephalus, n = 38; brachycephalus, n = 2) and pre- and 3, 6, 12, 18 and 30 months postoperative three-dimensional surface scans were obtained (3DShape, Erlangen, Germany) and morphometrically measured (Onyx Ceph, Image Instruments, Chemnitz, Germany). In addition, 49 healthy children who were not operated on were measured at equivalent ages (n = 25 [6 months]; n = 20 [9 months]; n = 4 [12 months]). RESULTS: All patient groups showed stable long-term results with regard to shaping of the forehead. Cranioplasty in patients with scaphocephalus resulted in a significant widening of the anterior (73.9 ± 3.5 mm; p < 0.001) and posterior (132.2 ± 5.2 mm; p < 0.001) cranial width, with no significant difference from the norm population 1 year after surgery (p = 0.6597). As parameters for the correction of trigonocephaly, the frontal angle showed significant improvement (145.9 ± 3.7°; p < 0.001). While the parietal angle 12 months after surgery showed similar values as the norm population, the frontal angle was about 10° smaller than in healthy children (p = 0.0055), despite a clinically inconspicuous physiognomy. As part of the correction of plagiocephaly, the patients tended to relapse in the postoperative course, although there was no statistically significant difference in the frontal angle compared to that in the norm population (153.3 ± 3.9°; p = 0.06). While 6 months after surgery all patients showed a normal cranial volume development compared to healthy children of the same age, the volumes of brachycephalic patients remained below the norm (1244.2 ± 153.2 cm3; p = 0.0244). Overall, the analysis of the norm population showed a growing dispersion of measurement values with increasing age, which was observed to be more concentrated in the operated cranial morphologies. CONCLUSION: The determination of new pathology-specific morphometric parameters on the three-dimensional surface scan enables an objective quantification of physiological and pathological cranial morphologies of children. A comparison of operated children with a healthy, age-appropriate comparison group showed that preoperative and statistically significant deviations of the new measuring parameters in long-term follow-up could be normalized through surgical intervention, although this does not apply without limitations to children with coronary suture synostosis.

Automated quantitative evaluation of brain MRI may be more accurate for discriminating preterm born adults.

OBJECTIVE: To investigate the structural brain abnormalities and their diagnostic accuracy through qualitative and quantitative analysis in term born and very preterm birth or with very low birth weight (VP/VLBW) adults. METHODS: We analyzed 3-T MRIs acquired in 2011-2013 from 67 adults (27 term born controls, mean age 26.4 years, 8 females; 40 VP/VLBWs, mean age 26.6 years, 16 females). We compared automatic segmentations of the white matter, deep gray matter and cortical gray matter, manual corpus callosum measurements and visual ratings of the ventricles and white matter with t tests, logistic regression, and receiver operator characteristic (ROC) curves. RESULTS: Automatic segmentation correctly classified 84% of cases; visual ratings correctly classified 63%. Quantitative volumetry based on automatic segmentation revealed higher ventricular volume, lower posterior corpus callosum, and deep gray matter volumes in VP/VLBW subjects compared to controls (p < 0.01). Visual rating and manual measurement revealed a thinner corpus callosum in VP/VLBW adults (p = 0.04) and deformed lateral ventricles (p = 0.03) and tendency towards more "dirty" white matter (p = 0.06). Automatic/manual measures combined with visual ratings correctly classified 87% of cases. Stepwise logistic regression identified three independent features that correctly classify 81% of cases: ventricular volume, deep gray matter volume, and white matter aspect. CONCLUSION: Enlarged and deformed lateral ventricles, thinner corpus callosum, and "dirty" white matter are prevalent in preterm born adults. Their visual evaluation has low diagnostic accuracy. Automatic volume quantification is more accurate but time consuming. It may be useful to ask for prematurity before initiating further diagnostics in subjects with these alterations. KEY POINTS: • Our study confirms prior reports showing that structural brain abnormalities related to preterm birth persist into adulthood. • In the clinical practice, if large and deformed lateral ventricles, small and thin corpus callosum, and "dirty" white matter are visible on MRI, ask for prematurity before considering other diagnoses. • Although prevalent, visual findings have low accuracy; adding automatic segmentation of lateral ventricles and deep gray matter nuclei improves the diagnostic accuracy.

Evidence for peri-ictal blood-brain barrier dysfunction in patients with epilepsy.

Epilepsy has been associated with a dysfunction of the blood-brain barrier. While there is ample evidence that a dysfunction of the blood-brain barrier contributes to epileptogenesis, blood-brain barrier dysfunction as a consequence of single epileptic seizures has not been systematically investigated. We hypothesized that blood-brain barrier dysfunction is temporally and anatomically associated with epileptic seizures in patients and used a newly-established quantitative MRI protocol to test our hypothesis. Twenty-three patients with epilepsy undergoing inpatient monitoring as part of their presurgical evaluation were included in this study (10 females, mean age ± standard deviation: 28.78 ± 8.45). For each patient, we acquired quantitative T1 relaxation time maps (qT1) after both ictal and interictal injection of gadolinium-based contrast agent. The postictal enhancement of contrast agent was quantified by subtracting postictal qT1 from interictal qT1 and the resulting ΔqT1 was used as a surrogate imaging marker of peri-ictal blood-brain barrier dysfunction. Additionally, the serum concentrations of MMP9 and S100, both considered biomarkers of blood-brain barrier dysfunction, were assessed in serum samples obtained prior to and after the index seizure. Fifteen patients exhibited secondarily generalized tonic-clonic seizures and eight patients exhibited focal seizures at ictal injection of contrast agent. By comparing ΔqT1 of the generalized tonic-clonic seizures and focal seizures groups, the anatomical association between ictal epileptic activity and postictal enhancement of contrast agent could be probed. The generalized tonic-clonic seizures group showed significantly higher ΔqT1 in the whole brain as compared to the focal seizures group. Specific analysis of scans acquired later than 3 h after the onset of the seizure revealed higher ΔqT1 in the generalized tonic-clonic seizures group as compared to the focal seizures group, which was strictly lateralized to the hemisphere of seizure onset. Both MMP9 and S100 showed a significantly increased postictal concentration. The current study provides evidence for the occurrence of a blood-brain barrier dysfunction, which is temporally and anatomically associated with epileptic seizures. qT1 after ictal contrast agent injection is rendered as valuable imaging marker of seizure-associated blood-brain barrier dysfunction and may be measured hours after the seizure. The observation of the strong anatomical association of peri-ictal blood-brain barrier dysfunction may spark the development of new functional imaging modalities for the post hoc visualization of brain areas affected by the seizure.

Head circumference - a useful single parameter for skull volume development in cranial growth analysis?

BACKGROUND: The measurement of maximal head circumference is a standard procedure in the examination of childrens' cranial growth and brain development. The objective of the study was to evaluate the validity of maximal head circumference to cranial volume in the first year of life using a new method which includes ear-to-ear over the head distance and maximal cranial length measurement. METHODS: 3D surface scans for cranial volume assessment were conducted in this method comparison study of 44 healthy Caucasian children (29 male, 15 female) at the ages of 4 and 12 months. RESULTS: Cranial volume increased from measurements made at 4 months to 12 months of age by an average of 1174 ± 106 to 1579 ± 79 ml. Maximal cranial circumference increased from 43.4 ± 9 cm to 46.9 ± 7 cm and the ear-to ear measurement increased from 26.3 ± 21 cm to 31.6 ± 18 cm at the same time points. There was a monotone association between maximal head circumference (HC) and increase in volume, yet a backwards inference from maximal circumference to the volume had a predictive value of only 78% (adjusted R2). Including the additional measurement of distance from ear to ear strengthened the ability of the model to predict the true value attained to 90%. The addition of the parameter skull length appeared to be negligible. CONCLUSION: The results demonstrate that for a distinct improvement in the evaluation of a physiological cranial volume development, the additional measurement of the ear-to ear distance using a measuring tape is expedient, and, especially for cases with pathological skull changes, such as craniosynostosis, ought to be conducted.

The self-defining axis of symmetry: A new method to determine optimal symmetry and its application and limitation in craniofacial surgery.

PURPOSE: Analysis of symmetry represents an essential aspect of plastic-reconstructive surgery. For cases in which reference points are either not fixed or are changed due to corrective intervention the determination of a symmetry axis is sometimes almost impossible and a pre-defined symmetry axis would not always be helpful. To assess cranial shape of surgical patients with craniosynostosis, a new algebraic approach was chosen in which deviation from the optimal symmetry axis could be quantified. MATERIALS AND METHODS: Optimal symmetry was defined based on a single central point in the fronto-orbital advancement (FOA) hyperplane and a corresponding landmark pair. The forehead symmetry evaluation was based on 3D-scans series of 13 children, on whom cranioplasty with FOA was performed and 15 healthy children who served as control group. RESULTS: Children with plagiocephaly showed considerable improvement in symmetry postoperatively, with stable values over one year, while those with trigonocephaly and brachycephaly showed constant good symmetry in the forehead both pre- and postoperatively. CONCLUSIONS: With the help of an optimally calculated symmetry axis this new analysis method offers a solution, which is independent of preset dimensions. Patients can be evaluated according to their individual needs regarding symmetry and also be compared with one another.

Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV infection. However, replication of hepatitis C virus (HCV) is not inhibited by HAART, and treatment-related hepatotoxicity is common. To clarify the effect of HAART in HIV/HCV-coinfected patients, we studied liver-related mortality and overall mortality in 285 patients who were regularly treated during the period 1990-2002 at our department. METHODS: Survival was analysed retrospectively by Kaplan-Meier and Cox's regression analyses after patients (81% haemophiliacs) had been stratified into three groups according to their antiretroviral therapy (HAART n=93, available after 1995; treatment exclusively with nucleoside analogues n=55, available after 1992; or no treatment, n=137). FINDINGS: Liver-related mortality rates were 0.45, 0.69, and 1.70 per 100 person-years in the HAART, antiretroviral-treatment, and untreated groups. Kaplan-Meier analysis of liver-related mortality confirmed the significant survival benefit in patients with antiretroviral therapy (p=0.018), and regression analysis identified HAART (odds ratio 0.106 [95% CI 0.020-0.564]), antiretroviral treatment (0.283 [0.103-0.780]), CD4-positive T-cell count (0.746 [0.641-0.868] per 0.05x10(9) cells/L), serum cholinesterase (0.962 [0.938-0.986] per 100 U/L), and age (1.065 [1.027-1.105] per year) as independent predictors of liver-related survival. Severe drug-related hepatotoxicity was seen in five patients treated with nucleoside analogues alone and 13 treated with HAART. No patient died from drug-related hepatotoxicity. INTERPRETATION: In addition to improved overall survival, antiretroviral therapy significantly reduced long-term liver-related mortality in our patients. This survival benefit seems to outweigh by far the associated risks of severe hepatotoxicity.