Whole blood interleukin-2 release test to detect and characterize rare circulating gluten-specific T cell responses in coeliac disease.

Whole blood cytokine release assays (CRA) assessing cellular immunity to gluten could simplify the diagnosis and monitoring of coeliac disease (CD). We aimed to determine the effectiveness of electrochemiluminescence CRA to detect responses to immunodominant gliadin peptides. HLA-DQ2·5+ CD adults (cohort 1, n = 6; cohort 2, n = 12) and unaffected controls (cohort 3, n = 9) were enrolled. Cohort 1 had 3-day gluten challenge (GC). Blood was collected at baseline, and for cohort 1 also at 3 h, 6 h and 6 days after commencing 3-day GC. Gliadin peptide-stimulated proliferation, interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and 14- and 3-plex electrochemiluminescence CRA were performed. Poisson distribution analysis was used to estimate responding cell frequencies. In cohort 1, interleukin (IL)-2 dominated the gliadin peptide-stimulated cytokine release profile in whole blood. GC caused systemic IL-2 release acutely and increased gliadin peptide-stimulated IFN-γ ELISPOT and whole blood CRA responses. Whole blood CRA after GC was dominated by IL-2, but also included IFN-γ, C-X-C motif chemokine ligand 10/IFN-γ-induced protein 10 (CXCL10/IP-10), CXCL9/monokine induced by IFN-γ (MIG), IL-10, chemokine (C-C motif) ligand 3/macrophage inflammatory protein 1-alpha (CCL3/MIP-1α), TNF-α and IL-8/CXCL8. In cohorts 2 and 3, gliadin peptide-stimulated whole blood IL-2 release was 100% specific and 92% sensitive for CD patients on a gluten-free diet; the estimated frequency of cells in CD blood secreting IL-2 to α-gliadin peptide was 0·5 to 11 per ml. Whole blood IL-2 release successfully mapped human leucocyte antigen (HLA)-DQ2·5-restricted epitopes in an α-gliadin peptide library using CD blood before and after GC. Whole blood IL-2 release assay using electrochemiluminescence is a sensitive test for rare gliadin-specific T cells in CD, and could aid in monitoring and diagnosis. Larger studies and validation with tetramer-based assays are warranted.

Serum cytokines elevated during gluten-mediated cytokine release in coeliac disease.

Cytokines have been extensively studied in coeliac disease, but cytokine release related to exposure to gluten and associated symptoms has only recently been described. Prominent, early elevations in serum interleukin (IL)-2 after gluten support a central role for T cell activation in the clinical reactions to gluten in coeliac disease. The aim of this study was to establish a quantitative hierarchy of serum cytokines and their relation to symptoms in patients with coeliac disease during gluten-mediated cytokine release reactions. Sera were analyzed from coeliac disease patients on a gluten free-diet (n = 25) and from a parallel cohort of healthy volunteers (n = 25) who underwent an unmasked gluten challenge. Sera were collected at baseline and 2, 4 and 6 h after consuming 10 g vital wheat gluten flour; 187 cytokines were assessed. Confirmatory analyses were performed by high-sensitivity electrochemiluminescence immunoassay. Cytokine elevations were correlated with symptoms. Cytokine release following gluten challenge in coeliac disease patients included significant elevations of IL-2, chemokine (C-C motif) ligand 20 (CCL20), IL-6, chemokine (C-X-C motif) ligand (CXCL)9, CXCL8, interferon (IFN)-γ, IL-10, IL-22, IL-17A, tumour necrosis factor (TNF)-α, CCL2 and amphiregulin. IL-2 and IL-17A were earliest to rise. Peak levels of cytokines were generally at 4 h. IL-2 increased most (median 57-fold), then CCL20 (median 10-fold). Cytokine changes were strongly correlated with one another, and the most severely symptomatic patients had the highest elevations. Early elevations of IL-2, IL-17A, IL-22 and IFN-γ after gluten in patients with coeliac disease implicates rapidly activated T cells as their probable source. Cytokine release after gluten could aid in monitoring experimental treatments and support diagnosis.

Isolated impact of liver herniation on outcome in fetuses with congenital diaphragmatic hernia - A matched-pair analysis based on fetal MRI relative lung volume.

PURPOSE: To evaluate liver-herniation as individual parameter on outcome in children with congenital diaphragmatic hernia. MATERIALS AND METHODS: In a retrospective matched-pair analysis based on observed to expected fetal lung volume (o/e FLV), birth weight, gestational age at time-point of examination, status of tracheal occlusion therapy and side of the defect the individual impact of liver-herniation on survival, need for extracorporeal membrane oxygenation (ECMO) therapy and chronic lung disease (CLD) was investigated. In total 61 pairs (122 patients) were included. Fisher's exact test was used to evaluate influence of liver-herniation and a p-value of <0.05 was defined as statistically significant. The study was approved by the local review board. RESULTS: Children with liver-herniation have lower survival rates (78.7% vs. 95.1%; p = 0.0073), need ECMO-therapy more often (41.0% vs. 16.4%; p = 0.0027) and are more likely to develop CLD (71.7% vs. 37.9%; p = 0.0004) than their corresponding matched-pair without liver-herniation. CONCLUSION: Liver-herniation itself and not further lung-volume restriction due to liver-herniation is responsible for poor outcome in CDH.

Cerebral Perfusion After Repair of Congenital Diaphragmatic Hernia with Common Carotid Artery Occlusion After ECMO Therapy.

AIM: To prospectively evaluate cerebral perfusion after repair of congenital diaphragmatic hernia (CDH) and right-common-carotid-artery (rCCA) occlusion after extracorporeal membrane oxygenation (ECMO) therapy. PATIENTS AND METHODS: A total of 29 2-year-old-children with a history of CDH repair underwent cerebral magnetic resonance perfusion imaging. In 14 patients, the rCCA was occluded after ECMO therapy. Fifteen patients with CDH without ECMO served as controls. Regional cerebral-blood-flow (rCBF) was measured cortically and subcortically in both hemispheres and compared intra-individually and between both groups. RESULTS: Patients with rCCA-occlusion showed intra-individual side differences between hemispheres, with significantly lower subcortical perfusion of the right hemisphere and reduced cortical perfusion. In one-third of patients with rCCA-occlusion, rCBF of the right-hemisphere was reduced by more than 20% when compared to the left hemisphere. Despite intra-individual side differences, mean rCBF in patients with rCCA occlusion was not reduced compared to controls. CONCLUSION: Beside intra-individual side differences, overall right hemisphere perfusion is sufficient after rCCA-occlusion due to collateral blood supply.

Radiation Dose Comparison Between 70 kVp and 100 kVp With Spectral Beam Shaping for Non-Contrast-Enhanced Pediatric Chest Computed Tomography: A Prospective Randomized Controlled Study.

OBJECTIVE: The aim of this prospective randomized controlled study was to compare 2 techniques for radiation dose reduction in non-contrast-enhanced pediatric chest computed tomography (CT): low peak kilovoltage imaging at 70 kVp and spectral beam shaping at 100 kVp using a dedicated tin filter (100-kVp Sn). MATERIALS AND METHODS: All chest CT examinations were performed on a third-generation dual-source CT system (SOMATOM Force; Siemens Healthineers, Germany). Fifty children (mean age, 6.8 ± 5.1 years) were examined using the 100-kVp Sn protocol, whereas 25 children received the 70-kVp protocol (mean age, 5.7 ± 5.2 years; 2:1 randomization scheme). Radiation metrics and organ doses were compared between acquisition techniques using commercially available radiation dose analysis software (Radimetrics Inc, Bayer AG, Toronto, Ontario, Canada). Objective image quality, expressed by signal-to-noise ratio and subjective image quality based on a 4-point scale (1, best; 4, worst image quality), were compared. RESULTS: Volume CT dose index and size-specific dose estimate were significantly lower in the 100-kVp Sn group compared with the 70-kVp group (0.19 ± 0.12 mGy vs 0.81 ± 0.70 mGy and 0.34 ± 0.13 mGy vs 1.48 ± 1.11 mGy; P < 0.0001 for both). Accordingly, mean effective dose was significantly lower for the 100-kVp Sn examinations (0.21 ± 0.10 mSv) compared with the 70-kVp examinations (0.83 ± 0.49 mSv; P < 0.0001). Calculated organ doses were also significantly lower using the 100-kVp Sn protocol when compared with the 70-kVp protocol; for example, breast dose was reduced by a factor of 4.3. Signal-to-noise ratio was slightly superior for 70-kVp images while lung image quality of the 100-kVp Sn protocol was preferred in subjective analysis (P = 0.0004). CONCLUSIONS: Pediatric chest CT performed at 100 kVp with an additional tin filter for spectral shaping significantly reduces radiation dose when compared with low peak kilovoltage imaging at 70 kVp and therefore should be preferred in non-contrast-enhanced pediatric chest CT examinations, particularly (given the improved subjective image quality) when the main focus is evaluation of the lung parenchyma.

Separate Evaluation of the Ipsilateral and Contralateral MR Fetal Lung Volume in Patients With Congenital Diaphragmatic Hernia.

OBJECTIVE: Our study had two objectives. First, we separately evaluated observed-to-expected MR fetal lung volume (FLV) of lungs ipsilateral and contralateral to a congenital diaphragmatic hernia (CDH). Second, we compared the prognostic value of observed-to-expected MR FLV of the ipsilateral and contralateral lungs with that of observed-to-expected MR FLV of both lungs with respect to survival, need for extracorporeal membrane oxygenation (ECMO), and development of chronic lung disease (CLD). MATERIALS AND METHODS: We evaluated observed-to-expected MR FLV of the lung ipsilateral to the diaphragmatic defect as well as in the contralateral lung in 107 fetuses with isolated CDH. ROC analysis and logistic regression analysis were performed to assess the prognostic value of the observed-to-expected MR FLV for association with outcome. RESULTS: In all fetuses with CDH, values in the ipsilateral (mean observed-to-expected MR FLV ± SD, 9.4% ± 9.6%) and the contralateral lung (mean observed-to-expected MR FLV, 48.9% ± 18.5%; p < 0.0001) were significantly lower than values measured in healthy fetuses. Observed-to-expected MR FLV of both lungs and of the contralateral and ipsilateral lung revealed significant differences regarding survival (p < 0.0001, p < 0.0001, and p = 0.0170, respectively), need for ECMO (p < 0.0001, p < 0.0001, and p = 0.0051, respectively), and development of CLD (p = 0.0004, p = 0.0002, and p = 0.0460, respectively). Compared with the observed-to-expected MR FLV of both lungs, the observed-to-expected MR FLV of the contralateral lung showed a slightly higher prognostic accuracy regarding survival (AUC = 0.859 vs 0.825) and development of CLD (AUC = 0.734 vs 0.732) and a similar prognostic accuracy regarding need for ECMO (AUC = 0.805 vs 0.826). Observed-to-expected MR FLV of the ipsilateral lung did not show good prognostic value regarding survival (AUC = 0.617), need for ECMO (AUC = 0.673), and development of CLD (AUC = 0.636). These AUCs were significantly smaller than the AUCs resulting from the observed-to-expected MR FLV of both lungs (each p < 0.05) and considerably smaller than the AUCs of the observed-to-expected MR FLV of the contralateral lung (each p < 0.10). CONCLUSION: Patients with CDH showed a substantially lower observed-to-expected MR FLV of both lungs compared with healthy fetuses. The observed-to-expected MR FLV of both lungs as well as of the lung contralateral to the CDH were reliable prenatal predictors of survival, need for ECMO, and development of CLD.

Region of interest-based versus whole-lung segmentation-based approach for MR lung perfusion quantification in 2-year-old children after congenital diaphragmatic hernia repair.

OBJECTIVE: With a region of interest (ROI)-based approach 2-year-old children after congenital diaphragmatic hernia (CDH) show reduced MR lung perfusion values on the ipsilateral side compared to the contralateral. This study evaluates whether results can be reproduced by segmentation of whole-lung and whether there are differences between the ROI-based and whole-lung measurements. METHODS: Using dynamic contrast-enhanced (DCE) MRI, pulmonary blood flow (PBF), pulmonary blood volume (PBV) and mean transit time (MTT) were quantified in 30 children after CDH repair. Quantification results of an ROI-based (six cylindrical ROIs generated of five adjacent slices per lung-side) and a whole-lung segmentation approach were compared. RESULTS: In both approaches PBF and PBV were significantly reduced on the ipsilateral side (p always <0.0001). In ipsilateral lungs, PBF of the ROI-based and the whole-lung segmentation-based approach was equal (p=0.50). In contralateral lungs, the ROI-based approach significantly overestimated PBF in comparison to the whole-lung segmentation approach by approximately 9.5 % (p=0.0013). CONCLUSIONS: MR lung perfusion in 2-year-old children after CDH is significantly reduced ipsilaterally. In the contralateral lung, the ROI-based approach significantly overestimates perfusion, which can be explained by exclusion of the most ventral parts of the lung. Therefore whole-lung segmentation should be preferred. KEY POINTS: • Ipsilaterally, absolute lung perfusion after CDH is reduced in whole-lung analysis. • Ipsilaterally, the ROI- and whole-lung-based approaches generate identical results. • Contralaterally, the ROI-based approach significantly overestimates perfusion results. • Whole lung should be analysed in MR lung perfusion imaging. • MR lung perfusion measurement is a radiation-free parameter of lung function.

Lung Perfusion MRI After Congenital Diaphragmatic Hernia Repair in 2-Year-Old Children With and Without Extracorporeal Membrane Oxygenation Therapy.

OBJECTIVE: In severe cases of congenital diaphragmatic hernia (CDH), extracorporeal membrane oxygenation (ECMO) therapy improves survival. Later on, lung morbidity mainly defines development. The purpose of this study was to investigate whether 2-year-old children who need ECMO therapy after delivery have reduced perfusion MRI values as a sign of more severe lung hypoplasia than do children who do not need ECMO. MATERIALS AND METHODS: After CDH repair, 38 children underwent dynamic contrast-enhanced MRI with a 3D time-resolved angiography with stochastic trajectories sequence. Fifteen (39%) of the children had received ECMO therapy in the neonatal period. Pulmonary blood flow (PBF), pulmonary blood volume (PBV), and mean transit time were calculated for both lungs. In addition, the ratio of ipsilateral to contralateral lung was calculated for all parameters. RESULTS: In all children, those with and those without ECMO requirement, PBF and PBV were significantly reduced on the ipsilateral side (p < 0.05). Children who had received ECMO therapy had significantly reduced PBF and PBV values on the ipsilateral side (p < 0.05) compared with children who had not needed ECMO therapy. The ratios of ipsilateral to contralateral lung for PBF and PBV were also significantly reduced after ECMO. CONCLUSION: Two-year-old children undergoing CDH repair who had needed neonatal ECMO had significantly reduced perfusion MRI values in the ipsilateral lung in comparison with children who had not needed ECMO. Perfusion MRI measurements are associated with the severity of lung hypoplasia and may therefore be helpful in follow-up investigations.

Correlation of Observed-to-Expected MRI Fetal Lung Volume and Ultrasound Lung-to-Head Ratio at Different Gestational Times in Fetuses With Congenital Diaphragmatic Hernia.

OBJECTIVE: The purpose of this study is to compare the observed-to-expected MRI fetal lung volume and the observed-to-expected ultrasound lung-to-head ratio intraindividually for prediction of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD) at different times of gestation (< 28, 28-32, and > 32 weeks) in fetuses with congenital diaphragmatic hernia (CDH), and to analyze the intraindividual correlation of observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio. MATERIALS AND METHODS: Two hundred one fetuses were included in our study. Observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio were calculated for 270 MRI and ultrasound examinations performed within 72 hours of each other. The prognostic accuracy of observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio was assessed by performing ROC analysis. Correlation was determined using linear regression analysis. RESULTS: The results revealed statistically significant differences between the observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio for the prediction of survival, the need for ECMO therapy, and the development of CLD in fetuses with left-sided CDH (p ≤ 0.0444), with the highest prognostic accuracy for survival (AUC = 0.863). Observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio correlated statistically significantly (p < 0.0001) for left-sided CDH with correlation coefficients (r) of 0.71, 0.71, and 0.56 for early, intermediate, and late times of gestation, respectively. The correlation was not statistically significant at any time for right-sided CDH (p ≥ 0.3947; r ≤ 0.26). CONCLUSION: Observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio are valuable prognostic parameters for prenatal prediction of survival, the need for ECMO therapy, and the development of CLD in fetuses with left-sided CDH at all times of gestation. Observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio correlate statistically significantly for left-sided CDH, and the correlation is best before 32 weeks' gestation, but they do not correlate statistically significantly for right-sided CDH.

Comparison of image quality and radiation dose between an image-intensifier system and a newer-generation flat-panel detector system ­ technical phantom measurements and evaluation of clinical imaging in children.

BACKGROUND: Many image-intensifier fluoroscopy systems have been replaced by flat-panel detectors in recent years. OBJECTIVE: To compare the level of contrast, image resolution and radiation dose between an image-intensifier and a newer-generation flat-panel detector system in a pediatric radiology unit. MATERIALS AND METHODS: We compared two systems ­ a conventional image intensifier and a newer-generation flat-panel system. We measured image quality and radiation dose using a technical phantom. Additionally, we retrospectively compared age-matched fluoroscopic pediatric voiding cystourethrography (n = 15) and upper gastrointestinal investigations (n = 25). RESULTS: In phantom studies image contrast was equal while image resolution was higher and mean radiation dose lower using the flat-panel system (P < 0.0001). In pediatric investigations, mean dose area product was significantly reduced on the flat-panel system for upper gastrointestinal investigation (45 ± 38 µGy*m2 vs. 11 ± 9 µGy*m2; P < 0.0001) and for voiding cystourethrography (18 ± 20 µGy*m2 vs. 10 ± 12 µGy*m2; P = 0.04). CONCLUSION: The newer flat-panel system performs at lower dose levels with equal to better image quality and therefore seems to be the more suitable technique for pediatric fluoroscopy in comparison to image-intensifier systems.

Ultra-high pitch chest computed tomography at 70 kVp tube voltage in an anthropomorphic pediatric phantom and non-sedated pediatric patients: Initial experience with 3rd generation dual-source CT.

PURPOSE: Minimizing radiation dose while at the same time preserving image quality is of particular importance in pediatric chest CT. Very recently, CT imaging with a tube voltage of 70 kVp has become clinically available. However, image noise is inversely proportional to the tube voltage. We aimed to investigate radiation dose and image quality of pediatric chest CT performed at 70 kVp in an anthropomorphic pediatric phantom as well as in clinical patients. METHODS AND MATERIALS: An anthropomorphic pediatric phantom, which resembles a one-year-old child in physiognomy, was scanned on the 3rd generation dual-source CT (DSCT) system at 70 kVp and 80 kVp and a fixed ultra low tube-current of 8 mAs to solely evaluate the impact of lowering tube voltage. After the phantom measurements, 18 pediatric patients (mean 29.5 months; range 1-91 months; 21 examinations) underwent 3.2 high-pitch chest CT on the same DSCT system at 70 kVp tube voltage without any sedation. Radiation dose and presence of motion artifacts was compared to a retrospectively identified patient cohort examined at 80 kVp on a 16-slice single-source-CT (SSCT; n=15; 14/15 with sedation; mean 30.7 months; range 0-96 months; pitch=1.5) or on a 2nd generation DSCT without any sedation (n=6; mean 32.8 months; range 4-61 months; pitch=3.2). RESULTS: Radiation dose in the phantom scans was reduced by approximately 40% when using a tube voltage of 70 kVp instead of 80 kVp. In the pediatric patient group examined at 70 kVp age-specific effective dose (ED; mean 0.5±0.2 mSv) was significantly lower when compared to the retrospective cohort scanned at 80 kVp on the 16-slice-SSCT (mean ED: 1.0±0.3 mSv; p<0.0001) and also considerably lower when compared to the cohort scanned at 80 kVp on the 2nd generation DSCT (mean ED: 0.9±0.5 mSv). None of the prospective, sedation-free CT examinations showed any motion artifacts whereas 13/15 examinations of the retrospective patient cohort scanned at 80 kVp with a pitch of 1.5 showed motion artifacts. CONCLUSION: 3.2 high-pitch chest CT performed with 70 kVp significantly reduces radiation dose when compared to 80 kVp while at the same time provides good image quality without any motion artifacts even without sedation.

Semi-automatic lung segmentation of DCE-MRI data sets of 2-year old children after congenital diaphragmatic hernia repair: Initial results.

In congenital diaphragmatic hernia (CDH), lung hypoplasia and secondary pulmonary hypertension are the major causes of death and severe disability. Based on new therapeutic strategies survival rates could be improved to up to 80%. However, after surgical repair of CDH, long-term follow-up of these pediatric patients is necessary. In this, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) provides insights into the pulmonary microcirculation and might become a tool within the routine follow-up program of CDH patients. However, whole lung segmentation from DCE-MRI scans is tedious and automated procedures are warranted. Therefore, in this study, an approach to semi-automated lung segmentation is presented. Segmentation of the lung is obtained by calculating the cross correlation and the area under curve between all voxels in the data set and a reference region-of-interest (ROI), here the arterial input function (AIF). By applying an upper and lower threshold to the obtained maps and intersecting these, a final segmentation is reached. This approach was tested on twelve DCE-MRI data sets of 2-year old children after CDH repair. Segmentation accuracy was evaluated by comparing obtained automatic segmentations to manual delineations using the Dice overlap measure. Optimal thresholds for the cross correlation were 0.5/0.95 and 0.1/0.5 for the area under curve, respectively. The ipsilateral (left) lung showed reduced segmentation accuracy compared to the contralateral (right) lung. Average processing time was about 1.4s per data set. Average Dice score was 0.7±0.1 for the whole lung. In conclusion, initial results are promising. By our approach, whole lung segmentation is possible and a rapid evaluation of whole lung perfusion becomes possible. This might allow for a more detailed analysis of lung hypoplasia of children after CDH.

Prenatal MR imaging of congenital diaphragmatic hernias: association of MR fetal lung volume with the need for postnatal prosthetic patch repair.

OBJECTIVE: To assess whether the need for postnatal prosthetic patch repair of the diaphragmatic defect in neonates with a congenital diaphragmatic hernia (CDH) is associated with the antenatal measured observed-to-expected magnetic resonance fetal lung volume (o/e MR-FLV). METHODS: The o/e MR-FLV was calculated in 247 fetuses with isolated CDH. Logistic regression analysis was used to assess the prognostic value of the individual o/e MR-FLV for association with the need for postnatal patch repair. RESULTS: Seventy-seven percent (77%) of patients with a CDH (190/247) required prosthetic patch repair and the defect was closed primarily in 23% (57/247). Patients requiring a patch had a significantly lower o/e MR-FLV (27.7 ± 10.2%) than patients with primary repair (40.8 ± 13.8%, p < 0.001, AUC = 0.786). With an o/e MR-FLV of 20%, 92% of the patients required patch repair, compared to only 24% with an o/e MR-FLV of 60%. The need for a prosthetic patch was further influenced by the fetal liver position (herniation/no herniation) as determined by magnetic resonance imaging (MRI; p < 0.001). Fetal liver position, in addition to the o/e MR-FLV, improves prognostic accuracy (AUC = 0.827). CONCLUSION: Logistic regression analysis based on the o/e MR-FLV is useful for prenatal estimation of the prosthetic patch requirement in patients with a CDH. In addition to the o/e MR-FLV, the position of the liver as determined by fetal MRI helps improve prognostic accuracy. KEY POINTS: • The o/e MR-FLV is associated with the need for postnatal patch repair in CDH. • The need for a patch is associated with a significantly lower o/e MR-FLV (p < 0.001). • The patch requirement is also influenced by fetal liver position. • Fetal liver position, in addition to the o/e MR-FLV, improves prognostic accuracy. • CDH-fetuses with a high probability for patch requirement can be identified prenatally.

High temporal versus high spatial resolution in MR quantitative pulmonary perfusion imaging of two-year old children after congenital diaphragmatic hernia repair.

OBJECTIVES: Congenital diaphragmatic hernia (CDH) leads to lung hypoplasia. Using dynamic contrast-enhanced (DCE) MR imaging, lung perfusion can be quantified. As MR perfusion values depend on temporal resolution, we compared two protocols to investigate whether ipsilateral lung perfusion is impaired after CDH, whether there are protocol-dependent differences, and which protocol is preferred. METHODS: DCE-MRI was performed in 36 2-year old children after CDH on a 3 T MRI system; protocol A (n = 18) based on a high spatial (3.0 s; voxel: 1.25 mm(3)) and protocol B (n = 18) on a high temporal resolution (1.5 s; voxel: 2 mm(3)). Pulmonary blood flow (PBF), pulmonary blood volume (PBV), mean transit time (MTT), and peak-contrast-to-noise-ratio (PCNR) were quantified. RESULTS: PBF was reduced ipsilaterally, with ipsilateral PBF of 45 ± 26 ml/100 ml/min to contralateral PBF of 63 ± 28 ml/100 ml/min (p = 0.0016) for protocol A; and for protocol B, side differences were equivalent (ipsilateral PBF = 62 ± 24 vs. contralateral PBF = 85 ± 30 ml/100 ml/min; p = 0.0034). PCNR was higher for protocol B (30 ± 18 vs. 20 ± 9; p = 0.0294). Protocol B showed higher values of PBF in comparison to protocol A (p always <0.05). CONCLUSIONS: Ipsilateral lung perfusion is reduced in 2-year old children following CDH repair. Higher temporal resolution and increased voxel size show a gain in PCNR and lead to higher perfusion values. Protocol B is therefore preferred. KEY POINTS: • Quantitative lung perfusion parameters depend on temporal and spatial resolution. • Reduction of lung perfusion in CDH can be measured with different MR protocols. • Temporal resolution of 1.5 s with spatial resolution of 2 mm (3) is suitable.

Management of parenteral nutrition associated hyperglycaemia: a comparison of subcutaneous and intravenous insulin regimen.

PN is associated with significant hyperglycaemia, which may be detrimental to clinical outcome. There are few data on the management of this phenomenon outside of intensive care units. In our unit, we studied the efficacy of protocol-based intravenous insulin delivery as compared to subcutaneous insulin prescribed individually outside of the critical care setting. In a retrospective review over a two-year period, we compared patients with PN-associated hyperglycaemia who had received both modes of insulin therapy. A total of 122 who developed PN-associated hyperglycaemia were identified. Those on the intravenous insulin regimen were within glycaemic target for more time than those on the subcutaneous regimen (62% Vs 43%, p = 0.008). We therefore conclude that outside of the critical care setting, intravenous insulin delivers better glycaemic control and should therefore be considered optimum therapy for patients with PN-associated hyperglycaemia.

MRI-based ratio of fetal lung volume to fetal body volume as a new prognostic marker in congenital diaphragmatic hernia.

OBJECTIVE: The objective of our study was to evaluate the prognostic accuracy of the MRI-based ratio of fetal lung volume (FLV) to fetal body volume (FBV) for predicting survival and the need for extracorporeal membrane oxygenation (ECMO) therapy in fetuses with congenital diaphragmatic hernia (CDH). MATERIALS AND METHODS: MRI was performed in 96 fetuses (34 females and 62 males; mean gestational age, 33 ± 5 [SD] weeks; range, 23-39 weeks) with CDH and 44 healthy control subjects. FLV and FBV were measured for each fetus by one of three investigators, and we calculated the FLV/FBV ratio. Additionally, a subgroup analysis of growth-restricted fetuses was performed. Logistic regression analysis was used to model the dependence of survival and ECMO requirement on the FLV/FBV ratio. Prognostic accuracy was evaluated by applying the area under the curve (AUC). RESULTS: Seventy-eight of the 96 (81%) fetuses survived and 35 (36%) neonates needed ECMO therapy. The FLV/FBV ratio was significantly higher in fetuses who survived (p < 0.0001; AUC = 0.829). Neonates who received ECMO therapy showed a significantly lower prenatal FLV/FBV ratio (p = 0.0001; AUC = 0.811) than neonates who did not need ECMO therapy. A subgroup analysis (n = 13) showed a trend toward a higher FLV/FBV ratio of survivors in comparison with nonsurvivors (p = 0.065; AUC = 0.875). CONCLUSION: In our study, the MRI-based FLV/FBV ratio was able to predict neonatal survival and ECMO requirement in children with CDH with high accuracy. Unlike other prognostic parameters, FLV/FBV ratio is independent of a reference to a control group and may enhance prognostic accuracy particularly in growth-restricted neonatal patients.

A holistic assessment of bariatric surgical outcomes in a Northern Irish cohort.

The King's Obesity Staging system was developed to evaluate the effect of obesity treatments in multiple physical, psychological and functional domains. In this prospective cohort study, a Northern Irish cohort was scored using the King's Obesity Staging system before and 1 year after bariatric surgery. 71 individuals underwent surgery and 31 (44%) had type 2 diabetes. Bariatric surgery improved each health domain (p < 0.05). A subgroup with type 2 diabetes showed a significantly greater improvement in gonadal disease (polycystic ovarian syndrome and sub-fertility) (p = 0.02), and a trend towards greater improvement in cardiovascular disease (p = 0.07) compared with the non-diabetic subgroup. Half of those with pre-diabetes were normoglycaemic postoperatively (p < 0.05). The King's Obesity Staging system can be used to holistically evaluate the outcomes of bariatric surgery. Patients benefit from bariatric surgery in many ways, but those with diabetes may benefit more.

Multiple aseptic splenic abscesses in a 15 year old patient.

BACKGROUND: Splenic abscesses in children are rare. In recent years aseptic abscesses have been recognized as a new disease entity, especially in adults. CASE PRESENTATION: We present a rare case of a 15 year old girl with aseptic abscesses, in whom antibiotic therapy comprising metronidazole and meropenem was partly beneficial in improving the patient's clinical condition and inflammatory parameters. Eventually corticosteroid therapy led to complete and long lasting resolution of symptoms. Further diagnostic work-up revealed autoimmune thyroiditis, but no signs of inflammatory bowel disease. CONCLUSION: Aseptic splenic abscesses should always prompt clinicians to initiate further diagnostics to determine a potential underlying condition and a regular follow-up. Anaerobic bacteria may play a role in the pathogenesis of the disease and besides corticosteroid treatment antibiotics covering anaerobes may be beneficial.

Bariatric surgery: the indications in metabolic disease.

As well as the pronounced effect on body mass index (BMI), bariatric surgery is increasingly recognized as being associated with improvements in morbidity and mortality in a range of conditions, from airways disease to cancer. In metabolic disease, the impact of bariatric surgery is particularly obvious with marked improvements in glycemic control in patients with type 2 diabetes mellitus, to the point of effecting diabetes remission in some. Hypertension and dyslipidemia, key components of the metabolic syndrome, also respond to bariatric surgery. Despite the increasing evidence of benefit in metabolic disease, the major national guidelines for selecting candidates for bariatric surgery retain their emphasis on body weight. In these guidelines, a BMI ≥35 kg/m(2) is needed to indicate surgery, even in those with profound metabolic disturbance. The recent International Diabetes Federation guidelines have identified the need to reorientate our focus from BMI to metabolic disease. In this review, we examine the developing indications for the use of bariatric surgery in metabolic disease. We will focus on type 2 diabetes mellitus and the metabolic syndrome. Within this, we will outline the data for using bariatric surgery as metabolic surgery, including those with a BMI <35 kg/m(2).

Pre-pregnancy care and pregnancy outcomes in type 1 diabetes mellitus: a comparison of continuous subcutaneous insulin infusion and multiple daily injection therapy.

BACKGROUND: Pre-pregnancy care improves pregnancy outcomes in type 1 diabetes mellitus (T1DM). Continuous subcutaneous insulin infusion (CSII) therapy and multiple daily injection (MDI) therapy can both be used to achieve glycaemic targets, but few data are available to compare their efficacy in pre-pregnancy care. AIM: To compare MDI and CSII in pre-pregnancy care in T1DM. METHODS: Retrospective database review of women with T1DM attending the Dublin Diabetes in Pregnancy Centre. RESULTS: 464 women with T1DM (40 treated with CSII) were included. Women attending for pre-pregnancy care had lower HbA1c levels at booking to antenatal services [52 ± 10 mmol/mol (6.9 ± 0.9 %) vs. 62 ± 16 mmol/mol (7.8 ± 1.5 %), p < 0.001], and booked at an earlier gestation (6 ± 2 vs. 8 ± 6 weeks, p < 0.001). In those who attended for pre-pregnancy care, the CSII group had lower HbA1c levels at booking than those using MDI [48 ± 8 mmol/mol (6.5 ± 0.7 %) vs. 53 ± 10 mmol/mol (7.0 ± 0.9 %), p = 0.03]. Gestational age at delivery and birth weight did not differ between groups. Caesarean section rates were associated with CSII use (p < 0.001), duration of diabetes (p = 0.002), and parity (p = 0.006). Nulliparous women using CSII with a longer history of diabetes were more likely to deliver by Caesarean section. There was no perinatal mortality. CONCLUSIONS: Pre-pregnancy care delivered by a specialist multi-disciplinary team effectively reduces HbA1c levels peri-conception. CSII use results in lower HbA1c levels in pre-pregnancy care in selected individuals and should be considered in women with T1DM planning pregnancy.