Application of Virtual Three-Dimensional Models for Simultaneous Visualization of Intracardiac Anatomic Relationships in Double Outlet Right Ventricle

Our goal was to construct three-dimensional (3D) virtual models to allow simultaneous visualization of the ventricles, ventricular septal defect (VSD) and great arteries in patients with complex intracardiac anatomy to aid in surgical planning. We also sought to correlate measurements from the source cardiac magnetic resonance (CMR) image dataset and the 3D model. Complicated ventriculo-arterial relationships in patients with complex conotruncal malformations make preoperative assessment of possible repair pathways difficult. Patients were chosen with double outlet right ventricle for the complexity of intracardiac anatomy and potential for better delineation of anatomic spatial relationships. Virtual 3D models were generated from CMR 3D datasets. Measurements were made on the source CMR as well as the 3D model for the following structures: aortic diameter in orthogonal planes, VSD diameter in orthogonal planes and long axis of right ventricle. A total of six patients were identified for inclusion. The path from the ventricles to each respective outflow tract and the location of the VSD with respect to each great vessel was visualized clearly in all patients. Measurements on the virtual model showed excellent correlation with the source CMR when all measurements were included by Pearson coefficient, r = 0.99 as well as for each individual structure. Construction of virtual 3D models in patients with complex conotruncal defects from 3D CMR datasets allows for simultaneous visualization of anatomic relationships relevant for surgical repair. The availability of these models may allow for a more informed preoperative evaluation in these patients.     

Non-enhanced ECG-gated respiratory-triggered 3-D steady-state free-precession MR angiography with slab-selective inversion: initial experience in visualisation of renal arteries in free-breathing children without renal artery abnormality

Background

ECG-gated non-enhanced balanced steady-state free precession (bSSFP) MR angiography requires neither breath-holding nor administration of contrast material.

Objective

To investigate the image quality of free-breathing ECG-gated non-enhanced bSSFP MR angiography of renal arteries in children.

Materials and methods

Fourteen boys and seven girls (mean age, 9.7?years; range, 7?weeks–17?years) with no history of renovascular disease were included. MRI was performed at 1.5?T. Subjective image quality of axial and coronal maximum-intensity-projection reconstructions of four segments (I, aorta and renal artery ostium; II, main renal artery; III, segmental branches; IV, intrarenal vessels) was evaluated using a 4-point scale (4?=?excellent, 3?=?good, 2?=?acceptable, 1?=?non-diagnostic).

Results

Image quality was excellent for segments I (mean ± SD, 3.9?±?0.3) and II (4.0?±?0.1), good for segment III (3.4?±?0.9) and acceptable for segment IV (2.3?±?1.1 ). Mean image quality did not differ between sedated and non-sedated children.

Conclusion

bSSFP MR angiography enables visualisation of renal arteries in children.     

Valved shunt as a treatment for obstructive uropathy: does pressure make a difference?

Purpose

A valved ventriculo-peritoneal shunt (V-P shunt) as a vesico-amniotic shunt (V-A shunt) preserves the filling/emptying cycle and normal bladder development in fetal lambs with bladder outlet obstruction. The optimal pressure for such shunts is unknown.

Materials and methods

We created obstructive uropathy in 60-day gestation fetal lambs. A V-A shunt was placed 3 weeks later, using a low-pressure (Group L: 15–54 mmH₂O) or a high-pressure (Group H: 95–150 mmH₂O) V-P shunt. We included non-shunted (obstructive uropathy, Group O) and control lambs (Group C). All were delivered at 130 days. Bladder volumes, bladder thickness, renal and bladder histology were compared.

Results

Seventeen lambs had an obstructive uropathy created. Five Group L (four survived), four Group H (three survived) and five Group O survived. Body weight and crown-to-rump lengths of the three groups were not significantly different. Group H lambs had a dilated urachus, urinary ascites and severe ureteral dilatation similar to Group O lambs. There were four Group C lambs. Bladder volume was 10, 15 and 1,150 ml in Group H, 115 ± 67.9 ml in Group L, 128 ± 99.8 ml in Group O and 24.5 ± 3.84 ml in Group C. Unlike Group O lambs, Group L did not have urinary ascites, urinomas or renal dysplasia.

Conclusion

Low-pressure shunts preserved both bladder volume and renal development. High-pressure shunts did neither.     

Right Ventricular Apical Flattening as an Echocardiographic Screening Tool for Right Ventricular Enlargement

Right ventricular dilation is a common complication after tetralogy of Fallot (TOF) repair. Traditional echocardiographic assessments are imprecise due to the RV’s location and complex geometry. We propose a novel echocardiographic measurement: RV apical flattening (RVAF) as a screening tool to help identify subjects with severe RV dilation. Patients with repaired TOF who had both echocardiograms and CMR’s within 6-month interval at our institution were included in the study. The RVAF was measured in the four-chamber echocardiographic view as the minor length of RV cavity at the level of RV apical endocardium. Subjects were divided into two groups (group I: RVEDVi ≥ 150 ml/m² and group II; RVEDVi < 150 ml/m²). Echocardiogram and CMR data were compared between groups. A total of 75 subjects were included in the study. Mean age was 12.8 ± 3.6 years. Group I had 36 subjects, and group II had 39 subjects. The mean RVAF was significantly higher in group I (2.7 ± 0.5 cm) compared with group II (1.7 ± 0.4 cm; p < 0.001). There was significant correlation between RVAF and RVEDVi (r = 0.81; p < 0.001). By ROC analysis, an RVAF cutoff value of 2.0 cm had 94 % sensitivity and 77 % specificity in identifying severe RV dilation (area under the curve 0.95). RVAF is a simple and effective echocardiographic screening tool to help identify severe RV dilation. In conjunction with other 2D echocardiographic parameters, this technique would help further refine echocardiography-guided patient selection for timing of CMR and pulmonary valve replacement.     

Novel Cardiac Magnetic Resonance Feature Tracking (CMR-FT) Analysis for Detection of Myocardial Fibrosis in Pediatric Hypertrophic Cardiomyopathy

Myocardial fibrosis is a risk factor for sudden cardiac death in hypertrophic cardiomyopathy (HCM) and is conventionally identified by cardiac magnetic resonance imaging (CMR) using late gadolinium enhancement (LGE). This study evaluates utility of a novel 16-segment CMR feature tracking (CMR-FT) technique for measuring left ventricular (LV) strain (S) and strain rate (SR) on non-contrast cine images to detect myocardial fibrosis in pediatric HCM. We hypothesized that CMR-FT-derived S and SR will accurately differentiate HCM patients with and without myocardial fibrosis. Consecutive children with HCM who underwent CMR with LGE at our institution from 2006 to 2014 were included. Global and regional longitudinal, radial and circumferential S and SR of the LV in 2D and 3D were obtained using a CMR-FT software. Comparisons were made between HCM patients with (+LGE) and without (?LGE) delayed enhancement. Of the 29 HCM patients (mean age 13.5 ± 6.1 years; 52 % males), 11 (40 %) patients (mean age 17.5 ± 8.4 years) had +LGE. Global longitudinal, circumferential and radial S and SR were lower in +LGE compared to ?LGE patients, in both 2D and 3D. Regional analysis revealed lower segmental S and SR in the septum with fibrosis compared to free wall without fibrosis. A global longitudinal S of ≤ ?12.8 had 91 % sensitivity and 89 % specificity for detection of LGE. In pediatric HCM patients with myocardial fibrosis, global LV longitudinal, circumferential and radial S and SR were reduced, specifically in areas of fibrosis. A global longitudinal S of ≤ ?12.8 detected patients with fibrosis with high degree of accuracy. This novel CMR-FT technique may be useful to identify myocardial fibrosis and risk-stratify pediatric HCM without use of contrast agents.     

Great Vessel Root and Artery Dimensions in Transposition of the Great Arteries Repaired With Atrial Switch Operation

To describe great-vessel dimensions in patients with D-loop transposition of the great arteries (TGA) who have undergone atrial switch operation (ATSO). Patients who have undergone arterial switch operation for TGA have a high incidence of dilation of the neoaortic root. The incidence and degree of great artery dilation in patients who have undergone ATSO for TGA has not previously been described. A retrospective database review identified patients with TGA and intact ventricular septum who underwent ATSO at <1 year of age with cardiac magnetic resonance (CMR) within the previous 5 years (n = 39). A control group of patients referred for CMR with normal findings was identified for comparison (n = 40). Measurements of the annulus, root, sinotubular junction, and great vessels were performed, and interobserver/intraobserver variability was assessed. Median age of subjects at ATSO was 3 months (range 1–12) with median age at CMR of 29 years (range 18–40). For aortic measurements, mean z scores (± SDs) for patients relative to body surface area (BSA)–adjusted normal controls were as follows: annulus 1.41 (0.80), root 2.04 (1.48), sinotubular junction 2.16 (1.26), and great vessel 1.86 (1.53). For pulmonary measurements, similar values were as follows: annulus 1.82 (1.42), root 3.25 (2.01), sinotubular junction 2.47 (1.79), and great vessel 3.96 (3.08). In all cases, the p value was <0.001, and no confidence interval included the value 0. Adult patients with TGA repaired with ATSO in infancy have a greater incidence of dilation of both great vessels, particularly the pulmonary artery. These results may indicate abnormalities in the vascular structure of both great arteries in TGA that may predispose to progressive arterial dilation.     

Arrhythmia Detection in Pediatric Patients: ECG Quality and Diagnostic Yield of a Patient-Triggered Einthoven Lead-I Event Recorder (Zenicor <Emphasis Type="Italic">EKG</Emphasis>-<Emphasis Type="Italic">2™</Emphasis>)

Symptoms that may be caused by arrhythmia are common in pediatric outpatient departments, though it remains challenging to reveal paroxysmal tachycardia. This investigation evaluated prospectively the quality and diagnostic yield of a newly available handheld patient-activated event recorder (ER) in children. In 226 children (pts) aged 0–17 years with or without congenital heart defects, pacemaker/ICDs or arrhythmia, a lead-I ER ECG was created. ER ECGs were recorded by pressing the patients’ thumbs on the device and were analyzed in comparison with a lead-12 ECG, as gold standard. Event recording and data transmission were possible in all cases. ECG quality of the ER showed a high accordance in measuring heart rate (ICC = 0.962), duration of QRS complexes (κ = 0.686), and PR interval (ICC = 0.750) (p < 0.001) although P wave detection remained challenging (p = 0.120). 36 % (n = 82) of the pts had heart rhythm disturbances. The ER yielded 92 % sensitivity in diagnosing supraventricular tachycardia plus 77 % sensitivity and 92 % specificity in identifying abnormal ECGs. In children, the application of the tested ER was suitable. ECGs of good quality could be performed and transmitted easily, and also complex arrhythmia analysis was possible. This ER is an excellent diagnostic device for the detection and exclusion of tachycardia in children.     

Tricuspid Annular Plane Systolic Excursion Does Not Correlate With Right Ventricular Ejection Fraction in Patients With Hypoplastic Left Heart Syndrome After Fontan Palliation

Tricuspid annular plane systolic excursion (TAPSE) reflects longitudinal myocardial shortening, the main component of right ventricular (RV) contraction in normal hearts. To date, TAPSE has not been extensively studied in patients with hypoplastic left heart syndrome (HLHS) and systemic RVs after Fontan palliation. This retrospective study investigated HLHS patients after Fontan with cardiac magnetic resonance (CMR) performed between 1 January 2010 and 1 August 2012 and transthoracic echocardiogram (TTE) performed within 6 months of CMR. The maximal apical displacement of the lateral tricuspid valve annulus was measured on CMR (using four-chamber cine images) and on TTE (using two-dimensional apical views). To create TTE–TAPSE z-scores, published reference data were used. Intra- and interobserver variability was tested with analysis of variance. Inter-technique agreement of TTE and CMR was tested with Bland–Altman analysis. In this study, 30 CMRs and TTEs from 29 patients were analyzed. The age at CMR was 14.1 ± 7.1 years, performed 11.9 ± 7.8 years after Fontan. For CMR–TAPSE, the intraclass correlation coefficients for inter- and intraobserver variability were 0.89 and 0.91, respectively. The TAPSE measurements were 0.57 ± 0.2 cm on CMR and 0.70 ± 0.2 cm on TTE (TTE–TAPSE z score, ?8.7 ± 1.0). The mean difference in TAPSE between CMR and TTE was ?0.13 cm [95 % confidence interval (CI) ?0.21 to ?0.05], with 95 % limits of agreement (?0.55 to 0.29 cm). The study showed no association between CMR–TAPSE and RVEF (R = 0.08; p = 0.67). In patients with HLHS after Fontan, TAPSE is reproducible on CMR and TTE, with good agreement between the two imaging methods. Diminished TAPSE suggests impaired longitudinal shortening in the systemic RV. However, TAPSE is not a surrogate for RVEF in this study population.     

Infant Cardiac Magnetic Resonance Imaging Using Oscillatory Ventilation: Safe and Effective

Cardiac magnetic resonance imaging (CMR) for infants and young children typically requires sedation. General anesthesia with controlled ventilation can eliminate motion artifact with breath-holds during imaging to limit respiratory artifact, but these may lead to atelectasis or other complications. High-frequency oscillatory ventilation (HFOV) provides ventilation with near-constant mean airway pressure and minimal movement of chest wall and diaphragm, thus obviating the need for breath-holding. Clinical data were collected for 8 infants who underwent CMR with HFOV and 8 controls who underwent CMR with conventional ventilator and breath-hold technique. Data included demographic information, adverse events, and scan-acquisition time. Studies were reviewed for image quality by two cardiologists who were blinded to type of ventilation. There were no significant differences in patient characteristics between the two groups. There was no significant difference in average image quality for cine short-axis or black blood imaging. Total CMR scan time was not significantly different between groups, but the short-axis cine stack was acquired more quickly in the HFOV group (1.8 ± 0.8 vs. 5.0 ± 3.6 min). There were no adverse events in the HFOV group, but scans were terminated early for two patients in the conventional ventilator group. HFOV during CMR is feasible and well tolerated. Image quality is equivalent to that obtained with conventional ventilation with breath-holding technique and allows shorter cine scan times for some sequences.     

Posterior sagittal anorectoplasty in vestibular fistula: with or without colostomy

Purpose

The aim of this study is to compare the results and complications of one- and three-stage repairs in females with vestibular fistula (VF) and make contribution to the discussion of whether the disadvantages outweigh the protective effect of a colostomy from wound infection and wound dehiscence following posterior sagittal anorectoplasty (PSARP).

Methods

Patients with a diagnosis of VF who underwent PSARP between October 2009 and November 2015 were retrospectively reviewed. The patients were divided into two groups: Group 1—patients treated by one-stage procedure (n = 30); Group 2—patients treated by three-stage procedure (n = 16).

Results

There were no statistically significant differences between the groups with respect to wound infection, recurrence of fistula and rectal mucosal prolapse. Minor wound dehiscence occurred slightly more common in Group 1, even if p value is not significant. No wound dehiscence has been observed since we switched to the protocol of keeping the child nil per oral for 5 postoperative days and loperamide (0.1 mg/kg) administration for 7 postoperative days. The mean time before resuming oral intake was 2.87 ± 1.7 and 1.19 ± 0.4 days in Group 1 and Group 2, respectively (p = 0.001). None developed major wound disruption or anal stenosis in either group. There were no statistical differences between the groups in terms of voluntary bowel movements, soiling and constipation.

Conclusions

PSARP performed without a protective colostomy in patients with VF has low morbidity, good continence rates and obvious advantages for both the patients and their parents.

     

The effect of the broad-spectrum antibiotics for prevention of postoperative intra-abdominal abscess in pediatric acute appendicitis

Background

We investigated the efficacy of broad-spectrum antibiotics for prevention of postoperative intra-abdominal abscess in pediatric acute appendicitis with our 3 risk factors:—WBC?>?16.5 (×?10³/µl), CRP?>?3.1 (mg/dl) and appendix maximum short diameter on diagnostic imaging?>?11.4 mm.

Methods

Four hundred twenty-two patients were reviewed. Patients with 0–1 risk factors were assessed as low-risk and those with 2–3 were high-risk. In the low-risk group, Group A (n?=?66) patients received broad-spectrum antibiotics and Group B patients (n?=?265) received narrow-spectrum monotherapy. In the high-risk group, Group C patients (n?=?63) received broad-spectrum antibiotics and Group D patients (n?=?28), narrow-spectrum antibiotics. The outcomes were the incidence of postoperative abscess and the total duration of intravenous (IV) antibiotics.

Results

The incidence of intra-abdominal abscess was 6.06% in Group A versus 1.89% in Group B (p?=?0.08), and 19.05% in Group C versus 3.57% in Group D (p?=?0.06). Total IV antibiotic duration (days) were 6.12?±?2.87 in Group A versus 3.83?±?0.69 in Group B (p?<?0.01), and 7.84?±?4.57 in Group C versus 4.00?±?0.82 in Group D (p?<?0.01).

Conclusion

Broad-spectrum antibiotics did not prevent postoperative intra-abdominal abscess in either low or high-risk groups.

     

5/6 Area Length Method for Left-Ventricular Ejection-Fraction Measurement in Adults with Repaired Tetralogy of Fallot: Comparison with Cardiovascular Magnetic Resonance

In patients with repaired tetralogy of Fallot (rTOF), left-ventricular ejection fraction (LVEF) predicts adverse outcomes. Two-dimensional echocardiographic (2DE) methods of measuring LVEF require geometric assumptions and may be limited in this population due to altered ventricular geometry. This study evaluated the performance of the 5/6 area × length (AL) method in this population as well as which factors limit agreement with the results of cardiovascular magnetic resonance (CMR). In 20 patients with rTOF (28.5 ± 14.7 years old) and CMR and 2DE within 3 months, two investigators blinded to CMR measured LVEF from 2DE by the AL method, biplane Simpson’s (BiS) method, and visual estimate. Two investigators blinded to 2DE measured LVEF from CMR by Simpson’s and AL methods. The AL method on 2DE more closely approximated LVEF by CMR (r = 0.73, p = 0.0003) than BiS method (r = 0.53, p = 0.02). AL method was not limited by geometric assumptions, as AL method on CMR closely approximated Simpson’s method on CMR (r = 0.90, p < 0.0001) despite median left-ventricular diastolic eccentricity index of 1.24. AL method on 2DE was primarily limited by short-axis area measurement rather than foreshortening of the ventricle. In conclusion, in adults with rTOF, AL method on 2DE moderately approximates LVEF by CMR, even in the context of altered left-ventricular geometry. Although the AL method may be the most appropriate 2DE method in this population, significant limitations remain for LVEF assessment by 2DE, and strategies to optimize image position and border detection are essential.     

Relation between amount of bile ducts in portal canal and outcomes in biliary atresia

Background

There is no good prognostic indicator for biliary atresia (BA). We reviewed liver biopsies taken during the initial procedure to find a prognostic marker.

Methods

Thirty-two BA cases underwent Kasai operation from 1976 to 2009. We compared two groups at 1, 3, and 9 years. Group A required liver transplantation or died. Group B survived with their native liver. Biopsies were analyzed for liver fibrosis, portal-central vein bridging (P–C bridging), ductal plate malformation (DPM) and the number of the bile ducts in portal canal/measured surface area of the portal canal (BDP ratio). Statistical comparisons of the multiple data were evaluated by Mann–Whitney U test, Student’s t test and Pearson’s Chi-square test. Regression analysis with P < 0.05 was considered significant.

Results

BDP ratios (/mm²) were 2.4 ± 1.5 in Group A1 (n = 9) vs 4.6 ± 2.4 in Group B1 (n = 23) (P = 0.01); 2.6 ± 1.4 in Group A3 (n = 14) vs 5.1 ± 2.5 in Group B3 (n = 18) (P < 0.01), 3.0 ± 2.2 in Group A9 (n = 15) vs 4.9 ± 2.5 in Group B9 (n = 15) (P < 0.05). There was no significant difference in any other finding.

Conclusion

The BDP ratio is a sound prognostic indicator in BA.

     

Predictive Value of Myocardial Delayed Enhancement in Duchenne Muscular Dystrophy

In other cardiomyopathies, cardiac magnetic resonance imaging (CMR)-derived myocardial delayed enhancement (MDE), a marker of myocardial fibrosis, is a risk factor for sudden cardiac death (SCD). In Duchenne muscular dystrophy (DMD), the prognostic value of MDE for ventricular arrhythmias and death is unknown. This study aimed to evaluate associations between MDE and electrocardiographic (ECG) changes, ventricular remodeling, risk of arrhythmias, and death in DMD. This retrospective study included all subjects with DMD who had undergone a CMR between January 2006 and December 2011 and had available ECG and 24-h Holter records from the same period. Left ventricular (LV) MDE was semiquantitatively graded from 0 to 4. Comparisons of demographic and clinical characteristics between MDE and no-MDE groups were made. Cox regression analysis was performed to assess factors associated with death. This study investigated 32 boys with a median age of 13.8 years (range, 7.2–17.4 years) and found MDE present in 25 (78 %) of the boys. Compared with the no-MDE subjects, the MDE subjects were older (15.7 ± 3.3 vs 12.1 ± 4.8 years) and had a wider QT dispersion (QTd: 74 ± 30 vs 55 ± 33 ms), a higher incidence of ventricular tachycardia (40 vs 0 %), a lower LV ejection fraction (46 ± 12 vs 56 ± 9 %), a larger LV end-diastolic volume (124 ± 58 vs 68 ± 14 ml/m²), and a larger end-systolic volume (57 ± 29 vs 28 ± 10 ml/m²) (p < 0.05 for all). During the study period, six of the subjects (19 %) died. The factors associated with mortality were increased age, advanced grade of MDE, higher LV end-systolic volume, lower LV ejection fraction, use of beta-blockers, and ventricular tachycardia. Myocardial fibrosis detected by CMR is an independent predictor of adverse cardiac remodeling, ventricular arrhythmias, and death in DMD. Cardiac MRI using MDE can be applied as a screening tool to detect patients at risk for ventricular arrhythmias, more advanced disease, adverse LV remodeling, and death.     

Clinical application of a three-dimensional imaging technique in infants and young children with complex liver tumors

Introduction

Three-dimensional (3D) imaging instead of two-dimensional (2D) computed tomography (CT) for diagnosis and preoperative planning in infants and young children with complex liver tumors is a promising technique for precision hepatectomy.

Methods

This study was a retrospective analysis of 26 infants and young children with giant liver tumors involving the hepatic hilum who underwent precise hepatectomy at the Affiliated Hospital of Qingdao University between February 2012 and January 2015. All patients received upper abdominal contrast-enhanced CT scanning before surgery. 16 patients used Hisense CAS system for 3D reconstruction as the reconstruction group. While ten patients underwent 3D CT reconstruction by the CT Workstation as the control group. The clinical outcomes were analyzed and compared between the two groups. The 3D reconstruction of abdominal organs and blood vessels was generated using the Hisense CAS system. Diagnosis and preoperative planning assisted by the system was used for preoperative and intraoperative decision-making for precise hepatectomy.

Results

All patients underwent successful surgery. The 3D models clearly demonstrated the association of liver tumors with the intrahepatic vascular system and provided a preoperative assessment of resectability, assisting surgeons in preoperative procedural planning. Anatomic hepatectomy was successfully completed in the reconstruction group. The mean operation time was shorter in the reconstruction group (137.81 ± 17.51 min) than in the control group (192 ± 34.66 min) (P < 0.01). The mean intraoperative blood loss was lesser in the reconstruction group (21.81 ± 14.05 ml) than in the control group (53.50 ± 21.35 ml) (P < 0.01). The difference was statistically significant.

Discussion

2D CT scan images cannot accurately display the spatial relationship between the tumor and surrounding vasculature. The 3D reconstruction model used in this study gave detailed and accurate anatomical information and allowed for the assessment of tumor resectability and provided a detailed road map for preoperative decision-making and predicted the postoperative liver function.

Conclusions

3D visualization technology provides preoperative assessment and allows individualized surgical planning. Surgical controllability, accuracy, and safety can be improved in infants and young children undergoing precise hepatectomy for complex liver tumors.

     

Effect of Inhaled Nitric Oxide on Blood Flow Dynamics in Patients After the Fontan Procedure Using Cardiovascular Magnetic Resonance Flow Measurements

Invasive hemodynamic studies have shown that nitric oxide (NO), a selective pulmonary vasodilator, can lower pulmonary vascular resistance in Fontan patients. Because oximetry-derived flow quantification may be unreliable, we sought to detect changes in blood flow within the Fontan circulation after inhalation of NO using cardiovascular magnetic resonance (CMR). Thirty-three patients (mean age 12.8 ± 7.0 years) after the Fontan procedure underwent CMR as part of their routine clinical assessment. Standard two-dimensional blood flow measurements were performed in the Fontan tunnel, superior vena cava (SVC) and ascending aorta (AAO) before and after inhalation of 40 ppm NO for 8–10 min. Systemic-to-pulmonary collateral (SPC) flow was calculated as AAO ? (SVC + tunnel). Heart rate (82 ± 18 to 81 ± 18 bpm; p = 0.31) and transcutaneous oxygen saturations (93 ± 4 to 94 ± 3 %; p = 0.13) did not change under NO inhalation. AAO flow (3.23 ± 0.72 to 3.12 ± 0.79 l/min/m²; p = 0.08) decreased, tunnel flow (1.58 ± 0.40 to 1.65 ± 0.46 l/min/m²; p = 0.032) increased, and SVC flow (1.01 ± 0.39 to 1.02 ± 0.40 l/min/m²; p = 0.50) remained unchanged resulting in higher total caval flow (Qs) (2.59 ± 0.58 to 2.67 ± 0.68 l/min/m²; p = 0.038). SPC flow decreased significantly from 0.64 ± 0.52 to 0.45 ± 0.51 l/min/m² (p = 0.002) and resulted in a significant decrement of the Qp/Qs ratio (1.23 ± 0.23 to 1.15 ± 0.23; p = 0.001). Inhalation of NO in Fontan patients results in significant changes in pulmonary and systemic blood flow. The reduction in SPC flow is accompanied by a net increase in effective systemic blood flow suggesting beneficial effects of pulmonary vasodilators on cardiac output, tissue perfusion and exercise capacity.     

Prognostic factors indicating survival with native liver after Kasai procedure for biliary atresia

Background

The number of the bile ducts in the portal canal/measured surface area of the portal canal (BDP ratio) indicates prognosis in biliary atresia (BA), as does an elevated cytokeratin 7 positivity percentage (PCK7). We compared these two markers.

Methods

We reviewed 32 BA cases undergoing Kasai operation from 1976 to 2016 with >5 portal canals in biopsy samples. Group I required liver transplantation or died within a year of operation (n = 8). Group II survived with their native liver (n = 24). We determined the BDP ratio (10²/mm²) and PCK7 (%), subdividing patients into three groups by their age at operation: Group A ≤60 days (n = 6, 1 Group I), 60< Group B ≤90days (n = 16, 5 Group I), Group C >90 days (n = 10, 2 Group I).

Results

PCK7 (%) was 2.71 ± 1.87 in Group I and 4.25 ± 2.56 in Group II (p = 0.13). BDP ratio (10²/mm²) was 1.19 ± 0.424 in Group I and 1.64 ± 0.534 in Group II (p = 0.04). Both markers were higher in Group C than in Group A or B (p < 0.01).

Conclusion

The BDP ratio is a better prognostic indicator than PCK7 in BA.

     

Relationship of Right Ventricular Size and Function with Respiratory Status in Duchenne Muscular Dystrophy

The relationship between pulmonary function and right ventricle (RV) in Duchenne muscular dystrophy (DMD) has not been evaluated. Using cardiac magnetic resonance (CMR), we describe the relationship of RV size and function with spirometry in a DMD cohort. Fifty-seven boys undergoing CMR and pulmonary function testing within 1 month at a single center (2013–2015) were enrolled. Comparisons of RV ejection fraction (RVEF) and end-diastolic volume index (RVEDVI) were made across categories of percent forced vital capacity (FVC%), and relationships were assessed. Mean age was 15.5 ± 3.5 years. Spirometry and CMR were performed within 3.9 ± 4.1 days. Median FVC% was 92.0 % (67.5–116.5 %). Twenty-three (40 %) patients had abnormal FVC% (<80 %) of which 13 (57 %) had mild (FVC% 60–79 %), 6 (26 %) had moderate (FVC% 40–59 %), and 4 (17 %) had severe (FVC <40 %) reductions. Mean RVEF was 58.3 ± 3.7 %. Patients with abnormal FVC% were older and had lower RVEF and RVEDVI. Both RVEF and RVEDVI were significantly associated with FVC% (r = 0.31, p = 0.02 and r = 0.39, p = 0.003, respectively). In a large DMD cohort, RVEF and RVEDVI were related to FVC%. Worsening respiratory status may guide monitoring of cardiac function in these patients.     

Propitious role of bone marrow-derived mononuclear cells in an experimental bile duct ligation model: potential clinical implications in obstructive cholangiopathy

Purpose

To evaluate the role of bone marrow-derived mononuclear cells (BMC) in rat bile duct ligation (BDL) model.

Methods

Wistar rats were categorized into four Groups A–D. Normal liver biopsy was taken from Group A. BDL model was created in Groups B and C (15 each). Normal saline and BMC were injected through portal vein (PV) in Groups B and C, respectively. In Group D (healthy rat), only BMC were infused through PV. Groups B and C were compared for body weight, liver functions, survival, and histopathological changes.

Results

Serum bilirubin was lower in Group C at day 6 (p = 0.0010). Median survival time was 5 (4, 6) and 13 (9, 17) days in Groups B and C (p = 0.0147), respectively. Portal edema (p = 0.013) and portal inflammation (p = 0.025) were less in Group C vs Group B. On post hoc subgroup analysis of rats surviving 8–26 days, portal inflammation (p = 0.004), bile duct proliferation (p = 0.016) and portal fibrosis (p = 0.038) were less in Group C vs Group B. Hepatocyte regeneration was found in four rats in Group C. CD34-positive cells were prominent in sinusoids and portal tracts in the BDL rat model.

Conclusions

BMC have shown to delay fibrosis, facilitate hepatocyte regeneration and improve survival in an experimental BDL model, with potential clinical implication in obstructive cholangiopathy.     

Mesenchymal expression of the <Emphasis Type="Italic">FRAS1/FREM2</Emphasis> gene unit is decreased in the developing fetal diaphragm of nitrofen-induced congenital diaphragmatic hernia

Purpose

Developmental mutations that inhibit normal formation of extracellular matrix (ECM) in fetal diaphragms have been identified in congenital diaphragmatic hernia (CDH). FRAS1 and FRAS1-related extracellular matrix 2 (FREM2), which encode important ECM proteins, are secreted by mesenchymal cells during diaphragmatic development. The FRAS1/FREM2 gene unit has been shown to form a ternary complex with FREM1, which plays a crucial role during formation of human and rodent diaphragms. Furthermore, it has been demonstrated that the diaphragmatic expression of FREM1 is decreased in the nitrofen-induced CDH model. We hypothesized that FRAS1 and FREM2 expression is decreased in the developing diaphragms of fetal rats with nitrofen-induced CDH.

Methods

Pregnant rats were exposed to either nitrofen or vehicle on gestational day 9 (D9), and fetuses were harvested on D13, D15 and D18. Microdissected diaphragms were divided into nitrofen-exposed/CDH and control samples (n = 12 per time-point and experimental group, respectively). Diaphragmatic gene expression levels of FRAS1 and FREM2 were analyzed by qRT-PCR. Immunofluorescence double staining for FRAS1 and FREM2 was combined with the mesenchymal marker GATA4 in order to evaluate protein expression and localization in pleuroperitoneal folds (PPFs) and fetal diaphragmatic tissue.

Results

Relative mRNA expression of FRAS1 and FREM2 were significantly reduced in PPFs of nitrofen-exposed fetuses on D13 (1.76 ± 0.86 vs. 3.09 ± 1.15; p < 0.05 and 0.47 ± 0.26 vs. 0.82 ± 0.36; p < 0.05), developing diaphragms of nitrofen-exposed fetuses on D15 (1.45 ± 0.80 vs. 2.63 ± 0.84; p < 0.05 and 0.41 ± 0.16 vs. 1.02 ± 0.49; p < 0.05) and fully muscularized diaphragms of CDH fetuses on D18 (1.35 ± 0.75 vs. 2.32 ± 0.92; p < 0.05 and 0.37 ± 0.24 vs. 0.70 ± 0.32; p < 0.05) compared to controls. Confocal laser scanning microscopy revealed markedly diminished FRAS1 and FREM2 immunofluorescence in diaphragmatic mesenchyme, which was associated with reduced proliferation of mesenchymal cells in nitrofen-exposed PPFs and fetal CDH diaphragms on D13, D15 and D18 compared to controls.

Conclusion

Decreased mesenchymal expression of FRAS1 and FREM2 in the nitrofen-induced CDH model may cause failure of the FRAS1/FREM2 gene unit to activate FREM1 signaling, disturbing the formation of diaphragmatic ECM and thus contributing to the development of diaphragmatic defects in CDH.