Postoperative graft thrombosis in Fontan procedure

Fontan repair could be used as the definitive palliation in many forms of complex cyanotic congenital heart disease. But thrombosis can occur after a modified Fontan operation (right atrium-right ventricular connection with a conduit). Appropriate management of this complication includes thrombolytic therapy, thrombectomy and revision (if surgically remediable causes of the thrombosis are identified) or redo operation. Two repair operations were performed for the treatment of thrombosis of the right side of the heart in patients in whom we had previously performed Bjork modification (right atrium-right ventricular connection with a conduit). The thromboses occurred 6 and 9 years after the operation, respectively. In both cases, the redo Fontan operation was successfully performed using a dacron tube graft. Patients were anticoagulated after the operation. Risk of thrombosis of the right side of the heart after the Fontan repair may be minimized with the use of prophylactic anticoagulation in high-risk patients soon after the operation.     

Liver abnormalities and post‐transplant survival in pediatric Fontan patients

The impact of liver parenchymal abnormalities on survival post‐heart transplant remains unknown in pediatric Fontan patients. We assessed pediatric Fontan patients who underwent heart transplant and had documented pretransplant hepatic ultrasound (U/S) studies. Liver U/S findings were classified as normal (Group 1), mildly abnormal (Group 2, hepatomegaly/vascular congestion), or severely abnormal (Group 3, heterogeneous echotexture/nodularity). Among 30 study patients, 8 were classified as Group 1, 14 as Group 2, while 8 met Group 3 criteria. Pretransplant liver biochemistry and synthetic function were similar in all groups. Six Group 3 patients underwent liver biopsy; 4 demonstrated perisinusoidal or centrilobular fibrosis, and 2 had cirrhosis. Overall mortality was 30% (n = 9). Median follow‐up was 5 years (range, 0.25‐13 years). One‐year survival was similar among all 3 groups (P = .37), with a trend toward higher cumulative 5‐year survival in Group 1 (100%). The majority of pediatric Fontan patients who underwent heart transplant demonstrated abnormal preoperative liver ultrasound findings. Heterogeneous echotexture or nodularity detected on U/S frequently indicates underlying liver parenchymal abnormalities. The presence of severe liver abnormalities was not associated with higher early mortality post‐heart transplant in pediatric Fontan patients; however, late outcomes must be further elucidated.     

Effectiveness of Carvedilol for Congestive Heart Failure that Developed Long after Modified Fontan Operation

We report a case of a patient with severe heart failure after Fontan procedure in whom carvedilol was very effective. A 27-year-old man had intractable congestive heart failure due to severe ventricular dysfunction after Fontan operation. Central venous pressure was elevated to 29 mmHg. A right-to-left shunt was noted across a large collateral vessel between the innominate vein and the pulmonary vein. He was administered carvedilol (initial dose, 2 mg/day; maximum dose, 30 mg/day). Cardiac catheterization performed 1 year after carvedilol administration revealed a decrease in atrial pressure and improvement of ventricular function. He underwent a conversion operation to total cavopulmonary connection (TCPC) and ligation of a collateral vein communicating with the innominate and pulmonary veins. Carvedilol may be a legitimate treatment before TCPC conversion or heart transplantation for the high-risk group of patients with a failed Fontan circulation.     

Cardiac Dysrhythmias in Pediatric Patients Before and 1 Year After Transcatheter Closure of Atrial Septal Defects Using the Amplatzer Septal Occluder

To prospectively assess the incidence of cardiac dysrhythmias before and after closure of atrial septal defects (ASDs) using the Amplatzer septal occluder (ASO), 24-hour Holter electrocardiograms (ECGs) were performed before and 1 year after the procedure in 23 pediatric patients (9 male and 14 female). Patients' ages ranged from 2 to 15 years (mean, 7.1 years). All had an ASD of the secundum type that was completely closed (n = 22) or had a small residual shunt (n = 1). No preexisting dysrhythmia was present in 22 patients; atrioventricular nodal reentrant tachycardia had been diagnosed in 1 patient. During the observation period, no clinical dysrhythmia occurred. Analysis of the Holter ECGs before the intervention showed regular sinus rhythm in 20 patients and sinus rhythm with intermittent atrial rhythm in 3 patients. Atrial premature complexes (APCs) were detected in 1 patient, and a ventricular couplet was present in 1 patient. The Holter ECG 1 year after the intervention showed sinus rhythm in 18 patients and sinus rhythm with intermittent atrial rhythm in 5 patients. APCs were still observed in 1 patient and seen for the first time in 1 patient; 1 patient and rare ventricular premature complexes. In conclusion, cardiac dysrhythmias on Holter ECG in pediatric patients before and 1 year after transcatheter ASD closure with the ASO device are rare and benign. Regular Holter monitoring seems to be useful in detecting late dysrhythmias.     

Sinus Node Dysfunction after Intraatrial Lateral Tunnel and Extracardiac Conduit Fontan Procedures

This study compares the effects of two techniques for the Fontan procedure-intraatrial lateral tunnel (IALT) and extracardiac conduit (ECC) -on sinus node dysfunction. Between January 1992 and December 1998, 54 patients underwent a total cavopulmonary connection Fontan procedure. Of these, 36 had follow-up 24-hour Holter recordings, and they constitute the population for this study. The 24-hour Holter recordings were performed between January 1998 and March 1999 and were evaluated for sinus node dysfunction and atrial tachycardia. Clinical follow-up (18 +/- 11 months for the IALT group vs 34 +/- 19 months for the ECC group; p = 0.002) and surface electrocardiograms were also reviewed. Among the 36 patients, 19 had an IALT and 17 had an ECC Fontan procedure. The incidence of sinus node dysfunction was 4/19 (21%) in the IALT group and 10/17 (59%) in the ECC group (p = 0.04). No patient from either group had an identified episode of atrial tachycardia. No permanent pacemaker was placed in the IALT group, whereas three were placed in the ECC group, all for sinus node dysfunction. In summary, patients with both IALT and ECC had an important incidence of sinus node dysfunction. The incidence of sinus node dysfunction was higher in the ECC group, which may have been due to longer follow-up in this group. Atrial tachycardia was not observed in either group. Although the IALT group had less sinus node dysfunction than the ECC group and appeared to require less permanent pacing, these data may be too limited to serve as the criteria for choosing between these two techniques for performing the Fontan procedure.     

The Fontan Patient: Inconsistencies in Medication Therapy Across Seven Pediatric Heart Network Centers

Patients who have undergone the Fontan procedure are at risk for thrombosis, ventricular dysfunction, and valve regurgitation, but data to guide the medical treatment and prevention of these adverse outcomes in this population are lacking. This analysis examined medication usage among Fontan patients by putative indication and by study center. The medical history and current medications of 546 Fontan subjects, ages 6–18 years, were assessed in a Pediatric Heart Network multicenter cross-sectional study. Cardiac imaging was performed within 3 months of enrollment. The majority of the subjects (64%) were taking two or more medications. Antithrombotics were taken by 86% of those with a history of stroke, thrombosis, or both and 67% of those without such a history (P = 0.01). Conversely, 14% of those with a history of stroke, thrombosis, or both were taking no antithrombotic. Angiotensin-converting enzyme inhibitor (ACEi) therapy was independently associated with moderate or severe atrioventricular valve regurgitation (P = 0.004), right ventricular morphology (P < 0.001), and shorter time since Fontan (P = 0.004) but not with ventricular systolic dysfunction. Glycoside therapy and diuretic therapy each was associated with older age at Fontan (P = 0.001 and P = 0.023, respectively) and a history of post-Fontan arrhythmia (P < 0.001 and P = 0.003, respectively) but not with ventricular systolic dysfunction. Medication use rates varied widely among the centers, even with controls for center differences in patient characteristics. Prospective therapeutic trials are needed to guide the medical treatment of Fontan patients.     

Serum soluble interleukin 2 receptor (sIL-2R) as a marker of acute rejection in renal transplant children

The aim of the study was to evaluate whether or not serum levels of soluble interleukin 2 receptor (sIL-2R) predict acute rejection in pediatric recipients. We studied 51 pediatric renal transplant recipients divided into three groups: Group 1) Biopsy-proven cellular acute rejection (n = 19), Group 2) Graft dysfunction with histological diagnosis other than acute rejection (n = 8) and Group 3) Patients with stable graft function, no biopsy (n = 24). Serum samples for sIL-2R measurement by sandwich ELISA were obtained at the time of renal transplant and at the time of renal biopsy due to graft dysfunction (Groups 1 and 2) or at six months post-transplant in the case of Group 3. The mean ± s.e. serum values of sIL-2R were higher in patients during acute rejection (6539 ± 1802 pg/mL) compared to patients with other causes of graft dysfunction (2217 ± 256 pg/mL) or stable graft function at six months (2183 ± 283 pg/mL) (Kruskal-Wallis p = 0.004). When the sIL2-R levels at the time of transplant were compared to those at the time of biopsy (Groups 1 and 2) or at six months post-transplant in Group 3, there was no significant difference between baseline and biopsy in the acute rejection group (paired t-test = 0.07), whereas there was a significant reduction in Groups 2 and 3.     

When should hydrocortisone therapy be instituted in children with hypopituitarism?

The records of 72 pediatric and adolescent patients with multiple hypothalamic and/or pituitary hormone deficiencies of nontumoral origin who were followed up for years and receiving somatotropin, thyroxine, and sex hormones at the appropriate age have been reviewed. According to their corticotropin-releasing factor-corticotropin-cortisol (CAC) axis function as evaluated by basal plasma cortisol levels and the response of cortisol to insulin hypoglycemia and to corticotropin-releasing factor, the patients were divided into three groups: group 1 (n = 25), patients with multiple hypothalamic and/or pituitary hormone deficiencies with normal CAC axis; group 2 (n = 38), patients with partial CAC deficiency without cortisol replacement therapy (hydrocortisone); and group 3 (n = 9), patients with CAC deficiency receiving hydrocortisone therapy (5 to 10 mg/d). Repeated CAC axis evaluation in patients of group 2 over years revealed a progressive decrease in the basal and stimulated cortisol levels with age and pubertal advancement. Despite the low cortisol levels and the low cortisol response to insulin hypoglycemia, these patients did not have clinical symptoms until the end of puberty when nine of 24 patients complained of abdominal pain, weakness, or anorexia. Linear growth, which was followed up in all patients at regular intervals, showed a lower growth velocity and irregular growth in response to somatotropin treatment in the patients receiving low doses of hydrocortisone (group 3 patients when compared with group 2 patients not receiving hydrocortisone).     

伴有并发症的儿童胆总管囊肿的临床处理

目的 讨论合伴有各类并发症的儿童胆总管囊肿的临床处理及手术时机和方法.方法 回顾性分析2013年1月至2015年12月上海新华医院小儿外科收治的45例合伴有各类并发症的儿童胆总管囊肿患儿的临床资料.其中,胆道穿孔7例,胆源性胰腺炎9例,胆管炎、阻塞性黄疸、肝功能受损29例,保守治疗效果不佳.7例胆道穿孔中,5例胆汁性腹膜炎行囊肿外引流和二期根治术;2例隐匿性胆道穿孔一期行根治术.9例胆源性胰腺炎给予内镜下鼻胆管引流,待淀粉酶正常后一期行根治术.29例阻塞性黄疸伴肝功能受损的患儿中,17例发病年龄小于3个月行一期根治手术;12例发病年龄大于6个月患儿先行ERCP置鼻胆管引流,待黄疸消退、转氨酶正常后一期行根治性手术.结果 伴胆道穿孔的7例胆总管囊肿患儿中,2例在外引流期间出现水电解质紊乱,1例T管脱落,1例隐匿性穿孔在根治术后出血再次手术,余者术后均痊愈出院.9例胆源性胰腺炎患儿置鼻胆管引流后淀粉酶均恢复正常,根治术后均痊愈出院.并发急性胆管炎、伴有梗阻性黄疸、肝功能受损29例中,12例发病年龄大于6个月,其中11例行内镜下置鼻胆管引流后并发症改善行根治手术,1例ERCP失败后改行外引流和二期根治术;小于3月龄婴儿直接行一期根治性手术,术后均痊愈出院.所有患儿保持随访,术后随访时间1～3年.1例术后慢性胰腺炎史,1例胆管炎史,均通过药物治疗缓解症状.结论 对合伴有各类并发症的儿童胆总管囊肿选择合理的处理手段和合适的手术方式将有效减少并发症所造成的危害.     

NT-proBNP as a Marker for Persistent Cardiac Disease in Children with History of Dilated Cardiomyopathy and Myocarditis

Children with myocarditis and dilated cardiomyopathy may recover clinically and echocardiographically. Plasma levels of the N-terminal segment of B-type natriuretic peptide prohormone (NT-proBNP), a sensitive marker for cardiac dysfunction, may reflect residual cardiac damage in these patients. The purpose of this study was to evaluate NT-proBNP status in pediatric patients with a history of myocarditis and dilated cardiomyopathy. Cardiac evaluation was performed and the levels of NT-proBNP were measured in 23 children who had a history of myocarditis or dilated cardiomyopathy. NT-proBNP levels were also measured in 56 age-matched control children. Nine of the 23 patients had evidence of left ventricular dysfunction (DCM group), whereas 14 had none (recovery). NT-proBNP levels were higher in the DCM group (3154 ± 2858 pg/ml) than in the recovery group (122 ± 75 pg/ml, p < 0.001) and the control group (113 ± 96 pg/ml, p < 0.001). There was no difference between the recovery and the control groups (p = 0.45), and none of the recovered patients had a NT-proBNP level higher than the upper limit of normal. The area under the receiver operating characteristics curve for the diagnosis of persistent left ventricular dysfunction was 0.984. NT-proBNP levels correlated with echocardiographically derived shortening fraction and with clinical score. NT-proBNP is a good marker for persistent left ventricular dysfunction in children who have had myocarditis or cardiomyopathy. In this group of patients, NT-proBNP levels are normal in children who recover echocardiographically, suggesting no residual hemodynamic abnormalities.     

Myocardial Perfusion Abnormalities in Patients Occurring More Than 1 Year After Successful Univentricular (Fontan Surgery) and Biventricular Repair (Complete Repair of Tetralogy of Fallot)

The outcome of children born with cyanotic congenital heart disease has markedly improved over the years. Follow up is recommended for most post-operated cases as complications may occur over long term. One of the complications is the development of ventricular dysfunction, often seen after a successful Fontan surgery (or one of its modifications) for single ventricle. The aim of this study was to determine the prevalence of myocardial perfusion abnormalities in the ventricular myocardium of asymptomatic patients, older than 8 years of age, who had earlier undergone either a univentricular palliation (modified Fontan procedure) or a biventricular repair for tetralogy of Fallot, more than a year ago. All eligible patients underwent screening electrocardiogram (to rule out rhythm disturbance) and echocardiography. Patients with ventricular ejection fraction of more than 50 % by echocardiography were included. Enrolled patients were subjected to gated stress–rest myocardial perfusion imaging using Technitium-99m tetrofosmin single photon emission-computerized tomography (SPECT). Ventricular ejection fraction was also calculated from gated rest study. For the Fontan group, we also analyzed data to see if the morphology of the systemic ventricle would make a difference as far as myocardial perfusion was concerned. Twenty-six patients were enrolled (11 had undergone Fontan surgery and 15 had complete repair of tetralogy of Fallot). Seven of 11 patients in the Fontan group had myocardial perfusion defects (63.6 %) as against none in the repaired tetralogy of Fallot group (p < 0.001). The ejection fraction was within normal range in both the groups; it was statistically higher in the post tetralogy of Fallot repair group (p < 0.04). There were two subgroups in the post Fontan group depending on the morphology of systemic ventricle-left (4 patients) and non-left (7 patients). Higher number and larger size of perfusion defects were present in the non-left ventricular systemic ventricle morphology as compared with left ventricular morphology, but this difference did not reach statistical significance. Myocardial perfusion defects are common in patients who have undergone univentricular repair more than one year ago in contrast to patients who had a biventricular repair for tetralogy of Fallot. In the Fontan group, the morphology of the systemic ventricle was not predictive of prevalence of perfusion defect.     

右心房异构引起的远期结果及心律失常

目的　回顾性研究右心房异构患儿的远期结果及有症状性心律失常的发生率及其与死亡的关系。方法　回顾 1980年 1月～ 2 0 0 0年 12月收治的 116例右心房异构婴幼儿和儿童的治疗和预后情况。将右心房异构的患儿分为肺静脉正常回流和肺静脉异位回流两组 ,通过比较两组患儿的预后来分析导致预后不良的因素 ,并对其中已经完成或准备接受外科手术治疗的 85例 ,分析其有症状性心律失常的类型、发病时间和发病诱因 ,从而了解有症状性心律失常对患儿的长期预后所造成的影响。结果　 116例中 ,大多数患儿 ( 96 % )的临床症状是紫绀 ,出现临床症状的年龄中位数为 1天(范围 1天～ 3 7岁 )。其中 31例 ( 2 7% )无手术适应证 ,最终死亡。早期肺静脉修复手术的死亡率为2 /8例 ) ,Fontan手术的早期死亡率为 2 6 % ( 5 /19) ,腔肺静脉分流术的早期死亡率为 8% ( 1/13) ,体肺循环动脉分流术的早期死亡率为 2 % ( 1/5 3)。晚期死亡与感染 (n =11)、原因不明的突然死亡 (n =7)和心律失常 (n =1)有关。肺静脉正常回流的患儿 ,其中 1、5、10和 15岁患儿的平均存活率分别为( 81± 5 ) %、( 6 7± 7) %、( 6 0± 8) %和 ( 4 3± 12 ) % ,与非阻塞性肺静脉异位回流患儿的平均存活率相似。导致高死亡率的危险因素包括肺静脉回流阻     

Diagnosis and treatment of post-transplantation lymphoproliferative disorder in pediatric heart transplant patients

PTLD is a severe complication in transplant recipients. Detection of increased EBV load in the peripheral blood acts as a surrogate marker for increased risk of PTLD development. We analyzed the time course of the disease, its severity, the organs involved, and mortality rates in our institutional experience of pediatric heart transplantation. This paper identifies risk factors for PTLD and describes the different ways of diagnosing and treating the disease. PTLD was screened for in 146 pediatric heart transplant patients using a retrospective analysis in patients who received transplantation before 1998. Prospective determination was performed in 72/146 patients transplanted after 1998 within the post-transplant follow-up. The occurrence of PTLD with all interventions, including tapering of immunosuppression, surgery, viral monitoring, and antiviral interventions, was recorded. PTLD was diagnosed in 12/147 (8.2%) children at a mean age of 7.2 +/- 3.3 yr after a mean post-transplant period of 3.2 +/- 2.2 yr. PTLD manifested in: lymph nodes (n = 4), intestine (n = 3), tonsils and adenoids (n = 2), eye (n = 2), and lung (n = 1). It was diagnosed in 7/12 as a monomorphic B-cell lymphoma and in four patients as a monomorphic Burkitt lymphoma, a polymorphic B-cell lymphoma, a T-cell rich or angiocentric lymphoma (Liebow) and as reactive plasmacytic hyperplasia (early lesion), respectively. Histology was not possible in one patient with ocular manifestation. EBV association was 83%. Risk factors in the comparison with patients without PTLD were age at time of Tx, primary EBV infection after Tx, use of Azathioprine and >or=3 doses of ATG. CMV mismatch and CMV infection, rejection episodes and steroids were not risk factors. Despite reduction of immunosuppression, treatment consisted of surgical procedures to remove tumor masses (n = 6), Rituximab (n = 5), polychemotherapy (n = 3), antiviral (n = 1) and autologous T-cell therapy (n = 1). All patients demonstrated full remission without death related to PTLD or treatment at 3.9 (1.3-6.2) yr median follow-up time. The manifestation of PTLD in pediatric heart transplant recipients is associated with EBV infection and is predominantly in the form of a B-cell lymphoma. A tight and specific follow-up including early assessment of immunity status and specific therapeutic intervention to improve cellular immunity is warranted and may contribute to a significant reduction of PTLD-related morbidity and mortality.     

Nadroparin therapy in pediatric patients with venous thromboembolic disease

Low-molecular-weight heparins are increasingly used for treatment of pediatric venous thromboembolic disease (VTE). Pediatric data about therapeutic doses of nadroparin are not available. To evaluate pharmacodynamics and safety of therapeutic doses of nadroparin, consecutive patients (age 0 to 18 y) with objectively diagnosed VTE and treated with nadroparin were included in this single center study over a 12-year period. All patients started with 85.5 IU/kg of nadroparin twice daily. The target therapeutic range (TTR) was set at 0.5 to 1.0 anti-Xa IU/mL 4 hours postdose. Safety end points were major bleeding and therapy-related death. A total of 84 patients were enrolled, of whom 8 patients did not undergo measurement of anti-Xa levels. Fifty-four (71%) of 76 patients achieved TTR. The maintenance dose (mean+/-SE) was 448+/-42 IU/kg/d in neonates (<2 mo, n=6), 253+/-22 IU/kg/d in infants (2 mo to 1 y, n=10), 214+/-8 IU/kg/d in children (2 to 11 y, n=13), and 183+/-5 IU/kg/d in adolescents (12 to 18 y, n=25). Neonates required significantly more dose adjustments and time to achieve TTR than adolescents. No major bleeding or therapy-related death occurred. In summary, an age-dependent response to nadroparin exists in pediatric patients. Nadroparin therapy seems to be safe for treatment of pediatric VTE.     

Long-term evaluation of cyclosporine and tacrolimus based immunosuppression in pediatric liver transplantation

Both calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are widely used in pediatric liver transplant recipients and currently data are limited with regards to long-term results using the one drug or the other in comparable low doses. We conducted the present study to assess the advantages and disadvantages of both drugs in children at least five yr post-liver transplantation. A total of 129 children were enrolled in the study. Thirty-eight of the children were switched to tacrolimus monotherapy for different reasons [steroid resistant graft rejection (n = 15), chronic rejection (n = 5), severe acute rejection (n = 4), repetitive acute graft rejection (n = 5), dysfunction of the transplant (n = 3), insufficient CsA metabolism (n = 3), hypertrichosis (n = 2), and CsA toxicity (n = 1)], four patients had primary tacrolimus therapy, and 87 patients are receiving cyclosporine. Mean trough levels were 5.3 +/- 2.3 ng/mL (tacrolimus) and 73.6 +/- 44.5 micro/L (cyclosporine), respectively at least five yr post-orthotopic liver transplantation (OLT). There was no significant difference in the calculated glomerular filtration rate between children on cyclosporine and tacrolimus (142.7 + 39.5 mL/min/1.73 m(2) vs. 151.1 +/- 44.1 mL/min/1.73 m(2)). The incidence of arterial hypertension was 7.1% vs. 9.2%, that of hepatotoxicity was 0% vs. 2.3%. Cosmetic changes were found in more than one-third of the patients on cyclosporine and in 4.8% of the patients receiving tacrolimus. Quality of life was excellent in both groups (self assessment). The impact of CNIs on chronic graft dysfunction cannot be assessed by our present study. We conclude from the results that cyclosporine and tacrolimus are both excellent drugs for maintenance immunosuppression in the long-term course following pediatric liver transplantation. However, this retrospective analysis is limited by the bias between children on CsA as compared with patients receiving tacrolimus. A prospective randomized controlled trial is needed in order to assess which CNI is the best for children following OLT.     

Nonsyndromic paucity of interlobular bile ducts: report of 10 patients

OBJECTIVES: Only a few reports of nonsyndromic paucity of interlobular bile ducts (NS-PILBD) have been published. The authors' aim was to outline the clinical and laboratory profile of patients with NS-PILBD diagnosed at a tertiary referral center. METHODS: The authors reviewed all the reports of pediatric liver biopsies performed between 1991 and 2000 at their institution. Upon diagnosis of NS-PILBD, patients' records were examined for clinical, laboratory, and histologic data, and liver biopsy specimens were re-evaluated. RESULTS: Three hundred biopsies were performed in children during the study period, of which 64 were in infants younger than 1 year. NS-PILBD was diagnosed in 10 of 64 (16%) biopsy specimens. Mean age at presentation was 10 days (range, 1 day-6 weeks), and mean follow-up was 4.5 years (range, 1-9 years). An underlying condition was identified in 70% of children with NS-PILBD: namely congenital cytomegalovirus (n = 2), progressive familial intrahepatic cholestasis (PFIC, n = 2), mitochondrial DNA depletion (n = 1), Niemann-Pick type C (n = 1), and arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC syndrome; n = 1). All children presented with jaundice. Four children had initially acholic stools. At their last follow-up visit, failure to thrive was present in five children, and cholestasis in six children. Mortality was noted only in children with metabolic diseases (n = 2). CONCLUSIONS: In the study, NS-PILBD was common in young children undergoing liver biopsy. Although NS-PILBD is nonspecific, a wide survey for inborn errors of metabolism should be included in the diagnostic work-up of NS-PILBD. In the authors' center, the association of certain metabolic diseases with NS-PILBD carries a grave prognosis.     

Right Ventricle and Tricuspid Valve Function at Midterm After the Fontan Operation for Hypoplastic Left Heart Syndrome: Impact of Shunt Type

This study aimed to evaluate clinical outcomes including hemodynamics, right ventricle (RV) function, and tricuspid valve (TV) function in patients with hypoplastic left heart syndrome (HLHS) at midterm after completion of staged palliation based on the source of pulmonary blood flow provided at stage 1. The records of all patients with HLHS who completed Fontan palliation between 2001 and 2007 were retrospectively reviewed. The outcome variables were RV dysfunction, TV, and neo-atrioventricular (neo-AV) regurgitation (from latest echocardiogram), cardiac index (CI), pulmonary vascular resistance (PVR), pulmonary artery pressure (PAp), and right ventricular end-diastolic pressure (RVEDp) (from latest catheterization). Clinical status was obtained from medical records and by contact with the referring cardiologist if necessary. Of 118 patients undergoing a Fontan for HLHS, 116 had a fenestrated lateral tunnel and 2 had an extracardiac conduit. At the time of stage 1 palliation, 36 patients had a right ventricle-to-pulmonary artery (RV-PA) conduit, and 82 patients had a modified Blalock-Taussig shunt (mBTS). All the patients except one who died of sepsis on extracorporeal membrane oxygenation (ECMO) survived the Fontan operation and were discharged home. At a mean follow-up post-Fontan period of 28.4 months (range, 0.16-95.3 months), three patients had died (2 on the transplantation list and 1 from pulmonary vein stenosis), and one patient had the Fontan circulation taken down. No patient had a heart transplantation. A follow-up echocardiogram was performed for 115 patients (after a mean of 15.6 months for RV-PA and 32.1 months for BTS), and 66 patients underwent a post-Fontan catheterization (after a mean of 15.8 months for RV-PA and 29.3 months for BTS). The hemodynamic results for RV-PA conduit versus BTS were a CI of 3.4 ± 0.8 versus 3.4 ± 1.2, a PVR of 1.8 ± 0.7 versus 1.7 ± 0.8, a PAp of 14.3 ± 3.1 versus 14.2 ± 4.5, and an RVEDp of 7.1 ± 3.3 versus 8.9 ± 5.3. No statistically significant differences were found between shunt types regarding survival or degree of RV dysfunction or in terms of neo-AV regurgitation, CI, PVR, PAp, RVEDp, or rhythm problems. Patients in the BTS group required more tricuspid valvuloplasties and had more tricuspid regurgitation at follow-up evaluation. The patients in the RV-PA group had more PA interventions. In conclusion, the contemporary results after Fontan palliation for HLHS were excellent. At the midterm follow-up evaluation, outcomes and hemodynamic data were similar between shunt types. However, the patients in the BTS group exhibited more tricuspid regurgitation, and the patients in the RV-PA group had increased pulmonary artery interventions.     

Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantation

Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 +/- 13.7 vs. 36.2 +/- 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 +/- 15.3 (CAD) vs. 87.6 +/- 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation.     

Reasons why some children receiving tacrolimus therapy require steroids more than 5 years post liver transplantation

Tacrolimus is a potent immunosuppressive agent and has been used in liver transplantation (LTx) for nearly a decade. More than 70% of children can be maintained on tacrolimus monotherapy, without steroids, by the end of 1 yr post-Tx. This freedom from steroids does not appear to change significantly in subsequent years. The use of steroids has obvious metabolic and cosmetic disadvantages, besides affecting linear growth in children. The present study identifies why some children still require steroid therapy after successful LTx. One hundred and sixty-six consecutive pediatric patients who had undergone primary LTx between October 1989 and December 1992, were included in this study. Follow-up ranged from 6 to 9 yr (mean 7.5 +/- 0.8 yr). One hundred and forty-one children were alive in November 1998 and these patients constituted the study group. Their current rate of prednisone use, reason for prednisone use, and prednisone dose were examined retrospectively. Of the 141 patients, 139 (98.5%) had stopped taking steroids at some time-point after LTx. Thirteen patients (9%) were off immunosuppression altogether (group I), 97 were undergoing tacrolimus monotherapy (group II), and the remaining 31 were receiving therapy with steroids and tacrolimus (group III). The mean prednisone dose at the last follow-up was 6.5 +/- 4.9 mg/day (median 5.0 mg/day). In group III, two children were never weaned off steroids because of inadequate follow-up (both lived outside the country), and the remaining 29 children completely stopped steroid therapy at some time-point after LTx; however, prednisone was re-introduced for clinically suspected or biopsy-proven rejection in 24. Seven children in group III had completely stopped immunosuppressive therapy either as part of an immunosuppression reduction protocol (n = 3) or for suspected or proven post-transplant lymphoproliferative disorder (PTLD) (n = 4). In eleven of the 18 children in group III, requirement of steroid for rejection was thought to be related, in part, to non-compliance. In three children in group III, steroids were re-introduced for renal dysfunction, and two of these patients subsequently received a kidney Tx. In one child with cerebral ischemia, steroids were used to reduce brain edema, and another child had features of auto-immune hepatitis. Hence, almost all children can be weaned off steroids when tacrolimus is used as primary immunosuppression after primary LTx. However, approximately 22% of children may need re-institution of steroids because of late acute rejection or renal dysfunction. The concomitant use of other non-steroidal immunosuppressive agents with tacrolimus may further reduce the dose and rate of steroid use.     

The effect of treatment with angiotensin-converting enzyme inhibitors on survival of pediatric patients with dilated cardiomyopathy

Summary Outcome in 81 pediatric patients with dilated cardiomyopathy was reviewed to assess whether treatment with angiotensin-converting enzyme (ACE) inhibitors affected survival. Age at onset was 3.6±0.6 years. Twenty-seven children (group 1) were treated with ACE inhibitors. Conventional therapy was used in the remaining 54 patients (group 2). There were no significant differences between the two groups in age at onset, left ventricular shortening fraction, left ventricular end-diastolic pressure, or mean pulmonary artery pressure. Patients treated with ACE inhibitors had a significantly better survival during the first year (p<0.05) with continuation of this trend throughout the second year (p=0.06). Beyond 2 years there was a tendency toward better survival in ACE inhibitor-treated patients, but the differences were no longer significant (p=0.14). These data, along with observations in adult patients with chronic cardiac failure, indicate that converting enzyme inhibitors have a beneficial effect on prolonging survival of infants and children with severe left ventricular dysfunction from dilated cardiomyopathy.