Isolated cutaneous anaplastic large cell lymphoma progressing to severe systemic disease with myocardial involvement and central nervous system infiltration.

Anaplastic large cell lymphoma (ALCL) is a rare tumor comprising around 10-15% of childhood lymphomas. We describe the case of a female who initially presented with localized skin disease associated with an insect bite. However, she subsequently relapsed with widespread systemic ALK-positive ALCL that included lymphoma deposits in the myocardium, a very rare manifestation. Her disease responded well to chemotherapy but she later developed a fatal relapse in the CNS. We also present data on an immune response to ALK, demonstrating a fluctuation in the levels of circulating antibodies to ALK corresponding to the different phases of her illness.

Bovine jugular vein valved conduit: up to 10 years follow-up.

OBJECTIVE: The present study evaluated the mortality and conduit failure in bovine jugular vein (BJV) conduits. METHODS: Between October 1999 and February 2009, 193 patients (mean age, 6.7 ± 5.8 years; range, 5 days to 18 years; mean weight, 23.9 ± 21.0 kg; range, 2.4-105.4 kg) had been discharged after BJV implantation. The reason for BJV implantation was right ventricular outflow tract reconstruction in 117 conduit replacement in 44, and the Ross procedure in 32. The diameter of the BJV was 12 mm in 18 patients (9.3%), 14 mm in 16 (8.3%), 16 mm in 42 (21.7%), 18 mm in 37 (19.2%), 20 mm in 15 (7.8%), and 22 mm in 65 (33.7%). RESULTS: At a mean ± SD follow-up of 4.6 ± 2.3 y/patient (range, 8 months to 10 years), 5 late deaths (2.6%) had occurred, all unrelated to conduit failure. Conduit-related problems required an interventional procedure as the first treatment in 10 patients (5.2%) within a mean interval of 2.5 ± 1.4 years (range, 8 months to 5.3 years) or surgical revision in 5 patients (2.6%) after 2.1 ± 1.9 years (range, 19 days to 4.1 years). Late deaths occurred in 5.9% (2/34) of patients with a BJV size of 12 to 14 mm versus 1.9% (3/159) in patients with a size of 16 to 22 mm (P = NS). An interventional procedure or surgical revision was required in 29.4% (10/34) of patients with a BJV size of 12 to 14 mm versus 3.1% (5/159) in patients with a size of 16 to 22 mm (P < .0005). CONCLUSIONS: After 10 years of experience with the BJV, this conduit has remained a reliable alternative to pulmonary homografts with respect to survival and freedom from conduit failure. However, the incidence was greater and the presentation of conduit failure was earlier in patients with a smaller size BJV conduit (12-14 mm).

Systematic survey of variants in TBX1 in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common variants.

BACKGROUND: Tetralogy of Fallot (TOF) is common in individuals with hemizygous deletions of chromosome 22q11.2 that remove the cardiac transcription factor TBX1. OBJECTIVE: To assess the contribution of common and rare TBX1 genetic variants to TOF. DESIGN: Rare TBX1 variants were sought by resequencing coding exons and splice-site boundaries. Common TBX1 variants were investigated by genotyping 20 haplotype-tagging SNPs capturing all the common variations present at the locus. Association analysis was performed using the program UNPHASED. PATIENTS: TBX1 exons were sequenced in 93 patients with non-syndromic TOF. Single nucleotide polymorphism analysis was performed in 356 patients with TOF, their parents and healthy controls. RESULTS: Three novel variants not present in 1000 chromosomes from healthy ethnically matched controls were identified. One of these variants, an in-frame 57 base-pair deletion in the third exon which removed 19 evolutionarily conserved residues, decreased transcriptional activity by 40% in a dual luciferase assay (p=0.008). Protein expression studies demonstrated that this mutation affected TBX1 protein stability. After correction for multiple comparisons, no significant associations between common genetic variants and TOF susceptibility were found. CONCLUSION: This study demonstrates that rare TBX1 variants with functional consequences are present in a small proportion of non-syndromic TOF.

Genetic variation in VEGF does not contribute significantly to the risk of congenital cardiovascular malformation.

Several previous studies have investigated the role of common promoter variants in the vascular endothelial growth factor (VEGF) gene in causing congenital cardiovascular malformation (CVM). However, results have been discrepant between studies and no study to date has comprehensively characterised variation throughout the gene. We genotyped 771 CVM cases, of whom 595 had the outflow tract malformation Tetralogy of Fallot (TOF), and carried out TDT and case-control analyses using haplotype-tagging SNPs in VEGF. We carried out a meta-analysis of previous case-control or family-based studies that had typed VEGF promoter SNPs, which included an additional 570 CVM cases. To identify rare variants potentially causative of CVM, we carried out mutation screening in all VEGF exons and splice sites in 93 TOF cases. There was no significant effect of any VEGF haplotype-tagging SNP on the risk of CVM in our analyses of 771 probands. When the results of this and all previous studies were combined, there was no significant effect of the VEGF promoter SNPs rs699947 (OR 1.05 [95% CI 0.95-1.17]); rs1570360 (OR 1.17 [95% CI 0.99-1.26]); and rs2010963 (OR 1.04 [95% CI 0.93-1.16]) on the risk of CVM in 1341 cases. Mutation screening of 93 TOF cases revealed no VEGF coding sequence variants and no changes at splice consensus sequences. Genetic variation in VEGF appears to play a small role, if any, in outflow tract CVM susceptibility.

Late presentation of cor triatriatum with persistent levoatrial cardinal vein.

An asymptomatic 10-year-old boy presented with reduced exercise tolerance and an echocardiographic diagnosis of cor triatriatum. Transthoracic and transesophageal echocardiography failed to reveal the persistent levoatrial cardinal vein discovered at surgery. In patients with late presentation of cor triatriatum with severe mitral inflow obstruction and a small patent foramen ovale, an alternative communication between the posterior collecting chamber and the systemic venous circulation should be sought with alternative imaging techniques.

Prioritization of congenital cardiac surgical patients using fuzzy reasoning--a solution to the problem of the waiting list?

Surgical waiting lists are of high importance in countries, where the national health system is unable to deliver surgical services at a rate that would allow patients to avoid unnecessary periods of waiting. Prioritization of these lists, however, is frequently arbitrary and inconsistent. The objective of our research was to analyze the medical decision-making process when prioritizing patients with congenital cardiac malformations for cardiac surgical procedures, identifying an appropriate representation of knowledge, and transferring this knowledge onto the design and implementation of an expert system ("PrioHeart"). The medical decision-making process was stratified into three stages. The first was to analyze the details of the procedure and patient to define important impact factors on clinical priority, such as the risk of adverse events. The second step was to evaluate these impact factors to define an appropriate "timing category" within which a procedure should be performed. The third, and final, step was to re-evaluate the characteristics of individual patients to differentiate between those in the same timing category. We implemented this decision-making process using a rule-based production system with support for fuzzy sets, using the FuzzyCLIPS inference engine and expert system shell as a suitable development environment for the knowledge base. The "PrioHeart" expert system was developed to give paediatric cardiologists a tool to allow and facilitate the prioritization of patients on the cardiosurgical waiting list. Evaluation of "PrioHeart" on limited sets of patients documented appropriate results of prioritization, with a significant correlation between the prioritization made using "PrioHeart" and those results obtained by the individual consultant specialist. We conclude that our study has demonstrated the feasibility of using an expert system approach with a fuzzy, rule-based production system to implement the prioritization of cardiac surgical patients. The approach may potentially be transferable to other medical subspecialities.