Nomenclature and Databases — The Past, the Present, and the Future

This review discusses the historical aspects, current state of the art, and potential future advances in the areas of nomenclature and databases for congenital heart disease. Five areas will be reviewed: (1) common language = nomenclature, (2) mechanism of data collection (database or registry) with an established uniform core data set, (3) mechanism of evaluating case complexity, (4) mechanism to ensure and verify data completeness and accuracy, and (5) collaboration between medical subspecialties. During the 1990s, both the Society of Thoracic Surgeons (STS) and the European Association for Cardiothoracic Surgery (EACTS) created congenital heart surgery outcomes databases. Beginning in 1998, the EACTS and STS collaborated in the work of the International Congenital Heart Surgery Nomenclature and Database Project. By 2000, a common congenital heart surgery nomenclature, along with a common core minimal data set, were adopted by the EACTS and the STS and published in the Annals of Thoracic Surgery. In 2000, the International Nomenclature Committee for Pediatric and Congenital Heart Disease was established; this committee eventually evolved into the International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD). The working component of ISNPCHD is the International Working Group for Mapping and Coding of Nomenclatures for Paediatric and Congenital Heart Disease, also known as the Nomenclature Working Group (NWG). By 2005, the NWG cross-mapped the EACTS–STS nomenclature with the European Paediatric Cardiac Code of the Association for European Paediatric Cardiology and created the International Paediatric and Congenital Cardiac Code (IPCCC) (). This common nomenclature (IPCCC), and the common minimum database data set created by the International Congenital Heart Surgery Nomenclature and Database Project, are now utilized by both EACTS and STS; since 1998, this nomenclature and database have been used by both the STS and EACTS to analyze outcomes of more than 75,000 patients. Two major multi-institutional efforts have attempted to measure case complexity; the Risk Adjustment in Congenital Heart Surgery-1 and the Aristotle Complexity Score. Efforts to unify these two scoring systems are in their early stages but are encouraging. Collaborative efforts involving the EACTS and STS are under way to develop mechanisms to verify data completeness and accuracy. Further collaborative efforts are also ongoing between pediatric and congenital heart surgeons and other subspecialties, including pediatric cardiac anesthesiologists (via the Congenital Cardiac Anesthesia Society), pediatric cardiac intensivists (via the Pediatric Cardiac Intensive Care Society), and pediatric cardiologists (via the Joint Council on Congenital Heart Disease). Clearly, methods of congenital heart disease outcomes analysis continue to evolve, with continued advances in five areas: nomenclature, database, complexity adjustment, data verification, and subspecialty collaboration.     

The Pre-Sports Cardiovascular Evaluation: Should It Depend on the Level of Competition,the Sport,or the State?

Sudden cardiac death (SCD) in an athlete is a rare but tragic event, and significant controversy exists regarding the most effective method to define those at highest risk. Recommendations of the American Heart Association require that a history and physical examination be used for preparticipation screening with an abnormal cardiac finding expected to prompt further evaluation. Given the lack of data documenting that electrocardiogram (ECG) screening in all competitive athletes is either feasible or appropriate, these same guidelines state that such screening is optional but not mandatory. The extremely low incidence of SCD events, in conjunction with the low sensitivity and specificity of ECG as a screening tool in athletes, contributes to this recommendation. Although these guidelines target all competitive athletes, however, there may be subgroups of athletes, based on age, level of competition, individual sport, or state of residence, for which mandatory ECG screening may be both appropriate and sensible. Given the lack of resolution of the ongoing ECG debate, it is perhaps reasonable to consider screening specific high-risk subgroups of athletes rather than continuing to dispute whether to screen all competitive athletes or none at all. Recent data suggest that such a program may be feasible and may provide a rationale basis for subsequent expansion of cardiovascular screening programs.     

What is the yield from asking,at the end of the consultation,if there are any further questions? An obserational study

AIM: I set out to determine how often families, when invited, have further questions at the end of a general paediatric consultation and to determine the nature of such questions. Results: Over a 2 1/2 -y period, there were 64 further questions arising from a total of 477 consultations (13%). CONCLUSIONS: Inviting questions is worthwhile; two-thirds of the responses provided evidence that there had been suboptimal communication during the consultation.     

Serotonin, inflammation, and IBS: fitting the jigsaw together?

Unexplained diarrhoea is a frequent indication for gastroenterologic referral, and after full investigation the most common final diagnosis is irritable bowel syndrome (IBS). Some patients with IBS describe an acute onset of symptoms following infective gastroenteritis. Postinfective IBS affects 7% to 31% of individuals infected, and appears to be a nonspecific response to injury which has been reported following Salmonella-, Campylobacter-, and Shigella-related IBS. The strongest risk factor for developing postinfective IBS is severity of the initial diarrhoea illness, but toxigenicity of the infected bacteria, age <60 years, and female sex also are important risk factors. Adverse life events, hypochondriasis, and depression are also important, as is increased enteroendocrine cell and lymphocyte numbers in rectal biopsies. Postinfective IBS and IBS with diarrhoea without an infectious onset both show increased postprandial release of serotonin, whilst constipated patients show a depressed release. Several studies suggest impairment of the serotonin transporter in IBS, which in animal studies has been shown to occur following a range of inflammatory insults. Clinical conditions with an inflammatory basis, such as coeliac and Crohn disease, also are characterised by excess postprandial serotonin release. Several studies report evidence of low-grade inflammation in IBS with diarrhoea. However, reliable markers of low-grade inflammation that may predict response to serotonin antagonists or other anti-inflammatory agents remain a goal for future research.     

Mosaic or chimera? Revisiting an old hypothesis about the cause of the 46,XX/46,XY hermaphrodite

OBJECTIVES: A cell lineage in a hermaphrodite infant showing a 46,XX/46,XY karyotype was analyzed to determine the genetic contribution from both parents and identify the underlying mechanism. STUDY DESIGN: Genotype analysis was performed by using 57 microsatellite markers, 39 distributed on 9 autosomes and 18 on the X-chromosome. Two X- and Y-specific markers were analyzed to confirm the presence and percentages of cells containing a Y-chromosome. RESULTS: The proband revealed a single maternal and paternal allele for all of the informative autosomal and X-chromosome markers. Analysis of the X- and Y-specific markers confirmed that approximately 20% of the patient's peripheral blood cells contained the Y chromosome. CONCLUSIONS: The data suggest that the patient's hermaphroditism was the result of a mosaic embryo and not a chimera. The most likely mechanism involved 2 separate nondisjunction events, resulting in the loss of 47,XXY cells during early embryonic development.     

Toll-like receptors, the NLRP3 inflammasome, and interleukin-1β in the development and progression of type 1 diabetes

Traditionally, type 1 diabetes (T1D) has been thought of as a disease of cellular immunity, but there is increasing evidence that components of the innate immune system, controlled largely by Toll-like receptors (TLRs), play a significant role in T1D development. TLRs are pattern-recognition molecules on immune cells that recognize pathogens, leading to the production of cytokines such as interleukin-1β (IL1β, encoded by the IL1B gene). IL1β is increased in patients with newly diagnosed T1D and likely acts as an early inflammatory signal in T1D development. Because hyperglycemia is a hallmark of T1D, the effects of hyperglycemia on IL1β expression in peripheral blood mononuclear cells (PBMCs) and islet cells have been examined, but with inconsistent results, and the mechanisms leading to this increase remain unknown. Fatty acids stimulate IL1β expression and may promote inflammation, causing hyperglycemia and insulin resistance. The mechanisms by which IL1β is involved in T1D pathogenesis are controversial. Overall, studies in pancreatic β-cells suggest that IL1β-mediated damage to islet cells involves multiple downstream targets. Potential therapies to decrease the progression of T1D based on IL1β biology include pioglitazone, glyburide, IL1 receptor antagonists, and agents that remove IL1β from the circulation.     

Azithromycin is the answer in paediatric respiratory medicine,but what was the question?

The first clinical indication of non-antibiotic benefits of macrolides was in the Far East, in adults with diffuse panbronchiolitis. This condition is characterised by chronic airway infection, often with Pseudomonas aeruginosa, airway inflammation, bronchiectasis and a high mortality. Low dose erythromycin, and subsequently other macrolides, led in many cases to complete remission of the condition, and abrogated the neutrophilic airway inflammation characteristic of the disease. This dramatic finding sparked a flurry of interest in the many hundreds of macrolides in nature, especially their anti-inflammatory and immunomodulatory effects. The biggest subsequent trials of azithromycin were in cystic fibrosis, which has obvious similarities to diffuse panbronchiolitis. There were unquestionable improvements in lung function and pulmonary exacerbations, but compared to diffuse panbronchiolitis, the results were disappointing. Case reports, case series and some randomised controlled trials followed in other conditions. Three trials of azithromycin in preschool wheeze gave contradictory results; a trial in pauci-inflammatory adult asthma, and a trial in non-cystic fibrosis bronchiectasis both showed a significant reduction in exacerbations, but none matched the dramatic results in diffuse panbronchiolitis. There is clearly a huge risk of antibacterial resistance if macrolides are used widely and uncritically in the community. In summary, Azithromycin is not the answer to anything in paediatric respiratory medicine; the paediatric respiratory community needs to refocus on the dramatic benefits of macrolides in diffuse panbronchiolitis, use modern – omics technologies to determine the endotypes of inflammatory diseases and discover in nature or synthesise designer macrolides to replicate the diffuse panbronchiolitis results. We must now find out how to do better!     

Miscellaneous conditions of the peritoneal cavity—Peritoneal tumors,pseudomyxoma, mesothelioma,fibroblastic reaction,cocoon, cystic lymphatic malformations,blue-bleb,and chylous ascites

The peritoneum is subject to both primary neoplasia and secondary malignancy from direct, trans-coelomic, or hematogenous spread from any cancer. The knowledge base in the pediatric age group is very limited due to the rarity of peritoneal conditions in children, and much of the information is extrapolated from adult literature. There have been few reports in the pediatric population on the diagnosis and management of peritoneal conditions including peritoneal malignancy. In this article, we aim to highlight some of these conditions and the treatments available with a special emphasis on the evolving role of cytoreduction surgery and hyperthermic intraperitoneal chemotherapy in the treatment of certain peritoneal malignancies in children.