The nomenclature, definition and classification of cardiac structures in the setting of heterotaxy

AbstractIn 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. The working component of this international nomenclature society has been The International Working Group for Mapping and Coding of Nomenclatures for Paediatric and Congenital Heart Disease, also known as the Nomenclature Working Group. The Nomenclature Working Group created the International Paediatric and Congenital Cardiac Code, which is available for free download from the internet at [http://www.IPCCC.NET].In previous publications from the Nomenclature Working Group, unity has been produced by cross-mapping separate systems for coding, as for example in the treatment of the functionally univentricular heart, hypoplastic left heart syndrome, or congenitally corrected transposition. In this manuscript, we review the nomenclature, definition, and classification of heterotaxy, also known as the heterotaxy syndrome, placing special emphasis on the philosophical approach taken by both the Bostonian school of segmental notation developed from the teachings of Van Praagh, and the European school of sequential segmental analysis. The Nomenclature Working Group offers the following definition for the term "heterotaxy": "Heterotaxy is synonymous with 'visceral heterotaxy' and 'heterotaxy syndrome'. Heterotaxy is defined as an abnormality where the internal thoraco-abdominal organs demonstrate abnormal arrangement across the left-right axis of the body. By convention, heterotaxy does not include patients with either the expected usual or normal arrangement of the internal organs along the left-right axis, also known as 'situs solitus', nor patients with complete mirror-imaged arrangement of the internal organs along the left-right axis also known as 'situs inversus'." "Situs ambiguus is defined as an abnormality in which there are components of situs solitus and situs inversus in the same person. Situs ambiguus, therefore, can be considered to be present when the thoracic and abdominal organs are positioned in such a way with respect to each other as to be not clearly lateralised and thus have neither the usual, or normal, nor the mirror-imaged arrangements."The heterotaxy syndrome as thus defined is typically associated with complex cardiovascular malformations. Proper description of the heart in patients with this syndrome requires complete description of both the cardiac relations and the junctional connections of the cardiac segments, with documentation of the arrangement of the atrial appendages, the ventricular topology, the nature of the unions of the segments across the atrioventricular and the ventriculoarterial junctions, the infundibular morphologies, and the relationships of the arterial trunks in space. The position of the heart in the chest, and the orientation of the cardiac apex, must also be described separately. Particular attention is required for the venoatrial connections, since these are so often abnormal. The malformations within the heart are then analysed and described separately as for any patient with suspected congenital cardiac disease. The relationship and arrangement of the remaining thoraco-abdominal organs, including the spleen, the lungs, and the intestines, also must be described separately, because, although common patterns of association have been identified, there are frequent exceptions to these common patterns. One of the clinically important implications of heterotaxy syndrome is that splenic abnormalities are common. Investigation of any patient with the cardiac findings associated with heterotaxy, therefore, should include analysis of splenic morphology. The less than perfect association between the state of the spleen and the form of heart disease implies that splenic morphology should be investigated in all forms of heterotaxy, regardless of the type of cardiac disease. The splenic morphology should not be used to stratify the form of disease within the heart, and the form of cardiac disease should not be used to stratify the state of the spleen. Intestinal malrotation is another frequently associated lesion that must be considered. Some advocate that all patients with heterotaxy, especially those with isomerism of the right atrial appendages or asplenia syndrome, should have a barium study to evaluate for intestinal malrotation, given the associated potential morbidity. The cardiac anatomy and associated cardiac malformations, as well as the relationship and arrangement of the remaining thoraco-abdominal organs, must be described separately. It is only by utilizing this stepwise and logical progression of analysis that it becomes possible to describe correctly, and to classify properly, patients with heterotaxy

The influence of neonatal hypoxia on cardiovascular structure and function in the rat at maturity

Innovations in the practice of pediatric cardiology and cardiovascular surgery have resulted in significant improvements in the survival of children born with congenital heart disease. This has resulted in a growing population of adults with repaired or palliated congenital heart disease. However, these patients are at increased risk of impaired cardiovascular health, including mortality, particularly under conditions of physiological stress, such as operative reintervention, in later life. We hypothesized that neonatal hypoxia engenders lasting changes in cardiovascular structure and function which may adversely influence myocardial and vascular responses to physiological stress at maturity. To test this hypothesis, Sprague-Dawley rats reared initially in hypoxic conditions (FiO2 = 0.12) for days 1 to 10 of life were compared to rats reared only in ambient air. Neonatal hypoxia was associated with significant changes in the left ventricular expression of 1945 and 422 genes in 10- and 90-day-old animals, respectively. Functional annotation revealed several genes involved in adaptive vascular remodeling and energy metabolism, as well as the regulation of apoptosis. Trends in gene expression suggested a proapoptotic paradigm which was corroborated by data showing decreased survival, following an ischemia-reperfusion insult, of cardiomyocytes isolated from adult animals exposed to neonatal hypoxia. Based on the above observations, we next sought to characterize additional changes in cardiovascular structure and function, induced by neonatal hypoxia, which might enhance cardiomyocyte vulnerability to physiological stress in the adult animal. Hypoxic animals had significant left ventricular hypertrophy, as well as impaired cardiomyocte calcium homeostasis and sarcomere relaxation, observations which were consistent with in vivo echocardiographic evidence of severe diastolic dysfunction. Neonatal hypoxia was also associated with the development of significant remodeling of left ventricular arterioles resulting in decreased lumen area. Significant reduction in agonist-induced activation of Akt and ERK1/2 survival signalling, as well as decreased mitochondrial hexokinase 2 expression, were observed. Finally, the left ventricular protein expression of Gαi3, Gαi2, and HIF-1α was significantly increased in adult animals following neonatal hypoxia.The above observations were evaluated in the context of the clinical challenges associated with the care of adult patients with congenital heart disease, and the potential clinical implications of these data are discussed.Les innovations dans la pratique de la cardiologie et de la chirurgie cardio-vasculaire pédiatrique ont entraîné des améliorations importantes dans la survie des enfants nés avec une cardiopathie congénitale. Cela a mené à une population croissante d'adultes ayant une maladie cardiaque congénitale réparée ou palliée. Cependant, ces patients sont à risque de santé cardio-vasculaire affaiblie, y compris la mortalité, en particulier dans des conditions de stress physiologique, tel que la réintervention opératoire. Notre hypothèse est que l'hypoxie néonatale engendre des changements durables dans la structure et la fonction cardio-vasculaire qui peuvent influencer négativement les réponses du myocarde au stress physiologique.Pour vérifier cette hypothèse, des rats Sprague-Dawley élevés initialement dans des conditions hypoxiques (FiO2 = 0,12) pour les jours 1 à 10 de vie ont été comparés à des rats élevés dans l'air ambiant. L'hypoxie néonatale a été associée à des changements significatifs dans l'expression, au niveau du ventricule gauche, de 1945 et de 422 gènes chez les animaux âgés de 10 et de 90 jours, respectivement. L'annotation fonctionnelle a révélé plusieurs gènes impliqués dans le remodelage vasculaire adaptatif et le métabolisme énergétique, ainsi que dans la régulation de l'apoptose. Les tendances dans l'expression des gènes ont suggéré un paradigme proapoptotique qui a été corroboré par des résultats montrant une diminution de la survie, suite à une insulte ischémie-reperfusion, de cardiomyocytes isolés chez les animaux adultes exposés à l'hypoxie néonatale.Sur la base des observations ci-dessus, nous avons ensuite cherché à caractériser les changements dans la structure et la fonction cardio-vasculaire, induits par l'hypoxie néonatale, qui pourraient accroître la vulnérabilité des cardiomyocytes au stress physiologique chez l'animal adulte. Les animaux hypoxiques avaient une hypertrophie ventriculaire gauche significative, ainsi que des altérations de l'homéostasie du calcium dans le cardiomyocyte et de la détente des sarcomères, des observations compatibles avec des observations échocardiographiques montrant une dysfonction diastolique sévère. L'hypoxie néonatale a également été associée au développement du remodelage des artérioles du ventricule gauche. Nous avons observé une réduction significative de l'activation d'Akt et ERK1/2 induite par l'isoproterenol, ainsi qu'une diminution de l'expression mitochondriale de hexokinase 2. Enfin, l'expression des protéines Gαi3, Gαi2, et HIF-1α a été significativement augmentée, au niveau du ventricule gauche, chez les animaux adultes suivant l'hypoxie néonatale.Les observations ci-dessus ont été évaluées dans le contexte des défis cliniques associés aux soins des patients adultes atteints de cardiopathies congénitales, et les implications cliniques potentielles sont discutées

Gβγ is a negative regulator of AP-1 mediated transcription

Following stimulation of G protein-coupled receptors (GPCRs) at the cell surface, heterotrimeric G proteins are activated. Both G alpha and G beta gamma subunits regulate specific effectors to transmit signals received by the receptor. Recent data suggest potential nuclear localization or translocation of the G beta gamma subunit. Here, we show that co-expression of the G beta gamma dimer decreased phorbol 12-myristate 13-acetate (PMA)-stimulated AP-1 gene reporter activity in HEK293 cells as well as the AP-1 dependent gonadotropin-releasing hormone-stimulated human follicle-stimulating hormone beta reporter activity in L beta T2 gonadotrope cells. Further, we identify Fos transcription factors as novel interactors of the G beta 1 subunit, using protein fragment complementation assays, as well as co-immunoprecipitation in vivo and in vitro. Fos proteins dimerize with Jun proteins to form activator protein-1 (AP-1) transcription factor complexes, which regulate target gene expression. G beta gamma did not interfere with the dimerization of Fos and Jun or their ability to bind DNA. Rather, G beta gamma co-localized with the AP-1 complex in the nucleus and recruited histone deacetylases (HDACs) to inhibit AP-1 transcriptional activity. Our data indicate a novel role for G beta gamma subunits as transcriptional regulators. (C) 2010 Elsevier Inc. All rights reserved

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally