Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.

The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.

The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.

OBJECTIVES/SPECIFIC AIMS: Respiratory viruses cause enormous medical burden, yet many of the specific virus and host genetic factors that impact pathogenesis are still largely unknown or poorly understood. To better understand the drivers of both acute clinical pathogenesis and long-term impacts, such as the development of asthma, we investigated the host response to respiratory syncytial virus (RSV) infections in pediatric patients. METHODS/STUDY POPULATION: We collected nasopharyngeal swabs from 32 pediatric patients with acute RSV infection. The swabs represented a mixed cell population including epithelial and immune cells at the active site of infection. Unbiased RNA sequencing with ribosomal RNA depletion allowed the simultaneous detection of host gene expression and RSV infection. We sequenced samples 2×75 bp on an Illumina NextSeq 500. Sequences were mapped to the human genome using the TopHat 2 aligner and FPKM estimation of reference genes and transcripts and assembly of novel transcripts were conducted with Cufflinks 2. RESULTS/ANTICIPATED RESULTS: During acute RSV infection we identified 7343 genes that were significantly expressed. Pathway analysis using KEGG revealed significant upregulation of pathways involved in innate immune response infection, ribosome function, oxidative phosphorylation, spliceosome and autoimmune disorders. We found high levels of innate immune response genes including CXCL8, IFITM1, IFITM2, IFITM3, IL1RN, and ISG15. In comparing RSV subtype A to RSV B we found significant differential expression of multiple noncoding RNAs. DISCUSSION/SIGNIFICANCE OF IMPACT: Examination of the host gene response during acute RSV infections, yielded important insight into the mechanisms that cause clinical pathogenesis and may provide understanding of the mechanisms that lead to known long-term impacts, such as the development of asthma. Together, this data may be used to guide clinical treatment and management decisions for children with severe RSV infections.

An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many “short list” versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various “short lists”. In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the “short list” for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.

Commensal epizoozoans and episkeletozoans are rarely preserved attached to the external exoskeleton of the Late Ordovician trilobite Flexicalymene. Of nearly 15,000 Flexicalymene specimens examined, 0.1% show epizoozoans or episkeletozoans. Factors limiting Flexicalymene fouling include a shallow burrowing life style, frequent molting of the host, larval preference for other substrates, observational bias caused by overlooking small fouling organisms, and the loss of the non-calcified, outermost cuticle prior to fossilization or as the trilobite weathers from the encasing sediment. Trepostome bryozoans, articulate and inarticulate brachiopods, cornulitids, and a tube-dwelling/boring nonbiomineralized organism represent the preserved members of the Late Ordovician marine hard substrate community fouling Flexicalymene. This assemblage of organisms is less diverse than the hard substrate community fouling Late Ordovician sessile epibenthic organisms. Fouling is not restricted to only large Flexicalymene specimens as observed in previous studies but occurs in medium to large individuals interpreted as early to late holaspid specimens.

Epizoozoans fouling the carcasses or molt ensembles of 16 Flexicalymene specimens provide insight into the life habits of the host and these fouling organisms. Trepostome bryozoans, articulate and inarticulate brachiopods, and cornulitids preferentially attached to elevated portions of the dorsal exoskeleton, and preferentially aligned in either the direct line or lee side of currents generated by Flexicalymene walking on the sea floor or swimming through the water column.

The reticuloceratid ammonoid Arkanites relictus (Quinn, McCaleb, and Webb, 1962) is represented by hundreds to thousands of individuals from horizons isolated both stratigraphically and geographically in northern Arkansas. These assemblages appear to represent mass mortality events resulting from a semelparous reproductive strategy. Arkanites relictus occurs as a dimorphic pair (depressed, widely umbilicate, cadiconic conchs and compressed, narrowly umbilicate, pachyconic conchs) thought to reflect sexual dimorphism. Late stage ontogenetic modifications, such as septal crowding and change in aperture profile, are widely cited evidence of sexual maturity in ammonoids. Septal crowding begins at a predictable ontogenetic stage in the compressed forms of A. relictus, but specimens with cadiconic conchs do not have crowded septa even at the largest diameters available.

Depending on the trait examined and the proxy for age of individuals, the dimorphism in Arkanites relictus (using the depressed form as the reference morph) is the result of acceleration, neoteny, or hypermorphosis plus neoteny. If size (diameter) is considered a proxy for age, the dimorphs were the same age at death, and the septa in the compressed variants developed via acceleration relative to the depressed variants. Regarding conch shape (width vs. diameter), the compressed morphs developed via neoteny relative to the depressed morphs. If septal count is considered a proxy for age, the dimorphs were not the same age at death, and the compressed forms were produced by a combination of hypermorphosis plus neoteny, i.e., they grew longer yet slower than the depressed forms. In A. relictus, the heterochronic processes of hypermorphosis and neoteny may have been operating simultaneously, which is an interesting possibility because it is an example of a combination of both peramorphic and paedomorphic processes.