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A Pregnant Adolescent with COVID-19 and Multisystem Inflammatory Syndrome in Children [Case Report]

Trostle, Megan E; Grossman, Tracy B; Penfield, Christina A; Phoon, Colin K L; Raabe, Vanessa N; Sloane, Mark F; Roman, Ashley S
Multisystem inflammatory syndrome in children (MIS-C), a new condition related to coronavirus disease 2019 (COVID-19) in the pediatric population, was recognized by physicians in the United Kingdom in April 2020. Given those up to the age of 21 years can be affected, pregnant adolescents and young adults are susceptible. However, there is scant information on how MIS-C may affect pregnancy and whether the presentation differs in the pregnant population. We report a case of a pregnant adolescent with COVID-19 and MIS-C with a favorable outcome. This case highlights the considerations in managing a critically ill pregnant patient with a novel illness and the importance of a multidisciplinary team in coordinating care.
PMID: 38370327
ISSN: 2157-6998
CID: 5633982

An Anterior Second Heart Field Enhancer Regulates the Gene Regulatory Network of the Cardiac Outflow Tract

Yamaguchi, Naoko; Chang, Ernest W; Lin, Ziyan; Shekhar, Akshay; Bu, Lei; Khodadadi-Jamayran, Alireza; Tsirigos, Aristotelis; Cen, Yiyun; Phoon, Colin K L; Moskowitz, Ivan P; Park, David S
BACKGROUND/UNASSIGNED:Conotruncal defects due to developmental abnormalities of the outflow tract (OFT) are an important cause of cyanotic congenital heart disease. Dysregulation of transcriptional programs tuned by NKX2-5 (NK2 homeobox 5), GATA6 (GATA binding protein 6), and TBX1 (T-box transcription factor 1) have been implicated in abnormal OFT morphogenesis. However, there remains no consensus on how these transcriptional programs function in a unified gene regulatory network within the OFT. METHODS/UNASSIGNED: RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:Our results using human and mouse models reveal an essential gene regulatory network of the OFT that requires an anterior second heart field enhancer to link GATA6 with NKX2-5-dependent rotation and septation gene programs.
PMID: 37772400
ISSN: 1524-4539
CID: 5606412

Knowledge is power: regarding SMFM Consult Series #64: Systemic lupus erythematosus in pregnancy [Editorial]

Cuneo, Bettina F; Buyon, Jill P; Sammaritano, Lisa; Jaeggi, Edgar; Arya, Bhawna; Behrendt, Nicholas; Carvalho, Julene; Cohen, Jennifer; Cumbermack, Kristopher; DeVore, Greggory; Doan, Tam; Donofrio, Mary T; Freud, Lindsay; Galan, Henry L; Groper, Melanie R F; Haxel, Caitlin; Hornberger, Lisa K; Howley, Lisa W; Izmirly, Peter; Killen, Stacy S; Kaplinski, Michelle; Krishnan, Anita; Lavasseur, Stephanie; Lindblade, Christopher; Matta, Jyothi; Makhoul, Majd; Miller, Jena; Morris, Shaine; Paul, Erin; Perrone, Erin; Phoon, Colin; Pinto, Nelangi; Rychik, Jack; Satou, Gary; Saxena, Amit; Sklansky, Mark; Stranic, James; Strasburger, Janette F; Srivastava, Shubhika; Srinivasan, Sharda; Tacy, Theresa; Tworetzky, Wayne; Uzun, Orhan; Yagel, Simcha; Zaretsky, Michael V; Moon-Grady, Anita J
PMID: 37394327
ISSN: 1097-6868
CID: 5538952

Cardiolipin prolongs the lifetimes of respiratory proteins in Drosophila flight muscle

Ren, Mindong; Xu, Yang; Phoon, Colin K L; Erdjument-Bromage, Hediye; Neubert, Thomas A; Schlame, Michael
Respiratory complexes and cardiolipins have exceptionally long lifetimes. The fact that they co-localize in mitochondrial cristae raises the question of whether their longevities have a common cause and whether the longevity of OXPHOS proteins is dependent on cardiolipin. To address these questions, we developed a method to measure side-by-side the half-lives of proteins and lipids in wild-type Drosophila and cardiolipin-deficient mutants. We fed adult flies with stable isotope-labeled precursors (13C6
PMID: 37690688
ISSN: 1083-351x
CID: 5594302

TGFβ-2 Haploinsufficiency Causes Early Death in Mice with Marfan Syndrome

Sachan, Nalani; Phoon, Colin K L; Zilberberg, Lior; Kugler, Matthias C; Ene, Taylor; Mintz, Shana B; Murtada, Sae-Il; Weiss, Dar; Fishman, Glenn I; Humphrey, Jay D; Rifkin, Daniel B
To assess the contribution of individual TGF-β isoforms to aortopathy in Marfan syndrome (MFS), we quantified the survival and phenotypes of mice with a combined fibrillin1 (the gene defective in MFS) hypomorphic mutation and a TGF-β1, 2, or 3 heterozygous null mutation. The loss of TGF-β2, and only TGF-β2, resulted in 80% of the double mutant animals dying earlier, by post-natal day 20, than MFS only mice. Death was not from thoracic aortic rupture, as observed in MFS mice, but was associated with hyperplastic aortic valve leaflets, aortic regurgitation, enlarged aortic root, increased heart weight, and impaired lung alveolar septation. Thus, there appears to be a relationship between loss of fibrillin1 and TGF-β2 in the post-natal development of the heart, aorta and lungs.
PMID: 37217119
ISSN: 1569-1802
CID: 5543662

The critical role of cardiolipin in metazoan differentiation, development, and maturation

Olivar-Villanueva, Melissa; Ren, Mindong; Schlame, Michael; Phoon, Colin K L
Cardiolipins are phospholipids that are central to proper mitochondrial functioning. Because mitochondria play crucial roles in differentiation, development, and maturation, we would also expect cardiolipin to play major roles in these processes. Indeed, cardiolipin has been implicated in the mechanism of three human diseases that affect young infants, implying developmental abnormalities. In this review, we will: (1) Review the biology of cardiolipin; (2) Outline the evidence for essential roles of cardiolipin during organismal development, including embryogenesis and cell maturation in vertebrate organisms; (3) Place the role(s) of cardiolipin during embryogenesis within the larger context of the roles of mitochondria in development; and (4) Suggest avenues for future research.
PMID: 36692477
ISSN: 1097-0177
CID: 5426542

Why Don't More Mitochondrial Diseases Exhibit Cardiomyopathy?

Singh, Nina; Ren, Mindong; Phoon, Colin K L
BACKGROUND:Although the heart requires abundant energy, only 20-40% of children with mitochondrial diseases have cardiomyopathies. METHODS:We looked for differences in genes underlying mitochondrial diseases that do versus do not cause cardiomyopathy using the comprehensive Mitochondrial Disease Genes Compendium. Mining additional online resources, we further investigated possible energy deficits caused by non-oxidative phosphorylation (OXPHOS) genes associated with cardiomyopathy, probed the number of amino acids and protein interactors as surrogates for OXPHOS protein cardiac "importance", and identified mouse models for mitochondrial genes. RESULTS:< 0.05). Mouse models exhibiting cardiomyopathy were found for 52/241 mitochondrial genes, shedding additional insights into biological mechanisms. CONCLUSIONS:While energy generation is strongly associated with cardiomyopathy in mitochondrial diseases, many energy generation defects are not linked to cardiomyopathy. The inconsistent link between mitochondrial disease and cardiomyopathy is likely to be multifactorial and includes tissue-specific expression, incomplete clinical data, and genetic background differences.
PMID: 37103033
ISSN: 2308-3425
CID: 5465302

Autoimmune Congenital Complete Heart Block: How Late Can It Occur?

Makadia, Luv; Izmirly, Peter; Buyon, Jill P; Phoon, Colin K L
PMID: 37168107
ISSN: 2157-6998
CID: 5544602

Characteristics of Cardiac Abnormalities in Pediatric Patients With Acute COVID-19

Pasternack, Daniel; Singh, Rakesh K; Minocha, Prashant K; Farkas, Jon S; Ramaswamy, Prema; Better, Donna; Verma, Sourabh; Phoon, Colin K
Introduction Coronavirus disease 2019 (COVID-19) is known to cause cardiac abnormalities in adults. Cardiac abnormalities are well-described in multisystem inflammatory syndrome in children, but effects in children with acute COVID-19 are less understood. In this multicenter study, we assessed the cardiac effects of acute COVID-19 among hospitalized children (<21 years) admitted to three large healthcare systems in New York City. Methods We performed a retrospective observational study. We examined electrocardiograms, echocardiograms, troponin, or B-type natriuretic peptides. Results Of 317 admitted patients, 131 (41%) underwent cardiac testing with 56 (43%) demonstrating cardiac abnormalities. Electrocardiogram abnormalities were the most common (46/117 patients (39%)), including repolarization abnormalities and QT prolongation. Elevated troponin occurred in 14/77 (18%) patients and B-type natriuretic peptide in 8/39 (21%) patients. Ventricular dysfunction was identified in 5/27 (19%) patients with an echocardiogram, all of whom had elevated troponin. Ventricular dysfunction resolved by first outpatient follow-up. Conclusion Electrocardiogram and troponin can assist clinicians in identifying children at risk for cardiac injury in acute COVID-19.
PMID: 37065296
ISSN: 2168-8184
CID: 5459202

Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies

Buyon, Jill P.; Masson, Mala; Izmirly, Caroline G.; Phoon, Colin; Acherman, Ruben; Sinkovskaya, Elena; Abuhamad, Alfred; Makhoul, Majd; Satou, Gary; Hogan, Whitnee; Pinto, Nelangi; Moon-Grady, Anita; Howley, Lisa; Donofrio, Mary; Krishnan, Anita; Ahmadzia, Homa; Levasseur, Stephanie; Paul, Erin; Owens, Sonal; Cumbermack, Kristopher; Matta, Jyothi; Joffe, Gary; Lindblade, Christopher; Haxel, Caitlin; Kohari, Katherine; Copel, Joshua; Strainic, James; Doan, Tam; Bermudez-Wagner, Karla; Holloman, Conisha; Sheth, Shreya S.; Killen, Stacy; Tacy, Theresa; Kaplinski, Michelle; Hornberger, Lisa; Carlucci, Philip M.; Izmirly, Peter; Fraser, Nicola; Clancy, Robert M.; Cuneo, Bettina F.
Objective: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). Methods: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti"“52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17"“26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. Results: Anti"“52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti"“60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. Conclusion: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms. (Figure presented.).
ISSN: 2326-5191
CID: 5615912