Late development of intra-atrial reentrant tachycardia in lateral tunnel Fontan patients and the preventive role of prophylactic cryoablation.

OBJECTIVE: Intra-atrial reentrant tachycardia is an important late-onset complication in patients undergoing the Fontan procedure. However, the protective effects of prophylactic cryoablation against late-onset intra-atrial reentrant tachycardia are unclear. This study investigated the late development of intra-atrial reentrant tachycardia in patients undergoing the lateral tunnel Fontan procedure and the role of prophylactic cryoablation. METHODS: This was a single-center retrospective cohort study of patients who underwent the lateral tunnel Fontan procedure between 1988 and 2003. Univariate and multivariable competing risks regression models were used to determine the associations of prophylactic cryoablation and covariates with the outcomes of interest: late-onset intra-atrial reentrant tachycardia, all-cause mortality, and cardiovascular mortality. RESULTS: In total, 130 patients who underwent the lateral tunnel Fontan procedure, 30 of whom had undergone prophylactic cryoablation, were included in this study and followed up for a median of 23.6 years (interquartile range, 17.7-26.5). Intra-atrial reentrant tachycardia was identified in 14 patients (10.8%), none of whom underwent prophylactic cryoablation. The median Fontan-to-intra-atrial reentrant tachycardia time was 17.2 years (interquartile range, 11.1-23.1). Prophylactic cryoablation was protective against late-onset intra-atrial reentrant tachycardia (P < .0001) and cardiovascular mortality (P < .0001) in the type 3 test. CONCLUSIONS: None of the patients who underwent prophylactic cryoablation developed late-onset intra-atrial reentrant tachycardia during a median follow-up time of 22.9 years. Our study demonstrated that prophylactic cryoablation was effective in preventing late-onset intra-atrial reentrant tachycardia and cardiovascular mortality in patients undergoing the lateral tunnel Fontan.

Severe protein C deficiency in a newborn caused by a homozygous pathogenic variant in the PROC gene: a case report.

BACKGROUND: Severe protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment. CASE PRESENTATION: A four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 µg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene. CONCLUSION: Severe protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae.

Lacrimo-auriculo-dento-digital syndrome: A novel mutation in a Korean family and review of literature.

BACKGROUND: Lacrimo-auriculo-dento-digital (LADD) syndrome is a rare autosomal dominant disorder caused by mutations in one of the three genes: fibroblast growth factor receptor 2 (FGFR2), FGFR3, or FGF10. Affected patients have hypoplasia/aplasia of lacrimal ducts/glands, hypoplasia/aplasia of salivary glands, dental anomalies, ear anomalies, hearing loss, and digital anomalies. CASE PRESENTATION: Proband was an 11-year-old male with xerostomia, xerophthalmia, and a referring diagnosis of Sjogren syndrome. He presented with microdontia, hypodontia, low-set/cupped ear auricles, and hearing loss in the left ear. METHODS: Whole exome sequencing (WES) was performed on proband. Variations and segregation within the family were verified using Sanger sequencing. RESULTS: Molecular studies revealed a novel heterozygous missense mutation in exon 11 of FGFR2: c.1547C>T (p.Ala516Val), compatible with LADD syndrome. CONCLUSION: To the best of our knowledge, this is the first report of a family with LADD syndrome in Korea. The combination of xerostomia and xerophthalmia, seen in patients with LADD syndrome, may be misdiagnosed as Sjogren syndrome. WES may be a useful clinical tool in ascertaining the affected gene in patients with suspected genetic disorders. Here, a literature review and summary of 23 case reports/series of LADD syndrome are presented, which may help to identify patients with this condition.

The Associations between Antenatal Corticosteroids and In-Hospital Outcomes of Preterm Singleton Appropriate for Gestational Age Neonates according to the Presence of Maternal Histologic Chorioamnionitis.

INTRODUCTION: This study aimed to assess the association between antenatal corticosteroid (ACS) and in-hospital outcomes of preterm singleton appropriate for gestational age (AGA) infants according to the presence of maternal histologic chorioamnionitis (HCA). METHODS: A retrospective study was performed with singleton AGA neonates of 23+0 to 33+6 weeks' gestation born between 2007 and 2014. We compared the clinical outcomes according to the presence of HCA and ACS use. We also divided the ACS group into 2 groups: infants who received ACS 2-7 days before birth (optimal ACS) or not (suboptimal ACS). Multivariate logistic regression with Firth's penalized likelihood was performed. RESULTS: In total, 254 neonates were eligible with 109 neonates with HCA (42.9%). In multivariate analysis adjusting for GA, sex, and cesarean section, ACS use was associated with reduced severe bronchopulmonary dysplasia (BPD) or death and hypotension within 7 postnatal days among the neonates with HCA. However, it was associated with increased patent ductus arteriosus (PDA) treatment. In the optimal ACS group, severe BPD or death (aOR 0.03, 95% CI 0.01-0.42), hypotension (aOR 0.02, 95% CI 0.01-0.26), and inhaled nitric oxide use (aOR 0.06, 95% CI 0.00-0.81) were lower, however, PDA treatment (aOR 8.14, 95% CI 1.20-55.24) and sepsis (aOR 6.85, 95% CI 1.02-46.07) were higher when compared with the no ACS group among HCA+ infants. Among HCA- infants, only PDA treatment was lower in the ACS group. CONCLUSION: In neonates with HCA, ACS treatment was associated with reduced morbidities. However, increased sepsis was associated with optimal ACS use.