Assessing the utility of atrial fibrillation induction to risk stratify children with Wolff-Parkinson-White syndrome.

BACKGROUND: Wolff-Parkinson-White syndrome is associated with sudden cardiac death from rapid conduction through the accessory pathway in atrial fibrillation. Adult patients are at higher risk for sudden cardiac death if the shortest-pre-excited-RR-interval in atrial fibrillation (SPERRI) is ≤250 milliseconds (msec) during electrophysiologic study. Exclusive conduction through the atrioventricular node in atrial fibrillation is presumed to convey lower risk. The shortest-pre-excited-paced-cycle-length with atrial pacing has also served as a marker for risk stratification. OBJECTIVE: To determine accessory pathway characteristic of patients undergoing induction of atrial fibrillation during electrophysiologic study. METHODS: We reviewed 321 pediatric patients that underwent electrophysiologic study between 2010 and 2019. Induction of atrial fibrillation was attempted on patients while on isoproterenol and SPERRI was measured if atrial fibrillation was induced. Shortest-pre-excited-paced-cycle-length (SPPCL) was determined while on isoproterenol. RESULTS: Atrial fibrillation was induced in 233 (73%) patients. Of those, 104 (45%) patients conducted exclusively through the atrioventricular node during atrial fibrillation (Group A). The remaining 129 (55%) patients had some conduction through the accessory pathway (Group B). In Group A, SPPCL was 260 msec with 48 (46%) conducting through the accessory pathway at ≤250 msec. In Group B, SPPCL was 240 msec with 92 patients (71%) conducting at ≤250 msec (p < 0.05). In Group B, SPERRI was 250 msec and had a positive correlation with SPPCL (p < 0.001, R2 = 0.28). Almost half (46%) of those with exclusive conduction through the atrioventricular node in atrial fibrillation had rapid accessory pathway conduction with atrial pacing. CONCLUSION: Conduction in atrial fibrillation during electrophysiologic study on isoproterenol via the atrioventricular node may not exclude high-risk accessory pathways in pediatric patients.

Development of a Model to Identify Febrile Children at Low Risk for Multisystem Inflammatory Syndrome.

OBJECTIVES: The case definition for multisystem inflammatory syndrome in children (MIS-C) is broad and encompasses symptoms and signs commonly seen in children with fever. Our aim was to identify clinical predictors that, independently or in combination, identify febrile children presenting to the emergency department (ED) as low risk for MIS-C. METHODS: We conducted a retrospective single-center study of otherwise healthy children 2 months to 20 years of age presenting to the ED with fever and who had a laboratory evaluation for MIS-C between April 15, 2020, and October 31, 2020. We excluded children with a diagnosis of Kawasaki disease. Our outcome was an MIS-C diagnosis defined by the Centers for Disease Control and Prevention criteria. We conducted multivariable logistic regression analyses to identify variables independently associated with MIS-C. RESULTS: Thirty-three patients with and 128 patients without MIS-C were analyzed. Of those with MIS-C, 16 of 33 (48.5%) had hypotension for age, signs of hypoperfusion, or required ionotropic support. Four variables were independently associated with the presence of MIS-C; known or suspected SARS CoV-2 exposure (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.9) and the following 3 symptoms and signs: abdominal pain on history (aOR, 4.8; 95% CI, 1.7-15.0), conjunctival injection (aOR, 15.2; 95% CI, 5.4-48.1), and rash involving the palms or soles (aOR, 12.2; 95% CI, 2.4-69.4). Children were at low risk of MIS-C if none of the 3 symptoms or signs were present (sensitivity 87.9% [95% CI, 71.8-96.6]; specificity 62.5% [53.5-70.9], negative predictive value 95.2% [88.3-98.7]). Of the 4 MIS-C patients without any of these 3 factors, 2 were ill-appearing in the ED and the other 2 had no cardiovascular involvement during their clinical course. CONCLUSIONS: A combination of 3 clinical symptoms and signs had moderate to high sensitivity and high negative predictive value for identifying febrile children at low risk of MIS-C. If validated, these factors could aid clinicians in determining the need to obtain or forego an MIS-C laboratory evaluation during SARS-CoV-2 prevalent periods in febrile children.

Ethanolamine ameliorates mitochondrial dysfunction in cardiolipin-deficient yeast cells.

Cardiolipin (CL) is a signature phospholipid of the mitochondria required for the formation of mitochondrial respiratory chain (MRC) supercomplexes. The destabilization of MRC supercomplexes is the proximal cause of the pathology associated with the depletion of CL in patients with Barth syndrome. Thus, promoting supercomplex formation could ameliorate mitochondrial dysfunction associated with CL depletion. However, to date, physiologically relevant small-molecule regulators of supercomplex formation have not been identified. Here, we report that ethanolamine (Etn) supplementation rescues the MRC defects by promoting supercomplex assembly in a yeast model of Barth syndrome. We discovered this novel role of Etn while testing the hypothesis that elevating mitochondrial phosphatidylethanolamine (PE), a phospholipid suggested to overlap in function with CL, could compensate for CL deficiency. We found that the Etn supplementation rescues the respiratory growth of CL-deficient Saccharomyces cerevisiae cells in a dose-dependent manner but independently of its incorporation into PE. The rescue was specifically dependent on Etn but not choline or serine, the other phospholipid precursors. Etn improved mitochondrial function by restoring the expression of MRC proteins and promoting supercomplex assembly in CL-deficient cells. Consistent with this mechanism, overexpression of Cox4, the MRC complex IV subunit, was sufficient to promote supercomplex formation in CL-deficient cells. Taken together, our work identifies a novel role of a ubiquitous metabolite, Etn, in attenuating mitochondrial dysfunction caused by CL deficiency.

Delayed presentation and sub-optimal outcomes of pediatric patients with acute appendicitis during the COVID-19 pandemic.

OBJECTIVE: Early presentation and prompt diagnosis of acute appendicitis are necessary to prevent progression of disease leading to complicated appendicitis. We hypothesize that patients had a delayed presentation of acute appendicitis during the COVID-19 pandemic, which affected severity of disease on presentation and outcomes. PATIENTS AND METHODS: We conducted a retrospective review of all patients who were treated for acute appendicitis at Morgan Stanley Children's Hospital (MSCH) between March 1, 2020 and May 31, 2020 when the COVID-19 pandemic was at its peak in New York City (NYC). For comparison, we reviewed patients treated from March 1, 2019 to May 31, 2019, prior to the pandemic. Demographics and baseline patient characteristics were analyzed for potential confounding variables. Outcomes were collected and grouped into those quantifying severity of illness on presentation to our ED, type of treatment, and associated post-treatment outcomes. Fisher's Exact Test and Kruskal-Wallis Test were used for univariate analysis while cox regression with calculation of hazard ratios was used for multivariate analysis. RESULTS: A total of 89 patients were included in this study, 41 patients were treated for appendicitis from March 1 to May 31 of 2019 (non-pandemic) and 48 were treated during the same time period in 2020 (pandemic). Duration of symptoms prior to presentation to the ED was significantly longer in patients treated in 2020, with a median of 2 days compared to 1 day (p = 0.003). Additionally, these patients were more likely to present with reported fever (52.1% vs 24.4%, p = 0.009) and had a higher heart rate on presentation with a median of 101 beats per minute (bpm) compared to 91 bpm (p = 0.040). Findings of complicated appendicitis on radiographic imaging including suspicion of perforation (41.7% vs 9.8%, p < 0.001) and intra-abdominal abscess (27.1% vs 7.3%, p = 0.025) were higher in patients presenting in 2020. Patients treated during the pandemic had higher rates of non-operative treatment (25.0% vs 7.3%, p = 0.044) requiring increased antibiotic use and image-guided percutaneous drain placement. They also had longer hospital length of stay by a median of 1 day (p = 0.001) and longer duration until symptom resolution by a median of 1 day (p = 0.004). Type of treatment was not a predictor of LOS (HR = 0.565, 95% CI = 0.357-0.894, p = 0.015) or duration until symptom resolution (HR = 0.630, 95% CI = 0.405-0.979, p = 0.040). CONCLUSION: Patients treated for acute appendicitis at our children's hospital during the peak of the COVID-19 pandemic presented with more severe disease and experienced suboptimal outcomes compared to those who presented during the same time period in 2019. LEVEL OF EVIDENCE: III.