Unlike adults, children with fluid-refractory shock are frequently hypodynamic and respond to inotrope and vasodilator therapy. Because hemodynamic states are heterogeneous and change with time, an incorrect cardiovascular therapeutic regimen should be suspected in any child with persistent shock. Outcome can be improved compared with historical literature.

Our group recently reported that cultured sheep pulmonary artery endothelial cells (SPAECs) became resistant to lipopolysaccharide (LPS)-induced apoptosis several days after constitutive synthesis of nitric oxide (NO) after adenoviral (Ad) transfer of inducible NO synthase (iNOS) or exposure to the NO donor S-nitroso- N-acetylpenicillamine (SNAP) (E. Tzeng, Y.-M. Kim, B. R. Pitt, A. Lizonova, I. Kovesdi, and T. R. Billiar. Surgery 122: 255–263, 1997). In the present study, we confirmed this observation by establishing stable transfectants after retroviral gene transfer [replication-deficient retrovirus (DFG)] of human iNOS (DFG-iNOS) SPAECs and then used all three approaches (Ad, DFG, and SNAP) to determine underlying mechanisms of this phenomenon. Continuous endogenous production of NO in itself did not cause apoptosis as assessed by phase-contrast microscopy, nuclear morphology, and internucleosomal DNA fragmentation. Prolonged (72–96 h) synthesis of NO, however, after DFG- or replication-deficient adenovirus (Ad.CMV)-iNOS or SNAP (100 μM, 96 h) inhibited LPS-induced apoptosis. The kinetics of such protection suggested that NO may be inducing other gene products. Ad-mediated transfer of manganese superoxide dismutase (MnSOD) decreased the sensitivity of wild-type SPAECs to LPS-induced apoptosis. MnSOD, however, was not induced in an N G-monomethyl-l-arginine (l-NMMA)-sensitive time-dependent fashion after Ad.CMV-iNOS. Other inducible genes that may be affected by NO and that may protect against potential oxidant-mediated LPS-induced apoptosis including 70-kDa heat shock protein, heme oxygenase-1, metallothionein, and Bcl-2 also were not elevated in an l-NMMA-sensitive, time-dependent fashion. Although the candidate gene product underlying NO-induced protection remains unclear, we did note that prolonged synthesis of NO inhibited LPS-induced activation of an interleukin-1β-converting enzyme-like cysteine protease (cysteine protease protein-32-like) in a dithiothreitol-sensitive fashion, suggesting that S-nitrosylation of an important downstream target of convergence of apoptotic signals may contribute to the sensitivity of SPAECs to LPS.

Background/Objectives Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be associated with febrile seizures, but the overall frequency and outcomes are unknown. The objectives of this study are to (1) determine the frequency of pediatric subjects diagnosed with febrile seizures and COVID-19, (2) evaluate patient characteristics, and (3) describe the treatments (medications and need for invasive mechanical ventilation) applied. Methods This was a retrospective study utilizing TriNetX electronic health record data. We included subjects ranging from 0 to 5 years of age with a diagnosis of febrile seizures (R56.00, R56.01) and COVID-19 (U07.1). We extracted the following data: age, race, ethnicity, diagnostic codes, medications, laboratory results, and procedures. Results During this study period, 8854 pediatric subjects aged 0-5 years were diagnosed with COVID-19 among 34 health care organizations and 44 (0.5%) were also diagnosed with febrile seizures (simple, 30 [68.2%]; complex, 14 [31.8%]). The median age was 1.5 years (1, 2), there were no reported epilepsy diagnoses, and a proportion required hospitalization (11; 25.0%) and critical care services (4; 9.1%). Conclusions COVID-19 infections in children can be associated with febrile seizures. In our study, 0.5% of COVID-19 subjects were diagnosed with febrile seizures and approximately 9% of subjects were reported to require critical care services. Febrile seizures, although serious, are not a commonly diagnosed neurologic manifestation of COVID-19.

Background: Aminophylline, an established bronchodilator, is also purported to be an effective diuretic and anti-inflammatory agent. However, the data to support these contentions are scant. We conducted a prospective, open-label, single arm, single center study to assess the hypothesis that aminophylline increases urine output and decreases inflammation in critically ill children.Methods: Children less than 18 years of age admitted to the pediatric intensive care unit who were prescribed aminophylline over a 24-h period were eligible for study. The use and dosing of aminophylline was independent of the study and was at the discretion of the clinical team. Data analyzed consisted of demographics, diagnoses, medications, and markers of pulmonary function, renal function, and inflammation. Data were collected at baseline and at 24-h after aminophylline initiation with primary outcomes of change in urine output and inflammatory cytokine concentrations.Results: Thirty-five patients were studied. Urine output increased significantly with aminophylline use [median increase 0.5 mL/kg/h (IQR: −0.3, 1.3), p = 0.05] while blood urea nitrogen and creatinine concentrations remained unchanged. Among patients with elevated C-reactive protein concentrations, levels of both interleukin-6 (IL-6) and IL-10 decreased at 24 h of aminophylline therapy. There were no significant differences in pulmonary compliance or resistance among patients invasively ventilated at both time points. Side effects of aminophylline were detected in 7 of 35 patients.Conclusion: Although no definitive conclusions can be drawn from this study, aminophylline may be a useful diuretic and effective anti-inflammatory medication in critically ill children. Given the incidence of side effects, the small sample size and the uncontrolled study design, further study is needed to inform the appropriate use of aminophylline in these children.

Children with complex, life-limiting conditions and their families referred to a palliative care service commonly verbalize goals related to health maintenance and independence. Anticipating this expectation may foster communication and improve patient care.