Diagnostic Yield of Cardiac Biomarker Testing in Predicting Cardiac Disease and Multisystem Inflammatory Syndrome in Children in the Pandemic Era.

OBJECTIVES: This study aimed to assess whether elevations in cardiac biomarkers are associated with pediatric cardiac diagnoses in the era of COVID-19 and multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: This single-center retrospective study analyzed children with a troponin drawn in the emergency department or inpatient unit between April 21 and December 31, 2020. The primary outcome was the presence of a cardiac diagnosis or MIS-C. Relationships among demographics, complaint, cardiac diagnostics, and cardiac biomarkers were analyzed. RESULTS: Four hundred eighty-six patients (mean ± SD; age 13.1 ± 7.8 years; 46.7% women) met inclusion criteria, for whom a cardiac diagnosis (excluding MIS-C) was made in 27 (5.6%) patients, with MIS-C diagnosed in 14 (2.9%) patients. The sensitivity and specificity of an elevated initial high-sensitivity troponin T (hsTropT) value (>14 ng/L) in predicting the composite outcome of a cardiac diagnosis or MIS-C were 54% and 89%, respectively. Four percent of patients with negative initial troponin values were found to have a cardiac diagnosis or MIS-C. Multivariable regression analysis demonstrated that elevated hsTropT (>14 ng/L; odds ratio [OR] [95% confidence interval]: 4.9 [1.70-14.0]) and elevated N-terminal pro B-type natriuretic peptide values (>500 pg/mL; 6.4 [2.01-20.1]) were associated with increased odds of a cardiac diagnosis or MIS-C. CONCLUSIONS: Children with elevated cardiac biomarkers have increased odds of a cardiac diagnosis or MIS-C and warrant workup regardless of indication for testing. Although a negative hsTropT may reassure providers, further investigation is critical in developing algorithms to reliably exclude cardiac disease.

Operational Innovation in the Provision of Pediatric Extracorporeal Membrane Oxygenation for Multisystem Inflammatory Syndrome in Children.

Treatment of multisystem inflammatory syndrome in children (MIS-C) can require significant critical care resources. Our aim is to alert mixed pediatric and adult hospitals worldwide of the possibility that pediatric and adult patients may simultaneously require cannulation to extracorporeal membrane oxygenation (ECMO) for MIS-C and severe COVID-19. We conducted a retrospective review of operations required to treat cardiogenic shock in 3 pediatric patients with a diagnosis of MIS-C admitted to a single medium-sized pediatric referral center located within a large academic medical center over a 14-day period. At this time, a large number of adult patients required ECMO for severe COVID-19 at our institution. Of the 11 pediatric patients who presented with MIS-C during the first surge of 2020, 2 patients required cannulation to venoarterial extracorporeal membrane oxygenation (VA-ECMO), and a third patient developed a life-threatening arrhythmia requiring transfer to a neighboring institution for consideration of VA-ECMO when our institution's ECMO capacity had briefly been reached. Pediatric referral centers located within institutions providing ECMO to adult patients with severe COVID-19 may benefit from frequent and direct communication with their adult and regional colleagues to devise a collaborative plan for safe and timely provision of ECMO to patients with MIS-C as the ongoing pandemic continues to consume this limited, lifesaving resource.

Ventricular tachycardia after naloxone administration in an adolescent.

Naloxone is a medication with a largely benign safety profile that is frequently administered in the emergency department to patients presenting with altered mental status. Ventricular tachycardia has been reported after naloxone administration in adult patients with prior use of opiate or sympathomimetic medications. However, no such reports exist in the pediatric population or in patients who have no known history of opiate or sympathomimetic medication use. We describe a case of ventricular tachycardia after naloxone administration in a 17-year-old male with no known prior use of opiate or sympathomimetic agents who presented to the emergency department with altered mental status of unknown etiology. Emergency physicians may wish to prepare for prompt treatment of ventricular arrythmias when administering naloxone to pediatric patients presenting with altered mental status.

Distinguishing Features of Patients Evaluated for Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: Given the significant overlap of multisystem inflammatory syndrome in children (MIS-C) with other common childhood illnesses presenting to the emergency department, extensive workup of this syndrome has become necessary. Nevertheless, little has been published on the factors differentiating MIS-C from other conditions in the acute care setting. We investigated differences in presentation and laboratory studies between suspected versus confirmed MIS-C patients. METHODS: This was a retrospective cohort study on patients 21 years or younger undergoing investigation for possible MIS-C at a single institution between April 21 and July 1, 2020. The primary outcome was diagnosis of MIS-C or an alternative final diagnosis. Clinical features and laboratory findings from initial presentation were collected and analyzed. RESULTS: A total of 106 patients (median, 4 years; 55.7% male) were included, of whom 17 (16%) of 106 met the criteria for MIS-C. Multisystem inflammatory syndrome in children patients were significantly more likely to report a coronavirus disease 2019 exposure (odds ratio (OR), 13.17 [3.87-44.9]), have gastrointestinal symptoms (OR, 3.81 [1.02-14.19]), and have a significantly higher odds of having abnormal laboratory values including high-sensitivity troponin T (OR, 13 [4.0-42.2]), N-terminal B-type natriuretic peptide (OR, 8.4 [2.3-30.1]), D-dimer (OR, 13 [1.6-103]), and ferritin (OR, 7.8 [2.2-27.2]). There were also differences between groups in inflammatory markers: C-reactive protein (median, 134.45 mg/L vs 12.6 mg/L; P < 0.05) and procalcitonin (1.71 ng/mL vs 0.14 ng/mL; P < 0.001). CONCLUSIONS: Higher elevations in key laboratory studies may help to distinguish between MIS-C patients and non-MIS-C patients presenting to the emergency department.

Pseudohyperkalemia and Pseudohyponatremia in Two Children with T-Cell Acute Lymphoblastic Leukemia.

Pseudohyperkalemia and pseudohyponatremia are phenomena in which hematologic disorders with high cell counts result in factitious electrolyte measurements that can result in inappropriate treatment. We describe 2 children with leukemia presenting with both disturbances to highlight the importance of correlating electrolyte results from plasma with those from whole blood before intervening.

Cell-specific activation of RIPK1 and MLKL after intracerebral hemorrhage in mice.

Receptor-interacting protein kinase-1 (RIPK1) is a master regulator of cell death and inflammation, and mediates programmed necrosis (necroptosis) via mixed-lineage kinase like (MLKL) protein. Prior studies in experimental intracerebral hemorrhage (ICH) implicated RIPK1 in the pathogenesis of neuronal death and cognitive outcome, but the relevant cell types involved and potential role of necroptosis remain unexplored. In mice subjected to autologous blood ICH, early RIPK1 activation was observed in neurons, endothelium and pericytes, but not in astrocytes. MLKL activation was detected in astrocytes and neurons but not endothelium or pericytes. Compared with WT controls, RIPK1 kinase-dead (RIPK1D138N/D138N) mice had reduced brain edema (24 h) and blood-brain barrier (BBB) permeability (24 h, 30 d), and improved postinjury rotarod performance. Mice deficient in MLKL (Mlkl-/-) had reduced neuronal death (24 h) and BBB permeability at 24 h but not 30d, and improved post-injury rotarod performance vs. WT. The data support a central role for RIPK1 in the pathogenesis of ICH, including cell death, edema, BBB permeability, and motor deficits. These effects may be mediated in part through the activation of MLKL-dependent necroptosis in neurons. The data support development of RIPK1 kinase inhibitors as therapeutic agents for human ICH.

Measured CPAP in a Noninvasive Pediatric Airway and Lung Model.

BACKGROUND: Bronchiolitis is the most common cause of admission in children < 2 y of age in the United States. The standard of care involves supportive measures, including noninvasive interventions such as CPAP. CPAP is traditionally delivered through a full face mask; however, pediatric ICUs have been exploring the use of the RAM cannula by Neotech as a mode of CPAP delivery. The level of CPAP delivered via the RAM cannula is uncertain. We performed an in vitro study to determine the level of CPAP delivered via the RAM cannula utilizing a pediatric lung model. METHODS: Models of 7 sizes of pediatric upper airways, produced with a 3-dimensional printer, were connected to a breathing simulator. We applied each size of RAM cannula to weight-appropriate airway and lung compliance parameters, delivering pressures of 5, 7, and 10 cm H2O using a ventilator in the CPAP mode. Leaks of 0%, 20%, 40%, and 60% were generated to emulate a complete seal, a poor fit, and open-mouth breathing. The outcome measure was the difference in CPAP, referred to as "%leak effect," measured by the lung simulator relative to the CPAP set on the ventilator. RESULTS: We found that set CPAP of 5-10 cm H2O generated measured CPAP ranging from 2.6 to 9.7 cm H2O. For the set CPAP levels of 5, 7, and 10 cm H2O, the mean %leak effect values of measured CPAP from the set CPAP were -25%, -26%, and -25.7%, respectively. For each specific cannula-airway combination, increasing the set pressure and decreasing the air leak resulted in higher levels of CPAP delivered. CONCLUSIONS: The RAM cannula delivered varying amounts of CPAP, with a percent loss of approximately -25% depending on the level of leak in the system. With minimal leak, it is conceivable that the RAM cannula can be used to deliver clinically meaningful CPAP.

Adult COVID-19 Patients Cared for in a Pediatric ICU Embedded in a Regional Biothreat Center: Disease Severity and Outcomes.

The objective of this study was to describe the clinical characteristics and outcomes of adult coronavirus disease 2019 (COVID-19) patients admitted to a pediatric intensive care unit (PICU), with assessment of respiratory clinical severity and outcomes when cared for by pediatric intensivists utilizing specific care processes. We conducted a retrospective cohort study of adult patients admitted to the 14-bed PICU of a quaternary referral center during the COVID-19 surge in Boston between April and June 2020. A total of 37 adults were admitted: 28 tested COVID-19 positive and 9 tested COVID-19 negative. Of the COVID-19-positive patients, 21 (75%), were male and 12 (60.7%) identified as Hispanic/Latino. Comorbidities in the patients included diabetes mellitus (39.3%), hyperlipidemia (39.3%), and hypertension (32.1%). Twenty-four (85.7%) required mechanical ventilation, in whom the lowest median ratio of arterial oxygen partial pressure to fractional inspired pressure was 161.5 (141.0 to 184.5), the median peak positive end-expiratory pressure (PEEP) was 14 (12.0 to 15.8) cmH2O and 15 (62.5%) underwent an optimal PEEP maneuver. Twelve (50%) patients were proned for a median of 3.0 (3.0 to 4.8) days. Of the 15 patients who were extubated, 3 (20%) required reintubation. Tracheostomy was performed in 10 patients: 3 after extubation failure and 7 for prolonged mechanical ventilation and weakness. Renal replacement therapy was required by 4 (14.3%) patients. There were 2 (7.1%) mortalities. We report detailed clinical outcomes of adult patients when cared for by intact pediatric critical care teams during the COVID-19 pandemic. Good clinical outcomes, when supported by adult critical care colleagues and dedicated operational processes are possible.

Respiratory Failure Leading to Intubation in the Setting of Flibanserin Ingestion in a Toddler.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Standardized Volume Dosing Protocol of 23.4% Hypertonic Saline for Pediatric Critical Care: Initial Experience.

Background: Standardized volume dosing of 23.4% hypertonic saline (HTS) exists for adults, but the concentration, dosing and administration of HTS in pediatrics is variable. With emerging pediatric experience of 23.4% HTS, a standard volume dose approach may be helpful. Objective: To describe initial experience with a standardized 23.4% HTS weight-based volume dosing protocol of 10, 20, or 30 mL in the pediatric intensive care unit. Methods: Standard volume doses of 23.4% HTS were developed from weight dosing equivalents of 3% HTS. Pre and post sodium and intracranial pressure (ICP) measurements were compared with paired t-test or Wilcoxon rank-sum test. The site of administration and complications were noted. Results: A total of 16 pediatric patients received 37 doses of 23.4% HTS, with the smallest patient weighing 11 kg. For protocol compliance, 17 doses (46%) followed recommended dosing, 19 were less volume than recommended (51%), and 1 dose (3%) was more than recommended. Mean increase in sodium was 3.5 mEq/L (95% CI = 2-5 mEq/L); P < 0.0001. The median decrease in ICP was 10.5 mm Hg (interquartile range [IQR] 8.3-19.5) for a 37% (IQR 25%-64%) reduction. Most doses were administered through central venous access, although peripheral intravenous administrations occurred in 4 patients without complication. Conclusion and Relevance: Three standard-volume dose options of 23.4% HTS based on weight increases sodium and reduces ICP in pediatric patients. Standard-volume doses may simplify weight-based dosing, storage and administration for pediatric emergencies, although the optimum dose, and safety of 23.4% HTS in children remains unknown.

VarR controls colonization and virulence in the marine macroalgal pathogen Nautella italica R11.

There is increasing evidence to suggest that macroalgae (seaweeds) are susceptible to infectious disease. However, to date, little is known about the mechanisms that facilitate the colonization and virulence of microbial seaweed pathogens. One well-described example of a seaweed disease is the bleaching of the red alga Delisea pulchra, which can be caused by the bacterium Nautella italica R11, a member of the Roseobacter clade. This pathogen contains a unique luxR-type gene, varR, which we hypothesize controls its colonization and virulence. We show here that a varR knock-out strain is deficient in its ability to cause disease in D. pulchra and is defective in biofilm formation and attachment to a common algal polysaccharide. Moreover complementation of the varR gene in trans can restore these functions to the wild type levels. Proteomic analysis of bacterial cells in planktonic and biofilm growth highlight the potential importance of nitrogen scavenging, mobilization of energy reserves, and stress resistance in the biofilm lifestyle of N. italica R11. Moreover, we show that VarR regulates the expression of a specific subset of biofilm-associated proteins. Taken together these data suggest that VarR controls colonization and persistence of N. italica R11 on the surface of a macroalgal host and that it is an important regulator of virulence.

Origins of the reassortant 2009 pandemic influenza virus through proteotyping with mass spectrometry.

The application of a proteotyping approach employing high resolution mass spectrometry based is shown to be able to determine the gene origin of all major viral proteins in a triple reassortant pandemic 2009 influenza strain. Key to this approach is the identification of unique swine-host-specific signature and indicator peptides that are characteristic of influenza viruses circulating in North American and Eurasian swine herds in the years prior to the 2009 influenza pandemic. These swine-and human pandemic-specific signatures enable the origins of viral proteins in a clinical virus specimen to be determined and such strains to be rapidly and directly differentiated from other co-circulating seasonal influenza viruses from the same period. The proteotyping strategy offers advantages over traditional RT-PCR-based approaches that are currently the mainstay of influenza surveillance at the molecular level.

Incorporation of a proteotyping approach using mass spectrometry for surveillance of influenza virus in cell-cultured strains.

The reemergence of deadly pandemic influenza virus strains has necessitated the development of improved methods for rapid detection and subtyping of influenza viruses that will enable more strains to be characterized at the molecular level. Representative circulating strains of human influenza viruses from primary clinical specimens were grown in cell culture, purified through polyethylene glycol precipitation, proteolytically digested with an endoproteinase, and analyzed and identified by high-resolution mass spectrometry using unique signature peptides that are characteristic of type A H1N1 and H3N2 and type B influenza viruses. This proteotyping approach enabled circulating strains of type A influenza virus to be typed and subtyped, cocirculating seasonal and pandemic H1N1 viruses to be differentiated, and the lineage of type B viruses to be determined through single-ion detection by high-resolution mass spectrometry. Results were obtained using virus titers comparable to those used in reverse transcription (RT)-PCR assays with clinical specimens grown in cell cultures. The methodology represents a more rapid and direct approach than RT-PCR and can be integrated into existing procedures currently used for the surveillance of emerging pandemic and seasonal influenza viruses.