Clinical Outcomes After Tracheostomy in Children With Single Ventricle Physiology: Collaborative Research From the Pediatric Cardiac Intensive Care Society Multicenter Cohort, 2010-2021.

OBJECTIVES: Multicenter studies reporting outcomes following tracheostomy in children with congenital heart disease are limited, particularly in patients with single ventricle physiology. We aimed to describe clinical characteristics and outcomes in a multicenter cohort of patients with single ventricle physiology who underwent tracheostomy before Fontan operation. DESIGN: Multicenter retrospective cohort study.SETTING: Twenty-one tertiary care pediatric institutions participating in the Collaborative Research from the Pediatric Cardiac Intensive Care Society. PATIENTS: We reviewed 99 children with single ventricle physiology who underwent tracheostomy before the Fontan operation at 21 institutions participating in Collaborative Research from the Pediatric Cardiac Intensive Care Society between January 2010 and December 2020, with follow-up through December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Death occurred in 51 of 99 patients (52%). Cox proportional hazard analysis was performed to determine factors associated with death after tracheostomy. Results are presented as hazard ratio (HR) with 95% CIs. Nonrespiratory indication(s) for tracheostomy (HR, 2.21; 95% CI, 1.14-4.32) and number of weeks receiving mechanical ventilation before tracheostomy (HR, 1.06; 95% CI, 1.02-1.11) were independently associated with greater hazard of death. In contrast, diagnosis of tricuspid atresia or Ebstein's anomaly was associated with less hazard of death (HR, 0.16; 95% CI, 0.04-0.69). Favorable outcome, defined as survival to Fontan operation or decannulation while awaiting Fontan operation with viable cardiopulmonary physiology, occurred in 29 of 99 patients (29%). Median duration of mechanical ventilation before tracheostomy was shorter in patients who survived to favorable outcome (6.1 vs. 12.1 wk; p < 0.001), and only one of 16 patients with neurologic indications for tracheostomy and 0 of ten patients with cardiac indications for tracheostomy survived to favorable outcome. CONCLUSIONS: For children with single ventricle physiology who undergo tracheostomy, mortality risk is high and should be carefully considered when discussing tracheostomy as an option for these children. Favorable outcomes are possible, although thoughtful attention to patient selection and tracheostomy timing are likely necessary to achieve this goal.

Early Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory illness occurring after severe acute respiratory syndrome coronavirus 2 infection. The optimal treatment of MIS-C is unknown, although prior studies have indicated benefits of intravenous immunoglobulin (IVIG) and glucocorticoids. We hypothesize that early treatment with glucocorticoids is associated with shorter hospital length of stay (LOS). METHODS: This study is a multicenter retrospective cohort study of patients hospitalized with MIS-C over a roughly 1-year period. The primary outcome was hospital LOS comparing subjects who received glucocorticoids within 48 hours of arrival to the treating hospital to those who did not. Secondary outcomes included ICU LOS. Unadjusted and adjusted analyses were performed. RESULTS: The final analysis included 131 subjects. Subjects who received early glucocorticoids were more likely to receive early IVIG and to require ICU admission. Early glucocorticoid administration was associated with shorter ICU LOS (4 vs 9 days, P = .004) in the unadjusted analysis. In the adjusted analysis, early glucocorticoid administration and early IVIG administration were both independently associated with shorter hospital LOS (incidence rate ratio 0.75, P = .025; incidence rate ratio 0.56, P = .026, respectively). CONCLUSIONS: Glucocorticoids and intravenous immunoglobulin were independently associated with shorter hospital length of stay when given early in hospitalization to MIS-C patients after accounting for potential confounding factors. The optimal dose and duration of treatment require further investigation, but this study supports early combination therapy with both IVIG and glucocorticoids for all children hospitalized with MIS-C.

Hypertension after multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is associated with SARS-CoV-2. Long-term consequences of MIS-C remain unknown. The objective was to describe the prevalence and clinical predictors of hypertension (HTN) and elevated blood pressure (BP) following MIS-C. METHODS: A retrospective study of children ≤ 18 years admitted to a tertiary center with MIS-C was performed. HTN and elevated BP were classified as per the 2017 American Academy of Pediatrics Clinical Practice Guidelines and indexed to the 95th percentile. Data included demographics, inpatient clinical measures, and echocardiograms over 1-year follow-up. Data were analyzed using Kruskal-Wallis, chi-square, and logistic regression. RESULTS: Among 63 children hospitalized with MIS-C (mean age 9.7 ± 4.2 years, 58.7% male, body mass index (BMI) z-score 0.59 ± 1.9), 14% had HTN, and 4% had elevated BP > 30 days post-hospitalization. Multivariate linear regression analysis showed that BMI z-score was significantly associated with higher mean systolic (ß = 2.664, CI = 1.307-3.980, p < 0.001) and diastolic (ß = 2.547, CI = 0.605-4.489, p = 0.012) BP index > 30 days post-hospitalization. Acute kidney injury (AKI) (23.8%) (OR = 2.977, CI = 1.778-4.987, p < 0.001), peak inpatient serum creatinine (OR = 2.524, CI = 1.344-4.740, p = 0.004), and maximum CRP (OR = 1.009, CI = 1.002-1.016, p = 0.014) were all associated with increased odds of post-hospitalization HTN. Left ventricular hypertrophy was present in 46% while hospitalized, compared to 10% at last follow-up. All had return of normal systolic function. CONCLUSIONS: Post-hospitalization HTN and elevated BP may be associated with MIS-C. Children with greater BMI or AKI may be at greater risk for developing HTN after MIS-C. MIS-C follow-up requires careful BP monitoring and antihypertensive medication consideration. A higher resolution version of the Graphical abstract is available as Supplementary information.

Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Postacute Sequelae of SARS-CoV-2: More in Common Than Not?

TOPIC IMPORTANCE: Postacute sequelae of SARS-CoV-2 (PASC) is a long-term consequence of acute infection from COVID-19. Clinical overlap between PASC and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been observed, with shared symptoms including intractable fatigue, postexertional malaise, and orthostatic intolerance. The mechanistic underpinnings of such symptoms are poorly understood. REVIEW FINDINGS: Early studies suggest deconditioning as the primary explanation for exertional intolerance in PASC. Cardiopulmonary exercise testing reveals perturbations related to systemic blood flow and ventilatory control associated with acute exercise intolerance in PASC, which are not typical of simple detraining. Hemodynamic and gas exchange derangements in PASC have substantial overlap with those observed with ME/CFS, suggestive of shared mechanisms. SUMMARY: This review illustrates exercise pathophysiologic commonalities between PASC and ME/CFS that will help guide future diagnostics and treatment.

Staged vs Complete Repair in Tetralogy of Fallot With Pulmonary Atresia.

BACKGROUND: We sought to compare outcomes for infants with tetralogy of Fallot with pulmonary atresia (TOF/PA) and confluent pulmonary arteries who underwent staged or primary complete surgical repair. METHODS: This retrospective study included infants undergoing initial surgical intervention between 0 and 60 days of age with TOF/PA without aortopulmonary collaterals from 2009 to 2018 at 20 centers. The primary outcome was days alive and out of the hospital in the first year of life (DAOH365). Secondary outcomes were mortality at 1 year of age and a composite major complication outcome. Multivariable modeling with generalized estimating equations were used to compare outcomes between groups. RESULTS: Of 221 subjects, 142 underwent staged repair and 79 underwent primary complete repair. There was no significant difference in median DAOH365 between the staged and primary repair groups (317 days [interquartile range, 278-336] vs 338 days [interquartile range, 314-348], respectively; adjusted P = .13). Nine staged repair patients (7%) died in the first year of life vs 5 primary repair patients (6%; adjusted odds ratio, 1.00; 95% CI, 0.25-3.95). At least 1 major complication occurred in 37% of patients who underwent staged repair vs 41% of patients who underwent primary complete repair (P = .75), largely driven by the need for unplanned cardiac reinterventions. CONCLUSIONS: For infants with TOF/PA with confluent pulmonary arteries, a surgical strategy of staged or primary complete repair resulted in statistically similar DAOH365, early mortality, and morbidity.

Angiotensin II enhances bacterial clearance via myeloid signaling in a murine sepsis model.

Sepsis, defined as organ dysfunction caused by a dysregulated host-response to infection, is characterized by immunosuppression. The vasopressor norepinephrine is widely used to treat low blood pressure in sepsis but exacerbates immunosuppression. An alternative vasopressor is angiotensin-II, a peptide hormone of the renin-angiotensin system (RAS), which displays complex immunomodulatory properties that remain unexplored in severe infection. In a murine cecal ligation and puncture (CLP) model of sepsis, we found alterations in the surface levels of RAS proteins on innate leukocytes in peritoneum and spleen. Angiotensin-II treatment induced biphasic, angiotensin-II type 1 receptor (AT1R)-dependent modulation of the systemic inflammatory response and decreased bacterial counts in both the blood and peritoneal compartments, which did not occur with norepinephrine treatment. The effect of angiotensin-II was preserved when treatment was delivered remote from the primary site of infection. At an independent laboratory, angiotensin-II treatment was compared in LysM-Cre AT1aR-/- (Myeloid-AT1a-) mice, which selectively do not express AT1R on myeloid-derived leukocytes, and littermate controls (Myeloid-AT1a+). Angiotensin-II treatment significantly reduced post-CLP bacteremia in Myeloid-AT1a+ mice but not in Myeloid-AT1a- mice, indicating that the AT1R-dependent effect of angiotensin-II on bacterial clearance was mediated through myeloid-lineage cells. Ex vivo, angiotensin-II increased post-CLP monocyte phagocytosis and ROS production after lipopolysaccharide stimulation. These data identify a mechanism by which angiotensin-II enhances the myeloid innate immune response during severe systemic infection and highlight a potential role for angiotensin-II to augment immune responses in sepsis.

T cell activation and IFNγ modulate organ dysfunction in LPS-mediated inflammation.

LPS challenge is used to model inflammation-induced organ dysfunction. The effects of T cell activation on LPS-mediated organ dysfunction and immune responses are unknown. We studied these interactions through in vivo administration of anti-CD3ε (CD3) T cell activating antibody and LPS. Mortality in response to high-dose LPS (LPSHi; 600 µg) was 60%; similar mortality was observed with a 10-fold reduction in LPS dose (LPSLo; 60 µg) when administered with CD3 (CD3LPSLo). LPSHi and CD3LPSLo cohorts suffered severe organ dysfunction. CD3LPSLo led to increased IFNγ and IL12p70 produced by T cells and dendritic cells (cDCs) respectively. CD3LPSLo caused cDC expression of CD40 and MHCII and prevented PD1 expression in response to CD3. These interactions led to the generation of CD4 and CD8 cytolytic T cells. CD3LPSLo responded to IFNγ or IL12p40 blockade, in contrast to LPSHi. The combination of TCR activation and LPS (CD3LPSLo) dysregulated T cell activation and increased LPS-associated organ dysfunction and mortality through T cell and cDC interactions.

Intubation practice and outcomes among pediatric emergency departments: A report from National Emergency Airway Registry for Children (NEAR4KIDS).

BACKGROUND: Tracheal intubation (TI) practice across pediatric emergency departments (EDs) has not been comprehensively reported. We aim to describe TI practice and outcomes in pediatric EDs in contrast to those in intensive are units (ICUs) and use the data to identify quality improvement targets. METHODS: Consecutive TI encounters from pediatric EDs and ICUs in the National Emergency Airway Registry for Children (NEAR4KIDS) database from 2015 to 2018 were analyzed for patient, provider, and practice characteristics and outcomes: adverse TI-associated events (TIAEs), oxygen desaturation (SpO2 < 80%), and procedural success. A multivariable model identified factors associated with TIAEs in the ED. RESULTS: A total of 756 TIs in 13 pediatric EDs and 12,512 TIs in 51 pediatric/cardiac ICUs were reported. Median (interquartile range [IQR]) patient age for ED TIs was higher (32 [7-108] months) than that for ICU TIs (15 [3-91] months; p < 0.001). Proportion of TIs for respiratory decompensation (52% of ED vs. 64% ICU), shock (26% vs. 14%), and neurologic deterioration (30% vs. 11%) also differed by location. Limited neck mobility was reported more often in the ED (16% vs. 6%). TIs in the ED were performed more often via video laryngoscopy (64% vs. 29%). Adverse TIAE rates (15.6% ED, 14% ICU; absolute difference = 1.6%, 95% confidence interval [CI] = -1.1 to 4.2; p = 0.23) and severe TIAE rates (5.4% ED, 5.8% ICU; absolute difference = -0.3%, 95% CI = -2.0 to 1.3; p = 0.68) were not different. Oxygen desaturation was less commonly reported in ED TIs (13.6%) than ICU TIs (17%, absolute difference = -3.4%, 95% CI = -5.9 to -0.8; p = 0.016). Among ED TIs, shock as an indication (adjusted odds ratio [aOR] = 2.15, 95% CI = 1.26 to 3.65) and limited mouth opening (aOR = 1.74, 95% CI = 1.04 to 2.93) were independently associated with TIAEs. CONCLUSIONS: While TI characteristics vary between pediatric EDs and ICUs, outcomes are similar. Shock and limited mouth opening were independently associated with adverse TI events in the ED.

Six Month Follow-up of Patients With Multi-System Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: Myocardial dysfunction and coronary abnormalities are prominent features of multisystem inflammatory syndrome in children (MIS-C). In this study we aim to evaluate the early and midterm outcomes of MIS-C. METHODS: This is a longitudinal 6-month cohort study of all children admitted and treated for MIS-C from April 17 to June 20, 2020. Patients were followed ∼2 weeks, 8 weeks, and 6 months postadmission, with those with coronary aneurysms evaluated more frequently. RESULTS: Acutely, 31 (62%) patients required intensive care with vasoactive support, 26 (52%) had left ventricular (LV) systolic dysfunction, 16 (32%) had LV diastolic dysfunction, 8 (16%) had coronary aneurysms (z score ≥2.5), and 4 (8%) had coronary dilation (z score <2.5). A total of 48 patients (96%) received immunomodulatory treatment. At 2 weeks, there was persistent mild LV systolic dysfunction in 1 patient, coronary aneurysms in 2, and dilated coronary artery in 1. By 8 weeks through 6 months, all patients returned to functional baseline with normal LV systolic function and resolution of coronary abnormalities. Cardiac MRI performed during recovery in select patients revealed no myocardial edema or fibrosis. Some patients demonstrated persistent diastolic dysfunction at 2 weeks (5, 11%), 8 weeks (4, 9%), and 6 months (1, 4%). CONCLUSIONS: Children with MIS-C treated with immunomodulators have favorable early outcomes with no mortality, normalization of LV systolic function, recovery of coronary abnormalities, and no inflammation or scarring on cardiac MRI. Persistence of diastolic dysfunction is of uncertain significance and indicates need for larger studies to improve understanding of MIS-C. These findings may help guide clinical management, outpatient monitoring, and considerations for sports clearance.

Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort.

BACKGROUND: Adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had high rates of thrombosis. A novel condition in children infected with SARS-CoV-2, multisystem inflammatory syndrome in children (MIS-C), has limited data on their prothrombotic state or need for thromboprophylaxis. OBJECTIVES: We aimed to analyze the prothrombotic state using coagulation profiles, rotational thromboelastometry (ROTEM) parameters and clinical outcomes, to determine if this could aid in risk stratification for thromboprophylaxis. METHODS: This analysis included patients (<21 years of age) with a diagnosis of MIS-C (n = 40) and controls (presenting with suspicion of MIS-C but later ruled out; n = 26). RESULTS: MIS-C patients had higher levels of inflammatory markers including D-dimer (p < .0001), compared with controls, along with evidence of hypercoagulability on ROTEM with elevated evaluation of fibrinogen activity (FIBTEM) maximum clot firmness (MCF) (p < .05). For MIS-C patients with D-dimers >1000 ng/ml, there was a significant correlation of FIBTEM MCF (p < .0001) with a mean value of 37.4 (standard deviation 5.1). D-dimer >2144 ng/ml was predictive of intensive care unit admission (area under the curve [AUC] 0.80; 95% confidence interval, 0.60-0.99; p < .01; sensitivity: 82%, specificity: 75%), and elevated FIBTEM MCF (AUC 1 for >2500 ng/ml). MIS-C patients (50%) received enoxaparin thromboprophylaxis (in addition to aspirin) with significant improvement in their inflammatory and ROTEM parameters upon outpatient follow-up; none developed symptomatic thrombosis. CONCLUSIONS: Despite an observed prothrombotic state, none of the MIS-C patients (on aspirin alone or in combination with enoxaparin) developed symptomatic thrombosis. ROTEM, in addition to coagulation profiles, may be helpful to tailor thromboprophylaxis in critically ill MIS-C patients.

Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19.

This study describes the incidence, associated clinical characteristics and outcomes of acute kidney injury in a pediatric cohort with COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C). We performed a retrospective study of patients 18 years of age and under admitted to four New York hospitals in the Northwell Health System interned during the height of the COVID-19 pandemic, between March 9 and August 13, 2020. Acute kidney injury was defined and staged according to Kidney Disease: Improving Global Outcomes criteria. The cohort included 152 patients; 97 acute-COVID-19 and 55 with MIS-C associated with COVID-19. Acute kidney injury occurred in 8 with acute-COVID-19 and in 10 with MIS-C. Acute kidney injury, in unadjusted models, was associated with a lower serum albumin level (odds ratio 0.17; 95% confidence interval 0.07, 0.39) and higher white blood cell counts (odds ratio 1.11; 95% confidence interval 1.04, 1.2). Patients with MIS-C and acute kidney injury had significantly greater rates of systolic dysfunction, compared to those without (80% vs 49%). In unadjusted models, patients with acute kidney injury had 8.4 days longer hospitalizations compared to patients without acute kidney injury (95% confidence interval, 4.4-6.7). Acute kidney injury in acute-COVID-19 and MIS-C may be related to inflammation and/or dehydration. Further research in larger pediatric cohorts is needed to better characterize risk factors for acute kidney injury in acute-COVID-19 and with MIS-C consequent to COVID-19.

Impaired angiotensin II type 1 receptor signaling contributes to sepsis-induced acute kidney injury.

In sepsis-induced acute kidney injury, kidney blood flow may increase despite decreased glomerular filtration. Normally, angiotensin-II reduces kidney blood flow to maintain filtration. We hypothesized that sepsis reduces angiotensin type-1 receptor (AT1R) expression to account for this observation and tested this hypothesis in a patient case-control study and studies in mice. Seventy-three mice underwent cecal ligation and puncture (a sepsis model) or sham operation. Additionally, 94 septic mice received losartan (selective AT1R antagonist), angiotensin II without or with losartan, or vehicle. Cumulative urine output, kidney blood flow, blood urea nitrogen, and creatinine were measured. AT1R expression was assessed using ELISA, qPCR, and immunofluorescence. A blinded pathologist evaluated tissue for ischemic injury. AT1R expression was compared in autopsy tissue from seven patients with sepsis to that of the non-involved portion of kidney from ten individuals with kidney cancer and three non-infected but critically ill patients. By six hours post ligation/puncture, kidney blood flow doubled, blood urea nitrogen rose, and urine output fell. Concurrently, AT1R expression significantly fell 2-fold in arterioles and the macula densa. Creatinine significantly rose by 24 hours and sham operation did not alter measurements. Losartan significantly exacerbated ligation/puncture-induced changes in kidney blood flow, blood urea nitrogen, creatinine, and urine output. There was no histologic evidence of cortical ischemia. Significantly, angiotensin II prevented changes in kidney blood flow, creatinine, and urine output compared to vehicle. Co-administering losartan with angiotensin-II reversed this protection. Relative to both controls, patients with sepsis had low AT1R expression in arterioles and macula densa. Thus, murine cecal ligation/puncture and clinical sepsis decrease renal AT1R expression. Angiotensin II prevents functional changes while AT1R-blockade exacerbates them independent of ischemia in mice.

Characteristics and risk factors associated with critical illness in pediatric COVID-19.

BACKGROUND: While much has been reported regarding the clinical course of COVID-19 in children, little is known regarding factors associated with organ dysfunction in pediatric COVID-19. We describe critical illness in pediatric patients with active COVID-19 and identify factors associated with PICU admission and organ dysfunction. This is a retrospective chart review of 77 pediatric patients age 1 day to 21 years admitted to two New York City pediatric hospitals within the Northwell Health system between February 1 and April 24, 2020 with PCR + SARS-CoV-2. Descriptive statistics were used to describe the hospital course and laboratory results and bivariate comparisons were performed on variables to determine differences. RESULTS: Forty-seven patients (61%) were admitted to the general pediatric floor and thirty (39%) to the PICU. The majority (97%, n = 75) survived to discharge, 1.3% (n = 1) remain admitted, and 1.3% (n = 1) died. Common indications for PICU admission included hypoxia (50%), hemodynamic instability (20%), diabetic ketoacidosis (6.7%), mediastinal mass (6.7%), apnea (6.7%), acute chest syndrome in sickle cell disease (6.7%), and cardiac dysfunction (6.7%). Of PICU patients, 46.7% experienced any significant organ dysfunction (pSOFA > = 2) during admission. Patients aged 12 years or greater were more likely to be admitted to a PICU compared to younger patients (p = 0.015). Presence of an underlying comorbidity was not associated with need for PICU admission (p = 0.227) or organ dysfunction (p = 0.87). Initial white blood cell count (WBC), platelet count, and ferritin were not associated with need for PICU admission. Initial C-reactive protein was associated with both need for PICU admission (p = 0.005) and presence of organ dysfunction (p = 0.001). Initial WBC and presenting thrombocytopenia were associated with organ dysfunction (p = 0.034 and p = 0.003, respectively). CONCLUSIONS: Age over 12 years and initial CRP were associated with need for PICU admission in COVID-19. Organ dysfunction was associated with elevated admission CRP, elevated WBC, and thrombocytopenia. These factors may be useful in determining risk for critical illness and organ dysfunction in pediatric COVID-19.

Acute on Chronic Heart Failure Secondary to Left Ventricular Noncompaction.

Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by hypertrabeculations and intertrabecular recesses most often seen in the left ventricle (LV). The patient may be asymptomatic or present with heart failure, arrhythmia, and sudden death. We discuss a previously healthy 7-year-old male who presented to the Emergency Department (ED) multiple times over a three-week period. His complaints evolved over the course of his illness, initially presenting with fatigue and suicidal ideation, followed by diffuse abdominal pain. Prior to his ICU admission, he had been discharged from the ED twice, due to well appearance and reassuring lab findings. He returned to the ED a final time with severe venous congestion and cardiogenic shock with acute hepatic injury. Echocardiogram revealed LV apical hypertrabeculation with a severe dilated cardiomyopathy and biventricular failure along with a large thrombus in the left ventricular cavity. Congestive heart failure and anticoagulation therapy was initiated, and the patient went on to biventricular assist device (BiVAD) placement and cardiac transplant. Although LVNC is rare, pediatric heart failure does present to the general pediatrician and has high morbidity and mortality. The presenting symptoms can be obscure and pose a challenge to pediatricians. This case report and review will assist in familiarizing the general pediatrician with pediatric heart failure presentation, treatment, and course.

Severe Coronavirus Disease 2019 Infection in an Adolescent Patient After Hematopoietic Stem Cell Transplantation.

Infection with the severe acute respiratory syndrome coronavirus 2 causes severe acute lung injury in approximately 5% of infected adults, but few reports have been made of severe pediatric disease. We present an adolescent patient who contracted severe acute respiratory syndrome coronavirus 2 one week after a paternal haplo-identical hematopoietic stem cell transplant, with development of severe hyperferritinemic acute lung injury and macrophage activation-like syndrome. We present her case and a comparison of her laboratory data with those of a cohort of pediatric patients with coronavirus disease 2019 without severe disease.

Are children with SARS-CoV-2 infection at high risk for thrombosis? Viscoelastic testing and coagulation profiles in a case series of pediatric patients.

The coagulopathy of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well documented in adults, with increases in D-dimer and prothrombin time found to be strong predictors of mortality, and anticoagulation shown to decrease this mortality. Viscoelastic parameters such as elevations in maximum clot firmness (MCF) on rotational thromboelastometry (ROTEM) have correlated with a hypercoagulable state in adults with SARS-CoV-2. We report our experience in children infected with SARS-CoV-2, with noted elevations in D-dimer and MCF on ROTEM (indicating hypercoagulability). Exploration of viscoelastic testing to provide additional laboratory-based evidence for pediatric-specific risk assessment for thromboprophylaxis in SARS-CoV-2 is warranted.

Cardiac Dysfunction and Shock in Pediatric Patients With COVID-19.

Coronavirus disease-2019 (COVID-19) has been reported to cause significant morbidity in adults, with reportedly a lesser impact on children. Cardiac dysfunction has only been described in adults thus far. We describe 3 cases of previously healthy children presenting with shock and COVID-19-related cardiac inflammation. (Level of Difficulty: Intermediate.).

Loss of ventricular preexcitation during noninvasive testing does not exclude high-risk accessory pathways: A multicenter study of WPW in children.

BACKGROUND: Abrupt loss of ventricular preexcitation on noninvasive evaluation, or nonpersistent preexcitation, in Wolff-Parkinson-White syndrome (WPW) is thought to indicate a low risk of life-threatening events. OBJECTIVE: The purpose of this study was to compare accessory pathway (AP) characteristics and occurrences of sudden cardiac arrest (SCA) and rapidly conducted preexcited atrial fibrillation (RC-AF) in patients with nonpersistent and persistent preexcitation. METHODS: Patients 21 years or younger with WPW and invasive electrophysiology study (EPS) data, SCA, or RC-AF were identified from multicenter databases. Nonpersistent preexcitation was defined as absence/sudden loss of preexcitation on electrocardiogram, Holter monitoring, or exercise stress test. RC-AF was defined as clinical preexcited atrial fibrillation with shortest preexcited R-R interval (SPERRI) ≤ 250 ms. AP effective refractory period (APERP), SPERRI at EPS , and shortest preexcited paced cycle length (SPPCL) were collected. High-risk APs were defined as APERP, SPERRI, or SPPCL ≤ 250 ms. RESULTS: Of 1589 patients, 244 (15%) had nonpersistent preexcitation and 1345 (85%) had persistent preexcitation. There were no differences in sex (58% vs 60% male; P=.49) or age (13.3±3.6 years vs 13.1±3.9 years; P=.43) between groups. Although APERP (344±76 ms vs 312±61 ms; P<.001) and SPPCL (394±123 ms vs 317±82 ms; P<.001) were longer in nonpersistent vs persistent preexcitation, there was no difference in SPERRI at EPS (331±71 ms vs 316±73 ms; P=.15). Nonpersistent preexcitation was associated with fewer high-risk APs (13% vs 23%; P<.001) than persistent preexcitation. Of 61 patients with SCA or RC-AF, 6 (10%) had nonpersistent preexcitation (3 SCA, 3 RC-AF). CONCLUSION: Nonpersistent preexcitation was associated with fewer high-risk APs, though it did not exclude the risk of SCA or RC-AF in children with WPW.

Characteristics, Cardiac Involvement, and Outcomes of Multisystem Inflammatory Syndrome of Childhood Associated with severe acute respiratory syndrome coronavirus 2 Infection.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

Use of Organ Dysfunction as a Primary Outcome Variable Following Cecal Ligation and Puncture: Recommendations for Future Studies.

Outcomes variables for research on sepsis have centered on mortality and changes in the host immune response. However, a recent task force (Sepsis-3) revised the definition of sepsis to "life-threatening organ dysfunction caused by a dysregulated host response to infection." This new definition suggests that human studies should focus on organ dysfunction. The appropriate criteria for organ dysfunction in either human sepsis or animal models are, however, poorly delineated, limiting the potential for translation. Further, in many systems, the difference between "dysfunction" and "injury" may not be clear. In this review, we identify criteria for organ dysfunction and/or injury in human sepsis and in rodents subjected to cecal ligation and puncture (CLP), the most commonly used animal model of sepsis. We further examine instances where overlap between human sepsis and CLP is sufficient to identify translational endpoints. Additional verification may demonstrate that these endpoints are applicable to other animals and to other sepsis models, for example, pneumonia. We believe that the use of these proposed measures of organ dysfunction will facilitate mechanistic studies on the pathobiology of sepsis and enhance our ability to develop animal model platforms to evaluate therapeutic approaches to human sepsis.