Humoral Immunodeficiency and Immune Globulin Replacement Therapy (IGRT) Usage in DiGeorge Syndrome.

PURPOSE: An analysis of patients in the United States Immunodeficiency Network (USIDNET) registry previously described a discordance in the reported prevalence of humoral immune deficiency in patients with DiGeorge syndrome (DGS) and its treatment. The primary purpose of this study is to evaluate the rates of humoral immunodeficiency and immune globulin replacement therapy (IGRT) use in patients with DiGeorge syndrome in the USIDNET registry as of September 2016, and to correlate IGRT use with prior infections and laboratory evidence of immune deficiency. METHODS: Current patients in the USIDNET registry with DGS were identified. Patients who were treated with immune globulin replacement therapy (IGRT) were compared with those who were untreated with respect to their laboratory findings and clinical history. RESULTS: Four hundred seventy-three patients were identified. The use of IGRT in patients with DGS has increased over time from 3 to 6.6%. IGRT was more common in patients with humoral immune deficiency (18.2% of those with hypogammaglobulinemia, 39.1% of those with documented low vaccine titers), but most patients with evidence of humoral immune deficiency remain untreated with IGRT. Patients treated with IGRT were more likely to have experienced episodes of pneumonia, sepsis, and bacterial skin infections (p < 0.01 for all). CONCLUSIONS: Humoral immune deficiencies were more common among patients with DGS than previously reported. IGRT was used most commonly in patients with DGS who demonstrated frequent or severe bacterial infections. There is still a significant deficit between those with DGS who have laboratory evidence of a humoral immune deficiency and those being treated for it.

A fatal case report of antibody-dependent enhancement of dengue virus type 1 following remote Zika virus infection.

BACKGROUND: Dengue virus (DENV) is endemic in many parts of the world. Antibody dependent enhancement (ADE) in DENV infections occurs when a person with primary immunity is infected by a second, different DENV strain. Antibodies to Zika virus (ZIKV), which emerged in the Western Hemisphere in 2015, are cross reactive with DENV and theoretically could provoke ADE in a DENV naïve individual. CASE PRESENTATION: DENV infection was suspected in a child who had recently returned from a one-month stay in the Dominican Republic. The child presented with fever, vomiting, abdominal pain, and in hypovolemic shock. Volume and pressor resuscitation were unsuccessful, and the child died less than 24 h after hospitalization. Laboratory results suggested an early acute first DENV infection since serum, plasma, and spinal fluid had DENV1 detected by polymerase chain reaction (PCR), yet the serum lacked IgG antibodies to DENV nonstructural protein 1 (NS1) of all four DENV serotypes. This acute DENV infection occurred in the presence of a remote ZIKV infection as determined by antibodies to ZIKV NS1 envelope by multiplex microsphere immunoassay and an exceptionally high plaque reduction neutralization titer to ZIKV. ZIKV IgG avidity index was high, confirming a past infection. DENV1 RNA was detected in all ten organs and tissues examined by PCR. The severe and fatal complications reported here suggest that a remote ZIKV infection may provoke an exaggerated immune response leading to hypovolemic shock when primarily infected by DENV1. CONCLUSION: We report the first known patient in the United States with a rapidly progressive and fatal case of travel-associated DENV in which prior exposure to ZIKV likely played a role in triggering an ADE phenomenon. This association of prior ZIKV immunity and subsequent new dengue infection is a worrisome phenomenon and an important contribution to the body of knowledge on immunity to flaviviruses.

Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Infection (MIS-C): A Multi-institutional Study from New York City.

OBJECTIVE: To assess clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2-associated multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: Children with MIS-C admitted to pediatric intensive care units in New York City between April 23 and May 23, 2020, were included. Demographic and clinical data were collected. RESULTS: Of 33 children with MIS-C, the median age was 10 years; 61% were male; 45% were Hispanic/Latino; and 39% were black. Comorbidities were present in 45%. Fever (93%) and vomiting (69%) were the most common presenting symptoms. Depressed left ventricular ejection fraction was found in 63% of patients with median ejection fraction of 46.6% (IQR, 39.5-52.8). C-reactive protein, procalcitonin, d-dimer, and pro-B-type natriuretic peptide levels were elevated in all patients. For treatment, intravenous immunoglobulin was used in 18 (54%), corticosteroids in 17 (51%), tocilizumab in 12 (36%), remdesivir in 7 (21%), vasopressors in 17 (51%), mechanical ventilation in 5 (15%), extracorporeal membrane oxygenation in 1 (3%), and intra-aortic balloon pump in 1 (3%). The left ventricular ejection fraction normalized in 95% of those with a depressed ejection fraction. All patients were discharged home with median duration of pediatric intensive care unit stay of 4.7 days (IQR, 4-8 days) and a hospital stay of 7.8 days (IQR, 6.0-10.1 days). One patient (3%) died after withdrawal of care secondary to stroke while on extracorporeal membrane oxygenation. CONCLUSIONS: Critically ill children with coronavirus disease-2019-associated MIS-C have a spectrum of severity broader than described previously but still require careful supportive intensive care. Rapid, complete clinical and myocardial recovery was almost universal.

Validation of a Novel Mobile Application for Assessing Pediatric Tracheostomy Emergency Simulations.

Objective: Pediatric tracheostomy is associated with high morbidity and mortality, yet clinician knowledge and quality of tracheostomy care may vary widely. In situ simulation is effective at detecting and mitigating related latent safety threats, but evaluation via retrospective video review has disadvantages (eg, delayed analysis, and potential data loss). We evaluated whether a novel mobile application is accurate and reliable for assessment of in situ tracheostomy emergency simulations. Methods: A novel mobile application was developed for assessment of tracheostomy emergency in situ simulation team performance. After 1.25 hours of training, 6 raters scored 10 tracheostomy emergency simulation videos for the occurrence and timing of 12 critical steps. To assess accuracy, rater scores were compared to a reference standard to determine agreement for occurrence or absence of critical steps and a timestamp within ±5 seconds. Interrater reliability was determined through Cohen's and Fleiss' kappa and intraclass correlation coefficient. Results: Raters had 86.0% agreement with the reference standard when considering step occurrence and timing, and 92.8% agreement when considering only occurrence. The average timestamp difference from the reference standard was 1.3 ± 18.5 seconds. Overall interrater reliability was almost perfect for both step occurrence (Fleiss' kappa of 0.81) and timing of step (intraclass correlation coefficient of 0.99). Discussion: Using our novel mobile application, raters with minimal training accurately and reliably assessed videos of tracheostomy emergency simulations and identified areas for future refinement. Implications for Practice: With refinements, this innovative mobile application is an effective tool for real-time data capture of time-critical steps in in situ tracheostomy emergency simulations.

Retrospective Outcomes Comparison by Treatment Location for Pediatric Mild and Moderate Diabetic Ketoacidosis.

OBJECTIVES: Pediatric diabetic ketoacidosis (DKA) is often treated in a PICU, but nonsevere DKA may not necessitate PICU admission. At our institution, nonsevere DKA was treated on the floor until policy change shifted care to the PICU. We describe outcomes in pediatric mild to moderate DKA by treatment location. METHODS: Patients aged 2 to 21 with mild to moderate DKA (pH <7.3 but >7.1), treated on the floor from January 1, 2018 to July 31, 2020 and PICU from August 1, 2020 to October 1, 2022 were included. We performed a single-center, retrospective cohort study; primary outcome was DKA duration (from emergency department diagnosis to resolution), secondary outcomes included hospital length of stay, and complication rates, based on treatment location. RESULTS: Seventy nine floor and 65 PICU encounters for mild to moderate pediatric DKA were analyzed. There were no differences in demographics, initial pH, or bicarbonate; PICU patients had more acute kidney injury on admission. Floor patients had a shorter DKA duration (10 hours [interquartile range 7-13] vs 11 hours [9-15]; P = .04), and a shorter median length of stay (median 43.5 hours [interquartile range 31-62] vs 49 hours [32-100]; P < .01). No patients had clinical signs of cerebral edema; other complications occurred at similar rates. PICU patients received significantly more intravenous electrolyte boluses, but there were no differences in dysrhythmia or electrolyte abnormalities on final serum chemistry. CONCLUSIONS: Our study did not find a clear benefit to admitting patients with mild to moderate DKA to the PICU instead of the hospital floor. Our findings suggest that some children with nonsevere DKA may be treated safely in a non-PICU setting.

Molecular Adsorbent Recirculating System for Acute Liver Failure in a New Pediatric-Based Extracorporeal Liver Support Program.

IMPORTANCE: Acute liver failure (ALF) carries significant morbidity and mortality, for both pediatric and adult patients. Albumin dialysis via the molecular adsorbent recirculating system (MARS) is a form of extracorporeal liver support (ELS) that can reduce hepatic encephalopathy (HE), a main driver of mortality in ALF. However, data on MARS and its benefit on mortality have been inconsistent. OBJECTIVES: We sought to report our experiences and patient outcomes from the first 2 years of operation of a new ELS program, within an established pediatric liver transplantation center. DESIGN SETTING AND PARTICIPANTS: Retrospective review of outcomes in pediatric and adult patients treated with MARS therapy for ALF, from 2021 to 2022. MAIN OUTCOMES AND MEASURES: Outcomes included reduction in HE and biochemical markers of ALF after MARS therapy, survival, and transplant-free survival. Comparisons were made via Wilcoxon signed-rank test. RESULTS: Five pediatric and two adult patients underwent MARS for ALF. Ages ranged from 2 to 29 years. Overall, 21 MARS runs were performed (median 3 runs per patient, 12.4 hr per run [interquartile range, IQR 10.1-17]). Overall survival was 85.7%, and transplant-free survival was 71.4%. There was a statistically significant reduction in HE score with MARS therapy (median 3 [IQR 3-4] to 1 [IQR 0-1], p = 0.03), and in ALF biomarkers including ammonia (256 µL/dL [195-265] to 75 µL/dL [58-101], p = 0.02), aspartate aminotransferase (6,362 U/L [920-8,305] to 212 U/L [72-431], p = 0.02), alanine aminotransferase (8,362 U/L [3,866-9,189] to 953 U/L [437-1,351], p = 0.02), and international normalized ratio (4.5 [3.3-6.7] to 1.3 [1.2-1.4], p = 0.02). CONCLUSIONS AND RELEVANCE: MARS therapy for ALF was well tolerated by both pediatric and adult patients, and resulted in significant improvement in clinical and biochemical parameters. We demonstrated encouraging overall and transplant-free survival, suggesting that early initiation of MARS with relatively long and frequent cycle times may be of significant benefit to ALF patients, and is worthy of additional study in larger cohorts.

Feeding Pathway for Children on High Flow Nasal Cannula Decreases Time to Enteral Nutrition.

High Flow Nasal Cannula (HFNC) is commonly used for children with respiratory failure, yet no standardized guidelines exist on how to initiate, escalate, and maintain enteral nutrition (EN) for these patients. EN in critically ill children is associated with decreased hospital length of stay, decreased ventilator days, and fewer acquired infections. We aimed to decrease the mean time to EN initiation by 50% after the start of HFNC in 6 months. Methods: This quality improvement project used the Model for Improvement to inform interventions. A multidisciplinary team created an EN pathway for critically ill patients on HFNC. We conducted Plan-Do-Study-Act cycles related to implementing a standardized pathway for EN on HFNC. The primary outcome was time to EN initiation once on HFNC. Secondary outcomes were time to goal caloric EN, duration of HFNC, and adverse events. Outcomes were plotted on statistical process control charts and analyzed for special cause variation between baseline and intervention periods. Results: We included 112 patients in the study. Special cause variation occurred for both primary and secondary outcomes. The mean time to EN initiation decreased from 24.6 hours to 11.7 hours (47.5%). Mean time to goal feeds decreased from 25.8 hours to 15.1 hours (58.5%). Mean HFNC duration did not show any special cause variation. There were no episodes of aspiration. Conclusion: Implementation of a standardized pathway for EN on patients receiving HFNC resulted in decreased time to initiation of EN and time to goal caloric EN with no significant increase in adverse events.

Increased Use of Noninvasive Ventilation Associated With Decreased Use of Invasive Devices in Children With Bronchiolitis.

To assess how a change in practice to more frequent use of high-flow nasal cannula for the treatment of bronchiolitis would affect the use of invasive devices in children. DESIGN: Retrospective cohort study of children under 2 years old admitted to the ICU with respiratory failure secondary to bronchiolitis. Outcomes and invasive device use were compared between two time periods, before and after the practice change. SETTING: Eighteen bed tertiary care PICU. PATIENTS: A total of 325 children: 146 from 2010 to 2012 and 179 from 2015 to 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were no significant differences between the two time periods regarding gender, race/ethnicity, medical history, and viral profile, although children were younger in the earlier cohort (median age of 1.9 mo [interquartile range, 1.2-3.5] vs 3.3 mo [1.7-8.6]; p < 0.001). There was an increased use of noninvasive ventilation in the second time period (94% from 69%; p < 0.001), as well as a decreased frequency of intubation (13% from 42%; p < 0.001) and reduced central venous catheter placement (7% from 37%; p < 0.001). There was no significant difference in mortality between the two groups. A logistic regression analysis was conducted, which found that time period, intubation, and hospital length of stay were all independently associated with central venous catheter placement. CONCLUSIONS: A practice change toward managing patients with bronchiolitis in respiratory failure with less invasive means was associated with a reduction in the use of other invasive devices. In our cohort, minimizing the use of invasive ventilation and devices was not associated with an increase in mortality and could potentially have additional benefits.