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Pfizer-BioNTech COVID-19 vaccine is authorized for use in children and adolescents aged 12-15 years and is licensed by the Food and Drug Administration (FDA) for persons aged ≥16 (1). A randomized placebo-controlled trial demonstrated an efficacy of 100% (95% confidence interval [CI] = 75.3%-100%) in preventing outpatient COVID-19 in persons aged 12-15 years (2); however, data among adolescents on vaccine effectiveness (VE) against COVID-19 in real-world settings are limited, especially among hospitalized patients. In early September 2021, U.S. pediatric COVID-19 hospitalizations reached the highest level during the pandemic (3,4). In a test-negative, case-control study at 19 pediatric hospitals in 16 states during June 1-September 30, 2021, the effectiveness of 2 doses of Pfizer-BioNTech vaccine against COVID-19 hospitalization was assessed among children and adolescents aged 12-18 years. Among 464 hospitalized persons aged 12-18 years (179 case-patients and 285 controls), the median age was 15 years, 72% had at least one underlying condition, including obesity, and 68% attended in-person school. Effectiveness of 2 doses of Pfizer-BioNTech vaccine against COVID-19 hospitalization was 93% (95% CI = 83%-97%), during the period when B.1.617.2 (Delta) was the predominant variant. This evaluation demonstrated that 2 doses of Pfizer-BioNTech vaccine are highly effective at preventing COVID-19 hospitalization among persons aged 12-18 years and reinforces the importance of vaccination to protect U.S. youths against severe COVID-19.

Background: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians)

Background The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. Methods We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. Results A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score–matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score–matched analysis. Conclusions Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.)

To describe antibiotic prescribing practices during the first 2 days of mechanical ventilation among previously healthy young children with respiratory syncytial virus-associated lower respiratory tract infection and evaluate associations between the prescription of antibiotics at onset of mechanical ventilation with clinical outcomes.Retrospective cohort study.Forty-six children's hospitals in the United States.Children less than 2 years old discharged between 2012 and 2016 with an International Classification of Diseases diagnosis of respiratory syncytial virus-associated lower respiratory tract infection, no identified comorbid conditions, and receipt of mechanical ventilation.Antibiotic prescription during the first 2 days of mechanical ventilation.We compared duration of mechanical ventilation and hospital length of stay between children prescribed antibiotics on both of the first 2 days of mechanical ventilation and children not prescribed antibiotics during the first 2 days of mechanical ventilation. We included 2,107 PICU children with respiratory syncytial virus-associated lower respiratory tract infection (60% male, median age of 1 mo [interquartile range, 1-4 mo]). The overall proportion of antibiotic prescription on both of the first 2 days of mechanical ventilation was 82%, decreasing over the study period (p = 0.004) and varying from 36% to 100% across centers. In the bivariate analysis, antibiotic prescription was associated with a shorter duration of mechanical ventilation (6 d [4-9 d] vs 8 d [6-11 d]; p0.001) and a shorter hospital length of stay (11 d [8-16 d] vs 13 d [10-18 d]; p0.001). After adjustment for center, demographics, and vasoactive medication prescription, antibiotic prescription was associated with a 1.21-day shorter duration of mechanical ventilation and a 2.07-day shorter length of stay. Ultimately, 95% of children were prescribed antibiotics sometime during hospitalization, but timing, duration, and antibiotic choice varied markedly.Although highly variable across centers and decreasing over time, the practice of instituting antibiotics after intubation in young children with respiratory syncytial virus-associated lower respiratory tract infection was associated with a shortened clinical course after adjustment for the limited available covariates. A prudent approach to identify and optimally treat bacterial coinfection is needed.

Rationale: MMPs (Matrix metalloproteinases) and their endogenous tissue inhibitors may contribute to lung injury through extracellular matrix degradation and modulation of inflammation and fibrosis. Objectives: To test for an association between MMP pathway proteins and inflammation, endothelial dysfunction, and clinical outcomes. Methods: We measured MMPs in plasma collected on acute respiratory distress syndrome (ARDS) Day 1 from 235 children at five hospitals between 2008 and 2017. We used latent class analysis to identify patients with distinct MMP profiles and then associated those profiles with markers of inflammation (IL-1RA, -6, -8, -10, and -18; macrophage inflammatory protein-1α and -1β; tumor necrosis factor-α and -R2), endothelial injury (angiopoietin-2, von Willebrand factor, soluble thrombomodulin), impaired oxygenation (Pa(O(2))/Fi(O(2)) [P/F] ratio, oxygenation index), morbidity, and mortality. Measurements and Main Results: In geographically distinct derivation and validation cohorts, approximately one-third of patients demonstrated an MMP profile characterized by elevated MMP-1, -2, -3, -7, and -8 and tissue inhibitor of metalloproteinase-1 and -2; and depressed active and total MMP-9. This MMP profile was associated with multiple markers of inflammation, endothelial injury, and impaired oxygenation on Day 1 of ARDS, and conferred fourfold increased odds of mortality or severe morbidity independent of the P/F ratio and other confounders (95% confidence interval, 2.1–7.6; P

IMPORTANCE: Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. OBJECTIVE: To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). SETTING, DESIGN, AND PARTICIPANTS: Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase–polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. EXPOSURE: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. RESULTS: Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P

Supplemental Digital Content is available in the text., Background: Influenza virus is a major cause of acute hypoxemic respiratory failure. Early identification of patients who will suffer severe complications can help stratify patients for clinical trials and plan for resource use in case of pandemic. Objective: We aimed to identify which clinical variables best predict prolonged acute hypoxemic respiratory failure in influenza-infected critically ill children. Acute hypoxemic respiratory failure was defined using hypoxemia cutoffs from international consensus definitions of acute respiratory distress syndrome in patients with ventilatory support. Prolonged acute hypoxemic respiratory failure was defined by acute hypoxemic respiratory failure criteria still present at PICU day 7. Derivation Cohort: In this prospective multicenter study across 34 PICUs from November 2009 to April 2018, we included children (< 18 yr) without comorbid risk factors for severe disease. Validation Cohort: We used a Monte Carlo cross validation method with N2 random train-test splits at a 70–30% proportion per model. Prediction Model: Using clinical data at admission (day 1) and closest to 8 am on PICU day 2, we calculated the area under the receiver operating characteristic curve using random forests machine learning algorithms and logistic regression. Results: We included 258 children (median age = 6.5 yr) and 11 (4.2%) died. By day 2, 65% (n = 165) had acute hypoxemic respiratory failure dropping to 26% (n = 67) with prolonged acute hypoxemic respiratory failure by day 7. Those with prolonged acute hypoxemic respiratory failure had a longer ICU stay (16.5 vs 4.0 d; p < 0.001) and higher mortality (13.4% vs 1.0%). A multivariable model using random forests with 10 admission and eight day 2 variables performed best (0.93 area under the receiver operating characteristic curve; 95 CI%: 0.90–0.95) where respiratory rate, Fio2, and pH on day 2 were the most important factors. Conclusions: In this prospective multicentric study, most children with influenza virus–related respiratory failure with prolonged acute hypoxemic respiratory failure can be identified early in their hospital course applying machine learning onto routine clinical data. Further validation is needed prior to bedside implementation.

Objective: To identify pediatric patients with sensory sensitivities during a hospital visit, and to implement a clinical pathway that can meet their sensory needs. The goal is to remove barriers to care delivery that is related to the sensory need for pediatric patients who present with an acute medical illness. Methods: The clinical pathway (identified as ‘Sensory Pathway’) was developed as a joint effort between key stakeholders within the community and medical providers. The pathway was conducted in a tertiary pediatric hospital from September 2016-April 2019. The main components of this pathway included- 1. Staff training; 2. Provision of sensory toolkits and story board; 3. Early collaboration with allied professionals; and 4. Early and continuous parental involvement. The Sensory Pathway was implemented first in the emergency department, followed by inpatient units. Patients triggered the pathway through caregiver or staff identification. Demographic of patients who triggered the pathway was extracted. A detailed qualitative analysis of any parents' feedback received was performed. Results: A cohort of patients with sensory needs was identified amongst pediatric patients who presented to the hospital with an acute illness. The most common comorbidity associated with sensory sensitivity/need was Autism Spectrum Disorder (48%), followed by cerebral palsy (22.8%) and Attention-Deficit/Hyperactivity Disorder (16%). 1337 patients (51.8%) had a single comorbidity while 45.9% patients had more than one comorbidity. Only 1.3% patients had a known diagnosis of sensory processing disorder. The pathway was triggered in 2,580 patient visits with 1643 patients and 937 repeat visits. The vast majority of patients who triggered the pathway had a medical presenting complaint (vs. behavioral). The following themes emerged from the parents' feedback: 1. Additional help received specific to the child's sensory needs; 2. Feeling of comfort; and 3. Improved overall experience. Conclusion: The Sensory Pathway identified a unique profile of pediatric patients who have sensory needs during their hospital stay. The pathway was successfully implemented for children with sensory need in our hospital across a wide range of demographic and with varied medical illness.

Background: Over the last several decades, the prevalence of Autism Spectrum Disorder (ASD) has continued to increase, creating a unique challenge for general physicians who are likely to encounter these patients in their practice. The primary aim of this cross-sectional study design was to identify potential knowledge gaps that were present among medical students and pediatric trainees (interns, residents, and fellows) particularly during the management of a sick child with ASD. Methods: A 23-question online survey was developed and distributed to medical students and pediatric trainees at a tertiary children's hospital affiliated with a medical school. Results: Medical students and pediatric trainees reported a low general knowledge of ASD and were unfamiliar with sensory issues that are often present in these children. Increased discomfort and insufficient didactic and clinical training for providing care to children with ASD during an acute illness were also identified. Both medical students and trainees reported the need for increased education and training, preferentially via patient interaction and small group-based learning. We found that as education/training levels increased, participants perceived increased comfort, and knowledge in managing an ill child with ASD. Conclusions: A perceived knowledge gap and discomfort is present amongst medical students and pediatric trainees on the management of children with ASD. Across all education levels, awareness for sensory dysregulation in ASD children is low. Education programs using direct patient interaction and small group learning were the preferred training modalities to learn how to provide optimal care for children with ASD.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS: Case series of patients (age

We could, if we wished, usher in an exceptional era of public education simply by employing the most powerful and obvious tactics and strategies that we already know will work. We have ignored, subverted, or postponed these priorities for the past 30 years of so-called reform. This failure, more than anything, explains why student learning as measured by the most legitimate assessments--NAEP, PISA, and TIMSS--has barely budged. The purpose of this column, my first for Kappan, is to champion this "first things first" approach. They are those few, straightforward elements and their corollaries that promise to reverse the trend of tepid improvement. Without a doubt, they will have an immediate and decisive impact on the proportion of students who would be ready for college, careers, and citizenship, in virtually in any school. First, we need to massively increase the amount of purposeful reading, writing, and discussion students engage in every day, across the disciplines. Next, we must create and ensure the implementation of decent, coherent, content-rich curriculum in every course. And third, we must ensure that teachers consistently observe the most fundamental elements of a good lesson, which we have known for decades. These will have a profound impact because, despite their unparalleled leverage for improving levels of learning, they are grossly and manifestly under implemented. We maintain current levels of education attainment, such as they are, in the relative absence of these most powerful practices. Few professions are in so propitious a situation. Even reasonable efforts to honestly address these priorities would have immediate and positive effects. There are precedents for swift, even startling improvements in other spheres. Last year, a doctor realized that the lives of thousands of patients hinged on something stunningly simple: the faithful implementation of the most obvious but critical medical procedures. Gathering representatives from a large network of hospitals, he implored them to set a goal to save 100,000 lives in 18 months by unswervingly focusing on the consistent implementation of simple practices known by the entire hospital staff, but consistently practiced by only a few. The result: 122,000 lives were saved, 20% higher than their original goal (Heath & Heath, 2011). Is similarly dramatic, near-term progress possible for schools? Most of us know individual teachers and schools who have made large, fast gains without cutting-edge gadgets, methods, or any of the perennial parade of new programs. A teacher who taught right down the road from my home was singlehandedly responsible for enabling his entire high school--in one year--to make the largest gains in the state on the English language arts exit exam. I watched him teach: He did nothing magical or extraordinary; his preferred technologies were a whiteboard and an overhead projector. He succeeded simply by always (if imperfectly) ensuring a decent curriculum, sound lessons, and plenty of reading and writing--every day. To better grasp the opportunity offered by the back-to-fundamentals approach, let's examine each of these priorities individually, while being fully aware that they're mutually reinforcing. (In future columns, I'll write about each of these facets and their corollaries.) Curricula Robert Marzano's metanalytic studies indicate that a decent, guaranteed curriculum--one that's actually taught by all teachers of the same course--may be the single largest in-school factor that affects learning. No innovation, however sexy or research-based, can overcome the havoc wrought by its opposite: the inevitable hodgepodge of self-selected topics that result in the absence of clear, content-rich curriculum. Moreover, as David Conley has discovered, such common curriculum means very little without clearly specified parameters for how much reading and writing will be required in each course. …

Importance Despite a high disease burden, there is no effective treatment for respiratory syncytial virus (RSV) infection. Objectives To determine whether administration of azithromycin (AZM) to children with RSV-induced respiratory failure is safe and to define the effect of AZM therapy on nasal matrix metalloproteinase 9 (MMP-9) levels. Design, Setting, and Participants This randomized, double-blind, placebo-controlled phase 2 trial was conducted at a single tertiary pediatric intensive care unit from February 2016 to February 2019. The study included children with RSV infection who were admitted to the pediatric intensive care unit and required respiratory support via positive pressure ventilation (invasive and noninvasive). A total of 147 children were screened; 90 were excluded for not meeting inclusion criteria, having an absent legal guardian, lacking pharmacy support, or having a language barrier and 9 declined participation, resulting in 48 patients enrolled in the study. Intervention Receipt of standard dose AZM (10 mg/kg/d), high-dose AZM (20 mg/kg/d), or a matching placebo of normal saline intravenously for 3 days. Main Outcomes and Measures Nasal and endotracheal samples were collected at baseline as well as at 24 hours and 48 hours after start of treatment. The secondary outcome was to determine treatment effect on clinical outcome measures, including days of positive pressure ventilation and length of hospital stay. Results A total of 48 patients were enrolled in the trial, with a median (range) age at randomization of 12 (1 to 125) months; 36 participants (75.0%) were younger than 2 years. Overall, 26 participants (54.2%) were boys, and 29 (60.4%) had a comorbidity. A total of 16 patients were randomized into each trial group (ie, placebo, standard-dose AZM, and high-dose AZM). Baseline demographic characteristics were comparable among the 3 groups. Both doses of AZM were safe, with no adverse events observed. No difference in nasal MMP-9 levels were observed between treatment groups. Among those who required mechanical ventilation and received high-dose AZM, endotracheal active and total MMP-9 levels were lower on day 3. Compared with baseline, active and total MMP-9 levels in endotracheal aspirates were 1.0 log lower in the high-dose AZM group (active MMP-9: 99.8% CI, −1.28 to −0.64;P Conclusions and Relevance In this phase 2 randomized clinical trial, both doses of AZM were safe. While nasal MMP-9 levels were unchanged among treatment groups, endotracheal MMP-9 levels were lower among those who received high-dose AZM. The positive secondary clinical outcome, while exploratory, provides insight for end points in a multicenter randomized trial. Trial Registration ClinicalTrials.gov Identifier:NCT02707523

Sepsis in children is typically presumed to be bacterial in origin until proven otherwise, but frequently bacterial cultures ultimately return negative. Although viruses may be important causative agents of culture-negative sepsis worldwide, the incidence, disease burden and mortality of viral-induced sepsis is poorly elucidated. Consideration of viral sepsis is critical as its recognition carries implications on appropriate use of antibacterial agents, infection control measures, and, in some cases, specific, time-sensitive antiviral therapies. This review outlines our current understanding of viral sepsis in children and addresses its epidemiology and pathophysiology, including pathogen-host interaction during active infection. Clinical manifestation, diagnostic testing, and management options unique to viral infections will be outlined.

Patient: Male, 11 Final Diagnosis: Chromobacterium violaceum infection Symptoms: Abscess • fever • rash Medication: — Clinical Procedure: ECMO Specialty: Critical Care Medicine Objective: Rare disease Background: Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. Case Report: We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. Conclusions: This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy.

Background Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. Methods The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing. rs12252 was genotyped in 54 African-American pediatric outpatients with influenza (FLU09), included in the population-based comparisons with 1000 genomes. Splice site analysis of rs12252_C was performed using PICFLU and FLU09 patient RNA. Results In PICFLU, 358 children had influenza infection. We identified 22 rs12252_C homozygotes in 185 white non-Hispanic children. rs12252_C was not associated with influenza infection in population or family-based analyses. We did not identify the Δ21 IFITM3 isoform in RNAseq data. The rs12252 genotype was not associated with IFITM3 expression levels, nor with critical illness severity. No novel rare IFITM3 functional variants were identified. Conclusions rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

Viral infections are an important cause of pediatric Acute Respiratory Distress Syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in ‘at risk’ populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.

Background Hematopoietic cell transplant (HCT) may be a risk factor for morbidity and mortality from respiratory syncytial virus (RSV). Previous studies have been limited by small sample size. We took a multicenter approach with the goal of better understanding the epidemiology, risk factors, treatment, morbidity, and mortality associated with RSV infections among children with HCT in the United States. Methods A retrospective, multicenter, cohort study of pediatric HCT recipients were diagnosed with RSV infection between January 2010 and December 2014. Results Of the 1522 HCT, 47 (3%) patients were diagnosed with RSV. Of those with RSV, 9 (19.1%) were admitted to the pediatric intensive care unit (PICU), 6 (12.8%) received invasive mechanical ventilation, and 1 died. Prophylactic palivizumab was uncommon. All who required critical care received ribavirin vs 7.3% of those who did not (P = .004). Cobacterial infections were found in 16 patients and were not associated with the need for critical care. We examined potential risk factors for severity of RSV disease. In those who received invasive ventilation, 100% had one of the preidentified risk factors. Half of those requiring mechanical ventilation were diagnosed with RSV during their conditioning for transplant as opposed to only 2.4% of those that did not require invasive mechanical ventilation (P = .005). Conclusions In this multicenter cohort, RSV was not common in children following HCT. Few children infected with RSV required critical care and mortality was low. Those diagnosed with RSV during conditioning for transplant were at higher risk for invasive mechanical ventilation.

Pediatric Acute Lung Injury (ALI) is associated with a high mortality and morbidity, and dysregulation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis and evolution of ALI. Here we examined MMP expression and activity in pediatric ALI compared with controls. MMP-8, -9, and to a lesser extent, MMP-2, -3, -11 and -12 were identified at higher levels in lung secretions of pediatric ALI patients compared with controls. Tissue Inhibitor of Matrix metalloproteinase-1 (TIMP-1), a natural inhibitor of MMPs was detected in most ALI samples, but MMP-9:TIMP-1 ratios were high relative to controls. In subjects who remained intubated for ≥10 days, MMP-9 activity decreased, with > 80% found in the latent form. In contrast, almost all MMP-8 detected at later disease course was constitutively active. Discriminating MMP-9:TIMP-1 ratios were found in those who had a prolonged ALI course. These results identify a specific repertoire of MMP isoforms in the lung secretions of pediatric ALI patients, and demonstrate inverse changes in MMPs -8 and -9 with protracted disease.

Objective To review the findings and to discuss the implications of hyperglycemia in critically ill children. Design A critical appraisal of an article with literature review. Findings In this single-center, retrospective cohort study, the authors report that the prevalence of hyperglycemia ranged from 16.7% to 75%, depending on the cutoff values (120 mg/dL, 150 mg/dL, and 200 mg/dL), among nondiabetic children admitted to a pediatric intensive care unit. Hyperglycemia correlated with an increased in-hospital mortality rate (relative risk, 2.5; 95% confidence interval, 1.26-4.93 for maximum glucose within 24 hrs, >150 mg/dL; and relative risk, 5.68; 95% confidence interval, 1.38-23.47 for highest glucose within 10 days, >120 mg/dL), as well as a longer length of stay in the pediatric intensive care unit. This finding is in concordance with other adult and pediatric studies. However, without adjustment for severity of illness, the study does not distinguish cause and effect, nor does it address the role of strict glucose control in this group of patients. Conclusions This study adds to the growing body of knowledge that associates the timing, intensity, duration, and variability of glycemia with outcomes in critically ill children. However, its limitations restrict drawing causal relationships and prevents insights regarding therapy.

Respiratory Syncytial Virus (RSV) is an important human pathogen associated with substantial morbidity and mortality. The present study tested the hypothesis that RSV infection would increase matrix metalloproteinase (MMP)-9 expression, and that MMP-9 inhibition would decrease RSV replication both in vitro and in vivo. RSV A2 infection of human bronchial epithelial cells increased MMP-9 mRNA and protein release. Cells transfected with siRNA against MMP-9 following RSV infection had lower viral titers. In RSV infected wild-type (WT) mice, MMP-9, airway resistance and viral load peaked at day 2 post infection, and remained elevated on days 4 and 7. RSV infected MMP-9 knockout (KO) mice had decreased lung inflammation. On days 2 and 4 post inoculation, the RSV burden was lower in the MMP-9 KO mice compared to WT controls. In conclusion, our studies demonstrate that RSV infection is a potent stimulus of MMP-9 expression both in vitro and in vivo. Reduction of MMP-9 (via siRNA knockdown, and in MMP-9 KO mice) resulted in decreased viral replication. Our findings suggest MMP-9 is a potential therapeutic target for RSV disease.

Introduction/Purpose Matrix metalloproteinases (MMP)-8 and -9 have been implicated in acute lung injury (ALI) in adults. Little is known about their role in pediatric ALI, particularly as the disease progresses from the acute, exudative phase to the chronic fibroproliferative phase. Methods Lower airway secretions from 26 pediatric patients (age Results Notable differences were seen in MMP-8 and MMP-9 expression profiles and regulation. Pooled samples from the first 10 days of ALI demonstrated up-regulation of MMP-8 (ALI 67 ± 24 ng/mg; 3.7-fold increase over control), and MMP-9 (ALI 599 ± 117 ng/mg; 2.6-fold increase over control), with MMP-9 activity exceeding MMP-8 (p Conclusion Our data suggest that in pediatric ALI, MMP-8 activity increases whereas MMP-9 activity decreases with disease progression. Determining whether this shifting MMP profile can be used as a marker for protracted respiratory failure or the development of the fibroproliferative stage in the pediatric population warrants further examination.

Purpose To highlight the need for pediatricians to have an awareness of metastatic thyroid carcinoma in the differential diagnosis of pulmonary miliary lesions by presenting an unusual case presentation. Method We report a previously healthy 4-year-old female patient with a 9-week history of persistent cough and exertional dyspnea associated with decreased appetite and weight lost. The review of systems was positive for exposure to Mycobacterium tuberculosis in her first year of life from her biological mother but otherwise negative. Her physical exam was notable for bilateral cervical lymphadenopathy, with the largest node measuring approximately 5 3 4 cm. Thyroid exam was normal. Chest roentgenogram revealed diffuse nodular densities in both lung fields. An extensive diagnostic work-up was undertaken to identify Mycobacterium tuberculosis as the causative agent. A skin PPD test was nonreactive and gastric lavages failed to identify acid fast bacilli with Ziehl-Neelsen stain and direct fluorescent antibody. Silver stain for fungal elements and HIV titers were also negative. A subsequent lung bronchoscopy revealed compression of the left lung bronchus and microscopic analysis of the bronchoalveolar lavage fluid demonstrated normal cellular distribution with no microbial pathogens. A fine-needle biopsy of her cervical lymph node revealed metastatic thyroid carcinoma. The metastatic nature of the miliary pulmonary lesions was confirmed by avid uptake of radioactive iodine by the lesions. Results Thyroid carcinoma is uncommon in the pediatric population, with an annual incidence of 0.02-0.3 cases per 100,000 population. It typically manifests as an asymptomatic mass in 60-80% of cases and often presents with advanced disease in children. Extensive regional nodal involvement has been reported in up to 70% of pediatric patients with distant metastasis to the lungs, bone, or liver present in 10-20% of patients. Diffuse miliary spread to the lungs is unusual, with bilateral total lung involvement reported only in several cases. Conclusion During the evaluation and diagnosis of diffuse interstitial lung lesions in pediatrics, it is important to identify any suspected infectious pathogens. When an infectious etiology is not identified, examination of tissues by nodal and/or lung biopsy is often necessary to confirm the diagnosis. Miliary dissemination of thyroid carcinoma is an unusual cause of diffuse interstitial nodular pulmonary infiltrates.