Faculty Decision Making in Ad Hoc Entrustment of Pediatric Critical Care Fellows: A National Case-Based Survey.

Phenomenon: Ad hoc entrustment decisions reflect a clinical supervisor's estimation of the amount of supervision a trainee needs to successfully complete a task in the moment. These decisions have important consequences for patient safety, trainee learning, and preparation for independent practice. Determinants of these decisions have previously been described but have not been well described for acute care contexts such as critical care and emergency medicine. The ad hoc entrustment of trainees caring for vulnerable patient populations is a high-stakes decision that may differ from other contexts. Critically ill patients and children are vulnerable patient populations, making the ad hoc entrustment of a pediatric critical care medicine (PCCM) fellow a particularly high-stakes decision. This study sought to characterize how ad hoc entrustment decisions are made for PCCM fellows through faculty ratings of vignettes. The authors investigated how acuity, relationship, training level, and task interact to influence ad hoc entrustment decisions. Approach: A survey containing 16 vignettes that varied by four traits (acuity, relationship, training level, and task) was distributed to U.S. faculty of pediatric critical care fellowships in 2020. Respondents determined an entrustment level for each case and provided demographic data. Entrustment ratings were dichotomized by "high entrustment" versus "low entrustment" (direct supervision or observation only). The authors used logistic regression to evaluate the individual and interactive effects of the four traits on dichotomized entrustment ratings. Findings: One hundred seventy-eight respondents from 30 institutions completed the survey (44% institutional response rate). Acuity, relationship, and task all significantly influenced the entrustment level selected but did not interact. Faculty most frequently selected "direct supervision" as the entrustment level for vignettes, including for 24% of vignettes describing fellows in their final year of training. Faculty rated the majority of vignettes (61%) as "low entrustment." There was no relationship between faculty or institutional demographics and the entrustment level selected. Insights: As has been found in summative entrustment for pediatrics, internal medicine, and surgery trainees, PCCM fellows often rated at or below the "direct supervision" level of ad hoc entrustment. This may relate to declining opportunities to practice procedures, a culture of low trust propensity among the specialty, and/or variation in interpretation of entrustment scales.

Novel Identification of Myeloid-Derived Suppressor Cells in Children With Septic Shock.

OBJECTIVES: Immunoparalysis in children with septic shock is associated with increased risk of nosocomial infections and death. Myeloid-derived suppressor cells (MDSCs) potently suppress T cell function and may perpetuate immunoparalysis. Our goal was to test the hypothesis that children with septic shock would demonstrate increased proportions of MDSCs and impaired immune function compared with healthy controls. DESIGN: Prospective observational study. SETTING: Fifty-four bed PICU in a quaternary-care children's hospital. PATIENTS: Eighteen children with septic shock and thirty age-matched healthy children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and stained for cell surface markers to identify MDSCs by flow cytometric analysis, including granulocytic and monocytic subsets. Adaptive and innate immune function was measured by ex vivo stimulation of whole blood with phytohemagglutinin-induced interferon (IFN) γ production and lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production, respectively. Prolonged organ dysfunction (OD) was defined as greater than 7 days. Children with septic shock had a higher percentage of circulating MDSCs, along with lower LPS-induced TNFα and phytohemagglutinin-induced IFNγ production capacities, compared with healthy controls. A cut-off of 25.2% MDSCs of total PBMCs in initial samples was optimal to discriminate children with septic shock who went on to have prolonged OD, area under the curve equal to 0.86. Children with prolonged OD also had decreased TNFα production capacity over time compared with those who recovered more quickly ( p = 0.02). CONCLUSIONS: This article is the first to describe increased MDSCs in children with septic shock, along with an association between early increase in MDSCs and adverse OD outcomes in this population. It remains unclear if MDSCs play a causative role in sepsis-induced immune suppression in children. Additional studies are warranted to establish MDSC as a potential therapeutic target.

Creation of a Combination Antibiogram for Pseudomonas aeruginosa in a Pediatric Intensive Care Unit.

OBJECTIVE: This study describes the creation of a combination antibiogram directed toward Pseudomonas aeruginosa to determine the most appropriate empiric antimicrobial regimen(s). METHODS: P aeruginosa isolates were collected from all sites between January 2013 and December 2017 for patients admitted to the PICU. Patients with cystic fibrosis and isolates from the same site and susceptibility pattern obtained within 30 days were excluded. ß-Lactam susceptibilities were determined and compared with the addition of an aminoglycoside or fluroquinolone and summarized in a combination antibiogram. RESULTS: One hundred ninety-nine P aeruginosa isolates were included for analysis. The addition of a second agent to piperacillin-tazobactam was shown to have the most significant improvement among the ß-lactams, with 70% susceptibility as monotherapy and increases to above 90% with the addition of an aminoglycoside or fluroquinolone. The addition of an aminoglycoside or fluroquinolone to cefepime and meropenem increased coverage to above 95%. The addition of a second agent was likely to increase susceptibility of a monotherapy backbone; however, as the susceptibility of the first-line agent decreased, the susceptibility of the second agent needed to be higher to achieve a 95% coverage threshold. CONCLUSIONS: Our results support use of a second agent to significantly improve the likelihood of appropriate empiric coverage of P aeruginosa. Use of a combination antibiogram may be more beneficial than a simple antibiogram for units with increasing resistance rates, or for coverage of specific resistant organisms.

The Autism Detection in Early Childhood Tool: Level 2 autism spectrum disorder screening in a NICU Follow-up program.

OBJECTIVE: Children born preterm are at increased risk for autism spectrum disorder (ASD). However, early diagnosis of ASD is challenging because conventional screening Level 1 tools are less reliable in this population. We sought to determine whether the Autism Detection in Early Childhood (ADEC) and Child Behavior Checklist (CBCL) could accurately identify children at risk for ASD in a NICU Follow-up setting and thus facilitate referral for formal ASD evaluation. METHOD: Children aged 18-36 months were recruited from a NICU Follow-up program. All children received presumptive diagnoses based on DSM-5 criteria and were screened for ASD risk with the ADEC and CBCL. Children scoring in the "at risk" range on either tool were referred for a full diagnostic ASD evaluation. RESULTS: Sixty-nine patients (median birth weight 1140 g; median gestational age 28 weeks) were included with 18 designated "at risk" for ASD. Nine (13 %) scored "at risk" on the ADEC and 12 (17 %) on the CBCL. Thirteen children underwent diagnostic ASD evaluation with 9 receiving a formal diagnosis of ASD. The ADEC demonstrated the best performance (sensitivity 89 %, specificity 98 %). The CBCL was less sensitive (sensitivity 50 %, specificity 90 %). Requiring elevated scores on both the CBCL and ADEC was specific but not sensitive (sensitivity 33 %, specificity 100 %). CONCLUSION: The ADEC performed well in identifying children at risk for ASD within this high-risk NICU cohort, adding benefit as an autism-specific screening tool over the CBCL alone.

Clinical Features, Prognostic Factors, and Treatment Interventions for Ulceration in Patients With Infantile Hemangioma.

Importance: Ulceration is a common complication of infantile hemangioma (IH), which leads to substantial morbidity. Ulceration in IH has not been systematically studied since the advent of ß-blocker therapy for IH. Objectives: To examine treatment interventions used for ulceration in IH and identify clinical prognostic indicators of healing time. Design, Setting, and Participants: A retrospective, multicenter cohort study was conducted on 436 consecutive patients with a clinical diagnosis of ulcerated IH and available clinical photographs. Patients receiving care at tertiary referral centers evaluated between 2012 and 2016 were included; statistical and data analysis were performed from February 7 to April 27, 2020. Exposures: Clinical characteristics, treatment interventions, course, complications, and resource use were analyzed. Treatment interventions for ulceration in IH included local (wound care, topical), systemic (ß-blocker, corticosteroids), and procedural (pulsed-dye laser). Main Outcomes and Measures: The primary end point was time to complete or nearly complete ulceration healing. Clinical characteristics were analyzed to determine the responses to most common interventions and prognostic factors for healing of ulceration. Results: Of the 436 patients included in the study, 327 were girls (75.0%); median age at ulceration was 13.7 weeks (interquartile range, 8.86-21.30 weeks). The median heal time was 4.79 weeks (95% CI, 3.71-5.86 weeks) with wound care alone, 5.14 weeks (95% CI, 4.57-6.00 weeks) with timolol, 6.36 weeks (95% CI, 5.57-8.00 weeks) with a systemic ß-blocker, and 7.71 weeks (95% CI, 6.71-10.14 weeks) with multimodal therapy. After adjusting for IH size, a dose of propranolol less than or equal to 1 mg/kg/d was associated with shorter healing time compared with higher propranolol doses (hazard ratio, 2.04; 95% CI, 1.11 to 3.73; P = .02). Size of the IH was identified as a significant prognostic factor for healing time in multivariable analysis. Increasing size of IH portends a proportionately longer time to heal of the ulceration. Conclusions and Relevance: Despite the use of ß-blockers, this cohort study found that a subset of patients with IH ulceration continued to experience prolonged IH healing times. Larger IH size appears to be a poor prognostic factor for time to heal. For patients requiring systemic therapy, initiation of propranolol at lower doses (≤1 mg/kg/d) should be considered.

Mental health history and social barriers impacting caregivers of infants with cystic fibrosis.

OBJECTIVES: Caregivers of infants with cystic fibrosis (CF) carry a heavy treatment burden for their child along with the inherent difficulties of raising an infant. This study investigated the impact of self-reported caregiver mental health diagnoses and social barriers during the 1st year of life on clinical outcomes. METHODS: A retrospective chart review was conducted for infants seen in a large tertiary hospital CF clinic over a 5-year period. Baseline characteristics were collected, and documentation from physician and social work notes were reviewed. Demographics and clinical characteristics were compared by the presence or absence of self-reported mental health diagnoses, social barriers, and "emotional concern." RESULTS: Analyses were conducted on 71 patients. Thirty-five percent of caregivers disclosed mental health diagnoses, 52% identified social barriers to care, and 55% reported feeling upset or fatigued. Having a caregiver with a self-reported mental health diagnosis was associated with tobacco smoke exposure (p < .001) and increased odds of hospitalizations (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.49-6.06), emergency department/urgent care visits (OR, 3.17; 95% CI, 1.32-7.64), and longer lengths of stay (OR, 1.93; 95% CI, 1.69-2.20). Caregivers who expressed emotional concern had infants with significantly lower weight-for-length percentiles (p = .012). DISCUSSION: Caregiver mental health and social barriers to care are important determinants to address as they may impact clinical outcomes in infants with CF. Identifying barriers and struggles early increases the likelihood that clinical teams can intervene and provide support. Further research into mental health and socioeconomic barriers faced by caregivers of infants with CF is crucial.

Autoimmune thyroid diseases, autoimmune hepatitis, celiac disease and type 1 diabetes mellitus in pediatric systemic lupus erythematosus: Results from the CARRA Legacy Registry.

OBJECTIVE: Polyautoimmunity (PA) with systemic lupus erythematosus (SLE) is reported as a poor prognostic factor, but little is known about its effect in childhood-onset SLE (cSLE). We describe PA in cSLE within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry and evaluate its association to lupus disease outcomes. METHODS: CARRA Legacy Registry is the largest pediatric rheumatology registry that collected data at enrollment and every 6 months thereafter. We describe the co-occurrence of selected autoimmune disorders (autoimmune thyroid diseases, autoimmune hepatitis, celiac disease and type 1 diabetes mellitus) in cSLE. To assess outcomes, we studied measures of lupus disease activity, complications, and patient's quality of life (QoL). Comparisons by PA status were made using chi-square, Fisher's exact test, two-sample t-tests, Wilcoxon rank sum tests, and mixed effects models as appropriate. RESULTS: 1285 patients met the American College of Rheumatology criteria for SLE. Of those, 388 (30%) had data on comorbidity. The prevalence of PA was 8.8%. Patients with PA reported more hospitalizations and aggressive immunotherapy use. SLEDAI and PGA scores improved over time, but did not differ by PA status. No significant differences were found in QoL measures or their trajectory over time by PA status. CONCLUSION: In cSLE, PA is associated with more hospitalizations and aggressive immunotherapy use. Although lupus disease activity improved over time, patients' QoL neither improved over time nor differed by having other autoimmune disease. Prospective, case-control, long-term follow-up studies on cSLE are needed to validate our results. MESH KEY INDEXING TERMS: Pediatric systemic lupus erythematosus; Autoimmune diseases; Outcome assessment.

Gastroesophageal reflux in cystic fibrosis across the age spectrum.

BACKGROUND: Scientific advances have improved longevity in cystic fibrosis (CF) patients and many of these patients can expect to experience age-related gastrointestinal co-morbidities. We aimed to assess the extent to which age might impact gastroesophageal reflux (GER) in patients with CF. METHODS: Our esophageal pH-multichannel intraluminal impedance monitoring database was searched for tracings belonging to CF patients ≥2 years old without prior fundoplication and not taking anti-reflux medications immediately prior (within 7 days) and during the study. Tracings were retrospectively analyzed; Impedance and pH variables were evaluated with respect to age and pulmonary function. RESULTS: Twenty-eight patients were enrolled; 16 children (3.1-17.7 years) and 12 adults (18.2-48.9 years). Among pH probe parameters, correlation analysis showed DeMeester score (P=0.011) and number of acid reflux events lasting >5 minutes (P=0.047) to be significantly correlated with age. Age was not significantly correlated with any of the impedance parameters. Age was negatively correlated with baseline impedance (BI) in the distal esophagus (r=-0.424, P=0.023) and BI was negatively correlated with several pH parameters, including reflux index (r=-0.553, P=0.002), number of total acid reflux events (r=-0.576, P=0.001), number of acid reflux events lasting >5 minutes (r=-0.534, P=0.003), and DeMeester score (r=-0.510, P=0.006). Pulmonary function (percent predicted forced expiratory volume in one minute; ppFEV1) was negatively correlated with age (r=-0.494, P=0.0007). The interaction of age and ppFEV1 and any of the reflux parameters, however, was not significant (P>0.05); the strongest evidence for an interaction was found for the number of acid reflux events reaching the proximal esophagus, but this interaction still did not reach statistical significance (P=0.070). CONCLUSIONS: In a small cohort, we found evidence that age may be associated with increased acid exposure and that both age and increased acid exposure are associated with reduced BI in the distal esophagus. The negative relationship between pulmonary function and age in our cohort is not related to GER. This pilot study supports the need for esophageal assessment and treatment of GER as standard components of clinical care for an aging CF population.

Validation of a risk screening tool for pediatric type 1 diabetes patients: a predictor of increased acute health care utilization.

Background Both psychosocial and socioeconomic risk factors contribute to poor glycemic control (GC). Previous research has identified that diabetes care behaviors are generally 'set' by late childhood, further highlighting the importance of psychosocial screening and intervention in the early course of disease management. The purpose of the current study was to determine whether this brief risk assessment tool is associated with GC and acute health care (HC) utilization, and to evaluate the discriminatory utility of the tool for predicting poor outcomes. Methods This was a retrospective cohort design in which we compared risk assessment scores with health outcomes at 6, 12, and 18 months after new-onset type 1 diabetes diagnosis for 158 patients between 2015 and 2017. The two primary outcome variables were GC and acute HC utilization. Results Our data demonstrate that the greatest utility of the tool is for predicting increased acute HC utilization. It was most useful in differentiating between patients with vs. without any acute HC utilization, with excellent discriminatory ability (area under the receiver operator characteristic curve [AUC] = 0.93), sensitivity (90%), and specificity (97%). Conclusions Knowledge of the risk category in addition to identification of individual risk factors within each domain allows for not only clear treatment pathways but also individualized interventions. The risk assessment tool was less effective at differentiating patients with poor GC; however, the tool did have high specificity (83%) for predicting poor GC at 18 months which suggests that the tool may also be useful for predicting patients at risk for poor GC.

Pulmonary findings in infants with cystic fibrosis during the first year of life: Results from the Baby Observational and Nutrition Study (BONUS) cohort study.

IMPORTANCE: Treatment recommendations for infants with CF standardize care, but most surveillance or treatment guidance of pulmonary manifestations are consensus-based due to sparse evidence. OBJECTIVE: To report observations about pulmonary correlates of growth and other clinical features in infants with CF. METHODS: We analyzed data from the prospective Baby Observational and Nutrition Study conducted in 28 centers across the US, including clinical features, medications, guardian diaries of respiratory symptoms, oropharyngeal swab cultures and chest radiographs (CXR) collected over the first year of life. RESULTS: Cough was reported in 84% of infants in the first year. Up to 30% had clinically important cough but only 6.3% had crackles; 16.5% had wheeze. Wisconsin CXR score was above 5 in 23% (normal = 0; maximum score = 100). Pseudomonas was recovered from at least one respiratory culture in 24% of infants and was associated with crackles/wheezes and use of proton pump inhibitors (PPI) (OR = 5.47; 95%CI = 1.36, 21.92; P = 0.02) or PPI plus histamine-2 (H2) blocker (OR = 8.2; 95%CI = 2.41, 27.93; P = 0.001), but not H2 blocker alone. Hospitalization for respiratory indications occurred in 18% of infants and was associated with crackles/wheeze and abnormal CXR but not low weight, Pseudomonas or use of acid blockade. CONCLUSIONS: Cough is common in infants with CF, but few present with crackles/wheeze or CXR changes. Pseudomonas is associated with use of PPI or PPI plus H2 blocker, but not with respiratory hospitalization. These observations cannot prove cause and effect but add to our understanding of pulmonary manifestations of CF in infants. TRIAL REGISTRATION: United States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).

A randomised controlled trial of protocolised music therapy demonstrates developmental milestone acquisition in hospitalised infants.

AIM: To compare the effectiveness of an intensive-intermittent vs. standard spaced protocolised music therapy intervention on supporting developmental milestone acquisition of infants >44 weeks postmenstrual age (PMA) hospitalised in a Neonatal Intensive Care Unit (NICU). METHOD: This was a comparative effectiveness study of infants 44-66 weeks PMA with a projected NICU stay of at least one month from recruitment. Infants were randomised to one of two treatment groups: traditional therapy (2x/week) and intermittent-intensive (4x/week, off, 4x/week, off). Both groups received the same number of sessions over a 4-week period. Sessions at the start and end of the treatment period were video recorded. Two masked researchers reviewed and coded videos. Milestones used for video recording were adapted from the Developmental Assessment of Young Children. RESULTS: Twenty-four infants participated, with groups matched for birth age, PMA at start of study, race, IVH severity, and respiratory support. Total and motor composite scores were higher post-intervention (Cohen's d = 0.71 and 0.97, both p < 0.01), with the same degree of skill acquisition found for both intervention groups. CONCLUSION: A developmental music therapy protocol supports developmental skills acquisition of post-term infants in a NICU. Similar outcomes for both groups provide therapists with varying treatment dosing options to best support their patients.

Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.

BACKGROUND: Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. METHODS: Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4-6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. RESULTS: We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. CONCLUSION: A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.

A Multidisciplinary Approach to a Pediatric Difficult Airway Simulation Course.

Objective To design and assess an advanced pediatric airway management course, through simulation-based team training and with multiple disciplines, to emphasize communication and cooperation across subspecialties and to provide a common skill set and knowledge base. Methods Trainees from anesthesiology, emergency medicine, critical care, pediatric surgery, and otolaryngology at a tertiary children's hospital participated in a 1-day workshop emphasizing airway skills and complex airway simulations. Small groups were multidisciplinary to promote teamwork. Participants completed pre- and postworkshop questionnaires. Results Thirty-nine trainees participated over the 3-year study period. Compared with their precourse responses, participants' postcourse responses indicated either agreement or strong agreement that the multidisciplinary format (1) helped in the development of team communication skills and (2) was preferred over single-discipline training. Improvement in confidence in managing critical airway situations and in advanced airway management skills was significant ( P < .05). Eighty-one percent of participants had improved confidence in following the hospital's critical airway protocol, and 64% were better able to locate advanced airway management equipment. Discussion Multiple subspecialists manage pediatric respiratory failure, where successful care requires complex handoffs and teamwork. Multidisciplinary education to teach advanced airway management, teamwork, and communication skills is practical and preferred by learners and is possible to achieve despite differences in experience. Future study is required to better understand the impact of this course on patient care outcomes. Implications for Practice Implementation of a pediatric difficult airway course through simulation-based team training is feasible and preferred by learners among multiple disciplines. A multidisciplinary approach exposes previously unrecognized knowledge gaps and allows for better communication and collaboration among the fields.

Early Immune Function and Duration of Organ Dysfunction in Critically III Children with Sepsis.

RATIONALE: Late immune suppression is associated with nosocomial infection and mortality in adults and children with sepsis. Relationships between early immune suppression and outcomes in children with sepsis remain unclear. OBJECTIVES: Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis or septic shock. METHODS: Children younger than 18 years of age meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy control subjects were sampled once. Innate immune function was quantified by whole blood ex vivo LPS-induced TNF-α (tumor necrosis factor-α) production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFN-γ production capacity. MEASUREMENTS AND MAIN RESULTS: One hundred two children with sepsis and 35 healthy children were enrolled. Compared with healthy children, children with sepsis demonstrated lower LPS-induced TNF-α production (P < 0.0001) and lower phytohemagglutinin-induced IFN-γ production (P < 0.0001). Among children with sepsis, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction syndrome and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased multiple organ dysfunction syndrome days (adjusted relative risk, 1.2; 95% confidence interval, 1.03-1.5) and organ dysfunction days (adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSIONS: Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early innate and adaptive immune suppression are associated with longer durations of organ dysfunction and may be useful markers to help guide future investigations of immunomodulatory therapies in children with sepsis.

Prefusion F, Postfusion F, G Antibodies, and Disease Severity in Infants and Young Children With Acute Respiratory Syncytial Virus Infection.

Background: Respiratory syncytial virus (RSV) is the most frequent cause of lower respiratory tract infection in infants. Maternally derived RSV-specific antibodies play a role in protection against RSV infection in early life, but data regarding the concentration and specificity of those antibodies are incomplete. Methods: We prospectively enrolled a cohort of previously healthy infants and young children hospitalized (n = 45) or evaluated as outpatients (n = 20) for RSV infection, and healthy noninfected age-matched controls (n = 18). Serum samples were obtained at enrollment to quantify the concentrations and neutralizing activity of serum immunoglobulin G antibodies to the RSV prefusion (pre-F), postfusion (post-F), and G glycoproteins. We also assessed the associations between antibody concentrations and clinical disease severity. Results: Concentrations of pre-F antibodies were ≥3-fold higher than post-F antibodies and >30-fold higher than G antibodies in serum from infants with acute RSV infection. Antibody concentrations and neutralizing activity inversely correlated with age. The pre-F antibodies displayed the greatest neutralizing activity (55%-100%), followed by G (0%-45%), and post-F (0%-29%) antibodies. Higher concentrations of pre-F and G antibodies, but not post-F antibodies, were associated with lower clinical disease severity scores. Conclusions: Maternal antibodies directed to pre-F, followed by antibodies directed to G, can modulate RSV disease severity in young infants.

Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux.

PURPOSE: Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. METHODS: Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis. RESULTS: Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis (p=0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. CONCLUSION: Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

Muscle MRI at the time of questionable disease flares in Juvenile Dermatomyositis (JDM).

BACKGROUND: The course of JDM has improved substantially over the last 70 years with early and aggressive treatments. Yet it remains difficult to detect disease flares as symptoms may be mild; signs of rash and muscle weakness vary widely and are often equivocal; laboratory tests of muscle enzyme levels are often normal; electromyography and muscle biopsy are invasive. Alternative tools are needed to help decide if more aggressive treatment is needed. Our objective is to determine the effectiveness of muscle Magnetic Resonance Imaging (MRI) in detecting JDM flares, and how an MRI affects physician's decision-making regarding treatment. METHODS: This study was approved by the Institutional Review Board of Nationwide Children's Hospital. JDM patients were consulted between 1/2005 and 6/2015. MRIs were performed on both lower extremities without contrast sequentially: axial T1, axial T2 fat saturation, axial and coronal inversion recovery, and axial diffusion weighted. The physician decision that a JDM patient was in a flare was considered the gold standard. MRI results were compared with physician's decisions on whether a relapse had occurred, and if there was a concordance between the assessment methods. RESULTS: Forty-five JDM patients were studied. Eighty percent had weakness at diagnosis, 100% typical rash, and 73% typical nail-fold capillary changes. At diagnosis, muscle enzymes were compatible with JDM generally (CK 52%, LDH 62%, aldolase 72%, AST 54% abnormal). EMG was abnormal in 3/8, muscle biopsy typical of JDM in 10/11, and MRI abnormal demonstrating myositis in 31/40. Thirteen patients had a repeat MRI for possible flares with differing indications. Three repeat MRI's were abnormal, demonstrating myositis. There was moderate agreement about flares between MRI findings and physician's treatment decisions (kappa = 0.59). In each abnormal MRI case the physician decided to increase treatment (100% probability for flares). MRI was negative for myositis in 10 patients, by which 7/10 the physicians chose to continue or to taper the medications (70% probability for non-flares). CONCLUSION: A muscle MRI would facilitate objective assessments of JDM flares. When an MRI shows myositis, physicians tend to treat 100% of the time. When an MRI shows no myositis, physicians continued the same medications or tapered medications 70% of the time. Further studies would help confirm the utility and cost-effectiveness of MRI to determine JDM flares.

Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes.

Sporadic inclusion body myositis, a variant of inflammatory myopathy, has features distinct from polymyositis/dermatomyositis. The disease affects men more than women, most commonly after age 50. Clinical features include weakness of the quadriceps, finger flexors, ankle dorsiflexors, and dysphagia. The distribution of weakness is similar to Becker muscular dystrophy, where we previously reported improvement following intramuscular injection of an isoform of follistatin (FS344) by AAV1. For this clinical trial, rAAV1.CMV.huFS344, 6 × 1011 vg/kg, was delivered to the quadriceps muscles of both legs of six sporadic inclusion body myositis subjects. The primary outcome for this trial was distance traveled for the 6-min walk test. The protocol included an exercise regimen for each participant. Performance, annualized to a median 1-year change, improved +56.0 m/year for treated subjects compared to a decline of -25.8 m/year (p = 0.01) in untreated subjects (n = 8), matched for age, gender, and baseline measures. Four of the six treated subjects showed increases ranging from 58-153 m, whereas two were minimally improved (5-23 m). Treatment effects included decreased fibrosis and improved regeneration. These findings show promise for follistatin gene therapy for mild to moderately affected, ambulatory sporadic inclusion body myositis patients. More advanced disease with discernible muscle loss poses challenges.

Isolated heart transplant and combined heart-liver transplant in adult congenital heart disease patients: Insights from the united network of organ sharing.

BACKGROUND/METHODS: The aging patient with severe congenital heart disease (CHD) faces many challenges: heart failure, arrhythmia, and in the Fontan patient, liver disease. Our goal was to define combined heart liver transplant (CHLT) and isolated orthotopic heart transplant (OHT) outcomes in U.S. adult CHD patients. The U.S. United Network for Organ Sharing (UNOS) thoracic and liver databases were queried for cardiac and CHD diagnoses, from inception-2014. RESULTS: In CHLT, CHD made up 22% of waitlist patients (non-CHD n=262 vs. CHD n=58), and 20% of transplanted patients (non-CHD n=137 vs. CHD n=27). Liver function tests in the non-CHD and CHD groups were similar and there was no difference in CHD and non-CHD survival (HR 0.93, CI: 0.36-2.38, p 0.48). In isolated OHT, CHD patients comprised 2% of those listed (non-CHD n=74,080 vs. CHD n=1599) and transplanted (non-CHD n=48,985 vs. CHD n=967) and had higher early (<1year) mortality (HR 1.36, CI: 1.18-1.57, p<0.0001), but better long-term survival (HR 0.66, CI; 0.57-0.76, p<0.001) than non-CHD. Both groups benefitted from mechanical support when used (non-CHD HR 0.34, CI: 0.31-0.37 and CHD HR 0.14, CI: 0.03-0.58) and prior sternotomy had no effect on mortality in CHD (HR 0.63, CI: 0.15-2.58). CONCLUSIONS: Survival of CHD patients undergoing CHLT is no different than in non-CHD, encouraging consideration of CHLT when clinically appropriate. Short-term mortality is higher in CHD (vs. non-CHD) patients undergoing OHT, regardless of prior cardiac surgery status. Modifications to CHD classification within UNOS would help better understand CHD CHLT and OHT outcomes.

Screening Criteria Improve Access to Palliative Care in the PICU.

OBJECTIVES: To test the ability of palliative care screening criteria to improve access to palliative care services in the PICU and examine the association between palliative care team involvement and ICU and hospital length of stay. DESIGN: Prospective interventional quality improvement study. SETTING: PICU at a quaternary academic medical center. PATIENTS: All patients admitted to the PICU who met criteria for palliative care referral over a 9-month period. INTERVENTION: Consensus palliative care consultation criteria were created by pediatric critical care medicine and palliative care providers, and palliative care referral was encouraged for all PICU patients meeting criteria. MEASUREMENTS AND MAIN RESULTS: Palliative care referral rates increased significantly after screening criteria implementation. We identified 100 patients who were eligible for palliative care services, and referrals were made for 70 patients (70%). Patients were divided into three groups based on palliative care status: patients new to the palliative care team, patients with an existing palliative care relationship, and patients who did not have a palliative care referral. By the end of study, patients who had an existing relationship with the palliative care team were more likely to still be alive and to have limitations of medical interventions in place, whereas patients who did not have a palliative care referral were more likely to be deceased and to have died in the PICU. After correcting for other factors, including severity of illness, patients who were new to the palliative care team experienced greater delay in palliative care referral and had significantly longer PICU and hospital length of stay than those who were already known to the palliative care team. CONCLUSIONS: Palliative care screening criteria are effective tools for improving access to palliative care services in the PICU; however, widespread adoption may produce a significant increase in palliative care demand. The association between an existing palliative care relationship and reduction in resource utilization deserves further investigation as does the perceived benefit of palliative care involvement in the patient, family, and staff experience.