The Evaluation and Management of Methimazole-Induced Agranulocytosis in the Pediatric Patient: A Case Report and Review of the Literature.

INTRODUCTION: Agranulocytosis is a rare, but serious complication of methimazole (MMI) use for Graves' disease (GD). Treatment requires discontinuation of MMI, and the use of propylthiouracil (PTU) is also contraindicated. Few reports exist about the optimal alternative treatment regimens for the management of thyrotoxicosis in these medically complex patients in the pediatric population. CASE REPORT: We report prolonged saturated solution of potassium Iodide (SSKI) use (29 days) in a 17-year-old female with GD and MMI-induced agranulocytosis, who presented with septic shock. Her treatment course also included beta-blockade, cholestyramine, and granulocyte colony stimulating factor. We performed a review of the literature on the use of SSKI in the management of thyrotoxicosis, as well as best practices from the view of endocrinology, infectious disease, hematology, surgery, and intensivists, for the evaluation and management of MMI-induced agranulocytosis. DISCUSSION: The management of MMI-induced agranulocytosis and associated sequelae require subspecialty input and intensive evaluation and monitoring. Alternative treatments to manage hyperthyroidism and control symptoms of thyrotoxicosis during agranulocytosis are a bridge to definitive therapy, and include beta-blockade, SSKI, cholestyramine, steroids, lithium, and plasmapheresis.

Online Learning and Residents' Acquisition of Mechanical Ventilation Knowledge: Sequencing Matters.

OBJECTIVE: Rapid advancements in medicine and changing standards in medical education require new, efficient educational strategies. We investigated whether an online intervention could increase residents' knowledge and improve knowledge retention in mechanical ventilation when compared with a clinical rotation and whether the timing of intervention had an impact on overall knowledge gains. DESIGN: A prospective, interventional crossover study conducted from October 2015 to December 2017. SETTING: Multicenter study conducted in 33 PICUs across eight countries. SUBJECTS: Pediatric categorical residents rotating through the PICU for the first time. We allocated 483 residents into two arms based on rotation date to use an online intervention either before or after the clinical rotation. INTERVENTIONS: Residents completed an online virtual mechanical ventilation simulator either before or after a 1-month clinical rotation with a 2-month period between interventions. MEASUREMENTS AND MAIN RESULTS: Performance on case-based, multiple-choice question tests before and after each intervention was used to quantify knowledge gains and knowledge retention. Initial knowledge gains in residents who completed the online intervention (average knowledge gain, 6.9%; SD, 18.2) were noninferior compared with those who completed 1 month of a clinical rotation (average knowledge gain, 6.1%; SD, 18.9; difference, 0.8%; 95% CI, -5.05 to 6.47; p = 0.81). Knowledge retention was greater following completion of the online intervention when compared with the clinical rotation when controlling for time (difference, 7.6%; 95% CI, 0.7-14.5; p = 0.03). When the online intervention was sequenced before (average knowledge gain, 14.6%; SD, 15.4) rather than after (average knowledge gain, 7.0%; SD, 19.1) the clinical rotation, residents had superior overall knowledge acquisition (difference, 7.6%; 95% CI, 2.01-12.97;p = 0.008). CONCLUSIONS: Incorporating an interactive online educational intervention prior to a clinical rotation may offer a strategy to prime learners for the upcoming rotation, augmenting clinical learning in graduate medical education.

Robust Cytokine and Chemokine Response in Nasopharyngeal Secretions: Association With Decreased Severity in Children With Physician Diagnosed Bronchiolitis.

BACKGROUND: Bronchiolitis causes substantial disease in young children. Previous findings had indicated that a robust innate immune response was not associated with a poor clinical outcome in bronchiolitis. This study tested the hypothesis that increased concentrations of cytokines and chemokines in nasal wash specimens were associated with decreased severity in bronchiolitis. METHODS: Children <24 months old who presented to the emergency department with signs and symptoms of bronchiolitis were eligible for enrollment. Nasal wash specimens were analyzed for viral pathogens and cytokine/chemokine concentrations. These results were evaluated with regard to disposition. RESULTS: One hundred eleven children with bronchiolitis were enrolled. A viral pathogen was identified in 91.9% of patients (respiratory syncytial virus in 51.4%, human rhinovirus in 11.7%). Higher levels of cytokines and chemokines (interferon [IFN] γ; interleukin [IL] 4, 15, and 17; CXCL10; and eotaxin) were significantly associated with a decreased risk of hospitalization. IL-17, IL-4, IFN-γ, and IFN-γ-inducible protein 10 (CXCL10 or IP-10) remained statistically significant in the multivariate analyses. CONCLUSIONS: The cytokines and chemokines significantly associated with decreased bronchiolitis severity are classified in a wide range of functional groups (T-helper 1 and 2, regulatory, and chemoattractant). The involvement of these functional groups suggest that a broadly overlapping cytokine/chemokine response is required for control of virus-mediated respiratory disease in young children.

Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity.

BACKGROUND: Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. OBJECTIVE: To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis. METHODS: Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. RESULTS: A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition. CONCLUSIONS: NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center.

Ciliary neurotrophic factor genotype does not influence clinical phenotype in amyotrophic lateral sclerosis.

Ciliary neurotrophic factor (CNTF) maintains survival of adult motor neurons. Mice lacking the CNTF gene develop mild, progressive motor neuron loss. In the normal human population, 1 to 2.3% are homozygous for a null allele, and reports suggest this mutant is associated with a younger onset of amyotrophic lateral sclerosis (ALS). We have tested this hypothesis in a study of 400 subjects with ALS and 236 controls. There was no difference in age of onset, clinical presentation, rate of progression, or disease duration for those with one or two copies of the null allele, excluding CNTF as a major disease modifier in ALS.