Acute Fulminant Cerebral Edema: A Newly Recognized Phenotype in Children With Suspected Encephalitis.

BACKGROUND: Encephalitis is a severe neurological syndrome associated with significant morbidity and mortality. The California Encephalitis Project (CEP) enrolled patients for more than a decade. A subset of patients with acute and fulminant cerebral edema was noted. METHODS: All pediatric encephalitis patients with cerebral edema referred to the CEP between 1998 and 2012 were reviewed. A case definition was developed for acute fulminant cerebral edema (AFCE) that included the CEP case definition for encephalitis and progression to diffuse cerebral edema on neuroimaging and/or autopsy, and no other recognized etiology for cerebral edema (eg, organic, metabolic, toxin). Prodromic features, demographic and laboratory data, neuroimaging, and outcomes were compared with non-AFCE encephalitis cases. RESULTS: Of 1955 pediatric cases referred to the CEP, 30 (1.5%) patients met the AFCE case definition. The median age for AFCE and non-AFCE cases was similar: 8.2 years (1-18 years) and 8.0 years (0.5-18 years), respectively. Asian-Pacific Islanders comprised a larger proportion of AFCE cases (44%) compared with non-AFCE cases (14%, P < .01). AFCE cases often had a prodrome of high fever, vomiting, and profound headache. Mortality among AFCE patients was significantly higher than among non-AFCE patients (80% vs 13%, P < .01). A confirmed etiology was identified in only 2 cases (enterovirus, human herpes virus type 6), while 10 others had evidence of a respiratory pathogen.Thirty pediatric patients referred to the California Encephalitis Project with a unique, and often fatal, form of encephalitis are reported. Demographic and clinical characteristics, possible etiologies and a proposed case definition for acute fulminant cerebral edema (AFCE) are described. CONCLUSIONS: AFCE is a recently recognized phenotype of encephalitis with a high mortality. AFCE may be triggered by common pediatric infections. Here, we propose a case definition.

Gamification and Microlearning for Engagement With Quality Improvement (GAMEQI): A Bundled Digital Intervention for the Prevention of Central Line-Associated Bloodstream Infection.

Central line-associated bloodstream infections (CLABSIs) cause major patient harm, preventable through attention to line care best practice standards. The objective was to determine if a digital self-assessment application (CLABSI App), bundling line care best practices with social gamification and in-context microlearning, could engage nurses in CLABSI prevention. Nurses caring for children with indwelling central venous catheters in 3 high-risk units were eligible to participate. All other units served as controls. The intervention was a 12-month nonrandomized quality improvement study of CLABSI App implementation with interunit competitions. Compared to the preceding year, the intervention group (9886 line days) CLABSI rate decreased by 48% ( P = .03). Controls (7879 line days) did not change significantly. In all, 105 unique intervention group nurses completed 673 self-assessments. Competitions were associated with increased engagement as measured by self-assessments and unique participants. This model could be extended to other health care-associated infections, and more broadly to process improvement within and across health care systems.

Real-Time Evolution of Zika Virus Disease Outbreak, Roatán, Honduras.

A Zika virus disease outbreak occurred in Roatán, Honduras, during September 2015-July 2016. Blood samples and clinical information were obtained from 183 patients given a clinical diagnosis of suspected dengue virus infection. A total of 79 patients were positive for Zika virus, 13 for chikungunya virus, and 6 for dengue virus.

Extended Sedation With Continuous Midazolam or Dexmedetomidine Infusion for Young Children Receiving 131 I-MIBG Radiopharmaceutical Therapy for Advanced Neuroblastoma.

BACKGROUND: (131) I-MIBG is increasingly used for treating neuroblastoma; however, administration requires careful adherence to radiation safety guidelines. We describe our experience using continuous sedation to facilitate safe (131) I-MIBG therapy for young children. PROCEDURE: Patients were included in this case series if they received continuous midazolam or dexmedetomidine infusion for sedation during (131) I-MIBG therapy from November 1, 2012, to October 1, 2014. Key outcomes included adequacy of sedation for both (131) I-MIBG infusion and the duration of radioactive isolation, as well as sedative-related toxicities. Additionally, nuclear medicine scans before and after (131) I-MIBG therapy were assessed using the Curie score. These scores were compared qualitatively between midazolam, dexmedetomidine, and control (no sedative infusion) groups. RESULTS: Of the 13 patients receiving continuous sedation for (131) I-MIBG therapy, seven achieved adequate sedation with midazolam, five achieved adequate sedation with dexmedetomidine, one patient (1.6 years old) failed to achieve adequate sedation with either medication and did not receive (131) I-MIBG therapy. Sedation was generally well tolerated. Common side effects for dexmedetomidine infusion included hypotension and relative bradycardia. Both treatment and control groups had multiple patients with increased Curie scores post-(131) I-MIBG therapy. However, one patient in the midazolam group and two in the dexmedetomidine group had decreased Curie scores after (131) I-MIBG therapy, while none decreased in the control group. CONCLUSIONS: Although we cannot exclude the possibility of some inhibition of (131) I-MIBG uptake by midazolam or dexmedetomidine, this case series suggests that continuous infusions of either agent can provide effective sedation to allow safe administration of (131) I-MIBG to young patients.

Verapamil-sensitive idiopathic left ventricular tachycardia in a 6-month-old: unique considerations in diagnosis and management in an infant.

Idiopathic left ventricular tachycardia of the Belhassen type is rare in infants. We present a 6-month-old infant girl with a wide-complex tachycardia with right bundle branch block QRS morphology, a superior axis, and atrioventricular dissociation, consistent with a left anterior fascicular tachycardia. Initial echocardiogram revealed depressed ventricular function. The tachycardia was unresponsive to therapeutic trials of adenosine, esmolol, procainamide, and lidocaine. There was brief conversion of the tachycardia to sinus rhythm with transesophageal atrial overdrive pacing, suggesting a reentrant mechanism of the arrhythmia. Ultimately, the judicious administration of intravenous verapamil resulted in termination of the arrhythmia, which has been sustained on oral therapy.

Anti-N-methyl D-aspartate receptor encephalitis mimics viral encephalitis.

We describe the clinical courses of 3 children with a psychochoreiform encephalitis associated with anti-N-methyl D-aspartate receptor autoantibodies. These cases, including the most severely medically complicated survivor to date, illustrate the challenges of diagnosis, supportive care, and immune-modulating therapy. Clinical and laboratory features are similar to those of viral encephalitis, and the condition is often reversible with appropriate diagnosis and treatment.

Failure of the Milwaukee protocol in a child with rabies.

Rabies has the highest case-fatality rate of all infectious diseases, with 50,000 cases occurring annually worldwide. In 2004 an unvaccinated adolescent survived after novel therapy. We report the management of a child with rabies. Although the implementation of this same therapeutic protocol was successful, the child died after 1 month of hospitalization.

Rhinovirus associated with severe lower respiratory tract infections in children.

Rhinovirus is a respiratory virus most typically associated with the common cold and asthma exacerbations, and has not traditionally been considered to play a major role in severe lower respiratory tract infections (LRTIs). As part of a surveillance program for respiratory pathogens of public health importance, children consecutively admitted to intensive care for LRTI at a large tertiary children's hospital were tested with polymerase chain reaction for 11 respiratory viruses and Mycoplasma pneumoniae from February 21 to October 31, 2007; 43 cases were enrolled and rhinovirus was the most frequently detected pathogen, with 21 (49%) positive. Rhinovirus cases frequently were young (median age, 1.4 years [range, 44 days-15 years]), hospitalized for pneumonia (10; 48%), had chronic underlying illnesses (15; 71%), had abnormal chest radiographs (18; 86%), required mechanical ventilation (12; 57%), and had prolonged hospitalization (median length, 7 days [range, 1-29 days]). Coinfection with other viruses or bacteria was common (10; 47%). Rhinovirus may be associated with more severe LRTI in children than previously reported, particularly in the noninfluenza, nonrespiratory syncytial virus season.

Phage versus phagemid libraries for generation of human monoclonal antibodies.

Non-immune (naïve) phage antibody libraries have become an important source of antibodies for reagent, diagnostic, and therapeutic use. To date, reported naïve libraries have been constructed in phagemid vectors as fusions to pIII, yielding primarily single copy (monovalent) display of antibody fragments. For this work, we subcloned the single chain Fv (scFv) gene repertoire from a naïve phagemid antibody library into a true phage vector to create a multivalently displayed scFv phage library. Compared to monovalently displayed scFv, multivalent phage display resulted in improved efficiency of display as well as antibody selection. A greater number of antibodies were obtained and at earlier rounds of selection. Such increased efficiency allows the screening for binding antibodies after a single round of selection, greatly facilitating automation. Expression levels of antigen-binding scFv were also higher than from the phagemid library. In contrast, the affinities of scFv from the phage library were lower than from the phagemid library. This could be overcome by utilizing the scFv in a multivalent format, by affinity maturation, or by converting the library to monovalent display after the first round of selection.

Generation and characterization of a protective monoclonal antibody to Pseudomonas aeruginosa PcrV.

Pseudomonas aeruginosa is a gram-negative pathogen causing life-threatening infections. Lung injury and the development of sepsis depend largely on the expression of type III secretion system (TTSS) virulence. TTSS functions as a molecular syringe to deliver toxins directly to the cytosol of cells, inhibit innate immune mechanisms, and prevent bacterial clearance. Polyclonal antibodies that bind to PcrV of P. aeruginosa inhibit the delivery of type III toxins and enhance the clearance of bacteria during acute lung infections. PcrV is a homologue of LcrV, a protective antigen in the Yersinia TTSS and an integral component of TTSS. In this study, a murine monoclonal antibody (MAb) to PcrV was generated: MAb 166, which is protective against P. aeruginosa when coinstilled with the bacterial inoculum or intraperitoneally transferred to mice. Fab fragments from MAb 166 prevent sepsis and death. The epitope bound by MAb 166 was mapped to the carboxyl-terminus of PcrV.

Resolution of severe Donath-Landsteiner autoimmune hemolytic anemia temporally associated with institution of plasmapheresis.

OBJECTIVES: To report a case of severe postinfectious autoimmune hemolytic anemia (AIHA) owing to the Donath-Landsteiner (DL) antibody resolving with plasmapheresis, and to review the pathophysiology of this underrecognized cause of pediatric AIHA and its potential susceptibility to plasmapheresis therapy. DESIGN: Descriptive case report. SETTING: A pediatric intensive care unit in a university children's hospital. PATIENT: A 5-yr-old Hispanic female had gastroenteritis followed by progressive intravascular hemolysis, initially attributed to acute postinfectious cold hemagglutinin (immunoglobulin M) disease. INTERVENTION: With no slowing in the rate of hemolysis, a continued need for frequent transfusions, and a lack of response to corticosteroid and intravenous immunoglobulin therapy, a 3-day course of plasmapheresis was administered. MEASUREMENTS AND MAIN RESULTS: The patient presented to an emergency department with an initial hematocrit of 22%, which fell to 12% by hospital admission. She received nine transfusions over 7 days, with her hematocrit reaching a nadir of 11% on the 5th day of hospitalization. Once plasmapheresis was initiated, she required no further transfusion. Analysis of serum from initial presentation demonstrated biphasic hemolysis, confirming the presence of the DL antibody. CONCLUSIONS: In AIHA, in which the direct antiglobulin test detects primarily C3 rather than immunoglobulin G, especially in children, the DL antibody must be considered. Confirming the diagnosis rapidly may be critical, especially in cases of severe hemolysis, because this may help direct therapy. A low titer of DL antibody can mediate severe intravascular hemolysis given its propensity to sensitize, detach, and rebind erythrocytes with changes in temperature in the microcirculation. However, given the transient and relatively brief production of the DL antibody in postviral illness, early clearance of the offending antibody may be possible with plasmapheresis, without the expectation for significant rebound antibody production, potentially decreasing the length of hospital stay and the need for transfusions.