Child With Red Eye and Blurry Vision.

Point-of-care ocular ultrasound can provide the clinician with more information about potential intraorbital and extraocular pathology, especially in cases when direct visualization of the eye is limited. This case report describes the findings in a pediatric patient who presented with a 1-month history of eye injection and worsening blurry vision. After point-of-care ultrasound demonstrated abnormal debris in the posterior vitreous cavity, subsequent evaluation revealed a diagnosis of pars planitis.

Point-of-Care Ultrasound Diagnosis of Diaphragmatic Hernia in an Infant With Respiratory Distress.

Neonatal respiratory distress is an emergent condition with a wide differential diagnosis. A 12-day-old newborn presented to the emergency department in respiratory distress. Point-of-care ultrasound allowed clinicians to rapidly exclude cardiac disease and pneumothorax as possible causes of the patient's respiratory distress, and expedited the identification of congenital diaphragmatic hernia. The ultrasound findings and technique, epidemiology, pathophysiology, and radiological diagnosis of congenital diaphragmatic hernia are reviewed.

Learning Curves for Ultrasound Assessment of Lumbar Puncture Insertion Sites: When is Competency Established?

BACKGROUND: Ultrasound (US) can be used to improve lumbar puncture (LP) success. How to achieve competency in LP US has not been defined. Cumulative sum statistics (CUSUM) characterized competency acquisition in other skills. OBJECTIVES: Identify the learning curve for 80% success rate in LP US insertion site (IS) identification among pediatric emergency medicine fellows. METHODS: This prospective study took place in a single pediatric emergency department. Fellows with limited ultrasound experience received didactics, training, and three proctored examinations. Skills were evaluated in three 2-h sessions: using US, subjects identified LP ISs on a convenience sample of patients ages 0-20 years old. Subjects' IS markings were compared to markings by an expert, an emergency US fellowship-trained attending. Successful IS identification was defined as markings within 2 mm or 5 mm of the expert mark in infants and older children, respectively. A second expert marked 17 cases for interrater agreement. CUSUM was used to analyze individual learning curves. RESULTS: Five fellows evaluated 72 patients (mean age 11.4 years [SD = 4, range 3-20], mean body mass index 20.5 [SD = 4.4, range 13.1-37.7]) over a 3-month period. Mean number of attempts per fellow was 14.4 ± 3.1 (R 11-19); mean time to landmark identification was 72 ± 46 s (R 27-240). The two experts demonstrated 100% observed agreement. Aggregate success rate for all fellows was 75% (54/72). Four fellows showed learning curves that trended toward, but did not achieve, the acceptable success rate of 80%. CONCLUSIONS: Nineteen attempts are insufficient among fellows to achieve competency in US-guided LP IS identification.

Intravenous Fluid Bolus Prior to Neonatal and Infant Lumbar Puncture: A Sonographic Assessment of the Subarachnoid Space After Intravenous Fluid Administration.

IMPORTANCE: Neonatal and infant lumbar puncture is a commonly performed procedure in emergency departments, yet traumatic and unsuccessful lumbar punctures occur 30% to 50% of the time. Dehydration may be a risk factor for unsuccessful lumbar punctures, but to our knowledge, no studies have investigated the use of intravenous (IV) fluid bolus prior to lumbar puncture. OBJECTIVE: To investigate the association of IV fluid bolus administration with the sonographic measure of the neonatal and infant lumbar subarachnoid space. We hypothesized that IV fluids would increase subarachnoid space size. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study conducted from August 2012 to April 2015.The study took place at the emergency department of the Children's Hospital Los Angeles, an urban pediatric emergency department with an annual census of 76,000 visits.A convenience sample of patients aged 0 to 3 months were enrolled if they had a clinical presentation consistent with pyloric stenosis. This population was used as a proxy because they are similar in age to patients undergoing lumbar puncture for evaluation of neonatal fever and are routinely given IV fluids for dehydration. EXPOSURES: Patients with a sonographic diagnosis of pyloric stenosis underwent additional ultrasonography evaluation to determine the size of the subarachnoid space before and after IV fluids. MAIN OUTCOMES AND MEASURES: Primary outcomes included the difference in the size of the subarachnoid space in millimeters squared before and 1 hour after administration of an IV fluid bolus in the emergency department. Interobserver consistency for the subarachnoid space measurement between attending radiologists was measured using intraclass correlation coefficient. The Wilcoxon signed-rank test was used to examine changes in subarachnoid space measurements (millimeters squared). RESULTS: The study sample consisted of 40 patients with a mean (SD) age of 37 (11.3) days (range, 15-71 days). The mean (SD) size of the subarachnoid space before and 1 hour after IV fluid bolus was 37.8 (11.1) mm(2) and 36.9 (11.2) mm(2) respectively (P = .42). The intraclass correlation coefficient ranged from 0.96 to 0.99 (95% CI, 0.90-0.99). CONCLUSIONS AND RELEVANCE: Intravenous fluid boluses were not associated with a significant increase in the sonographic measure of the neonatal and infant subarachnoid space.

A novel syndrome caused by the E410K amino acid substitution in the neuronal ß-tubulin isotype 3.

Missense mutations in TUBB3, the gene that encodes the neuronal-specific protein ß-tubulin isotype 3, can cause isolated or syndromic congenital fibrosis of the extraocular muscles, a form of complex congenital strabismus characterized by cranial nerve misguidance. One of the eight TUBB3 mutations reported to cause congenital fibrosis of the extraocular muscles, c.1228G>A results in a TUBB3 E410K amino acid substitution that directly alters a kinesin motor protein binding site. We report the detailed phenotypes of eight unrelated individuals who harbour this de novo mutation, and thus define the 'TUBB3 E410K syndrome'. Individuals harbouring this mutation were previously reported to have congenital fibrosis of the extraocular muscles, facial weakness, developmental delay and possible peripheral neuropathy. We now confirm by electrophysiology that a progressive sensorimotor polyneuropathy does indeed segregate with the mutation, and expand the TUBB3 E410K phenotype to include Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), stereotyped midface hypoplasia, intellectual disabilities and, in some cases, vocal cord paralysis, tracheomalacia and cyclic vomiting. Neuroimaging reveals a thin corpus callosum and anterior commissure, and hypoplastic to absent olfactory sulci, olfactory bulbs and oculomotor and facial nerves, which support underlying abnormalities in axon guidance and maintenance. Thus, the E410K substitution defines a new genetic aetiology for Moebius syndrome, Kallmann syndrome and cyclic vomiting. Moreover, the c.1228G>A mutation was absent in DNA from ∼600 individuals who had either Kallmann syndrome or isolated or syndromic ocular and/or facial dysmotility disorders, but who did not have the combined features of the TUBB3 E410K syndrome, highlighting the specificity of this phenotype-genotype correlation. The definition of the TUBB3 E410K syndrome will allow clinicians to identify affected individuals and predict the mutation based on clinical features alone.

An improved approach to diagnosing and treating conjunctival mucoepidermoid carcinoma.

The current case of conjunctival mucoepidermoid carcinoma offers features that expand the biologic spectrum afforded by this tumor. More focused strategies should be developed for its earlier histopathologic diagnosis and improved management (historical recurrence rate of 85%). A 63-year-old woman with a history of rheumatoid arthritis and idiopathic sclerosing cholangitis developed scleral thinning, anterior chamber cells and flare, and uveal prolapse. Biopsies of the epibulbar lesion were initially misinterpreted as a squamous cell carcinoma but on review harbored CK7-positive cells and contained rare goblet cells brought out with Alcian blue and mucicarmine staining. Intraocular extension exhibited micro-and macrocysts with minimal goblet cells. Focal CK7 immunopositivity in any epibulbar squamous dysplasia or in invasive carcinoma should lead to suspicion of a mucoepidermoid carcinoma. Behaviorally aggressive or rapidly recurrent epithelial squamous tumors with "inflammatory" features or unusual clinical characteristics should be initially stained at multiple levels for the detection of parsimonious mucus secretion. Surgical options include wide excision and partial sclerectomy with cryotherapy for superficial invasion and/or interferon therapy. Results with radiotherapy and cryotherapy for deep scleral invasion have been unpredictable or unacceptable compared with surgery.

HOXA1 mutations are not a common cause of Möbius syndrome.

The HOXA1-related syndromes result from autosomal-recessive truncating mutations in the homeobox transcription factor, HOXA1. Limited horizontal gaze and sensorineural deafness are the most common features; affected individuals can also have facial weakness, mental retardation, autism, motor disabilities, central hypoventilation, carotid artery, and/or conotruncal heart defects. Möbius syndrome is also phenotypically heterogeneous, with minimal diagnostic criteria of nonprogressive facial weakness and impaired ocular abduction; mental retardation, autism, motor disabilities, additional eye movements restrictions, hearing loss, hypoventilation, and craniofacial, lingual, and limb abnormalities also occur. We asked, given the phenotypic overlap between these syndromes and the variable expressivity of both disorders, whether individuals with Möbius syndrome might harbor mutations in HOXA1. Our results suggest that HOXA1 mutations are not a common cause of sporadic Möbius syndrome in the general population.

Brc1-mediated DNA repair and damage tolerance.

The structural maintenance of chromosome (SMC) proteins are key elements in controlling chromosome dynamics. In eukaryotic cells, three essential SMC complexes have been defined: cohesin, condensin, and the Smc5/6 complex. The latter is essential for DNA damage responses; in its absence both repair and checkpoint responses fail. In fission yeast, the UV-C and ionizing radiation (IR) sensitivity of a specific hypomorphic allele encoding the Smc6 subunit, rad18-74 (renamed smc6-74), is suppressed by mild overexpression of a six-BRCT-domain protein, Brc1. Deletion of brc1 does not result in a hypersensitivity to UV-C or IR, and thus the function of Brc1 relative to the Smc5/6 complex has remained unclear. Here we show that brc1Delta cells are hypersensitive to a range of radiomimetic drugs that share the feature of creating lesions that are an impediment to the completion of DNA replication. Through a genetic analysis of brc1Delta epistasis and by defining genes required for Brc1 to suppress smc6-74, we find that Brc1 functions to promote recombination through a novel postreplication repair pathway and the structure-specific nucleases Slx1 and Mus81. Activation of this pathway through overproduction of Brc1 bypasses a repair defect in smc6-74, reestablishing resolution of lesions by recombination.