An Adolescent Boy With Hypoxia, Microscopic Hematuria, and Hypertension.

A 13-year-old boy presented with hypoxia, microscopic hematuria, and elevated blood pressures. Persistent microscopic hematuria and hypertension led to investigation of glomerular and non-glomerular causes of hematuria. After reviewing his clinical course, family history, and laboratory testing, an additional test was sent, revealing the diagnosis.

Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications.

OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.

Health Care Professional and Caregiver Attitudes Toward and Usage of Medical Podcasting: Questionnaire Study.

BACKGROUND: Podcasts are used increasingly in medicine. There is growing research into the role of podcasts in medical education, but the use of podcasting as a tool for pediatric parent/caregiver health education is largely unexplored. As parents/caregivers seek medical information online, an understanding of parental preferences is needed. OBJECTIVE: We sought to explore health care professional and parent/caregiver awareness and views on podcasting as a health education tool. METHODS: This survey study was conducted and distributed via in-person collection from parents/caregivers (≥18 years old) in the waiting room of an academic pediatric primary care clinic, targeted social media promotion, and professional listservs for health care professionals in pediatrics. Statistical analysis included chi-square tests of independence between categorical variables. RESULTS: In total, 125 health care professionals and 126 caregivers completed the survey. Of those surveyed, 81% (101/125) of health care professionals and 55% (69/126) of parents/caregivers listened to podcasts (P<.001). Health care professionals and parents/caregivers listed the same top 3 quality indicators for medical podcasts. Podcast listeners were more likely to have higher incomes and use professional websites for information. The survey elicited a variety of reasons for podcast nonengagement. CONCLUSIONS: Health care professionals appear to be more engaged in medical education podcasts than parents/caregivers. However, similar factors were valued when evaluating the quality of a pediatric podcast: accuracy, transparency, and credibility. Professional websites may be one avenue to increase podcast uptake. More needs to be done to explore the use of podcasts and digital media for medical information.

Meta-analysis: Pharmacologic Treatment of Restricted and Repetitive Behaviors in Autism Spectrum Disorders.

OBJECTIVE: To examine the efficacy of pharmacological treatments for restricted and repetitive behaviors (RRB) in autism spectrum disorders (ASD). METHOD: We searched PubMed, Embase, and CENTRAL to identify all double-blind, randomized, placebo-controlled trials that examined the efficacy of pharmacological agents in the treatment of ASD and measured RRB as an outcome. Our primary outcome was the standardized mean difference in rating scales of RRB. RESULTS: We identified 64 randomized, placebo-controlled trials involving 3,499 participants with ASD. Antipsychotics significantly improved RRB outcomes compared to placebo (standardized mean difference [SMD] = 0.28, 95% CIs = 0.08-0.49), z = 2.77, p = .01) demonstrating a small effect size. Larger significant positive effects on RRB in ASD were seen in individual studies with fluvoxamine, buspirone, bumetanide, divalproex, guanfacine, and folinic acid that have not been replicated. Other frequently studied pharmacological treatments in ASD including oxytocin, omega-3 fatty acids, selective serotonin reuptake inhibitors (SSRI), and methylphenidate did not demonstrate significant benefit in reducing RRB compared to placebo (oxytocin: SMD = 0.23, 95% CI = -0.01 to 0.47, z = 1.85, p = .06; omega-3 fatty acids: SMD = 0.19, 95% CI = -0.05 to 0.43, z = 1.54, p = .12; SSRI: SMD = 0.09, 95% CI = -0.21 to 0.39, z = 0.60, p = .56; methylphenidate: SMD = 0.18, 95% CI = -0.11 to 0.46, z = 1.23, p = .22). CONCLUSION: The results of the present meta-analysis suggest that currently available pharmacological agents have at best only a modest benefit for the treatment of RRB in ASD, with the most evidence supporting antipsychotic medications. Additional randomized controlled trials with standardized study designs and consistent and specific assessment tools for RRB are needed to further understand how we can best help ameliorate these behaviors in individuals with ASD.

A meta-analysis on the relationship between interoceptive awareness and alexithymia: Distinguishing interoceptive accuracy and sensibility.

Alexithymia-a trait associated with difficulties understanding one's own emotions-is theorized to stem from deficits in interoceptive awareness, or the ability to detect, accurately monitor, and regulate internal bodily processes. The present meta-analysis analyzed all studies that empirically examined the relationship between alexithymia and interoceptive awareness. Across 66 independent samples (N = 7,146), alexithymia had a small, negative correlation with interoceptive awareness (r = -.162, p = .001, 95% CI [-.252, -.068]), but additional analyses revealed that the strength and directionality of this association was heavily influenced by the specific interoceptive awareness components measured (e.g., interoceptive accuracy vs. sensibility) and the methods used to measure interoceptive awareness (e.g., objective vs. self-report measures). The strength of this relationship was also moderated by diagnosis of participants such that alexithymia was moderately associated with interoceptive awareness in samples with psychiatric and developmental disorders, but the relationship was nonsignificant in healthy, typically developing samples. Results suggest interoception may represent a shared transdiagnostic vulnerability that underlies atypical emotional processing in a variety of disparate clinical populations but that current operationalization and measurement of interoceptive awareness continues to create confusion and inconsistency in the literature. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice.

Progranulin (GRN) and TMEM106B are associated with several common neurodegenerative disorders including frontotemporal lobar degeneration (FTLD). A TMEM106B variant modifies GRN-associated FTLD risk. However, their functional relationship in vivo and the mechanisms underlying the risk modification remain unclear. Here, using transcriptomic and proteomic analyses with Grn-/- and Tmem106b-/- mice, we show that, while multiple lysosomal enzymes are increased in Grn-/- brain at both transcriptional and protein levels, TMEM106B deficiency causes reduction in several lysosomal enzymes. Remarkably, Tmem106b deletion from Grn-/- mice normalizes lysosomal protein levels and rescues FTLD-related behavioral abnormalities and retinal degeneration without improving lipofuscin, C1q, and microglial accumulation. Mechanistically, TMEM106B binds vacuolar-ATPase accessory protein 1 (AP1). TMEM106B deficiency reduces vacuolar-ATPase AP1 and V0 subunits, impairing lysosomal acidification and normalizing lysosomal protein levels in Grn-/- neurons. Thus, Grn and Tmem106b genes have opposite effects on lysosomal enzyme levels, and their interaction determines the extent of neurodegeneration.

Functional recovery in new mouse models of ALS/FTLD after clearance of pathological cytoplasmic TDP-43.

Accumulation of phosphorylated cytoplasmic TDP-43 inclusions accompanied by loss of normal nuclear TDP-43 in neurons and glia of the brain and spinal cord are the molecular hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). However, the role of cytoplasmic TDP-43 in the pathogenesis of these neurodegenerative TDP-43 proteinopathies remains unclear, due in part to a lack of valid mouse models. We therefore generated new mice with doxycycline (Dox)-suppressible expression of human TDP-43 (hTDP-43) harboring a defective nuclear localization signal (∆NLS) under the control of the neurofilament heavy chain promoter. Expression of hTDP-43∆NLS in these 'regulatable NLS' (rNLS) mice resulted in the accumulation of insoluble, phosphorylated cytoplasmic TDP-43 in brain and spinal cord, loss of endogenous nuclear mouse TDP-43 (mTDP-43), brain atrophy, muscle denervation, dramatic motor neuron loss, and progressive motor impairments leading to death. Notably, suppression of hTDP-43∆NLS expression by return of Dox to rNLS mice after disease onset caused a dramatic decrease in phosphorylated TDP-43 pathology, an increase in nuclear mTDP-43 to control levels, and the prevention of further motor neuron loss. rNLS mice back on Dox also showed a significant increase in muscle innervation, a rescue of motor impairments, and a dramatic extension of lifespan. Thus, the rNLS mice are new TDP-43 mouse models that delineate the timeline of pathology development, muscle denervation and neuron loss in ALS/FTLD-TDP. Importantly, even after neurodegeneration and onset of motor dysfunction, removal of cytoplasmic TDP-43 and the concomitant return of nuclear TDP-43 led to neuron preservation, muscle re-innervation and functional recovery.