Predicting Delayed Shock in Multisystem Inflammatory Disease in Children: A Multicenter Analysis From the New York City Tri-State Region.

OBJECTIVES: Patients with multisystem inflammatory disease in children (MIS-C) are at risk of developing shock. Our objectives were to determine independent predictors associated with development of delayed shock (≥3 hours from emergency department [ED] arrival) in patients with MIS-C and to derive a model predicting those at low risk for delayed shock. METHODS: We conducted a retrospective cross-sectional study of 22 pediatric EDs in the New York City tri-state area. We included patients meeting World Health Organization criteria for MIS-C and presented April 1 to June 30, 2020. Our main outcomes were to determine the association between clinical and laboratory factors to the development of delayed shock and to derive a laboratory-based prediction model based on identified independent predictors. RESULTS: Of 248 children with MIS-C, 87 (35%) had shock and 58 (66%) had delayed shock. A C-reactive protein (CRP) level greater than 20 mg/dL (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.4-12.1), lymphocyte percent less than 11% (aOR, 3.8; 95% CI, 1.7-8.6), and platelet count less than 220,000/uL (aOR, 4.2; 95% CI, 1.8-9.8) were independently associated with delayed shock. A prediction model including a CRP level less than 6 mg/dL, lymphocyte percent more than 20%, and platelet count more than 260,000/uL, categorized patients with MIS-C at low risk of developing delayed shock (sensitivity 93% [95% CI, 66-100], specificity 38% [95% CI, 22-55]). CONCLUSIONS: Serum CRP, lymphocyte percent, and platelet count differentiated children at higher and lower risk for developing delayed shock. Use of these data can stratify the risk of progression to shock in patients with MIS-C, providing situational awareness and helping guide their level of care.

Accuracy of Point-of-care Lung Ultrasonography for Diagnosis of Acute Chest Syndrome in Pediatric Patients with Sickle Cell Disease and Fever.

OBJECTIVES: The objective was to determine the test performance characteristics for point-of-care lung ultrasonography (LUS) performed by pediatric emergency medicine (PEM) physicians compared with radiographic diagnosis of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) and fever. METHODS: This was a prospective study of patients up to 21 years with SCD and fever requiring chest X-ray (CXR) evaluation for ACS. Before obtaining CXR, a blinded PEM physician performed LUS using a standardized scanning protocol. Positive LUS for ACS was defined as lung consolidation. All patients received CXR and follow-up. The criterion standard for ACS was consolidation on CXR as determined by a blinded radiologist. LUS clips were reviewed by a blinded expert PEM sonologist. RESULTS: A total of 116 febrile events from 91 patients with a median age of 5.7 years were enrolled by 15 PEM sonologists. CXR was positive for ACS in 15 (13%) patients, and LUS was positive for ACS in 19 (16%) patients. Positive LUS had a sensitivity of 87% (95% confidence interval [CI] = 62% to 96%), specificity of 94% (95% CI = 88% to 97%), positive likelihood ratio of 14.6 (95% CI = 6.5 to 32.5), and negative likelihood ratio of 0.14 (95% CI = 0.04 to 0.52) for ACS. The interobserver agreement (kappa) was 0.77. There were two missed cases of ACS on LUS. CONCLUSIONS: LUS may be sensitive and specific for diagnosis of ACS in pediatric patients with SCD and fever. LUS may reduce the need for routine CXR and associated ionizing radiation exposure in this population.

Comparison of GlideScope Videolaryngoscopy to Direct Laryngoscopy for Intubation of a Pediatric Simulator by Novice Physicians.

Objective. To compare novice clinicians' performance using GlideScope videolaryngoscopy (GVL) to direct laryngoscopy (DL). Methods. This was a prospective, randomized crossover study. Incoming pediatric interns intubated pediatric simulators in four normal and difficult airway scenarios with GVL and DL. Primary outcomes included time to intubation and rate of successful intubation. Interns rated their satisfaction of the devices and chose the preferred device. Results. Twenty-five interns were included. In the normal airway scenario, there were no differences in mean time for intubation with GVL or DL (61.4 versus 67.4 seconds, P = NS) or number of successful intubations (19 versus 18, P = NS). In the difficult airway scenario, interns took longer to intubate with GVL than DL (87.7 versus 61.3 seconds, P = 0.018), but there were no differences in successful intubations (14 versus 15, P = NS). There was a trend towards higher satisfaction for GVL than DL (7.3 versus 6.4, P = NS), and GVL was chosen as the preferred device by a majority of interns (17/25, 68%). Conclusions. For novice clinicians, GVL does not improve time to intubation or intubation success rates in a pediatric simulator model of normal and difficult airway scenarios. Still, these novice clinicians overall preferred GVL.

Gene knockout of insulin-regulated aminopeptidase: loss of the specific binding site for angiotensin IV and age-related deficit in spatial memory.

The AT(4) ligands, angiotensin IV and LVV-hemorphin 7, elicit robust effects on facilitating memory by binding to a specific site in the brain historically termed the angiotensin AT(4) receptor. The identification of the AT(4) receptor as insulin-regulated aminopeptidase (IRAP) is controversial, with other proteins speculated to be the target(s) of these peptides. In this study we have utilized IRAP knockout mice to investigate IRAP in the brain. We demonstrate that the high-affinity binding site for angiotensin IV is absent in IRAP knockout mice brain sections in parallel with the loss of IRAP immunostaining, providing irrefutable proof that IRAP is the specific high-affinity binding site for AT(4) ligands. However, our characterization of the behavioural phenotype of the IRAP knockout mice revealed a totally unexpected finding. In contrast to the acute effects of IRAP inhibitors in enhancing memory, deletion of the IRAP gene resulted in mice with an accelerated, age-related decline in spatial memory that was only detected in the Y maze paradigm. Moreover, no alterations in behaviour of the IRAP knockout mice were observed that could assist in elucidating the endogenous substrate(s). Our results highlight the importance of analysing the behavioural phenotype of knockout mice across different ages and in distinct memory paradigms.