The Preschool Confusion Assessment Method for the ICU: Valid and Reliable Delirium Monitoring for Critically Ill Infants and Children.

OBJECTIVES: Delirium assessments in critically ill infants and young children pose unique challenges due to evolution of cognitive and language skills. The objectives of this study were to determine the validity and reliability of a fundamentally objective and developmentally appropriate delirium assessment tool for critically ill infants and preschool-aged children and to determine delirium prevalence. DESIGN AND SETTING: Prospective, observational cohort validation study of the PreSchool Confusion Assessment Method for the ICU in a tertiary medical center PICU. PATIENTS: Participants aged 6 months to 5 years and admitted to the PICU regardless of admission diagnosis were enrolled. MEASUREMENTS AND MAIN RESULTS: An interdisciplinary team created the PreSchool Confusion Assessment Method for the ICU for pediatric delirium monitoring. To assess validity, patients were independently assessed for delirium daily by the research team using the PreSchool Confusion Assessment Method for the ICU and by a child psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders criteria. Reliability was assessed using blinded, concurrent PreSchool Confusion Assessment Method for the ICU evaluations by research staff. A total of 530-paired delirium assessments were completed among 300 patients, with a median age of 20 months (interquartile range, 11-37) and 43% requiring mechanical ventilation. The PreSchool Confusion Assessment Method for the ICU demonstrated a specificity of 91% (95% CI, 90-93), sensitivity of 75% (95% CI, 72-78), negative predictive value of 86% (95% CI, 84-88), positive predictive value of 84% (95% CI, 81-87), and a reliability κ-statistic of 0.79 (0.76-0.83). Delirium prevalence was 44% using the PreSchool Confusion Assessment Method for the ICU and 47% by the reference rater. The rates of delirium were 53% versus 56% in patients younger than 2 years old and 33% versus 35% in patients 2-5 years old using the PreSchool Confusion Assessment Method for the ICU and reference rater, respectively. The short-form PreSchool Confusion Assessment Method for the ICU maintained a high specificity (87%) and sensitivity (78%) in post hoc analysis. CONCLUSIONS: The PreSchool Confusion Assessment Method for the ICU is a highly valid and reliable delirium instrument for critically ill infants and preschool-aged children, in whom delirium is extremely prevalent.

Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood.

IMPORTANCE: Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand. OBJECTIVE: To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. DESIGN, SETTING, AND PARTICIPANTS: Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data. EXPOSURES: A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior. RESULTS: Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = -0.2 (95% CI, -2.6 to 2.9); performance = 0.5 (95% CI, -2.7 to 3.7); and verbal = -0.5 (95% CI, -3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior. CONCLUSIONS AND RELEVANCE: Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.

Objective sinonasal functional outcomes in endoscopic anterior skull-base surgery: an evidence-based review with recommendations.

BACKGROUND: The use of endoscopic endonasal approaches to the anterior skull base has dramatically expanded in recent years, with clinical endpoints and complication rates that compare favorably to traditional approaches. The impact of the endoscopic approach on sinonasal function has been less rigorously evaluated. The purpose of this study was to systematically analyze the literature evaluating objective sinonasal outcomes in endoscopic anterior skull-base surgery, and provide evidence-based recommendations. METHODS: A systematic review of the literature was performed based on a published guideline for developing an evidence-based review with recommendations. Objective sinonasal outcomes included were olfaction, mucociliary clearance, and nasal airflow. RESULTS: Ten articles were identified addressing objective olfactory outcomes: 2 randomized controlled trials; 6 cohort studies; and 2 retrospective case series. One cohort study investigating mucociliary clearance was identified. Six studies reporting postoperative endoscopic outcomes were identified. CONCLUSION: Based on the available evidence, nasoseptal flap (NSF) elevation with or without use in reconstruction likely leads to impairment in objective olfactory function. Endoscopic sellar and parasellar surgery without the elevation of an NSF may lead to a transient reduction in olfactory function. In the absence of a high a priori risk of cerebrospinal fluid (CSF) leak, it is an option to avoid routine NSF elevation in sellar and parasellar procedures, with preservation of at least 1 vascular pedicle during the approach. Monopolar electrocautery for mucosal incisions may increase the risk of olfactory impairment. If an NSF is used, donor site defect reconstruction may be considered.

The subcellular distribution of calnexin is mediated by PACS-2.

Calnexin is an endoplasmic reticulum (ER) lectin that mediates protein folding on the rough ER. Calnexin also interacts with ER calcium pumps that localize to the mitochondria-associated membrane (MAM). Depending on ER homeostasis, varying amounts of calnexin target to the plasma membrane. However, no regulated sorting mechanism is so far known for calnexin. Our results now describe how the interaction of calnexin with the cytosolic sorting protein PACS-2 distributes calnexin between the rough ER, the MAM, and the plasma membrane. Under control conditions, more than 80% of calnexin localizes to the ER, with the majority on the MAM. PACS-2 knockdown disrupts the calnexin distribution within the ER and increases its levels on the cell surface. Phosphorylation by protein kinase CK2 of two calnexin cytosolic serines (Ser554/564) reduces calnexin binding to PACS-2. Consistent with this, a Ser554/564 Asp phosphomimic mutation partially reproduces PACS-2 knockdown by increasing the calnexin signal on the cell surface and reducing it on the MAM. PACS-2 knockdown does not reduce retention of other ER markers. Therefore, our results suggest that the phosphorylation state of the calnexin cytosolic domain and its interaction with PACS-2 sort this chaperone between domains of the ER and the plasma membrane.