Immunocompromised Children With Acute Respiratory Distress Syndrome Possess a Distinct Circulating Inflammatory Profile.

Immunocompromised status, with and without stem cell transplant, confers a worse prognosis in pediatric acute respiratory distress syndrome. An improved understanding of the biochemical profile of immunocompromised children with acute respiratory distress syndrome would inform whether specific pathways are targetable, or merely bystanders, in order to improve outcomes in this high-risk subgroup. OBJECTIVES: We aimed to identify a biomarker profile of immunocompromised children, with and without stem cell transplant, independent of illness severity. DESIGN SETTINGS AND PARTICIPANTS: This was a secondary analysis of a prospective cohort study of intubated children with Berlin-defined acute respiratory distress syndrome with existing biomarker measurements conducted in a large academic PICU between 2014 and 2019. MAIN OUTCOMES AND MEASURES: Biomarker levels were compared between immunocompetent and immunocompromised children, with and without stem cell transplant, both prior to and after adjusting for severity of illness. RESULTS: In 333 children with acute respiratory distress syndrome, 84 were immunocompromised, of whom 39 had a stem cell transplant. Circulating neutrophil levels were strongly correlated with biomarkers, with 14 of 18 measured proteins differentially expressed in patients with versus without neutropenia. In order to identify biomarker levels independent of severity of illness, acute respiratory distress syndrome etiology, and neutrophil levels, we computed predicted (log-transformed) biomarker levels after adjusting for confounders using linear regression and then compared these severity-adjusted levels between immunocompetent and immunocompromised (with and without stem cell transplant) subjects using analyses of variance and post hoc Bonferroni. After multivariable adjustment, 11 biomarkers were higher in immunocompromised subjects without stem cell transplant, relative to immunocompetent, implicating endotheliopathy (angiopoietin-2), tissue damage (procollagen type III N-terminal peptide), and innate immunity. A single biomarker, C-C motif chemokine ligand 22, was lower in immunocompromised subjects with and without stem cell transplant. CONCLUSIONS AND RELEVANCE: Immunocompromised children with acute respiratory distress syndrome were characterized by elevations in pro-inflammatory and endothelial damage biomarkers. Our study provides insight into mechanisms underlying the molecular heterogeneity of this population and potentially identifies targetable pathways to mitigate their increased mortality risk.

Excessive Oxygen Supplementation in the First Day of Mechanical Ventilation Is Associated With Multiple Organ Dysfunction and Death in Critically Ill Children.

OBJECTIVES: To determine if greater cumulative exposure to oxygen despite adequate oxygenation over the first 24 hours of mechanical ventilation is associated with multiple organ dysfunction syndrome at 7 days and inhospital mortality in critically ill children. DESIGN: Retrospective, observational cohort study. SETTING: Two urban, academic PICUs. PATIENTS: Patients less than 18 years old who required mechanical ventilation within 3 days of admission between 2010 and 2018 (Lurie Children's Hospital) or 2010 and 2016 (Comer Children's Hospital). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 5,406 mechanically ventilated patients, of which 960 (17.8%) had multiple organ dysfunction syndrome on day 7 of admission and 319 died (5.9%) during their hospitalization. Cumulative exposure to greater amounts of supplemental oxygen, while peripheral oxygen saturation was 95% or more during the first 24 hours of mechanical ventilation was independently associated with an increased risk of both multiple organ dysfunction syndrome on day 7 and inhospital mortality after adjusting for confounders. Patients in the highest quartile of cumulative oxygen exposure had an increased odds of multiple organ dysfunction syndrome on day 7 (adjusted odds ratio, 3.9; 95% CI, 2.7-5.9) and inhospital mortality (adjusted odds ratio, 1.7; 95% CI, 1.1-2.9), when compared with those in the lowest quartile of cumulative oxygen exposure after adjusting for age, presence of multiple organ dysfunction syndrome on day 1 of mechanical ventilation, immunocompromised state, and study site. CONCLUSIONS: Greater cumulative exposure to excess supplemental oxygen in the first 24 hours of mechanical ventilation is independently associated with an increased risk of multiple organ dysfunction syndrome on day 7 of admission and inhospital mortality in critically ill children.

Distinct neurotoxic effects of select local anesthetics on facial nerve injury and recovery.

BACKGROUND: Local anesthetic toxicity has been well-documented to cause neuronal injury, death, and dysfunction, particularly in a susceptible nerve. OBJECTIVE: To determine whether select local anesthetics affect neuron survival and/or functional recovery of an injured nerve. METHODS: This report describes 6 separate experiments that test immediate or delayed application of local anesthetics in 3 nerve injury models. Adult C57/black6 male mice underwent a facial nerve sham, transection, or crush injury. Local anesthetic or saline was applied to the facial nerve at the time of injury (immediate) or 1 day after injury (delayed). Average percent facial motoneuron (FMN) survival was evaluated four-weeks after injury. Facial nerve regeneration was estimated by observing functional recovery of eye blink reflex and vibrissae movement after facial nerve crush injury. RESULTS: FMN survival after: transection + immediate treatment with ropivacaine (54.8%), bupivacaine (63.2%), or tetracaine (66.9%) was lower than saline (85.5%) and liposomal bupivacaine (85.0%); crush + immediate treatment with bupivacaine (92.8%) was lower than saline (100.7%) and liposomal bupivacaine (99.3%); sham + delayed treatment with bupivacaine (89.9%) was lower than saline (96.6%) and lidocaine (99.5%); transection + delayed treatment with bupivacaine (67.3%) was lower than saline (78.4%) and liposomal bupivacaine (77.6%); crush + delayed treatment with bupivacaine (85.3%) was lower than saline (97.9%) and lidocaine (96.0%). The average post-operative time for mice to fully recover after: crush + immediate treatment with bupivacaine (12.83 days) was longer than saline (11.08 days) and lidocaine (10.92 days); crush + delayed treatment with bupivacaine (16.79 days) was longer than saline (12.73 days) and lidocaine (11.14 days). CONCLUSIONS: Our data demonstrate that some local anesthetics, but not all, exacerbate motoneuron death and delay functional recovery after a peripheral nerve injury. These and future results may lead to clinical strategies that decrease the risk of neural deficit following peripheral nerve blocks with local anesthetics.

Vocal Fold Paralysis after Esophagectomy for Carcinoma.

OBJECTIVES: (1) To recognize factors that contribute to vocal fold paralysis (VFP) after esophagectomy. (2) To describe the morbidity associated with VFP after esophagectomy. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care academic medical center. SUBJECTS AND METHODS: The medical records of 91 patients undergoing esophagectomy for malignancy were reviewed (2008-2014). Twenty-two patients with postoperative VFP were compared with 69 patients without VFP with regard to preoperative variables, surgical approach (transcervical vs other), and postoperative outcomes. A subset analysis of cervical approaches was performed, including those where an otolaryngologist assisted. RESULTS: There were no significant differences in preoperative variables between patients with and without VFP. Cervical approaches were associated with increased VFP (P < .0001). Recurrent laryngeal nerve (RLN) identification was associated with increased VFP (P = .0001). RLN dissection by head and neck surgeons was associated with decreased VFP (P = .0223). Patients with VFP had longer lengths of stay (P = .0078), higher rates of tracheotomy (P = .0439), and required more outpatient swallow evaluations (P = .0017). Mean time to diagnosis of VFP was 45.6 days (median, 7.5 days). CONCLUSIONS: Cervical approaches are associated with increased VFP in patients undergoing esophagectomy for malignancy. When cervical approaches and mobilization are required, the inclusion of an experienced cervical surgeon to identify the RLN may improve the rate of postoperative VFP. Patients with VFP after esophagectomy experience significantly more morbidity. Due to the potential delay in diagnosis and treatment of postoperative VFP, routine assessment of inpatient vocal fold function may be beneficial.