Adverse Tracheal Intubation Events in Critically Ill Underweight and Obese Children: Retrospective Study of the National Emergency Airway for Children Registry (2013-2020).

OBJECTIVES: Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being underweight or obese with adverse airway outcomes, including adverse tracheal intubation (TI)-associated events (TIAEs) and/or severe peri-intubation hypoxemia (pulse oximetry oxygen saturation < 80%) in critically ill children. DESIGN/SETTING: Retrospective cohort using the National Emergency Airway for Children registry dataset of 2013-2020. PATIENTS: Critically ill children, 0 to 17 years old, undergoing TI in PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Registry data from 24,342 patients who underwent TI between 2013 and 2020 were analyzed. Patients were categorized using the Centers for Disease Control and Prevention weight-for-age chart: normal weight (5th-84th percentile) 57.1%, underweight (< 5th percentile) 27.5%, overweight (85th to < 95th percentile) 7.2%, and obese (≥ 95th percentile) 8.2%. Underweight was most common in infants (34%); obesity was most common in children older than 8 years old (15.1%). Underweight patients more often had oxygenation and ventilation failure (34.0%, 36.2%, respectively) as the indication for TI and a history of difficult airway (16.7%). Apneic oxygenation was used more often in overweight and obese patients (19.1%, 19.6%) than in underweight or normal weight patients (14.1%, 17.1%; p < 0.001). TIAEs and/or hypoxemia occurred more often in underweight (27.1%) and obese (24.3%) patients ( p < 0.001). TI in underweight children was associated with greater odds of adverse airway outcome compared with normal weight children after adjusting for potential confounders (underweight: adjusted odds ratio [aOR], 1.09; 95% CI, 1.01-1.18; p = 0.016). Both underweight and obesity were associated with hypoxemia after adjusting for covariates and site clustering (underweight: aOR, 1.11; 95% CI, 1.02-1.21; p = 0.01 and obesity: aOR, 1.22; 95% CI, 1.07-1.39; p = 0.002). CONCLUSIONS: In underweight and obese children compared with normal weight children, procedures around the timing of TI are associated with greater odds of adverse airway events.

An inactivated multivalent influenza A virus vaccine is broadly protective in mice and ferrets.

Influenza A viruses (IAVs) present major public health threats from annual seasonal epidemics and pandemics and from viruses adapted to a variety of animals including poultry, pigs, and horses. Vaccines that broadly protect against all such IAVs, so-called "universal" influenza vaccines, do not currently exist but are urgently needed. Here, we demonstrated that an inactivated, multivalent whole-virus vaccine, delivered intramuscularly or intranasally, was broadly protective against challenges with multiple IAV hemagglutinin and neuraminidase subtypes in both mice and ferrets. The vaccine is composed of four ß-propiolactone-inactivated low-pathogenicity avian IAV subtypes of H1N9, H3N8, H5N1, and H7N3. Vaccinated mice and ferrets demonstrated substantial protection against a variety of IAVs, including the 1918 H1N1 strain, the highly pathogenic avian H5N8 strain, and H7N9. We also observed protection against challenge with antigenically variable and heterosubtypic avian, swine, and human viruses. Compared to control animals, vaccinated mice and ferrets demonstrated marked reductions in viral titers, lung pathology, and host inflammatory responses. This vaccine approach indicates the feasibility of eliciting broad, heterosubtypic IAV protection and identifies a promising candidate for influenza vaccine clinical development.

Pre-existing immunity to influenza virus hemagglutinin stalk might drive selection for antibody-escape mutant viruses in a human challenge model.

The conserved region of influenza hemagglutinin (HA) stalk (or stem) has gained attention as a potent target for universal influenza vaccines1-5. Although the HA stalk region is relatively well conserved, the evolutionarily dynamic nature of influenza viruses6 raises concerns about the possible emergence of viruses carrying stalk escape mutation(s) under sufficient immune pressure. Here we show that immune pressure on the HA stalk can lead to expansion of escape mutant viruses in study participants challenged with a 2009 H1N1 pandemic influenza virus inoculum containing an A388V polymorphism in the HA stalk (45% wild type and 55% mutant). High level of stalk antibody titers was associated with the selection of the mutant virus both in humans and in vitro. Although the mutant virus showed slightly decreased replication in mice, it was not observed in cell culture, ferrets or human challenge participants. The A388V mutation conferred resistance to some of the potent HA stalk broadly neutralizing monoclonal antibodies (bNAbs). Co-culture of wild-type and mutant viruses in the presence of either a bNAb or human serum resulted in rapid expansion of the mutant. These data shed light on a potential obstacle for the success of HA-stalk-targeting universal influenza vaccines-viral escape from vaccine-induced stalk immunity.

Automated Pupillary Measurements Inversely Correlate With Increased Intracranial Pressure in Pediatric Patients With Acute Brain Injury or Encephalopathy.

OBJECTIVES: The purpose of this study was to determine correlation and temporal association between automated pupillary measurements and intracranial pressure in pediatric patients with brain injury or encephalopathy requiring intracranial pressure monitoring. We hypothesized that abnormal pupillary measurements would precede increases in intracranial pressure. DESIGN: A prospective cohort study was performed. Automated pupillometry measurements were obtained at the same frequency as the patients' neurologic assessments with concurrent measurement of intracranial pressure, for up to 72 hours. Pupillary measurements and the Neurologic Pupil index, an algorithmic score that combines measures of pupillary reactivity, were assessed for correlation with concurrent and future intracranial pressure measurements. SETTING: Single-center pediatric quaternary ICU, from July 2017 to October 2018. PATIENTS: Pediatric patients 18 years or younger with a diagnosis of acute brain injury or encephalopathy requiring an intracranial pressure monitor. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-eight patients were analyzed with a total of 1,171 intracranial pressure measurements. When intracranial pressure was elevated, the Neurologic Pupil index, percent change in pupillary size, constriction velocity, and dilation velocity were significantly lower than when intracranial pressure was within normal range (p < 0.001 for all). There were mild to moderate negative correlations between concurrent intracranial pressure and pupillary measurements. However, there was an inconsistent pattern of abnormal pupillary measurements preceding increases in intracranial pressure; some patients had a negative association, while others had a positive relationship or no relationship between Neurologic Pupil index and intracranial pressure. CONCLUSIONS: Our data indicate automated assessments of pupillary reactivity inversely correlate with intracranial pressure, demonstrating that pupillary reactivity decreases as intracranial pressure increases. However, a temporal association in which abnormal pupillary measurements precede increases in intracranial pressure was not consistently observed. This work contributes to limited data available regarding automated pupillometry in neurocritically ill patients, and the even more restricted subset available in pediatrics.

Does hypertension at initial presentation adversely affect outcomes in pediatric traumatic brain injury?

BACKGROUND: Adults with traumatic brain injury (TBI) who present hypertensive suffer worse outcomes and increased mortality compared to normotensive patients. The purpose of this study is to determine if age-adjusted hypertension on presentation is associated with worsened outcomes in pediatric TBI. METHODS: A retrospective chart review was conducted on pediatric patients with severe TBI admitted to a single system pediatric tertiary care center. The primary outcome was mortality. Secondary outcomes included length of stay, need for neurosurgical intervention, duration of mechanical ventilation, and the need for inpatient rehabilitation. RESULTS: Of 150 patients, 70% were hypertensive and 30% were normotensive on presentation. Comparing both groups, no statistically significant differences were noted in mortality (13.3% for both groups), need for neurosurgical intervention (51.4% vs 48.8%, p = 0.776), length of stay (6 vs 8 days, p = 0.732), duration of mechanical ventilation (2 vs 3 days, p = 0.912), or inpatient rehabilitation rates (48.6% vs 48.9%, p = 0.972). In comparing just the hypertensive patients, there was a trend toward increased mortality in the 95th and 99th percentile groups at 15.8% and 14.1%, versus the 90th percentile group at 6.7% but the difference was not statistically significant (p = 0.701). CONCLUSIONS: Contrary to the adult literature, pediatric patients with severe TBI and hypertension on presentation do not appear to have worsened outcomes compared to those who are normotensive. However, a trend toward increased mortality did exist at extremes of age adjusted hypertension. Larger scale studies are needed to validate these findings. STUDY TYPE: Retrospective cohort study LEVEL OF EVIDENCE: III.

The middle layer of lumbar fascia can transmit tensile forces capable of fracturing the lumbar transverse processes: an experimental study.

BACKGROUND: Transversus abdominis and its aponeurotic attachment to the lumbar transverse processes via the middle layer of lumbar fascia are of proposed clinical and biomechanical importance. Moderate traction on these structures (simulating submaximal contraction of transversus abdominis) is reported to influence segmental motion, but their tensile capacity is unknown and the effects of sudden, maximal traction on these attachments and the transverse processes are uncertain. METHODS: In 15 embalmed cadaver abdomens, the middle layer of lumbar fascia was isolated, gripped and rapid tension applied in either a lateral or posteroanterior direction (simulating forces that may produce avulsion and traumatic fractures). Peak forces prior to tissue failure were recorded and the gross effects of traction documented. FINDINGS: Lumbar transverse process fractures were produced in all specimens; by transverse traction in 50% of tests and posteroanterior force in 80%. In the remainder the middle layer of lumbar fascia was torn. Mean transverse and posteroanterior peak forces reached in the middle layer of lumbar fascia prior to failure were 82 N (range 20-190 N) and 47 N (range 25-70 N), respectively. INTERPRETATION: The middle layer of lumbar fascia can transmit substantial tensile forces to lumbar vertebrae, capable of transverse process fracture under experimental conditions. Tensile capacity is likely to be even greater in-vivo. This suggests transversus abdominis and the middle layer of lumbar fascia can strongly influence vertebral motion, should be incorporated in biomechanical models of the spine and considered as potential contributors to transverse process fractures by avulsion.