Variability of oxygen requirements in critically ill COVID-19 patients.

Background: The global scarcity of medical oxygen has proven to be catastrophic during the surges in COVID-19 cases over the past two years, with the heaviest burden felt in low- and middle-income countries. Despite its criticality, data and analyses of oxygen consumption, even for typical clinical cases, are missing. Consequently, planning oxygen needs, particularly with variable surges in COVID-19 cases, has presented a substantial challenge to policymakers and hospital decision-makers. Methods: We performed a sub-analysis of the COVID-19 Critical Care Consortium database assessing the oxygen consumption requirements of COVID-19 patients admitted to intensive care units between February 2020 and October 2021. We calculated descriptive statistics for oxygen flow-rates, stratified by oxygen supplementation method, and developed a multi-state model for estimating the frequency, therapy duration, probability of transition, and number of oxygen therapy modes per patient. Results: Overall, 12 429 patients from 35 countries received oxygen support on at least one day of their hospitalisation. Of the patients with measurable flow rates, 6142 received invasive mechanical ventilation, 838 received high-flow nasal oxygen, and 257 received both modalities. The median flow rate for mechanical ventilation was 3.2 L per minute (interquartile range (IQR) = 2.0-4.9), with a median duration of 12 days (IQR = 6-24), while the median flow rate for high-flow nasal cannula was 40 L per minute (IQR = 15-55), with a median duration of three days (IQR = 2-6). Conclusions: Oxygen consumption among critical COVID-19 patients varies by mode of delivery (invasive ventilation vs high-flow nasal cannula), across patients, and over treatment duration. Therefore, it is essential that health facilities routinely monitor oxygen utilization to better inform oxygen delivery system design and regular supply planning. Registration: ClinicalTrials.gov: CTG2021-01 ACTRN12620000421932.

Advances in Neuroimaging and Monitoring to Defend Cerebral Perfusion in Noncardiac Surgery.

Noncardiac surgery conveys a substantial risk of secondary organ dysfunction and injury. Neurocognitive dysfunction and covert stroke are emerging as major forms of perioperative organ dysfunction, but a better understanding of perioperative neurobiology is required to identify effective treatment strategies. The likelihood and severity of perioperative brain injury may be increased by intraoperative hemodynamic dysfunction, tissue hypoperfusion, and a failure to recognize complications early in their development. Advances in neuroimaging and monitoring techniques, including optical, sonographic, and magnetic resonance, have progressed beyond structural imaging and now enable noninvasive assessment of cerebral perfusion, vascular reserve, metabolism, and neurologic function at the bedside. Translation of these imaging methods into the perioperative setting has highlighted several potential avenues to optimize tissue perfusion and deliver neuroprotection. This review introduces the methods, metrics, and evidence underlying emerging optical and magnetic resonance neuroimaging methods and discusses their potential experimental and clinical utility in the setting of noncardiac surgery.

Neurological Manifestations of Coronavirus Disease 2019: A Comprehensive Review and Meta-Analysis of the First 6 Months of Pandemic Reporting.

Background: There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence. Methods: MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients. Results: A total of 2,207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke (n = 226), delirium (n = 79), intracranial haemorrhage (ICH, n = 57), meningoencephalitis (n = 13), seizures (n = 3), and acute demyelinating encephalitis (n = 2). Peripheral nervous system manifestations included Guillain-Barrè Syndrome (n = 21) and other peripheral neuropathies (n = 3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9-1.8%, 102/7,715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0-4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0-0.8%, 6/1,006]. Conclusions: The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of individuals at higher risk for neurologic sequelae.

Predicting Neurological Recovery after Traumatic Brain Injury in Children: A Systematic Review of Prognostic Models.

Predictive modeling is foundational to treatment and long-term management of children with traumatic brain injury (TBI). Assessment of injury severity in the acute-care setting enables early stratification of patients based on their risk of death, lifelong disability, or unfavorable outcome. This review evaluates predictive models that have been developed or validated for pediatric TBI patients. The predictive accuracy of these models, the outcomes and time points predicted, and the variables and statistical methods utilized in model development were compared. Embase, Scopus, MEDLINE®, and Web of Science were searched for studies that developed statistical models for predicting patient outcomes following pediatric TBI. Studies were excluded if they focused on adults or non-traumatic brain injury, or if they did not assess classification accuracy. A total of 4538 entries were identified and screened, with 7 studies included for analysis. This included five studies in which adult predictive models were validated for use in the pediatric setting, and two in which new models were derived from a pediatric cohort. Trials of adult prediction tools in pediatric cohorts, including the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) and Corticoid Randomisation After Significant Head Injury (CRASH)-TBI models, showed comparable accuracy between classification of adults and children. Models derived from pediatric cohorts showed improved accuracy. Most studies solely focused on clinical variables, with two studies incorporating biochemical and imaging variables. Predictive models for pediatric TBI are primarily based on methods and variables identified in adult studies. Although adult models have proven effective in select pediatric cohorts, they may be suboptimal when compared with models derived or adjusted for children.

NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly.

The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly.