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This study sought to evaluate the candidacy of plasma osteopontin (OPN) as a biomarker of COVID-19 severity and multisystem inflammatory condition in children (MIS-C) in children. A retrospective analysis of 26 children (0–21 years of age) admitted to Children’s Healthcare of Atlanta with a diagnosis of COVID-19 between March 17 and May 26, 2020 was undertaken. The patients were classified into three categories based on COVID-19 severity levels: asymptomatic or minimally symptomatic (control population, admitted for other non-COVID-19 conditions), mild/moderate, and severe COVID-19. A fourth category of children met the Centers for Disease Control and Prevention's case definition for MIS-C. Residual blood samples were analyzed for OPN, a marker of inflammation using commercial ELISA kits (R&D), and results were correlated with clinical data. This study demonstrates that OPN levels are significantly elevated in children hospitalized with moderate and severe COVID-19 and MIS-C compared to OPN levels in mild/asymptomatic children. Further, OPN differentiated among clinical levels of severity in COVID-19, while other inflammatory markers including maximum erythrocyte sedimentation rate, C-reactive protein and ferritin, minimum lymphocyte and platelet counts, soluble interleukin-2R, and interleukin-6 did not. We conclude OPN is a potential biomarker of COVID-19 severity and MIS-C in children that may have future clinical utility. The specificity and positive predictive value of this marker for COVID-19 and MIS-C are areas for future larger prospective research studies.

There have been decades of interest in advanced computational algorithms with potential for clinical decision support systems (CDSS), yet these have not been widely implemented in clinical practice. One major barrier to dissemination may be a user-friendly interface that integrates into clinical workflows. Complicated or non-intuitive displays may confuse users and may even increase patient management errors. We recently developed a graphical user interface (GUI) intended to integrate a predictive hemodynamic model into the workflow of nurses caring for patients on vasopressors in the intensive care unit (ICU). Here, we evaluated user perceptions of the usability of this system. The software was installed in the room of an ICU patient, running for at least 4 hours with the display hidden. Afterward, we showed nurses a video recording of the session and surveyed their perceptions about the software's potential safety and usefulness. We collected data for nine patients. Overall, nurses expressed reasonable enthusiasm that the software would be useful and without serious safety concerns. However, there was a wide diversity of opinions about what specific aspects of the software would be useful and what aspects were confusing. In several instances, the same elements of the GUI were cited as most useful by some nurses and most confusing by others. Our findings validate that it is possible to develop GUIs for CDSS that are perceived as potentially useful and without substantial risk but also reinforce the diversity of user perceptions about novel CDSS technology. Clinical Relevance- This end-user evaluation of a novel CDSS highlights the importance of end-user experience in the workflow integration of advanced computational algorithms for bedside decision support during critical care.

RationalePublished evidence indicates that mean arterial pressure (MAP) below a goal range (hypotension) is associated with worse outcomes, though MAP management failures are common.ObjectivesCharacterize hypotension occurrences in ICUs and consider the implications for MAP management.MethodsObservational study of three retrospective and one prospective cohorts of adult ICU patients during continuous vasopressor infusion. Three cohorts of general, mixed ICU patients; one cohort of acute spinal cord injury patients. Hypotension clusters were defined wherever ≥50% of MAP measurements were hypotensive with ≥10 minutes of total hypotension. Trend analysis was performed (predicting future MAP using 14 min of preceding MAP data) to understand which hypotension clusters could likely have been predicted by clinician awareness of MAP trends.Measurements and Main ResultsIn cohorts of 155, 66, 16, and 10 subjects, respectively, hypotension occurred 12.9%, 5.5%, 21.5%, and 3.9% of the time. Hypotension occurred overwhelmingly within temporal clusters. MAP trend analysis predicted most substantial hypotension clusters (range: 66.6% to 80.0% sensitivity) prior to continuous hypotension occurring, usually before the occurrence of any hypotension at all. When MAP trend analysis predicted hypotension, positive predictive value ranged from 56% to 77% (probability of subsequent temporal cluster of hypotension or vasopressor up-titration).ConclusionsHypotension usually occurred in temporal clusters that can typically be predicted by extrapolation from trends. This implies that clinicians may be slow to identify incipient hypotension. In Cohort 4, analysis was performed in real-time, establishing a proof-of-principle for a computational tool with possible clinical utility.Statement of Clinical SignificanceThis analysis found that hypotension was relatively common in the bottom quartiles in each of four ICU cohorts, occurring in temporal clusters that could usually be predicted by trend extrapolation. This implies that clinicians may be slow to identify incipient hypotension in ICU patients. In one cohort, hypotension prediction was performed in real-time, establishing a proof-of-principle for future clinical usability.

Objective Pediatric traumatic brain injury is a major public health problem in the United States. Hypertonic saline therapy is a well-established treatment in patients with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) who have intracranial hypertension. In children, fluid overload is associated with increased mortality, ventilator duration, and length of PICU stay, even when controlling for severity of illness. This study reports prevalence of fluid overload in pediatric patients with severe traumatic brain injury treated with 3% hypertonic saline and effect on clinical outcomes. Design Single-center retrospective chart review. Setting PICUs at two tertiary children's hospitals. Patients One hundred thirty-eight patients with traumatic brain injury with postresuscitation Glasgow Coma Scale less than or equal to 8 who received hypertonic saline from September 1, 2010, to February 28, 2016, and intracranial pressure monitoring and survived at least 24 hours from admission. Interventions None. Measurements and main results We used fluid balance percentage greater than or equal to 10% as our definition of fluid overload. Ninety-one percent of patients less than 1 year old had fluid overload on day 10 of admission compared with 47% of patients greater than 1 year. Fluid overloaded patients did not have increased mortality, acute kidney injury, PICU length of stay, or ventilator days. Hypertonic saline was not the cause of fluid overload in these patients. Conclusions Patients with severe traumatic brain injury do have high rates of fluid overload. However, fluid overload did not contribute to mortality, longer days on the ventilator, increased risk of acute kidney injury, or increased PICU length of stay.

Traumatic brain injury (TBI) is the leading cause of death in children and adolescents in developed countries, but there are no blood-based biomarkers to support the diagnosis or prognosis of pediatric TBI to-date. Here we report that the plasma levels of osteopontin (OPN), a phosphoprotein chiefly secreted by macrophages and/or activated microglia, may contribute to this goal. In animal models of TBI, while OPN, fibrillary acidic protein (GFAP), and matrix metalloproteinase 9 (MMP-9) were all readily induced by controlled cortical impact in the brains of one-month-old mice, only OPN and GFAP ascended in the blood in correlation with high neurological severity scores (NSS). In children with TBI (three to nine years of age, n = 66), the plasma levels of OPN, but not GFAP, correlated with severe TBI (Glasgow Coma Score ≤ 8) and intracranial lesions at emergency department. In addition, the plasma OPN levels in severe pediatric TBI patients continued to ascend for 72 h and correlated with mortality and the days requiring ventilator or intensive care unit support, whereas the plasma GFAP levels lacked these properties. Together, these results suggest that plasma OPN outperforms GFAP and may be a neuroinflammation-based diagnostic and prognostic biomarker in pediatric TBI.

The purpose of this study is to determine both the frequency of repeat CT performed within 1 month after a patient visits the emergency department (ED) and undergoes CT evaluation for abdominal pain and the frequency of worsened or new CT-based diagnoses.Secondary analysis was performed on data collected during a prospective multicenter study. The parent study included patients who underwent CT in the ED for abdominal pain between 2012 and 2014, and these patients constituted the study group of the present analysis. The proportion of patients who underwent (in any setting) repeat abdominal CT within 1 month of the index CT examination was calculated. For each of these patients, results of the index and repeat CT scans were compared by an independent panel and categorized as follows: no change (group 1); same process, improved (group 2); same process, worse (group 3); or different process (group 4). The proportion of patients in groups 1 and 2 versus groups 3 and 4 was calculated, and patient and ED physician characteristics were compared.The parent study included 544 patients (246 of whom were men [45%]; mean patient age, 49.4 years). Of those 544 patients, 53 (10%; 95% CI, 7.5-13%) underwent repeat abdominal CT. Patients' CT comparisons were categorized as follows: group 1 for 43% of patients (23/53), group 2 for 26% (14/53), group 3 for 15% (8/53), and group 4 for 15% (8/53). New or worse findings were present in 30% of patients (16/53) (95% CI, 19-44%). When patients with findings in groups 1 and 2 were compared to patients with findings in groups 3 and 4, no significant difference was noted in patient age (p = 0.25) or sex (p = 0.76), the number of days between scans (p = 0.98), and the diagnostic confidence of the ED physician after the index CT scan was obtained (p = 0.33).Short-term, repeat abdominal CT was performed for 10% of patients who underwent CT in the ED for abdominal pain, and it yielded new or worse findings for 30% of those patients.

Usual care regarding vasopressor initiation is ill-defined. We aimed to develop a quantitative “dynamic practice” model for usual care in the emergency department (ED) regarding the timing of vasopressor initiation in sepsis. In a retrospective study of 589 septic patients with hypotension in an urban tertiary care center ED, we developed a multi-variable model that distinguishes between patients who did and did not subsequently receive sustained (>24 h) vasopressor therapy. Candidate predictors were vital signs, intravenous fluid (IVF) volumes, laboratory measurements, and elapsed time from triage computed at timepoints leading up to the final decision timepoint of either vasopressor initiation or ED hypotension resolution without vasopressors. A model with six independently significant covariates (respiratory rate, Glasgow Coma Scale score, SBP, SpO2, administered IVF, and elapsed time) achieved a C-statistic of 0.78 in a held-out test set at the final decision timepoint, demonstrating the ability to reliably model usual care for vasopressor initiation for hypotensive septic patients. The included variables measured depth of hypotension, extent of disease severity and organ dysfunction. At an operating point of 90% specificity, the model identified a minority of patients (39%) more than an hour before actual vasopressor initiation, during which time a median of 2,250 (IQR 1,200–3,300) mL of IVF was administered. This single-center analysis shows the feasibility of a quantitative, objective tool for describing usual care. Dynamic practice models may help assess when management was atypical; such tools may also be useful for designing and interpreting clinical trials.

BACKGROUND Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRgLITT) has been used successfully to treat epileptogenic cortical cerebral cavernous malformations (CCM). It is unclear whether MRgLITT would be as feasible or safe for deep CCMs. OBJECTIVE To describe our experience with MRgLITT for symptomatic deep CCMs. METHODS Patients' records were reviewed retrospectively. MRgLITT was carried out using a commercially available system in an interventional MRI suite with efforts to protect adjacent brain structures. Immediate postoperative imaging was used to judge ablation adequacy. Delayed postoperative MRI was used to measure lesion volume changes during follow-up. RESULTS Four patients with CCM in the thalamus, putamen, midbrain, or subthalamus presented with persistent and disabling neurological symptoms. A total of 2 patients presented with disabling headaches and sensory disturbances and 2 with recurrent symptomatic hemorrhages, of which 1 had familial CCM. Patients were considered by vascular neurosurgeons to be poor candidates for open surgery or had refused it. Multiple trajectories were used in most cases. Adverse events included device malfunction with leakage of saline causing transient mass effect in one patient, and asymptomatic tract hemorrhage in another. One patient suffered an expected mild but persistent exacerbation of baseline deficits. All patients showed improvement from a previously aggressive clinical course with lesion volume decreased by 20% to 73% in follow-up. CONCLUSION MRgLITT is feasible in the treatment of symptomatic deep CCM but may carry a high risk of complications without the benefit of definitive resection. We recommend cautious patient selection, low laser power settings, and conservative temperature monitoring in surrounding brain parenchyma.

Usual care regarding vasopressor (VP) initiation is ill-defined. We aimed to further validate a quantitative model for usual care in the Emergency Department (ED) regarding the timing of VP initiation in sepsis. We retrospectively studied a cohort of adult critically-ill ED patients who also received antibiotics in the ED. We applied a multivariable model previously developed from another patient cohort which distinguishes between time points at which patients were or were not subsequently started on a continuous VP infusion. The model has six independently significant predictors (respiratory rate, Glasgow Coma Scale score, systolic blood pressure, SpO 2 , administered intravenous fluids, and elapsed time). The outcome was initiation of VP infusion, either within the ED or within 6 hours after leaving the ED. We applied the model to all time points, beginning when all model input parameters were first available for a given patient, and ending when either VP were first started, or the patient left the ED. Out of 55,963 adult ED patients during the two-year study interval, we identified 1,629 who met our inclusion criteria. The area under the receiver operating characteristic curve was 0.81 for all patients, and 0.72 for the subset with at least one hypotensive blood pressure measurement. At a model threshold with sensitivity and specificity 0.74 and 0.74, respectively, the median advance detection time was 170.5 minutes (IQR 53 - 363).

We investigated whether a statistical model could predict mean arterial pressure (MAP) during uncontrolled hemorrhage; such a model could be used for automated decision support, to help clinicians decide when to provide intravascular volume to achieve MAP goals. This was a secondary analysis of adult swine subjects during uncontrolled splenic bleeding. By protocol, after developing severe hypotension (MAP < 60 mmHg), subjects were resuscitated with either saline (NS) or fresh frozen plasma (FFP), determined randomly. Vital signs were documented at quasi-regular time-step intervals, until either subject death or 300 min. Subjects were randomly separated 50%/50% into training/validation sets, and regression models were developed to predict MAP for each subsequent (i.e., future) time-step. Median time-steps for serially recorded vital signs were +15 min. 5 subjects survived the protocol; 17 died after a median time of 87 min (IQR 78 – 134). The final model consisted of: current MAP; heart rate (HR); prior NS; imminent NS; and imminent FFP. The 95% limits-of-agreement between true subsequent MAP vs. predicted subsequent MAP were +10/-11 mmHg for the 79 time-steps in the training set; and +14/-13 for the 64 time-steps in the validation set. A total of 10 sudden death events (i.e., rapid, fatal MAP decrease within one single time-step) were excluded from analysis. In conclusion, for uncontrolled hemorrhage in a swine model, it was possible to estimate the next documented MAP value on the basis of the subject’s current documented MAP; HR; prior NS; and the volume of resuscitation about to be administered. However, the model was unable to predict "sudden death" events. The applicability to populations with wider heterogeneity of hemorrhage patterns and with comorbidities requires further investigation.

OBJECTIVE: To examine levels of plasma osteopontin (OPN), a recently described neuroinflammatory biomarker, in children with abusive head trauma (AHT) compared with children with other types of traumatic brain injury (TBI). STUDY DESIGN: The study cohort comprised children aged

Penetrating traumatic brain injury (TBI) is uncommon in infancy. The consequences may be devastating, especially when the injury is extensive and affects eloquent areas of the brain. There is the potential for neuropsychological dysfunction that may impact the individual's development and well-being into adulthood. In the context of early brain injury, the developing brain is both remarkably resilient and vulnerable. The present case study describes a patient who experienced a penetrating TBI at 9 days of age, subsequently developed intractable seizures, and underwent left hemispherectomy. Neuropsychological testing at ages 5, 10, 11, and 19 years are presented alongside fMRI and Wada testing. While the patient initially developed cognitive functions in the low-average range by age 5, scores on neuropsychological assessments began to decrease thereafter. This case is discussed with attention to vulnerability and plasticity theories. It highlights the ability of the brain to reorganize and allow the development of functions that would normally be sub-served by damaged areas and the limits of plasticity. Further, this case illustrates the vulnerability of the early brain to insult, the potential to grow into deficits, and the need to consider a variety of factors when predicting outcomes for cases of pediatric brain injury.

OBJECTIVE The management of hydrocephalus resulting from intraventricular hemorrhage related to extreme prematurity remains demanding. Given the complexities of controlling hydrocephalus in this population, less commonly used procedures may be required. The authors examined the utility of ventriculogallbladder (VGB) shunts in a series of such children. METHODS The authors retrospectively reviewed the medical records of all children who underwent surgery for hydrocephalus in the period from 2011 through 2019 at Children’s Healthcare of Atlanta. Six patients who underwent VGB shunt placement were identified among a larger cohort of 609 patients who had either a new shunt or a newly changed distal terminus site. The authors present an analysis of this series, including a case of laparoscopy-assisted distal VGB shunt revision. RESULTS The mean age at initial shunt placement was 5.1 months (range 3.0–9.4 months), with patients undergoing a mean of 11.8 shunt procedures (range 5–17) prior to the initial VGB shunt placement at a mean age of 5.3 years (range 7.9 months–12.8 years). All 6 patients with VGB shunt placement had hydrocephalus related to extreme prematurity (gestational age < 28 weeks). At the time of VGB shunt placement, all had complex medical and surgical histories, including poor venous access due to congenital or iatrogenic thrombosis or thrombophlebitis and a peritoneum hostile to distal shunt placement related to severe necrotizing enterocolitis. VGB complications included 1 case of shunt infection, identified at postoperative day 6, and 2 cases of distal shunt failure due to retraction of the distal end of the VGB shunt. In all, there were 3 conversions back to ventriculoperitoneal or ventriculoatrial shunts due to the 2 previously mentioned complications, plus 1 patient who outgrew their initial VGB shunt. Three of 6 patients remain with a VGB shunt, including 1 who underwent laparoscopy-assisted distal shunt revision 110.5 months after initial VGB shunt insertion. CONCLUSIONS Placement of VGB shunts should be considered in the armamentarium of procedures that may be used in the particularly difficult cohort of children with hydrocephalus related to extreme prematurity. VGB shunts show utility as both a definitive treatment and as a “bridge” procedure until the patient is larger and comorbid abdominal and/or vascular issues have resolved sufficiently to allow conversion back to ventriculoperitoneal or ventriculoatrial shunts, if needed.

Objectives:Presenting symptoms in patients with sepsis may influence rapidity of diagnosis, time-to-antibiotics, and outcome. We tested the hypothesis that vague presenting symptoms are associated with delayed antibiotics and increased mortality. We further characterized individual presenting sympto

Objectives: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. Methods: We assessed male high school football players (ages 14–18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (Results: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. Conclusions: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781–792)

OBJECTIVEEvidence shows mixed efficacy of applying guidelines for the treatment of traumatic brain injury (TBI) in children. A multidisciplinary team at a children’s health system standardized intensive care unit–based TBI care using guidelines and best practices. The authors sought to investigate the impact of guideline implementation on outcomes.METHODSA multidisciplinary group developed a TBI care protocol based on published TBI treatment guidelines and consensus, which was implemented in March 2011. The authors retrospectively compared preimplementation outcomes (May 2009 to March 2011) and postimplementation outcomes (April 2011 to March 2014) among patients < 18 years of age admitted with severe TBI (Glasgow Coma Scale score ≤ 8) and potential survivability who underwent intracranial pressure (ICP) monitoring. Measures included mortality, hospital length of stay (LOS), ventilator LOS, critical ICP elevation time (percentage or total time that ICP was > 40 mm Hg), and survivor functionality at discharge (measured by the WeeFIM score). Data were analyzed using Student t-tests.RESULTSA total of 71 and 121 patients were included pre- and postimplementation, respectively. Mortality (32% vs 19%; p < 0.001) and length of critical ICP elevation (> 20 mm Hg; 26.3% vs 15%; p = 0.001) decreased after protocol implementation. WeeFIM discharge scores were not statistically different (57.6 vs 58.9; p = 0.9). Hospital LOS (median 19.6 days; p = 0.68) and ventilator LOS (median 10 days; p = 0.24) were unchanged.CONCLUSIONSA multidisciplinary effort to develop, disseminate, and implement an evidence-based TBI treatment protocol at a children’s hospital was associated with improved outcomes, including survival and reduced time of ICP elevation. This type of ICP-based protocol can serve as a guide for other institutions looking to reduce practice disparity in the treatment of severe TBI.