Hypercapnia Causes Injury of the Cerebral Cortex and Cognitive Deficits in Newborn Piglets.

In critically ill newborns, exposure to hypercapnia (HC) is common and often accepted in neonatal intensive care units to prevent severe lung injury. However, as a "safe" range of arterial partial pressure of carbon dioxide levels in neonates has not been established, the potential impact of HC on the neurodevelopmental outcomes in these newborns remains a matter of concern. Here, in a newborn Yorkshire piglet model of either sex, we show that acute exposure to HC induced persistent cortical neuronal injury, associated cognitive and learning deficits, and long-term suppression of cortical electroencephalogram frequencies. HC induced a transient energy failure in cortical neurons, a persistent dysregulation of calcium-dependent proapoptotic signaling in the cerebral cortex, and activation of the apoptotic cascade, leading to nuclear deoxyribonucleic acid fragmentation. While neither 1 h of HC nor the rapid normalization of HC was associated with changes in cortical bioenergetics, rapid resuscitation resulted in a delayed onset of synaptosomal membrane lipid peroxidation, suggesting a dissociation between energy failure and the occurrence of synaptosomal lipid peroxidation. Even short durations of HC triggered biochemical responses at the subcellular level of the cortical neurons resulting in altered cortical activity and impaired neurobehavior. The deleterious effects of HC on the developing brain should be carefully considered as crucial elements of clinical decisions in the neonatal intensive care unit.

Identification and Prediction of Clinical Phenotypes in Hospitalized Patients With COVID-19: Machine Learning From Medical Records.

BACKGROUND: There is significant heterogeneity in disease progression among hospitalized patients with COVID-19. The pathogenesis of SARS-CoV-2 infection is attributed to a complex interplay between virus and host immune response that in some patients unpredictably and rapidly leads to "hyperinflammation" associated with increased risk of mortality. The early identification of patients at risk of progression to hyperinflammation may help inform timely therapeutic decisions and lead to improved outcomes. OBJECTIVE: The primary objective of this study was to use machine learning to reproducibly identify specific risk-stratifying clinical phenotypes across hospitalized patients with COVID-19 and compare treatment response characteristics and outcomes. A secondary objective was to derive a predictive phenotype classification model using routinely available early encounter data that may be useful in informing optimal COVID-19 bedside clinical management. METHODS: This was a retrospective analysis of electronic health record data of adult patients (N=4379) who were admitted to a Johns Hopkins Health System hospital for COVID-19 treatment from 2020 to 2021. Phenotypes were identified by clustering 38 routine clinical observations recorded during inpatient care. To examine the reproducibility and validity of the derived phenotypes, patient data were randomly divided into 2 cohorts, and clustering analysis was performed independently for each cohort. A predictive phenotype classifier using the gradient-boosting machine method was derived using routine clinical observations recorded during the first 6 hours following admission. RESULTS: A total of 2 phenotypes (designated as phenotype 1 and phenotype 2) were identified in patients admitted for COVID-19 in both the training and validation cohorts with similar distributions of features, correlations with biomarkers, treatments, comorbidities, and outcomes. In both the training and validation cohorts, phenotype-2 patients were older; had elevated markers of inflammation; and were at an increased risk of requiring intensive care unit-level care, developing sepsis, and mortality compared with phenotype-1 patients. The gradient-boosting machine phenotype prediction model yielded an area under the curve of 0.89 and a positive predictive value of 0.83. CONCLUSIONS: Using machine learning clustering, we identified and internally validated 2 clinical COVID-19 phenotypes with distinct treatment or response characteristics consistent with similar 2-phenotype models derived from other hospitalized populations with COVID-19, supporting the reliability and generalizability of these findings. COVID-19 phenotypes can be accurately identified using machine learning models based on readily available early encounter clinical data. A phenotype prediction model based on early encounter data may be clinically useful for timely bedside risk stratification and treatment personalization.

Practice patterns and perceptions of influenza testing amongst pediatric urgent care providers.

INTRODUCTION: Despite a sensitivity of 50% to 70% the rapid influenza diagnostic test (RIDT) continues to play an important role in clinical decision-making due to its quick turn-around time, high specificity, relative simplicity of use, and low cost. METHODS: A quantitative study using a web-based survey was distributed to 110 members of the Society of Pediatric Urgent Care aimed to assess RIDT use for diagnosis and management of influenza in outpatient pediatric patients. RESULTS: Responses from 61 providers were received. Forty-two percent (95% CI 29.5-54.5%) of respondents report higher confidence in their diagnosis of influenza with the aid of a positive RIDT. 28% of respondents (95% CI 16.6-39.4%) report a higher likelihood of prescribing antiviral medications to low-risk patients if an RIDT is positive than without laboratory confirmation. CONCLUSION: Most pediatric urgent care respondents reported higher confidence in their diagnosis and higher likelihood of prescribing antivirals with a positive RIDT rather than by clinical symptoms alone.

Neuroprotective effect of Src kinase in hypoxia-ischemia: A systematic review.

Background: Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality worldwide. While the application of therapeutic hypothermia has improved neurodevelopmental outcomes for some survivors of HIE, this lone treatment option is only available to a subset of affected neonates. Src kinase, an enzyme central to the apoptotic cascade, is a potential pharmacologic target to preserve typical brain development after HIE. Here, we present evidence of the neuroprotective effects of targeting Src kinase in preclinical models of HIE. Methods: We performed a comprehensive literature search using the National Library of Medicine's MEDLINE database to compile studies examining the impact of Src kinase regulation on neurodevelopment in animal models. Each eligible study was assessed for bias. Results: Twenty studies met the inclusion criteria, and most studies had an intermediate risk for bias. Together, these studies showed that targeting Src kinase resulted in a neuroprotective effect as assessed by neuropathology, enzymatic activity, and neurobehavioral outcomes. Conclusion: Src kinase is an effective neuroprotective target in the setting of acute hypoxic injury. Src kinase inhibition triggers multiple signaling pathways of the sub-membranous focal adhesions and the nucleus, resulting in modulation of calcium signaling and prevention of cell death. Despite the significant heterogeneity of the research studies that we examined, the available evidence can serve as proof-of-concept for further studies on this promising therapeutic strategy.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. CONCLUSIONS: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.

Computational analysis of cortical neuronal excitotoxicity in a large animal model of neonatal brain injury.

BACKGROUND: Neonatal hypoxic brain injury is a major cause of intellectual and developmental disability. Hypoxia causes neuronal dysfunction and death in the developing cerebral cortex due to excitotoxic Ca2+-influx. In the translational piglet model of hypoxic encephalopathy, we have previously shown that hypoxia overactivates Ca2+/Calmodulin (CaM) signaling via Sarcoma (Src) kinase in cortical neurons, resulting in overexpression of proapoptotic genes. However, identifying the exact relationship between alterations in neuronal Ca2+-influx, molecular determinants of cell death, and the degree of hypoxia in a dynamic system represents a significant challenge. METHODS: We used experimental and computational methods to identify molecular events critical to the onset of excitotoxicity-induced apoptosis in the cerebral cortex of newborn piglets. We used 2-3-day-old piglets (normoxic [Nx], hypoxic [Hx], and hypoxic + Src-inhibitor-treatment [Hx+PP2] groups) for biochemical analysis of ATP production, Ca2+-influx, and Ca2+/CaM-dependent protein kinase kinase 2 (CaMKK2) expression. We then used SimBiology to build a computational model of the Ca2+/CaM-Src-kinase signaling cascade, simulating Nx, Hx, and Hx+PP2 conditions. To evaluate our model, we used Sobol variance decomposition, multiparametric global sensitivity analysis, and parameter scanning. RESULTS: Our model captures important molecular trends caused by hypoxia in the piglet brain. Incorporating the action of Src kinase inhibitor PP2 further validated our model and enabled predictive analysis of the effect of hypoxia on CaMKK2. We determined the impact of a feedback loop related to Src phosphorylation of NMDA receptors and activation kinetics of CaMKII. We also identified distinct modes of signaling wherein Ca2+ level alterations following Src kinase inhibition may not be a linear predictor of changes in Bax expression. Importantly, our model indicates that while pharmacological pre-treatment significantly reduces the onset of abnormal Ca2+-influx, there exists a window of intervention after hypoxia during which targeted modulation of Src-NMDAR interaction kinetics in combination with PP2 administration can reduce Ca2+-influx and Bax expression to similar levels as pre-treatment. CONCLUSIONS: Our model identifies new dynamics of critical components in the Ca2+/CaM-Src signaling pathway leading to neuronal injury and provides a feasible framework for drug efficacy studies in translational models of neonatal brain injury for the prevention of intellectual and developmental disabilities.

Pediatric sepsis phenotypes for enhanced therapeutics: An application of clustering to electronic health records.

OBJECTIVE: The heterogeneity of pediatric sepsis patients suggests the potential benefits of clustering analytics to derive phenotypes with distinct host response patterns that may help guide personalized therapeutics. We evaluate the relative performance of latent class analysis (LCA) and K-means, 2 commonly used clustering methods toward the derivation of clinically useful pediatric sepsis phenotypes. METHODS: Data were extracted from anonymized medical records of 6446 pediatric patients that presented to 1 of 6 emergency departments (EDs) between 2013 and 2018 and were thereafter admitted. Using International Classification of Diseases (ICD)-9 and ICD-10 discharge codes, 151 patients were identified with a sepsis continuum diagnosis that included septicemia, sepsis, severe sepsis, and septic shock. Using feature sets used in related clustering studies, LCA and K-means algorithms were used to derive 4 distinct phenotypic pediatric sepsis segmentations. Each segmentation was evaluated for phenotypic homogeneity, separation, and clinical use. RESULTS: Using the 2 feature sets, LCA clustering resulted in 2 similar segmentations of 4 clinically distinct phenotypes, while K-means clustering resulted in segmentations of 3 and 4 phenotypes. All 4 segmentations identified at least 1 high severity phenotype, but LCA-identified phenotypes reflected superior stratification, high entropy approaching 1 (eg, 0.994) indicating excellent separation between estimated phenotypes, and differential treatment/treatment response, and outcomes that were non-randomly distributed across phenotypes (P < 0.001). CONCLUSION: Compared to K-means, which is commonly used in clustering studies, LCA appears to be a more robust, clinically useful statistical tool in analyzing a heterogeneous pediatric sepsis cohort toward informing targeted therapies. Additional prospective studies are needed to validate clinical utility of predictive models that target derived pediatric sepsis phenotypes in emergency department settings.

Patient and Visit Characteristics of Pediatric Patients With High-frequency Low-acuity Emergency Department Visits.

INTRODUCTION: Pediatric patients account for a disproportionate number of low-acuity emergency department (ED) visits. The aim of this study is to describe pediatric patient and visit characteristics for high-frequency users for low-acuity visits. METHODS: This was a retrospective cohort study of children presenting to a tertiary care pediatric ED and an affiliated community ED, over a 2-year period, with at least 10 low-acuity visits. Twenty patients with the highest number of visits were classified as "superusers." We analyzed patient data from the larger sample of high-frequency users and visit specific data from superuser visits. IBM SPSS Statistics 25 (SPSS Inc., Chicago, IL) was used to perform descriptive statistics and to summarize demographic and visit specific variables. RESULTS: We identified 181 high-frequency users with a mean number of visits of 14.3 ± 4.3 and a subpopulation of 20 superusers accounting for 434 visits. The majority of high-frequency users (89%) identified as African American and had public insurance (96.1%). Many patients received primary care affiliated with the home institution. In the first year of the study, 50.3% of high-frequency users were infants younger than 1 year at the index visit and 47.4% of superusers were infants at the index visit.Superuser visits were evenly distributed among seasons and the majority of visits occurred during the weekdays (70.7%). The majority of visits were for medical complaints (86.6%) and almost half (47.6%) resulted in some testing (24.9%) or treatment (30.6%); however, only 1.4% resulted in hospital admission. CONCLUSIONS: In our sample, most high-frequency low-acuity ED patients were infants, African American and have public insurance. Many are seen during clinic hours and are paneled at affiliated clinics. Among superusers, the majority of the visits did not require any testing, intervention, or treatment.

Metabolic dysfunction and immunometabolism in COVID-19 pathophysiology and therapeutics.

The COVID-19 pandemic has emerged as a public health crisis and has placed a significant burden on healthcare systems. Patients with underlying metabolic dysfunction, such as type 2 diabetes mellitus and obesity, are at a higher risk for COVID-19 complications, including multi-organ dysfunction, secondary to a deranged immune response, and cellular energy deprivation. These patients are at a baseline state of chronic inflammation associated with increased susceptibility to the severe immune manifestations of COVID-19, which are triggered by the cellular hypoxic environment and cytokine storm. The altered metabolic profile and energy generation of immune cells affect their activation, exacerbating the imbalanced immune response. Key immunometabolic interactions may inform the development of an efficacious treatment for COVID-19. Novel therapeutic approaches with repurposed drugs, such as PPAR agonists, or newly developed molecules such as the antagomirs, which block microRNA function, have shown promising results. Those treatments, alone or in combination, target both immune and metabolic pathways and are ideal for septic COVID-19 patients with an underlying metabolic condition.

A Prospective Look at Career Aspirations Among Pediatric Emergency Medicine Trainees.

OBJECTIVES: Before delivering a contract negotiation workshop to pediatric emergency medicine fellows in training, we wanted to understand the group's career aspirations. We hypothesized that fellows would be interested in nonclinical skill building in addition to the clinical training. METHODS: A 9-question survey was anonymously administered to fellows registered for the national conference using SurveyMonkey before the conference date. Six questions were quantitative, 2 were qualitative and open ended, and 1 required ranking of elements. RESULTS: Seventy-seven (47%) of the conference attendees responded to the survey, and approximately 80 (48%) attended the workshop session.Of the 77 fellows responding when asked about desired percentage of time per week devoted to the 4 categories of clinical, research, education, and administrative work within a 40-hour week, 76 (99%) chose the clinical category with an average of 58% of total hours devoted, 71 (92%) chose education with an average of 14% of total hours, 69 (90%) chose administration with an average of 8% of total hours, and 62 (81%) chose research with an average of 11% of total hours.Seventy attendees provided 1 sentence with the description of their ideal job. Thematic analysis of these responses revealed the following 5 main themes: academic potential, clinical environment, remuneration, job location, and work-life balance. CONCLUSIONS: Diversification in pediatric emergency medicine training is becoming a growing area of importance. Our study highlights a discrepancy in the expected time dedicated for nonclinical activities from those seen in previous workforce studies.

Epidermal Growth Factor Receptor Inhibition Reverses Cellular and Transcriptomic Alterations Induced by Hypoxia in the Neonatal Piglet Brain.

Acute hypoxia (HX) causes extensive cellular damage in the developing human cerebral cortex. We found increased expression of activated-EGFR in affected cortical areas of neonates with HX and investigated its functional role in the piglet, which displays a highly evolved, gyrencephalic brain, with a human-like maturation pattern. In the piglet, HX-induced activation of EGFR and Ca2+/calmodulin kinase IV (CaMKIV) caused cell death and pathological alterations in neurons and glia. EGFR blockade inhibited CaMKIV activation, attenuated neuronal loss, increased oligodendrocyte proliferation, and reversed HX-induced astrogliosis. We performed for the first time high-throughput transcriptomic analysis of the piglet cortex to define molecular responses to HX and to uncover genes specifically involved in EGFR signaling in piglet and human brain injury. Our results indicate that specific molecular responses modulated by EGFR may be targeted as a therapeutic strategy for HX injury in the neonatal brain.

Exosomes in Nephropathies: A Rich Source of Novel Biomarkers.

The biomarkers commonly utilized in diagnostic evaluations of kidney disease suffer from low sensitivity, especially in the early stages of renal damage. On the other hand, obtaining a renal biopsy to augment clinical decision making can lead to potentially serious complications. In order to overcome the shortcomings of currently available diagnostic tools, recent studies suggest that exosomes, cell-secreted extracellular vesicles containing a large array of active molecules to facilitate cell-to-cell communication, may represent a rich source of novel disease biomarkers. Because of their endocytic origin, exosomes carry markers typical for their parent cells, which could permit the localization of biochemical cellular alterations in specific kidney compartments. Different types of exosomes can be isolated from noninvasively obtained biofluids; however, in the context of kidney disease, evidence has emerged on the role of urinary exosomes in the diagnostic and predictive modeling of renal pathology. The current review summarizes the potential application of exosomes in the detection of acute and chronic inflammatory, metabolic, degenerative, and genetic renal diseases.

Pediatric urgent care education: a survey-based needs assessment.

BACKGROUND: There is an increasing number of pediatric urgent care centers that are largely staffed by pediatric residency graduates. It is unclear if pediatric residency adequately prepares a physician to fully and successfully provide care in an urgent care setting. The goal of this study is to conduct an assessment of urgent care directors' perceptions of recent pediatric residency graduates' preparedness to successfully provide pediatric urgent care after graduation. METHODS: This is a 2018 cross-sectional survey of all pediatric emergency medicine division chiefs in the United States and all pediatric urgent care directors who are members of the Society for Pediatric Urgent Care. An electronic survey was distributed consisting of eight multiple choice questions regarding perceived preparedness and knowledge gaps of recent pediatric residency graduates for independent practice in urgent care. Descriptive statistics were used to analyze results and qualitative data were analyzed via an inductive thematic approach. RESULTS: Forty-two percent (65/154) of surveys were completed. No respondents believed that a recent pediatric residency graduate would be adequately prepared to independently practice in a pediatric urgent care and 81% of respondents recommended some additional training. Most respondents described this training as important (46%) or very important (35%). Most respondents recommended between 6 months and 1 year as the appropriate amount of time to achieve competency. CONCLUSIONS: Despite the growing number pediatric residency graduates staffing pediatric urgent care centers, the majority of surveyed pediatric emergency medicine division chiefs and pediatric urgent care directors do not think that pediatric residency adequately prepares graduates to successfully provide urgent care to pediatric patients. We recommend further exploration of gaps in knowledge of recent pediatric residency graduates as a next step towards developing systems for further training for pediatric residency graduates to gain competency in urgent care management.

Association between hemoglobin concentrations at discharge from the neonatal intensive care unit with markers of neurodevelopmental outcomes in premature neonates.

BACKGROUND: Premature neonates are often subjected to multiple transfusions with red blood cells during their hospitalization in the neonatal intensive care unit (NICU). The hemoglobin threshold for transfusion prior to discharge from the NICU varies significantly among different centers. The aim of the present study is to investigate the association between hemoglobin concentration at discharge with neurodevelopmental outcomes in premature neonates. METHODS: Retrospective observation study with regression analysis was performed with follow up assessment in the neuro-developmental outpatient clinic at 30 months of adjusted age. RESULTS: Data from 357 neonates born at less than 37 weeks' gestation were analyzed. Sensory and motor neurodevelopment at 30 months of adjusted age, were not associated with the hemoglobin concentration at discharge (p=0.5891 and p=0.4575, respectively). There was no association between the hemoglobin concentration at discharge with fine or gross motor development (p=0.1582 and p=0.3805, respectively). Hemoglobin concentration at discharge was not associated with poor neurodevelopmental outcomes up until 30 months of adjusted age. CONCLUSIONS: The data of the present study indicate that the hemoglobin concentration of premature neonates at the time of discharge is not associated with poorer markers of neurodevelopmental outcomes at 30 months of adjusted age. Comorbidities such as BPD and IVH that are present to premature neonates were identified as potential risk factors for certain aspects of the neurodevelopment.

Comparison of Resource Utilization and Length of Hospitalization Between Overweight and Healthy-Weight Pediatric Trauma Patients Presenting to a Pediatric Emergency Department With Moderate to Severe Injury: A Prospective Study.

OBJECTIVES: Our study aimed to compare overweight and healthy-weight pediatric trauma patient outcomes, specifically with respect to hospital length of stay and resource utilization. We hypothesized that overweight pediatric trauma patients would have increased hospital length of stay and radiographic study use compared with their healthy-weight counterparts. METHODS: This was a prospective, observational, cohort study of pediatric trauma patients aged 2 to 19 years presenting to an urban pediatric emergency department over a period of 1 year. Using measured height and weight values, body mass index (BMI) for age was calculated and plotted on the Centers for Disease Control and Prevention BMI-for-age growth charts. Patients were followed up throughout their hospitalization, and the following items were recorded: trauma alert level, mechanism of injury, age, sex, race, Glasgow Coma Scale score, total number of days in hospital, total number of intensive care unit days, total number of radiographs obtained, total number of computed tomography scans obtained, and mechanism of injury. RESULTS: Our study population included 109 subjects. The mean age of the subjects was 9.7 years. The number of patients meeting the definition of obese (BMI for age ≥95%) was 15, or 14% of the total study population. There was no significant difference between the overweight cohort and the healthy-weight cohort found among any of the variables recorded and analyzed. CONCLUSIONS: Although there are many chronic conditions in children associated with obesity, in the case of trauma, it does not seem to be a strong concern. A continued focus on preventing and reversing childhood obesity for other physical and mental health outcomes may be more important.

Towards Reliable ARDS Clinical Decision Support: ARDS Patient Analytics with Free-text and Structured EMR Data.

In this work, we utilize a combination of free-text and structured data to build Acute Respiratory Distress Syndrome(ARDS) prediction models and ARDS phenotype clusters. We derived 'Patient Context Vectors' representing patientspecific contextual ARDS risk factors, utilizing deep-learning techniques on ICD and free-text clinical notes data. The Patient Context Vectors were combined with structured data from the first 24 hours of admission, such as vital signs and lab results, to build an ARDS patient prediction model and an ARDS patient mortality prediction model achieving AUC of 90.16 and 81.01 respectively. The ability of Patient Context Vectors to summarize patients' medical history and current conditions is also demonstrated by the automatic clustering of ARDS patients into clinically meaningful phenotypes based on comorbidities, patient history, and presenting conditions. To our knowledge, this is the first study to successfully combine free-text and structured data, without any manual patient risk factor curation, to build real-time ARDS prediction models.

Sepsis Immunometabolism: From Defining Sepsis to Understanding How Energy Production Affects Immune Response.

OBJECTIVES: This review will examine current definitions and trends in sepsis management as well pathophysiologic mechanisms in animal and ex vivo studies that correlate decreased energy production with deranged inflammatory response during the septic process. DATA SOURCES: The latest articles in the literature that focus on the role of immunometabolism and associated mechanisms in sepsis were selected. STUDY SELECTION: The most relevant, original articles were included in the review. DATA EXTRACTION: All pertinent data for sepsis definitions as well as changes in immunometabolic pathways during the septic process was reviewed and assessed for inclusion in this article. DATA SYNTHESIS: Sepsis is a major cause of multiple organ dysfunction. It is the principal cause of death resulting from infection and one of the most expensive conditions treated in the United States. Despite current efforts to accurately define sepsis, novel treatments and highly trained providers, mortality rates for sepsis remain high, prompting a need for further investigation of underlying immunometabolic mechanisms to identify potential treatment targets. The definition of sepsis has shifted and changed in the past few decades due to poorly defined criteria, as well as unclear guidelines for providers with regards to management of severe sepsis and septic shock. The early identification of patients with a systemic inflammatory response that will progress to septic shock is critical since recent traditional therapeutic approaches, such as early goal-directed therapy, IV immunoglobulin, and anti-tumor necrosis factor-α antibodies have failed. CONCLUSIONS: There are no effective anti-sepsis drug therapies due to complex inflammatory and metabolic interactions. Further studies regarding the interface between innate immunity and metabolism should be investigated to effectively address septic patient mortality rates.

Hospital-Acquired Hyponatremia in Children Following Hypotonic versus Isotonic Intravenous Fluids Infusion.

Hypotonic solutions have been used in pediatrics for maintenance of intravenous (IV) hydration. However, recent randomized control trials and cohort studies have raised significant concerns for association with hospital-acquired hyponatremia (HAH). The study aimed to assess whether the use of hypotonic parenteral solutions (PS) compared with isotonic PS is associated with increased HAH risk in children with common pediatric conditions. Retrospective chart review of 472 patients aged 2 months to 18 years who received either isotonic or hypotonic PS as maintenance fluids. Administration of hypotonic PS was associated with a four-fold increase in risk of developing HAH in the univariate analysis, (unadjusted odds ratio (OR) = 3.99; 95% confidence interval (CI): 1.36⁻11.69, p = 0.01). Hypotonic PS were associated with HAH (p = 0.04) when adjusted for the level of admission serum CO2. There was a mean decrease of serum sodium of 0.53 mEq/L in the hypotonic group compared to the mean increase of 4.88 mEq/L in the isotonic group. These data suggest that hypotonic PS are associated with HAH in children admitted for common pediatric conditions. Isotonic PS should be considered as a safer choice for maintenance fluid hydration.