Virus-induced genetics revealed by multidimensional precision medicine transcriptional workflow applicable to COVID-19.

Precision medicine requires the translation of basic biological understanding to medical insights, mainly applied to characterization of each unique patient. In many clinical settings, this requires tools that can be broadly used to identify pathology and risks. Patients often present to the intensive care unit with broad phenotypes, including multiple organ dysfunction syndrome (MODS) resulting from infection, trauma, or other disease processes. Etiology and outcomes are unique to individuals, making it difficult to cohort patients with MODS, but presenting a prime target for testing/developing tools for precision medicine. Using multitime point whole blood (cellular/acellular) total transcriptomics in 27 patients, we highlight the promise of simultaneously mapping viral/bacterial load, cell composition, tissue damage biomarkers, balance between syndromic biology versus environmental response, and unique biological insights in each patient using a single platform measurement. Integration of a transcriptome workflow yielded unexpected insights into the complex interplay between host genetics and viral/bacterial specific mechanisms, highlighted by a unique case of virally induced genetics (VIG) within one of these 27 patients. The power of RNA-Seq to study unique patient biology while investigating environmental contributions can be a critical tool moving forward for translational sciences applied to precision medicine.

Pediatric Blood Management Protocol in Cranial Vault Surgery.

BACKGROUND: Cranial vault surgeries are invasive, extensive procedures with blood transfusions being frequently required. Previous interventions have been described to attempt to decrease the transfusion burden. The objective of this study is to determine if a Pediatric Blood Management (PBM) team can reduce transfusion requirements in children undergoing cranial vault surgery. METHODS: A protocol was developed which involved preoperative optimization of hemoglobin (Hb), intraoperative use of tranexamic acid, cell saver technology, and blood sparing operative techniques. Patients were preoperatively screened with basic laboratory testing. Retrospective data on 20 consecutive patients who underwent craniofacial surgery prior were used as controls. Prospective data on patients was collected. RESULTS: Groups were similar in age and weight. Postoperative Hb measurements were similar, with the control group 10.9 ±â€Š2.2 g/dL and the intervention arm 9.6 + 2.7 g/dL. Discharge Hb concentrations also were similar with 9.6 ±â€Š1.6 g/dL and 9.7 ±â€Š2.5 g/dL in the control and PBM group, respectively. The rate of transfusion decreased from 80% to 42% after protocol implementation (P = 0.007). During the last 6 months of data collection, the transfusion rate decreased further to 17%. Furthermore, 4 patients were found to have von Willebrand disease preoperatively with only 1 requiring a transfusion. CONCLUSIONS: The authors found that the institution of a PBM team reduced the transfusion burden of patients, including complex patients with von Willebrand disease. The use of a multimodal approach to hematologic management optimized patients for their procedures and helped minimize exposure to transfusion associated complications.

Intravenous Ferumoxytol in Pediatric Patients With Iron Deficiency Anemia.

BACKGROUND: Iron deficiency anemia (IDA) is common in children. Limited data exist on the efficacy and safety of ferumoxytol in children. OBJECTIVE: To assess the efficacy of 10 mg/kg dose given over 15-60 minutes in correcting IDA and report any adverse drug reactions (ADRs). METHODS: We conducted a retrospective review of all patients who received ferumoxytol infusions for the management of IDA by the Pediatric Blood Management Program between October 2010 and March 2015. RESULTS: A total of 110 infusions were given to 54 patients. Compared with baseline preinfusion hemoglobin (Hb; 9.2 ± 1.9 g/dL), a significant rise was seen at 1 week and 4 weeks postinfusion (11.5 ± 1.5 and 11.8 ± 1.7 g/dL, respectively, P < 0.001). Also, a significant rise in serum ferritin at 1 week and 4 weeks postinfusion was seen (51 ± 71 vs 192 ± 148 and 89 ± 135 ng/mL, P < 0.001 and <0.035, respectively). Patients who concomitantly received erythropoietin had a significantly larger Hb rise from baseline than those who did not at 4 weeks (2.7 ± 2.2 vs 1.6 ± 1.1 g/dL, P < 0.017). ADRs included pruritus (n = 1), urticaria (n = 1), and multisymptom episodes (n = 3) that included shortness of breath, chest tightness, back pain, and epigastric cramping that responded to therapy with IV diphenhydramine and methylprednisolone. CONCLUSION: Ferumoxytol was effective in treating IDA in our small study. Slow infusion rate and close monitoring allowed early detection of the infrequent ADRs.

A multicentered prospective analysis of diagnosis, risk factors, and outcomes associated with pediatric ventilator-associated pneumonia.

OBJECTIVE: To assess risk factors and outcomes associated with pediatric ventilator-associated pneumonia. DESIGN: Multicentered prospective observational cohort. SETTING: Children's hospitals in the United States. PATIENTS: Mechanically ventilated patients less than 18 years old. MEASUREMENTS AND MAIN RESULTS: Prospective evaluation of the prevalence, risk factors, and outcomes of pediatric ventilator-associated pneumonia along with evaluation of diagnostic criterion for pediatric ventilator-associated pneumonia. The prevalence of pediatric ventilator-associated pneumonia was 5.2% (n = 2,082), for a rate of 7.1/1,000 ventilator days. Patients with ventilator-associated pneumonia had a longer unadjusted ICU length of stay (p < 0.0001) and increased length of mechanical ventilation by more than 11 days (p < 0.0001). After adjustment for patient factors, ICU length of stay (p = 0.03) and mechanical ventilation days (p = 0.001) remained significant. Patients with ventilator-associated pneumonia were almost three times more likely to die (p = 0.007). Independent risk factors for ventilator-associated pneumonia were reintubation and part-time ventilation. CONCLUSIONS: Pediatric ventilator-associated pneumonia is common in mechanically ventilated pediatric patients. These patients have longer length of stay, longer duration of mechanical ventilation, and increased risk for mortality.

Evaluating Independent Double Checks in the Pediatric Intensive Care Unit: A Human Factors Engineering Approach.

OBJECTIVES: The goal of this human factors engineering-led improvement initiative was to examine whether the independent double check (IDC) during administration of high alert medications afforded improved patient safety when compared with a single check process. METHODS: The initiative was completed at a 24-bed pediatric intensive care unit and included all patients who were on the unit and received a medication historically requiring an IDC. The total review examined 37,968 high-risk medications administrations to 4417 pediatric intensive care unit patients over a 40-month period. The following 5 measures were reviewed: (1) rates of reported medication administration events involving IDC medications; (2) hospital length of stay; (3) patient mortality; (4) nurses' favorability toward single checking; and (5) nursing time spent on administration of IDC medications. RESULTS: The rate of reported medication administration events involving IDC medications was not significantly different across the groups (95% confidence interval, 0.02%-0.08%; P = 0.4939). The intervention also did not significantly alter mortality ( P = 0.8784) or length of stay ( P = 0.4763) even after controlling for the patient demographic variables. Nursing favorability for single checking increased from 59% of nurses in favor during the double check phase, to 94% by the end of the single check phase. Each double check took an average of 9.7 minutes, and a single check took an average of 1.94 minutes. CONCLUSIONS: Our results suggest that performing independent double checks on high-risk medications administered in a pediatric ICU setting afforded no impact on reported medication events compared with single checking.

Linguistic isolation correlates with length of stay and mortality for pediatric oncology patients in California.

OBJECTIVE: To evaluate social drivers of health and how they impact pediatric oncology patients' clinical outcomes during pediatric intensive care unit (PICU) admission via correlation with patient ZIP codes. METHODS: Demographic, clinical, and outcome variables from Virtual Pediatric Systems®, LLC for oncology patients (2009-2021) in California PICUs (excluding postoperative) using 3-digit ZIP Codes with social drivers of health variables linguistic isolation, poverty, race/ethnicity, and education abstracted from American Community Survey data for 3-digit ZIP Codes using the Environmental Protection Agency's EJScreen tool. Outcomes of length of stay (LOS), mortality, acuity scores, were compared with social variables. RESULTS: Positive correlation between mortality and minority racial groups (Hispanic/Latino) across ZIP Codes (correlation coefficients of 0.45 (95% CI: 0.22-0.64, p < 0.001) in 2017, 0.50 (95% CI: 0.27-0.68, p < 0.001) in 2018, 0.33 (95% CI: 0.07-0.54, p = 0.013) in 2020, and 0.32 (95% CI: 0.06-0.53, p = 0.018) in 2021). Median PICU length of stay significantly correlated with linguistic isolation (coefficient of 0.42 (95% CI: 0.18-0.61, p = 0.001) in 2021 versus -0.41 (95% CI: -0.61 to -0.16, p = 0.002) in 2019), which included PRISMIII (n = 7417). Mixed effects logistic regression model for other constant variables (PRISMIII, cancer type, race/ethnicity, year), random effect of patient, linguistic isolation (percentage as a continuous value) was significantly associated (95% CI: 1.01-1.06; p = 0.02) with mortality; (OR = 1.03). CONCLUSIONS: Linguistic isolation was correlated with LOS and mortality, however variable year to year.

Daily Nutritional Intake of Pediatric Patients (N = 64) on Extracorporeal Membrane Oxygenation from 2018 to 2022: A Single-Center Report.

Nutrition in pediatric populations who require life-saving extracorporeal membrane oxygenation (ECMO) remains a debate. We sought to identify if nutritional needs were met in a patient cohort. A retrospective chart review of patients (N = 64) requiring ECMO at Helen DeVos Children's Hospital between 2018 and 2022 was evaluated for demographics, daily nutritional data, laboratory values, ECMO complications, and outcome data, with primary outcome measures of percent protein and percent caloric intake. Secondary outcome measures included the intensive care unit length of stay, time on ECMO, mortality, and day 1 severity of illness scores (Pediatric Logistic Organ Dysfunction). The timeline partially overlapped with the COVID-19 pandemic. Data were collected for 467 ECMO days with a median age of 2.6 months; 57.8% of patients were male and 65.6% were with one pre-existing comorbidity. Venoarterial (VA) ECMO was utilized in 84.4% of patients; the ECMO indication was cardiac in 53.1% of patients. The 28-day mortality was 43.8%. The proportion of days in which the caloric goal was met was 0%; the proportion of days in which protein goals were met was 33.3%. Non-cardiac ECMO patients had a greater number of days where caloric goals were met (p-value = 0.04). Mortality at 28 days was not statistically significant (p-value = 0.28) for calories or protein administered. The patient cohort struggled to meet calorie and protein goals while on ECMO.

Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted "Shotgun" Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period, a Single-Center Observational Study.

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.

Comparative Effectiveness of Intranasal Dexmedetomidine-Midazolam versus Oral Chloral Hydrate Targeting Moderate Sedation during Pediatric Transthoracic Echocardiograms.

Objective To compare efficacy and safety of two moderate sedation regimens for transthoracic echocardiography (TTE): intranasal dexmedetomidine-midazolam (DM) versus oral chloral hydrate (CH) syrup. Method This was a retrospective cohort of 93 children under 4 years of age receiving moderate sedation with either DM or CH for TTE from January 2011 through December 2014. Measurements and Main Results Forty-nine patients received oral CH and 44 received the intranasal combination of DM. The demographics between groups were similar except the DM patients were slightly older and heavier (each p < 0.05). Failure rate between groups did not reach statistical significance (CH 14.3% vs. DM 6.8%; p = 0.324). Total sedation to discharge time was similar between groups (CH 89.4 minutes vs. DM 89.6 minute; p = 0.97). Cardiopulmonary data did reveal a significantly lower heart rate (101.9 vs. 91.7; p < 0.001) and respiratory rate (23.4 vs. 21.0, p = 0.03) in the DM group, but no difference in blood pressure measurements or echo determined shortening fraction. Conclusion These data support the use of intranasal DM as a safe and efficacious method of moderate sedation for children undergoing TTE.

Influence of positive end-expiratory pressure ventilation on survival during severe hemorrhagic shock.

STUDY OBJECTIVE: Although a moderate positive end-expiratory pressure (PEEP) level is widely recommended, it is unknown whether moderate PEEP during mechanical ventilation has adverse effects during severe hemorrhagic shock. Therefore, the purpose of our study was to evaluate the effects of 0 cm H2O PEEP versus 5 cm H2O PEEP versus 10 cm H2O PEEP on short-term survival in a porcine model of severe hemorrhagic shock. Secondary study endpoints were hemodynamic variables and blood gases. METHODS: Twenty-four anesthetized pigs were bled approximately 45 mL/kg, randomized into 3 groups, and then ventilated with 0, 5, or 10 cm H2O PEEP. Survival rates were compared using Kaplan-Meier methods with log rank (Mantel Cox) comparison of cumulative survival by treatment group. RESULTS: Seven of 8 0 cm H2O PEEP animals survived the 120-minute study period, but 8 of 8 5 cm H2O PEEP animals died within 30 minutes, and 8 of 8 10 cm H2O PEEP animals were dead within 20 minutes (P<.0001). Ventilation with 0 cm H2O PEEP prevented a further reduction of mean arterial blood pressure and cardiac output. When compared with the 0 cm H2O PEEP group, end-tidal CO2 declined in the 5 cm H2O PEEP and 10 cm H2O PEEP animals. Compared with the 0 cm H2O PEEP animals, those ventilated with 5 or 10 cm H2O PEEP had higher lactate levels after 10 minutes. CONCLUSION: When compared with pigs ventilated with either 5 or 10 cm H2O PEEP, those ventilated with 0 cm H2O PEEP during untreated, severe hemorrhagic shock had significantly improved short-term survival.