Balancing precision versus cohort transcriptomic analysis of acute and recovery phase of viral bronchiolitis.

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Patients with severe bronchiolitis had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand the totality of mechanisms of adverse outcomes in viral bronchiolitis.

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.

Cost and safety of pediatric intensive care physician-placed broviac catheters.

OBJECTIVE: To compare the cost and safety of placement of Broviac catheters in children by pediatric intensivists in a sedation suite versus placement by pediatric surgeons in the operating room. DESIGN: Single-center retrospective analysis. SETTING: Pediatric sedation suite and operating rooms in a tertiary care children's hospital. PATIENTS: All pediatric patients with Broviac catheters placed (n = 253) at this institution over a 3-year period from 2007 to 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed the charts of all pediatric patients with Broviac catheters placed, either by intensivists or surgeons, and compared cost and outcomes. Procedure safety was assessed and categorized into immediate, short-term (within 2 wk of procedure), and long-term outcomes. Anesthetic safety and billing data for the procedure were also collected. Among similar patient populations, immediate complications, such as pneumothorax, procedure failure (p > 0.999), and anesthetic complications (p = 0.60), were not significantly different. Short-term outcomes, including infection (p = 0.27) and catheter malfunction (p > 0.999), were not different. Long-term outcomes, including mean indwelling catheter days (p = 0.60) and removal due to catheter infection (p = 0.09), were not different between the groups. Overall cost of the procedure was significantly different: $7,031 (± $784) when performed by surgeons and $3,565 (± $311) when performed by intensivists (p < 0.001). CONCLUSIONS: Pediatric critical care physicians can place Broviac catheters as safely as pediatric surgeons and at a lower cost in a defined patient population.

Randomized controlled trial for intermittent versus continuous propofol sedation for pediatric brain and spine magnetic resonance imaging studies.

OBJECTIVES: Intermittent bolus propofol is an effective agent for pediatric magnetic resonance imaging sedation but requires constant vigilance and dose titration. Magnetic resonance imaging-compatible infusion pumps may make it possible to continuously infuse propofol, achieving a steady level of sedation at a lower total dose. This study investigates total propofol dose, recovery time, and magnetic resonance image quality in children receiving intermittent vs. continuously infused propofol sedation in children undergoing brain and spine magnetic resonance imaging studies. DESIGN: An open-label, prospective, randomized, controlled study. A single-blinded radiologist rated the quality of magnetic resonance images. SETTING: Children's hospital pediatric radiology sedation center. PATIENTS: One hundred seventy children age 1 month to 18 yrs undergoing deep sedation for brain, spine, or both brain and spine magnetic resonance imaging. INTERVENTIONS: After informed consent, patients were randomly assigned to two groups: group 1 (intermittent) received a propofol bolus of 2-4 mg/kg, followed by repeat boluses of 0.5-2 mg/kg/dose as needed. Group C (continuous) received a bolus of propofol 2-4 mg/kg, followed by a continuous infusion of 100 µg/kg/min with 1-mg/kg/dose boluses with drip titration to effect. MEASUREMENTS AND MAIN RESULTS: Patient demographics, sedation risk assessment, propofol dose, sedation recovery times, incidence of complications, and quality of the magnetic resonance imaging studies were measured. A total of 170 children were enrolled in the study, with 75 in group C and 95 in group I. Both groups were similar with regard to age, weight, gender, and magnetic resonance imaging study type. Group C required a lesser dose of propofol (132 ± 54 µg/kg/min) compared to (162 ± 74 µg/kg/min) in that required in group I (p = .018). There were no differences between the two groups with regard to quality of the imaging study, recovery time, or incidence of complications. CONCLUSIONS: Compared to intermittent bolus dosing, continuous propofol infusion provides lesser dose exposure without impacting recovery time or quality of the magnetic resonance imaging study.

Risk factors associated with pediatric intensive care unit admission and mortality after pediatric stem cell transplant: possible role of renal involvement.

BACKGROUND: Hematopoietic stem-cell transplant (HSCT) is associated with many risk factors for life-threatening complications. Post-transplant critical illness often requires admission to the pediatric intensive care unit (PICU). METHODS: A retrospective analysis was made on the risk factors associated with PICU admission and mortality of all HSCT patients at Helen DeVos Children's Hospital from October 1998 to November 2008. RESULTS: One hundred and twenty-four patients underwent HSCT, with 19 (15.3%) requiring 29 PICU admissions. Fifty patients received autologous, 38 matched sibling, and 36 matched un-related donor HSCT, with 10%, 13% and 25% of these patients requiring PICU admission, respectively (P=0.01). Among the HSCT patients, those who were admitted to the PICU were more likely to have renal involvement by either malignancy requiring nephrectomy or a post transplant complication increasing the likelihood of decreased renal function (21.1% vs. 4.8%, P=0.03). PICU admissions were also more likely to receive pre-transplant total body irradiation (52.6% vs. 27.6%, P=0.03). Among 29 patients with PICU admission, 3 died on day 1 after admission, and 5 within 30 days (a mortality rate of 17%). Thirty days after PICU admission, non-survivors had a higher incidence of respiratory failure and septic shock on admission compared with survivors (80% vs. 16.7%, P=0.01 and 80% vs. 4.2%, respectively, P=0.001). Two survivors with chronic renal failure underwent renal transplantation successfully. CONCLUSIONS: Total body irradiation and renal involvement are associated with higher risk for PICU admissions after HSCT in pediatric patients, while septic shock upon admission and post-admission respiratory failure are associated with mortality.

Zero balance ultrafiltration (Z-BUF) in blood-primed CRRT circuits achieves electrolyte and acid-base homeostasis prior to patient connection.

Infants requiring CRRT present a unique challenge due to the large circuit volume to blood volume ratio. Blood priming is often used, but some patients can become unstable during the initiation of CRRT due to electrolyte and acid-base imbalance. We postulated that using Z-BUF we could normalize electrolytes and improve the acid base status of the prime prior to patient connection. To test this we set up a circuit using the Baxter BM-25 CRRT pump, a polysulfone or AN-69 membrane, and a three-way stopcock. The circuit was primed with a 60/40 mix of expired autologous donor pRBCs and 5% albumin. The modalities of CVVH, CVVHD, and CVVHDF were compared for relative efficacy. Electrolytes, lactate, pH, cytokines (TNF-alpha, IL-1beta, bradykinin, and IL-6) were measured. Plasma hemoglobin levels were also measured before and after the Z-BUF procedure. Bradykinin production and elimination in AN-69 membrane circuits were assessed. All lab values equilibrated by 35 minutes. All CRRT modalities were equally efficacious for Z-BUF. Cytokine production or significant hemolysis was not found. In addition, no bradykinin accumulation occurred in AN-69 membrane-containing circuits. We conclude that Z-BUF is a simple and effective way to normalize electrolyte and acid-base status in the CRRT circuit when blood priming is required.

Survival and functional outcome in pediatric traumatic brain injury: a retrospective review and analysis of predictive factors.

OBJECTIVE: The aim of this study was to evaluate the relationship of patient care variables to survival and functional outcome in the pediatric population with traumatic brain injury. DESIGN: Retrospective chart review. SETTING: A 16-bed pediatric critical care unit in an academic community children's hospital. PATIENTS: A total of 320 consecutive pediatric patients with traumatic brain injuries admitted to our pediatric critical care unit between 1992 and 1996. INTERVENTIONS: Patients were managed using our standard traumatic brain injury protocol. MEASUREMENTS AND MAIN RESULTS: A total of 230 patient variables encompassing demographic data, prehospital, emergency department, and pediatric critical care unit care were recorded. A total of 79 patients were severely injured, with admitting Glasgow Coma Scale scores of < or =10. There were 18 deaths. Only two patients survived without cognition. Ninety-five of 302 survivors required inpatient rehabilitation. Of these, 73 were old enough to be compared using FIMTM scores. At the time of discharge from rehabilitation, 52 patients (71%) were functioning independently, 20 (27%) were moderately dependent, and one patient was completely dependent. Analysis of variables with respect to survival revealed that an inability to maintain a cerebral perfusion pressure of > or =50 mm Hg on the first pediatric critical care unit day (p =.0002) and the presence of bradycardia in the emergency department (p =.0139) were the strongest factors associated with mortality. By using the regression equation generated from this model, we could correctly identify survivors and nonsurvivors with a predictive value of 94%. CONCLUSIONS: The ability to maintain a cerebral perfusion pressure of > or =50 mm Hg was the single most important predictor of traumatic brain injury survival in this study. This suggests that monitoring and optimizing cerebral perfusion pressure is critical to the management of these patients. The relationship between cognitive outcome and therapeutic interventions used to optimize cerebral perfusion pressure is unclear and requires further evaluation in a large prospective study.