High Frequency of Neuroimaging Abnormalities Among Pediatric Patients With Sepsis Who Undergo Neuroimaging.

OBJECTIVES: This study was intended to describe and correlate the neuroimaging findings in pediatric patients after sepsis. DESIGN: Retrospective chart review. SETTING: Single tertiary care PICU. PATIENTS: Patients admitted to Cincinnati Children's Hospital Medical Center with a discharge diagnosis of sepsis or septic shock between 2004 and 2013 were crossmatched with patients who underwent neuroimaging during the same time period. INTERVENTIONS: All neuroimaging studies that occurred during or subsequent to a septic event were reviewed, and all new imaging findings were recorded and classified. As many patients experienced multiple septic events and/or had multiple neuroimaging studies after sepsis, our statistical analysis utilized the most recent or "final" imaging study available for each patient so that only brain imaging findings that persisted were included. MEASUREMENTS AND MAIN RESULTS: A total of 389 children with sepsis and 1,705 concurrent or subsequent neuroimaging studies were included in the study. Median age at first septic event was 3.4 years (interquartile range, 0.7-11.5). Median time from first sepsis event to final neuroimaging was 157 days (interquartile range, 10-1,054). The most common indications for final imaging were follow-up (21%), altered mental status (18%), and fever/concern for infection (15%). Sixty-three percentage (n = 243) of final imaging studies demonstrated abnormal findings, the most common of which were volume loss (39%) and MRI signal and/or CT attenuation abnormalities (21%). On multivariable logistic regression, highest Pediatric Risk of Mortality score and presence of oncologic diagnosis/organ transplantation were independently associated with any abnormal final neuroimaging study findings (odds ratio, 1.032; p = 0.048 and odds ratio, 1.632; p = 0.041), although early timing of neuroimaging demonstrated a negative association (odds ratio, 0.606; p = 0.039). The most common abnormal finding of volume loss was independently associated with highest Pediatric Risk of Mortality score (odds ratio, 1.037; p = 0.016) and oncologic diagnosis/organ transplantation (odds ratio, 2.207; p = 0.001) and was negatively associated with early timing of neuroimaging (odds ratio, 0.575; p = 0.037). CONCLUSIONS: The majority of pediatric patients with sepsis and concurrent or subsequent neuroimaging have abnormal neuroimaging findings. The implications of this high incidence for long-term neurologic outcomes and follow-up require further exploration.

Matrix Metalloproteinase-8 Augments Bacterial Clearance in a Juvenile Sepsis Model.

Genetic ablation or pharmacologic inhibition of matrix metalloproteinase-8 (MMP8) improves survival in an adult murine sepsis model. Because developmental age influences the host inflammatory response, we hypothesized that developmental age influences the role of MMP8 in sepsis. First, we compared sepsis survival between wild type (WT, C57BL/6) and MMP8 null juvenile-aged mice (12-14 days) after intraperitoneal injection of a standardized cecal slurry. Second, peritoneal lavages collected at 6 and 18 hours after cecal slurry injection were analyzed for bacterial burden, leukocyte subsets, and inflammatory cytokines. Third, juvenile WT mice were pretreated with an MMP8 inhibitor prior to cecal slurry injection; analysis of their bacterial burden was compared to vehicle-injected animals. Fourth, the phagocytic capacity of WT and MMP8 null peritoneal macrophages was compared. Finally, peritoneal neutrophil extracellular traps (NETs) were compared using immunofluorescent imaging and quantitative image analysis. We found that juvenile MMP8 null mice had greater mortality and higher bacterial burden than WT mice. Leukocyte counts and cytokine concentrations in the peritoneal fluid were increased in the MMP8 null mice, relative to the wild type mice. Peritoneal macrophages from MMP8 null mice had reduced phagocytic capacity compared to WT macrophages. There was no quantitative difference in NET formation, but fewer bacteria were adherent to NETs from MMP8 null animals. In conclusion, in contrast to septic adult mice, genetic ablation of MMP8 increased mortality following bacterial peritonitis in juvenile mice. The increase in mortality in MMP8 null juvenile mice was associated with reduced bacterial clearance and reduced NET efficiency. We conclude that developmental age influences the role of MMP8 in sepsis.

Psychometric Testing of the Debriefing Assessment for Simulation in Healthcare (DASH) for Trainee-led, In Situ Simulations in the Pediatric Emergency Department Context.

OBJECTIVES: Effective trainee-led debriefing after critical events in the pediatric emergency department has potential to improve patient care, but debriefing assessments for this context have not been developed. This study gathers preliminary validity and reliability evidence for the Debriefing Assessment for Simulation in Healthcare (DASH) as an assessment of trainee-led post-critical event debriefing. METHODS: Eight fellows led teams in three simulated critical events, each followed by a video-recorded discussion of performance mimicking impromptu debriefings occurring after real clinical events. Three raters assessed the recorded debriefings using the DASH, and their feedback was collated. Data were analyzed using generalizability theory, Gwet's AC2, intraclass correlation coefficient (ICC), and coefficient alpha. Validity was examined using Messick's framework. RESULTS: The DASH instrument had relatively low traditional inter-rater reliability (Gwet's AC2 = 0.24, single-rater ICC range = 0.16-0.35), with 30% fellow, 19% rater, and 23% rater by fellow variance. DASH generalizability (G) coefficient was 0.72, confirming inadequate reliability for research purposes. Decision (D) study results suggest the DASH can attain a G coefficient of 0.8 with five or more raters. Coefficient alpha was 0.95 for the DASH. A total of 90 and 40% of items from Elements 1 and 4, respectively, were deemed "not applicable" or left blank. CONCLUSIONS: Our results suggest that the DASH does not have sufficient validity and reliability to rigorously assess debriefing in the post-critical event environment but may be amenable to modification. Further development of the tool will be needed for optimal use in this context.

General surgery versus specialty rotations: a new paradigm in surgery clerkships.

BACKGROUND: The most common 3rd-year surgery clerkship uses general surgery services while limiting the involvement of subspecialty services. A novel surgery clerkship in which students were assigned to either general surgery or subspecialty services for the entire clerkship was tried at a large Midwestern medical school. The purpose of this study was to investigate the outcomes of clerks from subspecialty services and compare them with clerks from general surgery services. METHODS: Outcome measures included scores on the National Board of Medical Examiners Surgery Content Examination, faculty evaluation scores, and residency match results. A multivariate analysis of covariance compared National Board of Medical Examiners test scores and faculty evaluation ratings across service groups. United States Medical Licensing Examination Step 1 scores served as a covariate. RESULTS: Results showed significant differences between groups on faculty evaluation scores (F = 28.03; P

No more pediatric code blues on the floor: evolution of pediatric rapid response teams and situational awareness plans.

Reducing or eliminating code blues that occur on the inpatient, noncritical care units of children's hospitals is a challenging yet achievable goal. The mechanism to accomplish this involves several levels of effort. The implementation of effective pediatric rapid response teams is a well identified part of the process. Rapid response teams can allow for appropriate clinical interventions for deteriorating patients and may ultimately result in a reduction in hospital-wide mortality as well as efficient transfer to the pediatric intensive care unit (PICU) when necessary. The timely deployment of rapid response teams is dependent upon the appropriate recognition of patients at risk for deterioration. This recognition can be optimized by relying on assessments as simple as utilization of parental intuition to those as complex as big data models which utilize multiple predictor variables extracted from the electronic medical record. Ultimately, the goal to proactively identify patients at risk of deterioration may allow for prevention of clinical decline via appropriate and timely interventions, and if unsuccessful at that level, may allow for improved outcomes via optimized resuscitation care in the PICU.

Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment.

Biomarkers have great potential to improve the diagnosis and treatment of sepsis. The available literature supports the potential utility of sTREM-1, IL-27, suPAR, neutrophil CD64, presepsin, cfDNA and miRNAs as novel diagnostic, prognostic and treatment response biomarkers. The future of sepsis biomarkers lies in extensive validation studies of such novel biomarkers across heterogeneous populations and exploration of their power in combination. Furthermore, the use of a companion diagnostics model may augment the ability of investigators to identify novel sepsis biomarkers and develop specific therapeutic strategies based on biomarker information.

Burden of childhood rotavirus disease on health systems in the United States.

BACKGROUND: To determine the burden of rotavirus disease before the introduction of rotavirus vaccines. METHODS: From February 2005 to June 2006, prospective rotavirus surveillance was conducted in Cincinnati, Ohio, and Durham, North Carolina. Children < 5 years of age presenting at hospitals and outpatient clinics with acute gastroenteritis (AGE) of < 72 hours duration were enrolled. Stool samples were first tested for rotavirus by EIA and the VP7 type was determined by RT-polymerase chain reaction for rotavirus-positive samples. Medical costs were obtained from billing or accounting data. RESULTS: A total of 1998 children were enrolled, with a mean age of 16.9 months. Among 1601 (80%) patients with a stool specimen, 44% were rotavirus positive. The rotavirus detection rate was 38% for patients admitted to hospital, 60% for patients requiring a short-stay hospital visit (< 24 hour hospitalization), 49% for emergency department visits, and 37% for outpatient visits. During the rotavirus season, rotavirus accounted for 56% of all AGE cases. Only 11% of rotavirus-positive children were assigned the rotavirus-specific ICD-9-CM code and this proportion varied considerably by clinical setting. The VP7 genotypes identified were G1, 79%; G2, 14%; G3, 5%; G9, 1%; and G12, 1%. For children hospitalized with rotavirus, the estimated median direct cost was $4565, the average length of stay was 1.9 days, and parents lost 3.4 days of work. For short-stay, emergency department, and outpatient visits, the estimated median costs were $3160, $867, and $75, respectively. CONCLUSIONS: Before the widespread use of rotavirus vaccines in the United States, rotavirus was prevalent among children treated in hospital-based and outpatient settings and was associated with a substantial proportion of pediatric medical visits for AGE.