Modification and Assessment of the Bedside Pediatric Early Warning Score in the Pediatric Allogeneic Hematopoietic Cell Transplant Population

OBJECTIVES: To determine the validity of the Bedside Pediatric Early Warning Score system in the hematopoietic cell transplant population, and to determine if the addition of weight gain further strengthens the association with need for PICU admission. DESIGN: Retrospective cohort study of pediatric allogeneic hematopoietic cell transplant patients from 2009 to 2016. Daily Pediatric Early Warning Score and weights were collected during hospitalization. Logistic regression was used to identify associations between maximum Pediatric Early Warning Score or Pediatric Early Warning Score plus weight gain and the need for PICU intervention. The primary outcome was need for PICU intervention; secondary outcomes included mortality and intubation. SETTING: A large quaternary free-standing children's hospital. PATIENTS: One-hundred two pediatric allogeneic hematopoietic cell transplant recipients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 102 hematopoietic cell transplant patients included in the study, 29 were admitted to the PICU. The median peak Pediatric Early Warning Score was 11 (interquartile range, 8-13) in the PICU admission cohort, compared with 4 (interquartile range, 3-5) in the cohort without a PICU admission (p < 0.0001). Pediatric Early Warning Score greater than or equal to 8 had a sensitivity of 76% and a specificity of 90%. The area under the receiver operating characteristics curve was 0.83. There was a high negative predictive value at this Pediatric Early Warning Score of 90%. When Pediatric Early Warning Score greater than or equal to 8 and weight gain greater than or equal to 7% were compared together, the area under the receiver operating characteristic curve increased to 0.88. CONCLUSIONS: In this study, a Pediatric Early Warning Score greater than or equal to 8 was associated with PICU admission, having a moderately high sensitivity and high specificity. This study adds to literature supporting Pediatric Early Warning Score monitoring for hematopoietic cell transplant patients. Combining weight gain with Pediatric Early Warning Score improved the discriminative ability of the model to predict the need for critical care, suggesting that incorporation of weight gain into Pediatric Early Warning Score may be beneficial for monitoring of hematopoietic cell transplant patients

Normal Ribosomal Biogenesis but Shortened Protein Synthetic Response to Acute Eccentric Resistance Exercise in Old Skeletal Muscle.

Anabolic resistance to feeding in aged muscle is well-characterized; however, whether old skeletal muscle is intrinsically resistant to acute mechanical loading is less clear. The aim of this study was to determine the impact of aging on muscle protein synthesis (MPS), ribosome biogenesis, and protein breakdown in skeletal muscle following a single bout of resistance exercise. Adult male F344/BN rats aged 10 (Adult) and 30 (Old) months underwent unilateral maximal eccentric contractions of the hindlimb. Precursor rRNA increased early post-exercise (6-18 h), preceding elevations in ribosomal mass at 48 h in Adult and Old; there were no age-related differences in these responses. MPS increased early post-exercise in both Adult and Old; however, at 48 h of recovery, MPS returned to baseline in Old but not Adult. This abbreviated protein synthesis response in Old was associated with decreased levels of IRS1 protein and increased BiP, CHOP and eIF2α levels. Other than these responses, anabolic signaling was similar in Adult and Old muscle in the acute recovery phase. Basal proteasome activity was lower in Old, and resistance exercise did not increase the activity of either the ATP-dependent or independent proteasome, or autophagy (Cathepsin L activity) in either Adult or Old muscle. We conclude that MPS and ribosome biogenesis in response to maximal resistance exercise in old skeletal muscle are initially intact; however, the MPS response is abbreviated in Old, which may be the result of ER stress and/or blunted exercise-induced potentiation of the MPS response to feeding

Developing the DELTA: Capturing cultural changes in undergraduate departments

Departments are now recognized as an important locus for sustainable change on university campuses. Making sustainable changes typically requires a shift in culture, but culture is complex and difficult to measure. For this reason, cultural changes are often studied using qualitative methods that provide rich, detailed data. However, this imposes barriers to measuring culture and studying change at scale (i.e., across many departments). To address this issue, we introduce the Departmental Education and Leadership Transformation Assessment (DELTA), a new survey aimed at capturing cultural changes in undergraduate departments. We describe the survey’s development and validation and provide sugges-tions for its utility for researchers and practitioners

Transfusion Rates in Emergency General Surgery: High but Modifiable

Background: Transfusion of red blood cells (RBC) increases morbidity and mortality, and emergency general surgery (EGS) cases have increased risk for transfusion and complication given case complexity and patient acuity. Transfusion reduction strategies and blood-conservation technology have been developed to decrease transfusions. This study explores whether transfusion rates in EGS have decreased as these new strategies have been implemented. Methods: This is a retrospective review of the American College of Surgeons\u27 National Surgical Quality Improvement Program (ACS NSQIP) data from three academic medical centers. Operations performed by general surgeons on adults (aged ≥18 years) were selected. Data were analyzed from two periods: 2011-2013 and 2014-2016. Cases were grouped by the first four digits of the primary procedure Current Procedural Terminology code. Transfusion was defined as any RBC transfusion during or within 72 hours following the operation. Composite morbidity was defined as any NSQIP complication within 30 days following the operation. Results: Overall general surgery transfusion rates decreased from 6.4% to 4.8% from period 1 to period 2 (emergent: 16.6%–11.5%; non-emergent 4.9%–3.7%; Fisher’s exact p values \u3c 0.001). Among patients transfused, the number of units received decreased slightly (median 2 U (IQR 2–3) to median 2 U (IQR 1–3), Mann-Whitney U test p = 0.005). Morbidity decreased (overall: 13.8%–12.3%, p = 0.001; emergent: 26.3%–20.6%, p \u3c 0.001) while mortality did not change. Discussion: Rates of RBC transfusion decreased in both emergent and non-emergent cases. Efforts to reduce transfusion may have been successful in the EGS population. Morbidity improved over the time periods while mortality was unchanged. Level of Evidence: Level III

Randomized Trial of Tenecteplase or Placebo with Low Molecular Weight Heparin for Acute Submassive Pulmonary Embolism: Assessment of Patient-Oriented Cardiopulmonary Outcomes at Three Months

Background: Acute submassive pulmonary embolism (PE) with right ventricular (RV) injury and/or concomitant deep venous thrombosis can cause persistent symptoms that degrade quality of life. We tested the hypothesis that intravenous tenecteplase would improve the probability of a favorable outcome at three months after submassive PE. Methods: Multicenter randomized double-blind, placebo controlled trial. Eligible patients were ambulatory at baseline, had image-proven acute PE, a systolic blood pressure > 90 mm Hg and RV dysfunction (abnormal echocardiography, troponin or brain natriuretic peptide). Patients received anticoagulation with low molecular weight heparin (LMWH) and either tiered-dose tenecteplase or saline in an opaque syringe. Composite favorable outcome: 5 day survival to hospital discharge without shock, intubation, or major hemorrhage (any intracranial bleed or need for surgical or medical intervention for acute anemia), and at 90 days, normal RV on resting echocardiography, 6 minute walk distance>330 m, no dyspnea at rest, and no recurrent PE or DVT. Self-perception of wellness was assessed by the SF-16, VEINES-QOL and rank on 1-10 ordinal scale. Results: 83 patients were enrolled, including 33 women, 52 Caucasians, mean age 55+/-14 years, 43 received placebo, 40 received tenecteplase, and 38 had concomittant DVT. A favorable composite outcome occurred in 17/43(40%, 95% CI: 25-56%) treated with placebo, versus 26/40 (65%, 95% CI: 48-79%) treated with tenecteplase, p=0.02 Fisher’s exact. Acute deterioration occurred in 3 patients treated with placebo: fatal PE (1), intubation (1), thrombectomy (1) and in one patient treated with tenecteplase who had a fatal intracranial hemorrhage. At three months, a nonfavorable outcome was found in 23 additional patients treated with placebo, versus 13 patients treated with tenecteplase. Assessments of wellness were consistently higher in the tenecteplase group (e.g., p=0.03 for ordinal scale rank). Conclusions: In this randomized trial, patients with submassive PE treated with LMWH and tenecteplase were more likely to have a favorable patient-oriented outcome at three months than patients treated with LMWH and saline placebo

Infant behavioral reactivity predicts change in amygdala volume 12 years later

The current study examined the link between temperamental reactivity in infancy and amygdala development in middle childhood. A sample (n = 291) of four-month-old infants was assessed for infant temperament, and two groups were identified: those exhibiting negative reactivity (n = 116) and those exhibiting positive reactivity (n = 106). At 10 and 12 years of age structural imaging was completed on a subset of these participants (n = 75). Results indicate that, between 10 and 12 years of age, left amygdala volume increased more slowly in those with negative compared to positive reactive temperament. These results provide novel evidence linking early temperament to distinct patterns of brain development over middle childhood

Phagocytes produce prostaglandin E2 in response to cytosolic Listeria monocytogenes

Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L. monocytogenes drives robust CD8+ T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, as strains of L. monocytogenes that are unable to access the cytosol fail to elicit robust CD8+ T-cell responses and in fact inhibit optimal T-cell priming. Counterintuitively, however, activation of known cytosolic pathways, such as the inflammasome and type I IFN, lead to impaired immunity. Conversely, production of prostaglandin E2 (PGE2) downstream of cyclooxygenase-2 (COX-2) is essential for optimal L. monocytogenes T-cell priming. Here, we demonstrate that vacuole-constrained L. monocytogenes elicit reduced PGE2 production compared to wild-type strains in macrophages and dendritic cells ex vivo. In vivo, infection with wild-type L. monocytogenes leads to 10-fold increases in PGE2 production early during infection whereas vacuole-constrained strains fail to induce PGE2 over mock-immunized controls. Mice deficient in COX-2 specifically in Lyz2+ or CD11c+ cells produce less PGE2, suggesting these cell subsets contribute to PGE2 levels in vivo, while depletion of phagocytes with clodronate abolishes PGE2 production completely. Taken together, this work demonstrates that optimal PGE2 production by phagocytes depends on L. monocytogenes access to the cytosol, suggesting that one reason cytosolic access is required to prime CD8+ T-cell responses may be to facilitate production of PGE2

c-di-GMP modulates type IV MSHA pilus retraction and surface attachment in Vibrio cholerae.

Biofilm formation by Vibrio cholerae facilitates environmental persistence, and hyperinfectivity within the host. Biofilm formation is regulated by 3',5'-cyclic diguanylate (c-di-GMP) and requires production of the type IV mannose-sensitive hemagglutinin (MSHA) pilus. Here, we show that the MSHA pilus is a dynamic extendable and retractable system, and its activity is directly controlled by c-di-GMP. The interaction between c-di-GMP and the ATPase MshE promotes pilus extension, whereas low levels of c-di-GMP correlate with enhanced retraction. Loss of retraction facilitated by the ATPase PilT increases near-surface roaming motility, and impairs initial surface attachment. However, prolonged retraction upon surface attachment results in reduced MSHA-mediated surface anchoring and increased levels of detachment. Our results indicate that c-di-GMP directly controls MshE activity, thus regulating MSHA pilus extension and retraction dynamics, and modulating V. cholerae surface attachment and colonization

Exploring youth and caregiver preferences for asthma education video content

This study examines: 1) whether youth and their caregivers have different preferences for asthma education video topics and 2) if education topic preferences vary by youth and caregiver sociodemographic characteristics