. PPAR␥ agonists inhibit TGF-␤ induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis.

Objective Children undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to additional inflammatory and immunogenic insults from blood transfusions. We hypothesize that washing red blood cells (RBC) and platelets transfused to these patients will reduce post-operative transfusion-related immune modulation and inflammation. Design Prospective randomized controlled clinical trial. Setting University hospital pediatric cardiac intensive care unit. Patients Children from birth to 17 years old undergoing cardiac surgery with CPB. Interventions Children were randomized to an unwashed or washed RBC and platelet transfusion protocol for their surgery and postoperative care. All blood was leukoreduced, irradiated, and ABO identical. Plasma was obtained for laboratory analysis: pre-op, immediately, six and 12 hours after CPB. Primary outcome was the 12-hour post-CPB interleukin (IL)-6: IL-10 ratio. Secondary measures were IL levels, C-reactive protein (CRP), and clinical outcomes. Measurements and main results 162 subjects were studied, 81 per group. 34 subjects (17 per group) did not receive any blood transfusions. Storage duration of blood products was similar between groups. Among transfused subjects, the 12-hour IL ratio was significantly lower in the washed group (3.8 v. 4.8; p=0.04) secondary to lower IL-6 levels (post-CPB: 65 v.100 pg/ml; p = 0.06; 6 hour: 89 v.152 pg/ml; p = 0.02; 12-hour: 84 v.122 pg/ml; p = 0.09). Post-operative CRP was lower in subjects receiving washed blood (38 v. 43 mg/L; p = 0.03). There was a numerical, but not statistically significant decrease in total blood product transfusions (203 v. 260) and mortality (2 v. 6 deaths) in the washed group compared to the unwashed group. Conclusions Washed blood transfusions in cardiac surgery reduced inflammatory biomarkers, number of transfusions, donor exposures, and were associated with a non-significant trend towards reduced mortality. A larger study powered to test for clinical outcomes is needed to determine whether these laboratory findings are clinically significant.

Infants undergoing cardiac operation can be managed with a conservative RBC transfusion strategy. Clinical indications should help guide the decision for RBC transfusion even in this uniquely vulnerable population. Larger multicenter trials are needed to confirm these results, and focus on the highest risk patients would be of great interest.

rs12252 was not associated with susceptibility to influenza-related critical illness in children or with critical illness severity. Our data also do not support it being a splice site.

Objective To evaluate whether transfusion of cell saver salvaged, stored at the bedside for up to 24 hours, would decrease the number of post-operative allogeneic RBC transfusions and donor exposures, and possibly improve clinical outcomes. Design Prospective, randomized, controlled, clinical trial. Setting Pediatric cardiac intensive care unit. Patients Infants <20kg (n = 106) presenting for cardiac surgery with cardiopulmonary bypass. Interventions Subjects were randomized to a cell saver transfusion group where cell saver blood was available for transfusion up to 24 hours post-collection, or to a control group. Cell saver subjects received cell saver blood for volume replacement and/or RBC transfusions. Control subjects received crystalloid or albumin for volume replacement and RBCs for anemia. Blood product transfusions, donor exposures, and clinical outcomes were compared between groups. Measurements and Main Results Children randomized to the cell saver group had significantly fewer RBC transfusions (cell saver: 0.19 ± 0.44 v. control: 0.75 ± 1.2; p = 0.003) and coagulant product transfusions in the first 48 hours post-op (cell saver: 0.09 ± 0.45 v. control: 0.62 ± 1.4; p = 0.013), and significantly fewer donor exposures (cell saver: 0.60 ± 1.4 v. control: 2.3 ± 4.8; p =0.019). This difference persisted over the first week post-op, but did not reach statistical significance (cell saver: 0.64 ± 1.24 v. control: 1.1 ± 1.4; p =0.07). There were no significant clinical outcome differences. Conclusion Cell saver blood can be safely stored at the bedside for immediate transfusion for 24 hours post-collection. Administration of cell saver blood significantly reduces the number of RBC and coagulant product transfusions and donor exposures in the immediate post-operative period. Reduction of blood product transfusions has the potential to reduce transfusion-associated complications and decrease post-operative morbidity. Larger studies are needed to determine whether this transfusion strategy will improve clinical outcomes.

Background Infants and children undergoing open heart surgery routinely require multiple red blood cell (RBC) transfusions. Children receiving greater numbers of RBC transfusions have increased post-operative complications and mortality. Longer RBC storage age is also associated with increased morbidity and mortality in critically ill children. Whether the association of increased transfusions and worse outcomes can be ameliorated by use of fresh RBCs in pediatric cardiac surgery for congenital heart disease is unknown. Methods 128 consecutively transfused children undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass who were participating in a randomized trial of washed v. standard RBC transfusions were evaluated for an association of RBC storage age and clinical outcomes. To avoid confounding with dose of transfusions and timing of infection versus timing of transfusion, a subgroup analysis of patients only transfused 1–2 units on the day of surgery was performed. Results Mortality was low (4.9%) with no association between RBC storage duration and survival. The post-operative infection rate was significantly higher in children receiving the oldest blood (25–38 days) compared to those receiving the freshest RBCs (7–15 days); (34% v. 7%; p = 0.004). Subgroup analysis of subjects receiving only 1–2 RBC transfusions on the day of surgery (n=74) also demonstrates a greater incidence of infections in subjects receiving the oldest RBC units [0 of 33 (0%) with 7–15 day storage, 1 of 21 (5%) with 16–24 day storage and 4 of 20 (20%) with 25–38 day storage; (p=0.01)]. In multivariate analysis, RBC storage age and corticosteroid administration were the only predictors of post-operative infection. Washing the oldest RBCs (>27 days) was associated with a higher infection rate and increased morbidity compared with unwashed RBCs. Discussion Longer RBC storage duration was associated with increased postoperative nosocomial infections. This association may be secondary in part, to the large doses of stored RBCs transfused, from single donor units. Washing the oldest RBCs was associated with increased morbidity, possibly from increased destruction of older, more fragile erythrocytes incurred by washing procedures. Additional studies examining the effect of RBC storage age on post-operative infection rate in pediatric cardiac surgery are warranted.

Influenza-MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases.

Behavioral issues are a frequent problem in the pediatric population. Often, these are evaluated and considered to be psychiatric in origin. We report on a pediatric patient who presented with severe behavioral disturbance and developed organic symptoms including hypoventilation and dysautonomia and who was ultimately diagnosed with ROHHADNET syndrome, a syndrome of rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation associated with a neuroendocrine tumor. Autopsy findings revealed novel findings of the syndrome, including hypothalamic encephalitis.