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Extracorporeal membrane oxygenation (ECMO) is used to support patients with refractory cardiopulmonary failure. Given ECMO's increased use in adults and the fact that many ECMO patients are cared for by anesthesiologists, the Society of Cardiovascular Anesthesiologists ECMO working group created an expert consensus statement that is intended to help anesthesiologists manage adult ECMO patients who are cared for in the operating room. In the first part of this 2-part series, technical aspects of ECMO are discussed, and related expert consensus statements are provided. [ABSTRACT FROM AUTHOR]

Allergic diseases affect millions worldwide, with growing evidence of an increase in allergy occurrence over the past few decades. Current treatments for allergy include corticosteroids to reduce inflammation and allergen immunotherapy; however, some subjects experience treatment-resistant inflammation or adverse reactions to these treatments, and there are currently no approved therapeutics for the treatment of food allergy. There is a dire need for new therapeutic approaches for patients with poorly controlled atopic diseases and a need to improve the safety and effectiveness of allergen immunotherapy. Improved understanding of allergy through animal models and clinical trials has unveiled potential targets for new therapies, leading to the development of several biologics to treat allergic diseases. This review focuses on the mechanisms that contribute to allergy, with an emphasis on future targets for biologics for the treatment of food allergy. These biologics include immunotherapy with novel anti-IgE antibodies and analogs, small-molecule inhibitors of cell signaling, anti–type 2 cytokine mAbs, and T H 1-promoting adjuvants. [ABSTRACT FROM AUTHOR]

Malaria is one of the world?s most widespread parasitic diseases. The parasitic protozoans of the genus Plasmodium have developed resistance to several antimalarial drugs. Some patients are therefore infected by two or more strains with different levels of antimalarial drug sensitivity. We previously developed a model to estimate the drug concentration Math Eq that inhibits 50% of the growth of the parasite isolated from a patient infected with one strain. We propose here a new Two-Slopes model for patients infected by two strains. This model involves four parameters: the proportion of each strain and their IC50, and the sigmoidicity parameter. To estimate the parameters of this model, we have developed a new algorithm called PGBO (Population Genetics-Based Optimizer). It is based on the Metropolis-Hasting algorithm and is implemented in the statistical software R. We performed a simulation study and defined three evaluation criteria to evaluate its properties and compare it with three other algorithms (Gauss-Newton, Levenberg-Marquardt, and a simulated annealing). We also evaluated it using in vitro data and three ex vivo datasets from the French Malaria Reference Center. Our evaluation criteria in the simulation show that PGBO gives good estimates of the parameters even if the concentration design is poor. Moreover, our algorithm is less sensitive than Gauss-Newton algorithms to initial values. Although parameter estimation is good, interpretation of the results can be difficult if the proportion of the second strain is close to 0 or 1. For these reasons, this approach cannot yet be implemented routinely. [ABSTRACT FROM AUTHOR]

Interactions between exposure to ambient air pollutants and respiratory pathogens have been shown to modify respiratory immune responses. Emerging data suggest key roles for Toll-like receptor (TLR) and nucleotide-binding oligomerization domain–like receptor (NLR) signaling in pathogen-induced immune responses. Similarly, immune responses elicited by exposure to air pollutants are mediated by specific TLR- and NLR-dependent mechanisms. This review article will summarize current knowledge about how air pollutants modify TLR- and NLR-dependent signaling and host defense responses in the lung. [ABSTRACT FROM AUTHOR]

Policy makers have long considered how to best educate children for success. Thus, this research explored whether imaginative play serves as a positive context for developing executive functions (EF) and prosocial behaviors necessary for academic success. Specifically, we hypothesized that EF would explain links between imaginative play and prosocial behaviors. 284 preschool children and their teachers completed measures of imaginative play, EF, and prosocial behaviors. Structural Equation Modeling examined mediational links between these constructs. Imaginative play predicted both hot and cool EF, as well as prosocial behavior, even after controlling for age and vocabulary; furthermore, the relationship between imaginative play and prosocial behavior was fully mediated by hot EF. Results suggest that imaginative play may serve as a positive context for developing EF and prosocial behaviors. Curricula and teachers should consider encouraging imaginative play to facilitate the development of EF and prosocial behaviors. [ABSTRACT FROM AUTHOR]

We report the experience of a single surgeon who treated 20 patients, over a 9-year period, with acute complex instability of the elbow with hinged external fixation. Patients who presented greater than 6 months after the original injury were excluded. The mechanism of injury was typically a fall or a motor vehicle accident. Fixators were placed at a mean of 26 days (range, 0-66 days) after injury and initial management. Reconstruction of the collateral ligaments was not performed, but soft tissues were repaired en bloc to the humerus. All patients were available for follow-up at a mean of 2.1 years. Flexion-extension arcs averaged 93°, whereas pronation-supination arcs averaged 96°. Posttraumatic arthrosis was commonly seen at follow-up, with moderate or severe changes developing in 55% of patients. Arthrosis did not correlate with functional outcomes, however. Outcomes were measured by use of the Mayo Elbow Performance Index and the Hospital for Special Surgery Total Elbow Scoring System, with mean scores of 75 and 71 points, respectively. Although the severity of injury often precludes obtaining a high percentage of good and excellent results, the outcomes after treatment of acute complex elbow instability with hinged external fixation by use of the technique detailed in this series are comparable to those of similar series. [Copyright &y& Elsevier]

Purpose: To survey leaders in sports medicine who perform anterior cruciate ligament (ACL) reconstructions to determine the preferred management when ACL graft contamination occurs. Type of Study: Survey study of expert opinions and experiences on the management of ACL graft contamination. Methods: We mailed 337 surveys to directors of academic sports medicine programs and graduates from an accredited sports medicine fellowship. The survey questioned the incidence, treatment, and outcome of ACL graft contamination. Results: Twelve surveys were returned to sender; 196 surgeons responded from the remaining 325 surveys (60%). Forty-nine of 196 (25%) surgeons reported at least 1 contamination during their career. Of those 49, 43 surgeons (88%) had 1 contaminated graft, 5 (10%) had 2, and 1 had 4, for a total of 57 reported contaminated grafts. Of the surgeons who reported a contaminated graft, 22 (45%) performed between 40 and 100 ACL reconstructions annually, and 17 (35%) performed more than 100 ACL reconstructions annually. Forty-three of the 57 (75%) contaminated grafts were managed with cleansing of the graft and proceeding with reconstruction. Ten (18%) were managed by harvesting a different graft, and 4 (7%) were substituted with an allograft. No infections in any of the contaminated grafts were reported. Sixty-five of the 147 (43%) surgeons without graft contamination gave hypothetical management responses. Thirty-eight (58%) would cleanse the graft and proceed with the procedure, 22 (34%) would harvest a different graft, and 5 (8%) would use an allograft. Conclusions: Surgeons who perform a high volume of ACL reconstruction surgery most often choose graft cleansing as the preferred management for intraoperative ACL graft contamination. Level of Evidence: Level V, expert opinion. [Copyright &y& Elsevier]

When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell membranes or the lung lining fluid, generating chemically reactive oxysterols. The mechanism by which O3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and β (α-EpCh, β-EpCh) and Secosterol A and B (Seco A, SecoB), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O3 contained elevated levels of these oxysterol species. As expected, O3-derived oxysterols have a pro-inflammatory effect and increase NF-κB activity. Interestingly, expression of the cholesterol efflux pump ATP-binding cassette transporter 1 (ABCA1), which is regulated by activation of the liver X receptor (LXR), was suppressed in epithelial cells exposed to O3. Additionally, exposure of LXR knockout mice to O3 enhanced pro-inflammatory cytokine production in the lung, suggesting LXR inhibits O3-induced inflammation. Using alkynyl surrogates of O3-derived oxysterols, our data demonstrate adduction of LXR with Seco A. Similarly, supplementation of epithelial cells with alkynyl-tagged cholesterol followed by O3 exposure causes observable lipid-LXR adduct formation. Experiments using Seco A and the LXR agonist T0901317 (T09) showed reduced expression of ABCA1 as compared to stimulation with T09 alone, indicating that Seco A-LXR protein adduct formation inhibits LXR activation by traditional agonists. Overall, these data demonstrate that O3-derived oxysterols have pro-inflammatory functions and form lipid-protein adducts with LXR, thus leading to suppressed cholesterol regulatory gene expression and providing a biochemical mechanism mediating O3-derived formation of oxidized lipids in the airways and subsequent adverse health effects. [ABSTRACT FROM AUTHOR]

Background: The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective: This study compared influenza-induced activation of inflammasome and innate immune signaling in human bronchial epithelial cells from volunteers with and without asthma and investigated the role of caspase-1 in epithelial cell antiviral defense. Methods: Differentiated primary human bronchial epithelial cells from volunteers with and without asthma were infected with influenza A virus. An inflammasome-specific quantitative real-time polymerase chain reaction array was used to compare baseline and influenza-induced gene expression profiles. Cytokine secretion, innate immune gene expression, and viral replication were compared between human bronchial epithelial cells from volunteers with and without asthma. Immunofluorescence microscopy was used to evaluate caspase-1 and PYCARD colocalization. Tracheal epithelial cells from caspase-1–deficient or wild-type mice were infected with influenza and assessed for antiviral gene expression and viral replication. Results: Human bronchial epithelial cells from asthmatic volunteers had altered influenza-induced expression of inflammasome-related and innate immune signaling components, which correlated with enhanced production of IL-1β, IL-6, and TNF-α. Specifically, influenza-induced caspase-1 expression was enhanced and localization differed in human bronchial epithelial cells from asthmatic volunteers compared to volunteers without asthma. Influenza-infected tracheal epithelial cells from caspase-1–deficient mice had reduced expression of antiviral genes and viral replication. Conclusion: Caspase-1 plays an important role in the airway epithelial cell response to influenza infection, which is enhanced in asthmatic volunteers, and may contribute to the enhanced influenza-related pathogenesis observed in vivo. [Copyright &y& Elsevier]

Abstract: Influenza infection is a major cause of morbidity and mortality worldwide, especially during pandemics outbreaks. Emerging data indicate that phase II antioxidant enzyme pathways could play a role in virus-associated inflammation and immune clearance. While Nrf2-dependent gene expression is known to modify inflammation, a mechanistic role in viral susceptibility and clearance has yet to be elucidated. Therefore, we utilized differentiated human nasal epithelial cells (NEC) and an enzymatic virus-like particle entry assay, to examine the role Nrf2-dependent gene expression has on viral entry and replication. Herein, lentiviral vectors that express Nrf2-specific short hairpin (sh)-RNA effectively decreased both Nrf2 mRNA and Nrf2 protein expression in transduced human NEC from healthy volunteers. Nrf2 knockdown correlated with a significant increase in influenza virus entry and replication. Conversely, supplementation with the potent Nrf2 activators sulforaphane (SFN) and epigallocatechin gallate (EGCG) significantly decreased viral entry and replication. The suppressive effects of EGCG on viral replication were abolished in cells with knocked-down Nrf2 expression, suggesting a causal relationship between the EGCG-induced activation of Nrf2 and the ability to protect against viral infection. Interestingly, the induction of Nrf2 via nutritional supplements SFN and EGCG increased antiviral mediators/responses: RIG-I, IFN-β, and MxA at baseline in the absence of infection. Our data indicate that there is an inverse relationship between the levels of Nrf2 expression and the viral entry/replication. We also demonstrate that supplementation with Nrf2-activating antioxidants inhibits viral replication in human NEC, which may prove to be an attractive therapeutic intervention. Taken together, these data indicate potential mechanisms by which Nrf2-dependent gene expression regulates susceptibility to influenza in human epithelial cells. [Copyright &y& Elsevier]

Background While perioperative blood transfusion (BT) has been associated with adverse outcomes in multiple malignancies, the importance of BT timing has not been established. Objective The objective of this study was to evaluate whether intraoperative BT is associated with worse cancer outcomes in bladder cancer patients treated with radical cystectomy (RC). Design, setting, and participants Outcomes from two independent cohorts of consecutive patients with bladder cancer treated with RC were analyzed. Outcome measurements and statistical analysis Recurrence-free survival, cancer-specific survival (CSS), and overall survival were estimated and multivariate analyses were performed to evaluate the association of BT timing with cancer outcomes. Results and limitations In the primary cohort of 360 patients, 241 (67%) received perioperative BT, including 162 intraoperatively and 79 postoperatively. Five-year CSS was 44% among patients who received an intraoperative BT versus 64% for patients who received postoperative BT ( p = 0.0005). After multivariate analysis, intraoperative BT was associated with an increased risk of cancer mortality (hazard ratio [HR]: 1.93; p = 0.02), while receipt of postoperative BT was not ( p = 0.60). In the validation cohort of 1770 patients, 1100 (62%) received perioperative BT with a median postoperative follow-up of 11 yr (interquartile range: 8.0–15.7). Five-year RFS ( p < 0.001) and CSS ( p < 0.001) were significantly worse among patients who received an intraoperative BT. Intraoperative BT was independently associated with recurrence (HR: 1.45; p = 0.001), cancer-specific mortality (HR: 1.55; p = 0.0001), and all-cause mortality (HR: 1.40; p < 0.0001). Postoperative BT was not associated with risk of disease recurrence or cancer death. Conclusions Intraoperative BT is associated with increased risk of bladder cancer recurrence and mortality. Patient summary In this study, the effects of blood transfusion on bladder cancer surgery outcomes were evaluated. Intraoperative blood transfusion, but not postoperative transfusion, was associated with higher rates of recurrence and cancer-specific mortality. [ABSTRACT FROM AUTHOR]

Background context: Ketorolac Tromethamine (ketorolac) is a nonsteroidal anti-inflammatory drug (NSAID) with proven efficacy in decreasing postoperative pain in various surgical settings, including the treatment of spine deformities. However, some studies have raised questions regarding the potential side effects of this agent, such as increased bleeding and inhibition of bony fusion.Purpose: This study was conducted to determine whether there is any association between the use of ketorolac and postoperative complications in a group of children who underwent scoliosis surgery.Study design/setting: This is a retrospective review of a group of children who underwent spinal fusion between 1989 to 1999 at our institution.Patient sample: Data on a total of 208 children were analyzed in this study. Sixty received ketorolac and 148 did not.Outcome measures: Postoperative transfusion and reoperation rates were the two main outcome measures of interest.Methods: A retrospective review of 208 children who underwent scoliosis surgery was conducted, with a focus on ketorolac use. Univariate analysis and logistic regression were used to quantify the determinants of postoperative complications.Results: Our analyses detected no significant differences in a broad range of socioclinical variables between the two patient groups, including age at surgery, gender, type of scoliosis, surgical approach, use of erythropoietin, levels of curvature and degree of curvature. Analysis of complication rates focusing on postoperative transfusion and revision surgery showed that there were no significant differences between the two groups.Conclusions: In this retrospective study of 208 children undergoing spine surgery, postoperative use of ketorolac did not significantly increase complications, including transfusion and reoperation. [Copyright &y& Elsevier]