The objectives of this consensus conference were to evaluate the evidence for the efficacy and safety of perioperative drugs, technologies, and techniques in reducing allogeneic blood transfusion for ...adults undergoing cardiac surgery and to develop evidence-based recommendations for comprehensive perioperative blood management in cardiac surgery, with emphasis on minimally invasive cardiac surgery.
The consensus panel short-listed the potential topics for review from a comprehensive list of potential drugs, devices, technologies, and techniques. The process of short-listing was based on the need to prioritize and focus on the areas of highest importance to surgeons, anesthesiologists, perfusionists, hematologists, and allied health care involved in the management of patients who undergo cardiac surgery whether through the conventional or minimally invasive approach. MEDLINE, Cochrane Library, and Embase databases were searched from their date of inception to May 2011, and supplemental hand searches were also performed. Detailed methodology and search strategies are outlined in each of the subsequently published systematic reviews. In general, all relevant synonyms for drugs (antifibrinolytic, aprotinin, Latin Small Letter Open E-aminocaproic acid, tranexamic acid TA, desmopressin, anticoagulants, heparin, antiplatelets, anti-Xa agents, adenosine diphosphate inhibitors, acetylsalicylic acid ASA, factor VIIa FVIIa), technologies (cell salvage, miniaturized cardiopulmonary bypass (CPB) circuits, biocompatible circuits, ultrafiltration), and techniques (transfusion thresholds, minimally invasive cardiac or aortic surgery) were searched and combined with terms for blood, red blood cells, fresh-frozen plasma, platelets, transfusion, and allogeneic exposure. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of each recommendation.
Database search identified more than 6900 articles, with 4423 full-text randomized controlled trials assessed for eligibility, and the final 125 systematic reviews and meta-analyses were used in the consensus conference. The results of the consensus conference, including the evidence-based statements and the recommendations, are outlined in the text, with references given for the relevant evidence that formed the basis for the statements and recommendations. RECOMMENDATIONS FOR ANTIFIBRINOLYTICS: The lysine analogs ?-aminocaproic acid (Amicar) and tranexamic acid (TA) reduce exposure to allogeneic blood inpatients undergoing on-pump cardiac surgery. These agents are recommended to be used routinely as part of a blood conservation strategy especially in patients at risk of undergoing onpump cardiac surgery (Class I, Level A). It is important not to exceed maximum TA total dosages (50Y100mg/kg) because of potential neurotoxicity in the elderly and open-heart procedures (Class IIb, Level C). Aprotinin is not recommended in adult cardiac surgery until further studies on its safety profile have been performed (Class III, Level A). RECOMMENDATIONS FOR TA IN OFF-PUMP CORONARY ARTERY BYPASS: Tranexamic acid may be recommended as part of a blood conservation strategy in high risk patients undergoing off-pump coronary artery bypass (OPCAB) surgery (Class I, Level A).Tranexamic acid dosing in OPCAB surgery needs further study particularly with regard to possible neurotoxicity such as seizures.In addition, the benefit-risk ratio in OPCAB needs further eludication because of the lower inherent risk for bleeding in this group (Class IIb, Level C). RECOMMENDATIONS FOR DDAVP: DDAVP can be considered for prophylaxis in coronary artery bypass grafting (CABG) surgery, in particular, for patients onASA within 7 days or prolonged CPB more than 140 minutes (Class IIa, Level A). Caution should be used with the DDAVP infusion rate to avoid significant systemic hypotension (Class I, Level A). RECOMMENDATIONS FOR TOPICAL HEMOSTATICS: The routine use of topical antifibrinolytics in cardiac surgery isnot recommended (Class IIa, Level A). Topical fibrin sealants may be considered in clinical situations where conventional approaches of surgical and medical improvement of hemostasis are not effective, that is, with bleeding problems more local than generalized, bearing in mind the blackbox warning of bovine thrombin by the US Food and Drug Administration (Class IIb, Level C).Recommendations for FVIIa:Prophylactic use of FVIIa cannot be recommended because of a significant increase in the risk of thromboembolic events and stroke (Class IIa, Level A).Factor VIIa may be considered in clinical situations where conventional approaches of surgical and pharmacologic hemostasis have failed and uncontrollable hemorrhage poses a high risk of severe and life-threatening outcomes (Class IIb, Level B). RECOMMENDATIONS FOR ERYTHROPOIETIN PLUS IRON: It is reasonable to administer erythropoietin preoperatively to increase red blood cell mass in patients who are anemic or refuse blood products (such as for Jehovah’s Witness faith) or who are likely to have postoperative anemia (Class IIa, Level A). RECOMMENDATIONS FOR ANTIPLATELETS BEFORE CARDIAC SURGERY: Acetylsalicylic acid may be continued until surgery (Class IIa,Level B) For stable elective CABG procedures with no drug-elutingstent, stop clopidogrel 5 days before surgery (Class I, Level A).h For stable elective CABG procedures with drug-eluting stents less than 1 year old, consider continuing clopidogrel or heparin as abridge to surgery (Class IIb, Level C).h Direct-acting P2Y12 receptor antagonists may be a better alternative than clopidogrel in acute coronary syndrome patients undergoing CABG surgery (Class IIa, Level B). RECOMMENDATIONS FOR ANTIPLATELETS AFTER CARDIAC SURGERY: In stable CABG surgery (nonYacute coronary syndrome patients), the routine use of postoperative clopidogrel with ASAis not warranted (Class IIb, Level B). RECOMMENDATIONS FOR ACUTE NORMOVOLEMIC HEMODILUTION: Acute normovolemic hemodilution can be considered in selected patients with adequate preoperative hemoglobin to reduce post-CPB bleeding (Class IIa, Level A).The routine use of acute normovolemic hemodilution is not recommended (Class IIb, Level B). RECOMMENDATIONS FOR RETROGRADE AUTOLOGOUS PRIMING: Retrograde autologous priming is recommended as a blood conservation modality to reduce allogeneic blood transfusion for onpump cardiac surgery (Class I, Level A). RECOMMENDATIONS FOR CELL SALVAGE: Routine use of cell salvage is recommended in operations where an increased blood loss is expected (Class 1, Level A). Cell salvage should be used throughout the entire operation and not merely as a replacement for CPB cardiotomy suction (Class IIa, Level A).
BIOCOMPATIBLE CPB CIRCUITS: The routine use of biocompatible coated CPB circuitry may be considered as part of a multimodal blood conservation program. However, the heterogeneity of surface-modified products, anticoagulation management, and CPB technique does not significantly impact surgical blood loss and transfusion needs (Class IIb,Level A). RECOMMENDATIONS FOR MINIATURIZED EXTRACORPOREAL CARDIOPULMONARY CIRCUIT VERSUS CONVENTIONAL EXTRACORPOREAL CARDIOPULMONARY CIRCUIT: Miniaturized extracorporeal cardiopulmonary circuit can be considered as a blood conservation technique to reduce allogeneic blood exposure (Class IIa, Level A); however, issues related to heparinization management and biocompatible coatings remain to be clarified. RECOMMENDATIONS FOR ULTRAFILTRATION (CONTINUOUS OR MODIFIED):h Ultrafiltration may be considered for blood conservation (Class IIb, Level A); however, the impact on clinically relevant outcomes remains unknown. RECOMMENDATIONS FOR PLATELET PLASMAPHERESIS:It is reasonable to recommend platelet plasmapheresis for blood management in cardiac surgery (Class IIa, Level A), although the impact on clinically relevant outcomes remains unknown. RECOMMENDATIONS FOR POINT-OF-CARE MONITORING:The evidence is too premature to recommend point-of-caretechnology for routine use because its use has not been shown to impact clinical outcome (Class IIb, Level A). RECOMMENDATIONS FOR SURGICAL TECHNIQUES FOR OPCAB, MINIMALLY INVASIVE STERNOTOMY FOR AORTIC VALVE SURGERY, MINIMALLY INVASIVE STERNOTOMY FOR MITRAL VALVE SURGERY, AND TRANSCATHETHER AORTIC VALVE IMPLANTATION: Although these minimally invasive procedures are not primarily selected for the purpose of blood management, the reduced allogeneic blood exposure should be considered in the balance of benefits and risks when selecting the appropriate surgery for patients.
The coding sequence of a major xylem sap protein of tomato was identified with the aid of mass spectrometry. The protein, XSP10, represents a novel family of extracellular plant proteins with ...structural similarity to plant lipid transfer proteins. The
XSP10 gene is constitutively expressed in roots and lower stems. The decline of XSP10 protein levels in tomato infected with a fungal vascular pathogen may reflect breakdown or modification by the pathogen.
Abstract Immunoglobulin-free light chains (IgLC) secreted by B lymphocytes, have been shown to mediate hypersensitivity by inducing antigen-specific mast cell activation. Although both mast cells and ...sensory neurons contribute to the hypersensitivity response, the role of IgLC in relation to sensory neurons is unknown. We therefore aimed to investigate the effects of IgLC on cultures of murine dorsal root ganglion (DRG) neurons. Immunohistochemistry demonstrated that IgLC and IgE could specifically bind to DRG neurons, on which the presence of FcεRI, the specific receptor for IgE, was demonstrated by western blotting. Further, optical recordings with Fluo-4 showed that application of the corresponding antigen to IgLC- or IgE-sensitized DRG neurons induces a sustained increase in intracellular Ca2+ in about half of these neurons. These results show that IgLC and IgE can mediate antigen-specific responses in murine neurons. Our findings present a novel way of antigen-specific neuronal activation.
Abstract This study examined quality of life (QOL) and illness perceptions in Dutch and Japanese patients with non-small-cell lung cancer, thereby extending the body of knowledge on cultural ...differences and psychosocial aspects of this illness. 24 Dutch and 22 Japanese patients with non-small-cell lung cancer filled out questionnaires on three occasions: immediately before chemotherapy, 1 week later, and 8 weeks after the initial chemotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) assessed QOL, and the Brief Illness Perception Questionnaire (B-IPQ) illness perceptions. Scores on several QOL measures indicated (a) major impact of first chemotherapy sessions, and (b) some tendency to returning to baseline measures at 8 weeks. Differences between Japanese and Dutch samples were found on five EORTC QLQ-C30 dimensions: global health status, emotional functioning, social functioning, constipation, and financial difficulties, with the Dutch patients reporting more favorable scores. Regarding illness perceptions, Japanese patients had higher means on perceived treatment control and personal control, expressing a higher sense of belief in the success of medical treatment than Dutch patients. In both Japanese and Dutch patients, impact of chemotherapy on QOL was evident. Some differences in illness perceptions and QOL between the two samples were observed, with implications for integral medical management. Both samples reported illness perceptions that reflect the major consequences of non-small-cell lung cancer. Incorporating symptom reports, illness perceptions, and QOL into medical management may have positive consequences for patients with non-small-cell lung cancer.
High factor VIII levels increase the risk of venous thromboembolism, but the mechanisms that cause high factor VIII levels are unclear. In 301 thrombosis patients and 301 matched healthy controls, ...factor VIII antigen (VIII:Ag) levels ≥ 150 IU/dl increased the thrombosis risk more than fivefold. We investigated whether high factor VIII:Ag levels result from a genetic variation in the factor VIII or von Willebrand factor (VWF) genes. Six polymorphisms in the VWF gene and two CA‐repeats in the factor VIII gene were not associated with plasma VWF levels, factor VIII:Ag levels, or thrombosis risk. Our data do not support the hypothesis that a single functional sequence variation in the factor VIII or VWF gene explains the majority of high factor VIII levels and thrombotic risk.
Mammalian phosphatidylinositol transfer protein α (PITP) is an intracellular lipid transporter with a binding site that can accommodate a single molecule of phosphatidylinositol (PI) or ...phosphatidylcholine (PC). Phospholipids are a heterogeneous population of molecular species that can be distinguished by their characteristic headgroups as well as their acyl chains at the
sn-1 and
sn-2 position. In this study, we have defined the acyl chain preference for PITPα when presented with a total population of cellular lipids. Recombinant PITPα loaded with bacterial lipid, phosphatidylglycerol (PG), was incubated with permeabilised HL60 cells, followed by recovery of PITPα by affinity chromatography. Lipids extracted from the PITPα were analysed by tandem electrospray ionisation mass spectrometry (ESI-MS) and showed total exchange of acquired bacterial lipids for HL60 cellular PI and PC. Detailed comparison of the molecular species composition of bound phospholipids with those in whole cells permitted the assessment of selectivity of acyl chain binding. For both phospholipid classes, progressive fractional enrichments in bound species possessing shorter acyl chains were apparent with a preference order: 16:1>16:0>18:1>18:0>20:4. A recapitulation of this specificity order was also seen from a dramatically altered range of molecular species present in HL60 cells enriched with arachidonate over many weeks of culture. We speculate that short-chain, saturate-binding preferences under both conditions may reflect properties in vivo. This is consistent with target cell membranes actively remodelling newly delivered phospholipids after transport rather than relying on the transport of the specific molecular species conventionally found in mammalian membranes.
Antibacterial activity of human natural killer cells GARCIA-PENARRUBIA, P; KOSTER, F. T; KELLEY, R. O ...
The Journal of experimental medicine,
1989, 1989-Jan-01, 1989-01-01, 19890101, Volume:
169, Issue:
1
Journal Article
Peer reviewed
Open access
The in vitro effects of human NK cells on viability of Gram-negative and Gram-positive bacteria was investigated. PBLs depleted of glass-adherent cells showed a significant antibacterial activity ...that was increased as the concentration of NK cells became higher. Leu-11-enriched cells exhibited the most efficient bactericidal activity. Stimulation of NK cells with staphylococcal enterotoxin B for 16 h produced a significant increase in the antibacterial activity of all NK cells tested. The antibacterial activity of monocyte-depleted cells and Leu-11-enriched cells was also enhanced after culturing in vitro for 16-24 h without exogenous cytokines. Dependence of the antibacterial activity on the presence of serum in the culture medium was not found. Ultrastructural studies revealed close contact between NK cell membranes and bacteria, no evidence of phagocytosis, and extracellular bacterial ghosts, after incubation at 37 degrees C. Supernatants from purified NK cells exhibited potent bactericidal activity with kinetics and target specificity similar to that of effector cells. These results document the potent antibacterial activity of purified NK cells and suggest an extracellular mechanism of killing.
We use microfluidic devices to encapsulate, incubate, and manipulate individual cells in picoliter aqueous drops in a carrier fluid at rates of up to several hundred Hz. We use a modular approach ...with individual devices for each function, thereby significantly increasing the robustness of our system and making it highly flexible and adaptable to a variety of cell-based assays. The small volumes of the drops enables the concentrations of secreted molecules to rapidly attain detectable levels. We show that single hybridoma cells in 33 pL drops secrete detectable concentrations of antibodies in only 6 h and remain fully viable. These devices hold the promise of developing microfluidic cell cytometers and cell sorters with much greater functionality, allowing assays to be performed on individual cells in their own microenvironment prior to analysis and sorting.
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