Independent Risk Factors for Fast-Track Failure Using a Predefined Fast-Track Protocol in Preselected Cardiac Surgery Patients

ObjectisvesThe purpose of this study was to identify the independent risk factors for fast-track failure (FTF) in cardiac surgery patients.DesignA retrospective analysis.SettingA university-affiliated heart center.ParticipantsIn a 2-year period, 1,704 consecutive preselected patients undergoing elective cardiac surgery were treated according to the local fast-track protocol in the postanesthetic care unit (PACU), bypassing the intensive care unit (ICU).Measurements and ResultsIndependent risk factors for FTF in the univariate regression analysis were tested in a multivariate regression analysis. FTF was defined as any transfer of the preselected patient to the ICU. FTF was primary when the patient was transferred directly from the postanesthetic care unit to the ICU and secondary when the patient was transferred from the intermediate care unit or ward to the ICU. FTF rate was 11.6% for primary and 5.6% for secondary FTF. In the multivariate regression analysis, age>70 years, female sex, prolonged surgery, and prolonged cross-clamp time could be defined as independent risk factors for FTF.ConclusionsIn a preselected patient population, fast-track treatment could be done with a low FTF rate. Independent risk factors for FTF are age, female sex, prolonged surgery, and prolonged cross-clamp time

Real-time three-dimensional echocardiographic assessment of mitral valve: Is it really superior to 2D transesophageal echocardiography?

Aim of our study was to investigate the feasibility of use and possible additional value of real-time 3D transesophageal echocardiography (RT-3D-TEE) compared to conventional 2D-TEE in patients undergoing elective mitral valve repair. After ethical committee approval, patients were included in this prospective study. After induction of anesthesia, a comprehensive 2D-TEE examination was performed, followed with RT-3D-TEE. The intraoperative surgical finding was used as the gold standard for segmental analysis. Only such segments which were surgically corrected either by resection or insertion of artificial chords were judged pathologic. A total of 50 patients were included in this study; usable data were available from 42 of these patients . Based on the Carpentier classification, the pathology found was type I in 2 (5%) patients, type II in 39 (93%) patients and type IIIb in 1 (2%) patient. We found that 3D imaging of complex mitral disease involving multiple segments, when compared to 2D-TEE did not show any statistically significant difference.RT-3D-TEE did not show any major advantage when compared to conventional 2D-TEE for assessing mitral valve pathology, although further study in a larger population is required to establish the validity of this study

Carbohydrate-dependent B cell activation by fucose-binding bacterial lectins

International audienceBacterial lectins are typically multivalent and bind noncovalently to specific carbohydrates on host tissues to facilitate bacterial adhesion. Here, we analyzed the effects of two fucose-binding lectins, BambL from Burkholderia ambifaria and LecB from Pseudomonas aeruginosa, on specific signaling pathways in B cells. We found that these bacterial lectins induced B cell activation, which, in vitro, was dependent on the cell surface expression of the B cell antigen receptor (BCR) and its coreceptor CD19, as well as on spleen tyrosine kinase (Syk) activity. The resulting release of intracellular Ca 2+ was followed by an increase in the cell surface abundance of the activation marker CD8, increased cytokine secretion, and subsequent cell death, replicating all of the events that are observed in vitro upon canonical and antigen-mediated B cell activation. Moreover, injection of BambL in mice resulted in a substantial, BCR-independent loss of B cells in the bone marrow with simultaneous, transient enlargement of the spleen (splenomegaly), as well as an increase in the numbers of splenic B cells and myeloid cells. Together, these data suggest that bacterial lectins can initiate polyclonal activation of B cells through their sole capacity to bind to fucose

Predictive immunomonitoring - The COST ENTIRE initiative

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1)

Overexpression of the CXCR4 receptor is a hallmark of chronic lymphocytic leukemia (CLL) and is important for CLL cell survival, migration, and interaction with their protective microenvironment. In acute myelogenous leukemia (AML), PIM1 was shown to regulate the surface expression of the CXCR4 receptor. Here, we show that PIM (proviral integration site for Moloney murine leukemia virus) kinases 1-3 are overexpressed and that the CXCR4 receptor is hyperphosphorylated on Ser339 in CLL compared with normal lymphocytes. Furthermore, CXCR4 phosphorylation correlates with PIM1 protein expression and PIM1 transcript levels in CLL. PIM kinase inhibition with three different PIM kinase inhibitors induced apoptosis in CLL cells independent of the presence of protective stromal cells. In addition, PIM inhibition caused dephosphorylation of the CXCR4 receptor on Ser339, resulting in enhanced ligand-dependent CXCR4 internalization and reduced re-externalization after withdrawal of CXCL12. Furthermore, PIM inhibition in CLL cells blocked CXCR4 functions, such as migration toward CXCL12- or CXCL12-induced extracellular signal-regulated kinase (ERK) phosphorylation. In concordance, pretreatment of CLL cells with PIM kinase inhibitors strongly reduced homing of CLL cells toward the bone marrow and the spleen of Rag2(-/-)γc(-/-) mice in vivo. Interestingly, the knockdown of PIM kinases in CLL cells demonstrated diverging functions, with PIM1 regulating CXCR4 surface expression and PIM2 and PIM3 as important for the survival of CLL cells. Our results show that PIM kinase inhibitors are an effective therapeutic option for CLL, not only by impairing PIM2/3-mediated CLL cell survival, but also by blocking the PIM1/CXCR4-mediated interaction of CLL cells with their protective microenvironment