CD62L (L-selectin) shedding for assessment of perioperative immune sensitivity in patients undergoing cardiac surgery with cardiopulmonary bypass

OBJECTIVE: To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF)--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation. RESULTS: 25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p </= 0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p<0.001), plasma sCD62L (p </= 0.001). In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401). CONCLUSIONS: Monitoring granulocyte and monocyte sensitivity using the "CD62L shedding assay" in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF stimulus. Further long-term follow-up studies will address the predictive value of these observations for clinical purposes

Human antibodies targeting Zika virus NS1 provide protection against disease in a mouse model.

Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal antibodies (mAbs) from an infected patient that target the non-structural protein NS1. We show that while these antibodies are non-neutralizing, NS1-specific mAbs can engage FcγR without inducing antibody dependent enhancement (ADE) of infection in vitro. Moreover, we demonstrate that mAb AA12 has protective efficacy against lethal challenges of African and Asian lineage strains of Zika virus in Stat2-/- mice. Protection is Fc-dependent, as a mutated antibody unable to activate known Fc effector functions or complement is not protective in vivo. This study highlights the importance of the ZIKV NS1 protein as a potential vaccine antigen

A systematic review of the effects of residency training on patient outcomes

<p>Abstract</p> <p>Background</p> <p>Residents are vital to the clinical workforce of today and tomorrow. Although in training to become specialists, they also provide much of the daily patient care. Residency training aims to prepare residents to provide a high quality of care. It is essential to assess the patient outcome aspects of residency training, to evaluate the effect or impact of global investments made in training programs. Therefore, we conducted a systematic review to evaluate the effects of relevant aspects of residency training on patient outcomes.</p> <p>Methods</p> <p>The literature was searched from December 2004 to February 2011 using MEDLINE, Cochrane, Embase and the Education Resources Information Center databases with terms related to residency training and (post) graduate medical education and patient outcomes, including mortality, morbidity, complications, length of stay and patient satisfaction. Included studies evaluated the impact of residency training on patient outcomes.</p> <p>Results</p> <p>Ninety-seven articles were included from 182 full-text articles of the initial 2,001 hits. All studies were of average or good quality and the majority had an observational study design.Ninety-six studies provided insight into the effect of 'the level of experience of residents' on patient outcomes during residency training. Within these studies, the start of the academic year was not without risk (five out of 19 studies), but individual progression of residents (seven studies) as well as progression through residency training (nine out of 10 studies) had a positive effect on patient outcomes. Compared with faculty, residents' care resulted mostly in similar patient outcomes when dedicated supervision and additional operation time were arranged for (34 out of 43 studies). After new, modified or improved training programs, patient outcomes remained unchanged or improved (16 out of 17 studies). Only one study focused on physicians' prior training site when assessing the quality of patient care. In this study, training programs were ranked by complication rates of their graduates, thus linking patient outcomes back to where physicians were trained.</p> <p>Conclusions</p> <p>The majority of studies included in this systematic review drew attention to the fact that patient care appears safe and of equal quality when delivered by residents. A minority of results pointed to some negative patient outcomes from the involvement of residents. Adequate supervision, room for extra operation time, and evaluation of and attention to the individual competence of residents throughout residency training could positively serve patient outcomes. Limited evidence is available on the effect of residency training on later practice. Both qualitative and quantitative research designs are needed to clarify which aspects of residency training best prepare doctors to deliver high quality care.</p