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We retrospectively evaluated the effects of 6% hydroxyethyl starch (HES) 130/0.4 on postoperative blood loss and acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass grafting (OPCAB).Electronic medical records of 771 patients who underwent OPCAB in our hospital between July 2012 and July 2014 were reviewed, and 249 patients without intraoperative HES-exposure (group NoHES) were matched 1:N with intraoperative HES-exposed 413 patients (group HES) based on propensity score. The effects of intraoperative HES on postoperative cumulative blood loss within the first 24 hours, need for bleeding-related reoperation, and occurrence of postoperative AKI (determined by KDIGO and RIFLE criteria) were analyzed.In our propensity score matched cohort, there were no significant differences between groups for median postoperative 24 hours blood loss (525 mL in group HES vs. 540 mL in group NoHES, P = .203) or need for bleeding-related reoperation (OR, 2.44; 95% confidence interval [CI], 0.64-9.34, P = .19). However, postoperative AKI (assessed by 2 criteria) occurred more frequently in group HES than in group NoHES (by KDIGO criteria: 10.7% vs. 3.6%; OR 3.43 [95% CI, 1.67-7.04]; P < .001 and by RIFLE criteria: 9.6% vs. 2%; OR 3.32 [95% CI, 1.34-8.24]; P = .01). The median volume of infused HES per patient weight was 16 mL/kg in group HES.In the patients undergoing OPCAB, intraoperative 6% HES 130/0.4 did not increase postoperative bleeding. However, renal safety remains a concern. Intraoperative use of HES should be determined cautiously during OPCAB.

Background: Although anesthetic-induced inhibition of lipopolysaccharide (LPS)-induced lung injury has been recognized, the underlying mechanism is obscure. Some studies suggest that reactive oxygen species (ROS) by isoflurane play a crucial role for anesthetic-induced protective effects on the brain or the heart; however, it still remains controversial. In this study, we examined the role of isoflurane-derived ROS in isoflurane-induced inhibition of lung injury and nuclear factor κB (NFκB) activation in LPS-challenged rat lungs., Methods: Male Sprague-Dawley rats were subjected to inhalation of 1.0 minimum alveolar concentration of isoflurane for 60 minutes, and intratracheal LPS 0.1 mg was administered 60 minutes later. In some cases, ROS scavenger, 2-mercaptopropinyl glycine or N-acetylcysteine was given 30 minutes before isoflurane. ROS generation was measured by fluorometer before LPS challenge and 4 hours after. Isoflurane's preconditioning effect was assessed by histologic examination, protein content, neutrophil recruitment, and determination of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels in bronchoalveolar lavage fluid and lung tissue. Western blotting measured phosphorylation of inhibitory κB α (ser 32/36), NFκB p65, and inducible nitric oxide synthase (iNOS). TNF-α and IL-6 mRNA expression and immunofluorescence staining for iNOS were also assessed., Results: Isoflurane preconditioning reduced inflammatory lung injury and TNF-α, IL-1β, and IL-6 release in the lung. Isoflurane upregulated ROS generation before LPS but inhibited a ROS burst after LPS challenge. ROS scavenger administration before isoflurane abolished the isoflurane preconditioning effect as well as isoflurane-induced inhibition of phosphorylation of inhibitory κBα, NFκB p65, iNOS activation, and mRNA expression of TNF-α and IL-6 in acute LPS-challenged lungs., Conclusions: This study suggests a crucial role of upregulated ROS generation by isoflurane for modification of inflammatory pathways by isoflurane preconditioning in acute inflammation of the lung.

Background: Individuals with Type O blood have been reported to have a tendency toward reduced Factor VIII and von Willebrand Factor (vWF) levels. If this is true, patients with Type O blood might be vulnerable to coagulopathy during acute normovolemic hemodilution using hydroxyethyl starch (HES), both from hemodilution as well as HES-related coagulopathy., Methods: Thirty non-O and 15 type O ASA 1 or 2 patients scheduled for spinal surgery involving more than two spinal levels were enrolled for the study. After anesthesia induction, 30% of the estimated blood volume was removed, and the volume was simultaneously replaced with 6% HES (130/0.4). Coagulation profiles were measured before (T0) and 30 min after acute normovolemic hemodilution (T30)., Results: Factor VIII activity, vWF antigen levels (vWF:ag), and vWF ristocetin cofactor activity (vWF:RCof) were lower in the O group than in the non-O group before and after acute normovolemic hemodilution, and decreased below the normal range in the O group after acute normovolemic hemodilution. The decrease was beyond that expected from hemodilution alone. Maximum amplitude and coagulation index of the thromboelastogram decreased below the normal range in the O group after acute normovolemic hemodilution. The decrease in vWF:ag was related to the degree of blood loss, and was greater in patients in the O group., Conclusions: Patients with Type O blood may have increased coagulation compromise, and greater dilution of Factor VIII activity, vWF:ag, and vWF:RCof after acute normovolemic hemodilution with HES.

Anti-4-1BB (CD137) monoclonal antibody (mAb) has been reported to suppress immune responses and to have the potential for use as a therapeutic agent to block autoimmune diseases. Previously, the authors prepared an antagonistic anti-human 4-1BB (CD137) mAb, BBK2. Here the authors report the humanization of BBK2 using a phage display library. Four humanized single-chain Fv (scFv) fragments were selected from a combinatorial library expressing a phage-displayed humanized scFv. They were found to retain the epitope specificity of the original mAb and to have affinities higher than those of the original. Both the soluble and bound forms of the humanized scFv suppressed the proliferation of human peripheral blood mononuclear cells, similar to the original mAb. These results suggest that humanized anti-human 4-1BB scFvs can be used as a valuable reagent for clinical application.