Blood gas analysis in management of flail chest injuries

Six cases of flail chest injury were studied for changes in blood gases and acid-base status before and during respiratory management. Metabolic acidosis and mild to severe hypoxemia were found in most patients with flail chest at the time of admission, and there was a relationship between manifestation of paradoxical respiration and hypercarbia. Serial blood gas determinations are extremely important in assessment of the adequacy of the therapy, particularly in management of flail chest with continuous IPPB therapy.     

Anesthetic management of hypothyroid patients for coronary artery bypass grafting

Six hypothyroid patients with ischemic heart disease underwent coronary artery bypass grafting (CABG). Three of them were in euthyroid state by preoperative thyroid supplementation. Although remaining three who had not received preoperative supplementation were in overt hypothyroid state at CABG, their intra- and postoperative courses were satisfactory without any complications. We, therefore, found no benefit from preoperative thyroid supplementation. Serum TSH levels in hypothyroid patients were suppressed for more than three days postoperatively despite concomitant low FT3 and FT4 concentrations. The inhibition of TSH secretion could have been produced by therapeutic dose of dopamine which had been infused from intraoperative through postoperative period. Postoperative thyroid replacement should be initiated as soon as possible in hypothyroid patients to counteract the low FT4 concentration that could be prolonged and aggravated by the infusion of dopamine.     

TLR4 stimulation and corticosteroid interactively induce osteonecrosis of the femoral head in rat

We previously reported that a toll‐like receptor 4 signaling contributes to the development of osteonecrosis of the femoral head. Also, oxidative stress is suggested to be one of the possible pathogenesis of osteonecrosis of the femoral head. A recent study showed that toll‐like receptor 4 signaling leads to oxidative stress. The aim of the present study was to evaluate whether toll‐like receptor 4 stimulation and subsequent corticosteroid treatment lead to the development of osteonecrosis of the femoral head in rat, and oxidative stress is associated with it. Male Wistar rats were randomly divided into four treatment groups: Saline + Saline, Saline + Methylprednisolone, Lipopolysaccharide + Saline, Lipopolysaccharide + Methylprednisolone. Osteonecrosis of the femoral head at 14 days after the treatment was observed in 1 of 10 Lipopolysaccharide + Saline, and 5 of 10 Lipopolysaccharide + Methylprednisolone treated rats. However, it was not observed at all in the Saline + Saline and Saline + Methylprednisolone treated groups. Glutathione peroxidase activity in the liver at 1 day after the treatment was significantly increased when treated with lipopolysaccharide. However, methylprednisolone treatment reduced the activity. On the other hand, glutathione peroxidase activity in the femur did not change in any intergroup. In conclusion, the present study showed that toll‐like receptor 4 stimulation by lipopolysaccharide administration strengthen incidence of corticosteroid‐induced osteonecrosis of the femoral head, however, concomitant oxidative stress via toll‐like receptor 4 signaling may not contribute to the development of osteonecrosis of the femoral head in rats. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:342–345, 2016.     

Unrelated-Donor Bone Marrow Transplantation with a Conditioning Regimen Including Fludarabine, Busulfan, and 4 Gy Total Body Irradiation

We investigated the feasibility of reduced-intensity conditioning with 4 Gy total body irradiation, fludarabine (30 mg/m2 for 6 days), and busulfan (4 mg/kg for 2 days) for bone marrow transplantation from a serologically HLA-matched unrelated donor. Seventeen adult patients (median age, 55 years; range, 27-67 years) with various hematologic malignancies (6 in remission, 11 not in remission) were treated. Successful engraftment was achieved in all patients at a median of day 18 (range, day 14-35) after transplantation, although subsequent secondary graft failure was observed in 2 patients. The cumulative incidence of acute graft-versus-host disease (GVHD) of grades II to IV at day 100 was 48%. With a median follow-up of 286 days (range, 56-687 days), the rates of 1-year overall survival, 100-day nonrelapse mortality, and 1-year nonrelapse mortality were 41%, 14%, and 46%, respectively. Eleven patients died, and the causes of death were relapse (n = 4), pulmonary complications (n = 4), acute GVHD (n = 2), and sepsis (n = 1). The remaining 6 patients (at transplantation, 2 were in remission, and 4 were not in remission) are currently still in remission. These results suggest that this regimen reduces the risk of graft failure, but further studies are needed to ameliorate transplantation-related toxicities, primarily GVHD and/or pulmonary complications.     

Risk factors and prediction of bleeding after gastric endoscopic submucosal dissection in patients on antithrombotic therapy: newly developed bleeding prediction application software,SAMURAI model

Bleeding after gastric endoscopic submucosal dissection (ESD) remains problematic, especially in patients receiving antithrombotic therapy. Therefore, this study aimed to identify the risk factors. In this retrospective study, patients (n = 1,207) who underwent gastric ESD while receiving antithrombotic therapy were enrolled at Osaka Medical and Pharmaceutical University Hospital and 18 other referral hospitals in Japan. Risks of post-ESD bleeding were calculated using multivariable logistic regression. The dataset was divided into a derivation cohort and a validation cohort. We created a prediction model using the derivation cohort. The accuracy of the model was evaluated using the validation cohort. Post-ESD bleeding occurred in 142 (11.8%) participants. Multivariable analysis yielded an odds ratio of 2.33 for aspirin, 4.90 for P2Y12 receptor antagonist, 1.79 for cilostazol, 0.95 for other antithrombotic agents, 6.53 for warfarin, 5.65 for dabigatran, 7.84 for apixaban, 10.45 for edoxaban, 6.02 for rivaroxaban, and 1.46 for heparin bridging. The created prediction model was called safe ESD management using the risk analysis of post-bleeding in patients with antithrombotic therapy (SAMURAI). This model had good predictability, with a C-statistic of 0.77. In conclusion, use of the SAMURAI model will allow proactive management of post-ESD bleeding risk in patients receiving antithrombotic therapy.     

Metabolic changes induced by TGF-β1 via reduced expression of phosphatidylserine decarboxylase during myofibroblast transition

Metabolic alteration is increasingly recognized as an important pathogenic process that underlies fibrosis across many organ types, and metabolically targeted therapies could become important strategies for reducing fibrosis. In present study, target enzymes that are involved in changes in phospholipid metabolism during fibroblast-to-myofibroblast transition induced by transforming growth factor beta 1 (TGF-β1) were examined. Different amounts of phospholipids were found in the 2 groups. In response to TGF-β1 stimulation, 17 lipids decreased and 17 increased. The latter included the phospholipids phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE). Furthermore, among the rate-limiting enzymes that regulate these phospholipids, phosphatidylserine decarboxylase (PISD), which controls conversion of PS to PE and is localized in mitochondria, decreased in response to TGF-β1. Knockdown of PISD alone without TGF-β1 stimulation increased expression of α-smooth muscle actin mRNA and production of total collagen. Taken together, these results indicate that PISD is involved in the mechanism of fibrogenesis by regulating phospholipid metabolism.     

Reduction in the magnitude of serum potassium elevation in combination therapy with esaxerenone (CS‐3150) and sodium–glucose cotransporter 2 inhibitor in patients with diabetic kidney disease: Subanalysis of two phase III studies

Aims/IntroductionWe evaluated the effect of co‐administration of esaxerenone and a sodium–glucose cotransporter 2 (SGLT2) inhibitor on the magnitude of serum potassium elevation in Japanese patients with diabetic kidney disease.Materials and MethodsWe carried out a prespecified subanalysis of data from two phase III studies: a multicenter, randomized, double‐blind, placebo‐controlled trial in patients with type 2 diabetes and microalbuminuria (J308); and a multicenter, single‐arm, open‐label trial in patients with type 2 diabetes and macroalbuminuria (J309). Changes in serum potassium levels during the studies and other measures were evaluated according to SGLT2 inhibitor use.ResultsIn both studies, time‐course changes in serum potassium levels, and incidence rates of serum potassium elevation were lower in patients with co‐administration of SGLT2 inhibitor in both the placebo and esaxerenone groups than those without the inhibitor. In contrast, time‐course changes and mean percentage changes from baseline in urinary albumin‐to‐creatinine ratio, the proportion of patients with albuminuria remission and time‐course changes in blood pressure did not change with or without SGLT2 inhibitor, whereas the albumin‐to‐creatinine ratio and blood pressure were reduced with esaxerenone. The blood glucose‐lowering effect of SGLT2 inhibitor was not affected by esaxerenone.ConclusionsIn Japanese patients with type 2 diabetes and albuminuria treated with esaxerenone, concomitant use of SGLT2 inhibitor reduced the magnitude of serum potassium elevation without any change of its antihypertensive and albuminuria‐suppressing effects. Co‐administration of esaxerenone and SGLT2 inhibitor might be a beneficial treatment option for patients with diabetic kidney disease.