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.     

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.     

Histological changes of muscle in a patient with pyruvate dehydrogenase deficiency

Histological changes of muscle from a 17-month-old boy with pyruvate dehydrogenase deficiency are presented. The patient had muscle hypotonia, mental retardation, seizures, lactic acidosis and hyperalaninemia. Deficient activity of the pyruvate dehydrogenase complex was found in his platelets (about 25% of normal) and of pyruvate dehydrogenase in his biopsied muscle (about 5% of normal). A muscle biopsy specimen showed an increased proportion of type IIC fibers (24%), fiber-type grouping and lipid droplet accumulation.     

Changes in thrombomodulin level in plasma of endotoxin-infused rabbits.

Changes in the plasma thrombomodulin (TM) level were examined in endotoxin-infused rabbits. The plasma TM level in normal rabbits was 143.8 +/- 8.4 ng/ml (n = 67) and the molecular weight of the major TM was about 55 kd. Endotoxin (lipopolysaccharide, LPS, E. Coli B8:0127) was intravenously infused. LPS infusion increased the plasma TM level dose-dependently between 0.2 mg/kg and 5 mg/kg. When 5 mg/kg LPS was infused, the plasma TM level started to increase immediately and was 2.3 times higher than the control value within 1 hr. The molecular weight of the major TM was about 75 kd. This rapid increase in TM occurred before the decrease in fibrinogen content and the prolongation of prothrombin time. To examine the effect of circulating leukocytes on the TM increase in endotoxin-infused rabbits, 5 mg/kg LPS was infused into rabbits with leukocytopenia induced by X-ray irradiation. The maximum plasma level of TM was significantly lower than in the untreated rabbits given LPS. These data suggest that the increase in plasma TM is caused by LPS-stimulated leukocyte's prior to hemostaseological changes. It is well known that endothelial cells can be injured by stimulated leukocytes, so this increase in plasma TM probably reflects the deterioration of endothelial cells. This deterioration decreases the ability of endothelial cells to inhibit thrombosis, which would, in turn, contribute to the development of disseminated intravascular coagulation in endotoxin-infused rabbits.     

Significance of intravascular ultrasound and exercise stress echocardiography in diagnosis of exercise-induced vasospastic angina at the site of moderate stenosis

Recently, exercise-induced spastic coronary artery occlusion at the site of moderate stenosis, which Prinzmetal’s angina or cardiac syndrome X does not cover, was reported. Multi-modality imaging is important for the diagnosis of coronary artery disease with a complex ischemic mechanism. However, the previous report did not include findings from intracoronary imaging at the site of moderate coronary stenosis. We report a case of exercise-induced vasospastic angina at the site of moderate stenosis, where multi-modality imaging, including exercise stress echocardiography and intravascular ultrasound, was utilized to make a definitive diagnosis and investigate underlying causes.     

Effect of target saliency on human smooth pursuit initiation: interocular transfer

Our previous study showed that the saliency of a target increases the gain of smooth pursuit initiation. In this study, we examined the interocular transfer of this effect in five humans. A square red frame surrounding the target was used as a cue to indicate the initial target position. In the cue condition, the responses were similar, irrespective of the eye to which the cue was presented, and were significantly larger than in the no-cue condition. The result suggests that central pathways that receive input from both eyes mediate the effect of saliency on smooth pursuit initiation.