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Background: Vonoprazan, potassium-competitive acid blocker, is expected to reduce incidence of delayed bleeding after gastric endoscopic submucosal dissection (ESD); however, preliminary data to design a large-scale comparative study are lacking. This study aimed to assess the efficacy of vonoprazan in preventing delayed bleeding after gastric ESD., Methods: In this single-center randomized phase II trial, a modified screened selection design was used with a threshold non-bleeding rate of 89% and an expected rate of 97%. In this design, Simon's optimal two-stage design was first applied for each parallel group, and efficacy was evaluated in comparison with the threshold rate using binomial testing. Patients were randomly assigned in a 1:1 ratio to receive either vonoprazan 20 mg (VPZ group) or lansoprazole 30 mg (PPI group) for 8 weeks from the day before gastric ESD. The primary endpoint was the incidence of delayed bleeding, defined as endoscopically confirmed bleeding accompanied by hematemesis, melena, or a decrease in hemoglobin of ≥ 2 g/dl., Results: Delayed bleeding occurred in three of 69 patients (4.3%, 95% CI 0.9-12.2%, p = 0.047) in the VPZ group, and four of 70 (5.7%, 95% CI 1.6-14.0%, p = 0.104) in the PPI group. As only vonoprazan showed significant reduction in delayed bleeding compared with the threshold rate, it was determined to be efficacious treatment., Conclusions: Vonoprazan efficaciously reduced the delayed bleeding rate in patients with an ESD-induced gastric ulcer. A large-scale, randomized, phase III study is warranted to definitively test the effectiveness of vonoprazan compared with proton pump inhibitors.

Background and Aims: We performed a prospective multi-national study of patients presenting to the emergency department with upper GI bleeding (UGIB) and assessed the relationship of time to presentation after onset of UGIB symptoms with patient characteristics and outcomes., Methods: Consecutive patients presenting with overt UGIB (red-blood emesis, coffee-ground emesis, and/or melena) from March 2014 to March 2015 at 6 hospitals were included. Multiple predefined patient characteristics and outcomes were collected. Rapid presentation was defined as ≤6 hours., Results: Among 2944 patients, 1068 (36%) presented within 6 hours and 576 (20%) beyond 48 hours. Significant independent factors associated with presentation ≤6 hours versus >6 hours on logistic regression included melena (odds ratio [OR], 0.22; 95% CI, 0.18-0.28), hemoglobin ≤80 g/L (OR, 0.47; 95% CI, 0.36-0.61), altered mental status (OR, 2.06; 95% CI, 1.55-2.73), albumin ≤30 g/L (OR, 1.43; 95% CI, 1.14-1.78), and red-blood emesis (OR, 1.29; 95% CI, 1.06-1.59). Patients presenting ≤6 hours versus >6 hours required transfusion less often (286 [27%] vs 791 [42%]; difference, -15%; 95% CI, -19% to -12%) because of a smaller proportion with low hemoglobin levels, but were similar with regard to hemostatic intervention (189 [18%] vs 371 [20%]), 30-day mortality (80 [7%] vs 121 [6%]), and hospital days (5.0 ± 0.2 vs 5.0 ± 0.2)., Conclusions: Patients with melena alone delay their presentation to the hospital. A delayed presentation is associated with a decreased hemoglobin level and increases the likelihood of transfusion. Other outcomes are similar with rapid versus delayed presentation. Time to presentation should not be used as an indicator for poor outcome. Patients with delayed presentation should be managed with the same degree of care as those with rapid presentation., (Published by Elsevier Inc.)

Hypocholesterolemia is commonly found in critically ill patients; however, the aetiology of this condition remains unclear. Several clinical studies refer to the possible negative impact of haemodilution on cholesterol (CH) metabolism in acute medical conditions. The aim of this study was to examine the serum CH profile (total CH, LDL and HDL CH) during acute gastrointestinal bleeding which is a life-threatening condition characterised by alterations in lipid metabolism. Serum non-CH sterols (lathosterol, squalene, sitosterol and campesterol) concentrations as markers of CH synthesis and CH absorption were measured at the same time. Twenty-four patients with acute upper gastrointestinal bleeding (UGIB) were measured for these parameters over a 6-day period. The control group was 100 healthy blood donors.We found lower plasma levels of total CH (p < 0.001) and LDL CH (p < 0.05) in patients with UGIB than in the control group. The decreased HDL CH plasma levels in patients were not statistically significant. In addition, patients had significantly lower plasma levels of lathosterol, squalene, campesterol and sitosterol (p < 0.05).Our results showed abnormalities not only in the CH plasma profile, but also in plasma concentrations of non-CH sterols. These findings of alterations in both the CH synthesis and absorption process could be a contributory cause of hypocholesterolemia during acute gastrointestinal bleeding. However, further research is necessary.

We evaluated the significance of immature granulocyte (IG) count during the clinical course after liver transplantation. We counted IG using the flow cytometric method with CD16, CD11b, and CD45 antibodies. Samples were obtained from 31 patients in the Department of Transplantation and Immunology, and we determined (i) the distribution of IG peak value, (ii) the distribution of IG peak time-points, (iii) the clinical background of patients with high IG, and (iv) the clinical course of high IG cases. We observed the appearance of IG (100/microl or higher) in the majority of the patients (23 out of 31 patients; 74.2%). The IG peak was detected on the 19th day after transplantation. We observed serious complications, such as melena, rejection, or severe infection, in high IG (500/microl or higher) cases. We observed instances of inflammation with low C-reactive protein (CRP) value in the presence of IG. We believe that IG is a useful marker to monitor inflammation.

The urea/creatinine-ratio has been proposed as an instrument for differentiating upper from lower gastrointestinal haemorrhages. The predictability of this method was investigated in 105 cases with the source of bleeding to be in the upper gastrointestinal tract and in 31 cases in the lower gastrointestinal tract. Determination of the urea/creatinine-ratio predicted the site of bleeding in only 60% of the patients. The use of the ratio in diagnostic decision making would increase the number of unnecessary colonoscopies. Thus, the urea/creatinine-ratio does not appear to be clinically useful in predicting the localization of a gastrointestinal bleeding with adequate certainty.

The investigation of effective and ineffective erythropoiesis in long-term hemorrhages has shown that the index of normal erythroblasts maturation is decreased down to 0.7 +/- 0.01 (P < 0.01) that evidences disorders in the process of proliferation and differentiation of the erythron cells. A rise of ineffective erythropoiesis was observed at the level of polychromatophilic normal erythroblasts , the mean number of PAS (positive cells) comprised 22.9 +/- 4.1% (P < 0.05). Erythropoiesis intensity was lowered and erythrocyte life was shortened. The data obtained are important for the evaluation of the erythron system lesion and purposeful therapy.

Plasma atrial natriuretic factor, aldosterone, renin activity, and antidiuretic hormone were studied in low output heart failure syndromes: cardiogenic shock in ten patients with acute myocardial infarction of the anterior wall (first group), hypovolemic shock after melena from peptic ulcer in ten subjects (second group), and hypotension with bradycardia syndrome in ten patients with acute myocardial infarction of the inferior wall (third group). Circulating atrial natriuretic factor in patients with cardiogenic shock (102.4 +/- 7.4 pg/ml) was significantly higher than in healthy volunteers matched for sex and age (8.4 +/- 0.3 pg/ml). In these patients there was a positive correlation between atrial natriuretic factor and central venous pressure values. Atrial natriuretic factor and central venous pressure values in the second and third groups were within normal range. Plasma aldosterone was high in all groups, plasma renin activity was elevated in the first and third groups, and high antidiuretic hormone was observed in the first and second groups. These findings indicate that in low output heart failure syndromes only hemodynamic changes affecting the atria stimulate atrial natriuretic factor release. No correlations were found between plasma atrial natriuretic factor and other hormones. In particular, high atrial natriuretic factor levels in the patients with cardiogenic shock did not inhibit release of aldosterone, renin, or antidiuretic hormone. It may be surmised that in these patients the hemodynamic effects override the inhibitory effects of atrial natriuretic factor.

Specific, homologous human neurophysin I and II radioimmunoassays were established and used to measure the individual, immunoreactive neurophysin concentrations in human plasma. Circulating levels of human neurophysin I in normal individuals were less than 1 ng/ml and neurophysin II levels were 1-2 ng/ml. During dehydration, there was a significant rise in plasma neurophysin I, together with an increase in neurophysin II. Haemorrhage also was associated with a rise in plasma neurophysin I and II, but the percent increase was greater for I than II. In two subjects in whom nicotine inhalation caused a rise in plasma neurophysin I, there was no detectable increase in plasma neurophysin II. These stimuli which have been reported to release vasopressin from the posterior pituitary also are associated with the differential release of neurophysin I. Plasma neurophysin II levels could more clearly be shown to rise independently of plasma neurophysin I during events thought to be related to oxytocin release. Plasma neurophysin II levels were significantly elevated in women taking oral contraceptives. Similarly during pregnancy there was a progressive rise in plasma neurophysin II concentration which was proportional to the period of gestation. Plasma neurophysin II concentrations in seven of fifteen nursing women rose significantly during suckling. There was no detectable change in plasma neurophysin I concentrations during any of these events. Plasma neurophysin I and II levels were both significantly elevated in fourteen patients with chronic renal failure and rose over haemodialysis, suggesting that the kidney may be the major route of clearance of the neurophysins. In humans the independent release of neurophysin II was associated with stimuli thought to release oxytocin, but neurophysin I showed only a differential release compared to neurophysin II in vasopressin stimulated events.