• Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM.• The results support the use of myeloablative IV-BU vs TBIbased conditioning regimens for treatment of myeloid malignancies.We conducted a prospective cohort study testing the noninferiority of survival of ablative intravenous busulfan (IV-BU) vs ablative total body irradiation (TBI)-based regimens in myeloid malignancies. A total of 1483 patients undergoing transplantation for myeloid malignancies (IV-BU, N 5 1025; TBI, N 5 458) were enrolled. Cohorts were similar with respect to age, gender, race, performance score, disease, and disease stage at transplantation. Most patients had acute myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood (77%) from HLA-matched siblings (40%) or well-matched unrelated donors (48%). Two-year probabilities of survival (95% confidence interval [CI]), were 56% (95% CI, 53%-60%) and 48% (95% CI, 43%-54%, P 5 .019) for IV-BU (relative risk, 0.82; 95% CI, 0.68-0.98, P 5 .03) and TBI, respectively. Corresponding incidences of transplantrelated mortality (TRM) were 18% (95% CI, 16%-21%) and 19% (95% CI, 15%-23%, P 5 .75) and disease progression were 34% (95% CI, 31%-37%) and 39% (95% CI, 34%-44%, P 5 .08).The incidence of hepatic veno-occlusive disease (VOD) was 5% for IV-BU and 1% with TBI (P < .001). There were no differences in progression-free survival and graft-versus-host disease. Compared with TBI, IV-BU resulted in superior survival with no increased risk for relapse or TRM. These results support the use of myeloablative IV-BU vs TBI-based conditioning regimens for treatment of myeloid malignancies. (Blood. 2013;122(24):3871-3878)

The delay in gastric emptying which is evident in about 30±50 % of outpatients with longstanding Type I (insulin-dependent) or Type II (non-insulindependent) diabetes mellitus has been attributed to irreversible autonomic neuropathy [1±5]. It is now recognised, however, that acute changes in the blood glucose concentration have a major effect on gastric emptying as well as motor function in other regions of the gastrointestinal tract [1, 6±14]. The effects of acute hyperglycaemia on gastrointestinal motor function appear to be related directly to the blood glucose concentration [1, 15±19]. Hyperglycaemia slows gastric emptying markedly in patients with Type I and Type II diabetes [1,7,8] and healthy subjects [6]. The mechanisms mediating this effect are uncertain but hyperinsulinaemia might be an important factor. In normal subjects, hyperinsulinaemia, under euglycaemic conditions, slows emptying of Diabetologia (1999) Summary Hyperglycaemia slows gastric emptying in both normal subjects and patients with diabetes mellitus. The mechanisms mediating this effect, particularly the potential role of insulin, are uncertain. Hyperinsulinaemia has been reported to slow gastric emptying in normal subjects during euglycaemia. The purpose of this study was to evaluate the effect of euglycaemic hyperinsulinaemia on gastric emptying in Type I (insulin-dependent) and Type II (noninsulin-dependent) diabetes mellitus. In six patients with uncomplicated Type I and eight patients with uncomplicated Type II diabetes mellitus, measurements of gastric emptying were done on 2 separate days. No patients had gastrointestinal symptoms or cardiovascular autonomic neuropathy. The insulin infusion rate was 40 mU × m ±2 × min ±1 on one day and 80 mU × m ±2 × min ±1 on the other. Gastric emptying and intragastric meal distribution were measured using a scintigraphic technique for 3 h after ingestion of a mixed solid/liquid meal and results compared with a range established in normal volunteers. In both Type I and Type II patients the serum insulin concentration had no effect on gastric emptying or intragastric meal distribution of solids or liquids. When gastric emptying during insulin infusion rates of 40 mU × m ±2 × min ±1 and 80 mU × m ±2 × min ±1 were compared the solid T 50 was 137.8 ± 24.6 min vs 128.7 ± 24.3 min and liquid T 50 was 36.7 ± 19.4 min vs 40.4 ± 15.7 min in the Type I patients; the solid T 50 was 94.9 ± 19.1 vs 86.1 ± 10.7 min and liquid T 50 was 21.8 ± 6.9 min vs 21.8 ± 5.9 min in the Type II patients. We conclude that hyperinsulinaemia during euglycaemia has no notable effect on gastric emptying in patients with uncomplicated Type I and Type II diabetes; any effect of insulin on gastric emptying in patients with diabetes is likely to be minimal. [Diabetologia (1999) Corresponding author: Prof. I. A. Macdonald, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK Abbreviations: CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; RoIs, regions of interest; ALP, amylin and a...

In our university hospital, NAS was higher during the day and evening hours and lower at night. We also found that patients from accident and emergency had a higher NAS than those admitted to the MCU from other locations. NAS in the MCU was not lower than the NAS in the ICU. Because of its ability to discriminate between day and evening workloads and between patients from different sources, the NAS may assist MCU managers in assessing staffing needs.

Gastric emptying of solid and/or nutrient liquid meals is delayed in up to 50 % of patients with longstanding diabetes mellitus [1]. In addition, the blood glucose response to oral carbohydrate is related to the rate of gastric emptying of a carbohydrate load in both normal subjects and patients with diabetes. Gastric emptying may therefore be a previously under-recognized contributor to variations in glycaemic control which can have an impact on the management of patients with diabetes. Thus an understanding of the various factors influencing gastric emptying is important.Hyperglycaemia delays gastric emptying in both patients with diabetes and in healthy subjects [2±4]. The mechanisms involved are uncertain, but concomitant hyperinsulinaemia may have some effect. Eliasson et al. [5] reported that gastric emptying was slower during hyperinsulinaemia but only four subjects were studied and only a solid meal was used. Ideally, both solid and nutrient-liquid emptying should be measured because it is not unusual for an emptying abnormality to be limited to either the solid or liquid component of a meal. In the normal state, solids empty differently from liquids; emptying of solids is thought to be a function of propulsive and retropulsive mincing action of the antrum whereas liquid emptying seems to depend primarily on gastric tone [6,7]. Diabetologia (1998) Summary Several studies have shown that hyperglycaemia slows gastric emptying in normal subjects and patients with diabetes mellitus but whether hyperinsulinaemia per se has an effect remains debatable. In the present study we have assessed the effect of hyperinsulinaemia on gastric emptying of a solid and liquid meal in normal subjects. Ten men were studied three times in random order. After an overnight fast, subjects were infused with 0.9 % NaCl on two occasions and on the third with insulin, at 40 mU × m 2 × min 1 with 20 % glucose simultaneously to maintain euglycaemia. Steady-state glucose infusion rate was ensured before the subjects ate a standard meal of a pancake labelled with In-DTPA. Gamma-scintigraphic images were then obtained every 20 min for the next 3 h. There were no significant differences between the mean half-emptying times (T 50 ) of the solid and liquid during the two saline infusions (129.6 ± 28.5 vs 128.4 ± 23.8 min for the solid and 25.4 ± 7.0 vs 34.7 ± 18.0 min for the liquid, mean ± SD). Hyperinsulinaemia delayed both solid (mean T 50 149.6 ± 30.7, p = 0.031) and liquid emptying (mean T 50 39.8 ± 13.9, p = 0.042). There were no significant differences in the cholecystokinin and glucagon-like peptide 1 responses to the meal during either saline or insulin infusions. There was a tendency towards a greater insulin response to the meal during the hyperinsulinaemic study. Thus, hyperinsulinaemia delayed emptying of both the solid and liquid components of the meal.[ Diabetologia (1998) 41: 474±481]

The proposed dosing algorithm can significantly improve the sub-exposure of Bu. A shortened test PK study duration with reduced PK samples can provide as near as good estimate for Bu CL. A simplified CL estimation method is valid.