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Key Points In combination with cyclophosphamide, intravenous busulfan is associated with better leukemia-free and overall survival in AML than TBI.

The development of insulin resistance has been associated with impaired mitochondrial fatty acid oxidation (FAO), but the exact relationship between FAO capacity and glucose metabolism continues to be debated. To address this controversy, patients with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency underwent an oral glucose tolerance test (OGTT) and measurement of energy expenditure, body composition, and plasma metabolites. Compared with controls, patients with LCHAD deficiency had a trend toward higher total body fat and extramyocellular lipid deposition but similar levels of intramyocelluar and intrahepatic lipids. Resting energy expenditure was similar between the groups, but respiratory quotient was higher and total energy expenditure was lower in LCHAD-deficient patients compared with controls. High-molecular-weight (HMW) adiponectin levels were lower and plasma long-chain acylcarnitines were higher among LCHAD-deficient patients. Fasting and post-OGTT levels of glucose, insulin, and ghrelin, along with estimates of insulin sensitivity, were the same between the groups. Despite decreased capacity for FAO, lower total energy expenditure and plasma HMW adiponectin, and increased plasma acylcarnitines, LCHAD-deficient patients exhibited normal glucose tolerance. These data suggest that inhibition of the FAO pathway in humans is not sufficient to induce insulin resistance.

Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage, molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin signaling provide mechanistic insight into the clinical evidence for the links between obesity, metabolic syndrome, and airway diseases, setting the stage for novel therapeutic avenues targeting these conditions.

New onset diabetes after transplantation (NODAT) occurs less frequently in living donor liver transplant (LDLT) recipients than in deceased donor liver transplant (DDLT) recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52–0.75),P<0.001). Predictors for NODAT in LDLT recipients were hepatitis C (HCV) and treated acute cellular rejection (ACR). Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications.

A novel, hand-held Reference Point Indentation (RPI) instrument, measures how well the bone of living patients and large animals resists indentation. The results presented here are reported in terms of Bone Material Strength, which is a normalized measure of how well the bone resists indentation, and is inversely related to the indentation distance into the bone. We present examples of the instrument's use in: (1) laboratory experiments on bone, including experiments through a layer of soft tissue, (2) three human clinical trials, two ongoing in Barcelona and at the Mayo Clinic, and one completed in Portland, OR, and (3) two ongoing horse clinical trials, one at Purdue University and another at Alamo Pintado Stables in California. The instrument is capable of measuring consistent values when testing through soft tissue such as skin and periosteum, and does so handheld, an improvement over previous Reference Point Indentation instruments. Measurements conducted on horses showed reproducible results when testing the horse through tissue or on bare bone. In the human clinical trials, reasonable and consistent values were obtained, suggesting the Osteoprobe® is capable of measuring Bone Material Strength in vivo, but larger studies are needed to determine the efficacy of the instrument's use in medical diagnosis.