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Key Points Pomalidomide plus low-dose dexamethasone significantly improved PFS vs pomalidomide alone in relapsed and refractory multiple myeloma. Pomalidomide plus low-dose dexamethasone is an important new treatment option for RRMM patients who have received multiple prior therapies.

In this paper, the authors review the definition of high-risk plaque as developed by experienced researchers in atherosclerosis, including pathologists, clinicians, molecular biologists, and imaging scientists. Current concepts of vulnerable plaque are based on histological studies of coronary and carotid artery plaque as well as natural history studies and include the presence of a lipid-rich necrotic core with an overlying thin fibrous cap, plaque inflammation, fissured plaque, and intraplaque hemorrhage. The extension of these histologically identified high-risk carotid plaque features to human in vivo MRI is reviewed as well. The authors also assess the ability of in vivo MRI to depict these vulnerable carotid plaque features. Next, the ability of these MRI-demonstrated high-risk carotid plaque features to predict the risk of ipsilateral carotid thromboembolic events is reviewed and compared with the risk assessment provided by simple carotid artery stenosis measurements. Lastly, future directions of high-risk carotid plaque MRI are discussed, including the potential for increased clinical availability and more automated analysis of carotid plaque MRI. The ultimate goal of high-risk plaque imaging is to design and run future multicenter trials using carotid plaque MRI to guide individual patient selection and decisions about optimal atherosclerotic treatment strategies.

ABSTRACTBackgroundThe objective of this study was to evaluate citalopram for executive functioning in Huntington's disease (HD).MethodsThe study was randomized, double‐blind, and placebo‐controlled. Thirty‐three adults with HD, cognitive complaints, and no depression (Hamilton Depression [HAM‐D] rating scale ≤12) were administered citalopram 20 mg or placebo (7 visits, 20 weeks), with practice and placebo run‐ins. The primary outcome was change in executive functioning.ResultsThe intent to treat analysis was controlled for practice effects, comparing visits 1 and 2 to visits 5 and 6 for citalopram versus placebo. There were no significant benefits on the executive function composite (treatment‐placebo mean difference −0.167; 95% confidence interval [CI], −0.361 to 0.028; P = .092). Citalopram participants showed improved clinician‐rated depression symptoms on the HAM‐D (t = −2.02; P = 0.05). There were no group differences on motor ratings, self‐reported executive functions, psychiatric symptoms, or functional status.ConclusionsThere was no evidence that short‐term treatment with citalopram improved executive functions in HD. Despite excluding patients with active depression, participants on citalopram showed improved mood, raising the possibility of efficacy for subsyndromal depression in HD. © 2013 International Parkinson and Movement Disorder Society

Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 μg triiodothyronine (T3) in 7‐ and 27‐mo‐old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3‐mediated increase in the appetite‐regulating proteins agouti‐related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue‐specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3‐induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis.—Walrand, S., Short, K. R., Heemstra, L. A., Novak, C. M., Levine, J. A., Coenen‐Schimke, J. M., Nair, K. S. Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration. FASEB J. 28, 1499–1510 (2014). www.fasebj.org

Building on diamond characteristics such as hardness, chemical inertness and low electron emission threshold voltage, the current microscopic, spectroscopic and voltammetric investigations are directed towards improving the properties of electrode coating materials for their future use in clinical studies of deep brain stimulation via fast-scan cyclic voltammetry (FSCV). In this study we combine the capabilities of confocal Raman mapping in providing detailed and accurate analysis of local distributions of material constituents in a series of boron-doped polycrystalline diamond films grown by chemical vapor deposition, with information from the more conventional techniques of scanning electron microscopy (SEM) and infrared absorption spectroscopy. Although SEM images show a uniform distribution of film crystallites, they have the limitation of being unable to differentiate the distribution of boron in the diamond. Values of 1018–1021 atoms/cm3 of boron content have been estimated from the absorption coefficient of the 1290 cm−1 infrared absorption band and from the 500 cm−1 Raman vibration. The observed accumulation of boron atoms and carbon sp2 impurities at the grain boundaries suggests that very high doping levels do not necessarily contribute to improvement of the material’s conductivity, corroborating with voltammetric data. FSCV results also indicate an enhanced stability of analyte detection.

Purpose To determine the influence of modifiable lifestyle factors on the risk of cardiovascular disease after hematopoietic cell transplantation (HCT). Patients and Methods HCT survivors of ≥ 1 year treated from 1970 to 2010 (n = 3,833) were surveyed from 2010 to 2011 on current cardiovascular health and related lifestyle factors (smoking, diet, recreational physical activity). Responses (n = 2,362) were compared with those from a matched general population sample (National Health and Nutrition Examination Survey [NHANES]; n = 1,192). Results Compared with NHANES participants, HCT survivors (median age, 55.9 years; median 10.8 years since HCT; 71.3% allogeneic) had higher rates of cardiomyopathy (4.0% v 2.6%), stroke (4.8% v 3.3%), dyslipidemia (33.9% v 22.3%), and diabetes (14.3% v 11.7%; P < .05 for all comparisons). Prevalence of hypertension was similar (27.9% v 30.0%), and survivors were less likely to have ischemic heart disease (6.1% v 8.9%; P < .01). Among HCT survivors, hypertension, dyslipidemia, and diabetes were independent risk factors for ischemic heart disease and cardiomyopathy, and smoking was associated with ischemic heart disease and diabetes (odds ratios [ORs], 1.8 to 2.1; P = .02). Obesity was a risk factor for post-transplantation hypertension, dyslipidemia, and diabetes (ORs ≥ 2.0; P < .001). In contrast, lower fruit/vegetable intake was associated with greater risk of dyslipidemia and diabetes (ORs, 1.4 to 1.8; P ≤ .01), and lower physical activity level was associated with greater risk of hypertension and diabetes (ORs, 1.4 to 1.5; P < .05). Healthier lifestyle characteristics among HCT survivors attenuated risk of all cardiovascular conditions assessed. Conclusion Attention of clinicians to conventional cardiovascular risk factors and modifiable lifestyle characteristics offers hope of reducing serious cardiovascular morbidity after HCT.

SummaryMultiple myeloma, the second most common haematological malignancy in the U.S., is currently incurable. Disruption of the intrinsic apoptotic pathway by BCL2 and MCL1 upregulation is observed in >80% of myeloma cases and is associated with an aggressive clinical course. Remarkably, there is no approved drug with the ability to target BCL2 or MCL1. Thus, we investigated the anti‐tumour effects of a pan‐BCL2 inhibitor, AT‐101, which has high binding specificity for BCL2 and MCL1 in preclinical models of plasma cell cancers (Multiple myeloma and Waldenström macroglobulinaemia). Gene expression and immunoblot analysis of six plasma cell cancer models showed upregulation of BCL2 family members. AT‐101 was able to downregulate BCL2 and MCL1 in all plasma cell cancer models and induced apoptotic cell death in a caspase‐dependent manner by altering mitochondrial membrane permeability. This cytotoxic effect and BCL2 downregulation were further potentiated when AT‐101 was combined with lenalidomide/dexamethasone (LDA). NanoString nCounter mRNA quantification and Ingenuity Pathways Analysis revealed differential changes in the CCNA2, FRZB, FYN, IRF1, PTPN11 genes in LDA‐treated cells. In summary, we describe for the first time the cellular and molecular events associated with the use of AT‐101 in combination with lenalidomide/dexamethasone in preclinical models of plasma cell malignancy.

Purpose To develop a rapid proton MR elastography (MRE) technique that can quantify the absolute shear stiffness of lung parenchyma, to investigate the ability to differentiate respiration‐dependent stiffness variations of the lung, and to demonstrate clinical feasibility. Materials and Methods A spin‐echo echo planar imaging MRE sequence (SE‐EPI MRE) with a very short echo time was developed and tested in a series of five healthy volunteers at three different lung volumes: (i) residual volume (RV), (ii) total lung capacity (TLC), (iii) and midway between RV and TLC (MID). At each volume, lung density was quantified using a MR‐based density mapping sequence. For reference, data were acquired using the previously described spin‐echo lung MRE sequence (SE‐MRE). MRE data were also acquired in a patient with proven Idiopathic Pulmonary Fibrosis (IPF) to test clinical feasibility. Results The SE‐EPIMRE sequence reduced total acquisition time by a factor of 2 compared with the SE‐MRE sequence. Lung parenchyma median shear stiffness for the 5 volunteers quantified with the SE‐EPI MRE sequence was 0.9 kPa, 1.1 kPa, and 1.6 kPa at RV, MID, and TLC, respectively. The corresponding values obtained with the SE‐MRE sequence were 0.9 kPa, 1.1 kPa, and 1.5 kPa. Absolute shear stiffness was also successfully measured in the IPF patient. Conclusion The results indicate that stiffness variations due to respiration could be measured with the SE‐EPIMRE technique and were equivalent to values generated by the previously described SE‐MRE approach. Preliminary data obtained from the patient demonstrate clinical feasibility. J. Magn. Reson. Imaging 2014;40:1230–1237 . © 2013 Wiley Periodicals, Inc .