Citations

Abstract Background: Aortic valve stenosis (AS) commonly causes left ventricular (LV) pressure overload; thus, identifying patients with adverse remodeling/early LV dysfunction is critical. We compared 2-dimensional (2D) to 3-dimensional (3D) echocardiographic measures of LV myocardial deformation in patients with severe AS and studied the relation of LV preload and afterload (Zva) to myocardial deformation. Methods: We prospectively included 168 symptomatic patients (72±12 years) with severe AS and ejection fractions ≥50%. Strain parameters from those patients were compared with normal values found in the literature. 3D full-volume and 2D images were analyzed for global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), systolic strain rate (SRs), basal rotation (Rotmax-B), apical rotation (Rotmax-A), and peak systolic twist (Twistmax). Results: 2D–GLS and 2D–GCS decreased significantly compared with normal values (P˂.001 and P=.02, respectively); 2D Rotmax-B and Twistmax increased (P˂.001 vs normal values). Agreement between 2D–GLS and 3D–GLS by concordance correlation coefficient was 0.49 (95% CI, 0.39-0.57) in patients with AS. Both 2D– and 3D–GLS correlated with valvulo-arterial impedance (Zva) (r=0.34, P<.001; and r=0.23, P=.003, respectively). Conclusion: In patients with severe AS, GLS and GCS decreased, and basal rotation and twist increased to maintain LV ejection fraction. 2D– and 3D–GLS had a relatively fair agreement. Both 2D– and 3D–GLS correlated modestly with Zva.

Background:Multiple myeloma (MM) is a heterogeneous disease with varying survival outcomes depending on the presence of certain genetic abnormalities. Common abnormalities include trisomies, translocations involving the chromosome 14, and amplifications or deletions of chromosomes 1, 13, and 17. t(11;14), occurring in 15% of patients with myeloma, had been considered a standard risk abnormality, but recent data suggest inferior outcome. This is important as new therapeutic options such as the BCL‐2 inhibitor venetoclax has been shown to be particularly effective in t(11;14) patients.Aims: Primary objective: To describe the overall survival of myeloma patients with translocation t(11:14) Secondary objectives: To determine the response rates, progression free survival, time to progression, time to next treatment, duration of responses and overall survival with different regimens among patients with t(11;14), to determine the prognostic factors for overall survival among patients with t(11;14), and to identify the spectrum of co‐existing genetic abnormalities among patients with t(11;14)Methods:This was a multicenter study to identify the outcomes of patients with t(11;14), using a retrospectively assembled cohort. Patients with MM diagnosed between 2005 and 2015 with t(11;14) identified on FISH performed within six months of diagnosis, and with treatment details available and if alive, a minimum of 12 months of follow up, were enrolled.Results:The current analysis includes 848 patients; median age of 64.4 years; 60.0% male. The median follow‐up from diagnosis for the entire cohort was 46.5 months; 86.7% of the patients were alive at the last follow up. ISS stage distribution included: Stage I (35.3%), Stage II (38.9%) and Stage III (25.8%). The distribution of FISH abnormalities included: del 13q (14.5%), 1q amp (12.1%), del 17p or monosomy 17 (6.1%). Initial therapy included different regimens: 23.3% had an IMiD, 43.3% had a PI, 20.0% had both and 13.3% had no novel agent. The drug classes by line of therapy are shown in Table 1. A stem cell transplant (SCT), defined as within 12 months of start of first line treatment, was used in 39.1% of patients. The median time to next treatment (TTNT) after initial treatment was 13.7 (95% CI: 11.3 to 16.5) months. The median overall survival (OS) from diagnosis for the entire cohort was 82.5 (95% CI: 73.5 to 95.8) months; 4‐year estimates for those diagnosed from January 2005 to December 2009, and from January 2010 to December 2014 were 75.1% and 70.2%, respectively. Median OS by initial regimen is shown in Figure 1; those receiving an early SCT had median OS of 116.9 (95% CI: 85.6 to NA) months.Summary/Conclusion:This is the first study to examine the outcomes of a large group of myeloma patients with t(11;14) abnormality. Patients receiving a combination of a PI and an IMiD appear to have the best survival outcomes. Patients receiving an early SCT appear to have excellent survival with median OS approaching 10 years. Additional patients are being accrued to this study and additional analysis examining the variables affecting response duration and survival will be presented.image

The notion that cardiovascular disease (CVD) primarily occurs in men is slowly disappearing. More women than men die of CVD every year, and when women survive, the burden and consequences are worse than in men. Markers of stress and other psychosocial factors have been associated with poor outcomes. Multiple studies have demonstrated sex-based differences in the vascular and endothelial responses to mental stress. Psychosocial stressors were also found to be independent risk factors for the development and progression of CVD. This review arises from accumulating evidence suggesting that psychological well-being may improve cardiac-related outcomes, independent of cardiac risk factors. Despite the fact that positive physician-patient engagement is likely to play a critical role in promoting positive psychological traits and healthy behaviors, current physician awareness and advocacy are rather suboptimal, despite active awareness campaigns such as the American Heart Association's Go Red for Women ® . There is a need to further study the role and management of stress as a CVD risk factor, especially in women, who are disproportionately affected.

Abstract This paper, prepared by the EFLM Task and Finish Group on Allocation of laboratory tests to different models for performance specifications (TFG-DM), is dealing with criteria for allocating measurands to the different models for analytical performance specifications (APS) recognized in the 1st EFLM Strategic Conference Consensus Statement. Model 1, based on the effect of APS on clinical outcome, is the model of choice for measurands that have a central role in the decision-making of a specific disease or clinical situation and where cut-off/decision limits are established for either diagnosing, screening or monitoring. Total cholesterol, glucose, HbA 1c , serum albumin and cardiac troponins represent practical examples. Model 2 is based on components of biological variation and should be applied to measurands that do not have a central role in a specific disease or clinical situation, but where the concentration of the measurand is in a steady state. This is best achieved for measurands under strict homeostatic control in order to preserve their concentrations in the body fluid of interest, but it can also be applied to other measurands that are in a steady state in biological fluids. In this case, it is expected that the “noise” produced by the measurement procedure will not significantly alter the signal provided by the concentration of the measurand. This model especially applies to electrolytes and minerals in blood plasma (sodium, potassium, chloride, bicarbonate, calcium, magnesium, inorganic phosphate) and to creatinine, cystatin C, uric acid and total protein in plasma. Model 3, based on state-of-the-art of the measurement, should be used for all the measurands that cannot be included in models 1 or 2.

OBJECTIVE Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS From the MMTT, insulin secretion in T2DM was &gt;86% lower compared with NGT or PDM (P &lt; 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P &lt; 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (&gt;58%; all P &lt; 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P &lt; 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values &gt;0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use.

AbstractWe examined the specific cell types in normal human pituitaries that expressed PRL receptor (PRL-R) messenger ribonucleic acid (mRNA) by combined in situ hybridization and immunohistochemistry. The distribution of PRL-R mRNA in 28 pituitary adenomas was examined by in situ hybridization and reverse transcription-PCR in 12 cases of adenomas. In another set of experiments, 34 PRL adenomas from men, women, and bromocriptine-treated patients were analyzed for PRL-R by in situ hybridization.In the normal pituitary, PRL- and LH-producing cells had significantly more mean grain counts per cell and higher percentages of cells positive for PRL-R than GH and TSH cells. PRL-R mRNA was present in all groups of adenomas by in situ hybridization and reverse transcription-PCR. PRL adenomas had a significantly higher density of labeling compared to other adenoma types. Although there was no difference in the levels of PRL-R mRNA in PRL adenomas from men and premenopausal and postmenopausal women, patients treated with bromocriptine before pituitary surgery had significantly lower levels of PRL-R compared to all other groups. These results indicate that in the normal pituitary, PRL and LH cells have the highest level of PRL-R mRNA, whereas PRL adenomas have significantly higher levels of PRL-R mRNA than other types of adenomas, and bromocriptine treatment decreases the levels of PRL-R mRNA in PRL adenomas.