Citations

The past decade has witnessed a paradigm shift in the initial treatment of multiple myeloma with the introduction of novel agents such as thalidomide, lenalidomide, and bortezomib, leading to improved outcomes. High-dose therapy and autologous stem cell transplantation remains an important therapeutic option for patients with multiple myeloma eligible for the procedure. Before the advent of the novel agents, patients underwent stem cell collection prior to significant alkylating agent exposure, given its potential deleterious effect on stem cell collection. With increasing use of the novel agents in the upfront setting, several reports have emerged raising concerns about their impact on the ability to collect stem cells. An expert panel of the International Myeloma Working Group (IMWG) was convened to examine the implications of these therapies on stem collection in patients with myeloma and to develop recommendations for addressing these issues. Here we summarize the currently available data and present our perspective on the problem and potential options to overcome this problem. Specifically, we recommend early mobilization of stem cells, preferably within the first 4 cycles of initial therapy, in patients treated with novel agents and encourage participation in clinical trials evaluating novel approaches to stem cell mobilization.

Background— Appropriateness criteria for stress imaging have been published to promote the effective use of stress nuclear scintigraphy and stress echocardiography. We sought to evaluate the application of the stress echocardiography appropriateness criteria to patients undergoing stress echocardiography in an academic medical center. Methods and Results— The stress echocardiography criteria were applied to 298 consecutive patients who underwent stress echocardiography. Patients were rated as appropriate, uncertain, inappropriate, or not classifiable. Results were compared with those of a previous analysis in the same patients using the single-photon computed tomography myocardial perfusion imaging (SPECT MPI) criteria. The level of agreement between 2 cardiac nurse abstractors for categorizing appropriateness by the stress echocardiography criteria was good (κ=0.72). Overall, 54% of patients were classified as appropriate, 8% as uncertain, and 19% as inappropriate; 19% were not classifiable. By the SPECT MPI criteria, 64% of patients were classified as appropriate, 9% as uncertain, and 18% as inappropriate; 9% were not classifiable ( P <0.001 compared with stress echocardiography criteria). By the stress echocardiography criteria, 6 clinical situations or indications accounted for more than 90% of the inappropriate tests; most of these involved asymptomatic patients. Conclusions— Applying stress echocardiography appropriateness criteria to a patient population is feasible, although 1 in 5 of our patients was not classifiable. Overall, the stress echocardiography criteria classified patients differently compared with the SPECT MPI criteria. Future refinements of the appropriateness criteria for stress imaging should address gaps in the criteria and disparities between the stress echocardiography and SPECT MPI criteria.

Abstract Rationale Portopulmonary hypertension (PPHTN) occurs in 6% of liver transplant candidates. The pathogenesis of this complication of portal hypertension is poorly understood. Objectives To identify genetic risk factors for PPHTN in patients with advanced liver disease. Methods We performed a multicenter case-control study of patients with portal hypertension. Cases had a mean pulmonary artery pressure &gt;25 mm Hg, pulmonary vascular resistance &gt;240 dynes·s−1·cm−5, and pulmonary capillary wedge pressure ≤15 mm Hg. Controls had a right ventricular systolic pressure &lt; 40 mm Hg (if estimated) and normal right-sided cardiac morphology by transthoracic echocardiography. We genotyped 1,079 common single nucleotide polymorphisms (SNPs) in 93 candidate genes in each patient. Measurements and Main Results The study sample included 31 cases and 104 controls. Twenty-nine SNPs in 15 candidate genes were associated with the risk of PPHTN (P &lt; 0.05). Multiple SNPs in the genes coding for estrogen receptor 1, aromatase, phosphodiesterase 5, angiopoietin 1, and calcium binding protein A4 were associated with the risk of PPHTN. The biological relevance of one of the aromatase SNPs was supported by an association with plasma estradiol levels. Conclusions Genetic variation in estrogen signaling and cell growth regulators is associated with the risk of PPHTN. These biologic pathways may elucidate the mechanism for the development of PPHTN in certain patients with severe liver disease.

SummaryWe report a 16‐month‐old asymptomatic male with enzyme confirmed isovaleric acidaemia (IVA; isovaleryl‐CoA dehydrogenase deficiency; OMIM 243500) who, upon routine nutritional follow‐up, presented evidence of peroxisomal dysfunction. The newborn screen (2 days of life) revealed elevated C5‐carnitine (2.95 μmol/L; cutoff <0.09 μmol/L) and IVA was subsequently confirmed by metabolic profiling and in vitro enzymology. Plasma essential fatty acid (EFA) analysis, assessed to evaluate nutritional status during protein restriction and l‐carnitine supplementation, revealed elevated C26:0 (5.0 μmol/L; normal <1.3). Subsequently, metabolic profiling and molecular genetic analysis confirmed X‐linked adrenoleukodystrophy (XALD). Identification of co‐inherited XALD with IVA in this currently asymptomatic patient holds significant treatment ramifications for the proband prior to the onset of neurological sequelae, and critically important counselling implications for this family.

A considerable amount of effort has been made to seek the acoustic correlates of reduced speech intelligibility in dysarthria, although some acoustic variables are under debate: For example, articulation rate, F2 slope, and vowel space have been frequently discussed in previous studies as acoustic predictors of speech intelligibility of dysarthria [Kim (2007)]. One variable that is not well understood, with respect to its effect on speech intelligibility in dysarthria, is level of presentation. This includes level generated by a speaker as well as level of presentation after the speaker has recorded utterances. Clearly, variations in level of presentation of recorded utterances will have some effect when an intelligibility test requires some segmental analysis (as in a minimal pairs test), but the potential effect when speech intelligibility is scaled is not so clear. This is an important question because of the frequent use of scaled intelligibility in dysarthria research. In this presentation, we will report data on how scaled speech intelligibility is affected by level of presentation of speech samples produced by speakers with various types and severity of dysarthria. [Work supported by NIH DC00319.]

The American Heart Association’s (AHA’s) mission is “to build healthier lives, free of cardiovascular diseases and stroke.” This first article in a 2-part series will serve to present an overview of the work the AHA has undertaken to translate evidence into practice for healthcare professionals. It describes the extensive work of the AHA to support and further the delivery of evidence-based medicine, which includes the following: (1) supporting scientific discovery and the next generation of healthcare professionals and researchers; (2) disseminating scientific information; (3) developing evidence-based guidelines and statements; (4) creating and advocating for the implementation of performance indicators/measures; (5) developing clinical decision support and quality improvement tools; and (6) developing directed-cause campaigns, all of which can lead to improved patient care. This article also discusses the need for novel approaches and some of the AHA’s evolving strategies to help address gaps in care. The second article, which will be published shortly after this one, will examine the AHA’s efforts to engage and empower healthcare consumers to become more involved with their own health and health care.