Citations

Background— Congenital long QT syndrome (LQTS) is characterized by QT prolongation. However, the QT interval itself is insufficient for diagnosis, unless the corrected QT interval is repeatedly ≥500 ms without an acquired explanation. Further, the majority of LQTS patients have a corrected QT interval below this threshold, and a significant minority has normal resting corrected QT interval values. Here, we aimed to develop and validate a novel, quantitative T wave morphological analysis program to differentiate LQTS patients from healthy controls. Methods and Results— We analyzed a genotyped cohort of 420 patients (22±16 years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using a novel, proprietary T wave analysis program that quantitates subtle changes in T wave morphology. The top 3 discriminating features in each ECG lead were determined and the lead with the best discrimination selected. Classification was performed using a linear discriminant classifier and validated on an untouched cohort. The top 3 features were Tpeak–Tend interval, T wave left slope, and T wave center of gravity x axis (last 25% of the T wave). Lead V6 had the best discrimination. It could distinguish 86.8% of LQTS patients from healthy controls. Moreover, it distinguished 83.33% of patients with concealed LQTS from controls, despite having essentially identical resting corrected QT interval values. Conclusions— T wave quantitative analysis on the 12-lead surface ECG provides an effective, novel tool to distinguish patients with either LQT1/LQT2 from healthy matched controls. It can provide guidance while mutation-specific genetic testing is in motion for family members.

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 >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 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 (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 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 >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.

Myelofibrosis is a myeloproliferative neoplasm with cardinal features of extramedullary hematopoiesis, hepatosplenomegaly, cytopenias, and constitutional symptoms that result in shortened survival and leukemic transformation. It is a disease predominantly of the elderly, and currently available therapies only offer symptom control without curative benefit or ability to alter disease progression. Allogeneic hematopoietic stem-cell transplant (HSCT) is the only potentially curative intervention; however, this is only feasible in younger and medically fit patients and selectively offered to those with high-risk disease. Despite ongoing advancements, HSCT is associated with substantial morbidity and mortality, and the determination of which patients with myelofibrosis are ideal candidates and the selection of the opportune moment to proceed with transplantation remains challenging. This review summarizes our current recommendations for the role of and indications for HSCT in myelofibrosis.

Abstract Diagnostic testing is an integral component of patient evaluation in the emergency department ( ED ). Emergency clinicians frequently use diagnostic testing to more confidently exclude “worst‐case” diagnoses rather than to determine the most likely etiology for a presenting complaint. Increased utilization of diagnostic testing has not been associated with reductions in disease‐related mortality but has led to increased overall healthcare costs and other unintended consequences (e.g., incidental findings requiring further workup, unnecessary exposure to ionizing radiation or potentially nephrotoxic contrast). Shared decision making ( SDM ) presents an opportunity for clinicians to discuss the benefits and harms associated with diagnostic testing with patients to more closely tailor testing to patient risk. This article introduces the challenges and opportunities associated with incorporating SDM into emergency care by summarizing the conclusions of the diagnostic testing group at the 2016 Academic Emergency Medicine Consensus Conference on SDM . Three primary domains emerged: 1) characteristics of a condition or test appropriate for SDM , 2) critical elements of and potential barriers to SDM discussions on diagnostic testing, and 3) financial aspects of SDM applied to diagnostic testing. The most critical research questions to improve engagement of patients in their acute care diagnostic decisions were determined by consensus.