David M. Dudzinski

Diseases of the Aorta

Diseases of the aorta can affect any segment of the aorta or its branch vessels, may exhibit diverse and at times nonspecific protean manifestations, and might be chronic and indolent but also have the potential to present with acutely lethal consequences. Accordingly, it is imperative that both internists and cardiologists are familiar with principles of emergent management of aortopathies as well as of screening for these conditions, since detection and prophylactic treatment of diseases of the aorta will generally improve patient outcomes. Aortic aneurysms represent dilatation of all three layers of the vessel wall and may cause mass effects or progress toward dissection and/or rupture. Acute aortic dissections require prompt diagnosis and expert medical and interventional management. Endovascular techniques have become an adjunct to traditional open surgical repairs and may be utilized for select patient populations and scenarios, though comparative and long-term outcomes of the endovascular approach remain under investigation. Genetic and molecular techniques are elucidating novel pathophysiologic bases underlying diseases of the aorta and may reveal future therapeutic targets that can prevent or reverse aortopathy.

Crystal structure and activities of EXPB1 (Zea m 1), a beta-expansin and group-1 pollen allergen from maize.

Expansins are small extracellular proteins that promote turgor-driven extension of plant cell walls. EXPB1 (also called Zea m 1) is a member of the β-expansin subfamily known in the allergen literature as group-1 grass pollen allergens. EXPB1 induces extension and stress relaxation of grass cell walls. To help elucidate expansins mechanism of wall loosening, we determined the structure of EXPB1 by x-ray crystallography to 2.75-Å resolution. EXPB1 consists of two domains closely packed and aligned so as to form a long, shallow groove with potential to bind a glycan backbone of ≈10 sugar residues. The structure of EXPB1 domain 1 resembles that of family-45 glycoside hydrolase (GH45), with conservation of most of the residues in the catalytic site. However, EXPB1 lacks a second aspartate that serves as the catalytic base required for hydrolytic activity in GH45 enzymes. Domain 2 of EXPB1 is an Ig-like β-sandwich, with aromatic and polar residues that form a potential surface for polysaccharide binding in line with the glycan binding cleft of domain 1. EXPB1 binds to maize cell walls, most strongly to xylans, causing swelling of the cell wall. Tests for hydrolytic activity by EXPB1 with various wall polysaccharides proved negative. Moreover, GH45 enzymes and a GH45-related protein called “swollenin” lacked wall extension activity comparable to that of expansins. We propose a model of expansin action in which EXPB1 facilitates the local movement and stress relaxation of arabinoxylan–cellulose networks within the wall by noncovalent rearrangement of its target.

The Massachusetts General Hospital Pulmonary Embolism Response Team (MGH PERT): Creation of a Multidisciplinary Program to Improve Care of Patients With Massive and Submassive Pulmonary Embolism

Abstract New and innovative tools have emerged for the treatment of massive and submassive pulmonary embolism (PE). These novel treatments, when considered alongside existing therapy, such as anticoagulation, systemic intravenous thrombolysis, and open surgical pulmonary embolectomy, have the potential to improve patient outcomes. However, data comparing different treatment modalities are sparse, and guidelines provide only general advice for their use. Treatment decisions rest on clinician expertise and institutional resources. Because various medical and surgical specialties offer different perspectives and expertise, a multidisciplinary approach to patients with massive and submassive PE is required. To address this need, we created a novel multidisciplinary program – the Massachusetts General Hospital (MGH) Pulmonary Embolism Response Team (PERT) – which brings together multiple specialists to rapidly evaluate intermediate- and high-risk patients with PE, formulate a treatment plan, and mobilize the necessary resources to provide the highest level of care. Development of a clinical, educational, and research infrastructure, as well as the creation of a national PERT consortium, will make our experience available to other institutions and serve as a platform for future studies to improve the care of complex patients with massive and submassive PE.

Scientific and Legal Viability of Follow-on Protein Drugs

Many recombinant-protein drugs such as erythropoietin are now off patent, and the availability of generic versions of these drugs would reduce costs. The federal laws that simplify and expedite approval of generic forms of other drugs do not apply to recombinant-protein drugs. Congress is developing legislation to facilitate the approval of follow-on protein drugs.

Educational intervention to reduce outpatient inappropriate echocardiograms: a randomized control trial.

OBJECTIVES This study sought to prospectively study the impact of an appropriate use criteria (AUC)-based educational intervention on outpatient transthoracic echocardiography (TTE) ordering by physicians-in-training. BACKGROUND AUC were developed in response to concerns about inappropriate utilization. It is unknown whether an educational intervention can reduce inappropriate outpatient TTE. METHODS We conducted a randomized control trial in which physicians-in-training were randomized to an AUC-based educational intervention or a control group at an academic medical center in Boston, Massachusetts. The primary endpoints were the rates of inappropriate and appropriate TTE. RESULTS For the cardiology physicians-in-training, the proportion of inappropriate TTE was significantly lower in the intervention than in the control group (13% vs. 34%, p < 0.001). As a corollary, the proportion of appropriate TTE ordered by the intervention group was significantly higher than that of the control group (81% vs. 58%, p < 0.001). The odds of ordering an appropriate TTE in the cardiology intervention group was 2.7 (95% confidence interval [CI]: 1.5 to 5.1, p = 0.002) relative to the control group. The internal medicine physicians-in-training ordered a small number of TTE overall, and there was a trend toward significant odds of ordering an appropriate TTE in the intervention group relative to the control group (odds ratio [OR]: 8.1, 95% CI: 0.95 to 69.0, p = 0.055). Six clinical scenarios accounted for 75% of all inappropriate TTE, with the 3 most common inappropriate indications being routine surveillance (<1 year) of known cardiomyopathy without a change in clinical status, routine surveillance of known small pericardial effusion, and routine surveillance of ventricular function with known coronary artery disease and no change in clinical status. CONCLUSIONS In cardiology fellows with a high rate of ordering inappropriate TTE, an AUC-based educational and feedback intervention reduced the proportion of inappropriate outpatient TTE and increased the proportion of appropriate outpatient TTE. (Educational Intervention to Reduce Outpatient Inappropriate Transthoracic Echocardiograms; NCT01944202).

Multidisciplinary Pulmonary Embolism Response Teams

A 67-year-old man with no previous medical history presented to the emergency department with 5 days of insidious, progressive dyspnea and chest congestion. On physical examination, he was found to be tachycardic to 126 beats/min, borderline hypotensive with blood pressure of 95/50 mm Hg, and hypoxemic to 87% on 4 L of oxygen by nasal cannula. He underwent contrast-enhanced chest computed tomogram that demonstrated a bilateral pulmonary embolism (PE) (Figure 1). Urgent bedside echocardiography demonstrated a severely dilated and hypokinetic right ventricle, interventricular septal flattening, and a serpiginous mobile mass (clot-in-transit) in the right atrium, prolapsing across the tricuspid valve with each cardiac cycle (Figure 2 and online-only Data Supplement Movie). The emergency department team discussed administering systemic fibrinolytic therapy, but also considered consulting Cardiothoracic Surgery for possible surgical pulmonary embolectomy and Interventional Cardiology for catheter-directed therapy. The emergency department attending physician decided to activate the hospital’s newly instituted multidisciplinary PE response team through the page operator. Within 30 minutes, a team consisting of representatives from Vascular Medicine, Interventional Cardiology, Cardiothoracic Surgery, Pulmonology, Echocardiography, and Radiology convened to evaluate the patient’s case and review the imaging studies. Figure 1. Axial image from a contrast-enhanced chest computed tomogram showing significant right and left main pulmonary artery filling defects (arrows). Figure 2. The transthoracic echocardiogram, apical 4-chamber view, at end diastole shows dilatation of the right ventricle and a serpiginous intracardiac mass (arrow) in the right atrium, prolapsing across the tricuspid valve into the right ventricle. Please also see the online-only Data Supplement Movie. PE is a prevalent and potentially life-threatening cardiovascular condition that may be difficult to diagnose. It has protean and often nonspecific manifestations. It is the third most common cardiovascular cause of death in the United States, and yet, in comparison with ischemic heart disease, does not enjoy a similar robust clinical trial …

Educational intervention to reduce inappropriate transthoracic echocardiograms: the need for sustained intervention.

We previously demonstrated that an Appropriate Use Criteria (AUC)‐based educational intervention reduced inappropriate transthoracic echocardiograms (TTE) on an inpatient medical service. Whether improved TTE ordering is sustained after discontinuation of the intervention is unknown.

Who Decides When a Patient Can’t? Statutes on Alternate Decision Makers

U.S. states vary in their procedures for appointing and challenging default surrogates, the attributes they require of them, priority ranking of possible decision makers, and dispute resolution — with important implications for clinicians, patients, and public health.

Pulmonary embolism response teams.

Opinion statementPulmonary embolism (PE) is a complex and multidimensional pathophysiology, the diagnosis and management of which spans multiple disciplines. The high morbidity and associated mortality of “massive” and “submassive” acute PE may require prompt, definitive management; however, current consensus guidelines in this domain are not supported by high-level evidence. Randomized clinical trials comparing available pharmacologic and invasive treatment modalities—including anticoagulation, thrombolysis, and embolectomy—have not been conducted and continue to be challenging to conceptualize, design, and execute. Consequently, time-sensitive therapeutic determinations are largely not standardized, and rendered on a case-by-case basis in part depending on institutional practices and expertises. Chronic sequelae of PE, such as chronic thromboembolic pulmonary hypertension and right heart failure, are increasingly identified as conditions necessitating longitudinal specialty care. These and other challenges have created a niche for a multidisciplinary team which can respond rapidly to unstable patient scenarios, appropriately deploy resources, and offer highly specialized acute and chronic management of PE. The Massachusetts General Hospital Pulmonary Embolism Response Team (PERT), modeled after existing rapid response and collaborative care teams, is a novel approach that combines this clinical service with the development of an educational and research framework to advance the care of patients with PE.

Echocardiographic assessment of ischemic mitral regurgitation

Ischemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction. Echocardiographic diagnosis and assessment of ischemic mitral regurgitation are critical to gauge its adverse effects on prognosis and to attempt to tailor rational treatment strategy. There is no single approach to the echocardiographic assessment of ischemic mitral regurgitation: standard echocardiographic measures of mitral regurgitation severity and of LV dysfunction are complemented by assessments of displacement of the papillary muscles and quantitative indices of mitral valve deformation. Development of novel approaches to understand mitral valve geometry by echocardiography may improve understanding of the mechanism, clinical trajectory, and reparability of ischemic mitral regurgitation.