IntroductionMyocardial infarction (MI) is a major cause of left ventricular (LV) remodeling and, thus, of heart failure and sudden cardiac death. [1][2][3] Several lines of evidence supporting a key role for aldosterone in LV remodeling provided the rationale for clinical trials that demonstrated clinical effi cacy of aldosterone receptor antagonists to treat patients with established heart failure and MI. 4,5 Th ere is accumulating clinical and experimental evidence that female sex may play a signifi cant role in cardiovascular responsiveness to the aldosterone signaling pathway. For example, serum levels of aldosterone correlate with LV hypertrophy and LV mass index in women but not in men, 6 and in rodent models, activation of estrogen receptors protects the cardiovascular system against the detrimental eff ects of aldosterone-salt treatment, including eff ects on blood pressure, cardiac hypertrophy, and vascular fi brosis. 7Of critical importance, clinical and experimental studies have demonstrated that estrogen and mineralocorticoid receptors are both expressed in cardiac myocytes, fi broblasts, and vascular cells, 8,9 and sexual dimorphism in neurohumoral activation may infl uence cardiac remodeling, response to therapy, 10-13 and survival.14 Accordingly, we predicted that females would be more responsive to aldosterone receptor blockade post-MI compared with males. We addressed this hypothesis by administering eplerenone to rats of both sexes following MI. Methods Animal modelMI induced by permanent coronary artery ligation or sham surgery was performed in female and male 6-month-old Wistar rats. Briefl y, the rats were intubated and ventilated with 2% isofl urane in oxygen using a rodent respirator (Model 683; Harvard Apparatus, Inc., MA, USA). Th e heart was exposed via a left lateral thoracotomy, and the left anterior descending coronary artery was permanent ligated 2-3 mm below its origin with a 6-0 silk suture. Th e chest was closed, and the rat was allowed to recover under care.The animals were randomly assigned to receive either eplerenone (100 mg/kg/day in food; Research Diets, Inc., NJ, USA) or placebo starting from 3 days post surgery and up to sacrifi ce 4 weeks later. Th e 3-day post-MI time point was chosen for the initiation of treatment with eplerenone due to higher mortality within 48 hours. Th e institutional animal care and use committee of Th e Johns Hopkins University School of Medicine approved all protocols and experimental procedures. Echocardiographic measurementsEchocardiographic measurements were obtained at baseline, 5 days, 2 weeks, and 4 weeks. Echocardiographic assessments were performed in anesthetized (2% isofl urane inhalation) rats using a Sonos-5500 Echocardiogram (Philips, MA, USA) equipped with a 15-MHz transducer. Cardiac dimensions such as left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD) and fractional shortening (FS) were recorded from M-mode images using averaged measurements from three to fi ve consecutive cardia...

IMPORTANCE Small studies have implicated the association of specific autoantibodies with morphea subtype or severity, but no large-scale studies have been conducted. This prospective case-control study confirmed the presence of antinuclear antibodies (ANAs) and other autoantibodies in morphea but found they are of limited significance. OBJECTIVE To determine the prevalence of ANAs, extractable nuclear antigens such as antihistone antibodies (AHAs), and anti–single-stranded DNA antibodies (ssDNA abs) in patients with morphea vs a healthy control population and their association with clinical measures of morphea severity. DESIGN, SETTING, AND PARTICIPANTS Nested case-control study, conducted at the University of Texas Southwestern Medical Center, Dallas, and University of Texas Health Science Center, Houston. Study participants included individuals enrolled in the Morphea in Adults and Children (MAC) cohort and Scleroderma Family Registry and DNA Repository. MAIN OUTCOMES AND MEASURES Prevalence of ANAs, AHAs, ssDNA abs in patients with morphea vs matched controls and association of the presence of autoantibodies with clinical indicators of morphea severity. RESULTS The prevalence of ANAs, AHAs, and ssDNA abs in patients with morphea was 34%, 12%, and 8%, respectively. Antinuclear antibodies and AHAs, but not ssDNA abs, were present more frequently in cases than in controls. There was no difference in ANA prevalence among morphea subtypes. Among patients with linear morphea, the presence of autoantibodies was associated with clinical indicators of severe morphea including functional limitation (ssDNA ab, P = .005; and AHA, P = .006), extensive body surface area involvement (ssDNA ab, P = .01; and ANA, P = .005), and higher skin scores (ANA, P = .004). The presence of autoantibodies was not associated with clinical measures of morphea activity. CONCLUSIONS AND RELEVANCE Our results demonstrate that ANAs and AHAs are more prevalent among patients with morphea but are of limited clinical utility except in linear morphea, where their presence, although infrequent, is associated with greater lesion burden and functional impairment.

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All three of the TNFalpha antagonists have remarkable efficacy in patients with severe psoriasis. The risks of serious adverse events are relatively rare and comparable to the risks patients take on a regular basis such as driving a car. For many patients with severe psoriasis, the benefits of TNFalpha inhibitors may greatly outweigh the risks.