Prognostic significance of nonfatal reinfarction during 3-year follow-up: Results of the thrombolysis in myocardial infarction (TIMI) phase II clinical trial

Objectives.This study sought to assess the independent contribution of nonfatal reinfarction to the risk of subsequent death in patients with acute myocardial infarction undergoing thrombolytic therapy.Background.A composite of “unsatisfactory outcomes” as an end point has increased statistical power and facilitated evaluation of evolving treatment regimens in acute myocardial infarction. The significance of nonfatal reinfarction as a component of a composite end point has not been evaluated in the thrombolytic era.Methods.Event rate of nonfatal reinfarction over 3-year follow-up was evaluated in patients with acute myocardial infarction entered into the Thrombolysis in Myocardial Infarction Phase II trial. The independent risk of nonfatal reinfarction for subsequent death within various time intervals of follow-up was determined. The mortality rate after nonfatal reinfarction was compared with that of a matched control group.Results.During 3-year follow-up, 349 of 3,339 patients had a nonfatal reinfarction. Univariate predictors were history (antedating the index event) of angina (p = 0.01), hypertension (p = 0.01), multivessel disease (p = 0.007) and not a current smoker (p = 0.003); the latter was an independent predictor (relative risk [RR] 1.3, 99% confidence interval [CI]1.0 to 1.8). Forty-three of the 349 patients with a nonfatal reinfarction died: RR for death (vs. patients without a nonfatal reinfarction) was 1.9 (99% CI 1.1 to 3.2) if reinfarction occurred within 42 days of study entry, 6.2 (99% CI 3.0 to 12.9) if reinfarction occurred between 43 and 365 days and 2.9 (99% CI 0.6 to 13.4) if reinfarction occurred between 366 days and 3 years. The cumulative 3-year death rate was 14.1% in patients with a nonfatal reinfarction compared with 7.9% (p < 0.01) in a matched control group. Univariate predictors of death after nonfatal reinfarction were age ≥65 years (p < 0.001), not low risk category (p = 0.015) and history of heart failure before the index event (p < 0.001). Age ≥65 years was the only independent predictor (RR 5.4, 99% CI 2.3 to 12.4).Conclusions.Nonfatal reinfarction is a strong and independent predictor for subsequent death. It represents a powerful component for a composite end point in patients who received thrombolytic therapy after acute myocardial infarction

Translational development of an ADAMTS-5 antibody for osteoarthritis disease modification

SummaryObjective/MethodAggrecanase activity, most notably ADAMTS-5, is implicated in pathogenic cartilage degradation. Selective monoclonal antibodies (mAbs) to both ADAMTS-5 and ADAMTS-4 were generated and in vitro, ex vivo and in vivo systems were utilized to assess target engagement, aggrecanase inhibition and modulation of disease-related endpoints with the intent of selecting a candidate for clinical development in osteoarthritis (OA).ResultsStructural mapping predicts the most potent mAbs employ a unique mode of inhibition by cross-linking the catalytic and disintegrin domains. In a surgical mouse model of OA, both ADAMTS-5 and ADAMTS-4-specific mAbs penetrate cartilage following systemic administration, demonstrating access to the anticipated site of action. Structural disease modification and associated alleviation of pain-related behavior were observed with ADAMTS-5 mAb treatment. Treatment of human OA cartilage demonstrated a preferential role for ADAMTS-5 inhibition over ADAMTS-4, as measured by ARGS neoepitope release in explant cultures. ADAMTS-5 mAb activity was most evident in a subset of patient-derived tissues and suppression of ARGS neoepitope release was sustained for weeks after a single treatment in human explants and in cynomolgus monkeys, consistent with high affinity target engagement and slow ADAMTS-5 turnover.ConclusionThis data supports a hypothesis set forth from knockout mouse studies that ADAMTS-5 is the major aggrecanase involved in cartilage degradation and provides a link between a biological pathway and pharmacology which translates to human tissues, non-human primate models and points to a target OA patient population. Therefore, a humanized ADAMTS-5-selective monoclonal antibody (GSK2394002) was progressed as a potential OA disease modifying therapeutic

Asymptomatic cardiac ischemia pilot (ACIP) study: Effects of coronary angioplasty and coronary artery bypass graft surgery on recurrent angina and ischemia

ObjectivesThe Asymptomatic Cardiac Ischemia Pilot (ACIP) study showed that revascularization is more effective than medical therapy in suppressing cardiac ischemia at 12 weeks. This report compares the relative efficacy of coronary angioplasty or coronary artery bypass graft surgery in suppressing ambulatory electrocardiographic (ECG) and treadmill exercise cardiac ischemia between 2 and 3 months after revascularization in the ACIP study.BackgroundPrevious studies have shown that coronary angioplasty and bypass surgery relieve angina early after the procedure in a high proportion of selected patients. However, alleviation of ischemia on the ambulatory ECG and treadmill exercise test have not been adequately studied prospectively after revascularization.MethodsIn patients randomly assigned to revascularization in the ACIP study, the choice of coronary angioplasty or bypass surgery was made by the clinical unit staff and the patient.ResultsPatients assigned to bypass surgery (n = 78) had more severe coronary disease (p = 0.001) and more ischemic episodes (p = 0.01) at baseline than those assigned to angioplasty (n = 92). Ambulatory ECG ischemia was no longer present 8 weeks after revascularization (12 weeks after enrollment) in 70% of the bypass surgery group versus 46% of the angioplasty group (p = 0.002). ST segment depression on the exercise ECG was no longer present in 46% of the bypass surgery group versus 23% of the angioplasty group (p = 0.005). Total exercise time in minutes on the treadmill exercise test increased by 2.4 min after bypass surgery and by 1.4 min after angioplasty (p = 0.02). Only 10% of the bypass surgery group versus 32% of the angioplasty group still reported angina in the 4 weeks before the 12-week visit (p = 0.001).ConclusionsAngina and ambulatory ECG ischemia are relieved in a high proportion of patients early after revascularization. However, ischemia can still be induced on the treadmill exercise test, albeit at higher levels of exercise, in many patients. Bypass surgery was superior to coronary angioplasty in suppressing cardiac ischemia despite the finding that patients who underwent bypass surgery had more severe coronary artery disease

Subpubic cartilaginous cystic lesion presenting as a vulvar mass: a case report

<p>Abstract</p> <p>Introduction</p> <p>A subpubic cartilaginous cyst is a rare and innocent defect originating from the symphysis pubis and may present as a vulvar mass and/or chronic abdominal pain. The symphysis pubis is a non-synovial amphiarthrodial joint that forms a fibrocartilaginous union between the two pubic bones and in general lies without mainstream interest, despite its clinical relevance. This case report focuses attention on this joint.</p> <p>Case presentation</p> <p>A 55-year-old Caucasian woman presented with a painful and rapidly increasing vulvar mass. Imaging techniques revealed a cyst-like structure originating from a degenerated symphysis pubis. The cyst was excised, however, recovery was complicated by a symphysiolysis.</p> <p>Conclusion</p> <p>A subpubic cartilaginous cyst is a rare cystic lesion originating from the symphysis of the pubic bone which presents as a vulvar mass which might be complicated by symphysiolysis. Several diseases affect the symphysis pubis and result in significant discomfort and disability in patients. The symphysis pubis is therefore clinically important and should not be omitted in the differential diagnosis of a vulvar mass and/or chronic abdominal pain.</p

Pregnancy-related pelvic girdle pain: an update

A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women

Components in evaluation of complex interior truck sounds

In order to investigate influences on assessment of interior truck sounds two experiments have been carried out with emphasis on the low frequency content. In the first experiment the participants were presented with recorded sound from the interior of a truck cabin, with different alterations of the low frequency content. In the second experiment the balance between low and high frequency content was altered for the recorded sounds. Three main dimensions important for the assessment of truck sounds were found: an Annoyance factor, a Wakefulness factor and a Quality factor. Additionally it was found that a wellsuited spectral balance could improve positive impressions of truck sound