Ultrasound-assisted catheter-directed thrombolysis compared with anticoagulation alone for treatment of intermediate-risk pulmonary embolism.

It is unclear if ultrasound-assisted catheter-directed thrombolysis (UACDT) confers benefit over anticoagulation (AC) alone in the management of intermediate-risk ("submassive") pulmonary embolism (PE), defined by evidence of right ventricular (RV) dysfunction in hemodynamically stable patients. This study sought to evaluate any lasting advantage of UACDT on mortality and resolution of RV dysfunction in intermediate-risk PE at a large academic medical center. Adults aged ≤ 86 years admitted with intermediate-risk PE from 2011 to 2016 were retrospectively identified. Patients were excluded if there was a history of cancer, pre-existing pulmonary hypertension, pregnancy or postpartum status, contraindication to AC, or treatment with systemic thrombolysis. Baseline Pulmonary Embolism Severity Index (PESI) scores were computed. Outcomes including length of stay (LOS), bleeding complications, resolution of RV dysfunction, and mortality were compared between patients who received UACDT and those managed with AC alone. A total of 104 patients met inclusion criteria, 65 of whom underwent UACDT. The cohorts had similar PESI scores ( P = 0.45) and no clearly imbalanced confounding variables. There was no significant difference in LOS ( P = 0.11). UACDT was associated with more bleeding complications (exact P = 0.04). Follow-up transthoracic echocardiograms performed in 54 UACDT and 24 AC patients demonstrated similar rates of resolution of RV dysfunction (61% in UACDT patients versus 75% in AC patients, P = 0.25). Overall one-year mortality was approximately 5% in both groups (exact P > 0.99). In this limited retrospective analysis of intermediate-risk PE patients, UACDT treatment was not associated with mortality benefit or increased resolution of RV dysfunction.

Prevalence of paradoxical bronchoconstriction after inhaled albuterol.

PURPOSE: Paradoxical bronchoconstriction with resulting decreased airflow occurs in some patients after administration of bronchodilators. This study assessed the frequency of paradoxical bronchoconstriction in a real-life clinical setting at a large academic medical center. PROCEDURES: We analyzed data from 4593 patients who underwent pre- and post-bronchodilator spirometry testing. We assessed the forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) before and after the administration of an inhaled short-acting ß2-agonist. Patients were categorized into 3 groups: bronchodilation, no significant change and paradoxical bronchoconstriction. MAIN FINDINGS: When assessing response to bronchodilators, 201 (4.4%) patients demonstrated significant bronchoconstriction, whereas 849 (18.5%) showed bronchodilation. The majority (3543 or 77.1%) had no significant change. There were no significant relationships noted between paradoxical bronchoconstriction and sex, race/ethnicity or body mass index. CONCLUSIONS: A significant subset of patients experience paradoxical bronchoconstriction after albuterol administration. Further research to better understand the clinical implications of paradoxical acute bronchoconstriction is needed.

National trends in emergency room diagnosis of pulmonary embolism, 2001-2010: a cross-sectional study.

BACKGROUND: Little is known about the United States diagnosis and burden of pulmonary embolism (PE) in the emergency department (ED), and their evolution over the past decade. We examined nationally representative data to evaluate factors associated with and trends in ED diagnosis of PE. METHODS: We conducted a cross-sectional study using National Hospital Ambulatory Medical Care Survey (NHAMCS) data from January 1, 2001 to December 31, 2010. We identified all ED patient visits where PE was diagnosed and corresponding demographic, hemodynamic, testing and disposition data. Analyses were performed using descriptive statistics and multivariable logistic regression. RESULTS: During the study period 988,000 weighted patient visits with diagnosis of PE were identified. Among patients with an ED visit, the likelihood of having a diagnosis of PE per year increased significantly from 2001 to 2010 (odds ratio [OR] 1.091, 95% confidence interval [CI] 1.034-1.152, P = 0.002 for trend) when adjusted for demographic and hospital information. In contrast, when further adjusted for the use of computed tomography (CT) among patients in the ED, the likelihood of having a diagnosis of PE per year did not change (OR 1.041, 95% CI 0.987-1.097, P = 0.14). Overall, 75.1% of patients seen with a diagnosis of PE were hemodynamically stable; 86% were admitted with an in-hospital death rate under 3%. CONCLUSIONS: The proportion of ED visits with a diagnosis of PE increased significantly from 2001 to 2010 and this rise can be attributed in large part to the increased availability and use of CT. Most of these patients were admitted with low in-hospital mortality.

MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling.

RATIONALE: The rapid induction and orchestration of new blood vessels are critical for tissue repair in response to injury, such as myocardial infarction, and for physiological angiogenic responses, such as embryonic development and exercise. OBJECTIVE: We aimed to identify and characterize microRNAs (miR) that regulate pathological and physiological angiogenesis. METHODS AND RESULTS: We show that miR-26a regulates pathological and physiological angiogenesis by targeting endothelial cell (EC) bone morphogenic protein/SMAD1 signaling in vitro and in vivo. MiR-26a expression is increased in a model of acute myocardial infarction in mice and in human subjects with acute coronary syndromes. Ectopic expression of miR-26a markedly induced EC cycle arrest and inhibited EC migration, sprouting angiogenesis, and network tube formation in matrigel, whereas blockade of miR-26a had the opposite effects. Mechanistic studies demonstrate that miR-26a inhibits the bone morphogenic protein/SMAD1 signaling pathway in ECs by binding to the SMAD1 3'-untranslated region, an effect that decreased expression of Id1 and increased p21(WAF/CIP) and p27. In zebrafish, miR-26a overexpression inhibited formation of the caudal vein plexus, a bone morphogenic protein-responsive process, an effect rescued by ectopic SMAD1 expression. In mice, miR-26a overexpression inhibited EC SMAD1 expression and exercise-induced angiogenesis. Furthermore, systemic intravenous administration of an miR-26a inhibitor, locked nucleic acid-anti-miR-26a, increased SMAD1 expression and rapidly induced robust angiogenesis within 2 days, an effect associated with reduced myocardial infarct size and improved heart function. CONCLUSIONS: These findings establish miR-26a as a regulator of bone morphogenic protein/SMAD1-mediated EC angiogenic responses, and that manipulating miR-26a expression could provide a new target for rapid angiogenic therapy in ischemic disease states.

CT pulmonary angiography: increasingly diagnosing less severe pulmonary emboli.

BACKGROUND: It is unknown whether the observed increase in computed tomography pulmonary angiography (CTPA) utilization has resulted in increased detection of pulmonary emboli (PEs) with a less severe disease spectrum. METHODS: Trends in utilization, diagnostic yield, and disease severity were evaluated for 4,048 consecutive initial CTPAs performed in adult patients in the emergency department of a large urban academic medical center between 1/1/2004 and 10/31/2009. Transthoracic echocardiography (TTE) findings and peak serum troponin levels were evaluated to assess for the presence of PE-associated right ventricular (RV) abnormalities (dysfunction or dilatation) and myocardial injury, respectively. Statistical analyses were performed using multivariate logistic regression. RESULTS: 268 CTPAs (6.6%) were positive for acute PE, and 3,780 (93.4%) demonstrated either no PE or chronic PE. There was a significant increase in the likelihood of undergoing CTPA per year during the study period (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.04-1.07, P<0.01). There was no significant change in the likelihood of having a CTPA diagnostic of an acute PE per year (OR 1.03, 95% CI 0.95-1.11, P = 0.49). The likelihood of diagnosing a less severe PE on CTPA with no associated RV abnormalities or myocardial injury increased per year during the study period (OR 1.39, 95% CI 1.10-1.75, P = 0.01). CONCLUSIONS: CTPA utilization has risen with no corresponding change in diagnostic yield, resulting in an increase in PE detection. There is a concurrent rise in the likelihood of diagnosing a less clinically severe spectrum of PEs.

Ice cooling vest on tolerance for exercise under uncompensable heat stress.

This study was conducted to evaluate the effectiveness of a commercial, personal ice cooling vest on tolerance for exercise in hot (35°C), wet (65% relative humidity) conditions with a nuclear biological chemical suit (NBC). On three separate occasions, 10 male volunteers walked on a treadmill at 3 miles per hour and 2% incline while (a) seminude (denoted CON), (b) dressed with a nuclear, biological, chemical (NBC) suit with an ice vest (V) worn under the suit (denoted NBCwV); or (c) dressed with an NBC suit but without an ice vest (V) (denoted NBCwoV). Participants exercised for 120 min or until volitional fatigue, or esophageal temperature reached 39.5°C. Esophageal temperature (T(es)), heart rate (HR), thermal sensation, and ratings of perceived exertion were measured. Exercise time was significantly greater in CON compared with both NBCwoV and NBCwV (p < 0.05), whereas T(es), thermal sensation, heart rate, and rate of perceived exertion were lower (p < 0.05). Wearing the ice vest increased exercise time (NBCwoV, 103.6 ± 7.0 min; NBCwV, 115.9 ± 4.1 min) and reduced the level of thermal strain, as evidenced by a lower T(es) at end-exercise (NBCwoV, 39.03 ± 0.13°C; NBCwV, 38.74 ± 0.13°C) and reduced thermal sensation (NBCwoV, 6.4 ± 0.4; NBCwV, 4.8 ± 0.6). This was paralleled by a decrease in rate of perceived exertion (NBCwoV, 14.7 ± 1.6; NBCwV, 12.4 ± 1.6) (p < 0.05) and heat rate (NBCwoV, 169 ± 6; NBCwV, 159 ± 7) (p < 0.05). We show that a commercially available cooling vest can significantly reduce the level of thermal strain during work performed in hot environments.

Dissociation of bimolecular αIIbß3-fibrinogen complex under a constant tensile force.

The regulated ability of integrin αIIbß3 to bind fibrinogen plays a crucial role in platelet aggregation, adhesion, and hemostasis. Employing an optical-trap-based electronic force clamp, we studied the thermodynamics and kinetics of αIIbß3-fibrinogen bond formation and dissociation under constant unbinding forces, mimicking the forces of physiologic blood shear on a thrombus. The distribution of bond lifetimes was bimodal, indicating that the αIIbß3-fibrinogen complex exists in two bound states with different mechanical stability. The αIIbß3 antagonist, abciximab, inhibited binding without affecting the unbinding kinetics, whereas Mn²(+) biased the αIIbß3-fibrinogen complex to the strong bound state with reduced off-rate. The average bond lifetimes decreased exponentially with increasing pulling force from ∼5 pN to 50 pN, suggesting that in this force range the αIIbß3-fibrinogen interactions are classical slip bonds. We found no evidence for catch bonds, which is consistent with the known lack of shear-enhanced platelet adhesion on fibrinogen-coated surfaces. Taken together, these data provide important quantitative and qualitative characteristics of αIIbß3-fibrinogen binding and unbinding that underlie the dynamics of platelet adhesion and aggregation in blood flow.

Rhythm and conduction disturbances at midterm follow-up after the ross procedure in infants, children, and young adults.

BACKGROUND: To our knowledge, late electrophysiologic outcomes after the Ross procedure have not been described. The purpose of this study was to assess rhythm and conduction disturbances at midterm follow-up after the Ross procedure. METHODS: A cross-sectional analysis of Ross procedure survivors (January 1, 1995 to December 31, 2005) followed at our institution was performed, including resting and 24-hour ambulatory electrocardiography (Holter monitoring). Rhythm and conduction disturbances were described, and predictors of arrhythmia were identified. RESULTS: Of 64 eligible patients, 47 (71%) participated. Median age at surgery was 8.7 years (age range, 34 days to 34 years). Twenty-five patients (53%) had isolated aortic valve disease and 22 (47%) had complex left-sided heart disease. At median follow-up of 8.9 years (range, 2.6-11.1 years), 46 patients (98%) exhibited sinus rhythm. Sinus node dysfunction (SND), defined as a pause of 2 seconds or longer or bradycardia for age, was present in 7 patients (15%). Complete heart block requiring a pacemaker occurred in 2 patients (4%). Ventricular tachycardia (VT) was present in 7 patients (15%), including nonsustained VT in 5 patients on Holter monitoring, and sustained VT in 2 patients requiring defibrillator placement. In multivariate analysis, concurrent arch repair at the time of the Ross operation (p = 0.04), longer cross-clamp time at the time of Ross operation (p = 0.04), and right ventricular outflow tract obstruction on follow-up echocardiogram (p = 0.03) were associated with SND. Longer cross-clamp time (p = 0.03) was also associated with VT, along with older age at surgery (p = 0.06 for trend). CONCLUSIONS: At midterm follow-up after the Ross procedure, rhythm and conduction disturbances occur in one third of patients, including SND in 15%, atrioventricular block in 4%, and VT in 15%. Routine surveillance for late arrhythmias after the Ross procedure is warranted.

Photoacoustic effect for multiply scattered light.

We consider the photoacoustic effect for multiply scattered light in a random medium. Within the accuracy of the diffusion approximation to the radiative transport equation, we present a general analysis of the sensitivity of a photoacoustic wave to the presence of one or more small absorbing objects. Applications to tumor detection by photoacoustic imaging are suggested.