Toll-like receptors and NOD-like receptors in rheumatic diseases

The past 10 years have seen the description of families of receptors that drive proinflammatory cytokine production in infection and tissue injury. Two major classes have been examined in the context of inflammatory joint disease - the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs such as TLR2 and TLR4 are being implicated in the pathology of rheumatoid arthritis, ankylosing spondylitis, lyme arthritis and osteoarthritis. Nalp3 has been identified as a key NLR for IL-1β production and has been shown to have a particular role in gout. These findings present new therapeutic opportunities, possibly allowing for the replacement of biologics with small molecule inhibitors

Caval-Aortic Access to Allow Transcatheter Aortic Valve Replacement in Otherwise Ineligible Patients Initial Human Experience

ObjectivesThis study describes the first use of caval-aortic access and closure to enable transcatheter aortic valve replacement (TAVR) in patients who lacked other access options. Caval-aortic access refers to percutaneous entry into the abdominal aorta from the femoral vein through the adjoining inferior vena cava.BackgroundTAVR is attractive in high-risk or inoperable patients with severe aortic stenosis. Available transcatheter valves require large introducer sheaths, which are a risk for major vascular complications or preclude TAVR altogether. Caval-aortic access has been successful in animals.MethodsWe performed a single-center retrospective review of procedural and 30-day outcomes of prohibitive-risk patients who underwent TAVR via caval-aortic access.ResultsBetween July 2013 and January 2014, 19 patients underwent TAVR via caval-aortic access; 79% were women. Caval-aortic access and tract closure were successful in all 19 patients; TAVR was successful in 17 patients. Six patients experienced modified VARC-2 major vascular complications, 2 (11%) of whom required intervention. Most (79%) required blood transfusion. There were no deaths attributable to caval-aortic access. Throughout the 111 (range 39 to 229) days of follow up, there were no post-discharge complications related to tract creation or closure. All patients had persistent aorto-caval flow immediately post-procedure. Of the 16 patients who underwent repeat imaging after the first week, 15 (94%) had complete closure of the residual aorto-caval tract.ConclusionsPercutaneous transcaval venous access to the aorta allows TAVR in otherwise ineligible patients, and may offer a new access strategy for other applications requiring large transcatheter implants

Partitioning Evapotranspiration in Semiarid Grassland and Shrubland Ecosystems Using Diurnal Surface Temperature Variation

The encroachment of woody plants in grasslands across the Western U.S. will affect soil water availability by altering the contributions of evaporation (E) and transpiration (T) to total evapotranspiration (ET). To study this phenomenon, a network of flux stations is in place to measure ET in grass- and shrub-dominated ecosystems throughout the Western U.S. A method is described and tested here to partition the daily measurements of ET into E and T based on diurnal surface temperature variations of the soil and standard energy balance theory. The difference between the mid-afternoon and pre-dawn soil surface temperature, termed Apparent Thermal Inertia (I(sub A)), was used to identify days when E was negligible, and thus, ET=T. For other days, a three-step procedure based on energy balance equations was used to estimate Qe contributions of daily E and T to total daily ET. The method was tested at Walnut Gulch Experimental Watershed in southeast Arizona based on Bowen ratio estimates of ET and continuous measurements of surface temperature with an infrared thermometer (IRT) from 2004- 2005, and a second dataset of Bowen ratio, IRT and stem-flow gage measurements in 2003. Results showed that reasonable estimates of daily T were obtained for a multi-year period with ease of operation and minimal cost. With known season-long daily T, E and ET, it is possible to determine the soil water availability associated with grass- and shrub-dominated sites and better understand the hydrologic impact of regional woody plant encroachment

Five-Year Follow-Up of the Argentine Randomized Trial of Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease (ERACI II)

ObjectivesThe purpose of the present study is to report the five-year follow-up results of the ERACI II trial.BackgroundImmediate and one-year follow-up results of the ERACI II study showed a prognosis advantage of percutaneous coronary intervention (PCI) with stents over coronary artery bypass grafting (CABG).MethodsA total of 450 patients were randomly assigned to undergo either PCI (n = 225); or CABG (n = 225). Only patients with multi-vessel disease were enrolled. Clinical follow-up during five years was obtained in 92% of the total population after hospital discharge. The primary end point of the study was to compare freedom from major adverse cardiovascular events (MACE) at 30 days, 1 year, 3 years, and 5 years of follow-up.ResultsAt five years of follow-up, patients initially treated with PCI had similar survival and freedom from non-fatal acute myocardial infarction than those initially treated with CABG (92.8% vs. 88.4% and 97.3% vs. 94% respectively, p = 0.16). Freedom from repeat revascularization procedures (PCI/CABG) was significantly lower with PCI compared with CABG (71.5% vs. 92.4%, p = 0.0002). Freedom from MACE was also significantly lower with PCI compared with CABG (65.3% vs. 76.4%; p = 0.013). At five years similar numbers of patients randomized to each revascularization procedure were asymptomatic or with class I angina.ConclusionsAt five years of follow-up, in the ERACI II study, there were no survival benefits from any revascularization procedure; however patients initially treated with CABG had better freedom from repeat revascularization procedures and from MACE

New-Onset Atrial Fibrillation After Aortic Valve Replacement Comparison of Transfemoral, Transapical, Transaortic, and Surgical Approaches

ObjectivesThis study sought to determine the incidence of new-onset atrial fibrillation (AF) associated with different methods of isolated aortic valve replacement (AVR)—transfemoral (TF), transapical (TA), and transaortic (TAo) catheter-based valve replacement and conventional surgical approaches.BackgroundThe relative incidences of AF associated with the various access routes for AVR have not been well characterized.MethodsIn this single-center, retrospective cohort study, we evaluated a total of 231 consecutive patients who underwent AVR for degenerative aortic stenosis (AS) between March 2010 and September 2012. Patients with a history of paroxysmal, persistent, or chronic AF, with bicuspid aortic valves, and patients who died within 48 h after AVR were excluded. A total of 123 patients (53% of total group) qualified for inclusion. Data on documented episodes of new-onset AF, along with all clinical, echocardiographic, procedural, and 30-day follow-up data, were collated.ResultsAF occurred in 52 patients (42.3%). AF incidence varied according to the procedural method. AF occurred in 60% of patients who underwent surgical AVR (SAVR), in 53% after TA-TAVR, in 33% after TAo-TAVR cases, and 14% after TF-TAVR. The episodes occurred at a median time interval of 53 (25th to 75th percentile, 41 to 87) h after completion of the procedure. Procedures without pericardiotomy had an 82% risk reduction of AF compared with those with pericardiotomy (adjusted odds ratio: 0.18; 95% confidence interval: 0.05 to 0.59).ConclusionsAF was a common complication of AVR with a cumulative incidence of >40% in elderly patients with degenerative AS who underwent either SAVR or TAVR. AF was most common with SAVR and least common with TF-TAVR. Procedures without pericardiotomy were associated with a lower incidence of AF

Comparison of left ventricular function and contractile reserve after successful recanalization by thrombolysis versus rescue percutaneous transluminal coronary angioplasty for acute myocardial infarction

To determine how coronary reperfusion affects rest and exercise ventricular function after acute myocardial infarction (AMI), 63 patients with a patent infarct artery after intravenous thrombolytic therapy (lysis) were compared with 27 patients who failed thrombolysis but had successful acute recanalization by percutaneous transluminal coronary angioplasty (PTCA) as a "rescue" procedure. Contrast ventriculography was performed acutely and on day 7. Resting radionuclide ventriculography was performed at 24 hours and repeated with exercise on day 30. There were no differences in global ejection fraction (EF) between the 2 groups during acute contrast ventriculography. However, by 24 hours, the EF had deteriorated in the rescue group (40 +/- 17 vs 49 +/- 11% in the lysis group, p = 5%) increase in EF with exercise occurred in 64%, with either normal or exercise-enhanced regional wall motion present in 67% of patients. A significant increase in EF occurred within the rescue group, from 46 +/- 14% at rest to 50 +/- 15% at peak exercise (p <= 0.0005). The EF increased with exercise from 50 +/- 11 to 58 +/- 15% in the lysis group (p <= 0.0001). With equivalent workloads, the lysis group had a significantly greater EF response to exercise compared with rescue patients (7.5 +/- 7.5 vs 3.8 +/- 4.7%, p < 0.02). Despite successful acute recanalization in all patients, differences in ventricular function were apparent including: (1) greater preservation of ventricular function at 24 hours in patients with successful thrombolysis; (2) late improvement in resting EF with rescue PTCA; and (3) greater contractile reserve in patients with successful thrombolytic reperfusion. These data suggest that full recovery of myocardium may not be accurately assessed with a predischarge resting ventriculogram. Aggressive revascularization with thrombolysis or PTCA (or both) resulted in a normal EF response to exercise after AMI. Although successful thrombolytic reperfusion appears to be the most beneficial regimen, rescue PTCA may also be a viable strategy resulting in late improvement in EF and maintenance of EF response to exercise.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27160/1/0000155.pd

Macrosystems ecology: Understanding ecological patterns and processes at continental scales

Macrosystems ecology is the study of diverse ecological phenomena at the scale of regions to continents and their interactions with phenomena at other scales. This emerging subdiscipline addresses ecological questions and environmental problems at these broad scales. Here, we describe this new field, show how it relates to modern ecological study, and highlight opportunities that stem from taking a macrosystems perspective. We present a hierarchical framework for investigating macrosystems at any level of ecological organization and in relation to broader and finer scales. Building on well-established theory and concepts from other subdisciplines of ecology, we identify feedbacks, linkages among distant regions, and interactions that cross scales of space and time as the most likely sources of unexpected and novel behaviors in macrosystems. We present three examples that highlight the importance of this multiscaled systems perspective for understanding the ecology of regions to continents

Pulsed Doppler assessment of left ventricular diastolic filling in coronary artery disease before and immediately after coronary angioplasty

To determine if left ventricular (LV) diastolic filling abnormalities are detectable by Doppler echocardiography in patients with coronary artery disease (CAD), 34 patients with CAD and 24 normal, agematched control subjects underwent mitral valve pulsed Doppler examination. At catheterization, all CAD patients had typical angina, at least 70% diameter narrowing of 1 major coronary artery, ejection fraction of 50% or more and no valvular heart disease. Seventeen CAD patients underwent coronary angioplasty and had a Doppler examination 1 day before and 1 day after the procedure. Doppler diastolic time intervals, peak velocities at rapid filling (E velocity), atrial contraction (A velocity) and the ratio peak E/peak A velocities were measured. The following areas under the Doppler velocity envelope and their percentage of the total area were calculated: first third of diastole (0.33 area), triangular area under the peak E velocity (E area), and triangular area under the peak A velocity (A area). Patients with CAD and normal subjects were significantly different (p < 0.01) in peak E velocity (CAD 0.60 +/- 0.12 m/s, normal 0.68 +/- 0.12 m/s), peak A velocity (CAD 0.59 +/- 0.12 m/s, normal 0.48 +/- 0.11 m/s), ratio peak E/peak A velocities (CAD 1.0 +/- 0.27, normal 1.5 +/- 0.32), A area (CAD 0.052 +/- 0.015 m, normal 0.036 +/- 0.010 m), ratio E area/A area (CAD 1.7 +/- 0.53, normal 2.5 +/- 0.69), and all area fractions. In the CAD patients who had undergone coronary angioplasty, no differences were found in any Doppler index before and immediately after the procedure. Thus, abnormal patterns of LV diastolic filling occur in patients with CAD and normal global systolic function. The decreased percentage of the Doppler area occurring during rapid filling and the increased percentage of the Doppler area occurring in late diastole suggest that CAD patients have impaired early diastolic filling. These diastolic filling abnormalities are unimproved 24 hours after successful coronary angioplasty. Doppler echocardiography provides a useful, noninvasive technique for assessment of LV diastolic filling in patients with CAD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26727/1/0000277.pd

Infarct vessel status after intravenous tissue plasminogen activator and acute coronary angioplasty: Prediction of clinical outcome

To determine the risk of arterial reocclusion or recurrent ischemia after acute intervention in myocardial infarction, we analyzed the results of coronary arteriography performed acutely and at 1 week in 50 consecutive patients who received acute intervention. Successful recanalization of the infarct vessel was achieved in 46 (92%) patients after therapy with intravenous tissue plasminogen activator, percutaneous coronary angioplasty, or both. Follow-up angiography in 44 showed early reocclusion in 10 patients (23%). Intermittent patency during acute arteriography was always associated with reocclusion; suboptimal (Thrombolysis in Myocardial Infarction [TIMI] class 2) flow was associated with a 50% rate of reocclusion. Although residual stenosis of >50% alone was not predictive of rethrombosis, 90% of all reocclusions were associated with either stenosis >50%, TIMI 2 flow, or intermittent patency. Absence of these angiographic risk factors predicted a 95% patency rate at follow-up. In-hospital cardiac complications occurred in 17 of 23 (74%) patients with residual stenosis of >50% (death in four, ischemia in 13), and late revascularization was required in 53% of survivors. Only 15% of the group with p =50% appears to predict a high incidence of negative in-hospital clinical outcomes and the need for subsequent revascularization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27437/1/0000475.pd