Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation

OBJECTIVES: The present study was designed to evaluate the relationship between the presence of aortic sclerosis, serologic markers of inflammation, and adverse cardiovascular outcomes. BACKGROUND: Aortic sclerosis is associated with adverse cardiovascular outcomes. However, the mechanism by which such nonobstructive valve lesions impart excess cardiovascular risk has not been delineated. METHOD: In 425 patients (mean age 68 +/- 15 years, 54% men) presenting to the emergency room with chest pain, we studied the relationship among aortic sclerosis, the presence and acuity of coronary artery disease, serologic markers of inflammation, and cardiovascular outcomes. Patients underwent echocardiography and serologic testing including C-reactive protein (CRP). Aortic valves were graded for the degree of sclerosis, and cardiovascular outcomes including cardiac death and nonfatal myocardial infarction (MI) were analyzed over one year. RESULTS: Aortic sclerosis was identified in 203 patients (49%), whereas 212 (51%) had normal aortic valves. On univariate analysis at one year, patients with aortic sclerosis had a higher incidence of cardiovascular events (16.8% vs. 7.1%, p = 0.002) and worse event-free survival (normal valves = 93%, mild aortic sclerosis = 85%, and moderate to severe aortic sclerosis = 77%, p = 0.002). However, by multivariable analysis aortic sclerosis was not independently associated with adverse cardiovascular outcomes; the only independent predictors of cardiac death or MI at one year were coronary artery disease (hazard ratio [HR] 3.23, p = 0.003), MI at index admission (HR 2.77, p = 0.008), ascending tertiles of CRP (HR 2.2, p = 0.001), congestive heart failure (HR 2.15, p = 0.02) and age (HR 1.03, p = 0.04). CONCLUSIONS: The increased incidence of adverse cardiovascular events in patients with aortic sclerosis is associated with coronary artery disease and inflammation, not a result of the effects of valvular heart disease per se.     

Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(- )-inhibitor complexes in sepsis

Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(- )-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(- 4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.     

Pluronic F-68 reduces the endothelial adherence and improves the rheology of liganded sickle erythrocytes

A perfluorochemical blood substitute emulsified with Pluronic F-68 has been shown to improve the filterability of deoxygenated sickle red cells. We questioned whether some of the effect was independent of oxygen loading and studied the influence of Fluosol DA (Green Cross, Osaka, Japan) and Pluronic on the rheology and adhesion of sickle red cells saturated with oxygen and carbon monoxide. A 5-vol/vol% concentration of Fluosol or equivalent concentration of Pluronic was equally effective at improving the filtration of washed sickle cells through 5-micron-diameter pores at wall shear stresses approximating 1,000 dyne/cm2. The same concentration of Pluronic reduced the extensional static rigidity of irreversibly sickled cells (ISC) by 25% and also abolished the adherence of gravity-sedimented sickle cells to endothelial monolayers in the presence of saline or plasma. The inhibition of adherence was not reversible by washing and was accomplished with equal ease by isolated treatment of sickle cells or endothelium. Pluronic had no effect on the rheology or adhesion of normal adult red cells. Neither Fluosol nor Pluronic changed sickle or normal cell shape, mean cell volume, mean cell density, or cell density distribution. A lubricating effect of Pluronic on cell surfaces could explain all of the rheological observations and offers another direction of inquiry in the search for therapy for sickle cell disease.     

National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury

Objective Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention.Materials and Methods A national retrospective cohort of 1,620,898 patient hospitalizations from 116 Veterans Affairs hospitals was assembled from electronic health record (EHR) data collected from 2003 to 2012. HA-AKI was defined at stage 1+, stage 2+, and dialysis. EHR-based predictors were identified through logistic regression, least absolute shrinkage and selection operator (lasso) regression, and random forests, and pair-wise comparisons between each were made. Calibration and discrimination metrics were calculated using 50 bootstrap iterations. In the final models, we report odds ratios, 95% confidence intervals, and importance rankings for predictor variables to evaluate their significance.Results The area under the receiver operating characteristic curve (AUC) for the different model outcomes ranged from 0.746 to 0.758 in stage 1+, 0.714 to 0.720 in stage 2+, and 0.823 to 0.825 in dialysis. Logistic regression had the best AUC in stage 1+ and dialysis. Random forests had the best AUC in stage 2+ but the least favorable calibration plots. Multiple risk factors were significant in our models, including some nonsteroidal anti-inflammatory drugs, blood pressure medications, antibiotics, and intravenous fluids given during the first 48 h of admission.Conclusions This study demonstrated that, although all the models tested had good discrimination, performance characteristics varied between methods, and the random forests models did not calibrate as well as the lasso or logistic regression models. In addition, novel modifiable risk factors were explored and found to be significant.     

The Cognitive Therapy Scale and Cognitive Therapy Scale-Revised as Measures of Therapist Competence in Cognitive Behavior Therapy for Depression: Relations with Short and Long Term Outcome

Therapist competence is an important factor in treatment integrity. This study reports on a direct comparison of the original Cognitive Therapy Scale (CTS) with the revised version, the Cognitive Therapy Scale-Revised (CTS-R), as observational instruments designed to evaluate therapist competence in a completed trial of Cognitive Behavior Therapy (CBT) for depression. Treatment sessions (N?=?94) from 50 depressed participants (M age?=?39.2 years, 76% female, with an average of 5.9 depressive episodes) were evaluated on the CTS and CTS-R by trained independent observers who were blind to treatment outcome, as well as to subject, and session numbers. A comprehensive training program and inter-rater reliability monitoring protocol were employed. Two models were used to compare CTS and CTS-R in relation to change in depression symptoms at termination, 12 and 24 month follow-up while controlling for pre-treatment depression levels and working alliance. Both the CTS and CTS-R demonstrated comparable internal reliability, interrater reliability, and when assessed in early treatment phase, both predicted a statistically significant reduction in depressive symptomatology at termination. No significant competence-outcome relations were detected with late CTS and CTS-R ratings, and the significant positive interaction terms indicated relations with depressive symptomatology were not maintained at follow-up. Given these findings, we encourage future research to examine specific competence domains and “therapist drift” with an increased number of session assessments.     

Prospective randomized controlled trial comparing partially absorbable lightweight mesh and multifilament polyester anatomical mesh in laparoscopic inguinal hernia repair

Introduction

Tension‐free mesh repair is currently the gold standard treatment for inguinal hernia. Recent evidence has shown that both open and laparoscopic approaches to inguinal hernia repair can achieve good results. Lots of meshes with different properties are available on the market, but direct comparisons between them are scare. We conducted a prospective randomized controlled trial comparing a partially absorbable lightweight mesh (ULTRAPRO?) and a multifilament polyester anatomical mesh (Parietex?) in laparoscopic total extraperitoneal inguinal hernia repair.

Methods

This study was a single‐center, prospective randomized controlled trial to compare the surgical handling and clinical outcomes between two different types of meshes. All operations were performed using a standardized operative protocol. This study was approved by the Institutional Review Board of the Hong Kong East Cluster Health Service in 2009 (reference number: 2009‐087). The study was registered in the Australian New Zealand Clinical Trial Registry (ACTRN12610000031066).

Results

From October 2009 to August 2011, 85 laparoscopic total extraperitoneal inguinal hernia repairs were performed. The mean mesh handling time was 152 s for the ULTRAPRO group and 206 s for the Parietex group (P = 0.001). There were three cases of seroma formation in the ULTRAPRO group and nine in the Parietex group (P = 0.02). The overall recurrence rate was 2.5%.

Conclusion

It took less time to manipulate the flat mesh (ULTRAPRO) than the anatomical mesh (Parietex) in laparoscopic total extraperitoneal inguinal hernia repair, but the time difference was small. Lightweight mesh and heavyweight mesh offered similar clinical outcomes in terms of discomfort sensation and foreign body sensation during long‐term follow‐up.

     

Impact of a national smoking ban on hospital admission for acute coronary syndromes: a longitudinal study

Background:

A ban on smoking in the workplace was introduced in Ireland on March 29, 2004. As exposure to secondhand smoke has been implicated in the development of coronary disease, this might impact the incidence of acute coronary syndromes (ACS).

Hypothesis:

The smoking ban was associated with a decreased rate of hospital admissions for ACS.

Methods:

We analyzed data collected in a registry of all patients admitted to hospital with ACS in the southwest of Ireland, catchment population 620 525, from March 2003 until March 2007.

Results:

In the year following implementation of the ban, there was a significant 12% reduction in ACS admissions (177.9 vs 205.9/100,000; 95% confidence interval [CI]: 164.0‐185.1, P = 0.002). This reduction was due to fewer events occurring among men (281.5 vs 233.5, P = 0.0011) and current smokers (408 vs 302 admissions, P < 0.0001). There was no change in the rate of admissions for ACS in the following year (174.3/100,000; 95% CI: 164.0‐185.1, P > 0.1). However, a further 13% reduction was observed between March 2006 and March 2007 (149.2; 95% CI: 139.7‐159.2). Variation in admissions with time as a continuous variable also demonstrated a reduction on implementation of the smoking ban.

Conclusions:

A national ban on smoking in public places was associated with an early significant decrease in hospital admissions for ACS, suggesting a rapid effect of banning smoking in public places on ACS. A further reduction of similar magnitude 2 years after implementation of the ban is consistent with a longer‐term effect that should be further examined in long‐term studies. No funding was received for this study. The Coronary Heart Attack Ireland Registry (CHAIR) is funded by the Department of Health and Children, which had no role in the design, data collection, data analysis, data interpretation, writing or revising of the report. IJP is chairman of the Research Institute for a Tobacco Free Society. The other authors have no funding, financial relationships, or conflicts of interest to disclose.     

Muscle-tendon morphology and function following long-term exposure to repeated and strenuous mechanical loading

We mapped structural and functional characteristics of muscle-tendon units in a population exposed to very long-term routine overloading. Twenty-eight military academy cadets (age = 21.00 ± 1.1 years; height = 176.1 ± 4.8 cm; mass = 73.8 ± 7.0 kg) exposed for over 24 months to repetitive overloading were profiled via ultrasonography with a senior subgroup of them (n = 11; age = 21.4 ± 1.0 years; height = 176.5 ± 4.8 cm; mass = 71.4 ± 6.6 kg) also tested while walking and marching on a treadmill. A group of eleven ethnicity- and age-matched civilians (age = 21.6 ± 0.7 years; height = 176.8 ± 4.3 cm; mass = 74.6 ± 5.6 kg) was also profiled and tested. Cadets and civilians exhibited similar morphology (muscle and tendon thickness and cross-sectional area, pennation angle, fascicle length) in 26 out of 29 sites including the Achilles tendon. However, patellar tendon thickness along the entire tendon was greater (P < .05) by a mean of 16% for the senior cadets compared with civilians. Dynamically, cadets showed significantly smaller ranges of fascicle length change and lower shortening velocity in medial gastrocnemius during walking (44.0% and 47.6%, P < .05-.01) and marching (27.5% and 34.3%, P < .05-.01) than civilians. Furthermore, cadets showed lower normalized soleus electrical activity during walking (22.7%, P < .05) and marching (27.0%, P < .05). Therefore, 24-36 months of continuous overloading, primarily occurring under aerobic conditions, leads to more efficient neural and mechanical behavior in the triceps surae complex, without any major macroscopic alterations in key anatomical structures.