Prediction of a Good Response to Cardiac Resynchronization Therapy in Patients with Severe Dilated Cardyomyopathy: Could Conventional Echocardiography Be the Answer after All?

Objectives: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). Background: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. Methods: The 12‐month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler‐based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. Results: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver‐operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m² (P = 0.045) and for LVFS was 13% (P = 0.032). Conclusions: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. (Echocardiography 2012;29:267‐275)     

The role of Doppler ultrasound in rheumatic diseases

The use of Doppler techniques, including power, colour and spectral Doppler, has greatly increased in rheumatology in recent years. This is due to the ability of Doppler US (DUS) to detect pathological vascularization within joints and periarticular soft tissues, thereby demonstrating the presence of active inflammation, which has been reported to be correlated with the local neo-angiogenesis. In synovitis, DUS showed a high correlation with histological and MRI findings, thus it is considered a valid tool to detect pathological synovial vascularization. Moreover, it is more sensitive than clinical examination in detecting active joint inflammation and in the evaluation of response to treatment. In addition, DUS may be considered as a reference imaging modality in the assessment of enthesitis, MRI being not sensitive and histology not feasible. Moreover, it has been demonstrated to be able to detect changes in asymptomatic enthesis. In conclusion, DUS is a useful and sensitive tool in the evaluation and monitoring of active inflammation. Its widespread use in clinical rheumatological practice is recommended. The aim of this article is to review the current literature about the role of DUS in rheumatic diseases, analysing its validity, reliability and feasibility.     

Antithymocyte globulin induction therapy improves survival in lung transplantation for cystic fibrosis

Cystic fibrosis (CF) is an inherited condition that leads to respiratory failure and is the third most common indication for adult bilateral lung transplantation (LuTX). In contrast to other lung diseases, the immune system of CF patients is up‐regulated and we therefore hypothesized that these patients would benefit from induction therapy. In the current study, we investigated the impact of antithymocyte globulin (ATG) induction therapy in CF patients after LuTX. One hundred and forty six patients who underwent LuTX for CF at our centre between January 1999 and December 2010 were included in the study and retrospectively analysed. They were divided into two groups according to the immunosuppressive protocol: group‐A (n = 103) with and group‐B (n = 43) without induction therapy on top of the basic calcineurin inhibitor based triple immunosuppression with mycophenolate mofetil and steroids. Perioperative survival was significantly better in the ATG group, a benefit sustained for the entire follow‐up. ATG induction resulted in a significantly lower incidence of acute rejections without an increase in infectious complications. Taken together, our results indicate that ATG induction therapy confers a significant survival benefit in CF patients undergoing LuTX and reduces rejection. We advocate the use of induction therapy in this patient cohort.     

The Effect of Court Location and Available Time on the Tactical Shot Selection of Elite Squash Players

No previous research in squash has considered the time between shots or the proximity of the ball to a wall, which are two important variables that influence shot outcomes. The aim of this paper was to analyse shot types to determine the extent to which they are played in different court areas and a more detailed analysis to determine whether the time available had an influence on the shot selected. Ten elite matches, contested by fifteen of the world’s top right handed squash players (age 27 ± 3.2, height 1.81 ± 0.06 m, weight 76.3 ± 3.7 kg), at the men’s World Team Championships were processed using the SAGIT/Squash tracking system with shot information manually added to the system. Results suggested that shot responses were dependent upon court location and the time between shots. When these factors were considered repeatable performance existed to the extent that one of two shots was typically played when there was limited time to play the shot (< 1.20s). For example, it was clear that when players did not have a lot of time to hit the ball (low time i.e. < 1.06s, and mid time i.e. 1.06 - 1.20s) in the front left corner close to the side wall, the crosscourt lob was used frequently (44.30% and 36.31% respectively) whereas when there was more time this shot was seldom used (13.64%). Consequently variant and invariant behaviour were shown to exist in elite squash although for the first time it was suggested that the availability of time to play a shot contributed to which of these behaviours was evident. This analysis could be extended by adopting a case study approach to see how individual differences in strategy and tactics affect shot selections.

Key points

• Previous research has suggested that a playing strategy, elements decided in advance of the match, may be evident for elite players by examining court location and preceding shot type, however these parameters alone are unlikely to be sufficient predictors.
• At present there is no known analysis in squash, or indeed in any of the racket sports, that has quantified the time available to respond to different shot types. An understanding of the time interval between shots and the movement characteristics of the player responding to different shots according to the court positions might facilitate a better understanding of the dynamics that determine shot selection.
• Some elements of a general playing strategy were evident e.g. predominately hitting to the back left of the court, but tactical differences in shot selection were also evident on the basis of court location and time available to play a shot.

Key words: Strategy, tactics, SAGIT, invariant behaviour.     

Alterations in the striatal dopamine system during intravenous methamphetamine exposure: Effects of contingent and noncontingent administration

The continuing spread of methamphetamine (METH) abuse has stimulated research aimed at understanding consequences of its prolonged exposure. Alterations in nigrostriatal dopamine (DA) system parameters have been characterized in experimental studies after discontinuation of long‐term METH but fewer studies have included similar assessments during METH exposure. Here, we report METH plasma pharmacokinetics and striatal DA system alterations in rat after noncontingent and contingent METH administration for 7.5 weeks. Escalating METH exposure was delivered by dynamic infusion (DI) that incorporated a “humanized” plasma METH half life or by intravenous self‐administration (IVSA) that included binge intakes. Kinetic modeling of DI and IVSA for 24 h periods during the final week of METH exposure showed that plasma METH levels remained between 0.7 and 1.5 µM. Animals were sacrificed during their last METH administration for autoradiography assessment using [³H]ligands and D2 agonist‐induced [³⁵S]GTPγS binding. DA transporter binding was decreased (DI, 34%; IVSA, 15%) while vesicular monoamine transporter binding and substantia nigra DA cell numbers were unchanged. Decreases were measured for D2 receptor (DI and IVSA, 15–20%) and [³⁵S]GTPγS binding (DI, 35%; IVSA, 18%). These similar patterns of DI and IVSA associated decreases in striatal DA markers reflect consequences of cumulative METH exposure and not the drug delivery method. For METH IVSA, individual differences were observed, yet each animal's total intake was similar within and across three 24‐h binges. IVSA rodent models may be useful for identifying molecular mechanisms that are associated with METH binges in humans. Synapse 67:476–488, 2013. © 2013 Wiley Periodicals, Inc.     

The use of liquid latex for detecting traces of blood following thermal exposure

International Journal of Legal Medicine - In cases of crimes involving blood, the perpetrators often attempt to remove the traces they have left behind. Setting fire to the crime scene, aside from...     

Phase 3 evaluation of HP802‐247 in the treatment of chronic venous leg ulcers

In 2012 we reported promising results from a phase 2 clinical trial of HP802‐247, a novel spray‐applied investigational treatment for chronic venous leg ulcers consisting of human, allogeneic fibroblasts and keratinocytes. We now describe phase 3 clinical testing of HP802‐247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802‐247 to show efficacy in these two phase 3 trials was initiated immediately following the initial review of the North American trial results. Four hundred twenty‐one patients were enrolled in the North American (HP802‐247, 211; Vehicle 210) and 252 in the European (HP802‐247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802‐247, 61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802‐247, 47.0%; Vehicle 50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802‐247. Concordance between the two separate, randomized, controlled trials with distinct, nonoverlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks.