Silence of the limbs: pharmacological symptomatic treatment of intermittent claudication

Several oral "vasoactive" drugs claim to increase walking capacity in patients with intermittent claudication (IC). Naftidrofuryl, cilostazol, buflomedil, and pentoxifylline are the most studied molecules. Although spanning several decades, several studies underlying these claims were not properly designed, underpowered or showed clinically doubtful outcomes. The evidence for these "vasoactive" drugs has always been received with scepticism, creating the need for systematic reviews and meta-analyses. This brief review discusses the benefit-risk assessment of vasoactive drugs, by applying a systematic review to evaluate randomized, placebo-controlled trials. Oral naftidrofuryl and cilostazol have an acceptable safety profile as well as sustained evidence (documented by Cochrane analyses) of increased walking capacity. Subsequently, these drugs entered recommendations for peripheral arterial disease (PAD). In contrast, buflomedil and pentoxifylline have limited and/or doubtful evidence to increase walking capacity. Moreover, there were safety concerns about the narrow therapeutic range of buflomedil. Most other "vasoactive" drugs were either inappropriately or insufficiently tested or showed no significant if not negative effects on IC. "Vasoactive" drugs are no substitutes for lifestyle or exercise therapy but are adjuvant treatment to the well-appreciated triad of cardiovascular prevention (antiplatelet agents, statins and ACE-inhibitors), of which statins in their own right have documented claims to significantly increase walking capacity. "Vasoactive" drugs may have a place in the pharmacological management of symptomatic PAD in addition to the basic cardiovascular pharmacotherapy, when revascularization is not indicated, when exercise therapy is not feasible or when there is still insufficient benefit

Bio-inspired pulmonary surfactant-modified nanogels : a promising siRNA delivery system

Inhalation therapy with small interfering RNA (siRNA) is a promising approach in the treatment of pulmonary disorders. However, clinical translation is severely limited by the lack of suitable delivery platforms. In this study, we aim to address this limitation by designing a novel bioinspired hybrid nanoparticle with a core-shell nanoarchitecture, consisting of a siRNA-loaded dextran nanogel (siNG) core and a pulmonary surfactant (Curosurf (R)) outer shell. The decoration of siNGs with a surfactant shell enhances the colloidal stability and prevents siRNA release in the presence of competing polyanions, which are abundantly present in biofluids. Additionally, the impact of the surfactant shell on the biological efficacy of the siNGs is determined in lung cancer cells. The presence of the surfactants substantially reduces the cellular uptake of siNGs. Remarkably, the lowered intracellular dose does not impede the gene silencing effect, suggesting a crucial role of the pulmonary surfactant in the intracellular processing of the nanoparticles. In order to surmount the observed reduction in cellular dose, folate is incorporated as a targeting ligand in the pulmonary surfactant shell to incite receptor-mediated endocytosis. The latter substantially enhances both cellular uptake and gene silencing potential, achieving efficient knockdown at siRNA concentrations in the low nanomolar range. (C) 2015 Elsevier B.V. All rights reserved

Comparaison des performances de cinq tests rapides pour le diagnostic de l’angine à streptocoque du groupe A

Objet. Etude comparative des performances analytiques de tests immunochromatographiques pour la détection du streptocoque A dans les frottis de gorge : Quickvue (Quidel), bioNexia (bioMérieux), Clearview (Inverness medical), Dipromed et All-Diag. Méthodes. Les prélèvements utilisés ont été réalisés avec les E-Swab de chez Copan. Un total de 106 échantillons a été testé, dont 58 positifs et 48 négatifs. Environ la moitié des échantillons a été testée avec le format cassette et l’autre moitié avec le format dipstick pour les kits bioNexia et Clearview. Par ailleurs, les kits Dipromed et All-Diag (tous deux au format dipstick) ont été groupés dans cette étude car ils sont identiques (information confirmée par les fournisseurs). Les résultats des tests rapides ont été comparés à ceux de la culture prolongée. Les échantillons ont été ensemencés sur milieu CNA, avec disque de bacitracine pour l’identification présomptive du streptocoque A. Un groupage à l’aide de tests d’agglutination (Oxoid) et/ou une identification de la souche sur l’automate Vitek 2 (bioMérieux) ont été réalisés pour identification formelle. Sur base des résultats de l’étude, nous avons calculé la sensibilité et la spécificité de chaque kit. Ces valeurs ont ensuite été appliquées à la prévalence de cultures positives pour le streptocoque A observée au CHR Citadelle, en 2012. Nous avons ainsi pu calculer les valeurs prédictives positives (VPP) et négatives (VPN) sur notre population réelle. Résultats. La sensibilité est excellente pour tous les kits, comprise entre 93,1% (Clearview) et 96,6% (Quickvue). La spécificité est de 95,8% pour le Quickvue, tandis qu’elle est de 97,9% pour tous les autres kits. Sur la population du CHR Citadelle (2012), les VPP sont de 77,6% pour le Quickvue, et se situent aux alentours de 87% pour les autres kits. Les VPN sont excellentes et vont de 99 à 99,5%. Conclusion. Les valeurs de sensibilité et spécificité obtenues dans cette étude sont conformes à celles attendues pour ce genre de kit selon la littérature, c’est-à-dire respectivement supérieures à 90% et 95%. Les VPP observées avec le test Quickvue sont péjorées par l’existence d’un faux positif de plus. Les autres kits présentent une quasi-équivalence analytique dans notre série

Power absorption by closely spaced point absorbers in constrained conditions

The performance of an array of closely spaced point absorbers is numerically assessed in a frequency domain model Each point absorber is restricted to the heave mode and is assumed to have its own linear power take-off (PTO) system Unidirectional irregular incident waves are considered, representing the wave climate at Westhinder on the Belgian Continental Shelf The impact of slamming, stroke and force restrictions on the power absorption is evaluated and optimal PTO parameters are determined For multiple bodies optimal control parameters (CP) are not only dependent on the incoming waves, but also on the position and behaviour of the other buoys Applying the optimal control values for a single buoy to multiple closely spaced buoys results in a suboptimal solution for the array Other ways to determine the PTO parameters are diagonal optimisation (DO) and individual optimisation These methods are applied to two array layouts consisting of 12 buoys in a staggered grid and 21 buoys in an aligned grid Compared to DO, it was found that individually optimising the CP increased the energy absorption at Westhinder with about 16-18% for the two layouts, respectivel

CBCT of osteogenesis imperfecta of the inner ear

A 42-year-old female known with osteogenesis imperfecta (OI) was referred to our department with complaints of deteriorating hearing loss. The medical history, besides some limb fractures, secondary to the OI, was negative. During clinical examination, a sensorineural hearing loss was confirmed bilaterally

Insights into functional mitral regurgitation using the average pixel intensity method

Previously we introduced and validated the average pixel intensity (API) method for grading mitral regurgitation (MR) in a heterogeneous MR population. We now investigated the feasibility and added value of the API method more specifically in patients with functional MR (FMR). We consecutively enrolled 283 patients with pure FMR. Transthoracic echocardiography was performed and MR was assessed using the API method and guideline-recommended parameters, including color Doppler, vena contracta width (VCW) and proximal isovelocity surface area (PISA)-based methods. The API method had an applicability of 98% in this FMR cohort, which was significantly higher than VCW (84%) and PISA-based methods (75%). Overall, the API method had significant correlations with direct parameters of FMR severity, ejection fraction, atrial and ventricular dimensions, pulmonary pressures and New York Heart Association class. Analysis of the API dynamics during MR revealed a typical pattern with early and late systolic peaks in API and a midsystolic nadir, which matched the temporal changes of the effective regurgitant orifice (ERO) during FMR. Based on ROC curves of established FMR severity cut-offs, an API value of 125 au was considered the optimal cut-off to determine severe MR. Interestingly, this API severity cut-off is similar to the API severity cut-off for MR in degenerative MR (DMR), despite different EROA/RV cut-offs in current ESC guidelines for FMR and DMR. The API method is an easy, fast and feasible parameter for grading FMR and may complement the multiparametric assessment of FMR in daily clinical practice

Septal flash is a prevalent and early dyssynchrony marker in transcatheter aortic valve replacement-induced left bundle branch block

New-onset left bundle branch block (LBBB) is a frequent complication after transcatheter aortic valve replacement (TAVR) and provides an opportunity to study dyssynchrony immediately following acute LBBB. This study aims to (1) assess echocardiographic dyssynchrony in acute TAVR-induced LBBB (TAVR-LBBB), and (2) compare dyssynchrony parameters among different patient groups with LBBB. The study enrolled all TAVR-LBBB patients at Ghent University Hospital between 2013 and 2019. First, acute TAVR-LBBB dyssynchrony was assessed by: (1) septal flash (SF); (2) interventricular mechanical delay (IVMD; cut-off >= 40 ms) and (3) presence of 'classical dyssynchronous strain pattern' assessed with speckle tracking. Secondly, acute TAVR-LBBB patients with SF (LBBBTAVR+SF) were compared to randomly selected LBBB-SF patients with preserved (LBBBSF+PEF) and reduced ejection fraction (LBBBSF+REF). In TAVR-LBBB patients (n = 25), SF was detected in 72% of patients, whereas only 5% of TAVR-LBBB patients showed a classical dyssynchronous strain pattern. IVMD in these TAVR-LBBB patients was 39 ms. In 90% of LBBBTAVR+SF patients, SF was observed within 24 h after LBBB onset. Among LBBB-SF patients, a classical strain pattern was more prevalent in LBBBSF+REF patients compared to LBBBTAVR+SF patients (80% vs. 7%; p < 0.001). IVMD was significantly longer in LBBBSF+PEF patients (52 ms; p = 0.002) and LBBBSF+REF patients (57 ms; p = 0.009) compared to LBBBTAVR+SF patients (37 ms). SF is an early and prevalent marker of LV dyssynchrony in acute TAVR-LBBB, whereas strain-based measures and IVMD do not appear to capture dyssynchrony at this early stage. Our findings from the comparative analysis generate the hypothesis that progressive LBBB-induced LV remodeling may be required for a 'classical dyssynchrony strain pattern' or significant IVMD to occur in TAVR-LBBB patients